Cardiovascular Club I
11:00 AM
Thursday, February 20, 2014
1 INCREASED RHO-KINASE ACTIVITY IN RENAL AFFERENT ARTERIOLES OF ANGIOTENSIN II INFUSED HYPERTENSIVE RATS
Shao W, Bivona BJ, Kobori H, Navar L. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: It is known that Ang II activates Rho-kinase activity and Rho-kinase plays an important role in regulating afferent arteriolar tone. However, the role of Rho-kinase on afferent arterioles in chronic Ang II infused hypertensive rats has not been examined. Experiments were performed to determine if Rho-kinase inhibition with fasudil has greater vasodilatory effects on afferent arterioles in Ang II infused rats.
Methods Used: Kidneys from Sprague-Dawley rats were studied in vitro using the blood-perfused juxtamedullary nephron technique.
Summary of Results: Juxtamedullary nephrons were superfused with fasudil (1μM to 100μM) and Ang II (1 nM) in normotensive control rats (n = 6; systolic arterial pressure, 115 ± 1 mmHg) and hypertensive rats infused with Ang II (80ng/min) for 11 to 13 days (n= 5; systolic arterial pressure, 187 ± 6 mmHg). Fasudil alone markedly dilated afferent arterioles in both normotensive and hypertensive rats. During Ang II superfusion, fasudil caused afferent arteriolar vasodilation in both control and Ang II infused rats; however, the afferent arteriolar diameter response to 100 μM of fasudil in Ang II infused rats was significantly greater than in control rats (23 ± 2 vs. 18 ± 1 μm; p < 0.05). Compared with the Ang II superfusion only period, fasudil dilated afferent arterioles similarly in both control and Ang II infused rats (46 ± 6% and 50 ± 12%; p < 0.05). However, the afferent arteriolar diameter responses to 100 μM of fasudil in Ang II infused rats were significantly greater compared with those in control rats (97 ± 18 vs. 68 ± 10%; p < 0.05).
Conclusions: In conclusion, the afferent arteriolar activity of Rho-kinase in Ang II infused hypertensive rats was enhanced compared with normotensive rats. This augmented Rho-kinase activity may play an important role in mediating the enhanced afferent arteriolar sensitivity in chronic Ang II dependent hypertension.
2 INTERFERON ALPHA REDUCES NITRIC OXIDE PRODUCTION IN ENDOTHELIAL CELLS
Buie JJ1, Muise-Helmericks R2, Oates J1,3. 1 Medical University of South Carolina, Charleston, SC; 2 Medical University of South Carolina, Charleston, SC and; 3 Medical University of South Carolina, Charleston, SC.
Purpose of Study: Systemic lupus erythematosus (SLE) patients have accelerated atherosclerosis not fully explained by conventional risk factors. Type I interferon strongly associates with vascular endothelial dysfunction (VED) in SLE patients. VED results from diminished expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability and serves as the first step in the development of atherosclerosis. Herein, we examined the impact of interferon alpha (IFN-alpha) on eNOS gene and protein expression and on NO production in primary human umbilical vein endothelial cells (HUVECs).
Methods Used: HUVECs were treated with of IFN-alpha at 6hrs in the presence or absence of bradykinin. Cells were examined for eNOS gene expression using RT2PCR. mRNA stability was analyzed using an Actinomycin D based assay while changes in heteronuclear RNA (hnRNA) were examined using PCR. Protein abundance and post-translational modifications of eNOS (peNOS Ser1177 and Thr495) were evaluated using Western blot analyses. NO production was detected by flow cytometry using the NO sensitive dye DAF-FM (4-Amino-5-Methylamino-2′,7′-Difluorofluorescein) Diacetate.
Summary of Results: HUVECs treated with IFN-alpha exhibited a 50% reduction in eNOS gene expression after 6hrs (p<0.005). Changes in eNOS mRNA stability were insignificant, however, a 48% reduction in hnRNA expression was observed (p<0.05) suggesting that IFN alpha may impair eNOS transcription. IFN-alpha also reduced total eNOS expression and increased post-translational phosphorylation of eNOS at the threonine 495 site 1.7 fold. These changes were reversed by treatment with bradykinin. Lastly, pre-incubation with IFN-alpha lead to a 40% reduction in NO production (p<0.05). However, NO production was restored more than 50% with addition of bradykinin treatment.
Conclusions: These data further support a role for IFN-alpha in the development of endothelial dysfunction that may lead to atherosclerosis in SLE populations.
3 CHEMOTHERAPIES: CATION DYSHOMEOSTASIS AND DELAYED MYOCARDIAL REPOLARIZATION WITH CARDIAC ARRHYTHMIAS
Khan MU, Khalid H, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Chemotherapeutic agents, individually or in combination, can be cardiotoxic. Responsible mechanisms for their adverse effects are poorly understood. They can alter the absorption and/or excretion of cations which take place along epithelial cells of kidneys and intestine. We hypothesized resultant cation dyshomeostasis would be indirectly cardiotoxic accompanied by delayed myocardial repolarization and QTc interval prolongation on the ECG to increase the propensity for arrhythmias. We therefore studied serum electrolyte concentrations, QTc interval duration, and the appearance of arrhythmias in patients receiving chemotherapeutic agents reported to be associated with this pathophysiologic scenario.
Methods Used: A retrospective chart review of 30 consecutive patients (59±2 yrs; 19 females) who were started on chemotherapy, between January to December 2012, for various cancers. Patients with previously documented arrhythmia, chronic renal failure (serum creatinine >2 mg/dL), or who were receiving medications known to prolong repolarization were excluded. Lowest total serum [Ca2+], ionized [Ca2+]o, K+ and Mg2+, obtained within first 8 wks of initiation of chemotherapy, together with QTc interval and cardiac rhythm from standard ECG or rhythm records obtained within 3 wks of these laboratory values were noted.
Summary of Results: Hypocalcemia was present in 70% and ionized hypocalcemia in 67%; hypokalemia (K+ <4.0) in 90% and in 80% <3.5; hypomagnesemia (Mg2+ <2.0) in 100% and <1.8 in 87%. Prolonged QTc (>440 ms) was found in 73% when K+ was either <4.0, Mg2+ <2.0, and/or hypocalcemia was present. New-onset arrhythmias were seen in 67% when QTc was prolonged: supraventricular, 17; ventricular, 2; and both ventricular and atrial in 1.
Conclusions: Chemotherapeutic agents are accompanied by a dyshomeostasis of K+, Mg2+ and Ca2+ with QTc prolongation and a predisposition to supra- and ventricular arrhythmias. Serial surveillance and maintenance of cations within strictly defined limits (i.e., K+ ≥4.0 and Mg2+ ≥2.0) is recommended to avoid indirect cardiotoxicity with arrhythmias in response to chemotherapy.
4 DECREASING OXIDATIVE/NITROSATIVE STRESS IN RENAL INJURY FOLLOWING ISCHEMIA-REPERFUSION
Pacurari M1, Hage F2, Guo Y2, Ndebele K1, Kafoury R1. 1 Jackson State University, Jackson, MS and 2 University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: Acute kidney injury (AKI) is a highly prevalent condition among hospitalized patients. It is associated with high cardiovascular morbidity and mortality. A major process in AKI pathogenesis is oxidative/nitrosative stress (OS/NS). Due to high AKI prevalence and limited treatment options, finding novel interventions to prevent ischemia/reperfusion (I/R)-induced OS/NS is urgently needed. In the present study we tested the hypothesis that systemic transfusion of EC prevents OS/NS-induced vascular injury in I/R AKI model.
Methods Used: Male Sprague-Dawley rats were subjected to bilateral I/R injury to the kidneys by clamping the renal pedicle for 45 min under anesthesia (ketamine and pentobarbital). Immediately after renal pedicle de-clamping, rats were IV transfused with saline (I/R+Veh) or rat endothelial cells (0.5 × 105 cells/500 μl, I/R + EC). After 3 day, rats were euthanized and kidneys were collected, snap frozen in liquid nitrogen for gene expression or paraffin embedded for immunohistochemistry. A control negative group was subjected to sham bilateral surgery.
Summary of Results: A severe renal injury was found 3 days post-I/R determined by H&E staining. At 3days post-I/R, an increased myeloperoxidase (MPO) immunostaining was found in the kidney cortex of I/R + Veh compared to sham, whereas a diminished MPO immunostaining was found in I/R+EC. I/R significantly decreased vonWillebrand (vWF) immunoreactivity in kidney cortex and renal artery compared to sham, whereas EC transfusion minimally improved vWF immunoreactivity. Transfusion of EC robustly reduced nitrotyrosine immunostaining in kidney cortex of I/R+EC vs I/R+Veh. In summary, I/R in rats leads to increased OS/NS which is worsening kidney vascular/microvasculature and tubular injury. Transfusion of EC markedly decreases I/R-induced OS/NS, thus ameliorating renal injury and therefore may represent a new therapeutic strategy for attenuating I/R AKI. Presently, we are exploring alternative approaches to decrease OS/NS following I/R-induced AKI that could become clinically translated.
Conclusions: I/R causes a severe OS/NS in the kidney, therefore decreasing the production of OS/NS products following I/R may represent a novel therapeutic strategy to attenuate acute kidney injury.
Adult Clinical Case Symposium
12:00 PM
Thursday, February 20, 2014
5 HYPOTHALAMIC SARCOIDOSIS WITH VISION LOSS AND HYPOPITUITARISM—CASE SERIES AND REVIEW OF LITERATURE
Anthony J1, Esper GJ2, Ioachimescu A3,1. 1 Emory University, Atlanta, GA; 2 Emory University, Atlanta, GA and 3 Emory University, Atlanta, GA.
Case Report: Hypothalamic-pituitary (HP) neurosarcoidosis (NS) is extremely rare representing 0.5% of sarcoidosis and <1% of sellar region lesions. The prognosis is worse compared with sarcoidosis without HP involvement. We present a case series of NS with optic chiasm involvement and pituitary hormonal abnormalities (PHA).
Patients include four men (three African American and one white) with both PHA and optic chiasm involvement. Mean follow-up was 6.7 years (range 0.3-16). Mean age at diagnosis was 45.5 (range 34-59). All patients presented with anterior hypopituitarism (FSH, LH and TSH in 4/4, ACTH in 2/4) and diabetes insipidus (DI) in 2/4. Prolactin was normal in 4/4. All patients developed vision loss within a year. Systemic sarcoidosis was present in 3/4 (lung, mediastinal lymph nodes, sinuses). Diagnosis was made by histology in three and Zajicek clinical criteria in one. MRI showed a hypothalamic lesion in three cases and nodular thickening of the proximal infundibulum in one. The leptomeninges and geniculate ganglion were involved in one case.
Treatment with high dose glucocorticoids (GC) was begun in all cases. Vision stabilized and PHA persisted in all patients despite MRI improvement in 2/4. Steroid sparing agents were employed in 3/4. Hyperglycemia was common and weaning of therapy resulted in disease reactivation in 2/4 patients. Hormonal replacement with thyroid hormone and testosterone is currently administered 4/4, GC in 2/4 (while the other two patients are still taking high dose GC) and DDAVP in 2/4.
Review of four published series on HP NS (4, 5, 9 and 24 cases) indicates anterior hypopituitarism as a landmark of the disease, and DI in 50% cases. Of 42 total cases, only six showed improvement in PHA as a result of treatment. Symptomatic optic chiasm involvement occurred in 9/42 patients, but visual outcomes were not documented.
Presentation with PHA and vision loss in context of a suprasellar lesion should raise the suspicion for HP NS. Although hormone deficiencies are likely permanent, early treatment may improve the neurological outcomes and maintenance therapy is important to prevent relapse. Long term, multidisciplinary care is essential for patients with this serious condition.
6 ATYPICAL HEMOLYTIC UREMIC SYNDROME TREATED WITH ECULIZUMAB
Khawar MU1, Bhutta U2, Haragsim L2. 1 OUHSC, Oklahoma city, OK and 2 OUHSC, Oklahoma city, OK.
Case Report: Atypical hemolytic uremic syndrome (aHUS) is a rare, life threatening illness characterized by widespread thrombotic microangiopathy (TMA). We report a patient with acquired aHUS treated with Eculizumab resulting in resolution of her renal failure without the need for dialysis.
We were consulted for oliguric acute renal failure in a 36-years-old Hispanic female, admitted to the OB/GYN service with severe pre-eclampsia in her 31st week of pregnancy; had undergone emergent cesarean section, complicated by post operative bleeding from incision site requiring multiple blood transfusions. Physical examination was significant for elevated blood pressure, tenderness around the incision site & lower extremity edema. Pertinent laboratory abnormalities included an increase in creatinine from baseline of 0.6 to 6.8 mg/dl, anemia, thrombocytopenia, elevated LFTs, schistocytes on peripheral blood smear, elevated LDH level, low fibrinogen level & high fibrin degradation products (FDPs). She was initially thought to have HELLP syndrome & conservatively managed in the hope that her condition would improve after delivery of the baby, but her condition continued to worsen. Her ADAMTS13 activity was 61% of normal. She was diagnosed to have aHUS & started on Eculizumab for treatment. Her renal function and platelet count started improving the very next day. All other laboratory abnormalities trended back to normal. She did well over the next few days and was discharged home with renal function slightly above her baseline.
aHUS refers to the constellation of acute renal failure, thrombocytopenia, microangiopathic hemolysis without antecedent diarrhea & is caused by chronic uncontrolled activation of complement system. Because of its overlap with thrombotic thrombocytopenic purpura (TTP), it has been considered a variant of TTP and treated with plasma exchange (PE) in the past. Often PE does not reverse the renal process or stop the TMA and patients end up on dialysis. A major achievement in the treatment of aHUS is the recent availability of Eculizumab, a humanized monoclonal anti-C5 antibody that targets the underlying cause of TMA in aHUS. This case highlights the importance of distinguishing aHUS from TTP and starting definitive treatment to prevent irreversible loss of kidney function.
7 ACQUIRED METHEMOGLOBINEMIA BENZOCAIN INDUCED METHEMOGLOBINEMIA
Zedan A, Omar S, Suarez J. Texas tech university health science center, Lubbock, TX.
Purpose of Study: Methemoglobimemia is a rare cause of central cyanosis that could be a life threatening condition.Normally methemoglobin level in blood should be less than 1%. Methemoglobinemia could be acquired or congenital, with the acquired form being more common. Acquired methemoglobinemia occurs when the rate of methemoglobin formation exceeds the rate of its reduction. In clinical practice, Pharmacologic agents are the most frequent cause. Of these medications Benzocaine is one of the most commonly used medication as a topical anesthetic causing this type of hemoglobinopathy. In this abstract we will discuss a rare case of acquired drug induced Methemoglobimemia.
Methods Used: Case analysis and literature review
Summary of Results: We report a case of benzocaine-induced methemoglobinemia in a 42-year old male with past medical history of type 2 diabetes mellitus, hypertension and drug abuse who presented to the ER with right leg dragging and altered speech For which brain MRI was ordered and showed acute left anterior cerebral artery infarction. During the complete work up for stroke transesophageal echocardiography was done and 2 hours after the procedure during which benzocain was used as a local anesthetic, the patient developed central cyanosis and altered mental status with low oxygen saturation that was not improved with oxygenation. Arterial blood gases showed PH of 7.45, PCO2 42, and PO2 82. Methemoglobin level measured by co-oxymetry was found to be 36 percent, intravenous methelyne blue was started, 8 hours later methemoglobin level was measured again and found to be less than 1 percent. The patient’s cyanosis resolved and his mental status came back to norml with normal oxygen saturation.
Conclusions: Methemoglobinaemia is one of the uncommon causes of central cyanosis that could be a life threatening condition if not considered in the differential diagnosis and work up for centrally cyanosed patients who are refractory to oxygen administration especially after administration of topical anesthetics. Benzocain is one of those medications commonly used as a topical anesthetic in many procedures including TEE and bronchoscopy and can cause methemoglobinemia as a rare life threatening side effect. Methylene blue should be available in all areas where these procedures are performed to ensure rapid and prompt management of this condition.
8 FAR MORE THAN RED EYES
Fenire M, Mulkey Z, Ali E, Mazek H, Mohamed A. Texas Tech University Health Science Center, Lubbock, Lubbock, TX.
Purpose of Study: 1-To report a case of relapsing polychondritis (RP) with images. 2- Highlight that misdiagnosis is common and can lead to serious consequences.
Methods Used: Case analysis and literature review
Summary of Results: A 45-year-old man presented to the emergency center after one week of redness of his left eye and ear. He was diagnosed with possible cellulitis and discharged with antibiotics but returned three days later after his symptoms worsened and involved both eyes (Panel A and B). Of note, one year prior, similar symptoms resulted in him losing his hearing on the left side. Ophthalmological exam revealed iritis, acute diffuse scleritis and proptosis bilaterally. His cardiopulmonary exam was normal as was the electrocardiogram. A diagnosis of relapsing polychondritis was made and a course of high-dose corticosteroids was initiated to which he responded very well. The patient declined maintenance immunosuppressive treatment, electing to treat flare ups only and has remained symptom free for 8 months.
Conclusions: RP is rare. More than 600 cases have been reported worldwide. It is a multisystem disease that can be life threating, debilitating, and difficult to diagnose. In a series of 66 patients, the mean delay from time of medical attention was sought for symptom onset until diagnosis was 2.9 years, one third of those patients needed to see five or more physicians before diagnosis. The etiology is unknown, but the pathogenesis seems to be an immunologic reaction to type II collagen. The clinical features are the key in diagnosis of the RP. The onset is usually sudden. In the Isaak et al series auricular chondritis was the initial presenting symptom in 39% of the patients. Permanent hearing loss can occur as a consequence of sensorineural involvement believed to be secondary to vasculitis in the vestibular or cochlear branch of the internal auditory artery. Ocular manifestations occur in 60% of patients, the most common are scleritis, episcleritis, and conjunctivitis. Prednisone had been the main form of treatment, and methotrexate may help lessen corticosteroid requirement.
9 ELECTROCARDIOGRAM CHANGES IN COMMON VARIABLE IMMUNODEFICIENCY RELATED ADRENAL INSUFFICIENCY
Parekh N1, Modi F2, Patel B1, Byrd RP2,1, Roy T2,1. 1 ETSU, Johnson City, TN and 2 ETSU, Johnson City, TN.
Purpose of Study: We present an adult patient with known history of common variable immunodeficiency (CVID) who was identified to have adrenal insufficiency-associated QTc interval prolongation and t-wave inversion. Treatment with hydrocortisone resolved these endocrinopathy-associated myocardial electrical abnormalities.
Methods Used: A 70 year old male with past medical history of CVID was admitted for hypotension refractory to fluid challenge. He reported fatigue, loss of appetite and unintentional weight loss 40pounds in last year. His blood pressure was 82/42 mmHg. His hemoglobin was 11.9 g/dl and had an eosinophilia of 13.9%. He was hyponatremic with normokalemia. The electrocardiogram (ECG) showed a QTc prolongation of 600ms with nonspecific anterolateral T wave changes. A thorough history ruled out any prior use of glucocorticoids or other medications which could be the cause of adrenal insufficiency or QT interval prolongation prior to this hospitalization. Left heart catheterization ruled out acute ischemic process.In the1950s, ECG abnormalities in adrenal insufficiency were described. Studies of rat heart muscle show that glucocorticoid is essential for the calcium transport in sarcoplasmic reticulum and microsomal phosphorylase activity. Additional reports suggest adrenal insufficiency-related reversible cardiomyopathy and T wave changes in adult patient. The link between adrenal insufficiency and CVID was suggested when a literature review identified a pediatric case of autoimmune lymphocytic hypophysitis in association with CVID who presented in acute adrenal crisis.
Summary of Results: Adrenal insufficiency was confirmed by very low morning cortisol levels -1.3 ug/dl. Improvement in patient’s symptoms, blood pressure and EKG changes resolved in parallel with hydrocortisone supplementation. He was later diagnosed with low serum ACTH and a partially empty sella on magnetic imaging studies supporting secondary adrenal insufficiency.
Conclusions: To our knowledge, this is the first case report of an adult where CVID, adrenal insufficiency and QTc abnormality were coexistent. Consideration of adrenal insufficiency early in hospitalization lead to prompt diagnosis and treatment which prevented potential catastrophic consequences of ventricular arrhythmia or death.
10 FAMILIAL THORACIC AORTIC ANEURYSM AND DISSECTION PRESENTING WITH FLASH PULMONARY EDEMA IN A 26-YEAR-OLD MAN
Omar S, Moore T, Mulkey Z, Nugent K. Texas Tech University Health Science center, Lubbock, TX.
Purpose of Study: Familial thoracic aortic aneurysm (TAAD) is an autosomal dominant disease that usually involves the ascending aorta and presents with dissection of the involved segments. The genetic basis of familial TAAD, not associated with other genetic syndromes, has only been recently described. Several associated loci with relevantgenes mutations have been identified. This disease typically presents at a mean age of 56, which is ten years younger than non-familial cases.
Methods Used: Case analysis and literature review
Summary of Results: We are reporting one case of familial thoracic aortic aneurysm with a dissection in a 26-year old male with no significant past medical history and a family history of dissecting aortic aneurysm in his mother at age 40. The patient has normal physical appearance and does not have any features that suggest Marfan’s syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, or ANCA-positive vasculitis. He presented with cough, shortness of breath, and chest pain for 10 days. Chest x-ray at the time of presentation showed bilateral pulmonary infiltrates. He was treated outside the hospital as bronchopneumonia but did not improve. When CT scan of the chest showed dissecting ascending thoracic aortic aneurysm, the patient was transferred to our hospital and successfully underwent aortic aneurysm repair. Three months after aortic dissection repair, the patient returned to our hospital with new complaints of sharp back pain. CT angiography showed a new aortic aneurysm and dissection extending from the carotid arteries through the bifurcation and into the right iliac artery. The patient underwent aortic, carotid, and iliac repair
Conclusions: This case report focuses on a patient with familial TAAD and discusses the associated genetic loci and available screening methods. Screening begins with CT angiogram, MRI,or TEE. Genetic screening includestesting for the ACTA2 gene mutation and may involve sequencing of the seven other genes associated with familial TAAD. It is important to recognize potential cases of familial TAAD and understand the available screening methods because early diagnosis allows appropriate management of risk factors and treatment when necessary
11 CHANGES IN LIPIDS AND BLOOD SUGAR POST BARIATRIC SURGERY IN OBESE HISPANIC PATIENTS- POSSIBLE MECHANISMS
Hernández-Gil de Lamadrid JJ1, Altieri PI1,2, Mora-Lemus L1, Corretjer L1, Nieves JJ1, Banchs HL1,2, Suárez A1, Muñiz J1, Soto M1, Escobales N1, Crespo M1. 1 University of Puerto Rico, San Juan and 2 Cardiovascular Center of Puerto Rico and the Caribbean, San Juan.
Purpose of Study: Bariatric surgery is the most frequent used procedure to control obesity (o) and the metabolic syndrome (Mets). The purpose is to describe the changes after this procedure and possible mechanisms.
Methods Used: A retrospective analysis of 102 patients records who had bariatric surgery analysis was done preoperative and 12 months post-surgery.
Summary of Results: 97% had Roux-N-Y surgery with a mean age of 39 years. 79.4 were females and 20.6 were males. 44% were diabetics.
Metabolic Reductions:
1) BMI (Kg/m2) - 47 ± 9–33 ± 7) P < 0.0001
2) Weight (Lbs.)- 285 ± 62–198 ± 54) P < 0.0001.
3) Cholesterol (mg/dl) - 169 ± 30–151 ± 30 P < 0.0001.
4) LDL (mg/dl)- 101 ± 27–86 ± 25 P. < 0.0001.
5) Triglycerides (mg/dl)- 112 ± 47–84 ± 22 P < 0.0001.
6) FBS (mg/dl) - 98 ± 25–87 ± 20 P < 0.0001.
Metabolic Increase:
1) *HDL mg/dl) - 44 ± 10 to 49 ± 13 P < 0.0006. *Not significant
The correlation factor between weight loss and changes in FBS, Cholesterol, HDL and LDL fluctuated between .1 - .5.
Conclusions: These results shows that the metabolic changes and lipids, predominantly are due to weight reduction, but the poor correlation factor suggest other mechanisms:
1. Up regulation of Glu) -1 protein producing and increase in reabsorption of glucose from Jejunum.
2. Inflammation of the Jejunal mucosa producing adaptation (atrophy- proliferation) reducing the absorption of cholesterol (diabetics > non-diabetics).
3. More degradation of LDL in Jejunum (more in diabetics).
4. No degradation of HDL.
In summary the changes in blood sugar and lipids are complex and should be studied further as well as changes in gut microbiota. These changes are related to a further reduction in cardiovascular risks, especially in the Hispanic population who has a lower effect of risk factors in the development of ischemic heart disease.
12 AN INTERESTING CASE OF HYPOKALEMIC PERIODIC PARALYSIS
Sotello D1, Rivas M1, Castaneda J2, Lado-Abeal J1. 1 Texas Tech University Health Sciences Center, Lubbock, TX and 2 AtlantiCare Regional Medical Center, Atlantic City, NJ.
Case Report: A 31 year old Asian male without past medical history presented to the emergency for 1 day of multiple episodes of severe bilateral thigh pain, lasting 1-2 seconds each, occurring every time he tried to move the proximal lower extremity muscles, associated with 3 episodes of sudden lower extremity muscular weakness, the most significant one lasting >30 minutes. He had a similar episode 8 months before. Vital signs: BP: 132/84 mmHg, HR: 116 beats per minute, RR: 18 per minute and Temperature: 99.7° F. Physical examination: tachycardic, no murmurs, diminished lower extremity strength 2/4, with diffuse tenderness, and brisk patellar reflexes, the rest was normal. CBC, creatinine and liver enzymes were within normal limits; Na: 144 mEq/L, K: 1.7 mEq/L, Glucose: 140 mg/dl, Ca: 10.2 mg/dl, Magnesium: 1.9 mg/dl, Phosphorus 2.1 mg/dl, TSH: <0.01 ng/ml, free T3: 17.65 pg/ml, free T4: 5.01 ng/dl, diagnosing thyrotoxic periodic paralysis (TPP). Thyroid Stimulating and Thyrotropin binding inhibiting immunoglobulins, antithyroid peroxidase and antithyroglobulin antibodies were positive, suggesting Graves’ disease. The patient was started on IV potassium replacement, as well was treated with propylthiouracil, propranolol, iodine and dexamethasone, which resolved patient’s symptoms.
Hypokalemic periodic paralysis (HPP) is an heterogeneous group characterized clinically by hypokalemia and acute systemic weakness due to multiple mechanisms. The most common cause of HPP is an autosomal dominant defect in the Cav1.1 skeletal muscle voltage-gated Ca channel or the Nav1.4 Na channel which occurs more commonly in non-hispanic Caucasians. Nonfamilial causes of HPP includes TPP which is more common in Asian population and in males. The pathogenesis of TPP has long been thought related to increased Na-K ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. Recent findings show that loss of function mutations of the skeletal muscle-specific inward rectifying K (Kir) channel, Kir2.6, which cause an inadequate outward K efflux in skeletal muscle can lead to a vicious cycle of hypokalemia and paralysis. Treatment is with potassium replacement as well as restoration of euthyroidism.
13 MYSTERIOUS ORIGINS OF ANDROGEN EXCESS
Cosentino G, Friday K. LSUHSC-NO, New Orleans, LA.
Case Report: Androgen secreting tumors are notoriously hard to find when they are secreting small amounts of hormones. However, when testosterone secretion is ample enough to cause virilization, a neoplasm is usually evident on imaging. This case highlights the use of a laboratory evaluation for localization of a virilizing, androgen-secreting tumor.
This is the case of a 37 year old woman with a past medical history of lupus and obesity, status-post gastric bypass, who was referred to the endocrinology clinic with complaints of increasing facial hair and male pattern baldness for one year. She had been treated by another physician for non-classic congenital adrenal hyperplasia with steroids, but she had failed to improve. Other complaints included deepening of her voice and acne. Her medications included dexamethasone 0.5 mg twice daily and spironolactone 200 mg daily. Blood pressure was 116/78 and BMI was 38.4. Physical exam revealed male pattern hair distribution with terminal hair on cheeks and sideburns, neck, chest, and back. She had modest clitoral enlargement. Previous labs included a total testosterone of 1271 ng/dL and free testosterone of 301 (upper limits of normal for women are 45 and 6.4 respectively), a low DHEA-S of 22, hematocrit of 48.5%, estradiol 46, suppressed LH and FSH. Pelvic ultrasound, CT, and MRI failed to identify any definitive abnormalities of the adrenal glands nor of the ovaries. The patient was also sent for adrenal and ovarian vein sampling which did not identify the source of excess testosterone. The patient did not desire children, and she was so burdened by her symptoms that her gynecologist agreed to do a hysterectomy and oophorectomy. Although in the surgery there were no palpable abnormalities of the ovaries, pathology revealed a 2.5 cm Leydig tumor of the left ovary. Blood work done following the surgery confirmed that the patient’s testosterone levels had decreased to 3 ng/dL.
Neoplasm must be suspected when patients present with virilization that occurs over a short time. When the adrenal glands are the source of androgen excess, it is accompanied by elevated levels of DHEA-S. In our patient these levels were low. Often when serially imaged, these tumors are seen as the hormone levels rise. However, when the source remains elusive, hormone precursors can be used to identify the likely organ of secretion.
14 DIABETIC MUSCLE INFARCTION OR PYOMYOSITIS?
Pena C1, Argueta E1, Nantsupawat T1,2, Nugent K1,3. 1 Texas Tech University, Lubbock, TX; 2 Texas Tech University, Lubbock, TX and 3 Texas Tech University, Lubbock, TX.
Case Report Introduction: DMI is a rare complication of poorly controlled diabetes mellitus (DM) that occurs during spontaneous skeletal muscle necrosis. Muscle swelling and tenderness characterize it. The differential diagnosis includes PM, in which a muscle abscess develops. PM can present in three stages; muscle swelling and tenderness, then abscess formation, and finally sepsis. PM diagnosed in the first stage is challenging and can be delayed. We present a patient with PM, whose presentation suggested DMI with concurrent diabetic ketoacidosis (DKA), but developed PM in six weeks.
Case: 44-year-old woman with DM type II presented with left lower back pain of two weeks duration. She had tachycardia, no fever, left paraspinal swelling with no erythema or ecchymosis. Blood analysis revealed leucocytosis, 20.4 cells/mm3 (84% neutrophils), glucose 261 mg/dL, HbA1C 11.7%, normal CK, ESR 70 mm/hr, increased anion gap metabolic acidosis with acetone in serum. Abdomen CT imaging revealed isodense left paraspinal muscle enlargement. Ultrasound was negative for fluid or cystic collections. A non-contrast MRI showed paraspinal muscle T2 hyperintensity consistent with muscle infarction. She was discharged three days after DKA management with mild back pain. The patient presented six weeks later with increased back pain. A repeat CT showed left paraspinal muscle multiloculated fluid collections. An abscess was confirmed after aspiration, and culture was positive for oxacillin resistant Staphylococcus aureus.
Discussion: PM diagnosis depends on clinical infromation; the MRI is considered a sensitive method to demarcate inflamed muscle during infection. In early stages, the muscle may show preserved or increased signal intensity on T1 weighted images and abnormally high intensity in T2 weighted images. These findings have also been associated with DMI. Both conditions, DMI and PM, may have elevated ESR and CK levels, and usually affect the thigh muscles.
Conclusions: This case represents an early PM presentation without clear signs of infection. A confounding factor was the concurrent DKA with leucocytosis attributed to it, and absence of fever. Muscle pain and swelling in patients with poorly controlled DM needs close follow up.
15 WHEN YOU CAN NOT SEE, EAT, AND SPEAK, YOU COULD HAVE MILLER FISHER SYNDROME!
Bahaa Aldeen M, Talibmamury NB, Nadhem O, Al-alusi S, Smalligan RD. Texas Tech University, Amarillo, TX.
Case Report: A 56yo male presented with dysphagia, diplopia, dysarthria, saliva dribbling and facial droop that had worsened over 3 days. A week before he was admitted for gastroenteritis. He denied headache, fever, extremity weakness or sensory deficits and he denied fluctuations of symptoms during the day. He had no chemical exposure or sick contacts. PMH: neg except the recent admission; P/S: smokes, no ETOH or drugs; PE: BP 121/85, HR 97, RR 22, T 98.5, O2 sats 98% on RA. Heart, lungs, abd, extrem, skin normal; neuro: A&O with bilateral facial palsy, no nystagmus, weak abduction of left eye, absent gag reflex, weak tongue. Motor and sensory exams of extremities were normal and reflexes were decreased but present, gait nl. Labs: WBC 19k, electrolytes nl except AG 16, Cr 0.9, gluc 103, Ca 10, Alb 4.4, TP 7.5, LFTs and UA nl. LP nl with neg cmv/enterovirus. Botulism neg. Negative actin (smooth muscle) AB; CSF electrophoresis showed increased beta globulin; AChR blocking ABs, Asialo-GM1, GM1, GM2 and GD1b all neg, GD1a and GQ1b Abs positive. Images: CXR nl, CT head: nl except mild encephalomalacia due to remote infarction. Myasthenia tests were neg (Curtain sign and edrophonium). EMG was normal.
Discussion: Acute, progressive weakness is frightening to patients and if ascending pattern is followed it is usually Guillain-Barre Syndrome (GBS). Our patient’s weakness began in the face with the limbs preserved raising suspicion of Miller Fisher Syndrome (MFS). MFS is an acute immune-mediated demyelinating polyneuropathy, variant of GBS, which presents as a paralyzing illness provoked by a preceding infection. Signs and symptoms include ophthalmoplegia with ataxia and areflexia. 25% of MFS pts have extremity weakness but incomplete forms ophthalmoplegia without ataxia, and ataxic neuropathy without ophthalmoplegia. A brainstem stroke or Wernicke’s can mimic MFS except symptoms are more abrupt with stroke and Wernicke’s usually has nystagmus. Although Miller Fisher syndrome typically presents with ophthalmoplegia, ataxia, and areflexia, variant forms exist as in our case. 80+% of patients with MFS have a positive anti-GQ1b antibody in their CSF. Physicians should keep MFS in their differential of any patient with unexplained facial palsy or bulbar weakness.
16 DIABETES INSIPIDUS UNMASKED BY NAUSEA AND VOMITING OF PREGNANCY
Orellana-Barrios MA, Rivas M, Sotello D, Lado-Abeal J. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: A 33-year-old pregnant woman, G2P1, in her eleventh week of pregnancy was admitted for worsening nausea and vomiting of pregnancy. Her symptoms started at 5 weeks gestation and were associated with polyuria and polydipsia. She had a history of migraine headaches diagnosed 5 months prior to presentation, resolved gestational DM in her last pregnancy, and a positive family history for Graves’ disease in her mother and aunt. On admission, her vital signs were within normal limits, and her physical exam was remarkable for dehydration. Her serum sodium was 137 mmol/L, potassium 3.4 mmol/L, calcium 10.4 mg/dL, BUN 2 mg/dL, glucose 94 mg/dL, and urine specific gravity 1.005. She was started on intravenous (IV) fluids (D5WLR, 150 ml/h) and IV thiamine, esomeprazole and antiemetics. Her urinary output in the first 12 hours after admission was 3750 ml. Her symptoms improved but her serum sodium increased to 148 mmol/L ; further testing at that time revealed a serum osmolality of 300 mOsm, urinary osmolality of 103 mOsm, and urinary sodium of 40 mmol/L. Nasal desmopressin (dDAVP) was started at a dose of 10 mcg twice daily and IV fluids were changed to 1/2NS (45ml/h). The patient’s symptoms improved over 3 days with normalization of her urine output and serum sodium. Further work up revealed a low TSH and normal TSI, anti-TPO, anti-Thyroglobulin, SS-A and SS-b antibodies. Her head MRI was normal.
During pregnancy the metabolic clearance of ADH increases due to placental derived vassopressinase. In most pregnant women, this augmented clearance is compensated by an increase in vasopressin production. Insufficient vasopressin secretion or reserve can be unmasked by pregnancy, and inadequate oral intake secondary to NVP can exacerbate this clinical scenario. This case illustrates how this mechanism can be present even in very early pregnancy (1 month after the estimated date of conception) and how prompt diagnosis is imperative to avoid the reported maternal and fetal complications of hypernatremia, profound free water loss, and sometime inadvertent sudden changes in serum osmolality.
17 HOARSENESS, DYSPHAGIA - SUBTLE MANIFESTATIONS OF VERY RARE AND UNUSUAL TUMOR
Suvorava N1, Hosiriluck N1, Aulakh A1,2, Konala V1,2, Nguyen D1,2, Warraich I3. 1 TTUHSC, Lubbock, TX; 2 TTUHSC, Lubbock, TX and 3 TTUHSC, Lubbock, TX.
Case Report: Introduction: Alveolar Soft- Part Sarcoma (ASPS) is a rare malignant tumor which accounts to less than 1% of soft tissue sarcomas and 0.1% of all head and neck sarcomas. It has an indolent clinical course and a high metastatic potential with early metastases to lungs, bone and brain. Late metastases can occur years after resection of the primary tumor, even without local recurrence of the disease.
Case Presentation: A 58 year old male heavy smoker presented with progressive hoarseness, dysphagia and significant weight loss for over a year. The patient underwent flexible laryngoscopy, which revealed a pedunculated obstructing mass at the left supraglottic region. CT scan of neck revealed a 1.3cm soft tissue mass in the glottis. PET scan revealed a hyper-metabolic focus in the left posterolateral aspect superior to the vocal cords. Patient underwent resection of the left supraglottic mass and left neck radical lymph node dissection. Pathology reported poorly differentiated alveolar soft part sarcoma with lymph node metastases and perivascular invasion.
Patient was staged as IVA and completed 35 post operative radiation treatments. He was started on adjuvant treatment with Sunitinib. He developed a skin reaction to the drug that required dose adjustment, but he tolerated it well afterwards. Five months after starting treatment, PET scan showed increased hypermetabolic activity in left vocal cord region and suspicious left cervical lymph node on physical exam. Subsequent work up was negative for any recurrence. Patient later developed worsening fatigue and generalized weakness, and further treatment with Sunitinb was discontinued. He had a disease free survival of nine months with Sunitinib.
Discussion: Treatment of choice for ASPS is wide surgical resection with lymph node dissection for clinically suspicious lymph node involvement. Radiation therapy can be used in high risk patients to prevent local recurrence. No standard chemotherapy regimen is effective in ASPS. However, newer studies show promising results using targeted therapies such as Sunitinib and Sorafenib (multi-tyrosine kinase inhibitors), Cediranib and Bevacizumab.
18 ORGANIZING PNEUMONIA ASSOCIATED WITH HERPES SIMPLEX VIRUS INFECTION PROGRESSING TO ACUTE RESPIRATORY DISTRESS SYNDROME IN AN IMMUNOCMPETENT PATIENT
El-Bakush A, Kambali S, Nugent K. Texas Tech University Health Sciences Center, Lubbock, TX.
Case Report: Introduction: Organizing pneumonia (OP) an uncommon diffuse interstitial lung disease that affects the terminal and respiratory bronchioles, alveolar ducts, and alveoli. A definitive diagnosis requires adequate tissue biopsy showing the characteristic intra-alveolar buds of granulation tissue associated with fibroblasts, myofibroblasts, and loose connective tissue. Most cases are idiopathic; some are associated with infections, drugs, radiation, connective tissue disorders, transplantation, and environment agents. We present an uncommon case of OP associated with Herpes simplex virus (HSV).
Case: 40-year-old man with hypertension presented with dyspnea, fever and productive cough for 2 weeks. He was treated 5 days for acute bronchitis as an outpatient with no improvement. Exam revealed mild distress with an oxygen saturation of 92% on room air and right sided crackles. Labs included a WBC of 19.3. CXR showed bilateral infiltrates greater on the right. He was diagnosed with community-acquired pneumonia and started on broad spectrum antibiotics. Sputum cultures were negative. His respiratory status progressively deteriorated, and he was intubated for mechanical ventilation. Bronchoalveolar lavage was positive for HSV; transbronchial biopsies showed focal organizing pneumonitis with plentiful intra-alveolar macrophages. He received 10 days of IV antibiotics and 14 days of IV acyclovir. After being discharged home, he was readmitted10 days later with worsening symptoms and infiltrates on the CXR. He was intubated for respiratory failure. CT chest showed diffuse, patchy consolidation of both lungs, right more than left. Open lung biopsy showed extensive organizing pneumonia, diffuse alveolar damage, intra-alveolar macrophages, and pleural fibrosis. The diagnosis of OP was made, and he was treated with IV steroids. He was extubated after 10 days; within 2 weeks the CXR was markedly improved.
Discussion: Organizing pneumonia is usually idiopathic; infection is one of the secondary causes. To our knowledge only one case associated with HSV has been reported, and it was in a transplant patient on tacrolimus. Early diagnosis and treatment is crucial as it usually responds to steroid treatment.
19 WELLENS’ SIGN - A RELIABLE ECG SIGN OF CORONARY (WIDOW MAKER) ARTERY DISEASE FOR THE INTERNIST
Panikkath R, Panikkath D, Meyyerose G, Jenkins L. Texas Tech University Health Sciences Center, Lubbock, Lubbock, TX.
Case Report: Introduction: Although Wellens’ sign is reliable sign of significant proximal left anterior descending artery (LAD) disease, awareness of this among primary care doctors, hospitalists and emergency room physicians is very low.
Methods: This is a case report and review of literature
Case Report: A 56 year old man with history of coronary stenting and coronary artery bypass surgery (CABG) in 2011, presented to his primary care physician (PCP) with short episodes of chest pain. The cardiac biomarkers were negative. Although the PCP obtained an ECG, which showed T inversions in leads V2 and V3, suggestive of Wellens’ sign, it was disregarded due to lack of awareness regarding this sign. No urgent referral to a cardiologist occurred. Six months later, when the patient followed up with a cardiologist, myocardial perfusion study showed a large amount of anterior ischemia. Echocardiogram showed normal left ventricular function and no wall motion abnormalities. A coronary angiogram was performed, which showed near total occlusion of the stent in the proximal left anterior descending coronary artery. However, since the CABG graft to the mid LAD was patent, no intervention was performed.
Conclusion: Wellens’ sign is a reliable sign of proximal LAD disease with a sensitivity of 69%, specificity of 89% for significant (≥ 70% diameter) stenosis of the LAD with positive predictive value 86%. The objective of this abstract is to create better awareness among primary providers about this sign. It has been reported in 14%-18% of patients with unstable angina. This finding is usually signifies a pre-infarction stage of coronary artery disease. Its progression to anterior wall myocardial infarction is so likely that medical management alone is not considered enough to stop the natural course.The evolution to anterior wall MI is often rapid with a mean time of 8.5 days from onset of this sign to infarction. This sign often appears when the patient is pain free, signifying the importance of a follow up ECG in such patients. Infarction due to occlusion of the proximal LAD places the patient at risk for left ventricular dysfunction, heart failure, and death. Awareness of this sign among physicians helps in early detection of proximal LAD lesions.
Pediatric Clinical Case Symposium
12:00 PM
Thursday, February 20, 2014
20 THE BENZOCAINE BLUES; A CASE OF SEVERE METHEMOGLOBINEMIA INDUCED BY TOPICAL 20% BENZOCAINE IN A PEDIATRIC PATIENT
Broge T, Patel S, Neemuchwala F, Gorman S, Haggett L. Florida State University Pediatric Residency Program at Sacred Heart Hospital, Pensacola, FL.
Case Report: A three year-old male was admitted to the pediatric intensive care unit for altered mental status and hypoglycemia. Initial work-up was unremarkable. He was placed on intravenous fluids with dextrose and cardio-respiratory monitoring. He responded to therapy and exhibited gradual improvement of his mental status. However, on hospital day three, he experienced acute onset of cyanosis and altered mental status. He was tachycardic with a heart rate of 230 beats per minute and saturation by pulse oximetry of 86%. He was placed on 100% oxygen, with subsequent improvement of oxygen saturation to only 90%. A venous blood gas was obtained and yielded a pH of 7.35, pCO2 of 38.6mmHg, HCO3 of 21.2 mEq/l, hemoglobin of 7.6g/dL, lactate of 5.2 mmol/L and methemoglobin concentration was critically elevated at 66.3%. The blood sample was noted to be chocolate-colored. Methylene blue was administered at 1.85 mg/kg/dose. Subsequent blood gases showed a methemoglobin concentration of 16% and then 1.4%. A bottle of 20% benzocaine oral gel was found on the floor in patient’s room, which was originally in purse of the patient’s mother. The patient’s acute presentation was attributed to the ingestion of this topical over-the-counter agent.
Methemoglobin (MetHb) is a nonfunctional state of hemoglobin in which iron atoms from hemoglobin are oxidized from their ferrous form to a ferric state, rendering the heme incapable of carrying oxygen. MetHb is normally present in small amounts in the blood; however, at increased concentrations methemoglobinemia can be life threatening. All the commonly used benzocaine preparations have been reported to cause acquired methemoglobinemia including over-the-counter teething pain products. Although perceived to be relatively benign agents, topical benzocaine preparations have demonstrated potential to cause life-threatening methemoglobinemia. Primary care providers must be aware of the side effects of benzocaine products and ensure that parents are educated regarding the proper dosing and safe storage of topical benzocaine preparations.
21 A PRESENTATION OF KAWASAKI DISEASE SHOCK SYNDROME
Strachan S, Williard C, Wall T, Borasino S. The University of Alabama at Birmingham, Birmingham, AL.
Case Report: A 5 year old female presents in shock and respiratory failure after 6 days of fever, malaise, headache, rash, conjunctivitis and cervical lymphadenopathy. She was seen by her pediatrician who prescribed Amoxicillin and then an oral cephalosporin which had to be held for a rash reaction. In 48 hours she developed painful neck swelling and was admitted to a regional hospital. There she developed tachycardia and an increased work of breathing requiring transfer to a PICU. On arrival: T 38.9°C, HR 124 bpm, BP 66/38 (after a 40cc/kg normal saline bolus), and SpO2 92% (on 5L facemask). PE: bilateral erythematous conjunctiva with subconjunctival hemorrhages, a 4 x 4 cm firm right cervical lymph node, coarse breath sounds, a I/VI systolic murmur, delayed cap refill, and an erythematous maculopapular rash on her legs. She was started on antibiotics, required inotropic support, and was rapidly intubated for respiratory failure. Kawasaki Disease (KD) was suspected and IVIG was administered. After much improvement she was transferred to a general inpatient ward service. However, she remained febrile to 38.8 - 39.4°C. Physical exam showed injected conjunctiva, a diffuse erythematous maculopapular rash, and edema of her hands and feet with desquamation of her palms. Blood cultures finalized negative, and antibiotics were discontinued after 7 days. High dose methylprednisolone and a one-time dose of Infliximab were given which finally led to defervescence. KD is the leading cause of acquired heart disease among children in North America and Japan, and although the etiology is not well understood, recognition and treatment have been well defined. KDSS was first described by Kanegaye et al. in 2009 as signs of KD with hypotension (≥ 20% decrease from baseline). Recently there have been several case reports of KDSS; however, overall it has proven to be an uncommon presentation. It has been associated with higher markers of inflammation, low grade consumptive coagulopathy, and higher rates of coronary artery dilatation and aneurysm formation than KD without shock. Most cases showed improvement in cardiac function after IVIG; however, some remained refractory. Although the cause of this severe presentation of KD is unknown, clinicians need to be alerted to the possible increase in prevalence of this severe complication.
22 GRANULOMATOSIS WITH POLYANGIITIS PRESENTING AS ORBITAL PSEUDOTUMOR IN A PEDIATRIC PATIENT: A CASE DEMONSTRATING THE NEED FOR CONTINUED SUSPICION OF ANCA-ASSOCIATED VASCULITIS IN CASES OF ISOLATED ORBITAL PSEUDOTUMOR
Carlson AP1,2, Santucci K2,1, Church A2,1, Subtirelu M2,1. 1 University of Tennessee College of Medicine at Chattanooga, Chattanooga, TN and 2 The Children’s Hospital at Erlanger, Chattanooga, TN.
Case Report: Granulomatosis with polyangiitis (GPA), formerly called Wegener’s granulomatosis, is an uncommon adult disease with a prevalence of 8.4-11.3 per million per year among those greater than 15 years of age. In the adult population, GPA presents with ocular manifestations in 3.5-30% of cases, orbital disease being the most common form, composing 22% of all eye manifestations of GPA. GPA is less common in children, occurring 2.75 cases per million children per year. Children most commonly present initially with GPA with constitutional symptoms (90%), pulmonary manifestations (80%), upper respiratory disease (80%), and renal disease (75%). Only 19 % of children present initially with ocular manifestations, and the documentation of children with GPA who present with symptoms suggestive of orbital pseudotumor is limited to case reports and case series. While GPA infrequently presents with orbital inflammation, the renal and pulmonary manifestations of GPA are life-threatening if untreated. Early diagnosis of the rare childhood case of GPA is critical. This report documents the case of a 10-year-old female who presented with proptosis and eye pain. Initial evaluation was negative for a definite cause, and patient was diagnosed with orbital pseudotumor. After an interval of more than a year, the patient developed renal and respiratory involvement which led to a diagnosis of GPA. This case suggests the benefit of ongoing surveillance and high suspicion for GPA in children diagnosed with isolated orbital pseudotumor.
23 FOREIGN BODY INGESTION PRESENTING AS A MEDIASTINAL MASS
Thiagarajan A, Bradley J, Lawson K, Macariola D. East Tennessee State University, Johnson City, TN.
Case Report: A 4-year-old male presented with a 4-day history of fever & abdominal pain. Associated symptoms included poor oral intake, decreased activity & anorexia. Past medical history was significant for recurrent upper respiratory tract infections & pneumonia. On physical exam, he was afebrile, in no apparent distress with the rest of the exam findings being unremarkable. Pertinent laboratory tests include elevated ESR while chest x-ray demonstrated a right mediastinal mass. Chest CT confirmed the mediastinal mass of the upper third of the esophagus while barium swallow demonstrated a filling defect on the same site. Laboratory work up was unremarkable. He was treated initially with IV ceftriaxone for suspected infected bronchogenic cyst. On discharge he received a two-week course of cefdinir. Repeat chest CT after 2 weeks showed slight resolution of the mass. He underwent a right lateral thoracotomy. During surgery, this cystic mass was found to be an esophageal pseudodiverticulum resulting from a piece of plastic imbedded in the esophageal wall. The esophagus was repaired after removal of the plastic material. A gastrograffin swallow study demonstrated esophageal narrowing at the operative site without extravasation. He made a full recovery on follow up.
Foreign body ingestion is a common pediatric condition. Often, this is preceded by specific clinical history revealing the time of ingestion and the material ingested. However, occasionally patients may present with nonspecific symptoms such as fever, pain, cough, anorexia, and even respiratory distress necessitating an extensive evaluation. At times these patients can be misdiagnosed as having bronchitis, asthma or pneumonia & mistakenly treated for these conditions. Suspicion for foreign body aspiration should increase when symptoms persist or recur despite optimal therapy. Diagnosis is often obtained by bronchoscopy but may require surgical exploration. Delay in diagnosis of foreign body aspiration can lead to poor outcomes & therefore should be considered early in the course of the illness so that appropriate interventions can be initiated. Our case highlights a foreign body masquerading as a mediastinal mass or bronchogenic cyst. Clinicians should therefore think of foreign body ingestion in similar situations as depicted in our case.
24 HSV ENCEPHALITIS IN A PATIENT AFTER RADIOTHERAPY AND ADJUVANT CHEMOTHERAPY
Wisner E1, Steinhardt M1, Raulji C1, Morrison C1, Zakris E2, Velez M1. 1 Children’s Hospital, New Orleans, LA and 2 Touro Infirmary, New Orleans, LA.
Case Report: Herpes simplex encephalitis (HSE) is the most common identifiable cause of viral encephalitis. This infection leaves the majority of survivors with significant neurologic morbidities. Multiple case reports have demonstrated the relationship of HSE among cancer patients treated with CNS radiotherapy. This is the case of a nineteen-year-old female with a brainstem tumor who was diagnosed with HSE while being treated concurrently with radiotherapy, adjuvant oral chemotherapy, and high-dose steroids. It is with hope that this report will heighten the index of suspicion for HSE among cancer patients with altered mental status.
A 19-year-old female with a known brainstem tumor who had already begun treatment with radiotherapy (3960cGY-22fractions), Temozolamide (90mg/m2), and dexamethasone, presented to our emergency department with altered mental status. She developed new-onset seizure activity and fevers. Broad spectrum antibiotics were initiated and an infectious disease evaluation began. Her mental status remained depressed which was attributed to anti-epileptics versus sequelae from her brain tumor. An EEG at that time revealed global slowing and possible offending medications were discontinued. A MRI revealed a few non-specific, small high T2 hyperintensities within the deep white matter of the bilateral frontal lobes and a slightly smaller medullary tumor. HSV-I DNA PCR was found to be positive in the cerebrospinal fluid. The patient was started on Acyclovir which was escalated to Foscarnet after no improvement in her mental status. A repeat MRI one week after treatment revealed widespread disease. Despite aggressive treatment, the patient died nine months after the initial diagnosis.
In adjunct with supporting literature, this case demonstrates an association with radiation therapy and steroids with HSE. Our case is unique in that it presents a pediatric patient, of which there have only been three such cases reported. It is important to consider HSE in the differential diagnosis among oncology patients with altered mental status. This report highlights the need for a prospective study confirming the association of chemo-radiation and high dose steroids among patients with brain malignancies and HSE.
25 A NOVEL PRESENTATION OF POSTURING AND HEMIPLEGIA IN AN INFANT FEMALE
Hart R, Skeens R, Puri V. University of Louisville, Louisville, KY.
Case Report: We are reporting a case of a 6 month old female who presented over several months with progressive episodes of apparent neurologic events: paroxysmal dystonia, nystagmus, alternating hemiparalysis, and regression of milestones during attacks with restoration of normal development between episodes. After an extensive workup at multiple institutions, including multiple normal EEGs and MRIs, electrolytes, and genetic testing; the patient was diagnosed with Alternating Hemiplegia of Childhood (AHC). This disorder is exceedingly rare with an incidence of approximately 1 in 1,000,000 births but is often mistaken for seizures, a common pediatric diagnosis. These non-epileptiform episodes present unique diagnostic and management challenges. In this case presentation we will explore diagnostic criteria, etiologies, and treatments of AHC as well as a brief overview of neurologic channelopathies, the current proposed etiology of this disorder. We will provide an approach to evaluating infants with seizure-like activity and highlight features that distinguish AHC from epilepsy.
26 PILONIDAL CYST LEADS TO DIAGNOSIS OF AML IN 15 YEAR OLD MALE
Roebuck BM, Meyer WH, Dingeldein LM. University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Introduction: Acute myeloid leukemia (AML) is a malignant clonal proliferation of myeloid precursor cells; it is the second most common leukemia in children. While 80-90% of children obtain remission after induction, 30-40% of patients will suffer a recurrence with a poor 5 year survival rate. Most often children present with signs of bone marrow replacement by malignant cells. We report a case of a 15 year old male treated for a draining pilonidal cyst and subsequently diagnosed with AML.
Case presentation: A 15 year-old Hispanic male presented to the Emergency Department complaining of a lumbar lesion present for the past month that for the past three weeks had been draining brown fluid. Prior to admission, he was treated by an outside clinic with incision and drainage, ibuprofen, two different antibiotics, and a course of oral prednisolone. Upon arrival, the patient also complained of 3 months of fatigue, 6 weeks of subjective fevers, chills, and night sweats, as well as a two week history of bilateral neck swelling with tenderness to palpation and new onset snoring with intermittent difficulty breathing that improved with steroids. Physical exam was significant for diffuse lymphadenopathy, hepatosplenomegaly, and an open non-draining 7.8 cm gluteal cleft abscess. The initial CBC showed marked leukocytosis (231,000), with blasts (81%), anemia (9.2), and thrombocytopenia (29, 000); both uric acid (9.4), and LDH were elevated (606). Flow cytometry was consistent with AML, cytogenetics showed inv(16)(p13.1q22). Histology of the cyst showed extensive myeloblastic infiltration with rod-shaped bacilli. He was treated with combination chemotherapy (AML0531) and antimicrobials, and the pilonidal cyst slowly resolved.
Discussion: Our patient presented with a simple pilonidal cyst that failed I&D and standard oral antibiotic therapy. Further investigation resulted in a diagnosis of AML. Despite presentation of AML with high WBC, this patient had favorable cytogenetics, responded well to induction therapy, and currently remains in remission. A literature review revealed no cases with a similar presentation.
27 A CASE OF CONGENITAL HYPERINSULINISM PRESENTING WITH OPSOCLONUS-MYOCLONUS
Hoops K, Anderson T, Dure L, Pressey J. University of Alabama Birmingham, Homewood, AL.
Case Report: Katherine Hoops, MD MPH - University of Alabama Birmingham Department of Pediatrics; Birmingham, Alabama
Tori Anderson, MD - University of Alabama Birmingham Department of Pediatrics; Birmingham, Alabama
Leon Dure, MD - University of Alabama Birmingham Department of Pediatrics Division of Neurology; Birmingham, Alabama
Joseph Pressey, MD - University of Alabama Birmingham Department of Pediatrics Division of Hematology Oncology; Birmingham, Alabama
Abstract: In this report, we present a case of opsoclonus occurring coincidently with hypoglycemia in the absence of malignancy. The patient is a 5 month old term female infant who presented with a 3 month history of episodes concerning for seizure. The predominant type of episode was characterized by sustained, rapid, darting conjugate eye movements, and they often occurred when awakening from sleep (video available for display). These episodes were felt to be consistent with opsoclonus-myoclonus, so a neoplastic workup was initiated that was concerning for adrenal mass. During her workup, the patient was found to have multiple episodes of profound hypoglycemia. This prompted a thorough work up for neonatal hypoglycemia. Ultimately, work up was consistent with benign adrenocortical adenoma rather than neuroblastoma, but she was found to have congenital hyperinsulinism secondary to ABCC8 gene mutation. 18-F-DOPA PET/CT scan showed focal disease and partial pancreatic resection was performed. After treatment of focal hyperinsulinism, hypoglycemia resolved as did opsoclonus. This case presented numerous diagnostic dilemmas and a fascinating course with multi-specialty and inter-institutional collaboration to arrive at the ultimate diagnosis.
28 BREAST MILK AS A SOURCE OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS INFECTION IN PREMATURE NEONATES
Keefe R. Tulane University School of Medicine, New Orleans, LA.
Case Report: Methicillin-resistant Staphyloccus aureus (MRSA) infection is a well-known cause of severe life-threatening infections in patients in the Neonatal Intensive Care Unit (NICU). Transmission of MRSA to infants through their mother’s breast milk has previously been reported as a source of infection in premature neonates, typically in the setting of maternal mastitis or breast abscess. This is a case report of premature twin infants in our NICU who developed MRSA sepsis within days of initiating enteral feeds with MRSA positive expressed breast milk from their asymptomatic mother.
Twin A and Twin B were born at 27 weeks gestational age via emergent cesarean section for possible pericardial effusion in twin A. Both twins remained in critical, but stable, condition throughout the first week of life. Enteral feeds were begun on day of life (DOL) 8. The next day the condition of twin A rapidly deteriorated. On DOL 10, twin A died of overwhelming multi-system organ failure secondary to suspected sepsis. Two days following her death, Twin B’s condition worsened. Blood, urine and tracheal aspirate cultures obtained from twin B grew MRSA. On this same day, Twin A’s tracheal culture obtained on the day of her death grew MRSA. Although the mother did not have any clinical evidence of mastitis or other breast infection, given the temporal relationship to the initiation of enteral expressed breast milk feeds and clinical deterioration of both patients, consent was obtained from the twins’ mother to send a sample of her breast milk for culture, which resulted positive for MRSA. On DOL 20, despite aggressive antibiotic treatment, twin B also died of overwhelming multi-system organ failure secondary to MRSA sepsis.
Although there are many well documented benefits for early initiation of enteral feeds and breast milk for patients in the NICU, this case suggests that premature infants may be at higher risk of severe systemic infection secondary to gut exposure to MRSA positive breast milk. Given this tragic and likely preventable outcome, we recommend culturing the breast milk of mothers of premature infants in the NICU prior to initiating enteral feeds.
29 METASTATIC NEUROBLASTOMA WITHOUT PRIMARY SOURCE
Van Buren JW, Imran H, Wilson F, Siddiqui A. University of South Alabama, Mobile, AL.
Case Report: Neuroblastoma is an embryonic tumor arising from the sympathetic nervous system. Patients with bone metastases are considered high risk. Histological evaluation of the primary mass is important in establishing diagnosis and prognosis.Our objective is to report a case of neuroblastoma with unknown primary mass diagnosed through bone and bone marrow metastatic sites. A 5 year old male presented with persistent fevers, bone pain and refusal to walk for 3 weeks. Plain radiographs showed single lytic lesion in proximal humerus, but magnetic resonance imaging showed increased fluid signals in multiple vertebrae and long bones. Bone marrow biopsy showed extensive involvement with small round pleomorphic blue cells suggestive of neuroblastoma. Bone biopsies from the humeral and femoral lesions revealed similar lesions. The cells stained positive for neuron specific enolase but the diagnosis of neuroblastoma was confirmed after tyrosine hydroxylase stains were performed by Dr Shimada (second opinion). The MYCN gene was not amplified. Urine catecholamines were elevated. Metaiodobenzylguanidine (MIBG) scintiscan showed diffuse increased uptake in most bones but no primary mass was found. Since there are no systematic published data for treatment and outcome of such cases, it was decided to treat him per the Children’s Oncology Group protocol ANBL0532 for high risk neuroblastoma. He had a remarkable clinical response and post-induction chemotherapy evaluation revealed no histological evidence of cancer in the bone marrow. A small MIBG avid lesion in proximal femur remains that will require radiation. Upon parents’ request, he will now proceed to an immunotherapy trial instead of an autologous stem cell transplantation. To our knowledge there are 13 reported instances of metastatic neuroblastoma without a primary source. Only 5 had reported outcomes. At the conclusion of the respective studies, one patient had local recurrence, and two had died and 2 patients were disease free. Studies are needed to establish a treatment protocol for such unusual presentations of neuroblastoma. It is difficult to assess an accurate prognosis, but our patient has had an excellent response, so far, to chemotherapy per high risk protocol.
30 BUCCAL BIOPSY TO DIAGNOSE NEONATAL LIVER FAILURE
Ravisankar S1, Misra S2. 1 East Carolina University, Greenville, NC and 2 East Carolina University, Greenville, NC.
Case Report: A term male baby who was the product of an uncomplicated pregnancy presented with lethargy and hypoglycemia at 24 hours of life. Though hypoglycemia corrected easily with IV fluids, he clinically deteriorated to develop seizures and became encephalopathic. Concerned of an acute liver failure, work up was broadened from an infectious and metabolic standpoint including TORCH titers, Viral Hepatitis panel, genetic testing for PKU, Tyrosinemia pending newborn screen results. With no conclusive yield, results from an iron panel incited a working diagnosis of Neonatal Hemochromatosis which was eventually confirmed by salivary gland biopsy. The baby was transferred to a transplant center to be listed, but passed away shortly later secondary to worsening of his underlying disease process. Autopsy was denied by the family.
Neonatal Hemochromatosis is a rare condition resulting in severe liver disease with extrahepatic siderosis. About 100 cases have been reported in the literature. An alloimmune etiology has been proposed, but the exact etiopathogenesis remains unknown and no gene locus has been identified so far. Presentations vary from an uncomplicated pregnancy to history of IUGR, oligohydramnios, decreased fetal movement, with the birth of a baby who quickly develops signs of acute liver failure. Initiation of specific work up starts with an iron panel which shows an elevated serum ferritin, low transferrin with a high TIBC. Biopsy of the minor salivary glands is the gold standard and a positive iron stain confirms the diagnosis reflecting the extensive extrahepatic siderosis. Management strategies have evolved from using exclusive iron chelation therapy in the past to now, a combined approach of using an antioxidant cocktail of drugs, double volume exchange transfusion, IV Immunoglobulin and eventually listing for liver transplantation. Fulminant hepatic failure is rare in neonates. Data from the Pediatric Acute Liver Failure Registry reveals that Neonatal Hemochromatosis is a common cause of liver failure in this group. Hence a high index of suspicion is needed for early diagnosis, as timely initiation of the newer management strategies have shown promising outcomes with better prognosis for this otherwise devastating disease.
31 SUCCESSFUL MANAGEMENT OF INVASIVE FUNGAL SINUSITIS IN A PEDIATRIC LEUKEMIA PATIENT WITH PROFOUND NEUTROPENIA
LeBlanc D1, Fletcher M1, Prasad P1, Simon L3, Nuss D3, Seybolt L2, Velez M1. 1 LSU Health Sciences Center/Children’s Hospital New Orleans, New Orleans, LA; 2 LSU Health Sciences Center/Children’s Hospital New Orleans, New Orleans, LA and 3 LSU Health Sciences Center/Children’s Hospital New Orleans, New Orleans, LA.
Case Report: Invasive fungal sinusitis is a potential complication of prolonged neutropenia associated with significant morbidity and mortality (up to 50%). Treatment often necessitates extensive, potentially disfiguring, debridement. We describe a case of invasive fungal sinusitis in a child with acute lymphocytic leukemia (ALL) successfully managed with topical and systemic antifungals and minimally invasive surgical treatment.
A 3-year-old male with ALL in consolidation phase developed febrile neutropenia. Despite broad-spectrum antimicrobials he remained febrile with no identifiable source. Absolute neutrophil count (ANC) remained 0. On hospital day 6 right sided paranasal and infraorbital erythema and edema were noted. He underwent emergent nasal endoscopy and biopsy, revealing extensive black discoloration of mucosal surfaces. The biopsy was consistent with fungal infection with angioinvasion; culture grew Lichtheimia species.
The patient was started on granulocyte-colony stimulating factor (G-CSF) and aggressive antifungal treatment with IV liposomal amphotericin (5mg/kg/day), oral posaconazole (10 mg/kg BID) and intranasal amphotericin spray (5 mg/mL, 1 spray TID). Emergent surgical debridement demonstrated necrosis of mucosa and bone requiring extensive resection of his left paranasal sinuses and septum. Over the next month he underwent serial nasal endoscopies with debridement. The patient completed a 6-week course of daily liposomal amphotericin and an additional 6 weeks of 3 times per week dosing. Topical amphotericin and posaconazole were discontinued after 6 weeks. Subsequent surveillance endoscopies showed healing mucosa with no signs of recurrence.
There is limited literature regarding management of fungal sinusitis in neutropenic children. With aggressive medical management along with minimally invasive surgical debridement, this invasive fungal infection was contained and resolution achieved without the need for disfiguring or functionally compromising debridement.
32 GROUP C STREPTOCOCCUS SEPSIS IN A PEDIATRIC PATIENT WITH TUBEROUS SCLEROSIS
Schmit EO, Diaz F. University of Alabama at Birmingham, Birmingham, AL.
Case Report: Group C streptococci (GCS), a frequent cause of veterinary disease, are uncommon among human patients but most frequently cause illness in elderly or immunocompromised patients. We report a 2-year-old African American female with tuberous sclerosis and congenital lymphedema who presented with severe sepsis due to GCS. Initial symptoms were fever, abdominal pain, and pain in the right thigh. Labs revealed a neutropenia, lymphopenia, metabolic acidosis, and coagulopathy (DIC). She developed fluid-refractory shock requiring vasoactive drug support of dopamine at 10 mcg/kg/min and epinephrine at 0.08 mcg/kg/min and mechanical ventilation. Wide spectrum antibiotics (vancomycin, cefepime, nafcillin, clindamycin, and fluconazole) were started at admission. Blood cultures grew GCS 11 hours from admission, and antibiotic therapy was adjusted to vancomycin and gentamicin. No definite source for her GCS sepsis was found. The most likely primary infections in our patient included endocarditis related to underlying cardiac rhabdomyomas or cellulitis related to underlying lymphedema, but neither source could be proven despite echocardiograms, abdominal ultrasounds, abdominal CT, and Doppler ultrasound of her lower extremities. She had a prolonged hospital course including acute kidney injury with resultant hypertension and acute heart failure. She was extubated at day 12 after admission. She was treated with a 14-day course of antibiotics from her first negative blood culture. She clinically improved and was discharged home in her prior state of health after a 21 day admission.
GCS infections are often linked to exposure to domestic animals or unpasteurized dairy products, and can cause a variety of illnesses including upper and lower respiratory infections, meningitis, bacteremia, osteomyelitis, and soft tissue infections. GCS are a rare pathogen causing bacteremia, as they are only isolated from the blood in less than 1% of all positive blood cultures. Although uncommon, GCS are a clinically important pathogen as associated infections have a mortality rate of up to 25-30%. GCS are generally highly sensitive to penicillin. It has been suggested that a synergistic effect may be achieved with aminoglycosides, but this has not been consistently proven in studies.
33 CUTANEOUS LEISHMANIASIS ACQUIRED IN THE US IN A PEDIATRIC PATIENT -THERAPY WITH TOPICAL KETOCONAZOLE
Singh M1, Balan A2, Parham D3, Weingartner J4, Allen P4. 1 University of Oklahoma, Oklahoma City, OK; 2 University of Oklahoma, Oklahoma City, OK; 3 University of Oklahoma, Oklahoma City, OK and 4 University of Oklahoma, Oklahoma City, OK.
Case Report: Background: Leishmaniasis is a parasitic infection primarily affecting people in the tropics, subtropics and southern Europe. It is rare in the United States; occasional cases of cutaneous leishmaniasis have been acquired in Texas and Oklahoma.
To our knowledge, only one pediatric patient with this infection has been reported, making this the first detailed description of a child with cutaneous leishmaniasis acquired in the United States.
Methods: A 5-year-old boy presented with a one-year history of a 1.5 cm chronic ulcerative lesion, lateral to the right nasal alar crease. He lived in rural southern Oklahoma, and his only travel history included a visit to Corpus Christi, Texas, two years prior to presentation. He played in the yard and periodically got insect bites. The lesion remained stable in size, and he was otherwise asymptomatic. Treatment with topical antihistamines and cryotherapy did not help. Initial pathology was suggestive of leishmaniasis, so that he underwent a second biopsy for confirmation. CDC testing by Leishmania culture and PCR were negative but a definitive diagnosis was made by electron microscopy.
Results: The decision was made to treat with 2% topical ketoconazole cream twice daily. After six weeks, the lesion demonstrated significant improvement, so that topical ketoconazole was discontinued; however, the area soon developed erythema and edema. Topical ketoconazole treatment was restarted continued for 2 months until the lesion had healed completely, with only a small biopsy scar remaining.
Conclusion: We present the first detailed description of a pediatric patient with cutaneous leishmaniasis acquired in the United States, likely in Oklahoma. Tissue culture and biopsy were negative, and a definitive diagnosis was made by electron microscopy. Given his otherwise benign clinical course, the most likely species involved was L. mexicana. While illness caused by this species can be self-limited, our patient seemed to respond to topical ketoconazole treatment with no side effects, making it an attractive treatment option.
34 TWO CASES OF MYCOPLASMA ENCEPHALITIS: EARLY SUSPICION REQUIRED FOR THIS UNDERESTIMATED PATHOGEN
Onuegbu P1, Taylor S2, Lee A1. 1 Florida State University College of Medicine, Pensacola, FL and 2 Harbor-UCLA Medical Center, Torrance, CA.
Case Report: A 5 year old male presented with left eye twitching, left hand shaking and transient lethargy. EEG, neuroimaging and CSF viral and bacterial cultures were negative. The patient developed fever and choreiform movements, with negative workup for rheumatic fever. Neurologic deterioration continued with progressive dysphagia, dysarthria and self-mutilation. Finally, CSF Mycoplasma pneumoniae IgM resulted positive and azithromycin was initiated. Anti-NMDA receptor antibody was positive and despite a short course of steroids and two infusions of IVIG, dysarthria persisted, intermittent twitches remained and he required G-tube placement due to oromotor dysfunction.
Subsequently, a 7 year old male was admitted for concerns of meningitis. Physical exam revealed medial deviation of the left eye, photophobia and altered mental status. Empiric antibiotics were initiated; MRI brain was negative. CSF Mycoplasma titers were sent and empiric intravenous azithromycin initiated. CSF studies then resulted positive for Mycoplasma IgM, but negative for anti-NMDAR antibodies. Three weeks later the patient was appropriately responsive, but speech remained slow and ambulation difficult. Five months elapsed before he had returned to baseline health.
We have described two patients with Mycoplasma encephalitis and variable outcomes. We encourage clinicians to maintain a high index of suspicion for Mycoplasma in the acutely encephalopathic pediatric patient and recommend consideration of early intravenous azithromycin. Once infection is confirmed or neurologic condition deteriorates, testing for anti-NMDA receptor antibodies should be performed. Anti-NMDA receptor encephalitis is a debilitating illness manifested by psychiatric symptoms and seizures, presumably autoimmune in nature. Its incidence and possible association with Mycoplasma infection may be underestimated. Finally, our experience is consistent with literature describing prolonged hospitalization for these patients. We recommend such children receive care at a facility with rehabilitation services available.
Case Reports in Cardiovascular Medicine
2:00 PM
Thursday, February 20, 2014
35 HYPERTENSIVE URGENCY AS THE INITIAL MANIFESTATION OF RENAL CELL CARCINOMA
McShurley T, Jain N. LSUHSC, New Orleans, LA.
Case Report: Renal Cell Carcinoma (RCC) is often associated with paraneoplastic syndromes due to ectopic hormone production of renin, erythropoietin, insulin, glucagon and parathyroid hormone. Two cases exist of norepinephrine secreting RCC presenting as hypertensive urgency. We report a case of a 48 year-old male with history of CABG 6 years prior with subsequent PCI and well controlled hypertension until two months prior presented to the emergency department with sharp, 9/10, left sided chest pain exacerbated by exertion, relieved with rest and two sublingual nitroglycerin tablets. Medications included aspirin 81mg, clopidogrel 75mg, amlodipine 10mg and lisinopril 20mg. Temperature was 98.5, pulse 68, respirations 16, blood pressure 220/120, SpO2 98% on room air. Exam revealed a regular rate and rhythm, no murmurs or rub . There was no jugular venous distension. Pulses were bounding, equal and symmetric. Lungs were clear to auscultation. Abdomen was soft, non-tender, no masses or bruits appreciated. ECG revealed an old inferior MI and nonspecific ST changes. Renal function was normal and cardiac enzymes remained negative. Nitroglycerin infusion was initiated and carvedilol 6.25mg bid was added to his previous regimen. He continued to have chest pain associated with elevated blood pressure which was relieved with nitroglycerin. Despite increasing carvedilol to 25mg bid and the addition of nifedipine 60mg, hydrochlorothiazide 25mg and minoxidil 5mg to lisinopril 40mg daily, his blood pressure remained in the range of 160-200/90-110. Renal artery Doppler ultrasound showed no significant stenoses. MRI of the adrenal glands revealed normal appearing adrenals, however a 3.5cm complex cyst with a prominent mural nodule in the right kidney was found, highly suspicious for renal cell carcinoma. The patient underwent robotic-assisted right partial nephrectomy. Pathology revealed clear cell renal carcinoma confined within the capsulated cyst. Blood samples prior to surgical resection were as follows; renin activity level of 0.2ng/mL/hr [0.2-4.0 ng/mL/hr], TSH: 3.40 mIU/L [0.35-5.50mIU/L], serum aldosterone: <1.6 ng/dL (4.0-31.0ng/dL], ESR: 5 mm/hr [0-10mm/hr], erythropoietin level: 7.0 [4.0-27.0mU/mL] and D-Dimer: <150ng/mL. At one month follow up, his blood pressure was 120/80 on long acting nifedipine 60mg daily.
36 URINARY MAGNESIUM WASTING WITH HYPOMAGNESEMIA AND VENTRICULAR ARRHYTHMIAS
Askari R, Farah V, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Case Report: Purpose: Patients referred for the evaluation of their cardiac arrhythmias frequently have a disturbance in extracellular cations as the etiologic origin of their dysrhythmia. Marked hypokalemia and hypomagnesemia, alone or in combination, can be associated with life-threatening arrhythmias. Herein we present the case of an elderly woman with profound disturbances in serum K+ and Mg2+ that led to symptomatic ventricular tachycardia (VT).
Case Report: A 64-year-old female without past medical history of hypertension or diuretic use presented to the ER with shoulder pain. During the course of her evaluation she had a witnessed seizure with lost consciousness and was noted to have polymorphic VT (Torsades de pointes) requiring DC cardioversion. Electrolytes: K+ 1.6 mmol/L; Mg2+ 1.3 mg/dL; Ca2+ 8.7 mg/dL; and creatinine 1.1 mg/dL. Aggressive electrolyte replacement followed. During hospitalization, a self-limited, asymptomatic episode of VT was noted. UDS and alcohol level were negative. Baseline ECG: sinus rhythm with markedly prolonged QTc of 627 ms. Echocardiogram: normal ejection fraction without atrial or ventricular chamber enlargement. She was discharged home on K+ and Mg2+ supplements. Six months later, she again presented to the ER with VT and reported she had not taken her supplemental Mg2+ for 4 wks. Electrolytes: K+ 2.1 mmol/L; and Mg2+ 1.3 mg/dL with replacement therapy begun and the patient hospitalized. Chest X-ray, CT scan and abdominal ultrasound were negative. ECG: sinus rhythm, premature ventricular contractions in a bigeminal pattern and prolonged QTc (588 ms). Urinary Mg2+ excretion of 11.94% indicated Mg2+ wasting. Primary aldosteronism was excluded. Magnesium oxide supplement together with spironolactone (50 mg po daily), an aldosterone receptor antagonist, attenuated urinary Mg2+ wasting and stabilized serum Mg2+.
Conclusions: Marked reductions in serum K+ and Mg2+ can have profound adverse effects on the heart, including delayed myocardial repolarization and prolonged QTc interval, predisposing to life-threatening VT. Serial surveillance of these cations is recommended together with a medical regimen that preserves them within narrowly defined limits (i.e., K+ ≥4 and Mg2+ ≥2).
37 WARFARIN-INDUCED SKIN NECROSIS IN A PATIENT WITH HEPARIN-INDUCED THROMBOCYTOPENIA
Jimenez L1, Marcial JM1, Candelario N2, Mesa M3, Osterman A3, Rochet N3, Altieri PI1. 1 University of Puerto Rico School of Medicine, San Juan; 2 Department of Dermatology, University of Puerto Rico School of Medicine, San Juan and 3 Department of Medicine, University of Puerto Rico School of Medicine, San Juan.
Case Report: A 64-year-old obese woman with history of hypertension, diabetes mellitus, chronic renal insufficiency and coronary artery disease was admitted to the hospital due to a myocardial infarction for which she was treated with dual anti-platelet therapy and full dose low-molecular weight heparin. Four days after discharge, the patient returned to our institution with worsening shortness of breath, chest discomfort and bilateral lower extremity cyanosis associated with diminished lower extremities pulses. Platelet counts of 200,000/mm3 in previous admission had decreased to 121,000/mm3. Subsequent Heparin platelet factor 4 (PF4) antibody testing and 14C-serotonin release assay confirmed Heparin Induced Thrombocytopenia (HIT). The patient was started on argatroban and bridged to warfarin as therapy for HIT. Four days after starting warfarin, the patient developed ecchymosis of the entire right breast associated with hemorrhagic bullae. Biopsy of the skin lesion was performed and showed epidermal necrosis, vessel thrombosis with fibrin deposition in the superficial and deep dermis, and extravasation of erythrocytes; all suggestive of warfarin-induced skin necrosis (WISN). Anticoagulation therapy is commonly used in the hospital setting. These medications may result in serious complications, such as thrombocytopenia with the use of heparin or warfarin-induced skin necrosis. The prothrombotic environment of HIT makes selection of adequate anticoagulation therapy a challenge. Unopposed warfarin should be avoided in HIT in order to prevent systemic thrombotic events. Only a few reports have described an association between WISN and HIT.
38 UNUSUAL INFECTION CAUSING HEART FAILURE
Panikkath D, Soontrapa S, Panikkath R, Perez Verdia A. Texas Tech University of health sciences, Lubbock, LUBBOCK, TX.
Case Report: INTRODUCTION - Infection is a serious complication of pacemaker (PPM) and implantable cardioverter defibrillator (ICD) implantation.Cardiac device infections can present with pocket infection, blood stream infection (BSI) and device related endocarditis. METHOD - This is a case report of a patient who developed ICD related endocarditis. RESULTS - We present a 68-year-old female with weakness, fatigue, dyspnea on exertion and pedal edema of 6-8 weeks duration, which was gradually worsening. She denied fever, cough or chest pain. She had paroxysmal ventricular tachycardia (VT) for which ICD implantation was done in July 2011. She had systemic hypertension and rheumatoid arthritis for which she was on immunosuppressants, methotrexate and prednisone. Examination revealed a new systolic murmur and petechiae on the toes. The other systems were within normal limits. Lab investigations were significant for anemia, leucocytosis (34,400), elevated brain natriuretic peptide (34,600). The electrocardiogram was normal. New onset heart failure possibly due to Infective Endocarditis was suspected. Transthoracic echocardiogram showed a 2.6 x 1.1 cm vegetation in the right atrium, attached to the ICD lead as well as worsening of the ejection fraction to 30-34% compared to 54% previously. Blood cultures showed gram negative rods identified later as Morganella morgagni. The infected device and leads were subsequently removed. Culture of the lead tip grew the same organism with a colony count too numerous to count. Patient was given meropenam and vancomycin for 6 weeks along with an external defibrillator until the course was completed. The immunosuppressants were stopped for this time period. CONCLUSION - Device related infection is an important complication of cardiac device use with a reported incidence rates of 0-0.8%. Staph species accounts for more than two-thirds of cases in most series. Gram negative rods are implicated less often. Morganella morgagni is a very rare device related infection/endocarditis. This case highlights the importance of considering device related infection in patients who present with functional decline, even without clinical signs of infection. Early diagnosis, appropriate antibiotics and removal of infected hardware increase the chance of survival.
39 BRUGADA BLUES
Isaac J1, Bennett BA1,2. 1 University of Mississippi Medical Center, Jackson, MS and 2 University of Mississippi Medical Center, Jackson, MS.
Case Report: Brugada Syndrome (BrS) is associated with ventricular arrhythmias in structurally normal hearts and sudden cardiac death (SCD) is often its initial presentation. The condition has a genetic component involving myocardial sodium channel mutations. The characteristic findings of BrS on electrocardiogram (ECG) are a right bundle branch block pattern with coved ST elevation in leads V1-V3. While there are several known triggers that can induce ventricular arrhythmias in patients with BrS, this case presents a potential trigger that has never been described.
A 17 year old black male with a family history of SCD presented to the Emergency Department (ED) after a witnessed syncopal episode. He was intubated in transport for airway protection and sedated at the time of arrival in the ED. Pupils were sluggish and initial laboratory data was unremarkable. However, he was noted to have Brugada pattern on ECG (Figure). Computed Tomographic images of the head were unremarkable and neurologic evaluation including electroencephalogram suggested the patient suffered a hypoxic seizure. Echocardiography was normal. Initial history and medication review did not provide insight into the mechanism of the patient’s cardiac arrest. However, on the night of admission an anonymous caller reported that the patient smoked “Blue Cheese Weed” (a psychotropic variant of marijuana) on the day of his arrest. The patient regained consciousness and full neurologic function.
Several pathophysiologic (fever, infection, sympathomimetic activation) and pharmacologic stimuli for malignant arrhythmias in patients with BrS have been identified. Only a few case reports have identified marijuana as a potential trigger for BrS; however this is the first report of “Blue Cheese Weed” associated with SCD in BrS.
40 NOT JUST ACUTE CHEST
Adimora-Nweke D, Bowles E. Tulane University SOM, New Orleans, LA.
Case Report: A 16 year-old African American male with hemoglobin SS disease and history of acute chest syndrome presented with progressively worsening sharp substernal chest pain and dyspnea on exertion for one week. The pain was worse with any movement. He denied cough, any recent illnesses, but he complained of fatigue, nausea with one episode of vomiting. Prior vaso-occlusive crises were in limb joints. Family history was significant for sibling with sickle cell disease and lupus.
On exam, he was tachycardic to 140s with SpO2 of 90%. He spoke in full sentences and his lungs were clear to auscultation. His cardiac exam revealed muffled heart sounds without murmurs or rubs. There was no jugular venous distension.
Chest x-ray revealed enlarged cardiac silhouette. EKG showed electrical alternans. Echocardiogram showed large pericardial effusion with respiratory variation of mitral inflow with right atrial and ventricular collapse. The patient was diagnosed with cardiac tamponade and subsequently underwent emergent pericardial window with drainage of 850 mL of serous fluid. Pericardial fluid was sent for lab analysis.
When evaluating a pediatric patient with chest pain, it is important to consider the most common etiology and also the most life threatening. Musculoskeletal conditions including costochondritis and slipping rib syndrome account for the largest category of known etiologies. In patients with underlying comorbidities, diagnoses unique to these conditions must also be considered.
In patients with sickle cell disease, acute chest syndrome is a potentially fatal cause of chest pain and must be considered. Along with chest pain, these patient present with a new pulmonary infiltrate involving at least a lung segment, fever, tachypnea, wheezing, or cough. Conversely, other causes of chest pain including cardiac conditions must equally be considered. Cardiac conditions like myocarditis, pericarditis, tachyarrhythmia, aortic root anomalies, left ventricular outflow obstruction, and coronary anomalies are serious causes of chest pain and can also occur in patients with sickle cell disease as with other patients. Patients with angina chest pain, dyspnea on exertion not attributed to a respiratory cause, and syncope should be evaluated for an underlying cardiac etiology. This evaluation involves history, physical exam, EKG, CXR, and echocardiogram.
41 HOLT ORAM: THE FORGOTTEN HEART-HAND SYNDROME
Ricci Gorbea F, Cox Rosario R. University of Puerto Rico Medical Science Campus, San Juan.
Case Report: A 29 years-old male presented with two months history of palpitations, shortness of breath and near-syncope episodes. Physical exam was compatible with an irregularly-irregular rhythm and “long” thumbs of both hands. Family history revealed a father with associated upper limb abnormalities and an Atrial Septal Defect.
A 24-hour Holter revealed episodes of atrial flutter and atrial fibrillation, with associated sinus pauses greater than 3 seconds. Transthoracic echocardiogram revealed a normal structural heart with preserved LV systolic function. Electrophysiologic study showed a counterclockwise typical atrial flutter. A successful cavotricuspid isthmus ablation was performed. A permanent pacemaker was placed in view of symptomatic Sick Sinus Syndrome.
Holt Oram Syndrome also known as “Heart-Hand” Syndrome is an autosomal dominant inherited disorder characterized by skeletal abnormalities of the upper limbs and heart problems. It is estimated to affect 1 in 100,000 individuals. It is secondary to a mutation in the TBX5 gene that plays a role in dividing the heart into four chambers (cardiac septation) and plays a critical role in regulating the development of bones in the arms and hands. Cardiac abnormalities include ASD, VSD and conduction abnormalities like bradycardia and arrhythmias. Upper limb abnormalities include affected carpal bones in the wrist area, a hypoplastic thumb or a thumb that looks like a finger. These skeletal abnormalities may affect one or both upper limbs.
Adolescent Medicine and Pediatrics Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
42 PREVALENCE OF SEXUALLY TRANSMITTED INFECTIONS AMONG ADOLESCENTS ENTERING CHILD PROTECTIVE SERVICES
Benjamins L1, Montgomery D2,3, Cheung K3. 1 University of Texas School of Medicine, Houston, Houston, TX; 2 Texas Woman’s University College of Nursing, Houston, TX and 3 University of Texas School of Medicine, Houston, Houston, TX.
Purpose of Study: Adolescents and young adults ages 15-24 years old have the highest rates of sexually transmitted infections (STIs). Persons in this age group have been estimated to acquire about half of all incident STIs although they represent only 25% of the sexually active population. Many believe that adolescents in protective services custody are at even greater risk of acquiring STIs, however current recommendations from the American Academy of Pediatrics are to test for STIs based on history and/or symptoms. We set out to assess the prevalence of STIs among adolescents between the ages of 12 to 18 seen in the Harris County Protective Services Clinic in order to better assess the need for routine screening.
Methods Used: We conducted a retrospective chart review of adolescents presenting to the Harris County CPS clinic from January 2009 to December 2011. Results of STI testing were abstracted from the charts. Approval from the Institutional Review Board was obtained.
Summary of Results: Among 437 patients, about 60% were female, mean age of 15. Approximately 45% were African-American, not Hispanic; just over 20% were Hispanic. There were 27 (6%) cases of chlamydia, 12 gonorrhea, 3 cases of syphilis, and no cases of HIV. Three of the teens who reported never having sex were positive for an STI. Female, older than 14 and reporting having had sexual intercourse at least once were all significant risk factors for testing positive for an STI.
Conclusions: The prevalence of sexually transmitted infections in adolescents entering foster care was comparable to the national average. Screening by history alone would have missed about 10% of chlamydia infections. Therefore, a recommendation for routine screening of all youth in this population for STIs, including HIV testing, is important to ensure better detection and treatment.
43 PERMISSIVE CONTRIBUTIONS OF PROSTACYCLIN AND NO TO CEREBRALVASODILATION TO H2S IN NEWBORN PIGS
Chang K, Berger C, Fedinec AL, Leffler CW. UTHSC, Memphis, TN.
Purpose of Study: Hypoxic-ischemic brain injury is a leading cause of mortality and chronic disability in newborns, causing brain dysfunction and neuronal death. Therefore, it is important to understand the pathophysiology of hypoxic-ischemic insult and use modulators of cerebral vascular responses as potential key targets for intervention. Hydrogen sulfide (H2S) is a gaseous, endogenously produced, signaling molecule involved in control of blood pressure and tone of arteries and arterioles from certain vascular beds. H2S is a functionally significant dilator in the newborn cerebrovascular circulation. Regulatory mechanisms of dilation due to H2S exposure are unclear. Prostaglandins and nitric oxide (NO) are also important in regulation of neonatal cerebral blood flow that affect similar regulatory pathways as H2S. Therefore, this study is designed to address the hypothesis that prostacyclin and NO provide a permissive enabling influence on the newborn cerebrovascular circulation that allows vasodilation to H2S.
Methods Used: In vivo experiments were conducted using newborn pigs with surgically implanted, closed, cranial windows.
Summary of Results: Topical application of H2S (10-6, 10-5, and 2 x 10-5 M) dilated pial arterioles in a concentration-dependent manner. This dilation was blocked by indomethacin, a COX inhibitor (10-6 M) that blocks production of prostacyclin. The prostacyclin analog iloprost restored dilation in response to H2S in indomethacin-treated piglets. The NO donor sodium nitroprusside (SNP) also restored H2S-induced dilation blocked by indomethacin.
Conclusions: Overall, data indicate that both iloprost and SNP can restore responses to H2S that have been blocked by COX inhibition. These data in newborn pigs suggest that a signal common to PGI2 and NO is required for H2S-induced cerebrovascular dilation to occur.
44 EVALUATION OF FAMILY PERCEPTIONS OF SAFETY IN A PEDIATRIC EMERGENCY DEPARTMENT
Dick R1,2, Sidhu N1,2, Gohman T1,2, Willis C1,2, Thompson T1,2. 1 University of Arkansas for Medical Sciences, Little Rock, AR and 2 Arkansas Children’s Hospital, Little Rock, AR.
Purpose of Study: Arkansas Children’s Hospital utilizes the services of a national firm that specializes in improving health care by surveying customers after discharge from hospitals. The firm generates results of the surveys, compares findings from various hospitals and provides feedback to the hospitals. The emergency department staff at Arkansas Children’s Hospital wished to improve the scores they receive regarding safety. The questions that are asked on the standard survey administered by the national firm do not delineate specific aspects of safety. In this study, the specific issues considered by families concerning safety in the emergency department are investigated.
Methods Used: Parents and patients were surveyed during their visit to the Arkansas Children’s Hospital Emergency Department. The purpose of the survey was explained to parents or patients and they were asked if they would be willing to participate. The survey contained the following questions: “Using a scale from 1 to 5, 1 being the lowest and 5 being the highest, how would you rate the level of safety experienced during your visit? We are trying to understand what safety means to you. Specifically, what factors did you consider when scoring the question?” This project was deemed as a quality improvement project exempt from IRB review at our institution.
Summary of Results: Fifty four families agreed to participate in the survey and answer the questions. Families identified several factors that affect their perception of safety at Arkansas Children’s Hospital Emergency Department. Preliminary analysis of the data shows the most common issues as follows: security/police 29.6% (n=16), cleanliness 20.3% (n=11), staff 11.1% (n=9), metal detectors 12.9% (n=7), care 11.1% (n=6), security badges 11.1% (n=6) and multiple checks to determine correct patient 11.1% (n=6). The majority of those surveyed (92.6%) rated overall safety as 5.
Conclusions: Patients and families are generally satisfied with the level of safety at Arkansas Children’s Hospital Emergency Department. Multiple factors were identified that affect perceptions of safety. These factors may be utilized by leaders and staff to focus efforts in maintaining and improving safety for patients and families.
45 ASSOCIATION OF SYSTEMIC INFLAMMATORY RESPONSE SYNDROME WITH CLINICAL OUTCOMES OF PEDIATRIC PNEUMONIA PATIENTS
Frazier SB, Sepanski R, Zaritsky AL, Bovat C, Mangum C, Oelberg DG, Godambe SA. Children’s Hospital of The King’s Daughter’s, Norfolk, VA.
Purpose of Study: The systemic inflammatory response syndrome(SIRS) may complicate pneumonia; when present, it suggests the patient’s pneumonia is more severe. If so, recognition of SIRS in a child with pneumonia requires more careful evaluation. To evaluate this hypothesis, we examined the relationship between the presence of SIRS and adverse clinical outcomes amongst children with pneumonia.
Methods Used: Retrospective chart review was performed on children with community-acquired pneumonia who presented to the Children’s Hospital of The King’s Daughters Emergency Department(CHKD-ED) from Jan 1-Mar 31, 2013. Subjects were identified using ICD-9 codes for pneumonia. Vital signs and white blood cell counts while in the CHKD-ED were utilized for this analysis. SIRS was determined by a modified criteria developed by Goldstein et al. that requires an abnormal temperature-corrected heart rate or respiratory rate and either an abnormal temperature or white blood cell count(WBC). Abnormal vitals and WBC used to determine SIRS were adjusted based on the patient’s age. Morbidity endpoints included one or more of the following: inpatient(IP)/observation(Obs) status or subsequent return to the ED for pneumonia, need for video-assisted thoracoscopic surgery(VATS), and total hospital length of stay(LOS), measured from ED triage assessment to final discharge from the hospital(ED, Obs, or IP).
Summary of Results: 276 children met study criteria and were included in the analysis. Pneumonia patients with SIRS (n=38) had a 79% rate of hospital admission or ED readmission compared with 34.5% of SIRS (-) patients (n=238) (p<.0001). Pneumonia patients with SIRS were at greater risk of requiring VATS (18.4% vs. 0.8%, p<.0001). Additionally, pneumonia patients with SIRS had a significantly longer median LOS than pneumonia patients without SIRS (2.7 vs 0.19 days, p<.0001).
Conclusions: SIRS in children with community-acquired pneumonia is associated with a significantly higher likelihood of experiencing one or more of the following outcomes: IP/Obs hospital admission or later return to the ED; subsequent VATS procedure; or longer LOS. Based on these observations, a sepsis screening tool that identifies SIRS in children with pneumonia should increase the physician’s concern about the patient.
46 STEP WISE APPROACH TO TRANSITION OF CARE AND EXISTING CHALLENGES IN ADOLESCENTS WITH SICKLE CELL DISEASE (SCD)
Freeman B1,3, Benton M2, Gold H3, Wong S3, Chavan R2,3. 1 Tulane University, New Orleans, LA; 2 Tulane University, New Orleans, LA and 3 Tulane University, New Orleans, LA.
Purpose of Study: A patient education resource to help patients with SCD to successfully transition from adolescent to adult care and become aware of common complications of sickle cell disease in the adolescent and young adult age range.
Methods Used: Major organ complications that are associated with SCD and specific to adolescence were highlighted. Additionally, the most relevant and identifiable symptoms for each organ system were provided. Next, the challenges of transition to adult health care were addressed. Both the psychological effect on adolescent with SCD and the processes involved in adult-centered care are discussed. Finally, important tips for staying healthy and managing SCD are provided in an informative “dos and don’ts” format.
Summary of Results: With appropriate treatment and management, the life expectancies for children with SCD have significantly improved and many are surviving well into adulthood. However, the period of transition to adult care is a particularly vulnerable time, for the following reasons: 1) In addition to acute pain, SCD is associated with numerous organ complications, many of which are specific to adolescence; 2) SCD complications may be exacerbated by the inevitable developmental and lifestyle changes associated with adolescence; and 3) Compliance with self-care and medical treatments, as well as adjusting to the constraints of living with a chronic disease, is a challenging issue in this age group.
Conclusions: While the survival rates for children with SCD have dramatically increased, due to the many complications and challenges associated with adolescence, transition programs are critical in helping SCD patients successfully transition into adult care. As a part of a step-wise, patient-centered transition program, this information will serve as a patient education tool that will empower SCD adolescent patients and help them adequately prepare for transition.
47 A CROSS SECTIONAL STUDY OF INTESTINAL MICROBIOME IN CHILDREN WITH CYSTIC FIBROSIS
Kasi N1, Harris WT3, Morrow C2, Dimmitt R1, Matthew S1. 1 University of Alabama at Birmingham, Birmingham, AL; 2 University of Alabama at Birmingham, Birmingham, AL and 3 University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: Children with cystic fibrosis (CF) are prone to intestinal dysbiosis due to CFTR dysfunction in the intestinal epithelium, recurrent antibiotic exposure, and a CF-specific high fat diet. The clinical relevance of the disturbed intestinal microbiome to CF clinical outcomes is not well-understood.
We hypothesize that intestinal dysbiosis in pediatric CF leads to malnutrition and pulmonary deterioration.
Our study aims to analyze the microbiome in pediatric CF, identifying alterations in CF patients compared to healthy controls. We will study the presence of dysbiosis in children with CF and its relation to nutrition (BMI), vitamin deficiency, gastrointestinal manifestations (abdominal pain, GERD, hepatobiliary disease), and pulmonary function.
Methods Used: To test this hypothesis we conducted a Cross sectional observational study to profile the fecal microbiome in children with CF. We compared the fecal microbiome of children 3-18 yrs of age to age matched healthy controls. Intestinal microbiome analysis was performed on stool specimens using culture independent 16S rRNA gene sequencing technology.
Summary of Results: Children with CF had significantly lower microbial diversity compared to controls (Shannon index, p = 0.008 and Simpson index, p = 0.0114). There was also a significant variability of the microbiota between the samples, within the CF group compared to controls (beta diversity). The major intestinal phyla were comparable between the two groups. The CF group had significantly higher colonization by pathogenic enterobacteriales (p= 0.008).
Conclusions: The results of our study provides evidence of intestinal dysbiosis in children with Cystic fibrosis. A longitudinal study of the temporal variability in the intestinal microbiome in association with antibiotic exposure, nutritional status, gastrointestinal symptoms, and pulmonary function, will provide the foundation for understanding the impact of the intestinal microbiome in pediatric cystic fibrosis.
48 CLINICAL VARIABILITY OF OSTEOGENESIS IMPERFECTA WITHIN FAMILIES
Kavanagh K, Andersson H, Morava-Kozicz E. Tulane, New Orleans, LA.
Purpose of Study: Osteogenesis Imperfecta (OI) is a rare connective tissue disease affecting less than 200,000 patients in the U.S. The current classification system categorizes OI into types I, II, III and IV by clinical symptoms and genetic components. The difference between the four main clinical subtypes is their prognosis, dentinogenesis (DI), hearing loss, color of sclera, stature, skeletal dysplasia and heritability. The current classification system based on clinical phenotype makes it more difficult to diagnose OI subtype in members of families with differing phenotypes. We evaluated the variability of OI phenotypes within two families to assess the accuracy of clinical prognostication in affected offspring.
Methods Used: In one family, the patient had few postnatal fractures and blue sclera. Her mother had blue sclera, pathologic fractures, short stature and DI, while her maternal uncle had only hearing loss. All three family members carry the same mutation in the COL1A1 gene but exhibit differing levels of severity. In the second family, the patient was noted to have rhizomelic shortening of her lower limbs on prenatal ultrasound and at birth was found to have skeletal dysplasia and hearing loss. Her mother had postnatal fractures, short stature, DI and blue sclera. Family history revealed that Mom has a paternal aunt with a more severe form of OI and no other affected family members.
Summary of Results: Two families with OI showed phenotypes ranging from mild to severe with the same gene mutation. The first patient had few fractures and blue sclera, while her mother had blue sclera, pathologic fractures, short stature and DI, and her paternal uncle had only hearing loss. In the second family, the patient had prenatal skeletal dysplasia and hearing loss, while her mom had postnatal fractures, short stature, blue sclera and DI. Mom’s father was unaffected and mom’s paternal aunt had a more severe form with multiple fractures and inability to have children.
Conclusions: Based on the clinical variability observed within families carrying the same mutation, we suggest that OI is a clinical continuum, since even first degree family members could be diagnosed with the severe neonatal form (type III) or the mildest form (type IV). We emphasize that having a mild phenotype with OI doesn’t mean that the next generation cannot develop a life threatening form of OI.
49 CHARACTERISTICS OF PEDIATRIC PATIENTS ENROLLED IN DIABETES TRANSITION PROGRAM
Khawaja M, Lewis K, Paulo R, Bowlby D. Medical University of South Carolina, Charleston, SC.
Purpose of Study: Medical care for adolescents with diabetes mellitus (DM) as they transition from pediatric to adult care is important. Studies have shown poor glycemic control, higher rates of diabetic ketoacidosis (DKA) admissions and lower clinic attendance in adolescents. Several factors contribute to poor management of DM during this transition period. The multidisciplinary Diabetes Transition Program at the Medical University of South Carolina (MUSC) will improve patient care. The purpose of this study is to characterize the initial cohort enrolled in the Diabetes Transition Program at MUSC.
Methods Used: A retrospective chart review collected data (N=133) from May 31st 2012 to June 1st 2013 on patients enrolled in the Diabetes Transition Program.
Summary of Results: The average age was 17.05 ± 1.08 yrs with 51% males and 71% were non-Hispanic white. 88% of patients were type 1 DM, and 71% were using multiple daily insulin injections. The average A1C was 9.17 ± 1.92%, with only 19% of patients reaching their A1C goal. 6% of patients had a DKA admission. 9% had nephropathy, 8% had hyperlipidemia, 7% had thyroid disease, and 5% had celiac. 15% had ADHD and 9% had depression. 67% of patients lived in a 2 parent household; however Department of Social Services involvement was present in 7% of patients. Only 70% of patients received annual screening evaluation. Only 32% of patients had at least 4 annual clinic visits. 27% had Medicaid.
Conclusions: This study supports previous data that has shown adolescents are poorly managing their DM. The goal of the Diabetes Transition Program at MUSC is to improve DM care including attaining A1C goal, decreasing DKA admissions, and increasing clinic visits. This initial cohort data will be used to monitor outcomes as patients transition from pediatric to adult care in the Diabetes Transition Program.
50 NEUROLOGIC ADVERSE EVENTS DURING PEDIATRIC CHEMOTHERAPY PREDICT NEUROCOGNITIVE DEFICIT
McCulloch M1,2, Krull K2. 1University of Tennessee College of Medicine, Memphis, TN and 2St. Jude Children’s Research Hospital, Memphis, TN.
Purpose of Study: The impact of chemotherapeutic agents on health outcomes in cancer survivors is currently a popular area of study. However, there is a lack of studies examining the relationship between actual adverse events experienced during chemotherapy and post-therapy outcomes. This study was conducted to further investigate the potential of adverse events to predict specific deficits after chemotherapy. Specifically, this study examined the relationship between adverse events during pediatric acute lymphoblastic leukemia (ALL) chemotherapy and neurocognitive deficits at the end of therapy.
Methods Used: Adverse event data were collected according to National Cancer Institute criteria for patients on an ALL treatment protocol without prophylactic cranial irradiation. Patients underwent a comprehensive neurocognitive battery at the end of therapy to screen for deficits in intelligence, attention, academics, and behavior. Analyses were performed to examine associations between specific AEs and neurocognitive deficits.
Summary of Results: Thirty-three percent of enrollees experienced a neurological AE. The overall cohort showed significantly impaired means as well as impairment rates for attention (P<.0001) and psychosomatic measures (P<.0001). Patients who had a seizure showed a below-average math score compared to those without a seizure (P=.003). Patients who experienced neuropathy (sensory or motor) or more than two types of neurological AE demonstrated diminished intelligence quotients compared to those without neuropathy (P=.006 and P=.005, respectively). Finally, children with severe neuropathy showed highly impaired psychosomatic scores (P=.001).
Conclusions: These results support the role of neurological AEs in predicting the risk for neurocognitive deficit after chemotherapy in pediatric ALL. Specific AEs should be used as indicators to initiate interventions that limit associated neurocognitive deficits and chemotoxicities. More broadly, this study is one of the first to demonstrate that chemotherapy adverse events can predict impaired outcomes after treatment and thus hold great clinical utility.
51 CYTOGENOMIC ABERRATIONS ARE COMMON DEFECTS IN PATIENTS WITH ISOLATED MULTICYSTIC DYSPLASTIC KIDNEY
Monlezun D1, Chen T1,2, Ramalingam A1,2, Song R1,2, Janssen A1,2, Preston G1,2, Yospiv I1. 1 Tulane University School of Medicine, New Orleans, LA and 2Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: The pathogenic roles of cytogenomic aberrations for isolated multicystic dysplastic kidney (MCDK) has not been well investigated yet. We performed Array Comparative Genomic Hybridization (aCGH) in 10 children with isolated MCDK to reveal the pathogenic mechanisms underlying MCDK.
Methods Used: Patients (six female and four males, mean age 8.5+/- 1.1 years) were diagnosed with MCDK by ultrasonography. All patients had normal renal function at the time of blood specimen collection. Genomic DNA was isolated from blood leukocytes and buccal cells. aCGH was performed on Agilent 105K array according to the manufacturer’s protocol. Data was analyzed using Cytogenomic software package from Agilent. Quantitative PCR (qPCR) was performed on patients and their parents for each detected aberration with reference control. The relative copy number was calculated by DDCt method.
Summary of Results: Three pathogenic aberrations were detected in three patients. The first aberration (deletion of 2.07 Mb at 7p14.3) includes a region containing 12 genes, including BBS9 and BMPER genes. The second aberration (duplication of 3.28 Mb at 16p13.11p12.3) includes a region encoding 20 genes. The third aberration is a monosomy X for a female patient. qPCR demonstrated that deletion at 7p14.3 was paternally inherited, while the duplication at 16p13.11-p12.3 was maternally inherited. The third aberration was monosomy X that resulted from meiotic nondisjunction in oogenesis or spermatogenesis.
Conclusions: Our results demonstrate that 30% of MCDK patients possessed cytogenomic aberrations. Mutations in BBS9 and BMPER have been shown to produce cystic kidney dysplasia with cystic kidneys, suggesting the pathogenic function for the deletion at 7p14.3. However, these two aberrations were inherited from parents, indicating that complex molecular mechanisms underlie pediatric MCDK. We conclude that: 1) cytogenomic aberrations represent a common genetic defect in MCDK patients, and 2) aCGH is a valuable tool to reveal pathogenic mechanisms of MCDK in humans.
52 GASTROSCHISIS: OUTCOMES OF EXTREMELY PREMATURE INFANTS
Nice T1, Russell R1, Harmon CM1, Fineberg NS2, Rogers D1, Martin C1, Chaignaud B1, Anderson S1, Chen M1, Beierle E1. 1 Children’s of Alabama, Birmingham, AL and 2 University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: While prior research has examined the management of gastroschisis in premature infants, there has been little information focused on extremely premature infants. The purpose of this study was to identify potential differences in treatments and outcomes of gastroschisis in very premature versus later gestational age infants.
Methods Used: A retrospective review of all infants with gastroschisis was performed from October 1999 to December 2012. Infants were stratified based on gestational age: group 1 (very premature <32 weeks); group 2 (near-term 32-37 weeks); and group 3 (term > 37 weeks). Demographic and treatment data were collected. Outcome measures included length of stay, TPN days, total operations and non-CVL(central venous line)-related operations, sepsis, NEC, and death. Analysis was done using Chi square and ANOVA.
Summary of Results: A total of 247 infants were included: 13 very premature, 121 near-term, 113 term. Demographically the groups differ only by gestational age, birthweight, and lower APGAR scores in group 1. Treatment was similar across all groups. Group 3 had lower risk of complicated gastroschisis. Compared to both other groups, group 1 was more likely to require a non-CVL-related operation within the first year. Group 1 also experienced a longer length of stay, increased ventilator days, increased TPN days, increased risk of sepsis, and increased mortality. [Table 1]
Conclusions: Extremely premature infants with gastroschisis underwent similar treatment but required more operations, total parenteral nutrition and ventilator days, and had a higher risk for sepsis and death. While many did well, survival is markedly lower (62%) and proper parental counseling is important for these infants.
53 VERTEBRAL OSTEOMYELITIS DUE TO EIKENELLA CORRODENS AND STREPTOCOCCUS CONSTELLATUS IN A PEDIATRIC PATIENT
Nye S1, Balan A1, Ramji F2. 1 University of Oklahoma Health Science Center, Oklahoma City, OK and 2 University of Oklahoma Health Science Center, Oklahoma City, OK.
Case Report: Introduction: Vertebral osteomyelitis is an uncommon infection in children representing 1-2% of osteomyelitis cases. Infections due to Eikenella species have been described in adults; however pediatric infections due to Eikenella species have only rarely been reported. We present the case of an 11-year old boy with vertebral osteomyelitis due to Eikenella corrodens and Streptococcus constellatus.
Case Description: A previously healthy 11-year old Hispanic boy presented with a 6-month history of worsening right-sided occipital headaches and pain radiating down his neck. He reported phonophobia, but denied any visual changes, nausea, vomiting, or fever. He had been taking pain medications around the clock. On physical exam, he had trismus, decreased range of motion and tenderness to palpation over the right side of his neck, but no erythema or warmth was present.
An MRI of the head and cervical spine revealed a rim-enhancing fluid collection extending from the atlanto-occipital articulation into the surrounding soft tissues. In addition, hyper-intense changes in the marrow of the right petrous, mastoid and temporal bones, occiput, and C1 vertebra were demonstrated, consistent with osteomyelitis. The middle ear cavities were clear.
Given his chronic indolent course, tuberculosis was highly suspected, and he was briefly on anti-tuberculous drugs.
Though technically difficult, a CT-guided needle aspiration of the fluid collection was performed and the culture was positive for E. corrodens ampicillin MIC 0.25 mcg/ml and S. constellatus penicillin MIC<0.03 mcg/ml. The patient received antibiotics for six months. Follow up imaging revealed resolution of his osteomyelitis.
Discussion: While E. corrodens and S. constellatus are commensal organisms, they can cause serious infections, typically within the head and neck. Our report describes an uncommon infection due to uncommon organisms and illustrates the utmost importance of obtaining an adequate specimen for culture to ensure adequate therapy and excellent outcome.
Adolescent Medicine and Pediatrics Joint Plenary Poster Session and Reception 5:00 PM Thursday, February 20, 2014
54 FEVER AND A RECURRENT RASH: A CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Paccione R, Leong K, Khalique S, Roy M. LSUHSC-New orleans, New Orleans, LA.
Case Report: Introduction: Hemophagocytic lymphohistiocytosis (HLH) is an immune system over activation that can be life-threatening without appropriate diagnosis and treatment.
Case: A 16 month old female presented after a complicated course which initially began as three skin lesions on her left cheek associated with a high fever. She was placed on various antibiotics, but the rash persisted and progressed to extreme swelling of her face, eyes and lips. She was treated with IVIG and IV solumedrol for two weeks with apparent improvement. Upon discontinuation, the fever recurred. Upon arrival to CHNOLA, she was re-started on IV steroids, IVIG and covered with broad spectrum antibiotics. On laboratory workup, thrombocytopenia, anemia and an elevated ferritin of 3966 ng/ml were found. Further evaluation of NK function, soluble IL-2R and PRFl gene sequence revealed absent NK cell function. Bone marrow biopsy revealed hymophagocytosis. Based on these findings, the diagnosis of HLH was made.
Discussion: Hemophagocytic lymphohistiocytosis is a rare and life threatening condition. It involves over activation of histiocytes and T cells, which secrete numerous cytokines that will infiltrate and damage tissues causing multi-organ destruction. The natural killer cell activity will be depressed or absent in these patients.
Features of the disease may seem quite non-specific and can look similar to a febrile illness. The clinical signs can include a prolonged fever, hepatomegaly, lymphadenopathy, splenomegaly, neurological findings and rash. Laboratory findings are remarkable for cytopenias, a markedly elevated ferritin, elevated liver transaminases and hypertriglyceridemia. All patients with suspected HLH should have a bone marrow examination to assess for hemophagocytosis and/or the cause of cytopenias.
Conclusion: Hemophagocytic lymphohistiocytosis is a condition where the diagnosis can easily be missed due to lack of awareness. A judicious diagnosis is imperative for achieving optimal treatment results and reducing mortality from rapid disease progression.
55 KAWASAKI DISEASE, WHY SO COMPLICATED?
Patel B. University of South Alabama, Mobile, AL.
Case Report: Atypical Kawasaki disease presents with five days of fever and four of the five following criteria; erythema of palms, soles, edema of hands and feet, or periungual peeling of fingers and toes after 2-3 weeks, polymorphous exanthem, bilateral non-exudative conjunctival injection, changes in lips of oral cavity with erythema or cracking, strawberry tongue, or diffuse erythema of oral or pharyngeal mucosa, unilateral cervical lymphadenopathy, all in the absence of other confounding diseases. Atypical Kawasaki disease presents with fever of 5 days and two of the clinical features of Kawasaki disease. This disease has the potential for a variety of complications including: congestive heart failure, myocarditis, pericarditis, valvular regurgitation, coronary artery abnormalities, aneurysms of medium-sized non-coronary arteries, raynaud phenomenon, peripheral gangrene, arthritis, arthralgias, hepatic dysfunction, hydrops of gallbladder, aseptic meningitis, extreme irritability, sensorineual hearing loss, urethritis, meatitis, or anterior uveitis.
We encountered the case of a 5-year old African American male who presented in hypovolemic shock secondary to complications from atypical Kawasaki disease. This patient had an unusual and complicated hospital course developing transaminitis, acute renal failure secondary to renal vasculitis, and carditis with dilated right and left coronary arteries eventually leading to the formation of a saccular aneurysm.
This unique case illustrated the importance of knowing the common and uncommon complications associated with Kawasaki disease and being able to quickly recognize the disease process so that complications could be avoided.
56 MRSA STRIKES AGAIN
Patel SK, Monroe K, Diaz F. UAB, Birmingham, AL.
Purpose of Study: Patient is a 13yo AAM previously healthy presenting with shortness of breath. He was seen in the ED two days prior with left shoulder pain and subjective fever for several days. Shoulder Xray was read as normal and he was discharged with scheduled ibuprofen. That same day, he was getting off the couch and hit his left leg on the table. Over the next two days, he had worsening shoulder and leg pain. On day of admission, he began complaining of shortness of breath. On arrival, vitals were concerning for tachycardia and tachypnea and saturations of 96-99% on 4L O2 (88% on RA). He was afebrile. Physical exam revealed significant point tenderness on the left humerus and tibia with a 3cm circumferential difference of left calf compared to the right. His lung exam revealed diffuse rales and crackles bilaterally. He was alert and oriented. In addition, he had mild scleral icterus.
Methods Used: Lab work revealed a Lactate of 4.7 with a normal venous blood gas. WBC was 7.7. CMP was significant for Cr to 1.2, BUN of 40, Bicarbonate 16, Chloride 95, ALT 93, AST 225, and Total Bilirubin of 4.8 with direct predominance. LDH (1380), UA (26), ESR (16) and CRP (26) were elevated. CTa revealed multiple bilateral lung nodules and small pulmonary artery thrombus. D-dimer was >10,000.
Blood cultures were obtained and Vancomycin was started for coverage of potential underlying sepsis. Leg ultrasound showed a nonocclussive DVT from distal left superficial femoral vein through the popliteal vein.
Summary of Results: He was admitted to the PICU and remained on 4L of O2 for some time but was switched over to CPAP for respiratory support. He received multiple rounds of fluid resuscitation. Few hours later, he was intubated and required inotropes. He developed and continued to have fevers. Lovenox was started for DVT management. Vancomycin and Nafcillin were started for concern of MRSA/MSSA sepsis. The initial set of blood cultures grew staph, later speciated to MRSA. Repeat daily blood cultures continued to grow MRSA.
Conclusions: A bone scan revealed osteomyelitis of left femur and left tibia that was confirmed by MRI. The Orthopedics team performed serial taps to these locations with cultures that grew MRSA.
The patient was extubated to BIPAP two weeks after admission, and blood cultures 10 days after admission stopped growing MRSA. He made a full recovery and was discharged home.
57 DOES OBESITY CONTRIBUTE TO MISSED DIAGNOSIS OF APPENDICITIS IN CHILDREN AND ADOLESCENTS? A RETROSPECTIVE REVIEW
Patel S1, Shipon C1, Warner R2, Burns JJ1, Walck J1. 1 FSU College of Medicine, Pensacola, FL and 2 Lake Erie College of Osteopathic Medicine, Bradenton, FL.
Purpose of Study: Obesity rates in the United States among children and adolescents are approximately 17% with 12.5 million affected. Appendicitis is one of the most common pediatric conditions requiring emergent abdominal surgery. The diagnosis of appendicitis in the pediatric population can be challenging. Although in one study, obese patients had higher rates of perforation at presentation, there is scant literature that evaluates if obesity is associated with an increased frequency of missed-diagnosis of appendicitis.The purpose of this study is to determine if obesity is associated with missed-diagnosis of appendicitis in children and adolescents.
Methods Used: A retrospective chart review from 2008 to 2013, of children ages 0-17 years, with a confirmed diagnosis of appendicitis at a West Florida Children’s Hospital, were selected. Obesity was defined as having a BMI equal to or greater than the 95th percentile for age and sex based on CDC charts. Cases where BMI percentiles could not be calculated because of missing age, sex, height or weight data were excluded. The definition of missed-diagnosis was having had more than one visit to the Emergency Department prior to diagnosis being made. Additional data collected included: age, sex and MANTRELS score, which is a measure developed to improve diagnostic accuracy of appendicitis. Statistical analysis was performed using multiple 2×2 analysis for univariate categorical data analysis, and logistic regression analysis for multivariate analysis.
Summary of Results: There were a total of 209 patients who were entered into the analysis with 16.7% found to be obese. 25.4% had a missed-diagnosis on at least one health care visit. No statistically significant relationship was found between obesity status and missed-diagnosis of appendicitis (Chi-square 0.818, df 1, p=0.366). Using a multivariate logistic regression, with age, sex, MANTRELS score and obesity entered into the analysis only age and sex were related to missed-diagnosis with females (p=0.001) and younger patients (p=0.004) being more likely to have a missed-diagnosis.
Conclusions: Obesity did not relate to having missed-diagnosis of appendicitis at the time of diagnosis. Younger age and female sex were related to missed-diagnosis.
58 THE RELATIONSHIP OF MANTRELS SCORE TO APPENDICEAL PERFORATION IN PEDIATRIC PATIENTS: A RETROSPECTIVE REVIEW
Patel S1, Shipon C1, Warner R2, Burns JJ1, Walck J1. 1 FSU College of Medicine, Pensacola, FL and 2 Lake Erie College of Osteopathic Medicine, Bradenton, FL.
Purpose of Study: Appendicitis is one of the most common conditions needing emergent operation in the pediatric population and can be difficult to diagnose. Studies have reported appendiceal perforation to be more common in children than adults with duration of symptoms, minority race and Medicaid insurance as risk factors. The purpose of this study is to determine if MANTRELS score is related to appendiceal perforation.
Methods Used: Children (ages 0-17 years) who had confirmed diagnosis of appendicitis from 2008 to 2013, at a West Florida Children’s Hospital were included in a retrospective chart review. MANTRELS score, a measure that was developed to improve diagnostic accuracy of appendicitis, was calculated for each patient. The scoring system includes the following elements: 2 points given for right lower quadrant abdominal pain and leukocytosis, 1 point given for presence of migration of pain to the right lower quadrant (RLQ), anorexia, nausea/vomiting, rebound pain, elevated temperature, leftward shift of white blood cell differential. Scores ≥7 are considered “appendicitis likely”.The MANTRELS score ≥ 7 was evaluated for relationship to appendiceal perforation using Chi-square 2×2 analysis; age, sex and MANTRELS score ≥ 7 was used for multivariate analysis using logistic regression.
Summary of Results: There were 203 patients entered into the analysis. On univariate analysis, a statistically significant relationship between MANTRELS score ≥7 and appendiceal perforation was found. (Chi-squared 11.744; p = 0.001). Using a multivariate logistic regression, with age, sex, and MANTRELS score entered into the analysis, a MANTRELS score of ≥7 was related to appendiceal perforation (p=0.004).
Conclusions: A MANTRELS score ≥7 was associated with appendiceal perforation in a pediatric population.
59 PSYCHOLOGICAL AND NEUROCOGNITIVE OUTCOMES IN SURVIVORS DIAGNOSED WITH CANCER AS AYA: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY
Prasad P1, Hardy K2, Zhang N3, Armstrong G3, Krull K3. 1 LSUHSC, New Orleans, LA; 2 Children’s National Medical Center, DC, DC and 3 St Jude’s Research Hospital, Memphis, TN.
Purpose of Study: To characterize psychological and neurocognitive function in cancer survivors diagnosed during AYA in the Childhood Cancer Survivor Study (CCSS), and to identify risk factors associated with impairment.
Methods Used: Participants were survivors (n=6192; mean 23.6 years from diagnosis) and siblings (n=390) who completed the CCSS Follow-up 2003 (FU 2003) survey, including the Brief Symptom Inventory and the CCSS - Neurocognitive Questionnaire. The associations between functional outcomes (employment, education, and living independently) and psychological and neurocognitive impairment were examined using logistic regression.
Summary of Results: Among the 6192 survivors, 2589 were diagnosed as AYA (1602 between 11-15 and 987 between 16-21). Compared to siblings, survivors reported significantly higher rates of somatization (15.6 vs. 6.7%; OR 2.36, 95%CI 1.55-3.60), depression (11.7% vs. 8.0%; OR 1.55, 95%CI 1.04-2.30), and anxiety (7.4% vs. 4.4%; OR 2.00, 95%CI 1.17-3.43). AYAs had higher impairment on the CCSS-NCQ, including problems with Task Efficiency (17.2% vs. 10.8%; OR 1.72, 95%CI 1.21-2.43), Emotional Regulation (19.1% vs. 14.1%; OR 1.74, 95%CI 1.26-2.40), and Memory (25.9% vs. 19.0%; OR 1.44, 95%CI 1.09-1.89); compared to survivors diagnosed at younger ages. Among survivors with a history of central nervous treatment (i.e., brain tumors or acute lymphoblastic leukemia) those treated during AYA had greater memory impairment compared to those treated at younger ages (34.9% vs. 30.8%; OR 1.21, 95%CI 1.02-1.43). Adjusted for current age and sex, survivors diagnosed as AYAs with impaired task efficiency (OR 2.93, 95%CI 2.28-3.77, p<.0001) or depression (OR 1.94, 95%CI 1.43-2.63, p<.0001) were more likely to be unemployed, while survivors with memory problems demonstrated reduced educational attainment (OR 1.45, 95%CI 1.17-1.79, p=0.0006).
Conclusions: AYA is a critical period of socioemotional growth and the diagnosis of cancer during this period has the potential to disrupt developmental processes related to educational goals and functions required for independent living. Since psychological and neurocognitive impairment is related to functional outcomes, further follow-up with the AYA survivors is necessary.
60 OUTCOMES OF ARTHROSCOPICALLY TREATED FEMOROACETABULAR IMPINGEMENT IN ADOLESCENTS WITH SLIPPED CAPITAL FEMORAL EPIPHYSIS AND LEGG-CALVE-PERTHES DISEASE
Rudd J1, Suri M1,2, Heinrich S2, Choate S1. 1 Ochsner Clinical Foundation, Jefferson, LA and 2 Children’s Hospital, New Orleans, LA.
Purpose of Study: Legg-Calve-Perthes disease and slipped capital femoral epiphysis are childhood hip diseases that have lifelong effects. They are severe deformities that lead to femoroacetabular impingement and ultimately earlier symptomatic osteoarthritis of the hip. Traditional open procedures to treat FAI cause significant morbidity and have significant recovery time. Arthroscopic hip osteoplasty has been described to treat these patients in a minimally-invasive manner. The purpose of this paper is to report outcomes of arthroscopically-treated FAI in SCFE and Perthes patients 18 years of age and younger.
Methods Used: Each patient that underwent hip arthroscopy by the senior author completed the Modified Harris Hip Score, VAS numeric pain scale, and the SF 12 questionnaire at standard intervals as part of an on-going quality improvement project. The data was collected prospectively and maintained in a password-protected spreadsheet. With IRB approval, we performed a retrospective review of the collected data and medical records focusing on adolescents who were 18 years of age or younger with diagnosed SCFE or Perthes disease.
Summary of Results: We had 8 patients that conformed to the criteria: 3 previous SCFE patients and 5 patients with Perthes disease. All patients underwent femoral neck osteoplasty with 1 SCFE patient and 3 Perthes patients having their labrum repaired. Six of the 8 patients had at least 2 year follow up. With the exception of one Perthes patient, all patients improved per the administered questionnaires. The one Perthes patient that did not improve had drastically worsening hip pain with worsening of each score on the questionnaires.
Conclusions: To our knowledge, there have not been any published results for post-SCFE arthroscopic osteoplasty in adolescents. There have been reports of the management and successful outcomes of hip arthroscopy in Perthes disease, however these studies include all ages treated and do not focus specifically on the adolescent population. Our study demonstrates that FAI in SCFE and Perthes adolescents can be treated successfully arthroscopically with reliable results to relieve symptoms and providing a less invasive option than the traditional open procedures to these patients.
61 12Q24.31 MICRO DUPLICATION: A NEW CASE AND REVIEW OF THE LITERATURE DR.LOCHAN SUBEDI M.D; DR. MARTINEZ M.D
Subedi L, Martinez J. University of South Alabama Children’s & Women’s Hospital, MOBILE, AL.
Case Report: Duplication of chromosome 12q is uncommon. Previously there has been few case reported for deletion at chromosome 12,but till date only one case has been reported for 12q24.31 duplication. Going to report a case of a male child born full term,normal vaginal delivery,no complication. Mom had an uneventful pregnancy was not on any medication.He was healthy after birth At age of 4 month he started to have respiratory problem like stridor,wheezing. He also had a weak ankle for which he use to wear braces. As he was consistently having respiratory problem he was seen by Pulmonologist at the age of 17 month when he was diagnosed with laryngomalacia. He was noticed to have dysmorphic facial feature along with speech and motor delay.For this region he was referred to Genetics. During his visit it was noticed that his HC was at 25%ile, height was 75th %ile, weight was 50th %ile. He had craniofacial dimorphism for low posterior hairline, short neck, thin upper lip,downward turned mouth, high forehead and dysmorphic looking ear. He also had inverted nipples and hypoplastic genitalia with a small scrotum. He was hypotonic and had global developmental delay. Genetic work up was done with chromosome analysis, DNA analysis for Fragile X syndrome and CGH array.CGH chromosomal array reveled a duplication of 12q24.31 region. 12q24.31 duplication is a rare genetic condition,which is associated with developmental delay.The first case reported on 12q24.31 duplication was in 2004. It was reported that duplication of the 12q region is a recognizable syndrome characterized by abnormally shaped skull,hypertelorism,flat nasal bridge with a downturned mouth, short neck with redundant skin, widely spaced nipples,occasional brain malformation and heart defect,cryptorchidism and intellectual disability. Our patient does have some of the feature that has been already described like short neck,downturned mouth along with which he also has other features like low posterior hairline, thin upper lip, high forehead and dysmorphic looking ear. He also had inverted nipples and hypoplastic genitalia with a small scrotum. He is also hypotonic and has global developmental delay. On last visit when he was 5 year and 6 month old it was noticed that he has underdeveloped teeth, which is widely spaced.
Adult Clinical Case Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
62 RENAL INVOLVEMENT AS SOLE PRESENTATION OF GOODPASTURE’S SYNDROME
Ali E, Fenire M, Bashir M, Mazek H, Aly M, Mohamed A. Texas Tech University Health Science Center/Lubbock, Lubbock, TX.
Purpose of Study: 1. We report a case of Goodpasture’s with only renal involvement.
2. Highlight that early aggressive treatment and supportive care are crucial. 3- Absence of pulmonary manifestation does not rule out Goodpasture’s.
Methods Used: Case analysis and literature review.
Summary of Results: 34 years old female with no significant past medical history presented with dysuria, polyuria and foamy urine associated with nausea, vomiting, generalized weakness and facial puffiness of one week duration. She was also found to have blood pressure of 178/92. Labs revealed creatinine of 5.3mg/dl, blood urea nitrogen of 60mg/dl and glormerular filtration rate of 9.26. Urine analysis revealed red blood cell casts, 300mg/dl proteinuria, and microscopic hematuria. Additional labs revealed positive antinuclear antibody and negative double standard DNA antibody, antistreptolysin antibody, and hepatitis panel. Antigolmerular basement membrance antibodies (Anti-GBM antibody) were strongly positive at 7.5 AI. Renal biopsy confirmed Anti-GBM glomerulonephritis (GN) with crescentic GN and rapidly progressive GN (RPGN). Treatment with plasmapheresis, prednisolone and cyclophosphamide was started. Anti-GBM antibody level became negatives, however, the patient progressed to end stage renal failure along with nephrotic range prteinuria and needed hemodialysis. Patient is undergoing work up for renal transplant at this time.
Conclusions: Goodpasture’s syndrome is a rare but severe and could be a life-threatening organ-specific autoimmune disorder that involves kidney and lungs with incidence of 0.5 to 1 per million. GBM antigen triggers immune attack against non-collagenous domain of chain α3 of type IV collagen and lead to deposition of anti-GMB immune complexes that manifests as pulmonary hemorrhage and RPGN with subsequent renal failure. Studies have shown HLA types strongly influences susceptibility specially types DR15 and DR4. Timely diagnosis and triple therapy with plasmapheresis, corticosteroids, and immunosuppression has significant impact on prognosis and renal function outcome. Most studies have shown a clear association between the extent of glomerular crescent formation and renal outcome. In general 5-year survival rate exceeds 80%. However, no more than 40% of patients will have independent renal function at 1 year.
63 FULMINANT LIVER FAILURE IN PREGNANCY
Almeida Lalama MV, Rodriguez C, MA. Taylor S. LSU-HSC, New Orleans, LA.
Case Report: The etiology of liver disease in pregnancy ranges from pre-existing conditions like chronic hepatitis B or C or autoimmune hepatitis; liver disease related to pregnancy like intrahepatic cholestatis, acute fatty liver, pre-eclampsia, Eclampsia or HELLP; to liver disease co-incidental to pregnancy like drug induced or acute viral hepatitis.
A 32-year-old woman G2, P1 with 26 weeks gestation intrauterine pregnancy presented to an outside hospital with fever, chills, nausea and vomiting for 4 days. She was admitted with a diagnosis of urinary tract infection and was started on ampicillin and gentamicin. She continued to be febrile, developed respiratory distress and her liver enzymes were noted to be markedly elevated. Her temperature was 104.4, pulse 125x’, respirations 26x’ and blood pressure 110/58, she had an O2 sat of 95% (FiO2 40%). She was alert, oriented x3, she had conjunctival injection and oral thrush. She had bibasilar crackles. Abdomen was consistent with gestational age, and was tender in epigastrium. Extremities were edematous. Laboratory results demonstrated a WBC of 2.8 (N12% Bands 30%) and anemia but platelet count was normal. Electrolytes and renal function were normal except for a CO2 of 29. All cultures were negative. Upon transfer her AST was elevated at 2435 and ALT 1157. Total bilirubin was 1.2 and LDH 9003. PTT and PT/INR were prolonged. Chest x-ray showed mild bibasilar opacities. Due to multi-organ failure, she was intubated, and started on vasopressors, meropenem, linezolid, ampicillin, acyclovir, and micafungin. Further workup revealed a positive herpes simplex virus (HSV) type-2 IgM and IgG as well as a detectable serum PCR. At this point all of the antibiotics and antifungal were stopped. On day 5 she was weaned off pressors and was successfully extubated. She was discharge on day 12 on valacyclovir to be taken throughout pregnancy.
Approximately 63% pregnant women are HSV-1 positive, 22% are positive for HSV-2 and 13% are positive for both. Since the first reported case of gestational herpetic hepatitis in 1969, a total of 33 cases have been reported. The American College of Obstetrics and Gynecology recommends to treat genital herpes in pregnancy with Acyclovir for 7 to 10 days, with suppressive therapy through delivery but there is no consensus for treatment of disseminated herpes infection.
64 MARCHIAFAVA-BIGNAMI DISEASE IN A PATIENT WITH HISTORY OF ALCOHOL AND COCAINE ABUSE
Al-Obaidi M, Echendu CE, Ahmed M. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: Abstract: We report a case of a 59 year old African American male with history of alcohol and cocaine abuse, and a recent history of a fall with C2 and wrist fractures, presented with gait disturbance and change in mentation for the last few months, patient was admitted to the hospital and was found to have gait abnormalities, scoring low on Mini-Mental Examination. We started the patient on thiamine and folate treatment with mild alleviation of his symptoms. CT scan of the head was done and it did not show any significant findings, we ordered MRI of the brain, which showed lesions involving the corpus callosum, these latter findings with patient’s presenting history correlated with the diagnosis of Marchiafava-Bignami Disease (MBD). We continued thiamine and folate replacement therapy, and discharged the patient to follow up with his primary care physician and physical therapy as an outpatient. We also explore briefly the history of MBD, methods that have been implemented the diagnosis of this condition and the etiology behind it.
Key words: Marchiafava-Bignami Disease, MBD, Alcohol neurotoxicity, Cocaine related neurological impairment
65 HYPERCALCEMIC CRISIS AS THE FIRST MANIFESTATION OF RECURRENT NON-HODGKIN’S LYMPHOMA
Aly M, Bashir M, Nusrat M, Panikkath R, Prabhakar S. Texas Tech Lubbock, Lubbock, TX.
Purpose of Study: This case report highlights a rare presentation of Non-Hodgkin Lymphoma (NHL) recurrence with hypercalcemic crisis. Hypercalcemia is a rather uncommon feature of NHL and it is even rarer to see it as the presenting feature. Interestingly, this particular patient presented with extra-nodal manifestations (lung nodules, bone, and breast mass) which added to the complexity of differential diagnosis and lymphoma could have been overlooked easily. This emphasizes the importance of careful history, examination as well as keeping high level of suspicion about rarer presentations.
Methods Used: Case analysis and literature review.
Summary of Results: An eighty-two year old female with complex history of past B-cell lymphoma in 1995 and 2005 was in remission since 2007 and history of renal cell carcinoma in 2012 status post nephrectomy was admitted with rapidly deteriorating well-being and extreme fatigue over few days for no apparent reason. Physical exam showed signs of hypovolemia, altered consciousness, and left axillary lymphadenopathy. Lab investigations showed serum Ca 17mg/dl, BUN 57 mg/dl, serum Cr 2 mg/dl and low iPTH level. PET scan showed hypermetabolic pulmonary nodules, bone lesions in the spine, left breast mass with ipsilateral lymphadenopathy as well as supra and infra diaphragmatic lymphadenopathy. Steroids were used in addition to hydration, calcitonin and bisphosphonates. Left axillary node biopsy confirmed B-cell lymphoma and treatment with R-CHOP was initiated. The patient’s hypercalcemia responded adequately to this management.
Conclusions: Lymphoma as a cause of hypercalcemic crisis is a rare but should always be considered and investigated. A recent retrospective study documented 7% incidence of lymphoma in a large series (Majumdar et al, J Clin Pathol 2002). The cause of hypercalcemia is unclear although many are associated with increased PTHrp levels. Steroids play a role in the treatment of lymphoma related hypercalcemia. Hypercalcemia is associated with decreased mean survival and poorer prognosis in NHL. Extranodal lymphoma in the breast, lungs and bones can mislead the diagnosis but a careful history and considering lymphoma with such manifestations is important for precise diagnosis, optimal therapy and better prognosis.
66 SEVERE RHABDOMYOLYSIS AS PRESENTATION OF DISTAL RENAL TUBULAR ACIDOSIS
Aly M, Panikkath R, Ali E, Fenire M, Mohamed A, Buscemi D. Texas Tech Lubbock, Lubbock, TX.
Purpose of Study: This case highlights a rare case of rhabdomyolysis associated with severe hypokalemia as a presenting complaint of Distal Renal Tubular Acidosis (RTA).
We report a case of a patient who presented emergently with severe hypokalemia, rhabdomyolysis and paralysis; the final diagnosis was distal RTA. Clinicians need to have increased awareness of RTA as a cause of such an emergency condition.
Methods Used: Case analysis and literature review.
Summary of Results: A 55 year-old female was hospitalized due to new onset acute, severe weakness and paralysis. The patient reported no recent nausea, vomiting or diarrhea. Her past medical history was positive for hypertension, depression and hypothyroidism, but no diabetes mellitus. No history of rheumatologic or renal diseases but recalled a history of recurrent UTIs when she was young. Her medications were atenolol 50 mg daily and chlorthalidone 25 mg daily. She had no family history of hypokalemia.
Physical examination showed global hypotonia, with no focal neurological deficits. The patient was hypotensive on presentation and responded to fluid resuscitation and brief use of vasopressors.
Her serum potassium was 1.1 meq/L, phosphate 1.4mg/dl, Magnesium 1.4mg/dl, with normal gap metabolic acidosis. CK level was above 14K IU/L. Urine PH was 7 with high 24 hours urine potassium excretion; this remained high even after stopping chlorthalidone. Renal sonogram was consistent with chronic kidney disease.
The patient responded well clinically to holding chlorthalidone, replacing potassium, and adding sodium citrate; she was referred to a urologist to evaluate her recalled history of recurrent UTIs.
Conclusions: Distal RTA is a metabolic disorder characterized by nonazotemic defect of distal nephron with failure to excrete hydrogen ions causing inability to acidify the urine to below 5.5 despite the severity of the metabolic acidosis. Rarely, loss of potassium can severe enough to cause paralysis and/or rhabdomyolysis as in our case. A new recurrence of UTI can act as the trigger. In literature, few similar cases have been reported and had different underlying causes of Distal RTA. Physicians should have a high suspicious index to check for this disorder, especially when the patient has no apparent clinical explanation of hypokalemia or has been on a stable dose of diuretic for a long time.
67 AN UNUSUAL PRESENTATION OF A POSTERIOR MEDIASTINAL TUMOR
Babbar A, Ramsaran V, Jones L. UF Health, Jacksonville, FL.
Case Report: A 37 year old lady was admitted to the hospital for acute alcohol withdrawal. She had a history of cervical radiculopathy. Surgical history included an anterior cervical disk fusion 2 years prior with no relief of her symptoms of severe, incapacitating right shoulder and subscapular pain. She had a 20 pack year history of smoking. Examination revealed an anxious female in no distress with normal vital signs and a mild tremor. Chest examination revealed tenderness to palpation over her right scapula and normal breath sounds bilaterally. The rest of the physical examination was normal.
Laboratory investigations were all within normal limits including a toxicology screen and alcohol levels. A chest X-ray done on admission revealed a right suprahilar mass. Subsequent CT scan of the chest with intravenous contrast showed a right posteromedial pleural based mass. MRI showed the mass extending through the foramen at T5 into the spinal canal. A CT guided biopsy of the mass was performed that revealed a neural tumor consistent with neurofibroma. The patient underwent a tumor excision by Neurosurgery in conjunction with Cardiothoracic surgery with subsequent relief of her neuropathic symptoms.
The patient in this case was diagnosed with a Dumb-bell neurofibroma. Approximately 10% of all neurogenic tumors located in the posterior mediastinum extend into the spinal canal via intervertebral foramina and are called Dumb-bell tumors. Neurogenic tumors are usually asymptomatic and discovered during routine chest x-ray. However, they can cause neurological symptoms in 60% of patients with intraspinal extension.
Our patient presented with severe refractory pain. The region of the invasion on MRI was T5-T6, however the patient had pain suggestive of a lesion in the cervical spine. Her symptoms however were from the actual neurofibroma itself causing pain as it invaded the rib and intercostals muscles. After having the tumor excised she had complete resolution of her symptoms with full functionality and returned to work two months post operatively.
68 BRUGADA SYNDROME
Banchs H1, Rivera N2, Banchs-Pieretti H1, Altieri P1. 1 University of Puerto Rico School of Medicine, San Juan and 2 VA Caribbean Healthcare System, San Juan.
Case Report: We present the case of a 29 year old male who presented to the emergency room with chest pain and loss of consciousness. Physical examination was unremarkable as well as laboratory workup, including cardiac markers. An electrocardiogram (ECG) was concerning for cardiac ischemia due to anteroseptal ST segment elevation. Closer inspection revealed ST segment elevations of more than 2mm present in leads V1-V3 with inverted T waves, compatible with Brugada type I pattern. Echocardiogram showed preserved systolic function without structural abnormalities. Follow up ECG demonstrated resolution of Brugada pattern. Brugada Syndrome is a hereditary cardiac channelopathy associated with sudden cardiac death in patients with structurally normal hearts and has a distinctive ECG pattern which supports its diagnosis. This case reminds us that Brugada Syndrome should be kept in the differential diagnosis of a patient with ST segment elevation on the right precordial leads. It is important to note that the Brugada ECG pattern may be transient, as in this case. Associated symptoms are due to ventricular arrhythmias which may be lethal. Patients with Brugada Syndrome should be evaluated thoroughly for ICD placement and genetic counseling.
69 A RARE TYPE OF ANEMIA ASSOCIATED WITH MIXED CONNECTIVE TISSUE DISEASE
Brookins S, Landa C. University of Florida College of Medicine, Jacksonville, FL.
Case Report: A 70 year old African American female with a medical history of mixed connective tissue disease presented with malaise and fatigue. The patient reported onset of symptoms about one week prior with difficulty performing her usual housework. The patient denied any weight loss, anorexia, fever, chills, or ill contacts. Physical exam was significant for ulnar deviation bilaterally. Initial hemoglobin was 6.2 g/dL and a hemolytic work up revealed a haptoglobin less than 10 mg/dL, LDH of 300 U/L, and total bilirubin 2.4 mg/dL. Reticulocyte count was 11.3% with an index of 5. The patient was transfused without improvement. Direct antibody test was positive for both warm and cold agglutinins with no underlying allo-antibody. Prednisone 40 mg daily was started with a mild improvement of the anemia. Hematology was consulted and the patient was started on 4 cycles of Rituximab. The hemoglobin improved to 10 g/dL and Prednisone was tapered to 5 mg daily.
The phenomenon of mixed autoimmune hemolytic anemia was first proposed in 1975 by Crookston . The etiology of this syndrome can be idiopathic, or secondary to lymphoproliferative disorders or connective tissue diseases. Mixed autoimmune hemolytic anemia runs a chronic course with intermittent exacerbations that do not correlate to cold exposure and may not manifest with Raynaud’s phenomenom or acrocyanosis. In fact, most cold agglutinins have no clinical significance and occasionally have high enough titers to indicate cold agglutinin syndrome. This is the case with our patient who had not been exposed to the cold but developed significant hemolytic anemia. Since exposure to the cold does not necessarily trigger hemolysis in mixed hemolytic anemia, avoidance is not an adequate treatment modality. Mixed autoimmune hemolytic anemia patients seem to respond similar to the treatment for pure warm hemolytic anemia. Only two cases have reported the association of mixed hemolytic anemia with mixed connective tissue disease and have demonstrated the efficacy of using Rituximab, especially in refractory cases to corticosteroids. We postulate that Rituximab may affect or simultaneously treat the underlying mixed connective tissue disease, leading to significant resolution of ongoing hemolysis.
70 TREATMENT OF AXIAL PAIN WITH STIMULATION UTILIZING “CROSS-TALK” BETWEEN EPIDURAL AND SUBCUTANEOUS PERIPHERAL FIELD LEADS: A CASE-STUDY
Clasby CD1, Eissa H2. 1 Louisiana State University, New Orleans, LA and 2Ochsner Baptist, New Orleans, LA.
Purpose of Study: 51-year-old female with a 15 year history of chronic neck and upper back pain following two cervical fusions. Failed pain control included an unsuccessful trial with an epidural spinal cord stimulator, which failed to cover her pain when the lead was blocked by scar tissue at the C2 level.
Methods Used: Two disparately positioned Octrode® leads were used: one epidural lead at the C2 level and a second lead subcutaneously across the occiput. Both were connected to an MTS programmed to “cross-talk” and fully cover her upper back and neck pain. Individual programming of each lead provided only near-localized coverage of her upper back or neck respectively. The combined, joint-programming of leads provided near-total coverage of her pain.
Summary of Results: Previously, the patient reported pain levels averaging 10/10, with best and worst levels of 6/10 and 10/10. Following implantation, the patient reported greater than 50% relief of her pain, and continued to realize this initial level of pain control.
Conclusions: The patient responded favorably to combined epidural and subcutaneous field stimulation, with approximately 50% resolution of her pain. Review of the literature reveals this as the first reported case of combining epidural stimulation and subcutaneous field stimulation using cross-talk as a method for extending the effective range of SCS to areas otherwise inaccessible to conventional SCS lead placement.
71 PERICARDIAL TAMPONADE AS THE FIRST PRESENTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS
Copeland S, Rivas M, Hosiriluck N, Nugent K. TTUHSC, Lubbock, TX.
Case Report: Pericardial tamponade is a life threatening condition. It is rarely seen as the presenting symptom of SLE. We present a case of asymptomatic large pericardial effusion with echocardiographic evidence of early tamponade physiology. The patient is a 52 year old female with PMH of hypertension who presented to the emergency center with chief complaint of acute right hemiparesis. Neurologic symptoms resolved within 4 hours and a transient ischemic attack was diagnosed. A portable chest radiograph was performed in the EC which showed a “water bottle” shaped heart. The patient denied fever, chills, weight loss, arthralgias, or arthritis. Physical exam was positive for distant heart sounds. TTE was performed which showed a large pericardial effusion with early tamponade physiology. A pericardiocentesis was performed in which 2.3L or serous fluid was removed. Fluid analysis was sent which revealed, yellow hazy fluid with 3,675 white blood cells/mm3. The differential was reported as 53% lymphocytes, 35% macrophages. Viral and bacterial cultures were negative. Mycobacteria was also negative. There was no evidence of malignancy by cytological examination. Serum analysis was positive for ANA and anti DS DNA with an index of 9 IU/mL. Anti-Smith antibodies were negative. She was subsequently diagnosed with SLE. The patient was started on hydroxychloroquine and a prednisone taper. She currently is doing well with no evidence of recurrence of pericardial effusion. Cardiac involvement in the setting of SLE is common with symptomatic pericarditis occurring in about 25% of the patients and asymptomatic pericardial involvement in more than half of the cases. Less common is the diagnosis of pericardial tamponade as the first presentation of SLE. It is important to make the distinction of whether tamponade physiology is present because this affects treatment. In instances of effusion without tamponade, corticosteroids are usually effective in resolving symptoms and elimination of pericardial fluid. However, the treatment of cardiac tamponade is to remove the pericardial fluid. This is usually done by pericardiocentesis or pericardial window. Factors that suggest the development of tamponade are female sex, african american race, and low C4 complement levels.
72 EYE OF THE BEHOLDER: DIAGNOSIS OF ACROMEGALY
Cosentino G, Uwaifo G, Richards R, de Silva TN. LSUHSC-NO, New Orleans, LA.
Case Report: While the clinical signs of acromegaly are distinct, their onset is insidious. Often the patient, their family members, and primary care providers who see the patient will not notice the clinical signs of the disease and diagnosis only occurs when the patient presents to a new provider. Because of this, the average time from onset of symptoms to time of diagnosis is about 12 years, by which time most patients already have macroadenomas and associated mass effect. The consequences of excess growth hormone include risk of cardiac complications as well as damage to many other body systems. Many of the effects are reverseable with removal of the source of hormone production, usually a pituitary adenoma. In this case we describe a patient with the classic signs of acromegaly who was diagnosed by the urology team during evaluation of a kidney stone.
This is a 60 year old woman with arthritis who for the past couple years had struggled with difficult to control diabetes. She was on almost 200 units of insulin daily and still had glucoses in the 500–600 mg/dL range. She had arthritis, particularly the hands. She reported that 20 years ago her ring and shoe size had increased greatly —however both had stabilized many years prior. She denied vision changes, but she started to have headaches of increasing frequency and severity. Finally when she was admitted for removal of a nephrostomy tube, a urology resident noticed that she had coarse facial features and called for an evaluation by the endocrinology service for possible acromegaly. Her family history was notable for a lack of diabetes mellitus or any endocrine neoplasms. On physical exam, she was noted to have frontal bossing, prognathia, and coarse facial features. She had enlargement of the hands and feet and particularly enlarged joints. Laboratory evaluation revealed a hemoglobin A1c of 15% and a greatly elevated insulin-like growth factor-1 of 684 ng/mL. After hospital discharge, she was found to have a 3.1 cm pituitary macroadenoma displacing the anterior cerebral arteries and the optic chiasm as well as extending through the sphenoid sinus. Three months later she had transsphenoidal surgery to have the tumor removed and has done well post-operatively without evidence of diabetes insipidus. Two weeks after surgery she started to notice lower fasting and post-prandial glucose readings.
73 DIFFUSE ALVEOLAR HEMORRHAGE: A RARE COMPLICATION POST EPTIFIBATIDE INFUSION IN A PERIPHERAL PERCUTANOUS INTERVENTION
El-Bakush A, Edriss H, Nugent K. Texas Tech University Health Sciences Center, Lubbock, TX.
Case Report: Introduction: GP IIb/IIIa inhibitors are used in acute and subacute limb ischemia. Although there are no clear guidelines for their use in peripheral percutaneous interventions, studies have shown their use is associated with lower rates of embolization, less secondary reintervention and improved limb salvage. Bleeding is a common side effect of their use and can occur at the access site and in the gastrointestinal or genitourinary tracts. Alveolar hemorrhage is a rare complication. We present a patient who had a percutaneous lower extremity intervention for critical limb ischemia and developed diffuse alveolar hemorrhage and hematuria.
Case: A 76-year-old man with CAD, hypertension, peripheral arterial disease, and atrial fibrillation was admitted with a non-healing right foot wound and right leg pain. He had 80% stenosis of the right internal and external iliac arteries, right common femoral artery stenosis, right superficial femoral artery total occlusion, and 80% stenosis in the popliteal artery. He underwent percutaneous transluminal angioplasty and placement of stents. Following the procedure, he received aspirin and Plavix and was started on Eptifibatide infusion. Over the next two days he developed hematuria, shortness of breath, and hemoptysis. His exam revealed decreased breath sounds and crackles. His oxygen requirements increased from room air to 6L/min oxygen by nasal cannula. Chest x-ray showed bilateral diffuse alveolar opacification consistent with alveolar hemorrhage or pulmonary edema. His hemoglobin dropped 4g/dL, and he required 4 units of RBC transfusion. Platelets, APTT and INR were all normal. Echo showed severe pulmonary hypertension. Eptifibatide was discontinued after an 18 hour infusion; the patient was hemodynamically stable. Within 6 days the hematuria and hemoptysis resolved, and the chest x-ray improved. He was discharged home on room air.
Discussion: Alveolar hemorrhage is a rare complication of GP IIb/IIIa use but can be life threatening. Cases have been reported in the literature after use for acute coronary syndromes and related interventions but infrequently with percutaneous peripheral interventions. The diagnosis can mimic pulmonary edema and requires a high index of suspicion.
74 DIVERSE COMPLICATIONS IN A PATIENT WITH LITHIUM TOXICITY
El-Bakush A, Fuller A, Tello W, Nugent K. Texas Tech University Health Sciences Center, Lubbock, TX.
Case Report: Lithium has been used in management of many psychiatric disorders. It has frequent side-effects, a narrow therapeutic window and requires regular monitoring.
Case: 25 year-old woman presented with 2 weeks abdominal pain, nausea, and vomiting. History was significant for mental retardation, schizophrenia, bipolar disorder, and hypothyroidism. Medications included lithium, Seroquel, citalopram, Ambien, clonazepam, and levothyroxine. Lithium dose was recently increased. Exam: Respiratory rate of 50, temperature 106.7 F, and Glasgow coma scale 7. Her level of consciousness deteriorated, and she needed intubation. Labs showed K+ 2.1mmol/L, Na+ 153 mmol/L, and creatinine 2.7mg/dl. TSH was suppressed (0.002 mu/ml), and free T4 was high (1.96ng/dl); 5 months preadmission TSH was 2.540 mu/ml on levothyroxine 25mcg. Antithyroid peroxidase antibodies were 193 Iunits/ml. Lithium level was 4.6mmol/L. She was given propylthyouracil; cooling measures and hemodialysis were initiated. After hemodialysis the lithium level was 1.0. She developed polyuria and was diagnosed with diabetes insipidus. Seizures were present with jerky movements of her limbs, suppressed by propofol or lorazepam. She remained unresponsive 7 days. Encephalopathy evaluation included normal CSF analysis, negative bacterial and viral meningitides panels, including West Nile virus. Paraneoplastic autoantibodies, including AMPA-R, GABA-B-R, NMDA-R antibodies, were negative. EEG showed triphasic waves and continuous generalized slowing. MRI was unremarkable. Differential diagnosis: Hashimoto’s encephalopathy, immune mediated encephalopathy, or lithium-induced encephalopathy. She received intravenous steroids for five days. She slowly improved, became more responsive, and was extubated.
Discussion: Our patient had multiple complications during this episode of lithium toxicity even though dialysis was started on arrival. She had hyperthermia, diabetes insipidus, and several electrolyte disorders. Prolonged encephalopathy secondary to lithium toxicity is an uncommon complication, in our patient it developed over a very short period of time. Hypothyroidism and goiter are common side effects of lithium; our patient developed hyperthyroidism which occurs very infrequently and was probably secondary to silent thyroiditis.
75 TOXIC BELCH: A THREAT TO THE HEALTH CARE TEAM
Farooqi S1, Mughal A2. 1 TTUHSC-Lubbock, Lubbock, TX and 2 St. Elizabeth’s Medical Center, Boston, MA.
Case Report: In leading a team of health care providers, physicians must protect coworkers. This highlights a case of toxic ingestion, which may pose a risk to the safety of the health care team.
An 18 year old male with no significant history was transferred to our facility after being found unresponsive. The patient argued with his girlfriend and joked of ingesting a home pesticide. The patient arrived intubated, unresponsive, and on a dopamine drip. His skin had a grey, ashen appearance. Blood pressure was 50/30mmHg, pulses were faint, thready, and irregularly 30-40bpm. Bilateral crackles were present. Significant labs included an anion gap metabolic acidosis, remarkable hyperglycemia, and thrombocytopenia. The patient worsened and despite proper ACLS and three vasopressor support, the patient expired after 13 cycles of CPR. EMS provided a canister of aluminum phosphide (AIP). Post-mortem exam was consistent with AIP ingestion.
AIP is a boll weevil toxin, used in under developed countries, to protect grain and tobacco stores during storage and shipment. There are no other reported cases of intentional ingestion in the U.S. Singer et al hypothesized the toxicity involved decreased mitochondrial function and oxidative phosphorylation. Ingested orally, it reacts with water and stomach acid to produce phosphine gas. This is readily absorbed into the bloodstream and epithelium, and denatures oxyhemoglobin to disrupt enzymes for respiration and metabolism. Lemoine et al. reported the only U.S. cases of accidental exposure, involving 6 family members and two child fatalities. A Simplified Acute Physiology Score II (SAPSII)5 can be used to predict outcomes although survival is unlikely if >1.5g is ingested. Complications include cardiogenic shock, metabolic acidosis, respiratory failure and hemolytic anemia. This toxin poses a significant risk to all providers as in Iran two patients were noted to have flames erupt from the NGT lavage after mixing to potassium permanganate, which oxidizes phosphide to phosphate.
76 TRANSIENT LEFT VENTRICULAR APICAL BALLOONING SYNDROME
Fenire M, Mulkey Z, Mohamed A, Ali E, Mazek H. Texas Tech University Health Science Center, Lubbock, Lubbock, TX.
Purpose of Study: 1-Report a case of transient left ventricular (LV) apical ballooning syndrome. 2-Demonstrate the typical clinical and diagnostic features of the disease
Methods Used: Case analysis and review of literature.
Summary of Results: A 64-year-old woman presented to the emergency department two hours after the acute onset of chest pain (CP) while at her Mother’s Day party. She had not experienced CP prior to this and at the time, she was very depressed and less communicative after she remembered her son who had died two years prior. The CP was severe, central, and pressure-like which radiated to the left arm. Electrocardiogram (EKG) on arrival showed ST elevation in leads V2 and V3. Troponin T was 0.43 ng/ml and CK-MB was 14.7 ng/ml. Left heart catheterization showed no significant coronary artery disease, 40% ejection fraction (EF) and apical ballooning (panel 1). Transthoracic echocardiography (TTE) on the day of admission revealed inferoapical and anteroapical hypokinesis. A repeat TTE two days later showed normal EF and normal wall motion. Repeated Troponin T was 0.09 ng/ml and the patient was discharged home.
Conclusions: Transient LV apical ballooning syndrome is characterized by transient LV dysfunction, EKG changes that can mimic acute myocardial infarction (MI), and minimal release of myocardial enzymes in the absence of obstructive coronary artery disease (CAD). It was initially recognized in Japan in 1990 with the first report emerging from the United States in 1998. A recent study reported a prevalence of 0.9% in patients suspected of having ST segment elevation MI and admitted for primary percutaneous coronary intervention. Most reports have noted a clear gender discrepancy, with much higher prevalence in women. It is typically preceded by exposure to emotional or physical stressors such as an unexpected death in the family, abuse, a quarrel, or exhausting work, although in some cases, precipitant stressors have not been identified. The most frequent clinical symptoms on admission are chest pain and dyspnea, resembling acute MI. In another study, only 1.1% of reported patients died during the hospitalization period and almost all surviving patients recovered fully. In the absence of specific guidelines, the treatment remains standard supportive care and individualized according to the patient characteristics at presentation.
77 FAT EMBOLISM SYNDROME
Fenire M, Nugent K, Ali E, Edriss H, Zedan A, Mazek H. Texas Tech University Health Science Center, Lubbock, Lubbock, TX.
Purpose of Study: 1).To report a case of fatal fat embolism syndrome FES in a Down’s syndrome patient with bilateral femoral neck fractures, 2). Provide images of the typical skin, lung, and brain findings.
Methods Used: Case report and review of literature.
Summary of Results: A 59-year-old man with Down’s syndrome in foster care complained of hip pain. His care taker for the last 8 years woke him early that morning. He stood from bed and sat in his bedroom chair as usual. He did not come down for breakfast prompting her to check on him. She found him complaining that his hips hurt, and he was lying on the ground. His activity status is that he normally ambulates within the home without any assistive devices, bathes himself, and converse in a meaningful conversation. Extremity exam showed pain with log roll or any movement attempted on the hips. Skin exam failed to show any signs of trauma. X-rays revealed bilateral femoral neck fracture. He had bilateral hemiarthroplasty within six hours from his injury. He developed respiratory distress and decreased level of consciousness while in the post anesthesia care unit and had to be reintubated within an hour from his extubation. Over the subsequent 24 hours, he developed skin rash shown in the panel (1). Despite supportive care, he remained unresponsive, developed multiorgan failure, and eventually died.
Conclusions: Fat embolism (FE) occurs in nearly all patients (> 90%) with bone fractures during orthopedic prosthesis procedures and rarely in other pathologic conditions. Only 3 to 4% will acquire the classical triad of the FES, which consists of respiratory distress, cerebral abnormalities, and petechial hemorrhages; the rest of these patients remain asymptomatic. The clinical pattern of this syndrome involves a bimodal distribution; some patients clearly develop a fulminant course with the onset of symptoms within 12 hours of injury. Most patients tend to have a more progressive course with symptoms appearing 24 to 72 hours after injury. Eileen et al reported only 33% of patients in this study had documented petechiae in a 10-year retrospective review of FES. The most prominent manifestation of the syndrome is acute hypoxia. Even when lung injury is obvious, its cause may be attributed to infection, aspiration, or traumatic ARDS, rather than to FE. The main treatment for FES is supportive care.
78 EARLY DIAGNOSIS AND SUPPORTIVE CARE ARE KEY
Fenire M, Nugent K, Mazek H, Mohamed A, Edriss H. Texas Tech University Health Science Center, Lubbock, Lubbock, TX.
Purpose of Study: 1- To report a case of transfusion-related acute lung injury (TRALI), and discuss the differential diagnosis (DDx).2- Early recognition and supportive care are the key.
Methods Used: Case analysis and literature review.
Summary of Results: A 57-year-old man presented with the acute onset of hematemesis, epigastric pain, melena, and dizziness. He had a low blood pressure, tachycardia, and O2 sats of 98% on room air. His hemoglobin was 5.1gm/dl. He received immediate blood transfusion. Two hours later, the patient’s O2 sats dropped to 89%, and he started on O2. Upper endoscopy showed a duodenal ulcer spurting blood. He had progressive hypoxia, and 28h later he was intubated. Chest x-ray and computed tomography scan (CT) revealed diffuse bilateral infiltrates and air bronchograms (Panel 1). Transthoracic echocardiogram (TTE) revealed normal systolic and diastolic function. He continued to bleed and he underwent exploratory laparotomy and pyloroplasty. He stayed on ventilator support for 9 days before he was successfully extubated. Blood, urine, and lungs washings cultures were negative. Repeat CXR showed resolution of his lung infiltrates. He was seen in the clinic 18 months after his discharge with no residual lung disease.
Conclusions: TRALI is defined as a “new acute lung injury that occurs during or within 6hrs after transfusion of blood products with clear temporal relationship to transfusion, in patients without or with risk factors for acute lung injury (ALI) other than transfusion” According to the Food and Drug Administration, 45% of the fatalities related to blood transfusion in 2012 were caused by TRALI, making it as one of the leading causes of transfusion-related fatalities. DDx includes transfusion-associated cardiac overload (TACO). A history of heart disease, positive fluid balance, increased jugular venous pressure, and the presence of S3 will favor TACO. Radiographic features of TRALI are nonspecific. CXR initially shows interstitial opacities and lung haziness. This rapidly progresses to widespread bilateral alveolar and interstitial opacities. Parenchymal consolidation and air bronchograms are seen in heterogeneous distribution on CT scan. These lung opacities usually clear within 96h without long term sequellae. Diuretics may worsen TRALI. Supportive care is the main treatment.
79 THE DIFFICULTIES OF ALLOGENEIC STEM CELL TRANSPLANT: DIFFERENTIATING HEPATIC VENO-OCCLUSIVE DISEASE FROM ACUTE GRAFT VERSUS HOST DISEASE
Hansen DK, Milner CP, Elkins S, Buck T. University of Mississippi Medical Center, Jackson, MS.
Introduction: Hepatic Veno-Occlusive Disease (VOD) is a well-recognized complication of hematopoietic stem cell transplantation.
In this case report, we describe a non-fatal case of hepatic VOD in a patient who received allogeneic stem cell transplantation after cyclophosphamide and busulfan conditioning.
Case Report: A 25 year old African American male with acute myeloid leukemia with poor risk cytogenetics underwent mismatched unrelated donor allogeneic peripheral blood stem cell transplant with cyclophosphamide and busulfan conditioning.
The patient developed febrile neutropenia unresponsive to antibiotics and acetaminophen. Additionally, he developed a generalized skin rash concerning for graft versus host disease (GVHD). He received steroids and defervesced. However, by day + 9, he had a thirty pound weight gain and developed direct hyperbilirubinemia and transaminase elevation. Hepatic ultrasound demonstrated hepatomegaly but normal hepatic vasculature.
Differential diagnosis included hepatic VOD and hyperacute GVHD. Due to further weight gain, rise in bilirubin, and known risks of his conditioning regimen, the patient warranted treatment for VOD. He was transferred to the MICU for emergent tPA in the setting of pancytopenia. The following day, he was enrolled in a clinical trial with defibrotide therapy. His bilirubin and transaminases improved with defibrotide, but he required fresh frozen plasma frequently for supratherapeutic INR. Patient’s course improved with a decline in his bilirubin from a maximum of 32 to 16 mg/dL. However, on day + 36, his bilirubin began to rise again thus, he had a liver biopsy, which was consistent with only GVHD; VOD was likely to have been treated with defibrotide.
Discussion: Significant weight gain, direct hyperbilirubinemia and signs of hepatic congestion form the diagnostic cornerstone of hepatic VOD.
This case illustrates the formidable challenge of diagnosis and treatment of hepatic VOD in patients undergoing allogeneic stem cell transplantation. A high clinical index of suspicion is required to identify patients with VOD and to initiate timely treatment. In this case, it was difficult clinically to identify hepatic VOD due to concomitant presence of hyperacute GVHD.
80 WHEN A WHITE COUNT IS NEEDED THE MOST: THE FIRST CASE REPORT OF A NEUTROPENIC PATIENT SURVIVING SPOROPACHYDERMIA CEREANA FUNGEMIA
Hansen DK, Milner CP, Zamora A, Albrecht S, Webb R, Buck T, Herrin V. University of Mississippi Medical Center, Jackson, MS.
Introduction: Sporopachydermia cereana is a cactophilic yeast first identified in 1978.
Only three other cases of S. cereana have been reported. It is exceptionally rare as a human pathogen and has proved fatal in the other neutropenic patients.
Here, we report the first surviving patient with S. cereana fungemia per literature review.
Case Report: A 58 year old African American woman with acute myeloid leukemia underwent successful re-induction chemotherapy with cytarabine, etoposide, vincristine, and daunorubicin.
Following re-induction, she became profoundly pancytopenic and remained febrile despite broad spectrum antimicrobials, including thirty days of micafungin. Four consecutive blood cultures demonstrated an unidentifiable Candida species. Micafungin was discontinued and liposomal amphotericin B initiated.
Patient developed renal failure likely secondary to amphotericin B and respiratory failure from volume overload requiring intubation. Posaconazole and caspofungin replaced amphotericin for broad coverage of yeast. The candida isolate was identified by a reference laboratory as Sporopachydermia cereana. The patient denied having any previous or recent exposure to cactus.
While intubated with respiratory failure, patient’s white blood cell count returned in a timely manner, likely contributing to the resolution of her infection. Repeat cultures demonstrated no growth and the patient’s fevers resolved.
Clinically, patient continued to improve after 20 days of total treatment with caspofungin and posaconazole and remained without evidence of fungemia or residual leukemia.
Discussion: Sporopachydermia cereana is an opportunistic cactophilic yeast which has occured in the setting of refractory hematologic malignancy but previously resulted in death.
S. cereana is notoriously difficult to detect using conventional mycological identification techniques. Future work is needed to identify alternative hosts for S. cereana and to establish optimal treatment and antibiotic duration.
As far as we are aware, this patient represents the first literature report of patient survival after S. cereana infection acquired during recovery from induction chemotherapy.
81 LATE RECURRENCE OF LIGHT CHAIN DEPOSITION DISEASE AFTER KIDNEY TRANSPLANTATION TREATED WITH BORTEZOMIB: A CASE REPORT
Javed T, Moiz A, Garces J, Staffeld C. Ochsner Clinic Foundation, New Orleans, LA.
Case Report: Background: Herein, we present a case of a patient who developed recurrence of LCDD, several years after kidney transplantation, leading to allograft dysfunction requiring renal replacement therapy. The patient had a significant improvement in her renal function after receiving bortezomib and was able to come off dialysis.
Methods: A 55 YO Caucasian female with history of Type 2 DM and HTN, ESRD secondary to LCCD underwent living-unrelated kidney transplantation. Her induction consisted of IV solumedrol and rabbit thymoglobulin (4.5mg/kg in 3 divided dosages). She had immediate allograft function without the need of renal replacement therapy. Her creatinine stabilized between 0.8-1.0mg/dl. After 6 years of transplantation routine labs showed a Cr of 1.8mg/dl and nephrotic range proteinuria (9.5g/g) on spot protein to creatinine ratio. She subsequently underwent a kidney biopsy. A diagnosis of recurrent light-chain deposition disease was made based on the biopsy findings. Oncology was consulted and a bone marrow biopsy was performed which was consistent with a plasma cell dyscrasia and she met criteria for multiple myeloma. Patient initially received five cycles of plasmapharesis without any improvement. She eventually required renal replacement therapy three times a week. She then received one cycle of Bortezomib (Velcade 1.3mg/m2 intravenously) along with IV dexamethasone. She received 4 doses of Bortezomib on day 1, 4, 8 and 11. There was no immediate clinical response to the treatment and she remained dialysis dependent. She was discharged to a rehabilitation center due to significant debility and deconditioning. Her renal function was closely monitored while she remained on dialysis. She gradually exhibited signs of renal recovery after staying on dialysis for 2 months. Dialysis was held when her urine output improved (> 1L/day), and her creatinine eventually settled between 1.5-1.7 mg/dl.
Results:
Conclusions: Bortezomib may provide an alternative to currently available treatment options in patient with LCDD recurrence after transplantation.
82 A CASE OF HYPOKALEMIA IN A MAN WITH GENERALIZED WEAKNESS - THYROTOXIC PERIODIC PARALYSIS
Joseph Z, Gosmanov A. University of Tennessee, Memphis, TN.
Case Report: A 31-year old African American male presented to the hospital with history of sudden onset of generalized weakness in all extremities. Patient denied prior medical problems and drug abuse. His review of systems was positive for occasional palpitations and anxiety spells prior to this presentation. On examination, he had elevated blood pressure of 170/90 mmHg, heart rate of 109 bpm and was alert and oriented. He had significant proximal and distal weakness in extremities. He also had bilateral enlargement of thyroid gland with bruits. Initial laboratory evaluation was significant for potassium level of 1.3 (3.5-5.0 mmol/L). Computed tomography of head did not show any abnormalities. A 12-lead EKG showed sinus tachycardia, no QT prolongation, and normal QRS complexes. He was admitted for aggressive electrolyte repletion and telemetry monitoring. Two hours after initiation of intravenous potassium replacement, his neurologic symptoms resolved. Further inpatient studies demonstrated TSH of <0.05 (0.3-3.0 mIU/L), free T3 of 26 (1.4-4.2 mIU/L) and free T4 of 7.5 (1.4-3.6 mIU/L). Diagnosis of Thyrotoxic Periodic Paralysis (TPP) was made and the patient was started on methimazole 20 mg twice daily and metoprolol 25 mg twice daily. Two months after hyperthyroidism treatment, he became euthyroid and his potassium concentration was 4.4 mmol/L.
Discussion: Profound generalized weakness is a non-specific complaint with a broad differential diagnosis of potential causes. Intracranial pathology must be ruled out first. The diagnosis of global weakness requires obtaining a complete history with special consideration of timing, duration, and distribution of symptoms. Hypokalemia can cause generalized muscle weakness when potassium level is below 3 mmol/L. TPP is a disorder characterized by an abrupt onset of hypokalemia and paralysis in patients with hyperthyroidism. The clinical features of TPP are similar to those seen with other forms of hypokalemic periodic paralysis, but also include the symptoms of thyrotoxicosis such as weight loss, tachycardia, and anxiety. In patients who develop TPP, however, the symptoms of hyperthyroidism are often moderate and may be overlooked. Therefore, we recommend evaluation of thyroid function in patients presenting with severe hypokalemia.
83 FILLING DEFECT IS NOT ALWAYS A PULMONARY THROMBOEMBOLISM
Khawar MU1, Bhardwaj H2, Awab A2. 1 OUHSC, Oklahoma city, OK and 2 OUHSC, Oklahoma CIity, OK.
Case Report: Pulmonary artery sarcoma (PAS) is a rare malignancy arising from the mesenchymal cells of the intima of pulmonary artery. PAS is often misdiagnosed as pulmonary thromboembolism (PTE), as both diseases initially appear as intraluminal “filling defects” in the pulmonary artery system on contrast-enhanced CT-scans. The differentiation of these two entities is important to avoid misdiagnosis of a potentially fatal malignancy and unnecessary anticoagulation therapy. We describe a patient initially misdiagnosed as PTE not responsive to prolonged anticoagulation therapy, who later was found to have PAS.
A 76-years-old male with medical history of hypertension presented with dry non-productive cough, pleuritic chest pain and dyspnea. Computed tomographic (CT) angiography scan revealed a filling defect in the left main pulmonary artery. Unfractionated heparin was started and bridged to Coumadin; patient was discharged home with the diagnosis of PTE. After discharge, patient’s symptoms kept worsening with additional anorexia & weight loss. Due to worsening dyspnea and weight loss of 20 pounds over the next 3 months, a follow-up CT-Chest angiogram was performed. This revealed a 16 x 10 x 8 cm mass in the left main pulmonary artery which seemed to have originated from the filling defect seen on the initial CT-scan. An ultrasound-guided biopsy of the mass was consistent with the diagnosis of PAS on histo-pathological analysis. Due to extensive disease, only the palliative chemotherapy was offered, which he declined.
PAS is a rare and often lethal tumor usually diagnosed during surgery or autopsy. The absence of predisposing factors for PTE and the progressive worsening dyspnea in patients with an intraluminal filling defect despite anticoagulation therapy are factors suggestive of PAS. Recently, it has been reported that, positron emission tomographic scan (PET-CT) may help to make a differential diagnosis between PAS and PTE. If detected earlier, surgical resection remains the primary treatment. For these reasons, a correct early diagnosis is of fundamental importance. Clinicians should maintain high suspicion of PAS in patients with a filling defect in the pulmonary artery without any underlying risk factors for PTE and worsening of symptoms despite anticoagulation therapy.
84 ANOMALOUS ORIGIN OF THE RIGHT CORONARY ARTERY FROM THE LEFT CORONARY SINUS
Mazek H, Omar S, Strefling J, Edriss H, Mohamed A, Wischmeyer J. Texas Tech University Health Science Center, Lubbock, TX.
Purpose of Study: Right coronary artery anomalies are very rare and when present are found at birth. Usually these anomalies are asymptomatic and discovered incidentally during coronary angiogram or computed tomography scan. The most common coronary anomalies are related to left circumflex or left anterior descending arteries. We are reporting a rare case of a right coronary artery originating from the left coronary sinus.
Methods Used: Case analysis and literature review.
Summary of Results: We are reporting a case of an anomalous origin of the right coronary artery from the left coronary sinus in a 33 year old man with no significant past medical history . The patient was admitted to our hospital after he collapsed secondary to ventricular tachycardia requiring cardiopulmonary resuscitation and multiple defibrillating shocks. Electrocardiogram showed inferior ST segment elevation with elevated troponin. The patient was diagnosed with ST elevation myocardial infarction. The patient underwent urgent cardiac catheterization. Coronary angiogram showed an 80% stenosis of the proximal left anterior descending coronary artery as well as a likely anomalous takeoff of the right coronary artery from the left coronary cusp. Cardiac CT angiography was preformed: revealing a right coronary artery arising from left coronary cusp, the arterial course run anteriorly between the aorta and the pulmonary artery that appeared to be stenosis of 70% of right coronary artery secondary to impingement from gear vessels. The patient underwent coronary artery bypass grafting and recovered well postoperatively.
Conclusions: Our case report focuses on a right coronary artery anomaly which originated from the left coronary sinus. Although many C Anomalies are asymptomatic, an anomaly that courses between great vessels can lead to angina pectoris, myocardial infarction, or sudden cardiac death, our case can be explained by mechanical compression of the right coronary artery by the great vessels. Cardiac CT angiography is important to determine the relationship of the anomalies artery to the greats in order to guide for the best way to manage.
85 A RARE CASE OF ADULT ALVEOLAR SINONASAL RHABDOMYOSARCOMA
Mazek H, Konala V, Nusrat M, Omar S, Warraich I, D’Cunha N. Texas Tech University Health Science Center, Lubbock, TX.
Purpose of Study: Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to arise from cells committed to a skeletal muscle lineage. It is a common childhood tumor, but very rare in adults. There are four histological subtypes of RMS: embryonal, alveolar, pleomorphic and botryoid. Little et al. reported 43% pleomorphic, 34% embryonal, and 23% alveolar in adult population.
Methods Used: Case analysis and literature review.
Summary of Results: A 60-year-old gentleman presents with right nasal obstruction associated with minimal nasal bleeding. Physical examination was unremarkable. CT scan of the paranasal sinuses revealed a 1.5 x 2.7 cm polyp in the right nasal cavity. Patient underwent endoscopic transnasal resection of the right nasal mass. Immunohistochemical staining showed that the neoplastic cells are strongly reactive with antibodies to desmin, myogenin and CD56 but negative for CD99, S100 protein, CAM5, chromogranin, pankeratin or synaptophysin. These findings along with morphology strongly support the diagnosis of alveolar RMS . No evidence of distant metastases was found on further imaging. Patient treated with radiation to prevent local recurrence. He was started on chemotherapy with vincristine, dactinomycin, and cyclophosphamide and planned for a total of one year.
Conclusions: RMS can develop in almost any part of the body, the most common locations being head and neck (nearly 40% of all cases), genitourinary system and extremity. Histologically, the most common forms found in the head and neck are the embryonal. Sinonasal RMS (SNRMS) is a rare malignancy which often presents with nasal obstruction, rhinorrhea and epistaxis. Immunohistochemical analysis plays an important role in the definitive diagnosis. Treatment is multimodal, with surgical debulking followed by radiotherapy and chemotherapy, which appears to permit effective control and possible cure of this disease. A study from Wurm et al. reported 5-year survival with embryonal SNRMS and alveolar SNRMS to be 55% and 33% respectively. Adult alveolar RMS is more aggressive with a worse overall survival than pediatric alveolar RMS.
86 PATIENT WITH DIFFICULT BREATHING AND EPISTAXIS - A SUBTLE PRESENTATION OF A RARE AND AGGRESSIVE NEOPLASM
Mazek H, Omar S, Suvorava N, Konala V, Warraich I, Figueroa J. Texas Tech University Health Science Center, Lubbock, TX.
Purpose of Study: Melanoma is mostly of cutaneous origin, it can also occur in various extra cutaneous regions including ocular, mucosal and leptomeningeal sites. Mucosal melanoma of head and neck (MMHN) is a rare disease that makes up to less than 1% of all melanoma cases in United States. We present a 63 year old patient with MMHN.
Methods Used: Case analysis and literature review.
Summary of Results: A 63 -year-old male presented with difficult breathing and progressively increasing left nasal obstruction symptoms for about a month with some episodes of a small amount of epistaxis. He was referred to ENT surgeon for possible polyp or mass in the left nostril. Maxillofacial CT scan revealed a 6.1 x 1.2 x 8.4 cm left nasal cavity mass involving the left inferior turbinate. A staging PET/CT scan did not show any distant metastases. He underwent left endoscopic ethmoidectomy. The histopathology was consistent with mucosal malignant melanoma (MM). BRAF mutation was negative. Patient was treated with stereotactic radiation therapy to his nasal cavity. Repeat PET/CT scan shows resolution of metabolic activity in the left nasal maxillary region.
Conclusions: Mucosal MM within the nose and paranasal sinuses represents approximately 4% of all nasosinusal neoplasm’s, affecting predominantly age group over 60’s, equally in both sexes. They are asymptomatic in early stages, which delays diagnosis and reduce the possibilities of cure. The majority of the patients present with epistaxis, and progressively increasing nasal obstruction. The diagnostic tools include a thorough physical examination, imaging, biopsy, and even then diagnosis remains exceedingly difficult.
The treatment of choice in mucosal MM is surgery followed by radiation therapy in cases of small or doubtful margins of resection. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have poor prognosis with 8% to 30% five-year survival.
This case highlights that melanoma can occur at extracutaneous sites including mucosal origin. Given the delay in diagnosis because of minimal symptoms, high index of suspicion is required.
87 OPPORTUNISTIC INFECTION IN IMMUNOSUPPRESSED RENAL TRANSPLANT PATIENTS WITH RECURRENT DISEASE
Mazek H, Jamal F, Fenire M, Ali E, Aly M, Laski M. Texas Tech University Health Science Center, Lubbock, TX.
Purpose of Study: Treatment of allograft kidney involves risks of opportunistic and nosocomial infections, this risk increases if the treatment is altered for any recurrence of disease or rejection of transplant kidney.
Methods Used: Case analysis and literature review.
Summary of Results: 61 year old man with a history of deceased donor kidney transplant 20 years prior, for ESRD, secondary to glomerulonephritis. He had a good allograft function with a serum creatinine level of 1.6 mg/dl. He was treated with Cyclosporine 100mg bid and Azathioprine 50 mg daily. Cell counts of CD3 911, CD 4 475, CD8 403 and CD4/CD8 1.2.
Patient was noted to have a rise in serum creatinine to 2.5mg/dl. Urinalysis showed mild hematuria and mild proteinuria. ANCA levels were now positive for anti-PR3 antibody. Transplant kidney biopsy showed 40% interstitial fibrosis and tubular atrophy. Glomeruli showed cellular and fibrous crescents and moderate thickening and hyaline changes were seen with in the arterioles. Impression was recurrent pauci immune necrotizing glomerulonephritis. Patient was treated with 3 doses of IV Cyclophosphamide and pulse dose Solumedrol. After the 3rd dose, patient developed fever, chills and left sided neck swelling. Examination revealed firm, tender, left sided parotid gland. No dental caries or abcess were seen. Biopsy of parotid gland showed findings consistent with Actinomyces. Culture showed actinomyces. He was treated with one month course of high dose IV Penicillin. Cyclophosphamide was discontinued and immunosuppression changed to Cyclosporine, Azathioprine and Prednisone. Patient’s renal function remained stable after treatment.
Conclusions: Many Actinomyces species are opportunistic pathogens of humans. Greatest risk factor for actinomyces is poor oral hygiene and one predisposing factor is immunosuppression. Recurrence of Pauci-immune vasculitis with positive ANCA is common, with renal involvement in more than half of these recurrences but graft losses reported in only a minority. One of the side effects of Cyclophosphamide therapy is a risk for opportunistic infections like actinomyces infection and in this case is the probable cause of actinomyces infection.
88 FOREIGN BODY ASPIRATION MASQUERADING AS ASTHMA
McCurdy K1, Ramsaran V2, Cury J2. 1 UF COM Jacksonville, Jacksonville, FL and 2 UF COM Jacksonville, Jacksonville, FL.
Case Report: An 18 year old man with a three year history of asthma presented with a left lung collapse. We present his clinical course and discuss how a foreign body aspiration can mimic asthma.
The patient presented with fevers, dyspnea, and a productive cough after being hospitalized 1 year ago for similar complaints. He had been diagnosed with asthma 3 years prior.
On admission, he was in moderate respiratory distress. Lung examination revealed markedly decreased breath sounds on the left and left sided dullness to percussion. Right lung field examination was normal. CXR demonstrated near complete opacification of the left hemi thorax. CT chest showed diffuse consolidation of the left upper and lower lobes and occlusion of the distal left mainstem bronchus.
Bronchoscopy was performed showing pus from the left mainstem bronchus and a left lower lobe endobronchial lesion. A foreign body in the left lower lobe was visualized and removed intact. Gross pathology confirmed the object to be a pen cap cover and the patient remembered choking on this 3 years prior. He was discharged on a course of oral antibiotics. Since discharge, he has stopped using his asthma medications as he no longer wheezes. He is now able to perform physical activity at his normal level prior to this illness.
Foreign body aspiration is the 5th most common cause of unintentional injury-related mortality in the US claiming the lives of over 3,700 patients in 2007.
Our case demonstrates the importance of a thorough history including probing for remote events given the high incidence of remote inciting events among adults aspirating foreign bodies. Clues which suggest possible remote aspiration include; history of recurrent pneumonias or hospitalizations, unilateral wheezing, and patient propensity for aspiration.
Additionally, this case exemplifies the importance for clinicians to remain critical of prior diagnoses and always employ or obtain confirmatory studies prior to accepting past medical problems as true. Our patient had been incorrectly diagnosed and treated as asthma for 3 years following his aspiration episode despite never undergoing confirmatory testing (i.e. PFTs with bronchodilator challenge). Clinicians can learn from this and not hold prior diagnoses as true until adequately confirmed.
89 COULD TUBE FEEDING CAUSE WEIGHT LOSS?
Mohamed A, Fenire M, Soape M, Mazek H, Aly M, Rakvit A. Texas Tech university health science center, Lubbock, TX.
Purpose of Study: Clinicians should assess diarrhea closely and consider tube misplacement when the diarrhea is persistent, all other stool studies are inconclusive or a diarrhea not responding to abortive treatment in patients with percutaneous endoscopic gastrostomy (PEG) tube feeds.
Methods Used: Case Analysis and Review of Literature.
Summary of Results: Patient is a 66 years old male with history of cervical myelopathy lead to cervical fusion one year ago. He presented with intractable diarrhea, weakness, and 30 pounds weight loss. He denies any nausea, vomiting, abdominal pain or blood in the stool. The patient has a history of a PEG tube insertion due to pharyngeal muscle weakness and risk of aspiration 6 weeks prior to presentation. The patient looked cachectic. Abdominal exam revealed scant purulent discharge at the site of PEG tube. Labs showed normocytic, normochromic anemia and decreased levels of pre-albumin, albumin, magnesium and phosphorus. Stool studies were negative for any infection. A subsequent computed tomography scan of the abdomen showed the PEG tube balloon tip in the transverse colon which is subsequently confirmed by a tubogram. The patient then underwent a surgical repair. A well matured colocutaneous fistula (CCF) was found during surgery. A new G-tube was placed and tube feedings restarted. He was able to tolerate tube feeds at a goal of 60 mL/hr.
Conclusions: The PEG tube was first described in 1980 but has since been widely used as an option for nutritional replacement therapy. Known complications of the procedure range from minor incidents including wound infection and bleeding to rare incidents such as CCF formation. A CCF usually occurs weeks following insertion. It is thought that since the insertion of the PEG tube is to some extent blind, it is placed occasionally through the bowel before ending in the stomach. Over days to weeks, the balloon or bumper becomes dislodged and settles into the bowel, which is the transverse colon in the majority of cases. In a recent case series and review of literature that included 28 cases, a majority of the cases involved some sort of tube replacement or revision. Interestingly, in our case, the PEG tube was never modified, and the patient’s symptoms soon developed following placement suggesting early migration rather than late.
90 KERNICTERUS AS A COMPLICATION OF HYPERBILIRUBINEMIA IN ADULT PATIENT
Mohamed A, Aly M, Mazek H, Fenire M, Ali E. Texas Tech University Health Science Center, Lubbock, TX.
Purpose of Study: This case highlights an extremely rare condition of reversible bilirubin neurotoxicity in an adult with sickle disease and Q fever induced biliary stasis. Our case is clinically interesting as it shows one of the highest recorded bilirubin levels in a patient with sickle cell disease that can lead to a condition considered extremely rare in adults, kernicterus. The clinical picture can include myoclonus that could be easily misinterpreted as asterixis due to hepatic encephalopathy.
Methods Used: Case analysis and review of literature.
Summary of Results: The patient is 48 years old male with past medical history of sickle cell disease presented with abdominal pain, severe jaundice, spiking fever, fatigue and myoclonus. He has a history of recent travel to china and prolonged Doxycycline use. He denies any nausea, vomiting or change in the color of the stool. On examination, the patient is icteric with epigastric tenderness. Labs reveal a bilirubin level 77.5 (mainly indirect), normocytic normochromic anemia with elevated reticulocyte count. Liver enzymes including alkaline phosphatase were mildly elevated. Q fever Immunoglobulin M was positive. Abdominal imaging was suggestive of biliary stasis with no evidence of intrahepatic or extra hepatic ducts dilation. The patient developed myoclonus that was reversed with the reduction of serum bilirubin.
Conclusions: Bilirubin neurotoxicity is related to the free unconjugated bilirubin that can cross blood brain barrier. Early bilirubin neurotoxicity can be reversible before permanent damage occurs from precipitation of bilirubin (kernicterus). Kernicterus is known to happen in children and extremely rare in adults; however in extremely high bilirubin levels, adult blood brain barrier can fail, our case being an example. Reversibility of neurotoxicity can happen with prompt decrease in bilirubin. Myoclonic movement disorder is one of the manifestation of bilirubin neurotoxicity which should be differentiated from negative myoclonus (Asterixis). Clinicians should be aware of myoclonus as a feature of bilirubin neurotoxicity and not misinterpret it as asterixis, as management of both conditions are different.
91 TAKOTSUBO CARDIOMYOPATHY ASSOCIATED WITH HYPERTHYROIDISM TREATED WITH THYROIDECTOMY
Omar S, Soontrapa S, Ali E, Mazek H, Zedan A, Suarez J. Texas Tech University Health Science center, Lubbock, TX.
Purpose of Study: Takotsubo cardiomayopathy is an uncommon clinical entity, also called apical ballooning syndrome, characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle. This syndrome mimics myocardial infarction in the absence of obstructive coronary artery disease. The exact mechanism of the wall motion abnormalities is unknown. but it was thought to be related with hyperstimulation of endogenous catecholamines inducing myocardial dysfunction and stunning. It is usually associated with emotional and physical stress. Thyrotoxicosis is a rare cause of takotsubo cardiomyopathy related to its direct and indirect effect on the heart.
Methods Used: Case analysis and literature review.
Summary of Results: We are reporting a 61 year old female with unknown past medical history, who was admitted with shortness of breath and palpitation and subsequently found to have atrial fibrillation with rapid ventricular response secondary to hyperthyroidism. She was complaining of shortness of breath but the patient denied any chest pain. The electrocardiogarm showed atrial fibrillation with non specific ST-T wave changes and elevated troponin T. Due to moderately decreased left ventricular systolic function seen on echocardiography, coronary angiogram was done; however, it did not show any coronary artery stenosis, but large apical ballooning with an ejection fraction of 30 %. Propylthiouracil and corticosteroids were added to treat thyrotoxicosis but the hyperthyroid state was difficult to control, finally decision was made to proceed with thyroidectomy to control the symptoms. Five days later the patient’s clinical improved significantly.
Conclusions: we are reporting a rare case of takotsubo syndrome in the setting of thyrotoxicosis, which was resistant to supportive and medical management, and required thyroidectomy. The association of takotsubo syndrome and hyperthyroidism has been reported before. Awareness of this possible association is of importance in establishing the diagnosis and instituting a proper medical or surgical treatment plan.
92 DOCETAXEL ASSOCIATED EPIPHORA
Orellana-Barrios MA, Payne J, Sotello D, Riaz J, Cobos E. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: A 59 year old female presented to the ER with bilateral eye edema, onset approximately 24 hours before presentation. She was diagnosed with Stage 4 intraductal carcinoma with multiple bone metastases. Her breast cancer was ER positive (99%), PR negative, HER2/neu negative, Ki67 high at 60%. She received radiotherapy for painful bilateral hip bone metastasis, and was placed on monthly denosumab, daily anastrozole, and docetaxel every three weeks. Her last docetaxel dose was 24 hours before her eye symptoms began.
On admission, her vital signs were normal and eye exam revealed epiphora, moderate to severe bipalpebral bilateral eyelid edema, normal color conjunctiva, normal eye movements, direct and indirect pupillary light reflexes were normal and she complained of slight blurred vision. The rest of her physical exam was normal. Also, her basic metabolic panel and hematology were within normal limits. She was diagnosed with Docetaxel induced epiphora and eyelid edema, and was placed on intravenous antihistamines, corticosteroids and opthalmic moxifloxacin and ocular lubricant. Ophthalmologic evaluation for lacrimal outflow passages obstruction was negative, although the patient clinically continued with epiphora and eyelid edema. Her edema improved and she was discharged on day 3.
Doxetacel is a commonly used taxane with indication for prostate, breast and non-small cell carcinoma. Standard treatment dose of 60-100 mg/m2 every 3 weeks. Infrequently the Doxetacel is administered in weekly doses and a smaller dose of 20-40mg/m2. Common side effects include myelosuppression and leukopenia as well as asthenia and peripheral neuropathy. In this case we present a photo of epiphora (excessive tearing due to narrowing of the lacrimal duct). This adverse effect severely hampers quality of life for patients and if not treated quickly can be permanently detrimental.
93 AN UNUSUAL CASE OF CARDIAC ARREST - CARDIOLOGISTS BEWARE
Panikkath D, Panikkath R, Aly M, Jumper C. Texas Tech University of Health Sciences, Lubbock, TX.
Introduction: Coronary artery disease is undoubtedly the most common cause of out of hospital sudden cardiac arrest (SCA) accounting for more than 90% of cases. However, uncommonly SCA can be due to other reasons, and might have disastrous consequences with empirical treatment directed at coronary artery disease.
Case Report: A 28 year old man without any significant past medical illness except chronic pain was found unresponsive without pulse, one day morning. Family members started cardiopulmonary resuscitation (CPR) and called 911. The emergency medical response team found asystole. He regained pulse after 10 minutes of CPR. Advanced airway was secured and therapeutic hypothermia initiated. Cardiology was consulted by the emergency room physician for T wave inversions in lateral leads and gross elevation of cardiac troponins. Cardiology team was planning to start anti platelets and low molecular weight heparin for possible ACS as a cause for SCA. However, on detailed history, his wife reported that he had mild headache prior to going to bed, the previous night. This prompted a computerized tomography scan of the head, which showed diffuse subarachnoid hemorrhage (SAH). Patient remained unresponsive without brain stem reflexes. A brain scan later confirmed brain death. The relatives chose to withdraw care and patient expired.
Conclusion: Spontaneous subarachnoid hemorrhage is an unusual cause of cardiac arrest and has an extremely poor prognosis due to the combined damage to the brain due to SAH and ischemic insult due to cardiac arrest. Sympathetic stimulation and release of catecholamines could be the reason for ventricular arrhythmias and cardiac arrest. ECG changes in patients with SAH may be pronounced and might mimic myocardial infarction or ischemia. This might lead to delayed recognition/ non recognition of the primary problem. SAH as a cause of cardiac arrest needs to be recognized, as treatment with anti-platelets and low molecular weight heparin (for suspected ACS leading to cardiac arrest) can lead to disastrous consequences in such patients. Although severe headache prior to the arrest is the clue to the diagnosis, it is well known that almost half of these patients may develop sudden collapse without any prodromal symptoms.
94 AN UNUSUAL CASE OF PERICARDITIS
Sotello D, Rivas M, Nugent K, Mckenzie P, Temple B. Texas Tech University Health Sciences Center, Lubbock, TX.
Case Report: A 27-year-old African American man without a past medical history was admitted with 1 day of continuous substernal chest pain which radiated to the back, was relieved by leaning forward, and was associated with fever, dyspnea on exertion, and orthopnea. Vital signs: BP-109/78 mmHg, HR-131 beats per minute, RR-24 per minute, temperature-96.5 °F. Physical examination: mild respiratory distress, lungs clear to auscultation, tachycardic, no murmurs, muffled cardiac sounds, no JVD, diffuse abdominal tenderness, and no peripheral edema. Initial laboratory: WBC-10.6 x103/mm3, Hb-13.9 g/dl, Platelets-131 x103/mm3, electrolytes within normal limits, creatinine 2.9 mg/dl, BUN 30 mg/dl, and UDS positive for marijuana. ECG: Sinus tachycardia and diffuse ST elevation. Transthoracic echocardiogram (TTE): EF 20-24%, large pericardial effusion with tamponade physiology. Blood cultures were positive for Streptococcus pneumoniae. Eventually the patient developed cardiac tamponade and underwent pericardiocentesis with pericardial window removing 400 ml of purulent fluid which also grew Streptococcus pneumoniae. The patient completed 6 weeks of ampicillin/sulbactam, and his kidney function returned to normal. The patient returned 3 weeks after discharge with restrictive pericarditis requiring anterior pericardiectomy.
Discussion: Streptococcal pericarditis (SP) is an uncommon diagnosis. It generally presents with acute cardiovascular decompensation and signs of sepsis. Its incidence has declined with the introduction of antibiotics and with the implementation of pneumococcal vaccine. SP usually occurs secondary to hematogenous spread due to concomitant infection, such as pneumonia (93%), osteomyelitis, otitis media, mediastinitis, impetigo, meningitis, etc. Primary streptococcal pericarditis is a very rare diagnosis, usually occurring the setting of immunosuppression (hypogammaglobulinemia, alcoholism, and diabetes). The occurrence of primary SP in previously healthy patients is very unusual. Diagnosis is suspected with clinical findings, including TTE and ECG, and ultimately confirmed with pericardiocentesis and fluid analysis. Treatment is with intravenous antibiotics (penicillins) for at least 4 weeks and surgery when indicated.
95 A CASE OF SUBSEROSAL EOSINOPHILIC GASTROENTERITIS PRESENTING WITH ABDOMINAL PAIN AND DISTENSION
Spera M, Gupta M, Engel LS, Nicaud M, Raines D. LSU Health Sciences Center, New Orleans, LA.
Case Report: Eosinophilic gastroenteritis is a rare condition that presents with varying gastrointestinal complaints depending on layer of involvement; mucosal, muscular, or subserosal.
Case: A 27 year old Mexican woman presented with three weeks of intermittent supra umbilical abdominal pain and progressively worsening abdominal distension. On physical examination the patient was noted to have abdominal distension with shifting dullness but was non tender to palpation. The CBC with manual differential showed a WBC of 19.4 x103/ul with 39% eosinophils. Computed tomography of her abdomen and pelvis with contrast showed diffuse mural thickening and edema of the small bowel with a large volume of free mesenteric and intra peritoneal fluid. Upper double balloon enteroscopy revealed diffuse congested mucosa in the third and fourth part of the duodenum. Patchy congestion was found throughout the jejunum. Pathologic exam of biopsies taken from the stomach, duodenum and jejunum showed increased lamina propria and mildly increased epithelial eosinophilia with an epithelial eosinophil count of 14 per high power field (range of 0-14) in the duodenum and jejunum. Cytology was negative for malignant cells. Ultrasound guided paracentesis was performed for diagnostic purposes. The serum to ascites albumin gradient was 0.5 g/dL. The ascitic fluid was amber and clear with a WBC count of 9960/ul with the differential of 76% eosinophils, 19% mesothelial cells, 3% monocytes and 2 % lymphocytes. The ascites fluid adenosine deaminase level was unremarkable. The patient was treated with an empiric course of albendazole for possible underlying intestinal parasite infection prior to the initiation of oral steroids as a treatment for serosal eosinophilic gastroenteritis.
Discussion: Patient with serosal eosinophilic gastroenteritis typically present with eosinophilic ascites with abdominal bloating and a high peripheral eosinophilia. Diagnosis is made with endoscopic biopsy of the affected area which usually shows greater than 20 eosinophils per high power field. When endoscopic biopsy is non diagnostic, full thickness surgical biopsy should be undertaken.
96 SMALL CELL CARCINOMA IS NOT EXCLUSIVELY A LUNG CANCER
Suvorava N1, Konala V1,2, Aulakh A1,2, Tijani L1,2. 1 TTUHSC, Lubbock, Lubbock, TX and 2 TTUHSC, Lubbock, TX.
Case Report: Extra pulmonary small cell carcinoma (EPSCC) represents about 2-5% of all small cell carcinomas (SCC). It’s a rare malignancy with aggressive course, frequent recurrences and early metastases. EPSCC can affect any site within the body except the central nervous system. We present a patient with SCC of lymph nodes.
A 62-year-old male presents with rapidly growing painless left sided axillary mass noticed about a year ago. It was rapidly increasing in size over 8 weeks with no associated symptoms. His past medical history was significant for coronary artery disease and 15-pack-year smoking history. He quit smoking 21 years ago. On physical exam, a firm and non-tender mass was noted over left axilla, measuring approximately 10cmx5cm and a palpable left supraclavicular node with left arm edema. CT chest revealed lobulated mass at the left axilla, measuring 11.5cm in maximal dimension and multiple clustered left supraclavicular lymph nodes. Fine needle aspiration of the mass revealed a SCC. The PET/CT scan revealed extremely hypermetabolic bulky supraclavicular, retroclavicular lymphadenopathy as well as left axillary mass.
The patient underwent concurrent chemo-radiation with four cycles of cisplatin and etoposide along with external beam radiation for a total of 35 treatments. Repeat PET/CT scan after completion of treatment showed resolution of the left supraclavicular lymphadenopathy with marked reduction in the left axillary adenopathy.
Early recognition is important since limited stage disease has better outcome. Survival with EPSCC is variable, ranging from 5 to 50 months for limited stage disease and 5-12 months for extensive stage disease. Multi-modality therapy using surgery, chemotherapy, and radiation is essential for cure in patients with limited stage of disease.
This case highlights that SCC is not an exclusively lung malignancy and could be found in sites such as genitourinary tract, gastrointestinal organs, nasal cavity, head and neck, parotid gland, pancreas, lymph nodes. Depending on primary site the prognosis may be variable, with SCC localized to lymph nodes carrying a better prognosis. The limited number of reported cases makes this type of tumors challenging to deal with and more clinical trials are needed to determine the effective treatment options.
97 SPINAL METASTASIS AS INITIAL PRESENTATION OF HEPATOCELLULAR CARCINOMA IN A PATIENT WITH METASTATIC CARCINOID TUMOR
Suvorava N1, Konala V1,2, Aulakh A1,2, Tijani L1,2, Warraich I3. 1 TTUHSC, Lubbock, Lubbock, TX; 2 TTUHSC, Lubbock, TX and 3 TTUHSC, Lubbock, TX.
Case Report:
Introduction: Spinal metastasis can occur both in Carcinoid tumor and Hepatocellular carcinoma (HCC) with low incidence compared to other solid tumors. We present a patient with worsening abdominal, neck and back pain with metastatic neuroendocrine carcinoma of the intestine.
Case Presentation: 60 year old male with past medical history of Hepatitis C with liver cirrhosis and neuroendocrine carcinoma of the intestine with metastasis to liver diagnosed in 2011, treated with octreotide presented with worsening right sided abdominal pain, neck and back pain in spite of being on methadone and hydrocodone as needed for pain. He had 30 pack year smoking history, uses marijuana daily. Physical exam was significant for tenderness on palpation of the right upper quadrant.
CT scan of abdomen and pelvis showed osseous lytic lesions thoracic and lumbar spine with pathological fracture of ninth thoracic vertebrae. It also showed both carcinoid tumor at the primary site and liver metastases were stable compared to previous imaging. Subsequent MRI of the spine confirms multiple lytic lesions in cervical, thoracic and lumbar spine. Ultrasound guided biopsy of the cervical bone lesions revealed metastatic HCC. Alpha-Feto protein was mildly elevated at 17.7 International units/ml. Patient received symptomatic treatment with analgesics, pamidronate and was started on palliative radiation treatment to the spine.
Discussion: Carcinoid tumors metastasize to lymph nodes, liver, lungs. Skeletal metastases are becoming more prevalent due to longer survival and advances in earlier detection. Incidence of skeletal metastases is approximately 10%.
HCC commonly metastasizes to lungs, followed by the lymph nodes and bone. The incidence of bone lesions in HCC ranges from 1% to 20% in autopsied cases.
Given our patient has liver cirrhosis secondary to hepatitis C and stable metastatic carcinoid tumor on octeotride, new onset symptoms alerted to further investigate the cause of spinal metastasis. High index of suspicion is required when a patient presents with spinal metastasis in the presence of primary tumor to suspect a second tumor in the presence of risk factors.
98 PASTEURELLA MULTOCIDA CELLULITIS OF THE KNEE IN A PATIENT WITH RECENT TOTAL KNEE ARTHROPLASTY
Suvorava N1, Dobronski L1, Mazek H1, Nichols J1, Winn R1,2. 1 TTUHSC, Lubbock, TX and 2 TTUHSC, Lubbock, TX.
Case Report: Pasteurella multocida is part of the oral flora of wild and domestic animals, known to cause infection after animal bites. Infection may occur without physical contact or from contact with animal secretions. We present a case of P. multocida cellulitis after a dog lick.
A 59-year-old female developed fever, hypotension, vomiting, leg pain, redness and swelling over 9 hours. Heart disease, chronic kidney disease, obesity, and osteoarthritis with bilateral knee replacements were reported. She had 2 dogs and allowed them to lick her legs. The right knee was erythematous, edematous, hot and tender to palpation with limited ROM due to severe pain. Purulent drainage was noted from one of the previous surgical incision sites on the leg. Leukocyte count and inflammatory markers were elevated. X-rays showed no abnormalities of the prosthetic joint; moderate suprapatellar joint effusion and edema of subcutaneous tissues of the knee were present.
ICU admission with administration of vasopressors, fluids, levofloxacin, piperacillin-tazobactam and vancomycin was necessitated. Joint aspiration was declined due to overlying cellulitis. A culture from the wound revealed P. multocida. Blood cultures were negative. She improved and Infection was eradicated with continued outpatient antibiotics.
P. multocida cellulitis is characterized by rapid inflammatory signs within hours. Septic arthritis occurs in up to 6%. For prosthetic joint infection antibiotic therapy without removal of an infected TKA may be appropriate for acute infection, when the prosthesis is not loose and the infection is treated early. For wound infections due to P. multocida antimicrobics such as penicillin, amoxicillin/clavulanate or doxycycline can be used or, as alternative, second and third generation cephalosporins or aztreonam can be considered. Susceptibility testing is recommended.
P. multocida infection/disease may result in severe morbidity or death. History of animal exposures/bites particularly with coexisting immunocompromise, artificial valves or arthroplasties may be of critical importance. Direct injection of Pasteurella through bites or scratches clearly can lead to infection as can exposure to saliva from licking of open wounds by pets.
99 AN UNUSUAL CASE OF PCP PNEUMONIA IN A NON-HIV PATIENT
Tariq K, Landa C. University of Florida College of Medicine, Jacksonville, FL.
Case Report: A previously healthy 38 year old Caucasian male was admitted to the Intensive Care Unit for evaluation and treatment of acute respiratory failure and septic shock. He was found to have bilateral, multilobar infiltrates on CXR but initial respiratory gram stain and culture failed to reveal a causative agent. Blood cultures and urinalysis with culture were negative. Eventually a PCP smear showed Pneumocystis jiroveci. This discovery led to further investigation for an immunocompromised state. The patient did not have any risk factors per history. The work up included two negative HIV tests, including DNA PCR. A hepatitis panel was positive for Hepatitis C antibodies but RNA PCR was not detectable. Finally, the CD 4 T lymphocyte count returned at 73. The patient had a difficult hospital course requiring prolonged ventilator support and the use of pressors, complicated by bilateral pleural effusions requiring chest tube placement. After an extensive course, the patient fully recovered and was discharged home on appropriate medications.
HIV infection has become synonymous with immunosuppression and a low CD4+ T lymphocyte count. However, it is not the only cause of reduced levels. Idiopathic CD4+ T cell Lymphocytopenia (ICL) is a very rare syndrome that mirrors HIV/AIDs in many ways. The criteria for ICL was first established by the CDC in 1993, which includes a CD4 count less than 300 cells per microliter, or less than 20% of T lymphocytes are CD4+, lack of laboratory evidence of HIV infection and absence of any alternative explanation for the CD4 T cell lymphocytopenia. The most common opportunistic infections associated with ICL are Cryptococcus Neoformans, non-Tuberculous Mycobacteria, Progressive Multifocal Leukoencephalopathy, Kaposi Sarcoma and the genital Human Papilloma Virus. Pneumocystis pneumonia is a very uncommon infection in ICL. Our case emphasizes the importance to consider ICL in HIV negative patients affected by AIDS defining opportunistic infections.
100 WHAT’S IN THE DIFFERENTIAL? A CASE OF HYPEREOSINOPHILIC SYNDROME MASQUERADING AS CEREBRAL VASCULITIS
Weeks A, Williams JC, Grover I, Elkins S. University of Mississippi Medical Center, Jackson, MS.
Case Report: Peripheral blood eosinophilia is precipitated by reactive or clonal processes including atopic and allergic diseases, helminthic parasite infections, adverse drug reactions, and neoplasms. Classically a diagnosis of exclusion, hypereosinophilic syndrome (HES) is a rare disorder defined by persistent blood eosinophilia (≥ 1.5 x 10x9/L), eosinophil mediated end-organ damage, and absence of a secondary cause. Here we report a case of idiopathic HES manifesting as neurological dysfunction responsive to prednisone.
FISH for CHIC2, 4q Deletion (FIP1L1 and PDGFRA Fusion); Translocation (5;12) (PDGFRB); 8p11.2 (FGFR1) performed at Mayo Medical Laboratory. Routine imaging, CSF, blood, and cytogenetic testing were performed at our institution.
A 78 year old white female with history of diabetes mellitus, hypertension, COPD, and squamous cell skin cancer initially presented to an outside hospital with a 3 day history of right upper and lower extremity weakness, gait disturbance, confusion, and disorientation. Eleven days later, she was transferred to our facility with the diagnosis of worsening cerebral vasculitis. Physical exam was notable for right sided weakness, confusion, lethargy, diplopia, and decreased alertness. Review of outside records revealed an absolute eosinophil count of 17.5 10x9/L. Medication profile uncovered no drug related causes. CSF studies for multiple sclerosis, viral, bacterial, and fungal etiologies were negative. Parasitic infection was negated by serum and stool testing. MRI brain revealed multiple scattered infarcts suspicious for vasculitis; however, subsequent cerebral angiogram was normal. Cytogenetic and FISH analysis from peripheral blood and bone marrow were normal. The patient was immediately started on weight based prednisone. One week later, the patient’s mental status returned to baseline and she was discharged with an eosinophil count of 5.8 x 10x9/L.
Both early recognition of HES and introduction of eosinophil-reducing agents are vital to patient survival. This case highlights the importance of careful history taking and thorough evaluation when reporting a diagnosis of exclusion. Furthermore, it reinforces that clinical judgment combined with available data trumps isolated imaging reports and previous diagnoses.
101 “THE MIKE TYSON CHALLENGE: AN EXTREME CASE OF RHABDOMYOLYSIS”
Wright A, Spiegel J, Engel LS. LSU Health Sciences Center, New Orleans, LA.
Case Report:
Introduction: There are many causes of rhabdoymyolysis, including excessive exercise. One of the most serious complications of rhabdoymyolysis remains acute kidney injury (AKI), which is caused by non-protein heme pigment that is released from myoglobin. Furthermore, inflammation of the muscle can compress structures in the same fascial compartment resulting in compartment syndrome.
Case: A 24 year old inmate was brought to the emergency department with severe thigh pain and dark colored urine after participating in “The Mike Tyson Challenge” During this challenge he performed 372 squats over a 45 minute time interval. The thigh pain began the next morning followed by “coca cola” colored urine. On physical exam his thighs were extremely tense and he underwent emergent bilateral fasciotomy for compartment syndrome. He was found to have a creatinine kinase of 401,880 U/L, BUN of 45 mg/dl, serum creatinine 7.21 mg/dl, and potassium of 6.3 mmol/l. Urinalysis revealed 250 blood/ul but only 3-5 red blood cells/HPF. He received insulin, sodium polystyrene sulfonate, IV fluid hydration, and hemodialysis. He slowly improved while receiving 3 weeks of hemodialysis and physical therapy in the hospital.
Discussion: In his prime Iron Mike Tyson was the self proclaimed ‘baddest man on the planet’. A workout based on his physical training was developed and named the Mike Tyson Beast Workout or Challenge. Some rules of the ‘Beast Workout’ are as follows:1) The workout must be performed in no more than one hour; 2) The aim is to perform dead lifts, bench press, squats, chest press and dumbbell curls through-out the hour. Our patient barely survived the squats. Fortunately, aggressive surgical intervention, fluid hydration and hemodialysis were able to reverse the damage caused by the release of myoglobin from injured muscle.
102 ICE COLD IN MISSISSIPPI: A CASE OF NOSOCOMIAL FROSTBITE
Yates R, Isaac J, Grover I. University of Mississippi Medical Center, Jackson, MS.
Case Report: Frostbite is severe, localized tissue injury induced by cold temperatures. It varies in severity from first to fourth degree, fourth degree being most severe with muscle and bone involvement. We present a case of a young woman originally hospitalized for sepsis who developed severe frostbite requiring amputation of her bilateral lower extremities. A 39-year-old African American female with uncontrolled diabetes and neuropathy presented with sepsis secondary to pyelonephritis. She was admitted to the intensive care unit due to hypotension and started on norepinephrine and broad spectrum antibiotics. She improved and was transferred to the general medicine service. Two days later, we discovered new onset, sharply demarcated, hyperpigmented skin lesions with blistering in a stocking pattern on her bilateral lower extremities. No other areas were involved. Initial differential included contact dermatitis or a drug reaction, but further questioning revealed that the patient had retrieved a bucket of ice in which she soaked her feet for about 30 minutes to relieve burning, neuropathic pain. Pedal pulses were not palpable. Frostbite treatment protocol was initiated, including passive and active rewarming of the lower extremities. Vascular surgery was consulted and recommended computed tomography angiography with runoff for further evaluation. It confirmed lack of appropriate blood flow below the knees bilaterally. Heparin infusion was initiated. She was taken to the operating room to attempt intra-arterial tissue plasminogen activator, but this was unsuccessful. Due to imminent tissue necrosis and risk of infection, the patient underwent bilateral below the knee amputations. Pathology confirmed severe frostbite as the etiology of her skin findings. While frostbite is the most common cold injury, it is much more prevalent in northern climates and in groups frequently exposed to cold temperatures such as mountaineers. Only a handful of nosocomial cases are reported in the literature. In addition, diabetes and neuropathy are known risk factors for frostbite injury, and this case demonstrates this well. Finally, this case illustrates that frostbite should be included in the differential of dermatoses presenting in the stocking-glove distribution.
102A TRAVEL MEDICINE AND HEMOGLOBINOPATHIES
Henegan JC, Herrin V. University of Mississippi Medical Center, Jackson, Mississippi.
Introduction: As opposed to Hemoglobin SS disease, patients with Hemoglobin SC disease may have a functional spleen. However, they remain at risk for an acute splenic infarct. Knowledge of a destination’s altitude is an important component of travel medicine.
Case Report: A 32 year-old female dentist with Hemoglobin SC disease travels from Jackson, Mississippi, (elevation: 279 feet) to the capital of Bolivia (elevation: 9,220 feet) for a weeklong medical missions trip. Within an hour after landing in Bolivia she develops a dull abdominal ache that progresses to a continuous, intense pain. She is stabilized with available supplies that include intravenous hydration, analgesics, and supplemental oxygen. Her hematologist is contacted and recommends that the patient return to the United States as soon as possible. Three days after initially arriving the patient flies back to New Orleans, LA, where it has been arranged for her to be evaluated soon after arrival. She presents to a hospital aware of her recent travel where she is stabilized. Imaging reveals a massive splenic infarct. Serial exams and labs along with repeat imaging exclude splenic sequestration syndrome.
Discussion: As opposed to Hemoglobin SS disease in which patients almost universally develop functional asplenia, in Hemoglobin SC disease the incidence of functional asplenia in persons older than twelve is approximately 45%. People with Hemoglobin SC disease and a functional spleen remain at risk for splenic infarction throughout their life. Air travel and changes in altitude are recognized factors associated with acute splenic sequestration and splenic infarction for patients with Hemoglobin SC disease as well as for those with sickle cell trait alone. Our patient, who described herself as “never” having a pain crisis before, was at risk for experiencing an acute splenic infarct or acute splenic sequestration with her travel to Bolivia. This case highlights the importance of integrating knowledge about methods of travel and the destination’s altitude into travel medicine.
Allergy, Immunology and Rheumatology Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
103 CORNEAL MELT SYNDROME: A COMMON MANIFESTATION OF AUTO-IMMUNE DISORDERS
Bhawal J, Majithia V, McMurray R. UMMC, Jackson MS.
Case Report: Corneal melting is inflammatory condition of cornea involve disruption of epithelial and corneal stroma which are protective layer of cornea, and cause byconnective tissue disorder like RA, lupus, AS and wegners granulomatosis. it may be a rare complication of rheumatoid arthritis, Sjögren’s syndrome and may progress rapidly within days lead to complete blindness.
Cases: 1. An 84 y/o female with multiple PMH was evaluated due to positive ANA, SS-A, negative R,F previous uveitis and corneal melt. She had cataract surgery about 4 years ago and developed uveitis in right eye which lead to enucleation of the eye due to a complicated course. she developed infection in the left eye and perforation of the cornea leading to emergent corneal transplant.She did report dry mouth and dry eyes for a couple of years and raynaud’s. She was started on prednisone daily, and azathioprine 150 mg/day.
2. 79 y/o F with multiple medical problem including RA was, pt was evaluated due to necrotizing scleritis of left eye,pt described onset like had foreign body sensation in her Left eye started from About 4 weeks ago, subsequently effecting her vision and was prescribed prednisone eye drops, but lher vision started getting worse and Saw ophthalmologist, subsequently biopsy and scleral patching of her Eye was done and was started on prednisone, patient started complaining of severe pain and complete loss of vision in her left eye. She was started on solumedrol 125 mg IV daily and quantiferon and hepatitis profile negative and started on rituximab infusion every 2 weeks.
Discussion: Healthy cornea contains inactivators of proteinase and a nice tear film, which protects it from damage. Any disorder, trigger or decreased tearing leads to increased cytokines, tumor necrosis factor and interleukin-1 leading to activation of corneal proteinase, which cause keratolysis. A mild case of keratitis can be treated with NSAIDS alone, but a moderate to severe case requires treatment with methotrexate and prednisone. In the most severe cases oral cyclophosphamide may be needed followed by azathioprine or cyclosporine for maintenance therapy. Rituximab, TNF blockers and other biologics have been used successfully in some cases too.
104 A CASE OF DISSEMINATED MUCORMYCOSIS
Mains TB, Majithia V, McMurray R. University of Mississippi Medical Center, Jackson, MS.
Case Report: Case Report: Introduction: Mucormycosis is aggressive fungal infection, classically occurring in poorly controlled diabetics, or immunodeficient individuals. It may be possible that some medications used in the treatment of rheumatic diseases may increase the risk of this infection.
Case Presentation: 48 y.o white female with Systemic Lupus Erythematous (SLE) with severe arthritis presented to UMC after hospitalization at an OSH for CVA and thrombocytopenia. She was taking Plaquenil 200mg bid, Methotrexate 20mg/wk but stopped anti-TNF therapy 2 months prior to her hospitalization due to financial constraints.
Initially she presented with dysarthria, left facial droop, and Right sided weakness. Imaging was revealed a left cerebral infarct. CVA evaluation discovered a valvular vegetation on echo, left carotid stenosis, normal complements, leukocytosis, thrombocytopenia, negative cultures and APLS panel. The thrombocytopenia diagnosed as Immune thrombocytopenia purpura (ITP) secondary to her lupus after bone marrow and labs were not diagnostic. She was treated with IVIg, followed by 4 weekly doses of Rituxan. Prior to her family transferring her to UMC, the patient developed a thigh abscess that required surgical drainage and initiation of antibiotics.
At UMC she was found have SIRS with an acidosis and acute kidney injury, started on broad spectrum antibiotics and admitted to medicine. She quickly decompensated had an episode of cardiac arrest. EKG after transfer to the ICU revealed ST segment elevation. Cardiac catheterization revealed likely coronary vasospasm in the LAD. Clinical status further deteriorated and anoxic brain injury was suspected. Repeat imaging showed diffuse areas of ischemia. After another episode of cardiac arrest she expired. Autopsy revealed disseminated mucormycosis with fungal emboli.
Discussion: Mucormycosis is a fulminating, highly aggressive fungal infection, typically occurring in uncontrolled diabetics, or immunodeficient individuals. Many patients with rheumatic diseases frequently require immunosuppressive medications which may increase the risk the risk atypical infections such as mucormycosis.
105 “COMPARATORS OF PROTECTIVE FACTORS OF BONE MINERAL DENSITY IN A NEW ORLEANS SARCOIDOSIS POPULATION”
Walker M, Janot A, Yu M, Lammi MR, Saketkoo LA. LSU Health Sciences Center, New Orleans, LA.
Purpose of Study: The pathophysiology of sarcoidosis involves dysregulation of dependent factors of bone metabolism, such as vitamin D and calcium, and high dose persistent treatment with steroids may lead to low bone mineral density (LBMD). LBMD in sarcoidosis is presumed but has yet to be described.
Methods Used: A retrospective chart review of biopsy-proven patients with a diagnosis of sarcoidosis for >1 year was used to compare parameters of prevalence, age (at chart review), gender, smoking status and designation of LBMD based results of Dual Energy Xray Absorptiometry (DEXA) studies. All calculations are based on non-parametric analyses using Fisher’s exact for categorical data and Mann Whitney tests for continuous variables.
Summary of Results: 61 patients (86.9% African-American) were identified that met criteria, 38 (62.3%) with LBMD (30 with osteopenia and 8 with osteoporosis). A significant difference was found in occurrence of LBMD in patients with BMI > vs <30 with patients BMI > 30 having lower levels of LBMD (as is expected in the general population), but no significant differences (table) were found in occurrence of LBMD in patients age > vs < 65, in ever vs never smokers (age between ever smokers and never smokers was not significantly different), or in males vs females (with females being significantly older than males and female age range 34-79).
Conclusions: Factors protective against LBMD in the general population were not demonstrated in this population of sarcoidosis patients. A lower risk of LBMD was not conferred by age < 65, male gender, or non-smoking status. These trends including significantly older age of females vs males suggests an abnormal distribution of LBMD in our sarcoidosis population that is not expected in the general population. Further examination of LBMD in sarcoidosis may yield evidence to support increased vigilance in steroid use and perhaps consideration/consensus to initiate steroid sparing agents earlier in the disease course.
106 GENDER INFLUENCES ON ORGAN MANIFESTATIONS IN A NEW ORLEANS SARCOIDOSIS POPULATION
Walker M1, Janot A1,2, Grewal H1, Yu M1, Lammi MR1, Saketkoo LA1. 1LSU Health Sciences center, New Orleans, LA and 2Medical of Virgina, Richmond, VA.
Purpose of Study: Sarcoidosis is a multi-organ disease of unknown etiology characterized by granuloma formation and fibrosis in affected organs. Prior studies have shown a gender association with organ specific manifestations. Male gender is associated with a more severe radiographic picture and female gender with more frequent extra-pulmonary manifestations (EPM). We conducted a survey of gender-based differences of organ-specific manifestations of sarcoidosis in a New Orleans cohort from a tertiary care institution cohort.
Methods Used: A retrospective chart review on patients seen in our clinics from 2006-2012 with biopsy proven sarcoidosis and a diagnosis >1 year were included. Data was collected on gender, smoking status, presence of EPMs (cutaneous, ocular, cardiac, neurologic, GI, and renal), chest radiographs and pulmonary function testing (PFT). Differences in gender and presence of EPMs and pulmonary sarcoidosis were calculated. Gender differences in FVC, TLC, and DLCO were calculated using a t-test for the mean. PFTs were stratified by time of diagnosis in five year intervals.
Summary of Results: Of 511 charts reviewed, 156 pts met inclusion criteria. Males had ocular sarcoidosis (OS) more frequently (M=0.28, F=0.104, p=0.005) and relative risk was calculated to be 2.24 (p<0.05, 95% CI 1.09 to 4.63). Gender was not a significant risk factor for other EPMs, nor for all EPMs combined. However, N limited statistical analysis of an apparent trend in the presence of GI/splenic sarcoid disease favoring females (F=11%, M=6%). The presence of pulmonary sarcoidosis was not associated with gender (p=0.3). See table 1. PFTs showed significant gender difference in that males had worse FVC (M=69.0, F=82.2, p=0.030) and TLC (M=63.0, F=78.86, p=0.003) 5-10 years after diagnosis. Diffusing capacity also showed gender specific differences with females having a worse DLCO than males 10-15 years after diagnosis. (M=72.0, F=55.33, p= 0.024).
Conclusions: Male sex was a risk factor for ocular sarcoidosis. Though gender was not associated with radiographic sarcoidosis, when controlled for smoking, increased severity of restrictive lung disease was demonstrated in males. Differences in DLCO warrant investigation for risk of pulmonary vascular disease in females.
Cardiovascular Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
107 FUNCTIONAL AND DYSFUNCTIONAL HDL IN HEART TRANSPLANT: THE IMPORTANCE OF CHANGES POST TRANSPLANT
González W1, Altieri PI1,2, Banchs HL1,2, Iravedra D1, González-Cancel IF2, Calderón RE1,2, Gurrea C2, Escobales N1, Crespo M1. 1University of Puerto Rico, San Juan and 2Cardiovascular Center of Puerto Rico and the Caribbean, San Juan.
Purpose of Study: To study the metabolic changes post heart transplant.
Methods Used: 101 Patients (P.) with heart transplant were studied. 65 P. were males and 36 were female, with a mean age of 51 years.
Summary of Results: Pre and post metabolic changes were:
1. BMI (25 ± 4-28 ± Kg/m2 P < 0.05).
2. Systolic blood pressure (107 ± 13-131 ± 20 P <0.05).
3. Diastolic blood pressure (70 ± 13-81 ± 10 mmHg).
4. Fasting blood sugar (107 ± 37-117 ± 55 mg%) N.S.
5. Total cholesterol (170 ± 55-189 ± 32mg/dl) P < 0.05.
6. Total HDL (38 ± 16-52 ± 17mg/dl) P < 0.05.
7. Total LDL (99 ± 20-83 ± 15mg/dl) N.S.
8. Triglycerides (163 ± 10-188 ± 12mg/dl) N.S.
Conclusions: Our data shows that all the P. developed Mets. The HDL of the whole groups increased from 38 mg/dl to 52 mg/dl. These changes are not explained only by the immunosuppressive treatment, HDL has a role as an anti-inflammatory agent which is inherent in the lipoprotein. This will also increase the HDL. 16 P. died of rejection. The HDL of the rejected P. increased from 47 ± 22 to 71 ± 40 mg/dl P. < 0.007. This increase persisted through the course of the rejection period. The mean age of the transplanted heart was 22 years. The rejection occurred in less than 5 years. (3.5 years). Only 7 autopsies were done. 5 of them showed severe atherosclerotic changes in the coronaries and aorta. This is probably explained on basis of dysfunctional HDL. Probably the high levels and persistent elevation of HDL in the rejected group can be used as a marker to predict rejection.
108 AUGMENTATION INDEX IS ASSOCIATED WITH RENAL FUNCTION IN BLACK BUT NOT IN WHITE YOUNG ADULTS: THE BOGALUSA HEART STUDY
Fernandez C, Li S, Chen W, Srinivasan SR, Berenson GS. Tulane University, New Orleans, LA.
Purpose of Study: Increased Augmentation Index (AI) has been associated with kidney damage in patients with hypertension and type 2 diabetes mellitus. However, information is scant on the race-specific (black-white) association between AI and renal function/performance in asymptomatic young adults.
Methods Used: As a part of the Bogalusa Heart Study, a long term community-based study, 884 non-institutionalized participants with a mean age of 43.5 years (29.4-51.3years; 68.3% white and 41.9% male) were considered. AI was estimated non-invasively by applanation tonometry of the radial artery. eGFR was calculated using the MDRD study equation. Race-specific independent association of AI with eGFR was tested through multivariable adjusted linear regression analyses.
Summary of Results: Black vs white participants had higher AI and eGFR levels (p<0.01). As regards gender differences, black females had significantly higher levels of AI and eGFR compared to black males (p<0.01). In multivariable adjusted linear regression analyses, controlling for age, sex and traditional cardiovascular risk factors, AI was significantly and directly associated with eGFR in blacks ( β =1.12, p<0.001), but not in whites ( β =0.039, p=0.34)
Conclusions: These findings support the hypothesis that underlying mechanisms for cardiovascular disease related-end organ damage differ among blacks vs whites. Further, this may aid to focus on race-specific approaches to prevention and screening of cardio-metabolic risk factors, diseases and associated complications.
109 LIFESPAN PREDICTORS OF CARDIOVASCULAR MORBIDITY IN INDIVIDUALS REACHING MIDDLE AGE: THE BOGALUSA HEART STUDY
Fernandez C, Li S, Chen W, Srinivasan SR, Berenson GS. Tulane University, New Orleans, LA.
Purpose of Study: Considerable information is available on the clustering of cardiovascular (CV) risk factors across the lifespan and their impact on cardiovascular disease (CVD) morbidity and mortality. In spite of this, information is scarce on the individual contribution of CV risk factors measured longitudinally from childhood to adulthood, as well as their cumulative burden, on CVD morbidity.
Methods Used: The longitudinal study cohort comprised 118 individuals aged 25-46 years (mean age 34.2 years); 44.1% black and 63.6% female, who were residing in the semi-rural community of Bogalusa, Louisiana and participated in the study since childhood. These participants had at least 3 traditional CV risk factors measurements since childhood and self-reported information on adult CVD morbidity. Mean follow up period was 14.3 years. CVD was defined as positive personal history of one or more of the following: angina, percutaneous coronary intervention, coronary artery bypass grafting, myocardial infarction and/or stroke. The area under the curve (AUC) was used to assess the cumulative burden of risk factors.
Summary of Results: After accounting for the effect of age, race, sex, cigarette smoking and family history of CVD, significant predictors of CVD were: childhood body mass index (BMI) (Odds Ratio [OR], 1.36; 95% Confidence Interval [95% CI] 1.12-1.62) and non-high density lipoprotein cholesterol (nonHDL-C) (OR, 1.22; 95% CI, 1.15-1.73); adulthood BMI (OR, 1.13; 95%CI, 1.02-1.24), Systolic Blood Pressure (SBP) (OR, 1.32; 95%CI, 1.07-1.65) and nonHDL-C (OR, 1.39; 95%CI, 1.11-1.56); and long-term cumulative burden of BMI (OR, 1.29; 95%CI, 1.21-1.37) and nonHDL-C (OR, 1.47; 95%CI, 1.38-1.71).
Conclusions: The observed adverse associations of childhood/adulthood cardiovascular risk factors and their long-term cumulative burden on adult CVD morbidity, are indicative of the individual impact of these risk factors in the development of heart disease. Hence, risk factor-oriented interventions (through primordial prevention early in life) must continue to be implemented to avoid further deleterious effects caused by risk factors and subsequent disease complications.
110 TOBACCO SMOKING STRENGTHENS THE ASSOCIATION BETWEEN HIGH BLOOD PRESSURE AND ARTERIAL WALL STIFFNESS: THE BOGALUSA HEART STUDY
Yun M1,2, Ge S1, Li S1, Fernandez C1, Chen W1, Srinivasan SR1, Berenson GS1. 1Tulane Center for Cardiovascular Health and Department of Epidemiology, Tulane University, New Orleans, LA and 2College of Life and Environment Sciences, Minzu University, Beijing, China.
Purpose of Study: The synergistic effect of tobacco smoking and elevated blood pressure (BP) is not well known, especially for the long-term burden of elevated BP. This study assessed the hypothesis that smoking strengthens the association between long-term cumulative burden of BP since childhood and adult arterial stiffness.
Methods Used: The study cohort consisted of 945 adults (661 whites and 284 blacks, aged 24-43 years) who have BP measured 4-15 times since childhood (aged 4-16 years) in Bogalusa, LA since 1973. The adult arterial stiffness was measured as aorta-femoral pulse wave velocity (PWV); the total area under the curve (AUC) and incremental AUC were used as a measure of long-term burden and trends of BP, respectively.
Summary of Results: Higher systolic BP values of childhood (p=0.009), adulthood (p<0.001), total AUC (p<0.001) and incremental AUC (p<0.001) were all significantly associated with increased adult PWV, after adjusting for age, race, gender, body mass index and heart rate; diastolic BP showed similar patterns of association with PWV. Furthermore, years of smoking was a significant predictor of PWV (p=0.027). In the interaction analyses, the increasing trend of PWV levels with increasing adult BP (p=0.003, see the figure below), total AUC (p=0.010) and incremental AUC (p=0.049) among smokers was significantly greater than that among nonsmokers.
Conclusions: These results suggest that the adverse influence of BP levels on arterial stiffness begins in childhood, and tobacco smoking accelerates this process, indicating the importance of preventive strategies in early life involving healthy lifestyles.
111 THE UTILITY OF SERUM TROPONIN IN PATIENTS ADMITTED WITH SYNCOPE
Bhusri S, Pashkovetsky E, Bierzynski A, Armstrong DF, Daneshvar D, Panagopoulos G, Coplan NL. Lenox Hill Hospital, New York, NY.
Purpose of Study: The objective of this study is to evaluate the immediate clinical utility of measuring serum troponin in patients presenting with syncope.
Methods Used: Data from 200 consecutive admissions with an admitting diagnosis of syncope were collected from the Emergency Department. Each admission was categorized based on initial serum troponin (negative <0.015 ng/mL), age, sex, gender, cardiac risk factors, and ejection fraction to assess the prevalence of adverse cardiac outcomes. Exclusion criteria included significant ST changes and chest pain as part of the initial presentation. Statistical analysis was performed using the Mann–Whitney Test, Chi-Square, and T-test.
Summary of Results: After excluding patients that otherwise required a serum troponin check (i.e. chest pain and/or significant ST changes), levels were obtained in the remaining 178 patients. Of these patients, 28 patients (15.73%) had a positive troponin (>0.015). Troponin positive patients were all male (p<0.01) and had a significant past history of arrhythmia (p=0.007). In contrast, troponin negative patients were mostly female (p<0.01). Outcomes data suggest a longer length of stay (<0.01) in the troponin positive group without any significant differences in ejection fraction, arrhythmia detected and whether the patient was on a monitored unit.
Conclusions: Measurement of serum troponin levels has no significant impact on evaluation in patients with syncope.
112 CATION DYSHOMEOSTASIS AND DELAYED MYOCARDIAL REPOLARIZATION WITH CARDIAC ARRHYTHMIAS IN THE HOSPITAL SETTING
Spiegel SB, Khan MU, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: QTc interval prolongation, an ECG index of delayed myocardial repolarization, is known to increase the propensity for supra- and ventricular arrhythmias. A dyshomeostasis of K+, Mg2+ and Ca2+ resulting from acute stressor states and/or medications, such as diuretics, may lead to QTc prolongation (>440 ms) and appearance of arrhythmias. Herein, we studied the presence and association of a dyshomeostasis of these cations in patients found to have prolonged QTc on standard 12-lead ECG.
Methods Used: A retrospective chart review of 200 consecutive patients (52±1 yr) who were found to have QTc prolongation when presenting or admitted to the Regional Medical Center in Memphis between May and July 2013. We excluded patients with previously documented chronic renal failure (serum creatinine >2mg/dL), those receiving any other medications known to prolong QTc, and outpatients where sufficient laboratory data was not available. Lowest levels of serum Ca2+, K+, and Mg2+ were noted within 24 hrs of obtaining the ECG, together with cardiac rhythm and QTc interval duration.
Summary of Results: Potassium values <4.0 were present in 61% and in 19% it was <3.5; Mg2+ <2.0 in 51.4% and <1.8 in 19% of patients with prolonged QTc. Hypocalcemia was present in 30% of patients. Eighty percent were found to have any form of cation dyshomeostasis of which arrhythmias were seen in 52%. These arrhythmias were supraventricular in 39, ventricular in 12, and both supraventricular and ventricular in 8.
Conclusions: A prolonged QTc interval on standard 12-lead ECG and attendant cardiac arrhythmias are frequently associated with hypokalemia, hypomagnesemia and/or hypocalcemia. Serial surveillance and correction of serum cation levels within strictly defined limits (K+ ≥4.0 and Mg2+ ≥2.0), vis-à-vis laboratory-based range of nonbiologic normal values, is recommended to avoid arrhythmias.
113 RITUXIMAB: A DYSHOMEOSTASIS OF SERUM POTASSIUM, MAGNESIUM AND CALCIUM WITH CARDIAC ARRHYTHMIAS
Khalid H, Khan MU, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Rituximab is a chimeric monoclonal antibody that targets protein CD20 to destroy B cells. Its association with supra- and ventricular arrhythmias and cardiac arrest has recently been reported; however, their pathophysiologic origins are uncertain. We hypothesized rituximab is associated with dyshomeostasis of extra- and intracellular cations and accompanied by delayed myocardial repolarization, QTc interval prolongation on the ECG, and therefore an increased propensity for atrial and ventricular arrhythmias. Accordingly, we studied serum concentrations of K+, Mg2+ and Ca2+, QTc interval duration and the appearance of arrhythmias in patients receiving rituximab therapy.
Methods Used: A retrospective chart review of 15 consecutive patients (47±3 yrs; 5 females) who were started on rituximab, between January and December 2012, for various lymphomas, including B cell, Burkitt’s, Hodgkin’s, non-Hodgkin’s and follicular lymphomas. Patients with previously documented arrhythmia or chronic renal failure (serum creatinine >2 mg/dL), or receiving any other medications known to prolong QTc were excluded. Lowest total serum [Ca2+], ionized [Ca2+]o, K+ and Mg2+, obtained within the first 8 wks of initiation of therapy, together with QTc interval (ms) and cardiac rhythm from ECG or charted rhythm strips obtained within 3 wks of these data, were noted.
Summary of Results: Hypocalcemia was present in 73% and ionized hypocalcemia in 67%; hypokalemia (K+ <4.0) in 100% and in 87% it was <3.5; hypomagnesemia (Mg2+ <2.0) in 100% and <1.8 in 93%. Prolonged QTc (>440 ms) in 87% when K+ was either <4.0, Mg2+ <2.0, and/or hypocalcemia was present. New-onset arrhythmias were seen in 73% when QTc was prolonged: supraventricular, 9; and ventricular, 2.
Conclusions: Rituximab therapy was frequently accompanied by a dyshomeostasis of serum K+, Mg2+ and Ca2+ with prolonged QTc and supra- and ventricular arrhythmias. Serial surveillance and maintenance of these cations within strictly defined limits (i. e., K+ ≥4.0 and Mg2+ ≥2.0) is recommended to avoid this indirect cardiotoxicity during rituximab administration.
114 CISPLATIN: A DYSHOMEOSTASIS OF EXTRACELLULAR CATIONS AND CARDIAC ARRHYTHMIAS
King BJ, Khan MU, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Cisplatin is an antineoplastic agent that acts by binding to and causing crosslinking of DNA thereby leading to apoptosis of malignant cells. Cisplatin is known to cause renal toxicity which could interfere with the absorption and excretion of K+, Mg2+ and Ca2+ leading to hypokalemia, hypomagnesemia and hypocalcemia thereby predisposing to cardiac arrhythmias. We studied serum concentrations of these cations, QTc interval duration and cardiac rhythm on ECG in patients who had received cisplatin therapy.
Methods Used: A retrospective chart review of 19 consecutive patients (55±9 yrs; 18 males) who were started on cisplatin between January to December 2010, for various cancers, such as multiple myeloma and squamous cell carcinoma, who did not have previously documented arrhythmia or chronic renal failure (serum creatinine >2 mg/dL), or were receiving any other medications known to prolong QTc. Lowest total serum Ca2+, K+, Mg2+, obtained within first 8 wks of initiation of chemotherapy, together with QTc (ms) and cardiac rhythm, from ECG or rhythm records obtained within 3 wks of such labs, were noted.
Summary of Results: Hypocalcemia was present in 42%; K+ <4.0 in 74% and in 47% it was <3.5; Mg2+ <2.0 in 95% and <1.8 in 58%. Prolonged QTc was found in 15% when K+ was either <4.0, Mg2+ <2.0, and/or hypocalcemia was present. New-onset arrhythmias were seen in 100% when QTc was prolonged (>440 ms): 1 supraventricular and 1 ventricular. One instance of atrial fibrillation was noted with a normal QTc.
Conclusions: Cisplatin therapy is accompanied by a dyshomeostasis of extracellular concentrations of K+, Mg2+ and Ca2+ likely due to its renal toxicity. In this small study, we did not find a strong association between QTc prolongation, an important risk factor for the development of cardiac arrhythmias, and the presence of supra- or ventricular arrhythmias. This notwithstanding, serial surveillance and maintenance of cations within strictly defined limits (K+ ≥4.0 and Mg2+ ≥2.0) is recommended to avoid the potential for arrhythmias in patients receiving cisplatin.
115 CYCLOPHOSPHAMIDE: CATION DYSHOMEOSTASIS AND PROLONGED QTc INTERVAL LEADING TO CARDIAC ARRHYTHMIAS
Flatt DM, Khan MU, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Cyclophosphamide is a chemotherapeutic agent commonly used in the treatment of lymphoma and leukemia. Cyclophosphamide may contribute to proarrhythmic pathophysiology that is not associated with its known cardiomyopathic effects. Herein we hypothesized cyclophosphamide containing chemotherapy regimens lead to extra- and intracellular cation dyshomeostasis which increases the propensity for atrial and ventricular arrhythmias by delaying myocardial repolarization and causing QTc interval prolongation on the electrocardiogram.
Methods Used: A retrospective chart review of 200 consecutive patients was performed finding 10 patients (48 yrs; 6 men) who were treated with cyclophosphamide chemotherapy for various cancers. These patients did not have previously documented arrhythmia or chronic renal failure (serum creatinine >2 mg/dL) and were not receiving other medications known to prolong QTc. Our findings included lowest total serum Ca2+, K+, and Mg2+ (obtained within first 8 weeks of initiation of chemotherapy) and QTc (ms).
Summary of Results: Hypocalcemia was present in 90% of patients; hypokalemia in 100% and hypomagnesemia in 60%. Prolonged QTc (>440 ms) was found in 89% of patients and new-onset arrhythmias were seen in 67% with prolonged QTc. Of those arrhythmias 50% were supraventricular and 50% were ventricular. Mean electrolyte levels and QTc interval are indicated below.
Conclusions: Cyclophosphamide is accompanied by a dyshomeostasis of extracellular K+, Mg2+ and Ca2+ with QTc prolongation and a predisposition to supra- and ventricular arrhythmias. Serial surveillance and maintenance of QTc and cations within strictly defined limits (K+ ≥4.0 and Mg2+ ≥2.0) is recommended to avoid arrhythmias during cyclophosphamide treatment.
116 CATION DYSHOMEOSTASIS, QTc INTERVAL PROLONGATION AND ARRHYTHMIAS FOLLOWING MAJOR SURGERY
Flatt DM, Shahbaz AU, Atta ur Rehman B, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Neurohormonal activation with elevated circulating catecholamines accompanies major surgery. Epinephrine and norepinephrine promote the translocation of circulating K+, Mg2+ and Ca2+ to systemic tissues, including skeletal muscle. The resultant hypokalemia, hypomagnesemia and ionized hypocalcemia leads to the delay in myocardial repolarization, prolongation of the QTc interval of the electrocardiogram and increased propensity for supra- and ventricular arrhythmias. Herein, we hypothesized such a dyshomeostasis of these cations with QTc interval prolongation (>440 ms) would be associated cardiac arrhythmias following major surgery.
Methods Used: A prospective assessment of serum concentrations of K+, Mg2+ and Ca2+ with QTc interval in 40 patients (64.2±1.5 yrs; 11 women) having supra- and/or ventricular arrhythmias within 24 hrs of major surgery.
Summary of Results: Hypokalemia (3.48±0.08 mmol/L) was found in 88% of these patients while 70% had hypomagnesemia (1.76±0.06 mg/dL) and 73% ionized hypocalcemia (1.03±0.05 mmol/L). QTc prolongation was seen in 88% (496.83±9.4 ms) together with 10 having new-onset atrial fibrillation, 3 with ventricular tachycardia, and the remainder having PACs and PVCs, or both.
Conclusions: In patients having major surgery, hypokalemia, hypomagnesemia and ionized hypocalcemia, together with prolongation of the QTc interval, are frequently seen during the immediate postoperative period when they are accompanied by supra- and ventricular arrhythmias, including atrial fibrillation. Serial surveillance and maintenance of these cations and QTc interval within narrowly defined limits (e.g., K+ ≥4.0 and Mg2+ ≥2.0) is recommended to prevent arrhythmias following major surgery.
117 DOES CARDIAC SURGERY VASOPLEGIA TRIGGER THE POST PERICARDIOTOMY SYNDROME?
Edriss H, Lorenzana J, Nugent K. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: A 45-year-old healthy man underwent a mitral valve replacement for a flail posterior leaflet. The mitral valve was replaced through a right atrial incision and the foramen ovale using cardiopulmonary bypass for 73 minutes. He had multiple mean blood pressure readings below 50 mmHg during the operation; the lowest recorded value was 30 mmHg. A chest tube was placed in the anterior mediastinum and a drain in the posterior pericardial space after surgery. He had hypotension following the surgical procedure and required vasopressin for 1 day, norepinephrine for 2 days, and dopamine for 3 days. His chest x-ray revealed the development of a left and then right pleural effusions. The patient developed pleuritic chest pain and dyspnea. A CT scan revealed bilateral pleural effusions, bilateral atelectasis/infiltrates, and a pericardial effusion. He did not have fever but did have significant leukocytosis (peak WBC 39.8 K/ μ L) and transient acute kidney injury (peak Cr 2.8 mg/dl). He was started on Indocin (75 mg daily) on the 10th postoperative day and had a steady improvement in his symptoms and partial clearing of his chest x-ray. Workup for infection, cardiac tamponade, and other postoperative complications was negative.
This patient had a biphasic postoperative course with initial hypotension and then the development of the post pericardiotomy syndrome. This case suggests that inflammatory response and vasoplegia associated with cardiopulmonary bypass triggered an immune response which in conjunction with the surgical procedure produced the post pericardiotomy syndrome. Prospective studies are needed to determine whether or not this association allows the prediction of this post-operative cardiac surgery complication.
118 WOMEN HAVE HIGHER CENTRAL SYSTOLIC BP (cSBP) THAN MEN AS DETECTED BY APPLANATION TONOMETRY WITH SPHYGMOCOR AND OMRON DEVICES–COMPARATIVE DIFFERENCES
Hsu RC, Sander GE, Fernandez C, Giles T, Berenson GS. Tulane University, New Orleans, LA.
Purpose of Study: We have previously reported that women have a significantly higher cSBP as compared to peripheral systolic blood pressure (pSBP) than do men as measured by Omron applanation tonometry. We have now compared cSBP and augmentation index (AI) recorded with both SphygmoCor and Omron instruments to determine if our previous results were due to technological considerations.
Methods Used: Arterial pressure was measured with a standard cuff and applanation tonometers from Omron HEM-9000 and SphygmoCor on the same day on a total of 586 participants in the Bogalusa Heart Study; participants were 30.6% black, 69.4% white and 45.4% were male (mean age of 43.7 years ± 4.5). Linear correlation plot was used to describe the difference between cSBP and pSBP (cSBP-pSBP) and AI between Omron and SphygmoCor devices. Importantly, the SphygmoCor instrument generates central measurements by employing a transfer function from the radial artery pulse wave, while the Omron utilizes a regression analysis.
Summary of Results: cSBP detected by Omron confirmed our earlier findings that cSBP - pSBP was higher in women than men, suggesting reduced vascular compliance between sexes (Table 1). This observation was also noted with SphgymoCor tonometry, but here cSBP was lower in both men and women, but less reduced in women relative to men. A stronger linear correlation was detected for AI (r =0 .777) than for cSBP (r =0.679) between Omron and SphygmoCor devices.
Conclusions: Our study confirms that women have a higher cSBP relative to men regardless of the instrument being used. However, SphgymoCor provides consistently lower cSBP than Omron, and thus estimation of cardiovascular risk using cSBP measurement is dependent upon the instrument used–device-specific criteria are necessary. Furthermore, since both devices utilize AI to calculate cSBP, AI alone may be a better indicator for evaluating cardiovascular status.
119 LEFT VENTRICULAR PSEUDOANEURYSM: AN UNCOMMON COMPLICATION OF MYOCARDIAL INFARCTION
Saxon JT1, Sanders SW1, Aru G2, Moore CK1. 1 University of Mississippi Medical Center, Jackson, MS and 2 University of Mississippi Medical Center, Jackson, MS.
Case Report: The patient is a 60 year old woman who presented with chest pain, and was determined to have an NSTEMI. Three days later, she underwent percutaneous coronary intervention to the proximal left anterior descending artery, with drug-eluting stent placement. Left ventriculography revealed anteroapical dyskinesis, with an ejection fraction of 35%. One year later, the patient presented with decompensated heart failure. Transthoracic echocardiography revealed a massive left ventricular pseudoaneurysm arising from the cardiac apex. Repeat left ventriculography to further characterized the pseudoaneurym was performed. The patient underwent surgical repair including resection of the pseudoaneurysm and patch repair of the ventricular wall. The patient was discharged to an inpatient rehabilitation facility for deconditioning following a prolonged hospital stay.
In the era of early percutaneous intervention for acute coronary syndrome (ACS), mechanical cardiac complications, including ventricular pseudoaneurysm, are very uncommon. The natural course of the disease is variable and unpredictable, and patients are at risk for sudden death from rupture of the pseudoaneurysm due to increased wall stress. Surgical repair is the widely accepted treatment.
120 LEFT MAIN CORONARY ARTERY BIFURCATION STENTING
Saxon JT, Campbell WF. University of Mississippi Medical Center, Jackson, MS.
Case Report: This is a 90 year old man with a bioprosthetic aortic valve for history of aortic stenosis, who reported new-onset angina. He underwent coronary angiography, revealing 60% distal Left Main stenosis and 90% ostial Circumflex stenosis. Coronary artery bypass surgery was deemed too high-risk. Thus, he underwent high-risk percutaneous coronary intervention with stent placement to the left main and circumflex arteries, using a “Cone -Crush” bifurcation stenting technique. The result was excellent.
Discussion: Percutaneous coronary intervention is high-risk when performed at the bifurcation of the left main coronary artery and its branches, due to the large amount of myocardium at risk. This case demonstrates bifurcation stent technique for a patient who was not a candidate for bypass surgery.
121 LEAFLET ENTRAPMENT OF A PROSTHETIC MITRAL VALVE IN AN ANTICOAGULATED PATIENT
Perez RE, Calderon R, Banchs H. University of Puerto Rico, San Juan.
Case Report: We present the case of a 65 y/o female with history of Rheumatic Fever, severe mitral regurgitation requiring mitral valve replacement on 2005 with a bi-leaflet mechanical valve, and on therapeutic anticoagulation that was found with leaflet entrapment. Patient developed shortness of breath on exertion and increased abdominal girth two weeks prior to admission. Physical evaluation was remarkable for bilateral lung base crackles and mild ascites. INR consistent with proper anticoagulation.
Patient had undergone routine echocardiography by primary cardiologist every six months unremarkable. New transthoracic echocardiogram showed elevated transmitral gradients compatible with possible stenosis. TEE confirmed this findings but no evidence of thrombus or pannus. Left and right heart catheterization found an elevated transmitral mean pressure gradient of 26mmHg, a valve area of 0.75cm2, and mean pulmonary artery pressure of 44mmHg. Fluoroscopy revealed fixed movement of one of the prosthetic valve leaflets. The previous findings were consistent with leaflet entrapment and significant hemodynamic stenosis of the prosthetic valve.
Patient underwent replacement of the mitral prosthetic valve at which time a very small thrombus was found on gross description of the stenotic valve. This small thrombus, not visualized on other non-invasive tests, was located on the leaflet hinges and prevented movement on the leaflet, thus causing entrapment of the leaflet and severe hemodynamic dysfunction of the valve.
Studies show that 1.2-5.7% of mitral mechanical valves under adequate anticoagulation are complicated by thrombosis. It is estimated that 77% of mechanical valve obstructions are caused by thrombus formation, 11% by pannus, and 12% by a combination of both. It is extremely rare for a very small thrombus to cause valve obstruction.
122 THE CLINICAL SIGNIFICANCE OF ALCOHOLISM IN CONGESTIVE HEART FAILURE READMISSIONS - TO DRINK OR NOT TO DRINK
Panikkath R, Suvorava N, Ngo N, Umyarova E, Panikkath D, Meyyerose G. Texas Tech University Health Sciences Center, Lubbock, Lubbock, TX.
Purpose of Study: Literature paradoxically quotes both beneficial and deleterious effects of alcohol on the heart. The prevalence of alcohol consumption among those with CHF readmissions and the characteristics of such patients are not known.
Methods Used: This study comprises of all adult patients (>20 years of age) who were readmitted for CHF within 30 days, after a hospitalization for heart failure at a University hospital from January 1st 2007 to December 31st 2012. The subgroup of patients who had history of alcoholism were analyzed and their characteristics were compared to those who were readmitted with CHF but without history of alcoholism.
Summary of Results: Of the 204 patients with CHF who were readmitted, 130 were for CHF exacerbations. Seventy two (55.38%) were males (mean age 66.99 ± 14.63 years). The mean time of readmission was 14.24 days. Sixty nine (53.08%) had diabetes and 83 (63.85%) patients were hypertensive. Only 32 patients had history of alcoholism (24.46%). Mean brain natriuretic peptide (BNP) among them was 10290 ± 13953. The mean ejection fraction was 37.98 ± 17.04%. The mean length of hospital stay was 5.79 ± 3.97 days. In hospital mortality was observed in 6 (4.6%) patients.
The mean age was significantly lower in patients with history of alcoholism in comparison to those without (62.04 ± 11.40 vs. 67.35 ± 15.14 years; p=0.03) with a male to female ratio 78% vs. 52.31%; p=0.006). The mean BNP was lower in patients with history of alcoholism compared to those without history of alcoholism (82143 ± 14014 vs. 104486 ± 14264, p=0.51). The mean EF was significantly lower in patients with history of alcoholism compared to those without (35.43 ± 18.51% vs. 39.37 ± 16.47%, p=0.04). The length of stay was slightly longer in patients with history of alcoholism although it was not statistically significant 6.08 ± 4.52 vs. 5.41 ± 3.70 days, p=0.52).
Conclusions: Alcoholism contributed to only less than quarter of CHF hospital readmissions. However, the mean age of patients with alcoholism was significantly younger and they were predominantly males compared to the sex matched distribution of subjects without history of alcoholism. The mean ejection fraction was lower and the hospital stay was slightly longer in patients with history of alcoholism.
123 AN INCIDENTAL DIAGNOSIS OF PENETRATING AORTIC ULCER OF THE ASCENDING AORTA LEADING TYPE A AORTIC DISSECTION
Hwang I2,1, Giri S2,1, Mallisho M2,1, Alsafwah S1,2. 1 University of Tennessee, Memphis, TN and 2 University of Tennessee, Memphis, TN.
Case Report: A 51-year-old female with CHF with 20% EF on TTE, admitted for cardiac catheterization. Patient was found to have no significant CAD. However, she had an aneurysmal ascending aorta with a mass-like structure. CT chest with contrast showed type A aortic dissection likely secondary to a penetrating ulcer. It was also noted that her ascending aorta was severely dilated with a transverse diameter of 6.5 cm. Dissection starts just above the sinuses of Valsalva and terminates prior to the great vessel origins, does not extend into the great vessels or descending thoracic aorta.
124 HEART, MUSCLE AND LIVER NECROSIS FOLLOWING ENVENOMATION BY TIMBER RATTLE SNAKE
Askari R, Farah V, Koshy SK, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose: The timber rattle snake (Crotalus horridus) is considered North America’s most venomous snake. After envenomation, attendant toxins may be directed at nervous, hematologic and cardio/skeletal tissues. Herein, we present the case of a farmer who developed necrosis and failure of multiple organs after being bitten on the right lower extremity by a timber rattle snake.
Case Report: Upon transfer from another health care facility, this 61-year-old male presented with complaints of right leg and abdominal pain with shortness of breath. Blood pressure 128/76; tachycardia 128 bpm; and tachypnea 28/min. Cardiopulmonary and neurologic examinations were initially unremarkable. Following a seizure, the patient was intubated and soon thereafter was noted to be hypotensive requiring intravenous pressor agents. Initial ECG revealed sinus tachycardia without ST segment or T wave changes while laboratory panel did not indicate injury to renal, hepatic, muscular or hematologic systems. Antivenom treatment was initiated after consultation with Poison Control Center and continued for 3 days. However, over the next 24h the patient developed multiorgan injury and failure: i) serum troponin rose to 396 ng/mL without ECG changes, while echocardiogram revealed apical hypokinesis and ejection fraction of 30%; ii) rhabdomyolysis with peak creatinine phosphokinase of 8760 ng/mL; iii) hepatocyte necrosis with elevated serum transaminases; and iv) acute renal failure with elevated serum creatinine 3.5 mg/dL, which required hemodialysis. Despite aggressive antivenom administration and other necessary interventions, the patient succumbed days later.
Conclusions: Toxins contained in pit viper venom, such as that of the timber rattlesnake, can cause dose-dependent injury to multiple organs. As occurred in this patient with likely large-dose envenomation, there was putative ischemic necrosis of heart, muscle and liver parenchyma. Its pathophysiologic origins would therefore likely include: a) endothelial cell damage and occlusion of the corresponding conduit vessels supplying these ischemic organs; b) a thrombotic microangiopathy of involved organs; or c) a combination of these pathologic entities.
125 URINARY MAGNESIUM WASTING WITH HYPOMAGNESEMA AND ATRIAL FIBRILLATION IN A PATIENT WITH HYPERTROPHIC CARDIOMYOPATHY
McCullough RJ, Kabra R, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder with considerable phenotypic variability, including a less well-recognized association with altered Mg2+ homeostasis. Herein we present a young woman with HCM accompanied by marked hypomagnesemia, secondary hypocalcemia, QTc prolongation and the appearance of symptomatic atrial fibrillation (AF) found to be associated with pronounced urinary Mg2+ wasting.
Case Report: Over the past 12 months this 22-year-old female with known HCM presented to the Emergency Department on multiple occasions with paroxysms of rapid AF and complaints of chest tightness, dyspnea and palpitations. Previously, she had received an implantable cardioverter (ICD) and two ablation procedures for her AF. Positive family history included a brother, who died suddenly while playing sports, and her sister diagnosed with HCM. Pertinent physical findings included: an irregular, irregular rhythm and pulse deficit with systolic murmur that decreased with handgrip maneuver or leg raising. Laboratory studies: persistent normokalemia (>4.0 mEq/L); variable calcium ranging from low to normal (7.7-9.2 mg/dL); and marked hypomagnesemia (⩽1.5 mg/dL), which failed to correct despite intravenous and oral Mg2+ supplementation. ECG revealed rapid AF with QTc prolongation (468 ms). Fractional urinary Mg2+ excretion was 27% (normal 2%), consistent with marked renal wasting. Spironolactone, an aldosterone receptor antagonist, corrected her hypomagnesemia. Serum Mg2+ and Ca2+ in her sister were 1.9 and 8.6 mg/dL, respectively.
Conclusions: Mutations of the transient receptor potential melastatin 6 and 7 (TRPM 6 and 7) lead to dysfunctional epithelial cell ion channel Mg2+ resorption in kidney and colon and which is further downregulated by aldosterone released in response to reduced intracellular Mg2+. Ensuing marked urinary and fecal Mg2+ losses with profound hypomagnesemia can lead to AF and where these losses can be abrogated by spironolactone. Further interrogation of these Mg2+ transporters in HCM is merited.
126 AN UNUSUAL CAUSE OF PERICARDITIS
Waespe CK, Saxon J, Lopez-Ruiz A, Ashley K, Alexander M. University of Mississippi Medical Center, Jackson, MS.
Case Report: Kelly Waespe MD, John Saxon MD, Arnaldo Lopez-Ruiz MD, Kellan Ashley MD, Myrna Alexander MD
University of Mississippi Medical Center Department of Cardiology.
Pericarditis is a known cause of chest pain. Diagnostic clues are history, diffuse ST elevation on Electrocardiogram (ECG), friction rub, or pericardial effusion. Causes include aortic dissection, malignancy, or trauma, however most cases are viral or idiopathic. Effusions can lead to tamponade with anticoagulation and require observation. We describe an unusual cause of pericarditis, the management, and implications.
A 68-year-old female presented with positional chest pain and ST elevation in II, III, and aVF on ECG. She had no prodrome. Cardiac biomarkers were negative. Echocardiogram demonstrated a moderate pericardial effusion. A year prior she underwent a pancreatoduodenectomy, complicated by post-operative day 10 development of Deep Vein Thrombosis (DVT). An inferior vena cava (IVC) filter was placed. Later filter removal was thwarted by thrombus on the filter and anticoagulation was initiated.
Her unusual presentation led to further work up. Computed Tomography demonstrated a fractured fragment of the IVC filter in the right ventricle, and hemopericardium. The remaining filter was in its original position, without thrombus. Several services were involved in a hybrid approach to retrieval. After sternotomy, the fractured fragment was visibly protruding from the right ventricle and removed with a clamp. Via the right internal jugular vein, complex techniques were required to free the filter from the IVC. There were no apparent complications.
Diffuse ST elevation is pathognomonic for pericarditis, and segmental ECG changes are infrequent. In this case the ECG changes may be related to the cause of pericarditis, a rare complication of IVC filters. Filters are indicated for DVT with anticoagulation contraindications, however their use remains controversial. Complications are infrequent and fracture of a filter is reported in 1% of cases. Several filter types are retrievable, but attempts are made in only 34% of cases. Here, embolization of a fractured strut required surgical removal, followed by percutaneous retrieval of the filter. We present an unusual cause of pericarditis, complications of IVC filters, and the need for filter retrieval.
127 A RARE OCCURRENCE OF HAEMEPHILUS PARAINFLUENZAE AORTIC VALVE ENDOCARDITIS WITH EXTENSIVE DISRUPTION OF THE AORTIC ROOT
Swaminath D, Soape M, Singh P, Narayanan R, Desai V, Jenkins L. TexasTech University Health Science Center, Lubbock, TX.
Case Report: We present an unusual presentation of aortic valve endocarditis caused by H. parainfluenzae.
A 53-yr old male with PMH of alcohol abuse, illicit drug use, and DM presented with symptoms of dyspnea, peripheral edema, and productive cough for a month. A month ago he was diagnosed with Haemophilus parainfluenzae aortic valve endocarditis and was receiving intravenous (IV) antibiotics including ampicillin and vancomycin. Patient was admitted with diagnosis of CHF secondary to severe aortic regurgitation. A large aortic valve vegetation measuring 1.3 × 1.1cm, severe aortic regurgitation, a perivalvular abscess encircling the aortic root, and a fistula to the left ventricular outflow tract were noted on the TEE. At this point, surgery was contemplated, and the patient underwent a coronary artery angiogram showing a 40-50% stenosis in the right coronary artery. Patient was started on IV tobramycin and ceftriaxone. Emergent surgery was performed to replace the aortic valve. Post operatively patient recovered without complication.
HACEK group of organisms accounts for 3% of all endocarditis case. Endocarditis caused by Haemophilus species is even rarer: about 0.8% to 1.3% of all cases in adults. Risk factors for development of H. parainfluenzae endocarditis therefore include dental work, cleaning of teeth, nasopharyngeal infection, tongue pierg, and the use of tongue scrapers. Indication for surgical intervention in bacterial endocarditis is major or recurrent septic embolization, congestive heart failure due to valve stenosis or regurgitation, false aneurysms, large mobile vegetations, and persistent infection. HACEK endocarditis was treated by beta-lactam antibiotics such as ampicillin, with or without the addition of an aminoglycoside. However, because of resistance to betalactam current guidelines recommend empiric treatment with a 3rd-generation cephalosporin or ampicillin-sulbactam for 4-8 weeks as the first line of therapy for HACEK endocarditis. There were only two reports of extensive tissue invasion adjacent to the site of valve infection. This case demonstrates the importance of appropriate antibiotic therapy at the initial diagnosis of infective endocarditis to improve clinical outcomes.
128 MASSIVE PULMONARY EMBOLUS IN TRANSIT
Marcial JM1,2, Jimenez L1,2, Calderon R1,2, Grovas D2, Kareh J2. 1 University of Puerto Rico School of Medicine, San Juan and 2 Cardiovascular Center of Puerto Rico and the Caribbean, San Juan.
Case Report: A 73 year-old man with hypertension, dyslipidemia and history of smoking was evaluated in the emergency department for an acute episode of near syncope and chest pain associated to a week of progressive exertional dyspnea and recurrent dizziness upon standing. Transthoracic echocardiography demonstrated an echodense structure with origin in the inferior vena cava and protruding through the right heart chambers. Transesophageal echocardiography further characterized extension of the thrombus into the pulmonary artery. Chest computerized tomography and pulmonary arterial angiography confirmed multiple bilateral pulmonary emboli. Bilateral lower extremity ultrasound Doppler and duplex established culprit deep vein thrombosis in the right common femoral, superficial femoral and popliteal veins. In view of persistent hypotension despite anticoagulation, intravenous thrombolytics were administered. Although there was initial relief of cardiopulmonary symptoms with fibrinolytic therapy, the patient developed sudden cardiac arrest due to massive intracerebral hemorrhage with brainstem compression and ultimate demise. Discussion: Acute pulmonary embolism with visible right-heart thrombi is a rare phenomenon and is associated with a poor prognosis. Unstable patients should be considered for thrombolysis as an emergency, life-saving treatment. However, fibrinolytic treatment is not without its risk for complications, as was demonstrated in this case.
129 NATIVE MITRALVALVE ENDOCARDITIS COMPLICATED AFTER SURGICAL REPLACEMENT
Garcia D, Nascimento Cardoso R, Young L. University of Miami, Miami, FL.
Case Report
Introduction: Bacterial endocarditis can lead to serious complications such as valve leaflet rupture requiring replacement or repair. Mycobacterium abscessus and Kocuria species are rare causes of infections in humans. We report a case of native mitral valve bacterial endocarditis caused by both M. abscessus and Kocuria species complicated by mitral valve rupture.
Case Description: A forty-eight year old male intravenous drug abuser was admitted for 1 week of fevers, shortness of breath and abdominal pain. Upon initial evaluation he presented with thrombosis of the proximal celiac artery due to septic emboli. Blood cultures initially revealed Enterococus fecaelis and he was treated with ampicillin and gentamicin. The transesophageal echocardiogram disclosed a two centimeter vegetation on the posterior mitral valve leaflet with associated perforation leading to severe mitral regurgitation. Repeated blood cultures disclosed no organisms and therefore surgical mitral valve replacement was performed using a bioprosthetic valve. Post-surgical blood cultures and mitral valve tissue cultures revealed Kocuria species and M. abscessus. At this point the patient was not a candidate for further surgery and therefore he was treated for 6 months with clarithromycin, imipenem and amikacin, with resolution of symptoms. Repeated blood cultures were negative.
Discussion: Infective endocarditis caused by one of these agents has only been reported in 11 cases and there are no prior reports of combined infection. Prosthetic or native mitral valve can be affected equally; valve repair is the treatment of choice although in cases where the patient is not a surgical candidate, long-term antibiotic therapy is a feasible option. In our particular case initial negative cultures or in atypical cases of sub acute endocarditis, particularly if antibiotic resistance is an issue, acid-fast staining should be done in order to increase the diagnosis of this infection.
130 RECIPE FOR ADMISSION: ATYPICAL CHEST PAIN AND INCORRECT LEAD PLACEMENT
Spinks K, Arbour A, Engel LS, Amoss J. LSU Health Sciences Center, New Orleans, LA.
Case Report: Chest pain is one of the most common primary complaints in patients presenting to the Emergency Department, and electrocardiographic findings are often the cornerstone in making a diagnosis. We present a case where ECG lead misplacement significantly altered management.
Case: A 41 year old African American male presented to the emergency department with a chief complaint of chest pain, 5/10 in severity that began while at rest and had been constant since the prior evening. His chest pain was located in his left anterior chest and radiated to his shoulder and left arm. The pain was not associated with activity, shortness of breath, nausea, or vomiting. He had noted similar chest pain intermittently over the past two months. On arrival to the emergency department, the patient appeared comfortable, vital signs and his physical exam were unremarkable. The first set of cardiac enzymes was negative. His initial electrocardiogram demonstrated T-wave inversions in leads V3-V6 causing concern for myocardial ischemia and the need for possible admission to rule out acute coronary syndrome. Upon further examination of the patient, the precordial leads were noted to be placed incorrectly, extending laterally from the xiphoid process at the seventh intercostal space. A new set of leads were placed in the proper positions for leads V1-V6 in the fourth and fifth intercostal spaces, and a repeat electrocardiogram showed no T-wave inversions. A subsequent electrocardiogram was repeated with leads placed incorrectly, which again demonstrated the T-wave inversions. Based upon his history, physical, and corrected diagnostic evaluation, the patient was determined to be very low risk for having an acute coronary syndrome, and he was released home with outpatient follow-up.
Discussion: Chest pain prompts many emergency department visits requiring clinicians to risk stratify patients based upon history, physical, and initial diagnostic studies to determine the need for hospitalization to rule out acute coronary syndrome. Clinicians make important patient care decisions based upon electrocardiographic findings; therefore, clinicians must be aware of the potential pitfalls of incorrect lead placement in order to avoid potential mismanagement.
131 HYPERTROPHIC CARDIOMYOPATHY
Laura S, Singh M, Jain N. LSU Health Sciences Center, New Orleans, LA.
Case Report: A 47 year old woman female with family medical history (Figure 1), of sudden death at the age of 60-70 was diagnosed with hypertrophic cardiomyopathy after presenting for 3 weeks of chest pain described as left sided, dull/achy, without radiation, and occurring both at rest and with exertion. The pain was associated with shortness of breath, dyspnea on exertion and palpitations which had progressed to occurrence after a single flight of stairs and light housework over the past week. An echocardiogram on admission revealed normal LV function of >55% with severe asymmetric septal hypertrophy, septal thickness of 20-29mm, moderate systolic anterior motion of the mitral valve, with peak left ventricular outflow tract (LVOT) velocity of 6m/s and peak gradient of 144 mm Hg. The patient underwent left heart catheterization which revealed normal coronaries with a large first septal branch demonstrating dynamic systolic compression. Hemodynamics revealed LV body pressure of 200/15 mm Hg with a late-peaking dagger shape as in dynamic LVOT obstruction, LVOT pressure of 100/15 mm Hg, aortic pressure of 100/61 mm Hg. No aortic valve obstruction was present. Cardiac MRI was performed which revealed an interventricular septum thickness of 31mm, LVOT obstruction, and a mid myocardial scar in the inferoseptal segment. The patient underwent placement of an ICD for primary prevention.
Discussion: Hypertrophic Cardiomyopathy (HCM) is defined as left ventricular hypertrophy without an identifiable cause such as hypertension, aortic stenosis, or chronic renal failure that usually develops in the second decade of life. Prevalence in the general population is 1:500. HCM is inherited in an autosomal dominant pattern in approximately 50% of cases with the remaining due to new mutations. HCM, in the vast majority of cases, is associated with hypertrophy of the proximal anteroseptal wall, leading to obstruction of the left ventricular outflow tract in approximately 25% of cases.
132 SARCOID CARDIOMYOPATHY
Laura S, McShurley T, Jain N. LSU Health Sciences Center, New Orleans, LA.
Case Report: Sarcoidosis is a systemic disease with the formation of non-caseating granulomas in a variety of tissues. Cardiac involvement is one of the least common manifestations, however it has been suggested that it may be present in up to 25% of those individuals diagnosed with systemic sarcoidosis. Cardiac sarcoidosis may affect both the conduction system and myocardial function through granuloma deposition and fibrosis leading to ventricular dysfunction, congestive heart failure, atrioventricular block, atrial or ventricular arrhythmias, and even sudden death.
Case: 56 y/o obese female with past medical history of untreated sarcoidosis with pulmonary and neurological involvement (diagnosed by lumbar puncture several years prior), depression, anxiety, hypertension, hyperlipidemia, migraines, GERD, and asthma was referred for evaluation of chest pain and dyspnea on exertion. Her chest pain was described as sharp and left sided with radiation to the jaw. Patient stated pain lasted approximately 10-15 minutes, occurring 2-3 times per week for the past 3-4 months with exertion, rest, and coughing. Patient also described dyspnea when ambulating approximately 100 yards that was relieved with brief periods of rest, minimal intermittent pedal edema worsened by prolonged standing, and orthopnea for many years. Electrocardiogram showed normal sinus rhythm with occasional premature ventricular complexes. Two dimensional echocardiogram revealed left ventricular enlargement (LVIDd: 5.6 cm, LVIDs: 4.9cm) with an ejection fraction of approximately 45% and a thin, akinetic inferior wall consistent with scarring. Estimated pulmonary artery pressure was less than 35mmHg. Diastology revealed an abnormal relaxation pattern with normal left atrial pressure. The patient underwent coronary angiogram which revealed non-obstructive coronary artery disease. Chest radiography remained unchanged from computed tomography a few months prior which showed perihilar and suprahilar lymphadenopathy. Patient was discharged with pulmonary and cardiac follow up for continued management of her sarcoidosis.
133 LBBB ASSOCIATED WITH SPONTANEOUS PNEUMOTHORAX: A CASE REPORT
Johnson P, Paccione R, Burwell J, Lo B. LSU Health Sciences Center, New Orleans, LA.
Case Report: There are multiple reports in the literature of EKG changes associated with spontaneous pneumothoraces. However, there is no documentation of isolated left bundle branch block (LBBB) changes due to a right-sided pneumothorax. We will discuss a patient with a right-sided spontaneous pneumothorax with a new LBBB that resolved post treatment.
Case: Our patient is a 62-year old African-American male with a history of chronic atrial fibrillation, gout, diabetes, hyperlipidemia, and hypertension who presented to the ED with a chief complaint of “chest pain and shortness of breath x 10 hours.” His atrial fibrillation was rate-controlled without medications. Home medications included warfarin, allopurinol, atorvastatin, furosemide, lisinopril, and metformin. In the emergency department, the patient was found to have new LBBB and atrial fibrillation with rate of 90 bpm on EKG, moderate-sized right pneumothorax on CXR, and normal cardiac enzymes. After FFP administration, CT surgery placed a catheter in the right chest. Repeat CXR showed complete re-expansion of the right lung. The patient had multiple EKGs in the ER that showed LBBB prior to chest tube insertion. However, serial cardiac enzymes were negative and serial EKGs showed lateral T-wave inversions and LBBB. The patient remained chest-pain free after the chest tube placement, and the tube was removed by the third hospital day. The final EKG on the day of discharge showed AFIB with resolution of the LBBB and improvement of T-wave inversions. Cardiac enzymes remained negative.
Discussion: Common EKG changes that have been documented with pneumothoraces include ST-segment elevation, T-wave changes, axis deviation and incomplete right bundle branch block regardless of the side of the pneumothorax. Theoretically, pneumothoraces increase intrapleural pressures and decrease venous return and stroke volume; tachycardia then increases oxygen demand resulting in ischemic changes on EKG. However, this does not seem to be the case in our patient. Multiple sets of cardiac enzymes were normal despite the new LBBB and chest pain. This case emphasizes the importance of recognition of LBBB directly related to a pneumothorax rather than to myocardial ischemia thus avoiding unnecessary invasive procedures i.e. coronary angiograms.
134 A RARE CAUSE OF AORTIC STENOSIS
McShurley T, Laura S, Jain N. LSU Health Sciences Center, New Orleans, LA.
Case Report: A 33-year-old male presented with progressively worsening substernal chest pressure and dyspnea on exertion relieved with rest over three months duration. Physical examination revealed diminished carotid pulse with a II/VI systolic crescendo murmur radiating to both carotids. Transthoracic echocardiogram showed a heavily calcified aortic valve with limited motion consistent with aortic stenosis. Peak gradient across the aortic valve was 110 mmHg with a calculated aortic valve area of 0.6 cm2 consistent with severe aortic stenosis. The other valves appeared normal in structure and function. The patient underwent surgical aortic valve replacement. Gross examination revealed a heavily calcified, slit-shaped unicommissural aortic valve. Unicuspid aortic valve is a rare congenital malformation seen in 0.019% of patients undergoing echocardiography and in 5.59% of patients undergoing aortic valve replacement. Approximately 60% of unicuspid aortic valves in adults are diagnosed after surgical resection or at autopsy while only 20% are found on echocardiography. Two sub-types have been described. A pinhole-shaped UAV typically presents in early infancy while a slit-shaped unicuspid aortic valve commonly presents later in early adulthood.
135 TRICUSPID VALVE AVULSION: A CHALLENGING DIAGNOSIS ASSOCIATED WITH BLUNT CHEST WALL AND CARDIAC TRAUMA
Bomb R, Sethi PR, Garg N, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose: Posttraumatic avulsion of the tricuspid valve (TV) causing acute tricuspid regurgitation is a rare, often overlooked and potentially fatal complication of blunt chest wall trauma with attendant cardiac injury. Although it has been reported, acute tricuspid regurgitation can often be missed due to its subtle presentation in the setting of more obvious traumatic injuries. Unrecognized persistent tricuspid regurgitation will lead to right ventricular volume overload and dysfunction with poor prognosis.
Case Report: A 34-year-old obese man presented to the Trauma Unit of the Regional Medical Center with blunt trauma to his chest after being hit by a car. Notable injuries included fracture of left hemithorax involving 4 ribs, femur and tibia. A few hours after admission, his blood pressure (BP) fell to shock levels requiring intravenous pressor agents. On examination: BP 70/42 mmHg; and pulse 100/min. Neck veins were difficult to assess due to body habitus. A faint systolic murmur was noted. Urgent transthoracic echocardiogram was performed to assess the etiology of his hemodynamic instability: a flail anterior TV leaflet was seen with avulsion of the papillary muscle accounting for severe eccentric acute tricuspid regurgitation; and systolic flow reversal was noted in the hepatic veins. Transesophageal echocardiogram confirmed these findings, during which time his Swan-Ganz catheter, used for hemodynamic monitoring, was retracted to better visualize the TV. Unconventional views at mid-esophagus provided complete assessment of the TV. Consultation with cardiothoracic surgery was obtained for consideration of TV repair.
Conclusions: In patients with blunt chest trauma a high index of suspicion, careful physical examination and echocardiography can lead to prompt recognition of this rare but potentially fatal complication. If TV and its leaflets cannot be readily visualized, image optimization using non-conventional views and removal of any right heart catheters should be considered. Early surgical intervention may be necessary for prevention of long-term complications attendant with persistent tricuspid regurgitation.
136 TRACHEOSTOMY-RELATED SINUS BRADYCARDIA. A CASE OF INTERNAL CAROTID MASSAGE
Bomb R, Koshy SK, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose: The baroreceptor reflex emanating from the carotid sinus is integral to cardiovascular homeostasis, including the regulation of heart rate and blood pressure. Stretching the carotid sinus activates the parasympathetic nervous system with ensuing vagal stimulation causing sinus bradycardia and even hypotension. External compression of the neck over the carotid sinus, located at the bifurcation of the internal and external carotid arteries, has been used to raise vagal tone and convert tachyarrhythmias. Herein we present a unique case of inappropriate sinus bradycardia attributed to internal compression of the carotid sinus.
Case Report: A 57-year-old man was hospitalized at Regional Medical Center, Memphis where he was intubated after multiple rib fractures and pulmonary contusion following a motor vehicle accident. A tracheostomy was ultimately performed and several days later he was found to have developed asymptomatic sinus bradycardia (rate 30-40 bpm) without hypotension or arrhythmia. Serum K+ and Mg2+ were 4.6 mmol/L and 2.0 mg/dL, respectively; and arterial O2 saturation 95%. QTc interval remained normal and he was not receiving medications that would prolong it. No cause of his bradycardia could be ascertained other than the patient noting these episodes occurred with eating or moving his neck. This prompted careful manipulation of his tracheostomy tube, including withdrawal with reversion to normal sinus rhythm and increment in heart rate to 70-80 bpm. The tube was ultimately removed on day 5 and the patient discharged home with no further episodes of bradycardia.
Conclusions: Tracheal suction has been reported to cause vagal stimulation with ensuing sinus bradycardia. Herein, we report a hitherto unreported cause of intermittent, asymptomatic sinus bradycardia induced by internal carotid sinus massage by the tracheostomy tube. Awareness of this pathophysiologic response to unintended or intended manipulation of a tracheostomy tube can minimize its occurrence and prevent unnecessary evaluation.
137 BLUNT CHEST WALL TRAUMA WITH ST SEGMENT ELEVATION: A CASE OF MYOCARDIAL CONTUSION MIMICKING INFARCTION
Bomb R, Nayyar M, Garg N, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose: Damage to the heart following blunt chest wall trauma can range from myocardial contusion to rupture with death. ECG changes vary from minimal conduction defects to life threatening ventricular arrhythmias. Unfortunately there are no definitive diagnostic criteria for myocardial contusion except postmortem histopathologic findings. Herein, we present a case of a young man who presented after blunt chest wall trauma with significant ST elevation and minimal rise in serum troponin due to myocardial contusion mimicking an acute myocardial infarction.
Case Report: A 32-year-old man with no significant medical history presented to the Trauma Unit of the Regional Medical Center in Memphis after sustaining blunt chest wall trauma during a motor vehicle accident. He was also found to have multiple rib fractures along with lower extremity fractures and reported generalized chest pain that varied with respiration and posture. No other risk factors for coronary artery disease were identified in this otherwise healthy young male. Diffuse ST segment elevation was noted on his initial ECG compatible with an acute myocardial infarction: 0.5-1 mm ST segment elevation in leads I, II, III, aVF and V2-V6. Biomarkers of cardiomyocyte necrosis, including serum troponin, were minimally elevated with no significant further rise over the next 24 hours. Serum electrolytes were normal. A bedside transthoracic echo revealed a normal left ventricle with no regional wall motion abnormalities or pericardial effusion. The patient was managed conservatively and ST elevation resolved over the next 24 hours.
Conclusions: We conclude that ST elevation on initial ECG with minimal troponin release following blunt chest wall trauma with myocardial contusion can mimic an acute myocardial infarction and where anticoagulants would be contraindicated.
138 INSULIN-LIKE GROWTH FACTOR-1 INCREASES COLLAGEN TYPE I SYNTHESIS VIA INDUCING EXPRESSION OF THE MRNA BINDING PROTEIN LARP6 AND ITS BINDING TO THE 5′STEM-LOOP OF COL1A1 AND COL1A2 MRNA
Blackstock C, Higashi Y, Sukhanov S, Delafontaine P. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Collagen content in atherosclerotic plaque is important in prevention of plaque-rupture and is established as a hallmark of plaque stability. Our earlier studies showed that insulin-like growth factor-1 (IGF-1) increases collagen content in atherosclerotic plaques of Apoe-/- mice. To identify mechanisms, we investigated the effect of IGF-1 on the la ribonucleoprotein domain family member 6 (LARP6). LARP6 binds a stem-loop motif in the 5’UTR of the mRNAs encoding the collagen type I alpha subunits (α1(I) and α2(I)), and coordinates their translation into the heterotrimeric collagen type I molecule.
Methods Used: Human aortic smooth muscle cells (SMCs) and mouse embryonic fibroblasts (harboring a 5’stem-loop mutation) were cultured and collagen expression in response to IGF-1 was measured via western blot and 3H-proline accumulation. LARP6 expression and association with COL1a1 and COL1a2 mRNA was measured via western blot and immunoprecipitation of LARP6, followed by qPCR. Additionally, an adenovirus was used to overexpress a 5′Stem-loop RNA that served as a molecular decoy to sequester LARP6. IGF-1 upregulation of LARP6 and collagen expression was also assessed in aortic tissue in an Apoe-/- mouse model of atherosclerosis.
Summary of Results: IGF-1 rapidly increased LARP6 expression and the rate of collagen synthesis and extracellular accumulation. IGF-1 increased the association of LARP6 with COL1a1 and COL1a2 mRNA, and mutation of the 5’stem-loop of Col1a1 mRNA, which inhibits binding of LARP6, abolished the ability of IGF-1 to increase synthesis of collagen type I. Furthermore, overexpression of a 5’stem-loop RNA decoy prevented the ability of IGF-1 to increase pro-α1(I) and mature α1(I) expression in cultured medium. IGF-1 infusion in Apoe-/- mice increased expression of LARP6 and pro-α1(I) in aortic lysates, and SMC-specific IGF-1-overexpression robustly increased collagen fibrillogenesis in atherosclerotic plaque.
Conclusions: We identify the mRNA binding protein LARP6 as a critical mediator by which IGF-1 augments synthesis of collagen type I in vascular smooth muscle, which may play an important role in promoting atherosclerotic plaque stability.
139 SAPHENOUS VEIN GRAFT RUPTURE PRESENTING WITH CARDIAC TAMPONADE EARLY AFTER CORONARY ARTERY BYPASS SURGERY
Ababneh B, McShurley T, Gaines T, Jain N. LSUHSC, New Orleans, LA.
Case Report: Post coronary artery bypass surgery (CABG) cardiac tamponade due to spontaneous rupture of saphenous vein graft (SVG) as early as the third post-operative day has never been described before to our knowledge. We report a case of early rupture of SVG on the third day after CABG resulting in cardiac tamponade.
Case: A 70-year-old male with multiple risk factors was admitted for evaluation of accelerating angina and dyspnea. Physical examination was unremarkable. Electrocardiogram (ECG) was unchanged from one year prior. Serum chemistries including serial cardiac biomarkers were negative. Coronary angiography showed severe multivessel disease for which CABG including 3 SVG grafts was subsequently performed.
On post operative day 3, the pericardial drain was removed. Upon transfer to a chair five hours later, he suddenly collapsed. Pulse was absent and telemetry showed asystole. Resuscitation was performed and return of spontaneous circulation was achieved rapidly. Exam revealed muffled heart sounds and elevated jugular venous pressure consistent with tamponade. Emergent surgical exploration revealed hemopericardium and active bleeding from a tear in the SVG to the right coronary artery. The hemopericardium was evacuated and the SVG tear was repaired with marked improvement in hemodynamics.
Discussion: SVG rupture is a rare complication of CABG. It is typically associated with pathophysiological changes in the graft such as an aneurysm, pseudoaneurysm, or as a consequence of mediastinitis or infection. Spontaneous rupture of vein grafts has been reported in literature however nearly all presented years after surgery.
This case to our knowledge is the earliest occurring case of spontaneous SVG rupture, occurring on the third post-operative day. It is unclear what predisposing factors were present. Given the quiescent nature of the patient’s initial hospital course, it is unlikely that the observed rupture occurred as a manifestation of surgical technique mishap. Adding to that, there was no suggestion of graft aneurysm, mediastinitis or infection during this period. We cannot fully exclude SVG trauma resulting in rupture due to removal of the pericardial drain.
140 AORTIC PSEUDOANEURYSM CAUSING LEFT ATRIAL OBSTRUCTION
Aiello D, Lathia V, Jain N, Helmcke FR. LSUHSC–New Orleans, New Orleans, LA.
Case Report: A 26 year-old white male with heroin abuse presented to the emergency department with complaints of fever and malaise for a few days’ duration. His past medical history is significant for chest gun shot wound associated with a dime sized ascending aortic tear requiring emergent suture repair in 2007. A residual aortic pseudoaneurysm became apparent after his initial repair but he refused surgical correction. Since then, the pseudoaneurysm was not followed as intended with scheduled serial aortic imaging due to non-compliance.
During the current admission, he was diagnosed with pneumonia, sepsis, and newly diagnosed Acquired Immunodeficiency Syndrome. Despite adequate management of sepsis, his respiratory status continued to decline and the patient was intubated. A transthoracic echocardiogram was obtained revealing a very large aortic pseudoaneurysm, measuring 7.6cm x 5.5cm with subtotal obliteration of the left atrial cavity. In addition, severe tricuspid regurgitation and pulmonary hypertension were seen. Three-dimensional transesophageal echocardiography revealed compression of the bilateral pulmonary veins and erosion of the left atrial wall by the pseudoaneurysm resulting in thrombus formation in the left atrium. A CT angiogram of the patient’s chest confirmed these findings with additional compression noted of the right pulmonary artery by the pseudoaneurysm.
The cardiothoracic surgery service was consulted for expedited repair of the pseudoaneurysm. A bovine pericardial patch repair of the aortic wall defect was performed. After careful intraoperative evaluation, due to marked pseudoaneurysm erosion of the left atrial wall this lesion was left undisturbed as a repair complication would be life threatening. The patient’s immediate hospital course was uncomplicated.
This case illustrates the potential long-term complications associated with repaired aortic rupture and the need for regular surveillance.
141 MASKED VENTRICULAR TACHYCARDIA ETIOLOGY ATTRIBUTED TO SURREPETITIOUS DRUG INGESTION
Aiello D1, Jain N1, Celebi M2. 1 LSUHSC–New Orleans, New Orleans, LA and 2 Touro Infirmary, New Orleans, LA.
Case Report: A 55 year-old white male with no past medical history was brought into the emergency department (ED) in cardiac arrest after being found unresponsive. Bystander cardiopulmonary resuscitation was not immediately initiated and the patient was unconscious for over 12 minutes before emergency medical services (EMS) arrived to find the patient in pulseless ventricular tachycardia. Advanced cardiac life support measures were initiated by EMS services personnel and continued in the ED. Once resuscitated, his electrocardiogram showed a sinus rhythm with QRS widening, a prolonged QTc interval, and ST elevations in lateral leads. Hypothermia protocol was initiated and urgent cardiac work up revealed severe global left ventricular systolic dysfunction without obstructive coronary artery disease. His serum chemistries drawn upon arrival to the ED during active resuscitation revealed a normal serum potassium level. On examination, the patient had marked gynecomastia and absence of some male secondary sexual characteristics such as facial and axillary hair. After passively re-warming the patient, he was found to have clinical brain death and subsequently expired.
Given the patient’s examination findings as well as the ventricular tachycardia arrest and electrogardiographic signs of hyperkalemia, it was suspected that he was taking an aldosterone antagonist. The patient’s wife was able to confirm this after finding a stash of spironolactone and estradiol at home. He was taking spironolactone 100mg and 100 micrograms of transdermal estradiol daily. She informed the providers that the patient was a transsexual who was taking hormones for feminization purposes. She stated that he was not seeing a physician for this, but was obtaining the medications through an overseas online source.
It is postulated that some of the medications administered during the initial resuscitation efforts masked the hyperkalemia that caused this patient’s cardiac arrest. This case illustrates the fact that hyperkalemia should still be considered in those with normal serum potassium levels drawn during a cardiac arrest after “code drugs” are administered. Moreover, clinical findings such as electrocardiographic changes consistent with hyperkalemia should not be ignored.
142 A DEADLY “DUAL”
Foster MB, Glancy DL, Jain N. LSU-New Orleans, New Orleans, LA.
Case Report: Dual AV node physiology is a common finding during routine electrophysiology studies. Observing this phenomenon on a single surface lead electrocardiogram, however, is a rare occurrence. AV nodal reentrance is a common mechanism of paroxysmal supraventricular tachycardia. We report the case of a patient who developed AV nodal re-entrant tachycardia (AVNRT) as the first instance of dual conduction pathways. Subsequent surface lead recordings confirmed two distinct PR intervals consistent with dual AV-nodal physiology. A 56 year-old female with a significant medical history of nonischemic cardiomyopathy (EF = 30%), hypertension, paroxysmal atrial flutter, diabetes mellitus, tobacco abuse, severe COPD, and cor pulmonale presented to the ED complaining of productive cough, dyspnea, orthopnea, nightly PND, and worsening lower extremity edema for two weeks. She denied chest pain, palpitations, nausea, vomiting, fevers, or chills. Her past history was significant for a syncopal episode within the last year attributed to atrial flutter. Her initial vital signs revealed a blood pressure of 149/108 mm Hg, pulse of 115 beats per minute, respiratory rate of 20, temperature of 98.6°F, oxygen saturation of 97% on room air, and BMI of 45kg/sq m. Her initial labs revealed a BNP of 848 pg/mL and a potassium level of 3.4 mmol/L. Chest radiography revealed cardiomegaly and pulmonary vascular engorgement. Her initial electrocardiogram revealed sinus tachycardia with a rate of 112 and a PR interval of 164 milliseconds. The patient was admitted and started on intravenous furosemide. On hospital day 4 she suddenly developed supraventricular tachycardia with a rate of 160 to 170 beats/min with a pattern consistent with AVNRT. The patient’s QRS duration was 82 milliseconds on surface electrocardiogram. Prior to treatment the patient converted to a sinus rhythm with a curious finding. The following surface electrocardiograms demonstrate PR intervals prolonged to 340 to 360 milliseconds. One particular electrocardiogram demonstrated alternating 1:1 PR intervals. The fast conduction pathway showed a PR interval of 160 milliseconds. The slow conduction pathway showed a PR interval of 360 milliseconds. She was started on digoxin. The patient had no more episodes of supraventricular tachycardia during her hospital stay.
143 PURULENT PERICARDITIS: AN UNCOMMON CONDITION IN AN UNLIKELY PATIENT
Isaac J1, Saxon JT2. 1 University of Mississippi Medical Center, Jackson, MS and 2 University of Mississippi Medical Center, Jackson, MS.
Case Report: A 50 year old African American man with type 2 diabetes mellitus presented with positional chest pain of a few days duration. The initial electrocardiogram demonstrated diffuse ST segment elevation, most consistent with acute pericarditis. Transthoracic echocardiogram revealed normal left ventricular systolic function with a small pericardial effusion. The patient had a mild leukocytosis and normal cardiac biomarkers. He was discharged on colchicine and ibuprofen for treatment of acute pericarditis. However, his symptoms persisted following hospital discharge, and he had several subsequent visits to urgent care facilities, without a significant change in clinical status. One week later, he developed severe dyspnea at rest, and worsening severity of positional chest pain. He presented to the emergency room for evaluation. A pericardial friction rub was present on physical examination. Repeat transthoracic echocardiogram revealed a large circumferential pericardial effusion with echocardiographic evidence of cardiac tamponade. A pericardiocentesis was performed, with aspiration of thick purulent fluid. A pericardial drain was left in place at that time. Cultures of the pericardial fluid ultimately revealed methicillin-sensitive Staphylococcus aureus. The patient was initially treated with intravenous vancomycin and oxacillin, which was narrowed to intravenous cefriaxone alone once bacterial sensitivities became available. The pericardial space was lavaged daily with thrombolytic agents and sterile saline, to promote lysis of fibrin formation and discourage formation of pericardial adhesions. The patient’s symptoms improved dramatically following pericardiocentesis. Prior to discharge, right heart catheterization was performed, which demonstrated constrictive pericardial physiology.
Purulent pericarditis is an uncommon condition characterized by bacterial infection in the pericardial space. The condition most often affects immunocompromised patients. Pericardiocentesis is the initial diagnostic and therapeutic intervention. Late in the disease course, pericardial constriction due to fibrin formation is a common finding and usually necessitates operative pericardiectomy.
Endocrinology and Metabolism Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
144 46 XX PHENOTYPIC MALE WITH AMBIGUOUS GENITALIA AND MULLERIAN DUCT REMNANT
Ahrari B1, Diaz-Thomas A2, Sinha SK2. 1 University of Tennessee Health Science Center, Memphis, TN and 2 University of Tennessee Health Science Center, Memphis, TN.
Case Report: Although ambiguity of external genitalia is seen in 1 out of 5000 births, 46 XX disorder of sexual development (DSD) has an incidence of 1:20000. Discovering the etiology of the DSD is challenging. Lack of standard guidelines for evaluation and management of 46XX DSD makes this a particularly difficult condition to address.
14yr and 2mo old ex 31 week premature African American phenotypic male is referred for hormonal evaluation. The patient had been born with ambiguous genitalia. Initial evaluation included routine karyotype which revealed 46XX. Primed in situ labeling after birth had shown presence of the sex-determining region on the Y (SRY) at chromosome X P22.3, however fluorescent in-situ hybridization and chromosomal microarray later in life did not show any evidence of SRY.
At 14yr and 4mo patient underwent pelvic and scrotal ultrasound that revealed: 9-cm right paramedian elongated tubular structure likely a utricular Mullerian structure as well as bilateral gonads in the scrotum (right 2.8×1.1×1.9cm with a volume of 3.15 mL and the left 3.3×0.8×2.1 cm with a volume of 3.10 mL). Hormonal evaluation at 14yrs 2mo was sent.
Testosterone, Total 249 (>180 ng/dl)
Testosterone, Free 2.2 (pg/ml N/A)
DHT 43 (24-65 ng/dL)
AMH 19 (3-5.4 ng/mL)
17-OH-Progesterone 23 (24-175 ng/dL)
Discussion: More often than not, the etiology of 46 XX DSD is unknown. In cases where the molecular defect can be identified SRY translocation is the most common mutation with other possibilities including SOX-9 duplication, copy number variation of SOX3, loss of function mutations in RSPO1, and mixed gonadal dysgenesis. Our patient reveals an inconsistent SRY analysis and testosterone levels that are disproportionately high for prepubertal gonads. Gonadectomy is the standard of care in 46XX DSD given the increased risk of malignant transformation, however our patient’s gonads appear to be well functioning and easily palpable. The presence of a Mullerian remnant makes the possibility of mixed gonadal dysgenesis high and could explain the inconsistent SRY result. Testicular biopsy is planned and perhaps this in conjunction with molecular analysis can assist with risk stratification and long term management.
145 HIDE AND GO SEEK - A CASE OF INTRATHYROIDAL PARATHYROID ADENOMA IN A PATIENT WITH PRIMARY HYPERPARATHYROIDISM
Awoniyi O1, Samant S2, Gosmanov A1. 1 University of Tennessee HSC, Memphis, TN and 2 University of Tennessee HSC, Memphis, TN.
Case Report: Background: In patients with primary hyperparathyroidism (PHPT), parathyroid adenoma can rarely be located within the thyroid. Preoperative localization studies are not very reliable to allow accurate localization of intrathyroidal parathyroid adenoma; therefore proper identification is frequently performed during surgery.
Clinical Case: 83-year-old female with a history of hypertension, hypothyroidism and osteoporosis was referred for evaluation of hypercalcemia. Laboratory evaluation revealed total calcium level of 11.1 (8.6-10.2 mg/dl), ionized calcium level of 6.3 (4.5-5.6 mg/dl) and PTH level of 69 (10-65 pg/mL) with normal serum 25-OH vitamin D and 24-hr urine calcium levels. Repeat investigations showed persistently elevated calcium and PTH levels consistent with PHPT. Thyroid ultrasound revealed multinodular goiter and a 9x3x4 mm hypoechoic ovoid structure in the right thyroid lobe consistent with a lymph node. Sestamibi scan demonstrated asymmetric increase in activity in the right thyroid lobe without specific location of signal. Patient agreed for neck exploration and parathyroidectomy. Extensive neck exploration including the retroesophageal groove revealed no parathyroid adenoma and perioperative PTH levels remained elevated. After review of the sestamibi scan, right thyroid lobectomy was performed that resulted in marked decrease in intraoperative PTH level from 131 to 21 pg/mL. Pathology evaluation showed a parathyroid adenoma within the inferior portion of the thyroid lobe supporting diagnosis of intrathyroidal parathyroid adenoma.
Discussion: In PHPT, about 6-16% of parathyroid glands can be located in ectopic positions making localization and surgical procedures challenging. The incidence of intrathyroid parathyroid glands is rare ranging between 0.7-3.6%. While the positive predictive value of routine imaging modalities to localize parathyroid adenoma is between 90-93%, in the setting of multinodular goiter like in our case localization can be difficult. Studies suggest that sestamibi scan is superior to ultrasound in such cases. We propose that localization studies together with the expertise of the surgeon are required for successful resection of intrathyroidal parathyroid adenoma.
146 TNF-Α INDUCED INSULIN RESISTANCE: USE OF SIRNA TO DEMONSTRATE ROLE OF PTEN
Bulger D1,2, Conley J2, Conner S1,2, Majumdar G1,2, Solomon S1,2. 1 University of Tennessee Health Science Center, Memphis, TN and 2 Veterans Association Medical Center, Memphis, TN.
Purpose of Study: The incidence of Type 2 Diabetes Mellitus (DM2) has sharply increased, primarily due to obesity. Adipose tissue in obesity produces higher amounts of TNF-α, which leads to chronic low-grade inflammation and insulin resistance (IR). The mechanism is still unclear. Previous genomic and proteomic studies by us on this IR have revealed significant differences in PTEN. PTEN dephosphorylates PIP3 and induces IR. Herein we utilize siRNA knockdown of PTEN to elucidate its role in TNF-α induced IR.
Methods Used: With and without PTEN siRNA (25 nM)/Dharmafect 1, H411E rat hepatoma cells were treated with insulin (10,000 μU/ml), TNF-α (1.0 nM), and insulin + TNF-α. We also tested 3-hydroxypicolinate vanadium (IV) complex (VO-OHpic) (37.5 nM) and metformin (10 μM). Protein and mRNA were extracted from the cells and analyzed by Western blot (Wb) and Real Time RT-PCR. Levels of PTEN in treated cells were compared to untreated control. Sensitivity or resistance to insulin were reflected by results of p-Akt Wb.
Summary of Results: PTEN/β-actin protein levels as measured by quantitation of Wb bands are calculated as percentages of control: insulin (80%, ↓); TNF-α (197%, ↑↑, p < 0.05); and insulin + TNF-α (122%, ↑). For PTEN/β-actin mRNA levels as measured by Real Time RT-PCR, percentages of control were the following: insulin (65.8%, ↓↓); TNF-α (198%, ↑↑); and insulin + TNF-α (98%, ↓). Insulin inhibited and TNF-α stimulated PTEN levels. Phospho-Akt/Total-Akt protein levels: insulin (230%, ↑↑, p < 0.05); TNF-α (95%, ↓); and insulin + TNF-α (300%, ↑↑↑, P < 0.05). Both insulin and VO-OHpic each prevented TNF-α induced stimulation of PTEN (p < 0.05), and the combination was additive (p < 0.05). Metformin, previously shown to inhibit TNF-α, showed no significant effects in the current experiments.
Conclusions: Use of siRNA PTEN provides proof of concept of a critical role of this phosphatase in insulin signaling. Insulin inhibits and TNF-α stimulates PTEN. An increase in PTEN inhibits insulin signaling. Unexpectedly, TNF-α stimulation of PTEN did not alleviate IR (p-Akt). Despite this last inconsistency, our overall data supports a central role for PTEN in IR, making it a potential therapeutic target in DM2.
147 METABOLIC BONE DISORDER IN THE ELECTROPHYSIOLOGY LAB: AN UNUSUAL DIAGNOSIS OF PAGET’S DISEASE
de Silva TN, Ahmed J, LeLorier P. LSU Health Sciences Center, New Orleans, LA.
Case Report: A 59 year old man with non-ischemic cardiomyopathy underwent implantation of an implantable cardioverter defibrillator (ICD). He had New York Heart Association class II symptoms. Echocardiogram revealed ejection fraction of 15% and aortic valve sclerosis. Post-operative chest x-ray revealed coarsening of the trabecula involving the glenoid and lateral left scapula consistent with possible Paget’s disease. The patient was referred to Endocrinology. He reported having mild left shoulder pain for 1 year, but did not have other bony pain or history of fractures. His children reported that he had been recently increasing the volume on his television, but he denied symptoms of any cranial nerve deficit. He had multiple dental caries. Skull x-ray was negative for changes consistent with Paget’s disease. Alkaline phosphatase and bone specific alkaline phosphatase were found to be elevated at 226 U/L and 59.6 mcg/L, respectively, consistent with Paget’s disease. Treatment with a bisphosphonate was not initiated due to his poor dentition and risk of jaw osteonecrosis.
Paget’s disease is a disorder of bone metabolism characterized by abnormal bone remodeling. Focal areas of the skeleton undergo increased osteoclastic resorption followed by subnormal repair by osteoblasts. The axial skeleton is preferentially affected. Approximately 30-40% of patients are symptomatic at the time of diagnosis. Bone pain is the most common presenting symptom. Some patients with skull involvement may present with deafness. Most patients who are diagnosed with Paget's disease are asymptomatic and the disorder becomes apparent due to findings of an elevated serum alkaline phosphatase level or abnormal radiograph obtained for other reasons. Cardiac involvement can include calcific valvular disease, AV block, and high output heart failure, due to increased cardiac output secondary to high blood flow as disease becomes more widespread. Cardiac stroke volume has been found to be higher in patients with Paget’s disease and has been correlated with severity of bone resorption. It is possible that Paget’s disease in our patient is contributing to his poorly controlled heart failure; however as the extent of his disease is limited it is not likely to be the primary cause of his heart failure.
148 PARATHYROID ADENOMA WITH SEVERE SYMPTOMATIC HYPERCALCEMIA AND IMPAIRED KIDNEY FUNCTION
Edriss H, Mazek H, Aly M, Berdine G, Lado-Abeal J. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: We report a 49-year-old man with no past medical problems who presented with polyuria, polydipsia, nausea, fatigue, muscle weakness, weight loss and dehydration. His serum calcium was 15.9 mg/dl, PTH was 568 pg/ml (nl: 15-65 pg/ml), 24-hour urinary calcium level of 460 mg (nl: <320mg), blood urea nitrogen 21mg/dl, creatinine 1.2mg/dl, eGFR 43ml/min/1.73m2, alkaline phosphatase 152 (nl: 29-129IU/L), and AST 51 (nl: 5-40IU/L). His chest x-ray was normal. Sestamibi-scintigraphy showed increased signal in the right side of the thyroid lobe. CT neck showed soft tissue nodule just posterior to right lobe of the thyroid measuring 1.5 × 0.8 cm. The patient was initially treated with rehydration, calcitonin, and pamidronate. His clinical symptoms improved, serum calcium level decreased to 11.2mg/dl, and kidney function improved within 48 hours. He underwent parathyroidectomy, and the histopathology showed a parathyroid adenoma. His PTH decreased to 7 pg/ml a few hours after the surgery.
Hypercalcemia is defined as a serum calcium level greater than 10.3 mg/dl. Primary hyperparathyroidism (PHPT) is the autonomous overproduction of parathyroid hormone (PTH) and often causes hypercalcemia. The most common cause of hypercalcemia of PHPT is a single parathyroid adenoma (85%). Most patients with PHPT are asymptomatic and identified during routine care; these patients have calcium levels that fluctuate between 9.7-11.5 mg/dl. Severe symptomatic hypercalcemia of >14 mg/dl is a rare presenting symptom of parathyroid adenoma. PHPT or malignancy causes more than 90% of cases of hypercalcemia. PHPT accounts for up to more than 90% in the outpatient setting and about 20% in hospitalized patients; malignancy accounts for up to 70% of hypercalcemia in hospitalized patients.
We report this case whose presentation initially suggested malignancy since severe symptomatic hypercalcemia of more than15mg/dl in the inpatient setting is uncommon presentation of primary parathyroid adenoma and is usually associated with malignancy. Severe symptoms of PHPT, known as parathyroid storm, require immediate management of the hypercalcemic crisis to reduce mortality. However, mortality remains high, even with surgical treatment which is the definitive therapy.
149 METHIMAZOLE-INDUCED GOITEROGENESIS IN A PATIENT WITH THE SYNDROME OF RESISTANCE TO THYROID HORMONE
Glymph K, Gosmanov A. UT Health Science Center, Memphis, TN.
Case Report: Introduction: The syndrome of pituitary-selective resistance to thyroid hormone (RTH) is a rare disease characterized by an increased threshold of pituitary thyroid stimulating hormone (TSH) suppression by thyroid hormone due to mutation in the TSH receptor gene. Antithyroid medications were not shown to improve clinical manifestations of hyperthyroxinemia in these patients.
Case: A 63 year-old African American female presented to our endocrinology clinic in April of 2012 for second opinion on management of goiter. In 2005, she was diagnosed with hyperthyroidism due to pituitary-selective RTH and started on therapy consisting of methimazole 15mg daily and atenolol. On initial evaluation in 2005, TSH level was elevated at 6.964 (0.35-5.50 mIU/L) and over period of treatment with methimazole TSH slowly increased with a peak of 24.88 mIU/L. Free thyroxine (FT4) initially was 1.55 ng/dL (0.61-1.76 ng/dL) and normalized after initiation of methimazole. Having achieved biochemical euthyroxinemia, she noted thyroid gland enlargement associated with progressive symptoms of dysphagia and dyspnea. On our examination, she had a globally enlarged firm thyroid gland with areas of nodularity in both lobes. She had TSH of 16.57 mIU/L, FT4 of 1.10 ng/dL, and free T3 of 173 ng/dL (85-205 mg/dL). A computed tomography of the neck showed enlarged thyroid goiter with extension around bilateral sternocleidomastoid muscles and compression onto the trachea. We thought that chronic elevations in TSH level resulted in goiterogenesis and discontinued methimazole while continuing atenolol. In 12 months, she experienced marked clinical and radiographic improvement of the goiter size associated with TSH reduction to 1.26 mIU/L and modest FT4 increase to 2.31 ng/dL.
Discussion: Patients with the RTH develop symptoms of thyrotoxicosis due to elevated thyroid hormone levels; therefore, it seems appealing to treat these patients with antithyroid medications. However, in these patients thionomides will decrease thyroxine level, which will in turn stimulate TSH production. TSH is a growth factor whose chronic elevation predisposes to goiter formation. In our case, discontinuation of methimazole caused decrease in TSH production with resultant improvement in patient symptoms and decrease in thyroid goiter size.
150 A CASE OF THIAMINE DEFICIENCY PRESENTING AS HYPOTHERMIA IN AN AIDS PATIENT
Graebert A, McDougald L, Engel LS, Masri N. LSU Health Sciences Center, New Orleans, LA.
Case Report: Hypothermia is a condition in which the core body temperature is decreased to below 35°C (95°F).
Case: A 45 year old Hispanic male was brought to our facility after being found lying outside on a sidewalk. According to EMS reports, the patient initially had a blood pressure of 106/60 with a pulse of 48, respirations of 18, 100% oxygen saturation on room air, a blood glucose level of 125, and had admitted to alcohol use that day. Upon arrival to our facility, he was found to have a core body temperature of 84.2°F. On our exam, the patient was drowsy but arousable. He spoke but did not answer questions appropriately. He did not have any evidence of head trauma and pupils were sluggish but reactive to light, otherwise his physical exam was unremarkable. Initial laboratory studies revealed hemoglobin of 11.7 gm/dL and an MCV of 111.2 fL. Toxicology screen was negative. EKG changes were consistent with Osborn waves seen with hypothermia. Blood, urine, and sputum cultures were obtained to evaluate for possible sepsis as the cause of the patients hypothermia and he was started on broad spectrum antibiotic therapy. TSH normal and both random and 8:00am cortisol levels were not depressed. He had a normal vitamin B12 level and a borderline deficient folate level. The patients’ hypothermia was gradually corrected with active external re-warming techniques. After about 12 hours of monitoring in the ICU his core body temperature reached 96°F. Further history was then able to be obtained and it was learned that the patient was infected with HIV. An immunodeficiency panel was checked revealing an absolute CD4 count of 2 cells/uL. As thiamine deficiency was supported by a thiamine level of 22 ug/L. The patient was discharged with thiamine and folate supplementation
Discussion: The moderate hypothermia observed in our patient is most likely secondary to thiamine deficiency secondary to multiple etiologies including his malnourished state, AIDS and his alcohol abuse. Deregulation at the level of the hypothalamus is specifically responsible for the hypothermia seen in thiamine deficient individuals. Currently, there are no recommendations for administration of thiamine to patients with hypothermia.
151 REFRACTORY HYPONATREMIA IN AN INFANT
Hiebert R, Marin M, Krishnan S. University of Oklahoma Health Science Center, Oklahoma City, OK.
Purpose of Study: To investigate an uncommon cause of refractory hyponatremia in an infant.
Methods Used: Literature and chart review.
Summary of Results: Isolated hyponatremia is an uncommon presentation in neonates. When hyponatremia is associated with hyperkalemia, it is concerning for mineralocorticoid abnormalities. While congenital adrenal hyperplasia is the most common cause of such a presentation, rarely a neonate may have aldosterone deficiency or resistance.
A 1 month old child was admitted to the hospital with hyponatremia (131 mEq/L) and hyperkalemia (7.3 mEq/L) noted during a visit to her primary care physician. She was born at 33 weeks gestation and required a 2 week NICU stay for hyponatremia since birth and prematurity. At presentation she was clinically asymptomatic with adequate oral intake. Physical examination was completely normal and did not reveal any ambiguous genitalia. She was started on florinef with sodium chloride supplements which were titrated up to achieve eunatremia pending endocrine work up. Laboratory work up included plasma renin activity, corticosterone, ACTH, 17 hydroxyprogesterone, thyroid function tests, and an ACTH stimulation test, all of which were normal. Aldosterone level was elevated consistent with pseudohypoaldosteronism. She was discharged on sodium chloride supplementation at a dose of 21 mEq/kg/day. She has experienced stable growth and development since then.
Conclusions: Pseudohypoaldosteronism (PHA1) or mineralocorticoid resistance is an uncommon syndrome which can be further subdivided into two forms. The autosomal recessive form is associated with severe generalized salt loss in the skin and saliva and results from a mutation in the gene coding the epithelial sodium channel. The autosomal dominant, renal form is less severe and results from a mutation in the mineralocorticoid receptor gene NR3C2. The less severe renal PHA1 presents with salt loss, insufficient weight gain due to chronic dehydration, hyperkalemia, and elevated plasma renin and aldosterone levels. Our patient’s clinical picture is highly suggestive of the renal form of PHA1. Although unlikely given our patient’s negative sweat chloride test, the generalized form of PHA1 with a milder clinical course cannot be ruled out. Premature infants also have physiologic aldosterone resistance, which may have been exaggerated in our case, but must be a diagnosis of exclusion.
152 HYPOGLYCEMIA IN AN ELDERLY PATIENT-DON’T IGNORE INSULINOMA
Jacovino CA, Powell S, Gosmanov A. University of Tennessee Health Science Center, Memphis, TN.
Case Report: Insulinoma is a rare neuroendocrine tumor deriving mainly from pancreatic islet cells that secrete insulin. Prior studies suggested that the diagnosis of insulinoma is difficult in elderly and it is thought that the incidence of insulinoma in the elderly persons presenting with hypoglycemia can be underestimated.
An 81-year old African American female with a history of obesity, hypertension and hyperlipidemia and no history of diabetes presented to the emergency room with weakness. She was found to have blood glucose (BG) of 40mg/dL; hypoglycemic episode resolved after glucagon injection. After admission for short-term observation, she had another episode of hypoglycemia with a BG of 43 mg/dL associated with C-peptide of 3.44 ng/mL (0.8-3.80) and insulin of 73.0 μU/mL (4.2-27.9). Our evaluation showed normal adrenal and thyroid function, hemoglobin A1c of 5.4% (<5.7%), and no evidence of liver or kidney failure. A 72-hour fasting was initiated to exclude insulinoma. Symptomatic hypoglycemia with BG level of 49 mg/dL occurred 18 hours after initiation of fasting accompanied by inappropriately elevated C-peptide of 2.63 ng/mL and insulin of 43.7 μU/mL. Her sulphonylurea panel, chromogranin A, gastrin, and calcium levels were normal. A computed tomography of abdomen showed an 18 mm hyperdense focus within the uncinate process of pancreatic head. Patient underwent surgical resection of the tumor. The final pathological diagnosis demonstrated insulin-secreting islet cell tumor. During our follow up 6 months after surgery, the patient no longer had hypoglycemic episodes and was found to have mild type 2 diabetes.
The diagnosis of insulinoma depends on the exclusion of the more common causes of hypoglycemia and based on the demonstration of raised plasma insulin and C-peptide levels in the presence of hypoglycemia in fasting state. Few cases have been reported atypical presentation of insulinoma. In our patient, blood glucose levels were taken during fast confirmed biochemical diagnosis of insulinoma which was subsequently supported by the pathology report of the excised tumor. Though insulinoma is predominantly seen in young and middle age patients, it should be suspected in the elderly presenting with hypoglycemia that is not explained by other clinical processes.
153 RECURRENT MIXED-TYPE PAPILLARY AND FOLLICULAR THYROID CARCINOMA IN A PATIENT WITH DIGEORGE SYNDROME
Mikail J, Rincon-Subtirelu M. University of Tennessee College of Medicine at Chattanooga, Chattanooga, TN.
Case Report: DiGeorge syndrome is a 22q11.2 deletion syndrome that has characteristic signs and symptoms that often include neuromuscular problems, congenital heart defects, defects in the palate and recurrent infections. Recurrent infections are associated with a hypoplastic thymus. Initial clinical signs include hypocalcemia at birth due to malfunctioning parathyroid glands. Late-occurring consequences include hypothyroidism and hyperparathyroidism. There is no literature documenting patients with DiGeorge syndrome who develop thyroid carcinoma.
Case Report: This 13 year old female was diagnosed at three months of age with DiGeorge syndrome. In association with her DiGeorge syndrome, she had cleft palate and ventricular septal defect. Though, she never had symptoms of hypocalcaemia or any immunological deficits.
Her pediatrician noted a thyroid nodule during an office visit when she was 4 years old. An ultrasound study found the mass to be solid. She had a left thyroidectomy performed one month later. Histology on the tissue sample was found to contain papillary carcinoma, follicular variant. There was invasion of the capsule by the tumor and the tumor extended to the surgical margins in several areas. She subsequently had a total thyroidectomy performed one month later. No tumor was seen in the specimen. At least one parathyroid gland was preserved at the time of surgery. She was started on long term thyroid hormone replacement.
After an elevated thyroglobulin level was noted in her yearly follow up at age 13, she had a repeated scan that showed small areas of radioactivity in the left lung and right lung. The patient received a second I131 treatment with a follow-up scam showing small areas of radioactivity in the lower neck and left chest wall. Following this scan, the patient has remained stable despite new evidence of recurrence.
Conclusions: We report a new case of thyroid carcinoma in a female patient with DiGeorge syndrome. As both DiGeorge syndrome and papillary thyroid carcinoma, follicular variant are rare, it raises the question of whether this is the result of a genetic tumor suppressor gene that is affected in certain variants of DiGeorge syndrome.
154 A CASE OF COEXISTING DIABETES INSIPIDUS AND CEREBRAL SALT WASTING SYNDROME SUCCESSFULLY TREATED WITH DESMOPRESSIN AND FLUDROCORTISONE
Rivas AM, Laengvejkal P, Sotello D, Lado-Abeal J. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: Patients with central nervous system surgery or trauma can have complex electrolyte disorders.
A 76-year-old man with a history of essential hypertension on olmesartan presented with decreased level of consciousness caused by spontaneous bleeding inside a non-functioning pituitary macroadenoma diagnosed with head MRI. He underwent emergent evacuation of sella turcica. Sixteen hours after surgery he developed diabetes insipidus (DI) with good response to desmopressin (DDAVP). However, forty-eight hours later, he developed recurrent polyuria (128cc/hour) that didn’t respond to an increased dose of DDVAP. Subsequently, he became volume contracted and developed severe hyponatremia (129 mmol/L) secondary to high urine sodium excretion (186 mmol/L). Further workup showed serum aldosterone levels <1ng/dL and brain natriuretic peptide of 4581pg/mL; no signs of congestive heart failure or cardiac ischemia were present. Cerebral salt wasting syndrome (CSW) was suspected, and he was started fluid hydration with physiologic saline solution without improvement. Oral fludrocortisone (0.1mg twice daily) was added and corrected the polyuria and hyponatremia.
DI and CSW are well-known complications of intracranial surgery, but their coexistence is unusual. In our case, the recurrent polyuria was initially attributed to DDAVP resistance, but the lack of response to higher dosages of DDAVP together with hyponatremia, natriuresis, high BNP and aldosterone deficiency lead us to suspect CSW.
CSW is characterized by an abnormal release of natriuretic factors by injured brain tissue. These patients present with aldosterone depletion secondary to an inhibitory effect of brain natriuretic peptides on the renin-angiotensin-aldosterone system and decreased sympathetic stimulation of renin secretion after acute central nervous system injury. Repletion of mineralocorticoid was successful in the treatment of CSW in this patient. We recognize that our patient could have had some baseline aldosterone deficiency from chronic use of olmesaratan, which should not be overlooked. Even so, considering what is understood of the physiopathology of CSW, it is likely that fludrocortisone had an important role on its treatment.
155 HYPERPROLINEMIA AND PSYCHIATRY IN 22q11.2 DELETION SYNDROME
van Asbeck E1,2, Morava-Kozicz E1,2. 1 Radboud University, NIjmegen, Netherlands and 2 Tulane University, New Orleans, LA.
Purpose of Study: 22q11.2 deletion syndrome has a highly variable phenotype, despite the uniformity of the deleted region. It is associated with cleft palate, congenital cardiac abnormalities and learning disabilities, as well as thymus hypoplasia and hypoparathyroidism. A subgroup of these patients develop some degree of psychiatry, the most frequent of which is schizophrenia. Hyperprolinemia type 1 (HPI) is caused by mutations in the PRODH gene, which can be included in the deleted region. Here, we present a patient diagnosed with a 2,91 Mb deletion in 22q11.2 region. The patient started regressing at the age of 24 and had memory loss, seizures despite medication and psychiatry. We hypothesized that hyperprolinemia, which is known to cause psychiatry in PRODH related metabolic patients, could cause the psychiatry and seizures in our patient.
Methods Used: We did Array CGH to see whether PRODH was deleted in this patient, we measured proline levels and searched the literature for patients diagnosed with 22q11.2 deletion syndrome involving PRODH, to see whether they have hyperprolinemia.
Summary of Results: ArrayCGH showed that PRODH was deleted in our patient. The patients’ proline levels were variable but consistently elevated. We found other patients with deletions in 22q11.2 and hyperprolinemia. Thus, we confirmed our hypothesis.
Conclusions: Haploid insufficiency of PRODH can cause hyperprolinemia, which might play a role in psychiatry seen in 22q11.2 deletion patients. Symptoms of such psychiatry can be late onset. We suggest protein restriction as therapy in these patients, to lower proline levels and therefore patient outcome.
156 PERSISTENT HYPERTENSION FOLLOWING SUCCESSFUL TREATMENT OF BILATERAL RENAL ARTERY STENOSIS: A CASE OF TERTIARY HYPERALDOSTERONISM
Varughese Ag, Uwaifo G. Louisiana State University, New Orleans, LA.
Case Report: Introduction: Secondary hypertension (HTN) is known to be common and its recognition is growing in importance due to potentially reversible causes. Renovascular HTN is the most common cause of secondary HTN. Persistent HTN after treatment of renal artery stenosis (RAS) can be an alerting sign. The most common etiology in this setting is coexistent essential HTN but the possibility of another secondary etiology due to renovascular HTN needs to be sought.
Case: A 46 YO Black American woman with obstructive sleep apnea (OSA) presented with sixteen years of HTN. Patient developed hypertensive emergency and was found to have bilateral renal artery stenosis (RAS) with elevated serum aldosterone 30 ng/dl (1-21) and a plasma renin activity (PRA) 5ng/ml/hr (0.6-4.3). The RAS was due to fibromuscular dysplasia (FD) and she underwent bilateral renal artery angioplasty without improvement in HTN. Further work up showed an aldosterone of 12 ng/dl and PRA of 0.41 (ratio: 30). 24 hour urine aldosterone with oral sodium loading yielded an aldosterone of 12.9ng/dl and sodium of 314 ng/dl. Adrenal computerized tomography (CT) was normal and biochemical features typical of primary hyperaldosteronism (PAH) post successful RAS repair. Patient started on eplerenone 50mg daily resulting in reversal of HTN but higher aldosterone levels (44ng/dl). These finding are consistent with PAH following prior secondary hyperaldosteronism (SAH) caused by bilateral RAS. This suggests progression from prior SAH to autonomous tertiary hyperaldosteronism (TAH) probably due to bilateral adrenal hyperplasia.
Discussion: PAH is one of the common causes of Secondary HTN. In PAH, aldosterone production is inappropriately high and non-suppressible by sodium loading. Persistent HTN after treating the reversible causes of SAH suggests zona glomerulosa autonomy called TAH. TAH is uncommon and most commonly occurs in older patients with prior SAH due to atherosclerotic plaques of renal arteries. Her untreated OSA may have contributed to the development of TAH following SAH.
Conclusion: Recognition of this entity, TAH, is important to enable effective blood pressure control in patients with persistent HTN despite apparent hemodynamic correction of renovascular HTN.
157 PROFOUND MUSCLE WASTING AS A PRESENTATION OF HYPERTHYROIDISM IN AN ADOLESCENT
Walkup JD, Carlucci M, Rincon-Subtirelu M. University of Tennessee at Chattanooga College of Medicine, Chattanooga, TN.
Case Report: A 14-year-old male presented with a progressive symmetrical weakness of the upper and lower extremities over the course of approximately 3 weeks. This culminated in an event in which he was unable to rise out of a movie theater seat, and had enough strength only to fall forward and crawl. The patient reported that over the 3 weeks he had been unable to stand up from a sitting position and was falling forward, then pulling himself to stand. Prior to this, he had a weight loss of 74 lbs. over the preceding 7 months. This was not initially considered problematic by the family because he was undergoing a workout regimen to correct his obesity. They had noticed the patient was able to eat smaller meals and were proud of this accomplishment. However, from the patient’s perspective he was experiencing progressive early satiety and had no real increase in muscle mass.
On exam, the only positive finding was significant muscle wasting in the proximal muscles of the upper and lower extremities. The differential diagnosis for this patient’s muscle weakness and wasting included polymyositis, muscular dystrophy, neurological causes, psychiatric causes (due to a history of bullying because of obesity), and nutritional deficiency. Over the course of his hospital admission, he was found to have abnormal thyroid function test with a final diagnosis of hyperthyroidism, secondary to Graves’ disease. In retrospect, he did not have vital signs abnormalities, nor thyroid enlargement or ophthalmopathy to suggest the disease.
This case is unique because of the presentation of hyperthyroidism as rapid development of muscle wasting without the most classical signs and symptoms of the disease. Pediatricians should include thyroid dysfunction when evaluating severe myopathy in the context of weight loss.
Gastroenterology Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
158 MASSIVE UPPER GASTROINTESTINAL BLEED FOLLOWING FOUR-DAY THERAPY OF NAPROXEN AND DOXYCYCLINE: IS IT A SYNERGISTIC EFFECT?
Gharaibeh K1,2, Brewer M1,2, Patnana S1,2, Cook-Glenn C2, Bhagat R1,2. 1 University of Mississippi Medical Center, Jackson, MS and 2 G.V. Sonny Montgomery VA Medical Center, Jackson, MS.
Case Report: Introduction: Chronic prolonged naproxen-induced gastrointestinal (GI) mucosal injury/bleeding and doxycycline pill-induced esophagitis are well documented in literature. There is no information on the GI effects of the two together. We report a case of massive upper GI bleeding secondary to gastric ulcers after only 4 days of doxycycline and naproxen therapy.
Case-report: A 53-year-old male was admitted with 8 hours of bleeding per rectum. Patient reported mild epigastric pain with nausea but denied vomiting, hematemesis, or melena. Four days prior he was initiated on naproxen 500 mg and doxycycline 100 mg twice daily for presumed Lyme disease. On exam the patient had tachycardia (108/min), hypotension (90/60 mmHg) and mild epigastric tenderness. His admit hemoglobin was 7.1 g/dL (4 days prior was 15.6). Nasogastric lavage confirmed fresh blood. In the intensive care unit he was fluid resuscitated and initiated on pantoprazole and octreotide infusions. He required transfusion with 8 units of blood. Esophagogastroduodenoscopy revealed multiple ulcers and the bleeding gastric ulcer vessel was treated with a clip. H. pylori work up was negative. Patient recovered well off doxycycline and naproxen.
Discussion: Naproxen induced upper GI bleeding with <14 days of therapy is rare (0.026%) while doxycycline causes pill esophagitis and rarely gastritis. Our patient had received both together for only 4 days when he developed a massive upper GI bleed. Our report raises the possibility of synergistic effect between naproxen and doxycycline leading to “accelerated” GI injury. Naproxen, besides inhibiting cyclooxygenase, also disrupts the hydrophobic phospholipid protective mucosal barrier. In our patient we hypothesize this loss of protective barrier with caustic effect of acidic doxycycline lead to upper GI bleed with only 4 days of therapy.
Conclusion: The combination of naproxen and doxycycline should be prescribed with care. The possibility of the two drugs synergistically increasing the risk of accelerated upper gastrointestinal injury associated bleeding needs further exploration.
159 A RARE CAUSE OF CHRONIC DIARRHEA IN AN ENDOSCOPIC PERCUTANEOUS GASTROSTOMY PATIENT: A CASE REPORT AND LITERATURE REVIEW
Mankongpaisarnrung C, Dumrongmongcolgul N, Phisitkul S, Roberts J, Rakvit A. Texas Tech University Health Sciences Center (TTUHSC), Lubbock, TX.
Case Report: Introduction
Oropharyngeal dysphagia can be caused by external compression, such as cervical spondylosis, by luminal disorders in upper aerodigestive tract, and by neuromuscular weakness, such as previous stroke. The long-term management goal is to avoid parenteral nutrition and to maintain enteral feeding by placing a feeding tube surgically or endoscopically. However, complications, such as bleeding, infection, peritonitis, transverse colon injury, and buried bumper syndrome, can occur.
Case report: A 66-year-old man with COPD had oropharyngeal dysphagia from cervical myelopathy. He was status post 360° cervical fusion of C3-C7 with C4 corpectomy and required percutaneous endoscopic gastrostomy (PEG) tube placement due to difficulty swallowing. He was transferred from an outside facility with 30 pound involuntary weight loss over 6 months and chronic diarrhea 30-40 times a day after PEG tube placement. He described the tube feeding as “running right out of him”. He had adhered strictly to dietary recommendations. He denied nausea, vomiting, and fever. Physical examination was unremarkable except for cachexia. Abdominal examination showed PEG tube in place; no erosion or infection was seen. Initial labs revealed mild anemia with Hb of 11.5 gm/dl. He underwent computed tomography of abdomen for initial evaluation to assure the integrity and the position of the PEG tube. CT scan abdomen revealed PEG tube balloon tip was mal-positioned in the transverse colon; this was confirmed with gastrografin fistulogram. Intraoperative findings showed dislodged and misplaced PEG tube in mid-distal transverse colon.
Discussion: We are reporting a rare complication with a PEG tube, which resulted in profuse and intractable diarrhea. Recalcitrant diarrhea after PEG tube placement should alert the clinician to this complication. The PEG tube probably traversed and migrated into an adjacent structure, and the profuse diarrhea was caused by colonic irritation. Aspirating feculent material from the PEG tube can help recognize this complication early. CT scan and fistulogram can make this diagnosis. The only treatment option is surgical correction.
159A PANCREATIC BURKITT’S LYMPHOMA SHOULD ALERT PROMPT TREATMENT?
Mankongpaisarnrung C1, Kijsirichareanchai K2, Soape M1, Rassameehiran S1, Rakvit A1. 1 Texas Tech University Health Sciences Center (TTUHSC), Lubbock, TX and 2 University of Nebraska, Omaha, NE.
Case Report: Burkitt’s lymphoma (BL) is an aggressive NHL with a rapid doubling time of 24-48 hours. Its primary location is within the abdomen (60-80%), followed by the head and neck. The histopathology is classically described as a starry sky appearance. Pancreatic lymphoma (PL) can be divided into primary and secondary PL by the involvement of other lymph nodes (secondary). PL as an extra-nodal involvement can present without symptoms, with painless jaundice, or with pancreatitis.
A 45-year-old healthy Hispanic man presented with a 2-week history of LLQ pain and a 20-pound weight loss. He also reported a progressive swelling of neck. History of heavy smoking and IVDU were noted. Physical exam found a 5 × 5 cm matted right anterior cervical and supraclavicular LAD and LLQ tenderness. His labs were normal except elevated amylase (78 U/L), lipase (177 U/L), LDH (2201 U/L), and positive HIV. CEA and CA19-9 were normal. MRCP of the abdomen confirmed a 2.5-cm pancreatic head mass causing mild distal PD dilatation. CT scan also found an 8.6-cm mass in the right paratracheal node. Subsequent EUS showed a round, poorly defined, hypoechoic mass in the posterior mediastinum, 3.7 cm irregular and hypo-anechoic mass in the pancreatic head with portal vein invasion but no CBD dilatation. The dilated 2.4mm-PD was noted in the body and tail of pancreas. Pancreatic adenocarcinoma (PA) was preliminarily suspected from EUS. FNA showed anaplastic cancer cells, favoring a hematopoietic tumor. CT-guided lung BX confirmed BL. He lost to follow up but presented two weeks later with SVC syndrome and pericardial effusion. Cyclophosphamide-based chemotherapy (CMT) regimen was started but he died of tumor lysis syndrome soon after CMT began.
BL can grow rapidly if left untreated. Since pancreatic BL and PA require different therapeutic approaches, accurate diagnosis is crucial for prompt treatment. With the use of EUS, the findings may mimick PA. However, clinical correlation and cytology increase the diagnostic yield. We underscore the importance of detecting secondary PL from BL, which may reflect a significant tumor burden and lead to poorer outcomes. Hence, prompt aggressive workup and treatment once the definite diagnosis confirmed is essential.
160 A CASE OF PLUNGING GIST PRESENTING AS INTERMITTENT DYSPHAGIA
Nakshabendi R1,2, Clark M1,2, Munoz JC2,1, Nakshabendi I2. 1 University of Florida, Jacksonville, FL and 2 University of Florida, Jacksonville, FL.
Case Report: The patient is a 71-year-old woman with a past medical history of melenoma who presented to the hospital with progressively worsening intermittent dysphagia mainly for solid foods over the past year. Associated symptoms included reflux without significant weight loss. She typically had to chase solid food down with liquids in order to prevent any type of impaction. She has never had any food impaction which has required a food bolus removal. EGD 6 months prior was unremarkable.
Endoscopy revealed a large 4 to 5 cm subepithelial lesion in the mid-esophagus at around 30 cm. The lesion appears smooth with normal overlying smooth tissue. There were no obvious ulcerations. Biopsies were not taken at that time. CT scan of the chest confirmed the presence of a large submucosal mass in the distal esophagus. Repeat biopsy was performed with EUS and biopsy. No extra-esophageal masses were identified and biopsy was proven for the gastrointestinal stromal tumor. The patient was started on neoadjuvant chemotherapy with Gleevec with future plans for surgical resection.
Esophageal mass, FNA: Spindle cell neoplasm consistent with a gastrointestinal stromal tumor with necrosis. Comments: An immunohistochemical stain for CD117 (C-Kit) is positive within the spindle cells. An immunohistochemical stain for HMB-45 is negative. This pattern of staining is consistent with a gastrointestinal stromal tumor.
161 EOSINOPHILIC GASTROENTERITIS AND SYSTEMIC LUPUS ERYTHEMATOSIS; A RARE ASSOCIATION
Omer AA, Abdel Karim T, Akhter SR, Islam A, Ahmed M, Ali A. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: A 40 year old male presented to our hospital with a 3-month history of nausea, vomiting, abdominal distention and mild diarrhea. He denied any GI symptoms prior to his current illness. On physical exam, he was found to have positive shifting dullness. Laboratory data revealed a white count of 3100 cells/mm3 with eosinophils 0.4% and serum albumin of 2.4 g/dL. Positive serological markers were: ANA at 1:320; anti-dsDNA at 1:1280; anti-SSA antibodies at 144 AU/ml; anti-SSB antibodies at 68 AU/ml; a low C3 (54mg/dL) and C4 (14mg/dL) levels .Stool culture, ova and parasites were negative. Abdomino-pelvic CT scan showed diffuse small and large bowel wall thickening and ascites. Endoscopic evaluation revealed an edematous gastric wall with many areas of submucosal hemorrhage, edematous gastric antrum and edema of the colonic wall. Nonspecific chronic gastritis, chronic duodenitis and normal colonic mucosa were found on endoscopic biopsies. Exploratory laparotomy yielded 3 liters of ascitic fluid with 24% eosinophils. An excisional biopsy of the appendix revealed chronic serositis changes and focal eosinophilic infiltrates in the lamina propria and the submucosa. Liver biopsy demonstrated an increase in sinusoidal eosinophilis. When methylprednisilone was given, his symptoms improved dramatically and his ascites resolved.
Discussion: Eosinophilic gastroenteritis (EGE) is categorized as either primary (idiopathic) or secondary. In the former type, an allergy basis is very likely. This is derived from the positive allergic diathesis history in some patients, peripheral and tissue eosinophilia and elevated total and food-specific IgE levels. Secondary EGE has been associated with inflammatory bowel disease (IBD), hypereosinophilic syndrome, celiac disease, vasculitic disorders, drugs and parasitic infestations. More recently, an association of EGE with SLE has been reported. The relationship between these two disease entities is unclear, but an underlying immunological link is conceivable. Corticosteroids remain the cornerstone of treatment for EGE, with a reported response rate of 90%. In conclusion physicians should not ignore the differential diagnosis of EGE in SLE patients with unexplained gastrointestinal symptoms.
162 AN UNCOMMON CAUSE OF DRUG-INDUCED PANCREATITIS: DOXYCYCLINE
Rassameehiran S, Mankongpaisarnrung C, Rakvit A. Texas Tech University Health Sciences Center, Lubbock, Texas, Lubbock, TX.
Case Report: Acute pancreatitis is one of the common gastrointestinal causes of hospitalization. Although the incidence of drug-induced pancreatitis is low, this disease is associated with substantial morbidity and mortality. Identification of the offending medication and history taking are very important. Common offending medications include asparaginase, azathioprine, didanosine, pentamidine, and valproic acid. This is a case of an uncommon medication causing acute pancreatitis.
An 82-year-old African American woman with previous cholecystectomy presented with severe epigastric and right upper quadrant abdominal pain associated with nausea for 1 day, happened after 12-day usage of doxycycline for cellulitis. The rest of her medication list remained unchanged. She was hemodynamically stable. Physical examination revealed mild tenderness over the epigastric area without peritoneal signs. Laboratory findings revealed an elevated lipase level of 2,222 IU/L, elevated amylase level of 1,122 IU/L, unremarkable triglyceride, unremarkable total bilirubin level of 0.3 mg/dl, normal alkaline phosphatase level, and normal calcium level. Computed tomography of abdomen and pelvis revealed enlargement of head and uncinate process of the pancreas with peripancreatic stranding. Ultrasonography of abdomen showed normal size of common bile duct at 3.7 mm. She denied any alcohol use. She was diagnosed with acute pancreatitis. Doxycycline was stopped and she was treated conservatively with uneventful hospital stay.
Drug-induced pancreatitis from doxycycline is uncommon. There have been conflicting data about the effect of doxycycline on the pancreatitis. Some reports describe a protective effect of doxycycline by inhibiting pancreatic phospholipase A2, which reduces the tissue damage in acute pancreatitis. However, doxycycline has also been reported as a causative agent in drug-induced pancreatitis. In our case, we considered doxycycline-induced pancreatitis after eliminating other causes of pancreatitis. Antibiotic-associated pancreatitis usually has a mild course, and discontinuation of the offending medication is the mainstay of treatment.
Health Care Research and Quality Improvement Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
163 THE SAFEMED PROGRAM: EARLY LESSONS FROM A CARE TRANSITIONS PROGRAM WITH A FOCUS ON MEDICATION MANAGEMENT
Bailey JE1,2, Nault J1, Waters T2, Speck P3, Rashed S4, Ugwueke M5. 1 University of Tennessee Health Science Center (UTHSC), Memphis, TN; 2 UTHSC, Memphis, TN; 3 UTHSC, Memphis, TN; 4 UTHSC, Memphis, TN and 5 Methodist Le Bonheur Healthcare, Memphis, TN.
Purpose of Study: Previous research suggests that patients with multiple chronic conditions (MCC), high inpatient utilization, and polypharmacy are at high risk for readmissions and adverse outcomes. Early research suggests that care transitions programs with an emphasis on medication management have potential to result in better care and outcomes at lower cost. This study seeks to determine whether the SafeMed Program, a care transitions program emphasizing medication management funded through the Center for Medicare and Medicaid Innovation, significantly impacted readmission rate in the vulnerable population served.
Methods Used: This quasi-experimental prospective study assessed impact of the SafeMed Program on hospital readmission rates during first six months of program implementation. Patients were required to meet full eligibility criteria including: 1) hospital admission to either of two hospitals serving readmission hotspots, 2) two or more chronic health conditions, 3) high previous inpatient utilization, 4) Medicare and/or Medicaid, and 5) age > 18. Comparison population included individuals who were screened as eligible for participation. Main outcome measure was hospital readmission rate calculated using the UnitedHealth Group (UHG) counting methodology and utilization reports generated using an internal data management system for the region-wide hospital network.
Summary of Results: 57 enrolled patients had a 34% readmission rate whereas 76 comparison patients had a 46% readmission rate, however, this difference was not statistically significant at p<.05. These findings suggest that enhanced medication management is necessary but not sufficient to significantly impact the readmission rate.
Conclusions: Preliminary results suggest that enhanced medication management is necessary but not sufficient to significantly impact readmission rates. Care transitions programs emphasizing medication management have great potential but will likely need to provide robust symptom triage and care coordination services to address complex social needs to have major impact on readmissions.
164 QUALITY IMPROVEMENT IN DIABETES FOOT AND EYE CARE: A MULTIDISCIPLINARY APPROACH
Day B, Dreyer S, Furr A, Hill J, Myrick WM, Obih U, Price S, Tenini J, Saha A. Carolinas Medical Center, Charlotte, NC.
Purpose of Study: The purpose of our study is to improve the care of patients with diabetes through two quality improvement (QI) initiatives: one designed to increase the rate of annual diabetic foot examinations (goal of 80% in one year), and another to increase the rate of annual retinopathy screening (goal of 50% in one year).
Methods Used: We first formed a multidisciplinary team dedicated to ambulatory QI initiatives. We employed frequent Plan-Do-Study-Act (PDSA) cycles and Lean methodology as our main tools for improvement. Weekly electronic data capture with run chart tracking helped guide the effectiveness of our interventions. For the foot exam project, successful interventions included: having patients remove their shoes, having monofilaments visible, resident education at conferences, transparency in data publishing, and nursing-physician communication via a laminated card. For our newer eye exam project, our first PDSA intervention involved a nursing-driven protocol for documenting and requesting eye exams.
Summary of Results: We began with an estimated baseline rate of 28% of patients up to date on their annual diabetic foot exam. Within two months we were able to significantly increase our weekly foot exam rate, achieving our stated goal of 80%. However, success proved difficult to sustain, and along with incoming interns in July our rates dropped to 55.1%. With continued efforts, we have slowly and reliably increased our weekly rate back towards our stated goal once again. Initial eye exam data shows a baseline of 36% of patients documented as up to date. After our first PDSA cycle, we have not yet increased our rate of complete eye exams and are planning the next PDSA cycle.
Conclusions: Improving diabetic health maintenance is a challenging but vital task in primary care. In our study, we focused on improving rates of annual foot examinations and screening for retinopathy. Our foot exam project showcases successful quality improvement interventions which are currently proving sustainable and are likely easily replicable in similar primary care settings. Our eye exam project is still underway although we have not shown improvement here yet, we hope to apply the lessons learned from the foot exam project to achieve sustainable success in this area as well.
165 STANDARDIZATION OF WRITTEN HANDOFFS ON AN INTERNAL MEDICINE SERVICE
Edwards AL1, Shewchuk R2, Taylor B1, Rodriguez M1, Kraemer R1, Curry W1. 1 University of Alabama at Birmingham, Birmingham, AL and 2 University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: New duty hour standards have raised concern regarding increased numbers and quality of handoffs. We examined whether a standardized written handoff would improve resident satisfaction, perceived utility, and subjective efficiency of the handoff process.
Methods Used: Quasi-experimental design (pre-/post-intervention). Single academic internal medicine service (1,000-bed hospital) (Mar-May 2013). Residents used a standardized, word processor-based, written handoff template. A five-item survey assessed resident satisfaction, utility, and subjective efficiency of the handoff process at baseline (pre-) and at 3-month follow-up (post-). Respondents selected agreement with written handoff: 1) utility to accomplish daily duties, 2) ability to accomplish daily duties in a timely manner, 3) utility when answering cross-cover questions, 4) satisfaction, and 5) use of the standardized template almost always (last item, only at follow-up survey)(5-point Likert scale; 5 = strongly disagree, 1 = strongly agree). Respondents also estimated time spent composing written handoffs. We compared pre- and post-intervention responses with the Mann–Whitney U test.
Summary of Results: Of 48 individuals surveyed, 15 responded at baseline (31%) and 20 at 3-month follow-up (42%). The standardized handoff template was used almost always by 95% of respondents. Respondents reported increased written handoff utility in accomplishing daily duties, increased utility when answering cross-cover questions, and increased overall satisfaction with the written handoff process post intervention (Table). Unchanged were accomplishing daily tasks in a timely manner (P = 0.11) and time spent composing written handoffs (P = 0.36).
Conclusions: Standardization of the written handoff improved satisfaction and perceived utility with the handoff process without decreasing efficiency. Assessing and measuring perceived effectiveness at the local level is an important step to engage stakeholders for implementation and dissemination of national handoff recommendations.
166 WHAT DO COMPLAINTS TEACH US?
Foreman E2, Monroe K1, King A4, Bradley B3, Miller R4. 1 Univ of Alabama, Birmingham, AL; 2 University of Alabama, Bham, AL; 3 Childrens of Alabama, Bham, AL and 4 Childrens of Alabama, Bham, AL.
Purpose of Study: Pediatric Emergency Departments routinely receive complaints from families. Reviewing these complaints can serve as a guide to improve services.
Methods Used: A convenience sample of complaints received by patient relations for an 11 month period (august 1,2012 through july 14th 2013) were reviewed. The reviewer read each complaint and extracted data from patient relations database and hospital computer databases. Complaints were categorized as relating to wait times, attitudes of staff, diagnosis, quality of care, system errors and “nothing was done.” All data were entered into Excel.
Summary of Results: 82 complaints were reviewed. There were 49 Caucasian (59%)31 African American, and 1 Latino families represented. Insurance distribution was 61% (n=52) private insurance, 33% (n=27) medicaid; 2 no insurance,1 missing data. Most complaints occurred from patients seen during the evening shift 49% (n=42) (day 29%(n=24) and overnight 18% (16)). 18 were admitted 55 discharged and 9 left without treatment. We employ a five level triage category system with triage level 1 being the highest acuity and level 5 being the lowest. Only 2 of the complaints came from the families of patients triage level 1, nine from level 2, twenty one from level 3 with the highest percentage coming from level 4 (42) and only nine from level 5. Mondays and Thursdays accounted for 39% of total complaints. Of the 82 complaints, the categories were “rudeness/attitude of staff” (n=24); parents felt “nothing was done ”(n= 13),complaint about our system of care (NP/residents involved, follow up nurse, signage)(n=12) prolonged wait (n=10); parents felt quality of care was poor (n=8)insurance issues (n=5) and other such as TV didn’t work, angry that child was admitted to hospital, couldn’t find chewable prescription medication (n=7) and parent felt diagnosis was incorrect (n=3).
Conclusions: Evening shift accounted for most of complaints- adequate staffing during these times and having patient relations available is key. Better communication with families regarding diagnosis and treatment plan should be emphasized. The fewest complaints came from the highest and lowest levels of triage categories.
167 SKIN CANCER PROTECTION: WHAT DO PATIENTS KNOW AND DO?
Gutierrez M, Ross R, Harris K, Arnold C, Davis T. Louisiana State University Health Sciences Center, Shreveport, LA.
Purpose of Study: Identify patient skin cancer protection knowledge and practices and determine if this varies by income.
Methods Used: Adult patients in a private dermatology clinic were given a structured interview evaluating skin cancer protection knowledge and behavior, demographic information and literacy level.
Summary of Results: Of 230 patients enrolled, 68% were female, 14% were African American, 84% Caucasian, and 2% other. Patients ranged in age from 18 to 86, mean age 48; 14% had low literacy (<9th grade reading level). 63% of patients had a yearly household income of >$50,000, 26% had ⩽$50,000, 11% declined to answer. Almost all patients (94%) had heard of melanoma, 85% knew signs indicating a person might have skin cancer. 78% remembered having a sunburn that caused them to blister or peel as a child. Only 60% reported a doctor had ever talked to them about skin cancer. Over half of white patients (54%) reported they had used a tanning bed. Among all patients, those with higher income were more likely to believe that it is possible to get skin cancer from tanning beds (95.7% vs. 86.8%; p=0.003) and that tanning beds are not safer than tanning in direct sunlight (90.1% vs. 79.4%; p=0.023). Lower income patients were more likely to indicate they were unsure if tanning beds were safer than direct sunlight (14.7% vs. 4.3%). 92.9% higher income patients believed individuals can get skin damage in cold weather versus 80.6% with lower income (p=0.024). The majority of patients with both higher income (99.4%) and lower income (94.1%) indicated they knew ways to protect themselves from skin cancer. The most commonly known methods were wearing sunscreen (91%), avoiding the sun (45%), and using protective clothing (44%). About half indicated that they had sunscreen in a moisturizer (54%) or Chap Stick (51%). There was no significant difference between income groups in sun-protection behavior. 47% indicated they “often to always” wear sunscreen when in the sun for an hour and 75% indicated using sunscreen this often on their children.
Conclusions: Most patients were aware of skin cancer risk and protection methods but less likely to engage in protective behavior. Higher income patients were more aware of risks than their low income counterparts.
168 COMMUNITY HEALTH WORKER’S PERSPECTIVE ON BARRIERS TO CARE DELIVERY AMONG LATINOS WITH POORLY CONTROLLED DIABETES
Koshy L, Kenya S, Okoro I, Carrasquillo O. University of Miami Miller School of Medicine, Miami, FL.
Purpose of Study: Community health workers (CHWs) are a promising approach to improve care delivery to minority populations. Among Latinos, diabetes is an area where the role of CHWs has been identified as an important strategy. While many studies describe barriers to care that CHWs can help overcome, few have focused on challenges that CHWs may experience when caring for such populations.
Methods Used: We conducted key informant interviews with three CHWs who were delivering care to Latino patients enrolled in a NHLBI sponsored randomized trial. Each CHW managed a caseload of about 30 patients. We used semi-structured interviews that included 10 open-ended questions on barriers and challenges experienced by CHWs. Interviews were recorded, transcribed and coded to help us identify recurrent themes mentioned by all three CHWs.
Summary of Results: We were able to categorize responses into three over-arching themes that centered on barriers at the patient, CHW and health system level. At the patient level, CHWs noted that despite being of a similar background as their patients, some cultural ideologies such as machismo, ageism and sexism at times hindered their interactions. In addition, when patients did not follow through on agreed plans for diet, exercise, glucose self-monitoring, and taking medications as prescribed, the CHWs personally felt discouraged and disappointed. When patients remained non-adherent to basic diabetes care, CHWs realized this elicited feelings and attitudes within themselves that were not conducive to successful interactions with that patient or others. Lastly, at the health system level, the primary barrier mentioned was the disrespectful attitudes in the hospitals and clinics by some the physicians and staff towards the CHWs. One example was providers asking CHWs to remain quiet and not participate in any portion of the clinic visit.
Conclusions: These key informant interviews provide us with a richer understanding of the complex barriers faced by CHWs caring for Latino patients. By identifying such barriers, we can develop improved training and protocols for CHWs that can better address these patient, CHW and health system level challenges.
169 NEONATAL PATIENT SAFETY
McFalls K1, Ambalavanan N2, Bidez M3, Burke D3. 1 UASOM, Homewood, AL; 2 UAB, Birmingham, AL and 3 UAB, Birmingham, AL.
Purpose of Study: Medical errors are a major cause of morbidity and mortality, and little advancement has been made in eliminating serious medical errors. This research study was designed to explore and expose medical errors within the setting of a regional neonatal intensive care unit (NICU).
Methods Used: The first step of this project was to create a list of common medical errors occurring within the NICU using a random patient safety audit process. This was accomplished using 2 standard questionnaires, one for nurses and one for physicians, listing possible causes of adverse outcomes.
Summary of Results: Data consisted of responses collected from 50 of each survey. We found that 30% of the nurse surveys and 66% of the physician surveys identified potential or actual patient safety issues. The main safety issues were radiology studies and equipment/medical devices for nurses and intermittent suction not set to < 80 as well as inability to locate consultations for physicians.
Conclusions: Future steps are to construct a plan of action to eliminate the potential for errors happening in the NICU and improve patient safety. This technique may be useful in other health-care settings.
170 BACTERIAL ISOLATES IN COMMERCIAL YOGURT COMPARED TO PROBIOTICS
Panchavati PK2, Hassoun A1. 1 Alabama Infectious Diseases Center, Huntsville, AL and 2 Huntsville Hospital, Huntsville, AL.
Purpose of Study: Clostridium difficile associated diarrhea (CDAD) is one of the most common causes of healthcare associated infection. It’s associated with significant mortality and morbidity. Antimicrobial use is the main risk factor for CDAD. If taken with Antibiotics, Probiotics have been shown to reduce the risk of CDAD.
Methods Used: Sixteen different brands of commercial yogurts were cultured for 5 days to asses’ amount of bacterial growth and type of isolate of each type. We choose different brands and fat content, those with and without probiotics, those frozen, popsicle and regular as well as flavored. Also, we reviewed bacterial isolate of 16 commercially available probiotics capsule. In addition, we reviewed chart of patients from 1/2012- 4/2013 in our practice that have been on intravenous or oral antibiotic therapy and advised to take daily cup of yogurt of any type, to assess their rate of CDAD.
Summary of Results: All commercial yogurt grew at least one bacterial isolate except frozen yogurt popsicle did not grow any organisms. Each one had significant growth of more than 100,000 cfu/ml. the following organisms were found: Lactobacillus acidophilus, Enterococcus durans, Streptococcus thermophilus, Streptococcus viridians, other Lactobacillus species as well. Seven of these grew 2 different organisms and one grew 3 different organisms. There was no difference between those with or without probiotics, and no significant difference between brands. No gram negative organisms grew in any of them. Buttermilk showed similar growth. In comparison, Commercially sold probiotics randomly selected as we did with yogurt, 11 of them contained species of Lactobacillus and Bifidobacterium. Four had Saccharomyces boulardi and one contained Streptococcus thermophilus. Patient charts reviewed who discussed with them use of yogurt while on antimicrobial therapy showed only five developed CDAD.
Conclusions: Commercially available yogurts have at least one organism and can be considered as probiotic. Further studies are warranted to test the effectiveness of yogurt for prevention of CDAD.
171 PATIENT SATISFACTION WITH HURRICANE PLAN GIVEN TO HEMATOLOGY-ONCOLOGY PATIENTS AT CHILDREN’S HOSPITAL IN NEW ORLEANS
Raulji C, Velez M, Gardner R. LSUHSC/Children’s hospital of New orleans, New Orlenas, LA.
Purpose of Study: Because of increased frequency and intensity of hurricanes in the New Orleans region, many patients being followed at Hematology-Oncology clinic at Children’s Hospital (CHNOLA) are relocated temporarily during these periods. Each year at the beginning of Hurricane season patients are given a hurricane plan in form of a questionnaire, which asks them about pertinent patient identification data; their evacuation plan in case of a hurricane; if there is a hospital nearby; and if they know which pharmacy they will be using. They are also asked to have an updated copy of their roadmap with them. This information is then scanned to a flash drive along with their roadmap for treatment and is available to the staff in case of evacuation. The families are given information about where the clinic will be held in case of evacuation.Our goal was to assess the barriers to providing healthcare to Hematology-Oncology patients by evaluating the effectiveness of our hurricane plan given to the families.
Methods Used: We distributed a survey to patient’s families at the time of clinic visits. The patient or the family representatives were asked to participate in the study. We excluded patients who started following up with us after the hurricane season ended. The questionnaire included questions about diagnosis, previous evacuations, evacuation plan, factors that figured in their decision to evacuate, and if they had treatment plan and medicine available to them, etc.
Summary of Results: The majority of patients (73%) evacuated during previous hurricane seasons and most (77%) had a plan for where they were going to evacuate. The most important factor influencing that decision was availability of a children’s hospital nearby. Although a majority (71%) had medicines with them to last for 2 weeks, a significant number (43%) did not have treatment plans available with them and many (28%) did not have emergency contact information for staff as well. Most patients (78%) found information given to them by staff helpful.
Conclusions: Most of our patients found the hurricane action plan implemented at CHNOLA helpful. We suggest implementation of similar plans to other departments as well. We are in process of comparing our present data to data available before implementation of the action plan.
172 ADULT SICKLE CELL DISEASE AND DEPRESSION
Schumann SO, Brownfield E, Glass R, Khuu T, McDermott W. Medical University of South Carolina, Charleston, SC.
Purpose of Study: Sickle cell disease burdens patients with significant morbidity and mortality from birth, unlike other chronic medical conditions such as many forms of cancer and heart disease. Compounded by a lack of access to resources, social support systems, and coping skills, sickle cell disease often results in high utilization of emergency medical resources and prolonged inpatient stays. Small, non-randomized studies have correlated comorbid depression with severity of sickle cell disease. Other studies have shown the rate of depression in sickle cell disease to be similar to that of other chronic medical conditions (18% - 44%) compared to that of the general public (9%). There are currently no recommendations for the routine screening or treatment of depression in the care of adult sickle cell disease. Our project aims were to determine the rate of depression in MUSC’s sickle cell clinic and identify undiagnosed or undertreated depression.
Methods Used: In August 2012 a dedicated “Sickle Cell Clinic” was opened at MUSC to treat the acute and chronic complications of sickle cell disease in an effort to provide comprehensive care for this population. The fifty patients who were MUSC’s highest utilizers of emergency and inpatient medical services were enrolled. Upon enrollment the following were completed: past psychiatry history, medication history and PHQ-9 questionnaire. A score of > 9 on the PHQ-9 scale was used to identify undiagnosed and under treated depression.
Summary of Results:
- 35 of the 50 patients enrolled underwent a formal intake
- 31 of these 35 (88.5%) patients completed the PHQ-9 questionnaire
- 34.3% (12/35) of these patients carried a past history of depression, and 58.3% (7/12) of these patients were receiving treatment
- 22.9% (8/31) of patients scored > 9 on the initial PHQ - 9 scale and of these patients 5 (62.5%) did not have a history of depression
Conclusions: 22.9% of patients known to be high utilizers of the health care system and enrolled in an Internal Medicine Sickle Cell Clinic had undertreated or undiagnosed depression. Over half of these patients had a new diagnosis of depression. A significant portion (15/50 - 30%) did not complete the initial intake. Screening for depression should be included in treatment guidelines for patients with sickle cell disease.
Hematology and Oncology Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
173 EXTRAGONADAL GERM CELL TUMOR: A RAPID GROWER
Anazia G, Jones N, Yu M, Billeaud C, Englert D, Engel LS. LSU Health Sciences Center, New Orleans, LA.
Case Report: A 22-year-old man presented to the emergency room after acute onset of cough 3 days prior associated with severe weakness. On initial physical exam, he was afebrile, normotensive, but in mild respiratory distress, and mildly tachypneic at 32 respirations per minute. His oxygen saturation was 98% on room air. He had decreased breath sounds and dullness to percussion on the right. Testicular exam was unremarkable. Labs were remarkable for a slight leukocytosis, mild normocytic anemia, and hypoalbuminemia. Alpha fetoprotein (AFP) drawn on initial presentation was elevated at 860. β-hCG and CEA were within normal limits. Chest X-ray revealed complete opacification of the right hemithorax. CT of the chest with IV contrast demonstrated a large right-sided pleural effusion with right-to-left mediastinal shift, and numerous heterogeneously-enhancing pleural based lesions, highly concerning for neoplasm. An ultrasound of the scrotum and testicles was obtained and showed a small left-sided hydrocele, but no masses. Thoracentesis was performed and revealed 1,800cc of bloody fluid and biopsy was suggestive of either a synovial sarcoma or a poorly-differentiated germ cell tumor. One week following discharge, the patient developed increasing pain and shortness of breath. Repeat CT of the chest showed that the tumor had grown to occupy the entire right hemithorax, with shift of the mediastinal structures to the left. Due to his rapid clinical deterioration, he was intubated and started on empiric chemotherapy with etoposide, ifosfamide, and cisplatin, even before a final diagnosis was made. His tumor responded well to chemotherapy. Repeat biopsy was obtained and was consistent with a germ cell tumor most compatible with yolk sac origin.
DISCUSSION: Mediastinal germ cell tumors are aggressive, rapidly growing tumors, typically found in younger men. Standard treatment consists of platinum-based chemotherapy, usually followed by surgical resection of residual disease. Due to their rapidity of cell growth, these tumors are typically very responsive to chemotherapy.
174 TUMOR OF THE GLOMUS APPARATUS, EASY TO DIAGNOSE EASIER TO MISS
Bitar C, Sammour R. University of Balamand, Beirut, Lebanon.
Case Report: A 50 y.o male presents with a 5-year history of subungual lesion over the left thumb. The lesion was painful upon pressure and cold exposure, and failed multiple rounds of onychomycosis therapy. Physical examination revealed a tender solitary subungual longitudinal macule with a reddish-blue discoloration on a hyperkeratotic, dystrophic nail (A, B). MRI showed 9×7.5×5 mm rounded, well circumscribed subungual lesion with a characteristic low signal on T1 (D), hyperenhencement on T2 (C), and intense enhancement following gadolinium (E).
Glomus tumor is a benign neurovascular tumor originating from the neuromyoarterial glomus apparatus. It classically affects middle-aged women, but can also occur in men and other age groups. Glomus bodies are mainly localized in the fingernails were 75% of the tumors occur . The diagnosis is clinical and based on the triad of pain, cold hypersensitivity and tenderness on pressure. MRI can detect tumors as small as 2 mm, with a sensitivity of 90%. Treatment is surgical.
175 INTRAVASCULAR LARGE B-CELL LYMPHOMA OF THE DUODENUM: AN UNEXPECTED DIAGNOSIS
Chowdry RP1, Janbain M1, Safah H1, Vander Velde N1, Schmieg J2, Mayhall G2. 1 Tulane, New Orleans, LA and 2 Tulane, New Orleans, LA.
Case Report: Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal diffuse large B-cell lymphoma (DLBCL). It has an insidious presentation, often mimicking embolic or vascular pathology, and it almost always has an aggressive course. The majority of cases are found incidentally at autopsy. IVLBCL is characterized by the presence of malignant lymphocytes exclusively within the lumen of small vessels. It commonly involves the skin or central nervous system (CNS). Involvement of other organs is exceedingly rare, with a paucity of reports described in the literature. Primary gastrointestinal manifestations of IVLBCL are very rare. We present the first reported case of IVLBCL involving the duodenum. A 59 year old previously healthy African-American male presented with a one month history of increasing abdominal girth, nausea and vomiting. Computed tomography scan of the abdomen showed thickening of the proximal duodenum. The patient was taken to endoscopy for tissue biopsy. He was found to have a friable duodenal mucosa with circumferential thickening. Microscopic examination of the biopsied duodenal tissue revealed extensive necrosis, however no atypical or malignant duodenal cells were seen. Instead, an intravascular lymphoid infiltrate was found with large, atypical, mononuclear B-cells expressing CD20 and CD79a. There was no evidence of adjacent DLBCL within the biopsied tissue. These findings were most consistent with intravascular large B-cell lymphoma. No other suspicious lymph nodes were found on imaging. The patientunderwent staging workup with bone marrow biopsy and lumbar puncture and there was no evidence of lymphoma involvement of the bone marrow or CNS. Chemotherapy with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) was initiated after review of the literature and guidelines. The patient underwent 3 cycles of R-CHOP after which he had radiographic evidence of response with decreased duodenal thickening. He also received prophylactic high dose methotrexate for a high risk of CNS progression. The subtle manifestations of this rare entity make it a diagnostic and therapeutic challenge and we hope to increase awareness with this unique case.
176 GERM CELL TUMOR
Dhillon N, Castillo E, Puligothram S, Loch M. LSU New Orleans, New Orleans, LA.
Case Report: 22-year-old African American male presented to the ER with SOB and abdominal pain. He was recently found to have a right lung/mediastinal mass with biopsy result as spindle cell sarcoma versus germ cell tumor in the other facility. For further evaluation the path was forwarded to Mayo clinic pathologist as well as referral was made to our oncology clinic.
Before patient could make it to the clinic, he presented to the ED. He was found to be tachycardic and hypoxic, had a rapid response in the ED and was admitted to ICU.
CT chest showed marked mass effect on the great arteries displacing them into the right hemithorax secondary to extensive right lung mass. This mass crosses the midline and contacts the anterior margins of the aorta. The right main pulmonary artery is encased by mass. Additionally, there is question of opacity within the lumen of the right pulmonary artery which is suspicious for tumor thrombus.
Oncology was consulted. Though the pathology was not very clear at that point as well patient had very poor performance status. It was discussed with the patient and his mother that the outcome is death without any treatment but there is a chance that his tumor is germ cell, and they are usually very chemo responsive. Knowing that the chemotherapy itself can likely kill him, and he may not have a treatable tumor. He and his mom were willing to proceed.Patient was started on VIP chemotherapy, per multidisciplinary consensus it was decided not to intubate patient electively. While on chemotherapy patient was given tumor lysis prophylaxis. He did have SVTs as well as became more hypercapnic resulting in intubation on day 13. He was extubated within a week. His condition started to improve and was stepped down to floor. He was given second cycle of VIP on the floor. While on the floor patient started tolerating PO intake as well as physical therapy worked with him. He was discharged home soon after that. Before cycle 3, patient had staging scan that showed dramatic response to therapy and marked improvement in performance status.
The point of presenting this case to put emphasis on the fact that germ cell tumors are very chemo responsive and even when patient’s performance status is low; trial of chemotherapy should be given.
177 DOUBLE HIT LYMPHOMA
Dhillon N, Castillo E, Puligothram S, Reske T. LSU New Orleans, New Orleans, LA.
Case Report: 59 years old female was transferred from outside facility to neurosurgery as she presented there with lower extremity weakness. MRI of the lumbar and thoracic spine showed disc bulge at the level of L3-4, 4-5, L5 and S1, with compression of the cord at the level of L3 and 4. The patient also has a large mediastinal mass involving multiple structures and invading the spinal cord with extension into the foramen compression of the spinal cord at multiple levels. Neurosurgery did decompression laminectomy as well as tissue biopsy of the mass Patient was discharged soon. Pathology came back as high grade B cell lymphoma, favor B cell lymphoma unclassifiable, with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma. Patient was called back in the hospital. FISH studies detected both an IGH/BCL2 gene rearrangement and a MYC gene rearrangement in the malignant B cells, as well a gain of one to two copies of the BCL6 gene in a subset of the malignant B cells (but no BCL6 gene rearrangement). Chemotherapy with R-EPOCH was initiated. After cycle 1, patient started to have progressive cough especially whenever she will swallow. On imaging studies it was found that, as lymphoma started to resolve it resulted in development of large tracheoesophageal fistula. Eventually 12cm x 23mm fully covered self-expanding metal stent was placed. Patient so far has received total of 3 cycles of R - EPOACH and is doing well.
The point of presenting this case is to put emphasis on the new WHO classification, which now includes unclassifiable lymphoma. Double hit lymphomas represent a subset of B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma, and usually harbor both an IGH/BCL2 gene rearrangement and MYC gene rearrangement. In addition to these two gene rearrangements, double hit lymphomas frequently demonstrate a complex karyotype, which might account for the gains of the BCL6 gene seen in a subset of the malignant B cells. Double hit lymphomas are usually aggressive neoplasm, and most cases are associated with a poor prognosis regardless of treatment. Based on clinical significance and the fact that no other solid diagnostic tools are available to identify DH lymphomas, it seems advisable to test all diffuse large B-cell and related lymphomas for MYC and other breakpoints.
178 IMMUNE THROMBOCYTOPENIC PURPURA DURING MAINTENANACE THERAPY OF PRE-B ACUTE LYMPHOCYTIC LEUKEMIA
Erker CA, Sandler E. University of Florida, Jacksonville, FL.
Purpose of Study: Immune Thrombocytopenic Purpura is a common hematologic disorder in children, but is uncommon in the setting of malignancy. There is almost no literature on ALL therapy leading to a compounding diagnosis of ITP. We share our unique experience of 3 rare patient courses who develop ITP during their maintenance therapy of ALL, including the suspect causes and difficulty treating these patients for both ALL and ITP.
Methods Used: Retrospective case series using pediatric patients who developed ITP during their therapy for ALL.
Summary of Results: Patient one’s ITP resolved when he finished ALL therapy. However, patient’s two and three have had success with standard ITP therapy with IVIG, but they continue to have intermittent low platelets and are currently still undergoing ALL therapy.
Conclusions: Although rare, patients who have persistently low platelet counts during treatment for ALL must have ITP in the differential and their treatment will have to be adjusted.
179 PRIMARY THYROID LYMPHOMA: DIFFUSE LARGE B-CELL TYPE WITH INCIDENTAL PAPILLARY THYROID CARCINOMA IN A PATIENT WITH HISTORY OF CHRONIC LYMPHOCYTIC THYROIDITIS
Hosiriluck N, Mankongpaisarnrung C, Dumrongmongcolgul N, Nugent K. Texas Tech Health and Sciences Center, Lubbock, TX.
Case Report: Diffuse large B-cell lymphoma of thyroid is a rare aggressive thyroid malignancy. Papillary thyroid carcinoma is the most common type of thyroid cancer and carries an excellent prognosis. The synchronous development of both malignancies is extremely rare.
A 79-year-old man with history of hypothyroidism presented with an enlarging neck mass; a thyroid ultrasound revealed hypoechoic soft tissue distorting the size and configuration of both lobes (8.9 x 4.4 x 4.6 cm of right lobe and 7.1 x 3.6 x 3.6 cm of left lobe) and thickening of isthmus. Fine needle biopsy showed atypical cells. A subtotal thyroidectomy was performed without lymph node dissection. Pathological studies showed diffuse large B cell lymphoma with background of chronic lymphocytic thyroiditis and papillary carcinoma with negative margins and no capsular invasion. CT scan showed multiple subcentimeter lymph nodes in the mediastinum and multiple retroperitoneal lymph nodes, the largest 1.5 cm. Bone marrow aspiration and biopsy did not reveal any tumor. He was staged as IIIE, received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, but he could only tolerated five cycles of therapy. Follow up imaging demonstrated clinical remission.
Primary thyroid lymphoma is very rare, especially advanced stage which occurs in only 2-7% of cases. Simultaneous occurrence of primary thyroid lymphoma and well differentiated thyroid carcinoma is uncommon, but the association of both type of cancer with Hashimoto’s thyroiditis, can lead to this situation. The prognosis of the two diseases is different because of poor prognostic factors for B-cell lymphoma including male sex, advanced age and stage, diffuse large B-cell type, ECOG score, greater tumor size, rapid clinical growth, and intolerance to chemotherapy. Due to its aggressive course, patients with Hashimoto thyroiditis who present with thyroid nodules/masses must have prompt imaging and tissue diagnosis. Treatment must be prioritized by the diagnosis that carry the worst prognosis.
180 MALE GYNECOMASTIA DUE TO BLADDER CANCER
Kanji A, Raizada M, Islam A, Ahmed M. Texas Tech University Health Sciences Center, Amarillo, TX.
Case Report: Bladder cancer is the most common malignancy involving the urinary system. Urothelial (transitional cell) carcinoma is the predominant histologic type in the United States, where it accounts for 90 percent of all bladder cancers. Painless, gross, and episodic hematuria is the most frequent presenting manifestation of bladder cancer. Hyperestrogenemia and gynecomastia in males due to bladder cancer is rare. In this report, we present a case of an adult male with gynecomastia and nipple pain due to high-grade urothelial carcinoma of the bladder neck.
A 74 year old male presented with right nipple pain and gynecomastia. An ultrasound of the breast was done which reported normal tissue. Several blood tests conducted at the same time revealed a beta-hCG of 95 mIU/mL and an estradiol of 90.4 pg/mL. He developed hematuria shortly after, which prompted CT scans of the head and abdomen, as well as a prolactin level. CT scans showed a normal brain and empty sella but blood test revealed an elevated prolactin of 29.1 ng/mL. No abdominal abnormalities were noted on CT scan. Further investigation of the hematuria via cystoscopy revealed a bladder tumor in the superior aspect of the bladder neck. A transurethral resection of the bladder and pathological examination showed high-grade urothelial carcinoma with invasion into muscularis propria, lymphovascular and perineural invasion. Although symptoms of hematuria improved following resection, his gynecomastia progressed, and he developed increasing right nipple pain. Repeat imaging for staging showed pulmonary metastasis.
Bladder cancer typically does not present with a hyperestrogen state. Hyperestrogenemia and gynecomastia in men related to cancer are usually due to a paraneoplasm of testicular cancers of choriocarcinoma, teratomas, and embryonal carcinomas. An ectopic production of hCG from a urinary bladder urothelial carcinoma is a rare cause of gynecomastia. The ability to differentiate in the direction of syncytial trophoblasts in a urothelial carcinoma may have a genetic background. Though there have been few cases in the past of a bladder cancer with high levels of hCG, it leaves a possibility of treatment aimed towards blocking hCG via pharmacotherapy.
181 BREAKING BAD: A CASE OF MALIGNANT MELANOTIC SCHWANNOMA
Milner CP, Hamilton R. University of Mississippi Medical Center, Jackson, MS.
Case Report: Melanotic schwannoma is a very rare tumor, accounting for less than 1% of primary nerve sheath tumors. These tumors, once thought to behave benign, originate from the neuroectoderm and are characterized by melanotic pigmentation in the cytoplasm of neoplastic Schwann cells.
A 55-year-old African American man, with a history of a partially resected spinal melanotic schwannoma, presented to his neurosurgeon with complaints of left upper extremity weakness. Given his history of a previous incomplete resection of a C5-6 mass approximately 1.5 years prior, patient underwent spinal imaging which confirmed the presence of a cervical mass. He subsequently underwent partial tumor resection of the C5-C7 spinal tumor in conjunction with posterior cervicothoracic stabilization with rib autograft. Pathology was reviewed by Mayo Clinic, and found to be positive for Vimentin and S-100 immunoperoxidase staining and negative for GFAP and Cytokeratin-A immunoperoxidase staining. Pathology was confirmed to be a recurrent melanotic schwannoma. These tumors have not been associated with neurofibromatosis, and therefore NF1 and NF2 gene testing was not obtained. Further imaging revealed areas of metastatic disease in the lung, liver, and bones. He underwent radiation therapy to his cervical spine, but had a poor response to therapy. While awaiting systemic chemotherapy, patient underwent another surgical debulking due to further symptoms of pain with recurrent left upper extremity weakness and evidence of impending cord compression on imaging. Systemic chemotherapy was initiated with doxorubicin, ifosphamide, dacarbazine, and mesna to attempt to gain disease control. During the second cycle, patient developed ifosphamide neurotoxicity, and is currently preparing to start a cycle of gemcitabine and docetaxel.
These tumors have been described as slow growing and previously benign, but recent case reports emphasize the malignant behavior of this disease. The rarity of these tumors leaves much to be understood about the treatment and management of this malignancy. The standard of care is complete surgical resection, but little is known about the roles of radiation and chemotherapy in the management of unresectable disease. This case highlights a rare tumor and its malignant behavior while presenting a treatment dilemma.
182
183 THE GIST OF IT
Nagireddy S, Khansur T. University of Mississippi Medical Center, Jackson, MS.
Case Report: A 48 year old African American male with no significant past medical history presented with diffuse abdominal pain to the ER. A palpable mass, lead to CT scan of the abdomen, which showed a 28 X 20 cm mass arising from the stomach. He underwent image guided biopsy revealing a spindle cell neoplasm strongly positive for CD 117 (C-KIT), negative for smooth muscle antigen and S-100, consistent with GIST. The initial staging PET/CT showed a necrotic 15 x 23 x 30 cm mass in the left upper quadrant with SUV of 10.9 and a 1.5 cm metastatic lesion in the liver with SUV of 8. Following multi-disciplinary review, the mass was deemed marginally resectable as it was encroaching the liver hilum. He was started on neoadjuvant therapy with Imatinib. A repeat PET/CT obtained at 3 weeks to assess the response showed decrease in the size of the mass to 11 x 18 x 27 cm and a drop in SUV to 1.6. After 3 months of the Imatinib therapy he underwent partial gastrectomy. He is continuing on Imatinib and tolerating it well. There are plans to reassess the liver and ablate any residual disease if it fails to completely regress.
GIST represents 85% of mesenchymal neoplasms of gastrointestinal tract. Approximately 85-90% of GIST harbor C-KIT mutation that result in activation of the tyrosine kinase. 3-5% carry PDGFRA proto oncogene. GISTs are common in stomach followed by small intestine. They commonly present with abdominal pain, GI bleeding or palpable mass. GISTs are highly PET avid as tyrosine kinase augments the glucose transport protein signaling. Acute changes in the metabolic activity precede the anatomical changes, so PET is useful to assess response to Tyrosine kinase inhibitors. Surgery remains the main stay of therapy for primary GIST. In borderline resectable states the use of neoadjuvant Imatinib with down staging increases the likelihood of complete resection. If the tumor proves resistant to Imatinib, second line therapy with Sunitinib and Regorafenib is available. Here we present a rare giant GIST, that was borderline resectable at diagnosis. We assessed the response to pre-operative TKI therapy with a PET scan. The down-staged tumor was amenable to surgical resection. This case illustrates the potential use of neoadjuvant imatinib therapy and PET/CT to assess the response to this drug.
184 DIFFUSE LARGE B CELL LYMPHOMA OF LATISSIMUS DORSI
Nagireddy S, Elkins S. University of Mississippi, Jackson, MS.
Case Report: A 46 year old African American female came to the ER with complaints of back pain and mass in the right flank area for duration of 4weeks. It lead us to do CT of the chest and abdomen which showed a mass of size 9 × 6.5 × 13.5 cm arising from latissimus dorsi and MRI was recommended for further delineation of the mass. MRI of the back showed 9.6 cm heterogeneously enhancing mass with area of necrosis. A soft tissue sarcoma was suspected and a core biopsy was done. Pathology came back as high grade B-cell lymphoma consistent with diffuse large B cell lymphoma (DLBCL). Immunohistochemistry showed positive CD20, CD 79a, PAX 5, Ki 67 was 90% positive. She also underwent a PET/CT, which showed a hypermetabolic mass in the right flank with SUV of 10.6 with no other abnormality, so she was staged as IA extra nodal. Then she was started on chemotherapy with CHOP-R (Cyclophosphamide, Vincrsitine, Prednisone, Doxorubicin and Rituximab). A PET/CT scan was done after 4 cycles, which showed decrease in the size of the mass to 5 × 2 × 8 cm with a decrease SUV of 1.1. Chemotherapy with CHOP-R was continued and PET/CT was done after 6 cycles which showed a mass with size of 7.4 × 2.7 cm with no hypermetabolic activity. After completion of chemotherapy she underwent radiation to the mass, total dose of 4000cGy in 20 fractions. She finished chemotherapy & radiation with out any difficulty and now she is under observation.
Non Hodgkin lymphoma (NHL) is the common form of lymphoma and DLBCL being more common form of NHL. Although DLBCL is common in the lymph nodes, it can arise in the extra nodal sites like intestine, bone, breast, liver, skin and central nervous system. Primary skeletal muscle non Hodgkin Lymphoma is a rare tumor accounting for only 0.5% of all lymphoma. When skeletal muscle is involved, common sites are upper arms, pelvis and glutei. MRI and PET/CT are the main modes of imaging. Standard treatment is chemotherapy combined with radiation. Tissue diagnosis with histopathology and immunohistochemistry is still crucial in making exact diagnosis which can avoid unnecessary surgeries. Here we present a rare case of DLBCL which involved latissimus dorsi muscle and treated her successfully with chemotherapy and radiation.
185 BREAST CANCER PATIENT ON CHEMOTHERAPHY PRESENTING WITH PARTIAL SMALL BOWEL OBSTRUCTION: CAN IT BE CLOSTRIDIUM DIFFICILE?
Neppalli AK1, Devarakonda SS1, Raley M2, Marion J1. 1 Feist Weiller Cancer Center / LSU Health Shreveport, Shreveport, LA and 2 LSU Health Shreveport, Shreveport, LA.
Case Report: Introduction: Clostridium difficile colitis is a well-known disease entity with typical presentation of acute watery diarrhea with lower abdominal pain, low-grade fever and leukocytosis, which commences during or shortly after antibiotic administration due to alteration in normal gut flora. We present a case of chemotherapy associated clostridium difficile colitis, in a patient with no antibiotic use in the previous 3 months, presenting with partial small bowel obstruction possibly aggravated by the use of antidiarrheal medications.
Case: A 76-year-old Caucasian female with stage IV Breast cancer, who has been on oral Capecitabine (Xeloda) for 3 months, presented to the emergency room at outside hospital with nausea, vomiting and abdominal pain. Plain radiograph and computerized tomography of the abdomen were consistent with partial small bowel obstruction, and she was transferred to LSU for further management. Further questioning revealed that the patient had several weeks of diarrhea since starting Capecitabine and had been taking Imodium as needed at home. She denied any diarrhea for 2 days prior to presentation. Vital signs showed that she was normotensive, tachycardic, and afebrile. On exam she was mildly distressed with signs of dehydration and had normal bowel sounds. Labs were significant for leukocytosis (WBC count of 16.87 with left shift), AKI (Creatinine 2.2, with baseline of 0.7). Nasogastric tube was placed due to signs of partial small bowel obstruction, along with aggressive IV hydration and electrolytes replacement. Given the history of chronic chemotherapy associated diarrhea, use of Imodium and Leukocytosis, Clostridium difficile assay was ordered. This was positive for both C. Diff antigen and toxin. She was started on Metronidazole and her symptoms subsided over next few days.
Discussion: Clostridium difficile associated diarrhea can be seen in patients receiving chemotherapy due to disruption of normal mucosal barriers, even with out prior antibiotic use. It is rare with a few cases reported in literature. A high index of suspicion is warranted to make a timely diagnosis in patients receiving chemotherapy.
186 LIKELY GIANT CELL CARCINOMA OF THE LUNG BY PLEURAL FLUID CYTOLOGY EVALUATION
Oncale M1,2, Kimbrell H3,1, Barnhill M2,1. 1 Tulane, New Orleans, LA; 2 Tulane, New Orleans, LA and 3 Tulane, New Orleans, LA.
Case Report: A 75-year-old female ex-smoker with diabetes, hypertension, and renal disease presented with dyspnea and weakness. She noted weight loss, dry cough, and back pain for one month.
Acute respiratory failure and hemodynamic collapse prompted intensive care unit admission. Chest computed tomography noted right lung field/bronchial collapse, pleural effusion, and a 3x1.5cm hilar mass. There were lytic bone lesions and abnormal foci in the liver and adrenal gland concerning for metastases. Pleural fluid cytology revealed metastatic carcinoma consistent with pulmonary sarcomatoid carcinoma, likely giant cell subtype.
She required ventilatory and vasopressor support; tissue diagnosis or staging could not be done. She expired four days after admission. Autopsy was declined.
Sarcomatoid carcinomas (SC) are defined as poorly differentiated non-small cell lung carcinomas (NSCLC) with sarcomatoid differentiation or true sarcoma components. SC comprises 3% of lung cancers, is more common in males and smokers, and presents at a mean age of 59 years. Lesions are peripheral and metastases are similar to other NSCLC. SC have a poor prognosis; 6-month survival of less than 27%.
Giant cell carcinoma (GCCL) is a sub-category of SC composed only of giant tumor cells and can only be diagnosed on excisions or autopsy. Without autopsy, it is unknown whether our patient truly had GCCL. However, her pleural fluid had a pure population of discohesive, bizarre cells, an inflammatory background, and neutrophil emperipolesis by tumor cells, characteristic of GCCL. The lack of tumor cells with an epithelioid appearance suggests that the giant cells likely made up a significant proportion of the tumor.
Little information on SC treatment exists. Cases with platinum-based chemotherapy noted poor response. There are cases of 800-day survival with gefitinib in females with epidermal growth factor receptor mutations. Even with surgery in early disease, most patients die within 18 months. Radiation has no role in SC treatment.
We present a case of the rare entity of SC, likely GCCL that is unique as our patient was elderly, was female, and had a central lesion. As in prior cases, our patient presented at diagnosis with distant metastases and rapidly decompensated.
187 CHORIOCARCINOMA WITH METASTATIC BRAIN LESIONS
Paccione R, Hutchins K, Johnson D, Engel LS, Lillis R. LSU Health Sciences Center, New Orleans, LA.
Case Report: We describe a case of metastatic choriocarcinoma with brain lesions and the importance of its inclusion in the differential diagnosis of young men with testicular masses and neurological symptoms.
CASE: A 28 year old Hispanic man transferred to our hospital after initial evaluation demonstrated an intracranial mass with midline shift. He complained of worsening frontal headaches with concurrent nausea and vomiting for four days prior to presentation. He also reported a painless testicular mass which had increased in size over the last four months. At the time of our evaluation, his vital signs were: Blood pressure 104/42 mmHg, Pulse 88 bpm, Temp 98.4 °F, Resp 16 /min, BMI 25.18 kg/m2. Pertinent findings on physical exam included a 10 cm x 10 cm firm, non-tender left testicular mass. Gait abnormalities included a slight limp with a dragged left foot. Visual acuity was 20/20 OS, 20/40 OD. He had a peripheral field defects at his left lateral and lower visual fields. MRI of his brain showed a single lesion, 3.4 cm × 3.7 cm × 3.8cm with 12 mm midline shift. Initial testicular US showed a 13.5 cm × 12.3 cm × 10.5 cm heterogenous hypoechoic testicular mass. Further imaging with cat scan revealed multiple pulmonary metastases bilaterally and liver metastases. Initial beta-hCG and AFP were both significantly elevated. Craniotomy with resection of his brain metastases was performed and pathology revealed a malignant neoplasm with features consistent with choriocarcinoma. He was diagnosed with a nonseminomatous germ cell tumor stage IIIC, poor risk. Chemotherapy with Bleomycin, Etoposide, and Cisplatin (BEP) was initiated. His Beta-hCG, AFP, LDH decreased. An orchiectomy was scheduled.
DISCUSSION: Choriocarcinoma is the most malignant tumor of gestational trophoblast origin. Although a traditionally curable neoplasm, metastatic brain lesions significantly worsen prognosis. However, if there is a high index of suspicion for this neoplasm, increased the overall survival has occurred with aggressive surgical intervention and advances in chemotherapy and radiotherapy. Neurological symptoms in conjunction with a testicular mass should raise suspicion for this neoplasm with the possibility of metastatic disease.
188 ACQUIRED HEMOPHILIA TYPE A IN AN YOUNG PATIENT WITH ACQUIRED IMMUNE DEFICIENCY SYNDROME AND REMOTE HISTORY OF LYMPHOMA: A STEP-BY-STEP APPROACH TO SUCCESSFUL MANAGEMENT
Pasam A, Devarakonda SS, Nair B. LSU Health/ Feist Weiller Cancer Center, Shreveport, LA.
Case Report: Background: Acquired hemophilia is relatively rare in young patients, usually seen in patients >65 years of age, with an incidence of 0.2 to 1 per million per year.
Case: We report a case of a 48 year old man who was diagnosed with acquired hemophilia type A. He was initially admitted with complaints of sudden onset swelling, bruising, ecchymoses and intractable pain in both legs. Ultrasound doppler ruled out DVT, CT scan showed soft tissue swelling in bilateral calves. PT was 13.1, INR was 1.04, and aPTT was 71.9 sec. Mixing studies were suggestive of presence of a delayed inhibitor and factor VIII activity was <0.6 (50-150%). Factor VIII inhibitor levels were 432 Bethesda units (very high, Normal value <1.0) Of note, patient has a history of HIV/AIDS, on anti-retroviral therapy and has a history of anaplastic large B cell lymphoma treated with R-CHOP in 1998 and has been in remission. With careful consideration towards his immune status and precariously high inhibitor levels, we treated him with concurrent cyclophosphamide 150 mg/day for 2 weeks and rituximab 375 mg/m2 weekly for 4 weeks and prednisone started at 1 mg/kg/day initially and was tapered off slowly. Patient had remarkable improvement and had no further bleeding signs, pain resolved and aPTT slowly improved towards normal, with most recent value 24.8.
Discussion: Acquired hemophilia involves spontaneous development of autoantibodies against factor VIII molecule, leading to its inhibition. Etiology remains uncertain in most cases. It can be life threatening and should be suspected in cases of soft-tissue and systemic bleeding episodes with no apparent etiology. Hemarthroses are uncommon in this condition, unlike hereditary hemophilia. Workup includes mixing studies initially, followed by factor assays and factor inhibitor levels. Treatment strategies are based on the acuity and severity of bleeding manifestations, with goals of controlling active bleeding and eliminating the inhibitors, to achieve remission. Activated Factor VIIa or prothrombin complex needs to be administered in case of active bleeding. Prednisone, cyclophosphamide and rituximab can be used in various combinations to cause selective B-cell depletion.
189 HEPATOCELLULAR CARCINOMA TWENTY YEARS AFTER BONE MARROW TRANSPLANTATION FOR FANCONI ANEMIA
Ramirez LE. Tulane University, New Orleans, LA.
Case Report: Fanconi Anemia (FA) is a rare genetic disorder leading to bone marrow failure as well as cutaneous, musculoskeletal, and urogenital congenital abnormalities. The FA phenotype is caused by molecular defects in the pathway that regulates DNA repair. Patients with FA are at increased risk for development of hematologic and solid tumor malignancies. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure for FA. We present a case of hepatocellular carcinoma after HSCT for FA.
A 41 year old Caucasian man presented with right upper quadrant abdominal pain, 20 pound weight loss, nausea and vomiting, and decline in functional status over the past seven months. At 21 years of age he had an HSCT from his HLA identical brother for treatment of FA. Past medical history included hypospadias, severe chronic obstructive pulmonary disease, and diabetes mellitus. He had an aunt with FA. He lived with his wife and daughter, and previously worked in construction. He had a 30 pack year history of smoking, occasional alcohol consumption, and no illicit drug use. Physical examination revealed short stature, bilateral brachydactyly, wheezing in bilateral lungs, abdomen firm to palpation in right upper quadrant and diffusely tender with enlarged liver. Laboratory examination revealed INR 1.3, AST 170, ALT 61, alkaline phosphatase 455, albumin 2.7. Computed tomography revealed an enhancing mass in the right hepatic lobe (12x8x7cm) and numerous lesions scattered in the right and left hepatic lobes, all consistent with hepatocellular carcinoma. There were numerous pulmonary nodules consistent with metastatic disease, and portal vein thrombosis. Alpha-fetoprotein measured 9314. He was Child-Pugh class A at diagnosis, and was considered for palliative treatment with Sorafenib. His clinical condition rapidly declined and he died within six weeks of diagnosis, prior to initiation of treatment.
HSCT as treatment for FA is only curative for the associated hematologic manifestations. Patients with FA are still at increased risk of liver tumors and squamous cell carcinomas after HSCT. The risk of solid tumors increases with age, and 30% of patients develop a solid tumor by age 45. This case highlights the need for surveillance for solid tumor malignancies in patients with FA, even after HSCT.
190 INTRACRANIAL HEMORRAGHE IN A PATIENT RECEIVING ECULIZUMAB FOR TREATMENT OF ATYPICAL HEMOLYTIC UREMIC SYNDROME
Ruiz MA. Louisiana State University Health Sciences Center, New Orleans, LA.
Case Report: Background: Eculizumab, a terminal complement inhibitor, was recently approved for treatment of Atypical Hemolytic Uremic syndrome (aHUS) in adults. This drug has revolutionized treatment with improvement in clinical symptoms and laboratory abnormalities associated with aHUS (thrombocytopenia and microangiopathic hemolytic anemia). This appears to be a safe drug with few side effects including, hypertension, and mild infections
Case report: We report the case of a 26 year old patient from England with diagnosis of atypical hemolytic uremic syndrome that was started on Eculizumab six months prior to be hospitalized in our institution
Patient was admitted for sudden loss of conciousness Patient developed a severe case of intracranial hemorrhage. Initial vital signs when patient was admitted were stable and mild hypertension (145/85) was detected . No other medical problems were diagnosed. No history of drug abuse was elicited. There was not history of congenital vascular abnormalities or central nervous system aneurysms in the family. Patient underwent testing which showed a frontal lobe hemorrhage. MRA did not detect any vascular anomaly. Laboratory values were within normal limits including toxicology testing. In view of the absence of any other causes, his severe intracranial hemorrhage was attributed to Eculizumab
Discussion: Side effects associated with Eculizumab have been reported and include, headaches, hypertension, mild infections among others. To our knowledge there are no reports in the literature of eculizumab and severe intracranial hemorrhage
Conclusion: Eculizumab may cause intracranial hemorrhage and patients should be closely monitored. Further reports and studies are needed to demonstrate this association.
191 AN ATYPICAL PRESENTATION OF PRIMARY PULMONARY ADENOCARCINOMA
Salih H1, Gomez-Sanchez C1,2, Frost J1,2. 1 University of Mississippi, Jackson, MS and 2 G.V. Sonny Montgomery V.A. Medical Center, Jackson, MS.
Case Report: Adenocarcinoma cases represent 34% of primary lung cancers in men. Of all primary lung adenocarcinoma metastasis cases, 35% are reported to metastasize to the adrenal glands. However, only 2-4% of all cancer patients have a cancer in which primary location of origin can not be identified. We present a case of a patient with negative imaging for pulmonary mass who presented with a large adrenal mass and pathology demonstrating adenocarcinoma of pulmonary origin.
A 70 year old black male with Hypertension, Diabetes Mellitus type 2 and Gout presented with unintentional weight loss of 70 lbs over 5 months. An initial physical exam was unremarkable. Work-up was initiated with chest/abdomen/pelvis contrast CT demonstrating a large right adrenal mass. ACTH was not suppressed making Cushing’s unlikely. Aldosterone level was normal. Urinary metanephrines were only slightly elevated and not in range of a Pheochromocytoma. He underwent right adrenalectomy/nephrectomy and a large 12 cm adrenal tumor was visualized. Histopathology revealed a poorly differentiated carcinoma with TTF-1, CK-7, and CEA and negative for MART-1, Synaptophysin and CK-20. Markers and histopathology demonstrated likely primary adenocarcinoma of the Lung. A CT Chest showed no significant lung lesion. A follow up PET/CT demonstrated two retroperitoneal masses and no other sites of activity. The patient agreed to broad spectrum chemotherapy and has completed 6 cycles of Carboplatin/Taxol. The patient has tolerated chemotherapy well and post-treatment imaging demonstrated slightly diminished soft tissue mass adjacent to surgical site and no hepatic metastatic disease.
Adrenal gland metastasis are not uncommon for adenocarcinoma of the lung, but it is unusual to be the sole location of metastasis and even more unusual to lack any evidence of a primary location. The pathology from the adrenalectomy/nephrectomy was positive for TTF-1, indicating tissue arising from lung or thyroid, and CK-7, and CEA strongly indicating likely pulmonary origin. Broad spectrum chemotherapy stabilized the lesions in post-treatment imaging. In cases with an extra-pulmonary mass and no radiographic evidence of a pulmonary lesion, pulmonary cancer can not be ruled out and immunostaining is necessary to prove origin.
192 PNEUMOBILIA ATTRIBUTED TO BILIARY DUCT NEOPLASM
Umyarova E1, Suvorava N2, Rakvit A2. 1 MUSC, Charleston, SC and 2 TTUHSC, Lubbock, TX.
Case Report: Pneumobilia is an accumulation of air in the biliary tree. We report a case of a biliary duct neoplasm presented with pneumobilia. 75 yo female presented with fever and hypotension. She was evaluated for anemia and unintentional weight loss and had unremarkable colonoscopy results. She was admitted with diagnosis of sepsis underwent CT abdomen/pelvis which showed dilatation of bile ducts multiple intraabdominal and retroperitoneal LN, and pneumobilia (p1). Subsequent ERCP/EUS showed biliary stricture with dilatation of main hepatic ducts and mass on a bifurcation of hepatic ducts suspicious for adenocarcinoma. CBD brushing revealed atypical cells suspicious for well differentiated adenocarcinoma. Pneumobilia is an uncommon finding on imaging studies. Causes include recent biliary instrumentation, incompetent sphincter Oddi, biliary-enteric spihincter anastomosis, spontaneous biliary-enteric fistulas, PUD, neoplasms, emphysematous cholecystitis and liver abscess. Radiographically: large linear confluence of air located within a central portion of the liver. It is important to distinguish pneumobilia from portal and mesenteric vein gas since the mortality rate reaches 90% for the later if left surgically untreated. Our patient presented with signs of sepsis and was found to have pneumobilia on imaging studies. Unlike the other patients with hilar cholangiocarcinoma patient did not have signs of obstructive jaundice, abdominal pain or pruritus and experienced only refractory anemia and significant weight loss.
193 GO WITH THE FLOW: PLASMA CELL LEUKEMIA IN A PATIENT WITH LEUKOCYTOSIS, HYPERCALCEMIA, AND RENAL FAILURE
Wilkinson KJ1, Herrin V1, Lam JT2. 1 UMMC, Jackson, MS and 2 UMMC, Jackson, MS.
Case Report: Plasma cell leukemia is a rare variant of multiple myeloma defined by the presence of clonal plasma cells in the peripheral blood exceeding 2000/microL or comprising at least 20% of the peripheral leukocytes. Presenting characteristics are similar to those seen in myeloma and in other leukemias, and abnormal protein electrophoresis is not required for the diagnosis.
An 80-year-old female presented to the emergency room with complaints of flu-like symptoms. Laboratory studies revealed a leukocyte count of 85.5 x 109/L, hemoglobin of 7.7g/dL, calcium of 13.9 mg/dL, and creatinine of 4.10 mg/dL. Review of peripheral smear showed many smudge cells and atypical lymphocytic cells with scant basophilic cytoplasm, round nuclei with homogenously condensed chromatin, and no nucleoli comprising approximately 50% of the leukocytes. A few of these cells had a vague plasmacytic appearance with eccentrically placed nuclei, but this was very subtle. Chronic lymphocytic leukemia was considered in the differential but did not explain her other findings, thus a bone marrow aspiration and biopsy were performed. The marrow aspirate revealed sheets of atypical lymphoplasmacytic cells similar to those seen in the periphery. Aggregates of these cells encompassed 80-90% of the cellularity on the biopsy. Flow cytometry detected a cell population which expressed CD138, CD38, and myeloperoxidase with cytoplasmic kappa Ig light chain restriction. This immunophenotype was consistent with plasma cell leukemia. Interestingly, serum and urine protein electrophoresis did not reveal an elevated M-protein, however free kappa light chains were significantly elevated as well as the kappa/lambda light chain ratio.
She and her family strongly desired treatment, and she received one cycle of renally-adjusted VD PACE and liposomal doxorubicin. She developed neutropenia, and despite antifungal therapy, she died from candidemia sepsis.
Plasma cell leukemia can be difficult to diagnose given its rarity and subtle morphology. As this case demonstrates, an abnormal protein electrophoresis supports the diagnosis but is not necessary. Diagnosis requires the detection of a clonal population of plasma cells present in the periphery which can be confirmed with flow cytometry.
194 ONLY THE STRONG SURVIVE: A CASE OF PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Williams JC, Herrin V. University of Mississippi Medical Center, Jackson, MS.
Case Report: Hemophagocytosis is a phenomenon where by erythrocytes, leukocytes, platelets and the bone marrow precursors are engulfed by macrophages. It is an unspecified phenomenon found in several conditions such as hemolytic anemia, malignant disease, infections, and hemophagocytic syndrome. Hemophagocytic Syndrome, also known as Hemophagocytic Lymphohistiocytosis (HLH), is an uncommon; life-threatening hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated but ineffective immune process.
We present the case of a 37 year old African-American man diagnosed with secondary HLH. The patient initially presented as an inpatient consult to Hematology to identify the etiology for fever in the presence of pancytopenia. Review of patient’s history was unremarkable except for three week history of fever as high as 103 degrees Fahrenheit. Other than mild tachycardia, the patient’s physical exam was normal. With respect to his initial lab work, the patient had pancytopenia, transminitis, negative hepatitis panel, EBV negative, HIV negative, Parvovirus negative, normal rheumatoid factor, and normal ANA. Two bone marrow aspirates and biopsies revealed rare hemophagocytosis. The patient was discharged with follow up in Hematology clinic. One month after his initial presentation in the hospital, the patient was re-admitted with unresolved fever, worsening transminitis, ferritin of 76,000; ileus and weakness, and soluble IL-2 of 5453. The patient was diagnosed with secondary HLH. He was subsequently administered HLH 1994 protocol with intent for bone marrow transplant. Despite not having any bone marrow match, the patient tolerated the HLH 1994 protocol without difficulty and remains in remission.
HLH is an uncommon life-threatening hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated but ineffective immune process. This case illustrates that swift diagnosis and treatment with immunosuppression and cytotoxic agents can prolong disease free survival and overall survival in a disease with poor prognosis.
Infectious Disease, HIV, and AIDS Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
195 RAOULTELLA ORNITHINOLYTICA: A RARE HUMAN INFECTION
Akhter SR, Smalligan RD, Islam A, Chandra R. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: A 46yo woman was admitted for fever and right flank pain despite 7d of amox/clav for UTI. No hx of hematuria or nephrolithiasis. PMH: Hepatitic C with cirrhosis, recurrent UTIs. No illicit drug use and no HIV risk factors. PE: A&O, BP 140/78, HR 100, RR 17, T 103. Heart and lung exams normal. Abdomen soft without fluid wave but CVA tenderness present on the right. Neurologic exam without flapping tremor. Lab: WBC 2.8k, 80% segs, Hgb 10.8, platelets 74k, bili 2.0, Cr 1.0, HIV neg. UA had WBCs and nitrite pos and cx: Raoultella ornithinolytica resistant to amp but sensitive to quinolones and carbapenems. Abd CT: right pyelonephritis without stones or obstruction. She responded to levofloxacin and was discharged home within 3 days.
Discussion: Internists encounter complicated UTI and pyelonephritis on a daily basis. The vast majority are due to E. coli with the less common appearance of Proteus, Klebsiella and Enterobacteriaceae species. This case was caused by an uncommon Enterobacter. family organism: Raoultella ornithinolytica. In the past Raoultella was thought to be a Klebsiella organism but molecular techniques have shown it to be a separate genus consisting of R. ornithinolyticia, R. planticola, and R. terrigena. This is a gram-negative encapsulated aerobic bacillus that is found in aquatic environments and soil. It is found in the gut of fish, and that of soil insects like earthworms and millipedes, hence contaminating the water and soil. Risk factors include eating contaminated fish, fecal-oral spread and contact with soil. Immunocompromised patients are particularly susceptible, including cirrhotics like our patient. There are reports of Raoultella genus causing skin and soft tissue infections, bacteremia, and UTIs. A distinctive feature of this bacterium is its ability to convert histidine to histamine in scombroid fish causing redness and flushing on the skin (histamine fish poisoning).
Raoultella spp can be quite resistant with some being resistant. Macrolides are ineffective, as are rifampicin, glycopeptides and fusidic acid. Carbapenemases have been found in Raoultella spp as well hence it is best to guide treatment by current sensitivities. Effective choices often include cephalosporins, cotrimoxazole, fluoroquinolones, aminoglycosides, or nitrofurantoin.
196 ANOTHER DOMESTIC CHAGAS DISEASE IN THE US
AlBaalbaki F, Land M. University of Tennessee, Germantown, TN.
Case Report: 36 year Caucasian female with no significant past medical history, referred to our Infectious disease clinic for positive serology of Trypanosoma cruzi. The patient works in Memphis, TN, and lived most of her life in rural areas of northern Mississippi. She denied any cardiac or GI symptoms. She had no history of blood transfusion, needle stick, or organ transplantation. She had never traveled to an endemic area, had an insect bite, or involved in outdoor hunting. Her mother had never lived in an endemic area and had negative serology. Her physical exam was basically unremarkable. Electrocardiogram showed no evidence of conduction abnormality. Her basic laboratory came back normal. Repeat T. Cruzi antibodies came back positive for IgG with titer of 12 (positive 5-16). Another blood sample was sent to the CDC and was IFA positive with titers of 1:32 (reactivity at 1-32 or greater sample dilution is defined as a reactive test). The patient was diagnosed with chronic indeterminate chagas disease and offered treatment with Benznidazole according to CDC recommendation. She tolerated the medicine well with no significant side effect.
Chagas disease is most commonly transmitted through defecation by T cruzi-infected triatomine insects after a blood meal. Chagas infection first presents as an acute illness that can either be asymptomatic or a self-limiting febrile illness. After a decrease in parasitemia, patients enter the indeterminate chronic stage. About 70% of patients in the indeterminate stage will never experience symptoms. The remaining 30% of patients will develop chagasic cardiomyopathy or digestive symptoms, including megaesophagus or megacolon, often 10 to 30 years after the initial infection.
Chagas disease has long been known to be an important parasitic infection in Latin America, with 11 million people or more currently infected. However, there is an increasing attention to the presence of the disease in the US, with more than 300,000 chronically infected persons residing in the country. It is well known that triatomine vector can be found across the southern half of the country. It is assumed that most of the Chagas disease cases in the US result from immigration; however, new evidence documents at least 23 cases of autochthonous, vector-borne transmission within the US.
197 INTRACRANIAL TUBERCULOMA IN A PATIENT PRESENTING WITH CONFUSION AND HEMIPARESIS
Bojanowski CM, Beck S, Krauland J, Gruber M, Engel LS, Amoss J. LSU Health Sciences Center, New Orleans, LA.
Case Report: Central nervous system (CNS) tuberculosis is a rare severe extra-pulmonary form of Mycobacterium tuberculosis disease that manifests as either tuberculoma or meningitis. The majority of CNS cases occur in children and immunocompromised patients. Common presenting symptoms include headache, seizures, and hemiparesis. Radiological diagnosis of a brain tuberculoma is difficult as the imaging presentation is varied and can be non-specific.
CASE: A 55 year old African American woman with end stage renal disease on hemodialysis, anemia of chronic disease and severe de-conditioning presented with altered mental status and left sided hemiparesis. Initial brain CT and sequential MRI brain with and without contrast showed a ring enhancing lesion high in the right parietal lobe with restricted diffusion, calcifications, and associated vasogenic edema. Also noted on admission imaging was the presence of right supraclavicular and cervical chain lymphadenopathy. Excisional biopsy of a supraclavicular lymph node revealed granulomatous type inflammation and mycobacterium tuberculosis grew from culture at 2 weeks. Serum Interferon gamma release assay (IGRA) was also positive. She was started on dexamethasone and phenytoin for seizure prophylaxis. Empiric antimicrobial coverage for both brain abscess and tuberculoma was provided with vancomycin, ceftazidime, and RIPE therapy.
DISCUSSION: Tuberculomas typically appear on imaging as either solitary or multiple, round lesions often located in the frontal or parietal lobes with irregular walls and with signs of ring enhancement after contrast. The “target sign” (a ring enhancing lesion with a central area of enhancement or calcification) has been described as characteristic of tuberculomas. MRI findings vary according to the stage of the lesion. Despite advancements in imaging and laboratory diagnostics, tuberculomas of the central nervous system remain a diagnostic challenge. Early diagnosis is imperative, since clinical outcomes are largely dependent on timely treatment. Standard medical care includes prolonged treatment (12–30 months) with rifampicin, isoniazid, pyrazinamide, and streptomycin or ethambutol.
197A DISSEMINATED HISTOPLASMOSIS WITH ORAL AND CUTANEOUS MANIFESTATIONS IN AN IMMUNOCOMPETENT PATIENT
Bojanowski CM, Johnson P, Salassi M, Mohan M, Engel LS. LSU Health Sciences Center, New Orleans, LA.
Case Report: Occurrence of the disseminated histoplasmosis is rare in HIV seronegative patients. Here we describe a case of disseminated histoplasmosis with both oral and cutaneous manifestations in an immunocompetent patient.
CASE: A 40 year old construction and oil field worker from Louisiana presented with a 4 month history of weight loss, night sweats, fever, nonproductive cough, shortness of breath and pleuritic chest pain after failing treatment for presumed bronchitis and pneumonia. The patient also reported inguinal erythematous papules and ulcers and a recent onset of oral ulcerations. At the time of admission, he was not febrile. On physical exam, he was described as a well-built thin Caucasian male in no acute distress who had a right superior gingival 2mm ulceration. His skin had multiple (> 10) small erythematous nodular papules located bilaterally in his inguinal folds and a large erythematous and plaque-like lesion with rolled borders and central erosion in his left inguinal fold. Initial labs revealed microcytic anemia. HIV, RPR, HSV, T-Spot, Blastomycosis antibody, Histoplasma urine antigen, and blood culture were negative. CXR on admission showed a right upper lobe opacified nodule with central lucency, a right lower lobe nodule. CT guided fine needle aspiration of lower lobe lung mass demonstrated suppurative non-caseating granulomatous inflammation with organisms consistent with Histoplasma identified within the macrophages. GMS staining also revealed abundant fungal elements consistent with Histoplasma. Fungal culture grew Histoplasma capsulatum. Inguinal punch biopsy also showed abundant dermal histiocytes heavily loaded with fungal elements. The patient was started on a 12 month course of itraconazole.
DISCUSSION: Manifestations of disseminated histoplasmosis include fever, weakness, weight loss, hepatosplenomegaly, and mucocutaneous lesions. Systemic histoplasmosis has emerged as an important opportunistic infection among immunocompromised patients as well as in immunocompetent patients residing in endemic areas. Biopsy of lung, mucosal or cutaneous lesions is the most rapid method of arriving to the correct diagnosis.
198 HISTOPLASMOSIS AND MYCOBACTERIUM KANSASII PRESENTING AS A RECURRENT PLEURAL EFFUSION
Bojanowski CM, Krauland J, Engel LS, Amoss J. LSU Health Sciences Center, New Orleans, LA.
Case Report: Mycobacterium kansasii is the second most common nontuberculous mycobacterium (NTM) species isolated from patients with HIV infection and is considered to be one of the most virulent. Confounding the presentation of this disease is the high rate of coinfection with other pulmonary pathogens.
CASE: A 67 year old African American man with HIV/AIDS (CD 4 count 11) presented with a six month history of unintentional weight loss and a one month history of dyspnea on exertion and cough productive of yellow-brown sputum. At the time of presentation, he denied any chest pain, fevers, or night sweats. Social history was significant for a remote incarceration and a 50 pack year smoking tobacco history. His last negative PPD was 2 years prior around the same time he discontinued taking his HAART therapy. Pertinent exam findings included a respiratory rate of 18 with 97% oxygen saturation on room air, cachexia with temporal wasting, seborrheic keratosis, and a lung exam significant for increased fremitus, dullness to percussion to the level of scapula, and decreased breath sounds on the right. Imaging (CXR and CT chest with contrast) showed a large right sided pleural effusion with a right to left cardiomediastinal shift. He was placed on respiratory isolation and AFB sputum samples were obtained. The patient was started on RIPE therapy after AFB smears were positive. Pleural fluid culture eventually grew Histoplasma capsulatum. He was started on Ambisome IV and continued on RIPE therapy. Cerebrospinal fluid was negative for histoplasmosis, AFB, and Cryptococcus. Gen-probe of both sputum and pleural effusion were positive for Mycobacterium kansasii as well. Treatment was tailored to include rifampin, INH, ethambutol and intraconazole.
DISCUSSION: The literature suggests that up to 69% of HIV positive patients with pulmonary consolidations and M. kansasii, also had a another pulmonary pathogen concurrently isolated from respiratory specimens. Due to the highly variable clinical and radiographic presentation and frequent occurrence of coexisting pathogens, all patients with HIV/AIDS and respiratory symptoms should be evaluated for mycobacterial disease and opportunistic infections such as Histoplasmosis.
199 NEONATAL CONGENITAL HIP DISLOCATION COMPLICATED BY GROUP B STREPTOCOCCOS SEPTIC ARTHRITIS AND OSTEOMYELITIS
Brosset Ugas M1, Balan A2, DeLeon S1. 1 University of Oklahoma Health Sciences Center, Oklahoma City, OK and 2 University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Septic arthritis and osteomyelitis are unusual in the newborn period, which may cause a delay in diagnosis. Their presentation is variable and can be associated with dislocation or physeal separation. We present the case of a female neonate with a congenital hip dislocation found to have septic arthritis complicated by osteomyelitis.
Our patient was an 18 day old infant born at term via spontaneous vaginal delivery after an uncomplicated pregnancy; her mother tested negative for HIV and Group B Streptococcus (GBS), and she was discharged home at 48 hours of life. Since discharge, her family reported decreased spontaneous movement and pain with passive movements of her right leg. She was otherwise well, had no fevers, and demonstrated normal activities. On day of life 17, she was seen at an Emergency Department due to persistent parental concerns about her leg. On physical exam her right hip was non-erythematous but did have tenderness with passive motion. Pelvis X-ray showed a right hip dislocation, metaphyseal lucency, and signs of a septic right hip joint. Hip ultrasound showed a large heterogeneous multiloculated joint effusion with displacement of the femoral head laterally. Her initial CBC showed a WBC count of 26,300 and a normal differential, normal hematocrit, and elevated platelets of 725,000; ESR and CRP were also markedly elevated. Orthopedics performed an open drainage and washout and obtained grossly purulent synovial fluid with negative gram stain. She was placed in a Pavlik harness and started on vancomycin and cefotaxime. Blood and spinal fluid cultures were sent and ultimately were negative. The joint culture, however, grew GBS. Our patient was switched to ampicillin, and ultimately penicillin, once sensitivities were known.
A literature search reveals few cases of neonatal osteomyelitis. This case shows that osteomyelitis/septic arthritis in a newborn may present with only decreased motion of an extremity, and physicians should maintain a high index of suspicion. In our case maternal and delivery risk factors for infection and hip dislocation were not present, which caused an even greater delay in diagnosis.
200 INFANT BOTULISM IN OKLAHOMA: A CASE REPORT
Daniels BS1, Nabavizadeh N1, Balan A1, Johnson M1, Ng Y2. 1 University of Oklahoma Health Sciences Center, Oklahoma City, OK and 2 University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Infant botulism is a rare disease caused by Clostridium botulinum toxin and characterized by descending symmetrical paralysis, cranial nerve and bulbar dysfunction, and hyporeflexia.
In Oklahoma there were only 8 cases reported in the past 23 years. We present a 1-month old patient with an unusual presentation of infant botulism.
A 1-month old infant presented with acute onset of poor feeding, fussiness and constipation. Parents reported weakness and a faint cry, but denied fever, apnea, seizures, or rash. On physical exam, she was hypotonic with head lag and poor suck reflex, but with normal deep tendon reflexes. She underwent a full sepsis work up which was negative. On hospital day 3, she had increasing weakness and respiratory distress. A blood gas revealed severe respiratory acidosis requiring intubation. Just prior to intubation she appeared weak with a “ragdoll” appearance, and with poor gag but intact cough reflex. Genetic and thyroid studies, EEG, brain and spine MRI were normal. With no apparent cause, and in view of rapid respiratory failure and progressive paralysis, infant botulism became high on our differential. After discussion with specialists at the California Department of Health, human botulism immune globulin, BabyBig©, was given on hospital day 5, and a stool sample was sent to the CDC for botulinum toxin bioassay.
Within two days of BabyBig© administration her strength improved. On hospital day 10, she was reported to have positive botulinum toxin in stool, extubated on hospital day 12, and discharged on day 19.
Infant botulism is rare in Oklahoma; the source of the spores remains unknown but it likely was from the environment, as her house was in a construction zone near recent tornado damage. Our report describes an atypical presentation given the young age (median 2-8 months) and intact distal deep tendon reflexes despite respiratory failure. Her strength seemed to improve after intubation, which confounded the diagnosis. Our case illustrates that in an infant with acute weakness and rapid progressive respiratory failure, botulism must be considered, as prompt diagnosis and treatment ensures faster full recovery and lower hospitalization costs.
201 THE CAT SOLVED IT: A CASE OF PULMONARY HISTOPLASMOSIS IN A 58 YEAR- OLD FLORIST
Echendu CE1, Khasawneh FA1, Trybus J2. 1 Texas Tech Univ Health Sciences Center, Amarillo, TX and 2 Texas Veterinary Medical Diagnostic Laboratory, Amarillo, TX.
Case Report: Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. It is reported throughout the United States but is most endemic along the Mississippi and Ohio River valleys. The primary source of infection is contaminated soil and most cases are acquired via inhalation of microconidia, hence pulmonary infection is most common. Histoplasmosis diagnosis relies on identifying the fungus in infected tissues by culture, histopathological examination, serology/antigen detection or new molecular diagnostic methods in combination with consistent history and imaging studies. Pulmonary histoplasmosis can be successfully treated with amphotericin B or itraconazole. A 58 year-old female florist was admitted with a small subdural hematoma after falling down due to a vasovagal syncope. She was found to be hypoxic. A computed tomography of the chest was done to rule out pulmonary embolism. It showed bilateral pulmonary nodules with hilar lymphadenopathy. On further questioning, the patient reported weight lose and night sweats and she recalled losing her cat 2 months ago to a fungal infection. The veterinarian was contacted for the histopathology report, which showed feline histoplasmosis. The patient refused invasive testing. Histoplasma serology was positive. She was discharged home on oral itraconazole to be followed up in clinic. Animal to human transmission of histoplasmosis has not been reported. In our case, both cat and owner acquired their infection from same or similar source. The patient lived just to the west of histoplasma endemic areas. Furthermore, exposure to conidia by being a florist who gets flowers and plants from all over the county could have been a second potential source of infection. Obtaining detailed history aided in the management of our patient.
202 NON-FATAL GASTRIC MUCORMYCOSIS
Ferrara AP, Lewis T. Baptist Health Systems of Alabama, Birmingham, AL.
Case Report: Gastric mucormycosis is a rare form of fungal infection that most commonly affects immunocompromised patients with high rates of mortality. Predisposing conditions include metabolic acidosis and defects in neutrophil or monocytic function. Patients generally present with fever, abdominal pain, distention, nausea, vomiting, and hematochezia. The diagnosis is established with histopathologic specimens often acquired through upper endoscopy. First line therapy of treatment is amphotericin B combined with surgical debridement. Posaconazole additionally can be used in conjunction with these therapies or in the case of failure or inability to tolerate amphotericin B. Our patient was a 56 year old African American woman with a history of controlled diabetes mellitus type 2 and end-stage renal disease on peritoneal dialysis. She was found to have gastric mucormycosis after hematemesis prompted upper endoscopy. She was successfully treated with liposomal amphotericin B with total gastrectomy and a right hemicolectomy.
203 HEPATIC ENCEPHALOPATHY: A CASE OF KILLER FUNGUS
Googe A, Grover I. University of Mississippi, Jackson, MS.
Case Report: Cryptococcal infections are unanimously associated with HIV and are an AIDS defining illness. However, approximately 10% of cases are related to other causes of immune compromise such as cirrhosis. We present a case of rapidly fatal disseminated Cryptococcus neoformans in a non-HIV cirrhotic patient.
We present a 58-year-old male with alcoholic cirrhosis presented with new onset gait disturbance followed by altered mental status, bladder and bowel incontinence, and hallucinations favoring a diagnosis of hepatic encephalopathy. The patient’s family reported alcohol and tobacco use, and previous treatment of cancer without residual disease. Physical exam findings included jaundice, abdominal distention, upper extremity fasciculations, and disorientation. Studies included blood cultures, ammonia level, and hepatic function panels. HIV screen was negative, CT of the head showed no lesions or enhancement, hepatic function panels revealed elevated ammonia of 99 umol/L. On day 2, blood cultures were positive for fungus and empiric treatment with Abelcet and flucytosine were started. Suspicion for cryptococcal meningitis was high despite decreasing ammonia levels and persistent confusion. Tachycardia and anuria following initial dose of abelcet suggested acute renal failure with creatinine of 1.47 ng/dL from admission level of 0.57 ng/dL and was subsequently discontinued. On day 4, further patient decline lead to mechanical ventilation and vasopressors. Family decided to withdraw support, and the patient expired 72 hours after diagnosis of disseminated cryptococcus without evidence of HIV.
Currently, there are limited reports of cryptococcal infections in non-HIV patients; however, with immune dysfunction secondary to chronic diseases like cirrhosis and diabetes, such infections are possible. With a low index of suspicion, invasive fungal infections in non-HIV infected patient may delay testing and therapy. Early recognition and treatment of cryptococcal infections can decrease mortality.
204 WEST NILE VIRUS ENCEPHALITIS MASKED BY ALCOHOL WITHDRAWAL
Graebert A, Jones N, Engel LS, Maffei J. LSU Health Sciences Center, New Orleans, LA.
Case Report: West Nile virus is an arbovirus transmitted by mosquitoes most commonly from a host bird. Often asymptomatic West Nile virus may present as self-limited febrile illness or as a neuroinvasive disease manifested as meningitis, encephalitis, or flaccid paralysis.
CASE: A 57 year old Caucasian male with a medical history significant for hypertension and alcohol use presented to the emergency department after a witnessed episode of syncope. The patient admitted to a 2-3 week history of generalized weakness. Upon presentation vital signs and physical exam were unremarkable. Comprehensive metabolic panel revealed sodium of 127 mmol/L, potassium of 2.8 mmol/L, creatinine of 0.97 mg/dL, and mildly elevated total bilirubin. Overnight, the patient became febrile up to temperatures of 104 °F and developed a tremor. Blood and urine cultures were drawn, and he was started on empiric antibiotic therapy. He was also placed on a multivitamin, thiamine, and folate, along with ativan as needed for suspected alcohol withdrawal. Head CT and MRI showed only chronic cerebral atrophy and chronic ischemic changes. He continued to have febrile episodes. However, multiple sets of blood and urine cultures did not reveal evidence of infection and chest x-ray did not reveal an infiltrate. Lumbar puncture produced clear and colorless cerebrospinal fluid with 41% white blood cells, glucose of 61mg/dL, and protein of 48.1 mg/dL. Routine CSF cultures, acid fast bacillus, CSF VDRL, HSV PCR, nasal swabs for influenza A and B antigens, and serum cryptococcal antigen were negative. His West Nile virus IgG and IgM were positive and a diagnosis of West Nile virus was confirmed. Over the course of the next week the patient’s mental status improved and strength was regained through physical therapy.
DISCUSSION: The patient’s initial presentation was his manifestation of West Nile fever characterized by fevers, chills, and generalized weakness. The progression of disease to encephalopathy was likely secondary to his history of alcohol abuse, as older age, alcohol abuse, and diabetes in patients with West Nile virus have been associated with encephalitis. There is no specific treatment for West Nile virus, and patients are managed with supportive care.
205 FAR MORE THAN A CYCLING INJURY
Gravolet R, Doan C, Engel LS, Guillory S. LSU Health Sciences Center, New Orleans, LA.
Case Report: Approximately 300 episodes of miliary TB were reported in the US in 2010, accounting for only 1-2% of all TB cases.
CASE: A 73 year old man presented with a 4 day history of hematuria and a 4 week history of dysuria and lower back pain. The patient attributed his problems to a recent biking injury in which his groin collided with the bike’s handlebars. He was trearted with ciprofloxacin for 10 days for a suspected UTI. His symptoms continued to worsen over the next two weeks, however, and his lower back pain intensified to a 9/10. On presentation to our facility, further questioning revealed a 10 year history of cough that in previous weeks was more productive of darker colored sputum. He reported a 40 lb weight loss in the previous months. He affirmed a 20 pack year smoking history, a history of incarceration five years prior, and current homelessness. Vital signs were unremarkable. On physical exam, the patient had decreased breath sounds in his lower lobes, tenderness to palpation along his lower back, and a hyperpigmented hardened nodules on the skin of his scrotum and behind his right shoulder. Urinalysis was positive for blood (250/microliter) and protein (150/microliter), and PSA was 28.5. Chest CT showed cavitary changes, miliary changes, and calcified nodules distributed throughout the lungs bilaterally. Abdominal/pelvic CT revealed L5-S1 discitis & osteomyelitis, an enlarged heterogenous prostate, and an 8 mm UVJ stone; US of the testicle revealed a hydrocele and possible scarred fibrous tissue. The pt’s sputum tested AFB 3+ positive, and an IR biopsy of the lumbar spine was AFB smear positive, both subsequently grew Mycobacterium tuberculosis. Urinary involvement was also confirmed with a urine culture grew TB. The patient was diagnosed with disseminated TB, and RIPE + B6 therapy was administered with plans to treat for 9 months.
DISCUSSION: Due to nonspecific signs and symptoms, miliary TB is often missed (20% of cases diagnosed post mortem) and requires a high index of suspicion. Our patient’s diverse problems including a long history of productive cough, weight loss, back pain, dysuria and hematuria are united under one pathological process of disseminated TB.
206 A RARE ASSOCIATION:INFLUENZA TYPE B WITH SEVERE THROMBOCYTOPENIA
Habib S, Moti D, Chandra R. Texas Tech Univ Health Science Center, Amarillo, TX.
Case Report: A 32 year old male had acute presentation with 3 days of generalized bodyaches, headache and malaise, sore throat and fever. He also had been coughing out blood for a day with shortness of breath. He had no past medical history. He came to US from Cuba 1 month prior, but had been healthy all along until this current presentation. He did not consume alcohol or any medications. On examination BP was 120/70,P 80 R 22, temperature 100F. Heart, lung exam was clear. Skin had mild petechiae. Abdomen was without any splenomegaly. No lymph node enlargement. Nonfocal neurologic exam. Labs showed WBC count of 3,000,normal Hb, platelet count of 17,000. Renal and liver function was normal.CT scan of the chest showed bilateral “tree in bud” infiltrates more consistent with diffuse bronchopneumonia rather than alveolar hemorrhage. Investigations for thrombocytopenia noted for peripheral blood smear with a very low platelet count. No platelet clumping. No schistocytes, no signs of hemolysis or microangiopathy. Dengue IgM was normal and malarial parasite was normal. Vitamin B12 and Folic acid levels were normal. Rapid strep test,monospot test, HIV serology, hepatitis panel, ANA, ADAMTS13 test, were all negative. Regarding his pneumonia, his blood cultures were negative. Sputum cultures and AFB stain were negative.Influenza antigen was positive for Influenza B. Patient was treated for Influenza B pneumonia with oseltamivir. He clinically improved and platelet count spontaneously recovered to 101,000/cmm after 6 days.
While moderate thrombocytopenia has been described with many viral illness, a severe thrombocytopenia of this level is seen very rarely with Influenza type B. Less than 1.8 % of type B influenza will have thrombocytopenia per one study.In general,mechanisms of thrombocytopenia in influenza are mostly to do with transient viral suppression of platelets production in the bone marrow. These patients would spontaneously recover without any specific therapy as in our patient.Thrombocytopenia in TypeA influenza has been associated with higher mortality.RT PCR testing is not always readily available, low platelet counts can be a clue to certain aggressive strains.Newer emerging potentially fatal Type A( H7N9) variants in 2013 have been associated with thrombocytopenia and alveolar hemorrhage.
207 TULAREMIA : A CAUSE OF LYMPHADENITIS IN A PEDIATRIC PATIENT FROM OKLAHOMA
Hines L1, Lich A1, Balan A2, Ramji F3. 1 University of Oklahoma Health Sciences Center, Oklahoma City, OK; 2 University of Oklahoma Health Sciences Center, Oklahoma City, OK and 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Tularemia is an uncommon cause of lymphadenitis in Oklahoma. It is a disease caused by the bacteria Francisella tularensis, most commonly transmitted through the bite of an infected tick. Approximately 120 cases of tularemia are reported each year in the United States. In 2010, states with the highest number of cases were Arkansas, Missouri, Kansas and South Dakota, with a range of 11-19 cases per year; Oklahoma was the 4th state, with only 8 reported cases, all patients were 17 years and older.
A 9-year-old female presented with fever, tenderness, erythema and lymphadenopathy of left inguinal area. Her symptoms began 5 days after a tick bite to the area. She was started on trimethoprim/sulfamethoxazole, but symptoms worsened and she was admitted for further management. She received intravenous clindamycin. Doxycycline was added due to history of a tick bite and presence of thrombocytopenia. She developed a small ulceration at the site. Her fever improved and she completed a 10-day course of oral clindamycin and doxycycline. The ulceration healed and lymphadenitis improved. One week after discontinuation of antibiotics, she experienced recurrence of fever and worsening of lymphadenitis, at which point tularemia was considered and serology was obtained; oral doxycycline and clindamycin were given. A week into restarting her antibiotics treatment tularemia titer was reported at 1:1280 (positive >1:160). She developed a large, tender, erythematous and fluctuant mass in her inguinal region; incision and drainage, and therapy with gentamicin was initiated. She completed a 2-week course of gentamicin without relapse of her symptoms.
We present a pediatric case of ulceroglandular tularemia. While this is an uncommon cause of lymphadenitis, it has to be considered in states with relatively high prevalence, like Oklahoma, especially in patients reporting a tick bite. Our case illustrates relapse with therapy with doxycycline. The recommended treatment of choice remains an aminoglycoside like gentamicin; doxycycline is associated with a high relapse rate especially with a short duration of therapy.
208 WHO’S TO BLAME?
Jethwa SD, Thomas WH, Bocchini J. LSU Health Sciences Center, Shreveport, LA.
Case Report: 17 year old female with extensive past medical history, presented with facial and lip edema. Previously, she developed a left nostril abscess, was drained, and treated with 10 days of doxycycline. Upon completion of her antibiotics, she noted facial swelling and pain. She received Rocephin, Keflex and Bactrim at another facility. She presented to clinic with increased pain and swelling. She was admitted with facial cellulitis. IV Clindamycin was started. Lab values were within normal limits; sed rate elevated at 36. Sinus CT showed only soft tissue swelling. Blood and facial exudate cultures were negative. Her facial swelling and drainage worsened. She was changed to Vancomycin with continued worsening of symptoms. High dose IV steroids were initiated. By 24 hours, she showed vast improvement of facial swelling and pain. During her initial course of steroids no changes were made to her home medication including: lisinopril, risperdal, metformin, insulin. Within 48 hours of discontinuing steroids, her symptoms reoccurred. All medications with potential to cause angioedema were stopped. Despite changing her medications, lisinopril to diltiazem and risperdal to fluoxetine, she continued to swell. IV steroids were restarted and continued with a 2 week taper. She was discharged with no facial swelling. The differential diagnosis of this her pain and swelling are the following: drug induced hypersensitivity reaction, infection, or C1 esterase deficiency. Her C4 complement level was slightly elevated at 44.6 mg/dl (range 10-40 mg/dl); therefore, C1 esterase deficiency has not been completely ruled out. Classic patients with C1 esterase deficiency do not respond to steroids as our patient did.
209 CHYLOUS ASCITES IN KAPOSI SARCOMA: A CASE REPORT
Johnson P, Chang E, Smith E, Lo B. LSU Health Sciences Center, New Orleans, LA.
Case Report: A 26 year old Caucasian male with a history of AIDS (CD4 - 123), KS, pleural effusion, and pulmonary emboli was admitted for diffuse abdominal pain and scrotal edema. Physical exam was notable for tachycardia, pallor, decreased basilar breath sounds, diffuse abdominal pain with distention, positive fluid wave and shifting dullness without rebound or guarding, tender scrotal edema, inguinal adenopathy, and purple lesions on his upper palate and torso consistent with KS. A prior EGD and colonoscopy showed Kaposi’s lesions throughout the GI tract. An abdominal CT revealed diffuse adenopathy. A paracentesis was performed and 1510mL of milky, turbid, blood-tinged fluid was removed. Fluid analysis was negative for malignancy but demonstrated 36,300; RBC’s and triglycerides concentration of 740 mg/dL. The patient was started on liposomal doxorubicin for his KS during his hospitalization and finally achieved adequate pain control and improvement of his ascites and scrotal edema after three rounds of treatment as an outpatient.
DISCUSSION: Chylous ascites is an uncommon finding that is caused by the presence of intestinal or thoracic lymph in the peritoneal cavity. The incidence is reportedly 1 per 20,464 admissions at Massachusetts General Hospital during a 20-year period. It is diagnosed by milky ascitic fluid with a triglyceride content typically greater than 200 mg/dL. Causes of chylous ascites include: malignancy, trauma, chronic liver disease, inflammation, infection, postoperative. The underlying mechanism for the formation of chylous ascites is due to the disruption of the lymphatic system from obstruction or traumatic injury. While the exact cell of origin for KS remains unclear, the current opinion is that KS tumor cells are derived from lymphatic endothelium. Hence, the development of chylous ascites may possibly be due to in-situ KS in that region rather than metastasis to the thoracic duct as once thought. Chemotherapy for KS can often improve symptoms (response rate 60-90%) as was seen in our patient.
210 A POPULATION-BASED INVESTIGATION OF OUTCOMES OF CANDIDEMIA
Kabbani S1,2, Stein B1,2, Hollick R4, Harrison LH4, Farley M1,2,3. 1 Emory University School of Medicine, Atlanta, GA; 2 GA Emerging Infections Program (EIP), Atlanta, GA; 3 VA Medical Center, Atlanta, GA and 4 Maryland Active Bacterial Core surveillance (EIP), Baltimore, MD.
Purpose of Study: Describe risk factors associated with mortality from candidemia.
Methods Used: Demographic and clinical data were collected prospectively between 3/1/08 and 2/28/13 for candidemia cases identified through active, population-based, laboratory surveillance in Georgia and Maryland EIP. Univariate analysis of risk factors associated with mortality at 30 days in children and adults was performed; p<0.05 was significant.
Summary of Results: Overall, 3,782 candidemia cases were identified with a mean annual incidence of 14.5/100,000 population. While only 64.9% of cases were hospital-onset (HO), 93.1% had at least one of the following risk factors: use of central venous catheter (CVC) (84.6%), total parenteral nutrition (TPN) (34%), or antibiotics within 14 day (78.8%). Death occurred in 917 (26.4%) adults and 32 (13.8%) children. Fluconazole resistance was found in 7.2% of cases and was not associated with mortality. Among adults, mortality was significantly higher with age ≥45 (OR 2.28 CI 1.82-2.84), HO (OR 1.86, CI 1.57-2.21), antibiotics(OR 1.6, CI 1.31-1.97), CVC (OR 1.46, CI 1.17-1.83), ICU stay (OR 3.85, CI 3.18-4.65), renal disease (OR 1.72, CI 1.43-2.06), liver disease (OR 1.74, CI 1.42-2.13), malignancy (OR 1.43, CI 1.18-1.72), prior antifungal use (OR 1.37, CI 1.11-1.69), and infection with Candida krusei (OR 2.21, CI 1.3-3.76) or C. tropicalis (OR 1.38, CI 1.08-1.75). Black race (OR 0.8, CI 0.69-0.94), TPN administration (OR 0.84, CI 0.72-0.99), CVC removal within 7days (OR 0.25, CI 0.21-0.3), antifungal treatment (OR 0.2 CI 0.16-0.25) and C. parapsilosis (OR 0.54, CI 0.43-0.69) were associated with lower odds of death. In children, death was significantly associated with male gender, CVC, antibiotics, ICU stay, and malignancy; antifungal treatment and CVC removal were associated with lower odds of death.
Conclusions: Candidemia was strongly associated with use of CVCs, TPN, and systemic antibiotics. Mortality from candidemia was higher in older adults, those with underlying diseases or on systemic antibiotics, and infection with C. krusei or C. tropicalis. Multivariable analysis will be conducted to determine independent risk factors for mortality associated with candidemia.
211 SIADH SYNDROME SECONDARY TO WEST NILE MENINGOENCEPHALITIS
Karim A, Nakhla E, Akhter SR, Ahmed M, Islam A. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: Learning objective: Recognize the association of West Nile Meningoencephalitis with SIADH syndrome.
Case Presentation: A 58 year old Caucasian male presented with encephalopathy worsening over 1 week. He had H/O Afib, HTN for which he was on warfarin, valsartan and HCTZ. On admission he was drowsy but arousable,oriented only to person, vitals were normal. Physical examination was significant for bilateral lower extremity weakness against resistance. Labs were significant for sodium 119, potassium 2.5, cortisol, TSH, T4 levels were normal. Urine sodium 12, potassium 20, calculated serum osmolality 250, effective osmolality 248, normal lipids and total protein, urine osmolality 447. Drug screening, alcohol level, RPR negative. With the initial 0.9% NS IV 100cc/hr kept Serum sodium around 125. For ongoing confusion 3% sodium chloride was given following which sodium level came around 132. Corresponding urine sodium was 167. SIADH syndrome was highly suspected. He had one time fever at home a week ago. Emperic antibiotic started. CT head showed old right frontal stroke. CSF study was significant for aseptic meningitis. West Nile serology was positive.A diagnosis of SIADH syndrome secondary to West Nile Meningoencephalitis was made.
Discussion: WNV is an RNA arbovirus. The transmission of the disease in humans occurs most commonly from a bite of an infected Culex mosquito. Person-to-person transmission is not common but can result from blood transfusion, organ transplantation, intrauterine or breastfeeding exposure. The incubation period of WNV is 2-15 days. Approximately 20% will develop a self-limited flu-like illness called West Nile fever with no neurological manifestation. Less than 1% of infected persons develop neurological disease. For patients with neuro invasive disease, 35-40% has meningitis, 55-60% has encephalitis, and only 5-10% have poliomyelitis. About 40% of patients have an initial CSF that shows a pleocytosis with a neutrophil predominance that then becomes predominately lymphocytes. Hyponatremia is seen in 1/3rd of patients. Our patient had hyponatremia with low effective osmolality, high urine osmolality, high urine sodium with clinical euvolemia with normal TSH and cortisol. A diagnosis of SIADH secondary to West Nile Meningoencephalitis was made.
212 BACTERICIDAL ACTIVITY OF AFFINITY PURIFIED HUMAN ANTIBODIES AGAINST M-RELATED PROTEINS OF GROUP A STREPTOCOCCI AND IMPLICATIONS FOR VACCINE DEVELOPMENT
Murrell DS1,2, Agbaosi T1,2, Niedermeyer SE1,2, Penfound TA1,2, Hysmith ND1,2,3, Dale JB1,2. 1 University of Tennessee Health Science Center, Memphis, TN; 2 Veterans Affairs Medical Center, Memphis, TN and 3 St. Jude Children’s Research Hospital, Memphis, TN.
Purpose of Study: Group A streptococcal (GAS) infections cause significant morbidity and mortality throughout the world. Although multivalent M protein-based vaccines evoke a broad range of potentially protective antibodies, the epidemiology of GAS infections in developing countries has prompted a search for additional vaccine components that may result in broader protection. M-related proteins (Mrp) are expressed by 83% of clinical isolates of GAS and they contain opsonic epitopes. In contrast to M proteins, the structures of Mrp’s are highly conserved within three related families represented by Mrp2, Mrp4, and Mrp49. In the current study we evaluated the potential protective efficacy of human antibodies against Mrp.
Methods Used: Human sera were assayed for the presence of Mrp antibodies by ELISA. Antibodies were affinity purified over columns containing immobilized recombinant Mrp. Indirect bactericidal tests were performed by the Lancefield method.
Summary of Results: Sera from normal adults containing significant levels of Mrp antibodies were chosen for affinity purification. Affinity purified Mrp4 antibodies (AP α-Mrp4) reacted in high titer with recombinant Mrp4 but not with Mrp2 or Mrp49. AP α-Mrp4 were bactericidal against M28 GAS, which is a heterologous serotype expressing Mrp4. Similar results were obtained with AP α-Mrp2, which demonstrated bactericidal activity against M2 GAS. In related studies, 56% of serum samples from pediatric subjects contained significant levels of antibodies against at least one of the three recombinant Mrp’s.
Conclusions: Human serum contains antibodies that are bactericidal against GAS and a significant number of children and adolescents develop Mrp antibodies in response to infection. Taken together, our results indicate that Mrp’s may represent additional vaccine antigens that could broaden the potential protective efficacy of GAS vaccines.
213 ALPS: THE ABYSS AND THE PEAK
Mushatt DM, Subedee A. Tulane University School of Medicine, New Orleans, LA.
Case Report: A 57-year-old male with history of chronic alcoholism presented to the ER with severe respiratory distress. He had noted myalgia, malaise and non-productive cough at the onset of his illness a week earlier. Progressive dyspnea with worsening cough and scant whitish sputum developed in the following days. He reported drinking at least 1 bottle of wine and smoking more than 1 pack daily for 3 decades.
At presentation, he was diaphoretic and unable to complete sentences. He was afebrile and normotensive with tachycardia, tachypnea and oxygen saturation 71% on room air. Auscultation revealed rales in all lung fields. There was no murmur or gallop, or peripheral edema. Initial tests showed severe leukopenia (0.30 X 103/μL) with absolute neutrophil count 0/mL, platelets 150 X 103/μL and creatinine 2.3 mg/dL. Blasts or schistocytes were not seen. HIV test was negative. Chest X-ray showed patchy opacities in all lung fields.
Treatment with ceftriaxone and azithromycin was started. WBC count increased to 10.4 X 103/μL by day 3, but respiratory status worsened and mechanical ventilation was begun. Blood cultures from admission grew Streptococcus pneumoniae sensitive to penicillin and ceftriaxone. WBC peaked at 31.8 X 103/μL at day 7. Fevers abated on day 9, and the WBC normalized. On day 13, fever and worsening WBC and oxygen requirements were again noted. Chest CT showed dense confluent opacities in all pulmonary lobes. Antibiotics were changed to meropenem and vancomycin. On day 17, he became severely hypoxemic and expired.
Discussion: The syndrome of alcoholism, leukopenia and pneumococcal sepsis (ALPS) was first recognized when it was observed that in patients with Streptococcus pneumoniae bacteremia, alcoholism increased risk of leukopenia, and the latter was associated with higher mortality (80% vs. 20.5%). ALPS is fatal in 83% of cases. Our patient had "rebound" leukocytosis after initial leukopenia, which has been noted in ALPS. Dual antibiotic therapy has shown better survival than single antibiotic therapy in cases with severe bacteremic pneumococcal pneumonia. The poor outcome despite appropriate antibiotics in our patient probably was a result of severe initial pulmonary inflammatory burden. This case highlights the importance of suspecting ALPS in alcoholic patients who present with sepsis and leukopenia.
214 PERSISTENT FEVER IN AN INFANT WITH MENINGITIS
Palm S1, Balan A1,2, Ramji F1,3. 1 Oklahoma University Medical Center, Oklahoma City, OK; 2 Oklahoma University Medical Center, Oklahoma City, OK and 3 Oklahoma University Medical Center, Oklahoma City, OK.
Case Report: Tuberculous meningitis is associated with high morbidity and mortality rates; most survivors of advanced stages have permanent disabilities: blindness, deafness, paraplegia, and mental retardation. Early diagnosis and treatment can result in great outcomes. We present a 12-month old infant with tuberculous (TB) meningitis diagnosed due to persistent fever. A 12-month healthy female presented with 2 weeks of fevers, cough and emesis. In the emergency room she was alert, active, but wheezing, tachypneic and hypoxic. She developed seizures, so CSF obtained consistent with meningitis: WBC 397 cells/mm3, RBC 60 cells/mm3, protein 221 mg/dl and glucose of 43 mg/dl. Ceftriaxone and vancomycin was started empirically. PCR for influenza was positive and a CXR with left upper lobe infiltrate, so oseltamivir was begun. On hospital day (HD) 4, MRI brain showed basilar meningitis and cerebritis involving inferior left frontal and temporal lobes. She remained febrile without clinical improvement and negative CSF bacterial cultures, so on HD 6, CSF was repeated showing worsening indices: WBC 251, RBC 43, protein 260 and glucose of 29. TB was suspected due to lower CSF glucose and positive tuberculin skin test. Further epidemiological inquiry revealed a history of contact with family members in Honduras treated for TB. A final lumbar puncture was performed on HD 8 prior to starting antituberculous drugs showing WBC 223, RBC 15, protein 225 and glucose 22. Gastric aspirates and CSF cultures returned positive for Mycobacterium tuberculosis complex. After initiation of antiTB therapy she became afebrile and clinically improved except for development of right-sided hemiparesis. At discharge on HD 17, hemiparesis was improving. She completed an 18-month therapy course. While her MRI still showed abnormalities, she was clinically developing well without deficits. Persistent fever despite antibiotic therapy, presence of basilar meningitis and worsening CSF indices, particularly low CSF glucose, in a patient with family from an endemic country should raise suspicion for TB meningitis. As our patient made a full recovery, our report illustrates the importance of early diagnosis and treatment of TB meningitis.
215 INTRAVENOUS IMMUNOGLOBULIN THERAPY FOR SEVERE CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA
Panchavati PK2, Hassoun A1. 1 Alabama Infectious Diseases Center, Huntsville, AL and 2 Huntsville Hospital, Huntsville, AL.
Purpose of Study: Clostridium difficle Associated Diarrhea (CDAD) is the most common cause of hospital acquired diarrhea especially in elderly patients and those with impaired antitoxin response. Severe CDAD can be associated with significant morbidity and mortality even with the use of recommended therapy. We report our experience with use of Intravenous Immunoglobulin (IVIG) in severe CDAD.
Methods Used: Retrospective chart review
Summary of Results: Retrospective chart review of seven patients with severe CDAD treated with IVIG from October 2007 to February 2013, three females and four males. The mean age was 78.16 (range, 71-89) years, with mean hospital stay of 13.83 (range, 4-31) days. All patients were diagnosed with CDAD by fecal Clostridium Difficile toxin by polymerase chain reaction (PCR) and severe cases was diagnosed with more than 15 episode of Diarrhea per day, organ dysfunction and significant leukocytosis. Most common presentation was Diarrhea, and hypotension with 70% of patients been on pressers. Most common co-morbidities were diabetes mellitus and malignancy. Most common risk factors were antimicrobial therapy and immunosuppressive. Mean WBC was 32.58 (range 22.31-46.97), while renal insufficiency was present in 66.6%, with mean serum Cr of 2.18 (range 1.6-4.3), none of them had megacolon. All patients received Metronidazole (500 mg PO TID) for mean 7 (range 4-11) days before the IVIG infusion as well as Vancomycin (125 mg PO daily) before and after the IVIG infusion for mean 15 (range 2-20) days, however two of them received additional treatment, one received Rifaximin (200 mg PO TID) and Fidoxamicin (200 mg PO BID) for total 4 day and 8 days respectively. All patients received one dose of IVIG of (400 mg/kg) and had significant resolution of symptoms including diarrhea within 2-4 days. Leukocytosis resolved within 4 days and renal insufficiency return to baseline in all of them within 7 days. Only one patient (16.6%) had recurrence of the CDAD after 6 month and none of them needed surgical intervention. None of the patient had any associated toxicity with IVIG.
Conclusions: Intravenous immunoglobulin is a useful adjuvant therapy for the treatment of severe Clostridium Difficile Infection, further studies needed to confirm its benefit.
216 INHIBITION OF TOXIN PRODUCTION IN STAPHYLOCOCCUS AUREUS KERATITIS
Patel R2,1, Bierdeman M1, Arana A1, O’callaghan R1. 1 University of Mississippi Medical Center, Jackson, MS and 2 University of Mississippi Medical Center, Jackson, MS.
Purpose of Study: Staphylococcus aureus, the most common cause of eye infections, presents challenging antibiotic resistance and secretes multiple damaging toxins. Killing these bacteria does not arrest the activity of the previously secreted toxins and there is no drug that can stop these toxins from damaging tissue. Mediating the greatest ocular damage is α-hemolysin, a secreted protein able to lyse cells and cause apoptosis. The present study hypothesizes that a flavonoid, able to inhibit α-hemolysin production in vitro, can be developed into a formulation able to arrest toxin production in the S. aureus infected cornea.
Methods Used: S. aureus (strain 8325-4) was grown overnight in tryptic soy broth with or without the flavonoid (500 mg/mL). Each culture supernatant was quantitatively assayed for toxin-mediated hemolysis of rabbit erythrocytes. To test the inhibitor in vivo, S. aureus (100 CFU) was injected into corneas (n = 4 per group) of anesthetized rabbits and the inhibitor or its vehicle was topically applied. Damage was quantified by grading seven ocular parameters on a scale of 0 to 4 and adding the grades to obtain a slit lamp examination score (SLE).
Summary of Results: The results of this study show that the inhibitor reduces toxin production in vitro by >1,000 fold. However, the SLE scores (P = 0.58) and epithelial erosion area (P = 0.10) from this study were not statistically different from the control group.
Conclusions: The in vitro data provides evidence that the flavonoid decreases the production of the cytolytic toxin. The in vivo data demonstrates that the decrease in α-toxin production did not significantly reduce S. aureus keratitis pathology in the rabbit eyes. However, the corneas were injected with 1,000 CFU rather than 100 CFU (10-fold increase). More studies are needed to correctly assess the treatment’s affect on 100 CFU injections and furthermore, to enhance the in vivo effectiveness of the toxin inhibitor
217 A CASE OF THE NO FUN FUNGI
Patel R2, Grover I1. 1 University of Mississippi Medical Center, Jackson, MS and 2 University of Mississippi Medical Center, Jackson, MS.
Case Report: The incidence of spontaneous pneumothorax (SP) in Acquired Immunodeficiency Syndrome (AIDS) patients is 2-7 per 1,000 person-years [4,6]. The frequency of pneumothorax complicating Pneumocystis carnii is approximately 5%-10%. We report a case of 43-year-old African-American male with a history of Hepatitis C, HIV/AIDS and non-compliance with HAART regimen who presented with productive cough and hemoptysis for two weeks and associated fevers, chills, chest pain and shortness of breath. The patient was empirically started on Bactrim and steroids for presumed Pneumocystis carnii pneumonia (PCP). The patient underwent bronchoscopy with bronchoalveolar lavage that was positive for PCP. The patient experienced an acute shortness of breath approximately 12 hours following the procedure and imaging showed development of a large left tension pneumothorax that resolved with chest tube placement. The patient then developed another acute episode of shortness of breath, tachycardia and tachypnea 24 hours after removal of the chest tube. Imaging showed a new left apical pneumothorax. The second pneumothorax resolved with 100% non-rebreather mask. Data supports that current or previous PCP increases the rate of pneumothoraces in AIDS patients. Furthermore, mortality rate increases linearly with recurrent pneumothoraces. The overall mortality rate of patients with pneumothorax in AIDS is approximately 34% (range between 10% and 81%) [3,4,5]. Early recognition and treatment of the underlying PCP is the key in decreasing mortality.
218 UNUSUAL INFECTION IN A REPAIRED HEART
Powner JT1,2, Gallaher T1,2, Powner JT2,1. 1 Georgia Regents University, Augusta, GA and 2 Charlie Norwood VAMC, AUGUSTA, GA.
Case Report: A 57 year old male with congenital transposition of the great vessels, mitral and tricuspid bioprosthetic valves, atrial fibrillation on coumdain, congestive heart failure, two previous cerebrovascular accidents, and dual chamber pacemaker presented to an outside hospital with bleeding and a supra-therapeutic INR. He was admitted for anemia and hypotension complicated by acute kidney injury due to hypoperfusion, recurrent fever and leukocytosis. He was initially started on levofloxacin for a possible pneumonia. Two sets of blood cultures at the sending hospital were positive for diphtheroids. After transfer, again two sets of blood cultures drawn from different sites again diphtheroids. A transesophageal echocardiogram revealed vegetations on his prosthetic mitral valve. Listeria monocytogenes was later identified from his blood. After discussion with the patient, he revealed that he had been eating soft cheeses.
The patient received intravenous vancomycin until the identification of Listeria. He was then switched to intravenous ampicillin and gentamicin and treated for a total of six weeks. He declined all surgical intervention, and is doing well as of 2 months of follow up.
Infective endocarditis is usually caused by Streptococcus, Enterococcus or Staphylococcus. The microorganism Listeria monocytogenes is a rare cause of infectious endocarditis. Listeria monocytogenes is an aerobic gram-positive rod that causes self-limited febrile gastroenteritis in healthy patients, but can cause more severe disease in pregnant, neonatal, immunocompromised or elderly populations. Listeriosis can be a highly fatal infection due to the difficulty in the diagnosis and patient populations usually susceptible to Listeria monocytogenes. Listeria endocarditis is a complication of listeriosis and can also occur as a single infectious entity. Mortality has actually been decreasing, but historical mortality rates are 35%. There may even be certain Listeria monocytogenes strains that have increased ability to infect cardiac tissue. Treatment of choice is ampicillin and gentamicin, but other case studies report using linezolid or linezolid and trimethoprim/sulfamethoxazole with success. Valve replacement is recommended in valve dehiscence, cardiac failure, or cardiac abscess.
219 BIRDS OF A FEATHER: A CASE OF DISSEMINATED YERSINIA ENTEROCOLITICA INFECTION IN A PREVIOUSLY HEALTHY FEMALE
Pryor J, Macariola D. East Tennessee State University, Johnson City, TN.
Case Report: A previously healthy 7 year old female presented with cellulitis of the scalp. The patient noticed a small, “pimple-like” area on her scalp associated with pain that was first observed 3 weeks prior to admission. On further questioning, it is revealed that an unidentified flying animal defecated on her head 2 days before the initial pain and lesion were noticed. 4 days prior to admission a wound culture was obtained at her pediatrician’s office, and she was empirically treated with clindamycin. Physical exam was notable for a 2 cm raised ulcer with an eschar and a small amount of purulent drainage on the scalp with cellulitis, bilateral tender posterior auricular lymphadenopathy, and fever. She was started on IV vancomycin and ceftriaxone with oral TMP-SMX and topical gentamicin. On hospital day 2, her previous wound culture returned positive for Yersinia enterocolitica. Vancomycin was discontinued. Despite appropriate therapy, she remained quite ill with intermittent fevers and painful lymphadenitis, so Gentamicin was added. Due to the development of an urticarial rash, TMP-SMX and ceftriaxone were discontinued and IV ciprofloxacin was started. Symptoms continued to improve, and cervical lymph nodes spontaneously drained. Hospital blood cultures were repeatedly negative. The patient was discharged on day 8 with IV gentamicin and ciprofloxacin.
Yersinia, a Gram-negative bacillus, can cause differing degrees of illness that ranges from gastroenteritis to serious systemic infections. Septicemia has most commonly been seen in children and infants with iron overload and various hemoglobinopathies. Common risk factors for infection include consumption of chitterlings (pork intestines) and contaminated food and water. Yersinia has been isolated in the feces of various bird species such as pigeons. Signs and symptoms of infections may include diarrhea (possibly bloody), leukocytosis, mesenteric adenitis, fever, liver/spleen abscesses, and reactive arthritis. Infection is treatable with TMP-SMX, gentamicin, and 3rd generation cephalosporins. Though other common organisms are often responsible for cellulitis, Yersinia should be considered, especially if contact with birds is noted, as disseminated infection may occur.
220 HIV-ASSOCIATED HODGKIN LYMPHOMA:BEATING THE ODDS
Reske T, Loch M, Ruiz MA, Parsons C. LSU, New Orleans, LA.
Case Report: HIV-associated Hodgkin Lymphoma (Ha-HL) is a non-AIDS defining malignancy. Compared to the general population HIV patients have a 14 times higher incidence to develop HL. Ha-HL is found in patients with moderate immunologic impairment.
We present a 49 year old female, who was diagnosed 11 years prior with HIV. She was on and off ART, when she presented 9 years later with weight loss and lymph adenopathy. A LN and BM biopsy confirmed classical HL (CD4 752 cells/mm3/ viral load 190 copies/ml). A PET scan showed diffuse LNs and BM uptake. She was diagnosed with stage IV HL (IPS 3). At the time of diagnosis she started to be compliant with her ART and was started on ABVD chemotherapy. After 2 cycles she developed SOB and was diagnosed with low DLCO. Following this treatment related complication she developed ongoing pulmonary mycobacterium infections that precluded her from restart of therapy. A PET scan 2.5 years after diagnosis showed complete resolution of her disease.
Ha-HL presents commonly as advanced stage disease. Classical HL with mixed cellularity or lymphocyte depletion is the most common variant in Ha-HL. This differs from HL in the general population. Co-infection with EBV is found in almost all HIV patients, whereas only in 1/3 of non-HIV infected individuals. Chronic antigen stimulation provoked by the HIV virus is felt to lead to clonal cell expansion and promote lymphoma emergence. Introduction of antiretroviral therapy (ART) has altered outcomes in HIV-HL significantly. Before ART the median OS was 15 months. A recent prospective trial showed a 90.7% OS after 4 cycles of ABVD chemotherapy+/- radiation or 8 cycles of BEACOPP. Treatment is complicated by drug to drug interactions and treatment related toxicities. Even though literature reports improved outcomes in HIV HL patients, biology and response to therapy remain at question. Micro environmental changes provoked by the HIV and co-EBV infection continue to be part of ongoing study. Our patient’s response to only 2 cycles of chemotherapy appears to beat the odds of appropriate therapy for optimal survival based on recent prospective trials. Mechanism of disease and tailored treatments continue to be poorly understood and need continued investigation. The question remains on how to appropriately characterize individuals that require less aggressive treatment.
221 HYPERBARIC OXYGEN THERAPY IN THE TREATMENT OF REFRACTORY OSTEOMYELITIS IN THE PEDIATRIC PATIENT
Sexton TD, Jubran I. University of South Alabama, Mobile, AL.
Purpose of Study: To present a case series of novel treatments of chronic osteomyelitis refractory to traditional antibiotic therapy in pediatric patients and to discuss the therapeutic benefits of hyperbaric medicine in refractory osteomyelitis.
Methods Used: A case series of four patients ranging 11 to 18 years old were given hyperbaric oxygen therapy for refractory osteomyelitis. MRI showed osteomyelitis in all of these cases. Intravenous antibiotics were initiated in these patients. Wound debridement/drainage was done when indicated. This management was continued for six weeks with worsening CRP and ESR per protocol this led to hyperbaric therapy treatments. US Navy Table 66 consisted of 90 minute treatments, 5x’s/week. Within weeks the CRP and ESR dropped. ESR, CRP and MRI results were followed throughout treatments.
Summary of Results: All patients were on the USN Table 66 mentioned protocol, All patients were started on culture directed antibiotic therapy that included cephalosporin and aminoglycosides. Prior to these Hyperbaric treatments every patient in this case series presented with CRP> 24.0 and ESR > 120 and after these treatments were conducted, significant improvement in MRI images and CRP/ESR were seen. Averagge CRP/ESR on discharge was 1.1mg/dl and 35mm/hr. respectively. Every patient had complete resolution of Osteomyelitis.
Conclusions: When children present with osteomyelitis conservative management of antibiotics and wound care should begin. With little improvement after 6 weeks or the osteomyelitis is refractory, adjunctive HBOT should be considered. Refractory osteomyelitis that persists or recurs presents a high probability of morbidity or mortality. Using these increased pressures; Hyperbaric oxygen delivery can ameliorate both acute and chronic sources of ischemia. The decreased oxygen tensions in bone and tissue typically associated with bony infections can be returned to normal or above normal levels while undergoing HBOT. HBOT shows considerable synergistic effects when partnered with aminoglycosides and cephalosporins
222 NEUROSYPHILLIS IN A PENICILLIN-ALLERGIC PATIENT
Smith M, Gendusa P, Coleman R, Engel LS, Thien P. LSU Health Sciences Center, New Orleans, LA.
Case Report: Neurosyphilis, caused by infection fo the brain by Treponema pallidum, can be classified as early or late forms. Early neurosyphilis is more common and can be asymptomatic or cause meningitis, cerebral arteritis, or ocular disease. Late neurosyphilis can manifest as general paresis or tabes dorsalis. The diagnosis is made with CSF studies. Current preferred treatment is Penicillin G.
CASE: A 68 year old African American man presented with an extensive history of progressive lower extremity weakness and dementia. Initially the patient was able to ambulate without assistance, and then in sequential order required crutches, cane, walker and finally he has been wheelchair bound for the past three years. He required assistance with all activities of daily living including transfers to and from his wheelchair. Previous medical records revealed a serum RPR titer of 1:132. He underwent a lumbar puncture and his CSF was positive for FTA/ABS. CSF protein was elevated at 63mg/dl, and CSF VDRL was nonreactive. The patient had a history of a penicillin allergy so penicillin desensitization was undertaken in the intensive care unit. He successfully received three days of intravenous penicillin in the hospital and was discharged home completion of IV penicillin therapy.
DISCUSSION: Neurosyphillis should not be discounted in a patient with a negative CSF VDRL; the false negative rate approaches 30%. Patients with a penicillin allergy may ceftriaxone or high dose doxycycline may be used to treat patients with penicillin allergy but data is limited and titers should be closely monitored if using these therapies. Patients who do not respond to the alternate therapies may be candidates for penicillin desensitization. Of note, there are no current controlled trials on the efficacy of the penicillin therapy. Recommendations are based on penetrance of antibiotics into the CSF.
223 IS AZITHROMYCIN MODULATING INFLAMMATION VIA TOLL LIKE RECEPTOR (TLR) PATHWAYS IN GROUP B STREPTOCOCCUS (GBS) SEPSIS?
Upadhyay K1, Meals E1, English B2, Talati AJ1. 1 CFRI, UTHSC, Memphis, TN and 2 Michigan State University, Grand Rapids, MI.
Purpose of Study: Combination of ampicillin(AMP) and azithromycin(AZM) improved clinical signs, mortality and cytokine levels in our mouse model of GBS sepsis. We proposed to study if the effect of AZM in modulation of inflammation is secondary to bacterial factors[using AZM resistant strain(AZR) of GBS] or host factors[using MyD88-/-, TLR9-/-, TLR2-/-mice].
Methods Used: Swiss Webster mice (wt 18g, age 3 wks) were injected intraperitoneally (IP) with AZR GBS Ia (log 7-8 cfu/ml) and MyD88-/-, TLR9-/- mice (wt 15 gm, age 3 wks) were injected with GBS Ia (log6 cfu/ml). Mice were divided in 4 groups(grp). Grp 1 -no antibiotics, grp 2- treated with AMP(100mg/kg/d; MIC ⩽0.25 mcg/ml), grp 3- treated with AZM (10 or 50mg/kg/d; MIC 16ug/ml for AZR GBS and MIC ⩽0.125ug/ml for AZM sensitive strain ) and grp 4- treated with AMP+AZM. Antibiotics were administered q24h IP. Mice were monitored using “clinical sepsis score (CSS)”. Mice were sacrificed at 120h and blood was obtained for later cytokine assay.
Summary of Results: For AZR GBS experiment; case fatality rate was found to be 100% in grp 1 and grp 3; 50% in grp 2 and 0% in grp 4. Mean serum TNF-α was lower in grp IV(246±67 pg/ml) compared to grp 1 (6952±701 pg/ml), grp 2 (7209±1826 pg/ml) and grp 3 (5980±626 pg/ml) (p⩽0.05) The CSS was significantly lower in grp 4 compared to other grps (fig). Also the case fatality rate was 100% in grp 1; 50% in grp 2 and 0% in grp 3 and 4 using MyD88-/- mice. However, no difference was seen in mortality among TLR9-/- mice. Similarly, the CSS was significantly lower in grp 3 and grp 4 compared to grp 1 and grp 2 in MyD88-/- mice but no significant difference was seen in TLR9-/- mice.
Conclusions: The effect of AZM in modulation of inflammation may be related to TLR9 and is seen even in mice infected with AZR GBS.
Medical Education, Medical Ethics and Advocacy Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
224 EMBRACING THE GREY: ADVOCATING FOR PATIENTS WHEN THE STORY AND THE SCIENCE DON’T ADD UP
Burge L, Shropshire DL. University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Skeletal fractures in children less than 1 year of age are concerning for child abuse. Fractures that are unaccompanied by a reasonable trauma history usually result in further medical evaluation and a referral to Child Protective Services (CPS).
Our patient is a 2 month old breast-fed, African American female who reported to the ED after being seen by her PCP for acholic stools and direct hyperbilirubinemia. HIDA scan was consistent with biliary atresia, and the patient was admitted for further testing and treatment. A chest xray demonstrated multiple healing rib fractures. A full skeletal survey revealed an acute corner fracture involving the distal left ulna and a concern for a second fracture involving the distal right femur. There was no evidence of brain injury or retinal hemorrhage. CPS was notified of the concern for child abuse given the xray findings, and the patient and her siblings were placed in emergency foster care. A social evaluation of the family did not reveal previous reports of abuse, neglect, or other familial risk factors.
The patient underwent a Kasai procedure but was unexpectedly found to be profoundly hypocalcemic postoperatively and required IV calcium supplementation. Further evaluation revealed low levels of Vit. D and elevated PTH; therefore, the patient was started on Vit. D and calcium supplementation. This case spurred a spirited debate among physicians as to the cause of the fractures. The radiology literature contains a few case reports of children with Vit. D deficiency and fractures. but these are disputed by most child abuse experts. However, this particular child is more medically complex than a typical infant with Vit. D deficiency. Ultimately, due to the medical uncertainty and clean social history, the child was reunited with her parents.
The physical signs of child abuse can be found in certain uncommon medical conditions. Usually the combination of medical and social facts provides the diagnosis; however, at times the answer is unclear. It is in these times we must be willing to embrace the uncertainty of medicine and advocate for our patients and their families.
Pediatric Clinical Case Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
225 DON’T JUST ASSUME INFECTION: A CASE OF NONINFECTIOUS CERVICAL LYMPHADENOPATHY
Adimora-Nweke D, Freeman B. Tulane University SOM, New Orleans, LA.
Case Report: A 9 year-old girl with history of right neck swelling previously treated with antibiotics represented one week later with fever, new left-sided neck pain and swelling. She denied sore throat, stridor, dysphagia, animal exposure, recent travel, weight loss and night sweats. Her exam showed an indurated and tender left neck mass.
CBC showed neutrophil-predominate leukocytosis. CRP was elevated. Throat culture, monospot, and PPD were negative. CT showed left sided cervical lymphadenopathy. Surgical debridement was performed and she was empirically re-treated with antibiotics. Lymph node biopsy returned with diagnosis of Sinus Histiocytosis with Massive Lymphadenopathy. She was treated with steroids and her cervical adenopathy improved.
Cervical lymphadenopathy (LAD) is a common pediatric complaint and can be categorized into infectious and noninfectious causes, with infectious causes being more common. Infections include viral respiratory illness, oropharyngeal infections, bacterial adenitis, EBV, CMV, tuberculosis, and cat scratch disease. Noninfectious causes include leukemia, lymphoma, connective tissue disease, autoimmune diseases, and histiocytosis.
Rosai Dorfman Syndrome (Rd), also known as Sinus Histiocytosis with Massive Lymphadenopathy, is a noninfectious cause of cervical LAD. This disorder may present with unilateral or bilateral tender cervical LAD and is often misdiagnosed leading to mismanagement with antibiotics, excessive imaging, and debridement.
Laboratory examination for Rd includes CBC, CMP, urinalysis to assess vital organ involvement. ESR, ferritin, and serum gammaglobulins are usually elevated. Diagnosis is made via nodal fine needle aspiration or excisional biopsy. Histopathology shows distinctively large histiocytes with abundant pale cytoplasm and phagocytosed lymphocytes.
Rosai-Dorfman most commonly affects the cervical lymph nodes, however extra-nodal disease occurs in up to 43% of affected patients. Imaging such as ultrasound, CT, and MRI are used to determine disease extent in patients with systemic symptoms. Patients with vital organ compromise or nodal disease with complications require therapy. Treatment options include excisional biopsy, debulking procedures, radiotherapy, corticosteroids, and chemotherapy agents.
226 1Q21.1 DELETION SYNDROME:FURTHER EVIDENCE OF PHENOTYPIC VARIABILITY
Almannai M, Martinez J. University of South Alabama Children’s & Women’s Hospital, Mobile, AL.
Case Report: Deletions of chromosome 1q21.1 have been associated with intellectual disability, microcephaly,and varieties of congenital anomalies and dysmorphic features. We report four children with 1q21.1 chromosomal deletion who presented with diverse clinical manifestations suggesting that this genomic imbalance does not offer a specific clinical phenotype.
Case#1: A male child presented at 19 months with FTT, dysmorphic features and speech delay. He has history of hypospadias and hypoplastic proximal radii bilaterally. He has a 1.06 MB deletion that overlaps with the TAR region.
Case#2: A male ascerteined at 20 months of age because of developmental delay, abnormal behavior, and dysmorphic features. He has periorbital swelling, thick lips, puffy cheeks, and joint laxity. He has Ebstein anomaly and was initially suspected to have Williams Syndrome. Family History was positive for intellectual disabilities. He was found to have a deletion of 1.1 Mb in size. No parental genetic testing was done.
Case#3: A 33 months old Boy with autisim. He presented with microcephaly and language delay. He had no associated anomalies or dysmorphic features and the family history was negative. He has a deletion of 2.4 Mb in size.
Case#4: A 10 years old male presented with developmental delay and learning difficulties. He is overweight and has dysmorphic features(See table). Later he developed goiter. His father has intellectual disabilities, but no parental testing was done. He was found to have deletion of 1.23 Mb in size.
Conclusion: 1q21.1 genomic region is extremely complex. Patients with deletions are more common than those with a reciprocal duplication of this region and most affected patients have a deleted region that spans 1.35 Mb. Our experience confirms that although 1q21.1 microdeletions are associated with human disease, the broad range of clinical manifestations prevent its characterization as a syndromic entity. In addition, no genotype-phenotype correlation could be established, further complicating genetic counselling in these families.
227 TESTICULAR ADRENAL REST TUMORS IN TWO SIBLINGS WITH CONGENITAL LIPOID ADRENAL HYPERPLASIA
Alsaheel A1, Roth C2, Congeni J3, Vargas A1. 1 LSUHSC, New Orleans, LA; 2 LSUHSC, New Orleans, LA and 3 Children’s Hospital, New Orleans, LA.
Case Report: Introduction: Congenital lipoid adrenal hyperplasia(CLAH) is a rare and the most severe form of adrenal hyperplasia, frequently caused by mutations in the steroidogenic acute regulatory protein (StAR)gene. Patients with CLAH typically present with adrenal crisis in early infancy and those with a 46,XY karyotype have female genitalia due deficient fetal sex steroid synthesis. Recently it has been recognized that the phenotype can be quite variable due to partial activity of StAR mutations(non-classical). Adrenals and testes share common embryological origin and the testes harbor nests of adrenal cells susceptible to ACTH stimulus.
We report two French brothers whom had been diagnosed with CLAH(mutations in p.Gly221Ser, p. Arg53Leu, p. Arg188Cys of StAR gene) with normal male genitalia presented with testicular adrenal rest tumors (TARTs).
Case A: A 14 year old Caucasian French boy, diagnosed with CLAH at age 2 years, presented with mild testicular discomfort and negative history for trauma, fever or genitourinary symptoms. He had a similar episode six months earlier. Testicular ultrasound (U/S) showed two lesions in each testicle, largest one in the left testis 2.6×3.6×1.7 cm. Hormonal studies showed elevated ACTH and PRA; tumor markers were negative. Hydrocortisone dose was adjusted up 18 mg/m2/day, encouraging adherence to medication. Follow up U/S showed diminishing tumor size.
Case B: The 15.5 year old brother was first diagnosed with CLAH at age 1.5 y. Screening testicular U/S showed solid masses bilaterally; largest one was in the right 1.0 × 0.8 ×1.1 cm. Hormonal studies showed elevated ACTH and PRA. Hydrocortisone was adjusted up 16 mg/m2/day and like his brother the TARTs showed improvement in follow up U/S.
Conclusion: To our knowledge this is the first report of two brothers being affected by non-classical CLAH and TARTs. It expands the current knowledge of the disease and its variable presentations. It also emphasizes the importance of testicular U/S screening for early diagnosis and management of TARTs.
228 NEONATAL AORTIC THROMBOSIS
Astrug L. 1 UT Southwestern Dallas - Childrens Medical Center Dallas, Dallas, TX and 2 UT Southwestern Dallas - Parkland Hospital NICU, Dallas, TX.
Case Report: Coagulation issues in neonates are rare. Sources of thrombosis can be due to abnormal anatomical features of vasculature, central line complications, or coagulation disorder. Much is unknown regarding etiology/location of thrombosis given its low incidence rates and limited literature. There have been reported cases of neonates with aortic arch thrombosis with unstable clinical presentations like seizures or cardiac disease symptoms. Unlike previously reported cases, this neonate did not present with hemodynamic instability, signs of cardiogenic shock or seizures. Born at 34 weeks EGA, the infant had partial systemic color change and lacked palpable femoral pulses in the first minute of life. The infant’s father and kin have a strong history of thrombotic disease. An exact diagnosis and etiology remains unknown despite extensive hematologic evaluation. On initial examination, the neonate had partial color change with a clear demarcation line superior to the umbilicus that horizontally transcribed across the lower abdomen; superiorly pink, inferiorly pale. The femoral and pedal pulses were not present on palpation. After ruling out coarctation of the aorta with an emergent echocardiogram, an abdominal/pelvic sonogram with Doppler studies revealed an aortic thrombus that spanned from the abdominal aorta into the common iliac arteries, only partially obstructing blood flow. After full body surveillance sonography, no additional thrombi were found. Head ultrasound was normal. The infant was treated with heparin and transitioned to aspirin therapy. Prior to discharge, abdominal and pelvic MRA demonstrated complete dissipation of the abdominal thrombus without any further clot formation. This case is significant due to minimal presenting clinical symptoms and questionable timing of thrombosis occurrence. Presentation at birth with minor perfusion difficulties suggests that the thrombus had formed in utero. There were no anatomical abnormalities or complications consistent with prolonged decreased blood flow, suggesting that the thrombus likely formed later in fetal life. Besides partial color change, the neonate did not present with any other symptoms. Aortic thrombosis can be extremely detrimental, increasing morbidity and mortality if not diagnosed immediately.
229 OXYGEN REQUIREMENTAS A SCREENING TOOL FOR THE DETECTION OF LATE PULMONARY HYPERTENSION IN EXTREMELY LOWBIRTH WEIGHT NEONATES
Aswani R1, Hayman L1, Nichols G1, Isshiki G1, Luciano A1, Amankwah E2, Leshko J2, Dadlani GH2,1. 1 University of South Florida, Tampa, FL and 2 All Children’s Hospital- Johns Hopkins Medicine, St. Petersburg, FL.
Purpose of Study: Many Extremely Low Birth Weight(ELBW) neonates develop Pulmonary Hypertension (PH) late in their clinical course and over 60% go undetected by early screening echocardiography.The signs of PH are subtle and may be masked by underlying broncho-pulmonary dysplasia(BPD). No standardized screening protocol exists for the detection of late PH. The Purpose of this study is to assess the utility of oxygen supplementation as a predictor of late PH in ELBW neonates.
Methods Used: A retrospective single center review of 230 ELBW neonates surviving more than 30 days between January 2008 to December 2011 was performed.Logistic regression was used to estimate odds ratio(OR) and 95% confidence intervals(CI) for the association between oxygen supplementation and the diagnosis of PH.
Summary of Results: The incidence of late PH was 8.3%(19/230). Unadjusted logistic regression analysis revealed that compared to neonates with oxygen supplementation<30%, neonates requiring oxygen supplemental ≥30%had an increased risk of developing PH (OR=3.77, 95% CI=1.42-10.00, p=0.008). After adjusting for birth weight, the elevated risk attenuated and was of borderline statistical significance (OR=2.47, 95% CI=0.89-6.84, p =0.08). Receiver operating characteristic curve analysis showed an area under the curve of 0.69.
Conclusions: The need for oxygen supplementation ≥30% at day of life 30 may be a good screening tool for detecting late PH in ELBW neonates.
230 FIRST REPORTED CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS PRESENTING AS VENO-OCCLUSIVE DISEASE IN A LEUKEMIA PATIENT
Barros T, Gratias E. UT Chattanooga, Chattanooga, TN.
Case Report: Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory disorder. There are many reported cases of HLH in bone marrow transplant (BMT) leukemia patients, and a known association between HLH and hepatic veno-occlusive disease (VOD). There are only scattered cases of severe VOD in non-BMT oncology patients, and none associated with HLH. This is the first reported case of fatal HLH presenting as severe VOD in a non-BMT acute lymphoblastic leukemia (ALL) patient.
Case: 18 year old female with existing autoimmune disease was diagnosed with ALL. During chemotherapy she was admitted for zoster encephalitis and developed platelet refractoriness, encephalopathy, and sudden clinical deterioration. Laboratory/radiographic evaluation identified macrophage activation syndrome and VOD. Bowel sloughing and abdominal distension prompted an exploratory laparotomy and liver biopsy which confirmed histologic HLH. The patient eventually succumbed to fulminant HLH despite receiving optimal therapy.
Discussion: HLH is a rare histiocytic reactive process due to mutations in the perforin, MUNC13-4, or syntaxin 11 genes, or secondary to malignancy, infection, or autoimmune disease. The predominant symptoms are fever and organomegaly. Lab testing reveals abnormalities in blood counts, liver function, fibrinogen, lipids, albumin, and electrolytes. HLH is most commonly a secondary process rather than a primary disease. There are two reported cases of familial HLH progressing to acute leukemia, one heterozygous for MUNC13-4 and the other with reduced natural killer (NK) cell function and perforin expression. This patient had potential HLH triggers that were both infectious and autoimmune without any genetic predisposition to HLH.
Conclusion: Severe VOD can be a presenting sign of HLH in a non-BMT oncology patient. Early initiation of HLH-specific therapy may decrease morbidity and mortality risk for these patients.
231 SACROCOCCYGEAL TERATOMA WITH MULTIPLE RECURRENCES BY INTRADURAL EXTENSION IN THE NEONATE
Bechtel AS1, Gauger CA2. 1 University of Florida Jacksonville, Jacksonville, FL and 2 Nemours, Jacksonville, FL.
Case Report: Sacrococcygeal teratomas are one of the most common tumors of the newborn, and the most common site of germ cell tumors. These can be classified by the Altman classification which breaks them in to four types (Table 1). These can be complicated by relapse, as well as, on rare occasions, growing teratoma syndrome (GTS). GTS is defined as an enlarging mass during or after chemotherapy with normal serum markers. Recurrence, does occur, but to our knowledge multiple recurrences are seemingly rare, and even more so, via intradural extension. While this case did not fit criteria for GTS, these multiple recurrences were also unique as they were distant from the original site. This case will discuss the presentation of a preterm infant, prenatally diagnosed with a sacrococcygeal teratoma. Her initial presentation and course, from newborn to two years of age. This included multiple recurrences in varying sites, multiple histological types and both medical management via chemotherapy and surgery. Review of this case gives insight into the differing presentations of recurrence and a more complex course, as well as the importance of strict, regular and prolonged follow-up.
232 PEDIATRIC EDUCATION FOR PATIENTS WITH SICKLE CELL DISEASE
Bluett-Mills GM1, Garry C2, Chiu M2, Chavan R1. 1 Tulane University, New Orleans, LA and 2 Tulane University, New Orleans, LA.
Case Report: The following was presented in longer form at an educational day aimed at patients with Sickle Cell Disease (SCD) and their family members. The case is an amalgamation of multiple patients.
S is the first baby born to his parents. When he is a day old, a sample of blood is taken for a newborn screen and sent to a state lab, where he is diagnosed with sickle cell disease (SCD).
S and his parents are sent to a hematologist, where they learn that both his parents are carriers with one normal hemoglobin gene and one sickle gene. If they have another child together, there is a 25% chance that their next child will have SCD. At this first visit S is started on PCN prophylaxis. He has more blood work drawn during the first year of life that shows he has HbSS, the most common and severe form of SCD.
At six months old, S has lower levels of hemoglobin that other children his age.
At nine months old, S’s parents notice pain and swelling of the fingers of his right hand. He is treated at home for dactylitis.
At twelve months old, S has a fever. He is taken to the emergency room, where blood cultures are drawn and he is given antibiotics.
At three years old, S is more tired than usual and pale. He is complaining of belly pain. His mother is able to palpate his spleen several centimeters below his rib. He is admitted to the hospital for splenic sequestration.
At 5 years old S has a fever. A few days later he is tired and pale. He is much more anemic than usual and not making any new red blood cells. He is diagnosed with an infection called parvovirus B19.
At 7 years old, S has his first pain crisis in his right leg. Over the year, he learns ways to try to prevent crisis, including drinking plenty of water, avoiding extreme temperatures, regular visits to his hematologist and pediatrician, and staying up to date on shots. In addition to standard shots, he makes sure to get a yearly flu shot and gets pneumovax to prevent against bacteria normally killed by the spleen.
As a child and teenager, S also gets screening and prevention for longer term effects of SCD, including yearly eye exams starting at age ten, transcranial doppler to measure of risk of stroke in children, and pulmonary function tests.
233 PERSISTENT HYPOXEMIA IN A NEWBORN: AN EARLY PRESENTATION OF NEHI SYNDROME
Bojanowski CM1,2, Messer A2, Levine S3, Beatty K2. 1 LSUHSC-NO, New Orleans, LA; 2 LSUHSC, New Orleans, LA and 3 LSUHSC, New Orleans, LA.
Case Report: Neuroendocrine cell hyperplasia of infancy (NEHI) is a recently described children’s interstitial lung disease (chILD) of unknown etiology. This is a rare disorder defined by clinical features, radiographic findings, and lung tissue bombesin immunostaining. Typical presentation includes tachypnea, hypoxia, and crackles in infants aged 1-24 months. High resolution CT (HRCT) of the chest typically reveals a characteristic pattern of ground glass opacities, most commonly in the right middle lobe and lingula as well as mosaic air trapping in the lower lung fields. However, the diagnostic gold standard is lung biopsy demonstrating increased numbers of bombesin-immunopositive pulmonary neuroendocrine cells within bronchioles and alveolar ducts without evidence of other pulmonary abnormalities. The term "NEHI syndrome" is used to indicate a diagnosis of NEHI without lung biopsy based on a consistent clinical presentation and radiographic findings. Here we describe the presentation and diagnosis of NEHI syndrome in an 11 do ex 39 WGA female born via NSVD with no significant interval history and an unremarkable neonatal course. She presented with tachypnea, subcostal retraction and hypoxia (O2 saturation of 71% on room air). Septic work up remained negative. Echocardiogram was positive only for a small patent foramen ovale. HRCT showed a fine reticulonodular pattern. She was eventually weaned to room air at two months of age. Treatment of this disease is supportive with oxygen supplementation and optimization of nutrition as the mainstays of care. Given the general good outcomes of this disease, with median duration of symptoms approximately 18 months, correct diagnosis provides ensuring prognostic information for family members.
234 NOW YOU C-PAM, NOW YOU DON’T
Bowles E DeBord J. Tulane University, New Orleans, LA.
Case Report: A three-month-old boy with a history of community-acquired pneumonia diagnosed clinically one month prior was admitted for recurrence of cough, congestion, and abnormal findings on chest radiograph. His parents described a dry cough, worse at night, which responded minimally to bronchodilators. Symptoms during the prior episode were similar, but had resolved weeks before the onset of his current symptoms. There was no associated fever, apnea, cyanosis, vomiting, diarrhea or rash. On exam, he had diffusely course breath sounds, without nasal flaring, wheeze or supplemental oxygen requirement. Labs noted leukocytosis and chest radiograph revealed a cavitary lesion in the right upper lung field and round opacities in the right middle and lower lung fields. Chest CT revealed a thick-walled cystic lesion in the right upper lobe without air fluid level, an area of consolidation immediately inferior to this, and a second area of consolidation in the right middle lobe.
Given these findings and history of pneumonia, there was concern for anatomic abnormality such as congenital pulmonary airway malformation (CPAM) versus a complication of pneumonia. After a 14-day course of antibiotics, repeat chest radiograph revealed interval decrease in size of the right middle and lower lung consolidations, with continued demonstration of the right upper lobe cystic lesion. Chest radiograph one month later showed interval resolution of the right upper lobe cystic lesion and right middle and lower lung consolidations.
CPAMs are hamartomatous lesions which originate from tracheal, bronchial, bronchiolar, or alveolar tissue. Patients may be diagnosed prenatally, in the newborn period, or remain asymptomatic until later in life. Severity of symptoms reflects the extent of pulmonary involvement. In neonates, findings include tachypnea, cyanosis and respiratory distress. Cough, dyspnea and recurrent pneumonia may be seen later in childhood. Imaging findings may include cysts with or without fluid or air, and typically involve only one lung. Up to 59 percent of cases regress prenatally. Post natal resolution is much rarer, making a pneumatocele more likely in our case. These are thin walled cysts which occur in association with bacterial pneumonia, particularly Staphylococcus aureus. Often, pneumatoceles involute spontaneously without long term sequelae.
235 COLCHICINE TOXICITY
Brennard MG, Monroe K. University of Alabama at Birmingham, Birmingham, AL.
Case Report: An 18yo female presented with acute onset of nausea and non-bloody, non-bilious vomiting thought to be due to food poisoning by the patient’s mother, but the patient quickly admitted to ingestion of her mother’s colchicine in a suicide attempt. The ingestion happened 6 hours prior to presentation. On review of systems, she also complained of blurry vision, frontal headache, sore throat, shortness of breath with intermittent sharp chest pain and slight cough. She also felt light-headed and had body aches “all over”. Vital signs were as follows: T 100.5F, HR 95, BP 113/76, RR 21, O2 sat 98% on room air. On exam, she appeared moderately ill with normal breath sounds, tachycardia and regular rhythm with no murmur. Her abdomen had hypoactive bowel sounds and tenderness at suprapubic area and right upper quadrant. She was neurologically intact but had poor effort in strength exam due to muscle aches. She was oriented with flat affect and depressed mood, but easily irritated. Initial labs revealed negative urine pregnancy test and drug screen, normal electrolytes and blood counts, normal acetaminophen and aspirin levels. Abnormal labs had elevation of transaminases, amylase and lipase, and creatine kinase. The effects of colchicine toxicity have been documented based on amount ingested and timing post-ingestion. There is a direct relationship between the amount ingested and severity of symptoms. During the first 24 hours, GI symptoms predominate with abdominal pain, vomiting, diarrhea, and nausea. This loss of fluid can lead to dehydration, electrolyte imbalance, and even hypovolemic shock. Hematologic factors may also be evident in the first stage, such as leukocytosis and coagulation factor consumption by the liver. Stage 2 is the most dangerous and lasts from about day 2 until one week after ingestion. Critical changes to organ function can lead to hepatic failure, renal failure, arrythmias, cardiogenic shock, and even acute respiratory distress syndrome (ARDS). In addition, bone marrow hypoplasia causes pancytopenia with a high risk of sepsis. If the patient survives this devastation, the third stage of toxicity brings resolution of organ failure, rebound leukocytosis, and alopecia. Our patient developed pancytopenia and required 2 weeks for full recovery of organ function, resolution of pain, and ability to tolerate nutrition by mouth.
236 EMERGENCY DEPARTMENT DIAGNOSIS OF SEVERE ORBITAL PROPTOSIS AND FUNGAL RHINOSINUSITIS REQUIRING EMERGENT ETHMOIDECTOMY
Burhop J, Clingenpeel J, Poirier MP. Eastern Virginia Medical Center, Children’s Hospital of the King’s Daughters, Norfolk, VA.
Case Report: 15 year-old male, worsening right periorbital swelling, headache associated nocturnal awakening and diplopia. Prompted to visit emergency department due to 5 days of bifrontal headache and emesis. Child admits to history of asthma treated with albuterol and inhaled steroids along with chronic nasal congestion. Child denies travel or trauma history.
A CT of the orbits and sinuses obtained along with an MRI directly from the emergency department revealing the diagnosis. Emergent ethmoidectomy, maxillary antrostomy and sphenoidotomy performed in OR. Surgical pathology and culture consistent with fungal hyphae and eosinophilic infiltration without neoplastic changes. The right eye was saved with complete restoration of vision.
With aggressive eosinophilic and IgE mediated inflammatory response, patients with history chronic sinusitis are a setup for invasive allergic fungal rhinosinusitis. Most patients are immunocompetent, with rare findings of diplopia, in additional to proptosis and headache, as was the case with our patient. The involvement of ophthalmic signs is of particular concern. Early identification in the emergency department, or acute care setting, along with aggressive surgical intervention and debulking procedures, aids in resolution of diplopia and irreversible ophthalmic damage.
237 CHYLOUS EFFUSION IN A NINE YEAR OLD
Chan J1, Gillispie M2, Demissie S3. 1 University of South Florida, Tampa, FL; 2 University of South Florida, Tampa, FL and 3 All Children’s Hospital, St Petersburg, FL.
Case Report: A 9-year-old boy presented with chest pain while playing football that resolved with rest. On exam, he was comfortable without dyspnea or distress. There were decreased breath sounds and dullness to percussion on the right side. Chest x-ray and CT thorax revealed significant amount of complex fluid filling the right hemithorax.
Chest tube placement yielded 2.5L of cloudy exudative fluid. Output had not subsided and the fluid color became milky white. Fluid triglyceride and cholesterol levels were low. On day 16, lymphoscintigraphy (Fig. 1) identified a right apical leakage point. A medium-chain triglyceride (MCT) diet was started but output persisted. On day 36, he was placed exclusively on total parenteral nutrition (TPN) and started on octreotide. On day 41, he underwent mechanical pleurodesis and ligation of his thoracic duct. Chest tube output gradually decreased and he was discharged on day 60.
The likely etiology of the effusion is trauma. Presentation is consistent with a gradual accumulation of chyle. Though his fluid analysis was equivocal for a chylous effusion, lymphoscintigraphy ultimately confirmed the diagnosis.
Management relies on a MCT diet. Persistent output may warrant exclusive TPN. Octreotide is reported as an effective adjunct. Those who fail conservative therapy need pleurodesis and/or thoracic duct ligation.
Clinicians need to recognize and initiate therapy early to reduce long-term morbidities including malnutrition, immunodeficiency, and eventual respiratory compromise.
238 METASTATIC PEDIATRIC PARATHYROID CARCINOMA: A THERAPEUTIC ROLE FOR CINACALCET
Davidson J1, Lam C2, Bahrami A2, Diaz-Thomas A1. 1 University of Tennessee Health Sciences Center, Memphis, TN and 2 St. Jude Children’s Research Hospital, Memphis, TN.
Case Report: Parathyroid carcinoma is an exceedingly rare form of primary hyperparathyroidism with an estimated prevalence of 0.005% of the US adult population. It is even more unusual in children as only ten cases have been reported. An 8-year-old African-American girl with neck pain, hypercalcemia (12.5 mg/dL), and elevated parathyroid hormone (453 pg/mL) was originally diagnosed with parathyroid adenoma. Parathyroidectomy was performed, but after multiple recurrences and escalating hypercalcemia over a period of five years, the patient’s disease was reclassified as malignant. Germline mutation analysis of the MEN1 and CDC73 genes revealed no previously described mutations. The disease eventually metastasized to the lungs, and the patient underwent palliative bilateral lung metastasectomies followed by post-operative initiation of cinacalcet. She has maintained near-normal serum calcium levels and has been symptom free for a period of 12 months. We demonstrate that cinacalcet is a safe and efficacious component of the chronic management of hypercalcemia in this setting.
240 MIDAORTIC SYNDROME IN PEDIATRIC PATIENT WITH KNOWN RENOVASCULAR HYPERTENSION
Doose M. Tulane Hospital, New Orleans, LA.
Case Report: A 5 year-old African American female presented with decreased appetite and urine output, fatigue, abdominal pain, emesis and headache. She was born full term with no complications. Family history revealed presence of hypertension of unknown etiology in both parents. Examination revealed blood pressure (BP) of 170-210/120-160 mmHg (95% of BP 110/70 mmHg), serum creatinine of 0.4 mg/dL, potassium of 2.7, bicarbonate of 24 mmol/L and trace protein in the urine. Intravenous infusion of sodium nitroprusside was initiated to manage hypertensive emergency. Additional data showed elevated plasma renin activity (PRA) of 300 ng/ml/h, consistent with renovascular hypertension. CT of the abdomen demonstrated that the left kidney was 30% smaller than the right. MAG3 nuclear scan showed decreased function of the left kidney at 15%. Angiogram demonstrated 99% stenosis of the left renal artery and slightly diminished caliber of infrarenal abdominal aorta. Following left nephrectomy, patient did not require any anti-hypertensive medications for a number of years. At follow-up clinic visit at age of 15 years, BP was measured at 155/87 in left arm and 149/70 in right arm. CT angiogram revealed a normal appearing right renal artery and a 12 cm-long narrowing of the infrarenal aorta with maximum diameter of 6-7 mm compared to proximal and distal segments, both with diameter of 11 mm. Given normal GFR, absence of symptoms or signs of inflammation, and ability to control BP with two medications, no surgical intervention was required to treat midaortic syndrome (MAS). This case illustrates association of unilateral renal artery stenosis presenting as hypertensive emergency early in life with later development of progressive symptomatic idiopathic MAS. Physicians should consider MAS in the differential diagnosis of hypertension in children. In the absence of renal dysfunction or target organ damage, medical management of MAS is feasible if BP is well controlled on two antihypertensive medications.
241 DUPLICATION 11Q22.3: CASE REPORT AND DELINEATION OF A DISTINCTIVE ENTITY
Gallois JB1, Lacassie Y2. 1 LSU Health Sciences Center, New Orleans, LA and 2 Children’s Hospital, New Orleans, LA.
Purpose of Study: With the advance of new molecular tests, new syndromes are being quickly delineated. However, new information is sometimes difficult to interpret and proves challenging to determine if it is pathogenic or represents normal variation. We report a 3-years-7-months-old girl, who presents a quite evident abnormal phenotype including developmental delay/intellectual disability, some autistic features, many dysmorphic features and dermatoglyphic findings highly suggestive of a chromosomal abnormality in which the aCGH showed a duplication 11q22.3 of 2.9 Mb involving at least 14 genes. However, the report was unclear due to the lack of published data implicating this duplication in human disease. The recent observation (personal communication and one published reference) of at least 2 other patients with developmental delay/autistic and dysmorphic features and similar duplication allow us to suggest that this duplication is pathogenic and would represent a new distinctive disorder. After this report, we believe that additional similar patients will be identified and the existence of this new entity confirmed and recognized.
Methods Used: Clinical evaluation and microarray were used.
Summary of Results: Duplication 11q22.3
Conclusions: This duplication seems to be pathogenic and represent a new distinctive disorder.
242 A CASE OF BACK PAIN AND LOWER EXTREMITY WEAKNESS PRESENTING TO THE PEDIATRIC EMERGENCY DEPARTMENT. PALLAVI GHUGE MD, MPH UNIVERSITY OF ALABAMA AT BIRMINGHAM. KATHY MONROE MD UNIVERSITY OF ALABAMA AT BIRMINGHAM
Ghuge P, Monroe K. University of Alabama at Birmingham, Birmingham, AL.
Case Report: Our patient is an 11 year old previously healthy Caucasian female who presented with inability to move her legs for the last 4-5 hours. She had one week history of bilateral leg and lower back pain that was associated with her legs falling asleep which would resolve in a few hours. She denied any trauma, URI symptoms, vomiting, bowel or bladder incontinence, upper extremity weakness, difficulty with speech, vision or swallowing. Review of systems was otherwise negative. Physical exam revealed an alert but anxious girl with stable vital signs. She had intact cranial nerves and a normal neuro exam in upper extremities. Strength was 1+ at her hips, knee and ankle, sensory exam demonstrated absent sensations from mid thigh downwards with no 2 point differentiation and absent pain sensation. Plantars were upgoing on the left but no clonus. Reflexes were intact. She was tender to palpation over her lower thoracic and upper lumbar vertebrae. Differential included mass occupying lesion, secondary metastasis, transverse myelitis, or possibly early Guillian Barre syndrome. Labs showed normal CBC, urinalysis, CMP, CRP and ESR. MRI of thoracic and lumbar spine was normal. Neurology was consulted, CSF studies were obtained which were normal. Mom mentioned that she saw a flicker of movement in the patients legs while she was in the MRI and further stated that patient had a hard time trying to adjust since the arrival of her sibling 2 yrs ago. On repeat assessment, her sensory level was not consistent with a dermatomal distribution. Gradually over the course of time in the emergency department her exam improved. She initially walked to the bathroom with assistance and later walked out of the ED on discharge with plans to follow up with neuro psychologist and a counselor.
Conclusion: In summary her findings were consistent with Conversion disorder as her neurological exam gradually returned to normal. Patients like this one can pose a medical dilemma and there is a danger of misdiagnosis without a thorough work up to look for medical and organic etiologies of the presenting symptom.
243 BRONCHOCENTRIC GRANULOMATOSIS IN A TWO YEAR OLD WITH TUBERCULOSIS
Gipson K1, Harrison E1, Price E1, Stark M2, Seybolt L1, Pepiak D1. 1 LSUHSC School of Medicine, New Orleans, LA and 2 LSUHSC School of Medicine, New Orleans, LA.
Case Report: Bronchocentric granulomatosis (BCG) is a rare histologic pattern of palisading histiocytes forming necrotizing granulomas of the distal airways centered on bronchi/bronchioles. The most common etiology is a hypersensitivity reaction to Aspergillus, with majority of cases culture positive. This pattern may be observed in other fungal, viral and mycobacterial infections. CXR of BCG may manifest as single/multiple nodules or as extensive areas of consolidation.
We present a two-year-old male with exposure to active Mycobacterium tuberculosis (TB), positive interferon-gamma release assay and positive PPD with persistent right perihilar and basilar opacification on serial CXR (Figure 1). Transbronchial biopsy of the right lower lobe showed predominately uninucleate cells with reniform nuclei forming loose palisading necrotizing granulomas, a histologic pattern consistent with BCG, and was negative for TB by cultures and special stains.
This case illustrates the histologic pattern of BCG as a complication of pulmonary TB in a very young patient. Interestingly, this child initially had difficulty taking anti-TB medications, requiring a gastrostomy tube to facilitate treatment. We propose that the child’s initial poor medication adherence may have contributed to the development of this rare complication. Considering this patient presentation, BCG should be added to the clinician’s differential when evaluating a ‘persistent opacification’ on CXR.
244 HEART FAILURE IN A PATIENT WITH CARNITINE-ACYLCARNITINE TRANSLOCASE DEFICIENCY
Gradidge E, Asbeck E, Yang S, Andersson H, Morava-Kozicz E. Tulane University School of Medicine, New Orleans, LA.
Case Report: An hours-old Caucasian female presented with hypothermia, hypoglycemia and hyperammonemia. At 4 days, she became pulseless, was resuscitated, and started on ammonia removal. Family history included consanguineous parents and SIDS. Newborn screening and acylcarnitine (AC) profile showed elevated long-chains and low free carnitine. Gene sequencing showed a homozygous deletion for carnitine-AC translocase (CACT) deficiency. A low fat formula with intermittent feeds, medium chain triglyceride oil and carnitine were started. Immediately, long-chains and long-chain to medium-chain ratio (LC:MC) decreased. Her echocardiogram showed normal heart function at 1 month-old.
AC profiles were alike at 4 and 9 months-old with low free carnitine and improving LC:MC. Though she was asymptomatic, her follow-up echocardiogram at 9 months-old showed dilated left ventricle (LV) with moderate to severely decreased LV systolic function (LVSF). She was diagnosed with dilated cardiomyopathy (DCM), and furosemide and captopril were begun. Continuous feeds were begun to support euglycemia and to avoid long-chain fat recruitment. After 3 weeks of treatment, echocardiogram revealed low-normal LVSF. At 1 year-old, AC profile showed improved LC:MC and low free carnitine, however echocardiogram revealed LV dilation and worsened LVSF. 1 week after optimizing feeds, LVSF improved substantially.
After birth, the infant experiences periods of fasting and must mobilize free fatty acids. CACT transports long-chain fatty acids (acylcarnitine) into the mitochondrial matrix, so they can be converted for use in the beta-oxidation cycle; generating acetyl-CoA for ketogenesis and gluconeogenesis. Patients with CACT deficiency often present as neonates with cardiac arrest, hypoketotic hypoglycemia, hyperammonemia and lactic acidemia. Lethal cardiac arrhythmias are due to an accumulation of long-chain AC, which causes an increase in intracellular Ca2+. Treatment goals are to: avoid hypoglycemia, prevent long-chain AC production and supply ample carnitine.
We postulate the improvement in heart function was due to nutrition optimization, although she was treated with usual medications for DCM. Due to the high risk of mortality in CACT deficiency and the rapid weight gain of infants, nutrition is vital.
245 POINT OF CARE ULTRASOUND IDENTIFICATION OF AN INTRACRANIAL FOREIGN BODY
Hanna PJ, Baker MD. UAB, Birmingham, AL.
Purpose of Study: To describe how point of care ultrasound was used to describe skull fracture and intracranial foreign body
Methods Used: Case Report
Summary of Results: A 7 year old male presented to the emergency department 1 day following a gunshot wound to the forehead. Patient was reportedly shot by an air rifle (760 Pump Master ®) at close range by a 4 year old relative. There was no alteration of mental status or loss of consciousness. Vital signs, Glasgow Coma Scale (15), and neurological exam were all normal. A 1 mm puncture wound was noted in the right frontal scalp without palpable foreign body, soft tissue swelling, or bony step off. Plain radiograph revealed a metallic foreign body without evidence for skull fracture. Point of care ultrasound demonstrated a right frontal skull cortical discontinuity with hyperechoic foreign body with ring artifact. Computed tomography revealed small open calvarial frontal skull fracture with frontal cerebral hemorrhage. The patient was admitted to the Pediatric Neurosurgery service and underwent removal of an intracranial, extradural foreign body. The patient had an uneventful recovery and was discharged the following day.
Conclusions: Utility of Point of care Ultrasound has been well described for soft tissue foreign bodies and fractures. Ultrasound is not generally useful for identifying foreign bodies embedded in bone. Bone acts as a strong reflector of sound waves making foreign body identification with ultrasound difficult. We described a case in which a metallic foreign boy was localized immediately beneath a skull fracture.
246 ELEVEN-MONTH-OLD WITH ALTERED MENTAL STATUS
Hines K, Dietiker K, Monroe K. University of Alabama at Birmingham, Birmingham, AL.
Case Report: An eleven-month-old male was transferred from an outside hospital emergency department with coffee-ground emesis and altered mental status. He had no accompanying family to provide further history. He had presented earlier in the day with viral symptoms and had been discharged home. Vital signs on arrival were notable for bradycardia and hypothermia. He was awake, but had no spontaneous movements, and was only intermittently withdrawing to pain. Initial glucose was < 20 mg/dL. Blood gas, electrolytes, and blood counts were normal. Liver enzymes and coagulation studies were significantly elevated. Serum iron and acetaminophen levels were mildly elevated. Urine drug screen was negative. Abdominal films, chest films, and head CT were normal.
The clinical presentation following ingestion is extremely broad. Occult ingestion should be considered in any child who presents with unexplained laboratory derangements and multi-system organ dysfunction. This patient’s constellation of symptoms could not be explained by a single poison, and presentation was thought to be the result of polypharmacy. Iron ingestion could account for coffee-ground emesis, elevated serum iron level, and transaminitis, though these signs/symptoms are typically seen in different phases following ingestion. Acetaminophen ingestion could also account for vomiting and transaminitis, though again, these are often seen at different time points following ingestion. Multiple medications, including sulfonylureas and beta-blockers, can cause hypoglycemia, which can in turn cause altered mental status and hypothermia. Bradycardia can also be caused by numerous agents, including beta-blockers.
The patient’s family arrived three hours after the patient arrived in our emergency department. The mother was a poor historian, though denied having any medications, including over-the-counter medications, in the home. He was treated with deferoxamine and N-acetylcysteine for presumed iron and acetaminophen ingestions, and required a significant amount of dextrose-containing intravenous fluids to maintain euglycemia. He was admitted to the intensive care unit for monitoring. Mental status, transaminitis, coagulopathy, and hypoglycemia all improved within 24-48 hours.
247 CONGENITAL ABDOMINAL MASS IN A NEONATE
Huff LL, Kiger J, Caplan MJ. Medical University of South Carolina, Charleston, SC.
Case Report: A female neonate was delivered at 35 weeks GA to a Hispanic 25 year old G1 mother via SVD. Maternal history was significant for HSV with no lesions noted at the time of delivery. Maternal GBS status was unknown. Maternal labs were otherwise negative. At 20 minutes of life, the infant was noted to have respiratory distress. Further examination revealed an asymmetric abdomen with a right-sided large, smooth, solid abdominal mass. The mass was palpable from the liver edge to pelvic rim and it nearly crossed the midline.
The infant’s respiratory distress resolved by 24 hours of life. An abdominal X-ray revealed significant radiopacity of the right abdomen with displacement of bowel towards the midline. Abdominal ultrasound and CT were also performed which revealed a heterogeneous mass arising from the lower pole of the right kidney with associated grade 3 hydronephrosis of the upper pole collecting system.
Radical right nephrectomy with partial ureterectomy was performed. On gross pathologic examination of the right kidney, it weighed 117.8g, and was 6.5 x 5.8 x 5.5 cm. It had a whorled “leiomyomatoid” pattern on gross examination and well-defined fascicles of cytologically bland myofibroblastic cells on microscopic examination.
The clinical presentation and pathological examination were consistent with a congenital mesoblastic nephroma (CMN), classical type. Originally thought to be a congenital form of Wilms tumor, congenital mesoblastic nephroma is defined as a separate entity and is rare, albeit the most common renal tumor in infants under the age of 3 months.
Surgical nephrectomy with wide margins is considered the treatment of choice; however, chemotherapy should be considered in stage III tumors, if resection is incomplete, or if the tumor ruptures during surgery. The tumor may recur locally or metastasize 5-10% of the time, which usually occurs within 12 months of the diagnosis. Prognosis is excellent with a 5 year survival around 96%.
248 FOAMY URINE AND SICKLED CELLS
Huntwork MP1, Howell MP2, May J2, Yospiv I2, Singleton T2. 1 Tulane University School of Medicine, New Orleans, LA and 2 Tulane University School of Medicine, New Orleans, LA.
Case Report: A 19 year-old girl with known sickle cell disease presented with a one day history of lower back and thigh pain. The patient recently had two ER visits and one hospital admission for vaso-occlusive crisis and pneumonia.
Symptoms were typical of her usual pain crisis. On review of systems, the patient reported “foamy” urine and a swollen face. She felt dizzy when standing up rapidly. Chart review revealed that she received ten doses of ketorolac over the past month, at various ER visits, clinic visits, and from her hospital admission.
Physical exam was notable for scleral icterus, tachycardia without murmur, and orthostatic hypotension. Laboratory studies were significant for BUN of 43 mg/dL, creatinine of 3.6 mg/dL (baseline is 0.5 mg/dL), bicarbonate of 17 mmol/L, albumin of 1.3 g/dL, and total bilirubin of 3 mg/dL. Hemoglobin was 5.7 mg/dL, and reticulocyte count was 10%. Urinalysis revealed protein greater than 500 mg/dL. The urine protein to creatinine ratio was 27.
A renal biopsy was performed to determine the cause of acute kidney injury (AKI) and acute-onset nephrotic syndrome. Light microscopy demonstrated focal segmental glomerulosclerosis (FSGS) and the absence of eosinophils. Electron microscopy revealed diffuse podocyte effacement and the absence of dense deposits. A diagnosis of nephrotic syndrome due to FSGS and minimal change disease was established.
Sickle cell disease can cause a nephrotic picture entirely on its own. Increased renal blood flow results in hyperfiltration, increased GFR and lower serum creatinine. Chronic glomerular hyperperfusion can lead to glomerular injury or FSGS, and proteinuria. Sickle cell crisis is associated with a decrease in creatinine clearance with a return to baseline around four weeks after the episode, suggesting a transient glomerular dysfunction during acute episodes.
Our patient also had recent documented NSAID use. In children, NSAID-induced AKI often occurs in conjunction with other comorbid conditions, like sickle cell disease. NSAIDs inhibit cyclooxygenase, which impedes prostaglandin-mediated vasodilation of the afferent arteriole, causing decreased renal blood flow, decreased GFR, ischemic injury and acute tubular necrosis.
249 AMBIGUOUS GENITALIA AND LARGE ABDOMINAL MASS IN A NEONATE: A CASE REPORT
Jones M1, Voelker C3, Lutfallah C2. 1 Our Lady of the Lake Regional Medical Center, Baton Rouge, LA; 2 Our Lady of the Lake Regional Medical Center, Baton Rouge, LA and 3 Woman’s Hospital, Baton Rouge, LA.
Case Report: Introduction: Ambiguous genitalia is an example of a disorder of sexual development, in which the external genitalia do not have the typical appearance of either sex. The birth of a child with ambiguous genitalia is a challenging and distressing event for the family and physician and one with life-long consequences. The most common cause of ambiguous genitalia is congenital adrenal hyperplasia. True hermaphrodites are extremely rare.
Case Presentation: A 22 year old G3P2002 with no significant past medical history was referred to Maternal Fetal Medicine specialists for a suspicious finding on prenatal ultrasound. A prenatal MRI was performed and showed a large fetal abdominal mass and indeterminate genitalia. The infant was born via spontaneous vaginal delivery at 39 weeks and 1 day with APGAR scores of 8 and 8. The physical exam showed no abnormalities with the exception of a firm, distended abdomen and ambiguous genitalia. Within 2 weeks of birth, the patient developed urosepsis and required placement of a vaginostomy tube transabdominally and antibiotics.
Discussion: Extensive work up revealed a true female hermaphrodite with XX chromosomes and both ovarian and testicular tissue. The patient’s large abdominal mass was discovered to be a hydrocolpos.
Conclusion: Due to the unique formation of the patient’s anatomy regarding the genital tract, a situation was created in which the patient had reflux of bladder contents into a hydrocolpos. This process began in utero enlarging the vaginal area which folded over itself preventing emptying of the hydrocolpos. This process lead to stagnant urine and an environment primed for urosepsis.
Next Steps: The family has decided to raise the infant as a female. She will require extensive corrective surgery to normalize the function and appearance of her genitalia. The male testicular tissue will be removed. The patient will also be followed long term by endocrinology to manage hormone regulation.
250 PROPTOSIS: AN EYE POPPING DIAGNOSIS
Kant S. University of Alabama Birmingham, Birmingham, AL.
Case Report: Case Report: A 12 yo M presented to our Emergency Department (ED) with chief complaint of right eye swelling and pain. His symptoms started 10 days prior to presentation with right eye discharge, pain, diplopia and fever to 101. The fevers lasted for 2-3 days then self-resolved. In addition to eye swelling and pain he developed light sensitivity and pain with eye movement. Treatment prior to ED presentation included acyclovir, erythromycin ophthalmic ointment and tobramycin/dexamethasone eye drops. On the day of ED presentation he had worsening pain and his eye seemed to be bulging. Physical exam was notable for an alert patient who appeared to be in pain. He had erythema and swelling of the right upper eyelid, conjunctival injection along with mild proptosis of the eye. Eye movement was restricted in all directions. Pupil was round and reactive to light. Examination of the left eye was normal. Visual acuity: right eye 20/40, left eye 20/20. Our initial concern was for orbital cellulitis. Patient was given a dose of clindamycin while we obtained a CT scan with contrast of the orbits. The CT scan showed thickening of the right extra-ocular muscles, stranding within the post-septal and intracoronal fat, right scleral thickening and proptosis. The prime consideration was pseudotumor of the right eye vs. orbital involvement by thyroid disease. Ophthalmology was consulted who agreed with the diagnosis. Thyroid function studies including free T4, TSH and thyroglobulin antibody were found to be normal. Patient was admitted to the general pediatric service and given IV methyl-prednisone. After 24 hours of IV steroids, patient had improvement in symptoms. He was discharged home on oral steroids for 1 month.
Discussion: Orbital pseudotumor, also known as idiopathic orbital inflammatory syndrome (IOIS) is a rare unusual inflammatory condition. IOIS is likely an autoimmune-mediated entity. Factors implicated in causation include viral, genetics and environmental. Although more common in the fifth decade of life, it can occur at any age and has been described in patients as young as 2 years. Differential diagnosis includes orbital cellulitis, thyroid ophthalmopathy, sarcoid, lymphoid tumor, lymphangioma, metastatic carcinoma and rheumatologic disorders. Diagnosis is made with the help of imaging (CT or MRI). Prompt response to steroids is a key feature of IOIS.
251 EXCRUCIATING PAINFUL GOITER SECONDARY TO HASHIMOTOS THYROIDITIS REQUIRING THYROIDECTOMY FOR PAIN CONTROL
Kashyap L1, Chalew S1, Simon L2, Gomez R1. 1 LSUHSC, New Orleans, LA and 2 LSUHSC, New Orleans, LA.
Case Report: Hashimotos thyroiditis usually presents as painless thyroid swelling. Painful Pediatric Hashimotos thyroiditis is a rare condition with limited literature on pain management. We report a 15 yr old female who presented with a month history of fatigue, malaise and progressive painful midline thyroid swelling, no difficulty in swallowing, no fever or recent URI symptoms. Exam was remarkable for diffusely visibly enlarged, very tender, and non-nodular thyroid. Thyroid function tests, CRP, complete blood count were normal. Ultrasound revealed diffusely enlarged non-nodular, non-cystic gland with mild increased vascularity. Diagnosis of Hashimoto’s thyroiditis was confirmed by biopsy and thyroid antibodies. Over 6 weeks period pain management with Ibuprofen, Levothyroxyne, corticosteroid, Gabapentin and Amitryptilline was not successful. Finally total thyroidectomy resulted in complete resolution of thyroid pain.
Conclusion: Thyroidectomy could be considered for the rare case of painful Hashimotos thyroditis in children.
252 A CASE OF UNDIAGNOSED CYSTINOSIS AND WAARDENBURG SYNDROME PRESENTING IN A CHILD WITH CONGENITAL HEARING LOSS, VOMITING, CONSTIPATION, AND FAILURE TO THRIVE
Langford S, Workman L, Multerer S, Kenagy D. University of Louisville, Louisville, KY.
Case Report: We are reporting a 20 month old F with history of congenital deafness who presented with complaint of several episodes of non-bloody, non-bilious vomiting and severe constipation over the last several months. She was noted to be below the 3rd percentile for weight and exhibited motor delays. Serum electrolytes, a head CT and skeletal survey were performed and the patient was admitted to the hospital for further work up of failure to thrive.
On exam the child was small for age, unable to stand, social and smiling yet nonverbal. She had light blonde hair with a central forelock of white hair, pale skin, wide set eyes and wide nasal bridge, but an otherwise unremarkable physical exam. Family medical history included congenital deafness in mother, maternal grandmother, and brother. Given these exam findings and family history, the patient and her family were diagnosed clinically with Waardenburg syndrome after genetics consultation.
Her initial labs were notable for hypernatremia, hyperchloremia, hypophosphatemia, and an anion gap metabolic acidosis along with glycosuria and a pH of 7 on urinalysis. Repeat serum chemistry after fluid resuscitation revealed worsening metabolic acidosis—a finding not explained by Waardenburg syndrome. Head CT was normal and skeletal survey had findings suggestive of rickets. Slit lamp exam showed crystalline deposition in the eye and later leukocyte cystine assay was elevated to 3.92 (normal range 0.12 +/− 0.06). This confirmed the cause of the patient’s metabolic acidosis—Fanconi syndrome due to nephropathic cystinosis.
This is an unusual case pairing two rare and unrelated genetic diagnoses, cystinosis and Waardenburg syndrome. Cystinosis is a lysosomal storage disease that is the leading cause of Fanconi syndrome in children and Waardenburg is an autosomal dominant disorder that accounts for 2 to 35% of cases of congenital hearing loss. Waardenburg syndrome and nephropathic cystinosis have not previously been associated in the literature and each can present at different times with chronic constipation, fair pigmentation, and hearing loss.
253 A FATAL CASE OF ROCKY MOUNTAIN SPOTTED FEVER
LeJeune G, Vanchiere J, Bocchini J, Scott L. LSU Health Shreveport, Shreveport, LA.
Case Report: A 5-year old female visiting east Texas from North Carolina was transferred to the PICU at LSU Health Shreveport with suspected RMSF. She had multiorgan failure and was transferred for evaluation of ECMO. Upon arrival, patient GCS was 3 and she required multiple vasopressors to maintain blood pressure. After aggressive resuscitation, the patient was stabilized and determined not a candidate for ECMO. CRRT and plasma exchange therapy were initiated. 2 weeks prior, a tick was found on her shoulder. 5 days later she developed fever, sore throat and a maculopapular rash. She was seen by her doctor a week following the tick bite and started on cephalexin for Strep throat. A petechial rash developed 10 days after the tick bite and the her condition deteriorated during the drive to Texas. She became lethargic and not taking liquids or food. At a local ER, her platelets were 20,000 and a full sepsis workup was done. She was begun on vancomycin, ceftriaxone and doxycycline and admitted to a community hospital PICU. She continued to deteriorate and had cardiac arrest following her admission. She was transferred to our facility due to worsening clinical status. In addition to CRRT and plasma exchange, patient was continued on broad spectrum antibiotics including doxycycline for coverage for suspected RMSF. She had minimal response with no improvement in neurological status. A nuclear medicine study noted no effective cerebral perfusion. Brain death was confirmed and she was removed from mechanical ventilation. She expired 11 days following onset of symptoms. Subsequently, the PCR sent to CDC confirmed the diagnosis of RMSF. RMSF, caused by Rickettsia rickettsii, a gram-negative, obligate intracellular bacterium, is the most common rickettsial infection in the US. It can be characterized by a wide spectrum of symptoms and typically is curable, but potentially can be lethal. According to the CDC, case fatality rates have dropped from 20-30% to 1.1-4.9% after antibiotic therapy was implemented as standard of care. Early recognition and initiation of therapy are important factors for reducing risk of mortality. This case demonstrates the importance for Primary Care doctors to recognize the signs and symptoms of RMSF and implement prompt empiric therapy that could save the life of their patient.
254 LINEAR AND WHORLED HYPERMELANOSIS: AN INTERESTING NEWBORN FINDING
Leysath A, Burns JJ, Lee A. Florida State University College of Medicine, Pensacola, FL.
Case Report: A full term newborn was evaluated by the physician on the first day of life. Physical exam noted a linear, horizontal, hyperpigmented skin pattern on the newborn’s back. Per nursing staff, the pattern was present and birth and had not changed. Exam was unremarkable otherwise. Family history was negative for a similar dermatologic problem. Due to the cutaneous findings, a cranial ultrasound and an echocardiogram were obtained; both were normal. A diagnosis was subsequently made and the mother counseled accordingly. The infant was discharged on day of life 3 with routine follow up.
Linear and whorled nevoid hypermelanosis (LWNH) is a rare cutaneous disorder characterized by hyperpigmented, streaky and whorled macules in Blaschko’s lines. Blaschko’s skin line patterns may take the shape of a “V”, “S” or perpendicular lines for regions involving the trunk, arms and legs. Diagnosis is based on classically described “zebra striped” hyperpigmentation on physical exam. Differential diagnosis includes incontinentia pigmenti, linear epidermal nevus and nevoid hypermelanosis. It can be distinguished on physical exam by absence of pustules or vesicles in the hyperpigmented areas. LWNH is usually an isolated finding, but can be associated with intracranial and cardiac abnormalities. There is no specific treatment. Dermatology referral may be made if the diagnosis is uncertain or for cosmetic concerns. Otherwise, individuals with isolated cutaneous findings experience no adverse affects.
255 NEURONAL CEROID-LIPOFUSCINOSIS PRESENTING WITH REGRESSION OF MILESTONES, SEIZURES AND ASPIRATION
Lowe GS, Dunlap M. University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Neuronal Ceroid-Lipofuscinoses (NCLs) are a devastating type of inherited neurodegenerative disorders primarily presenting with loss of milestones, seizures & progressive visual, cognitive and motor deterioration resulting in premature death. We present a case with these symptoms in addition to the presenting symptom of aspiration. Diagnosis was made by Electron Microscopy of a conjunctival biopsy and aided by the discovery of a biological sibling with similar neurodegenerative symptoms admitted to our hospital at the same time.
A 5 year old female with a history of complex partial seizures and mild to moderate global developmental delay presented to our hospital with symptoms of aspiration, difficulty breathing and fever. She was slowly achieving milestones until she began having seizures at age two. Her seizures became increasingly difficult to control but by age 3 she was able to walk and speak a few words. She had a complex social situation and was placed in foster care at age 3 due to medical neglect with an unknown family history. In the three months preceding her admission, she had rapid regression with increased seizure activity causing falls with ambulation, speaking fewer words, and incontinence. She became nonverbal and non-ambulatory one month prior to admission and began having difficulty feeding. She was admitted for aspiration pneumonia after she failed outpatient treatment and received a gastrostomy tube and fundoplication to address her feeding issues; intractable seizures continued. Due to vision loss ophthalmologic evaluation was performed which suggested Batten disease, conjunctival biopsy was recommended. The EM evaluation of this biopsy yielded large lysosomal inclusions within vascular pericytes containing curvilinear membranous profiles characteristic of NCLs Classic Late Infantile variant.
NCLs are described in the genetic literature. This case report aims to raise awareness in General Pediatrics of NCLs as important in the differential diagnosis in a patient with regression of milestones, seizures and aspiration. It also demonstrates the importance of family history in diagnosis and need for genetic counseling for affected families.
256 FOUR MONTH OLD WITH VOMITING POST HEAD TRAUMA
Maldonado L, Takagishi J. University of South Florida, Tampa, FL.
Case Report: A four month old male fell off his grandmother’s bed, approximately three feet high, onto a tile floor. He cried immediately and there was no loss of consciousness. He was evaluated in the Emergency Department, cleared, and sent home to follow up in his pediatrician’s office the next day.
In the office, parents report a significant change from baseline since leaving the ED. He has had emesis with all feeds, decreased appetite, fussiness, and decreased interaction with the family. Parents deny fever, diarrhea, shortness of breath or rash. The emesis was non-bloody and yellow to green in color. Mother noted that she felt ill and that grandmother had been diagnosed with “the flu.”
His physical exam revealed a temperature of 98 degrees Fahrenheit, pulse 140, respiratory rate 40 and a weight of 7.74 Kg, 250 grams less than the day prior. He appeared sleepy and uncomfortable, fussy but consolable by father. His skin was warm with no rash or lesions. His head was normocephalic and atraumatic. The anterior fontanel was open and soft. Pupils were equal and reactive to light. His lungs were clear to auscultation bilaterally with no increased work of breathing. His heart rate was regular and without murmurs. His distal pulses were brisk. Abdomen was soft, mildly distended, not tender, without masses, and with positive bowel sounds. His neurologic exam showed decreased activity from baseline, fussy but intermittently consolable.
He was referred to the Emergency Department for further workup. A head CT without contrast was within normal limits. During the collection of blood, urine and CSF, the patient produced a small bloody stool. An abdominal ultrasound showed multiple distended loops of bowel, suspicious for obstruction, and a mass in the right upper quadrant with concentric rings, consistent with an intussusception. An air contrast enema was performed and did not reduce the intussusception. He was then taken to the operating room for an exploratory laparotomy for intussusception reduction and appendectomy. He was admitted to the PICU post operatively and after two days he was discharged home with stooling, tolerating feeds, and an improved activity level. Follow up visits showed adequate intake, output, weight gain, and neurologic examination.
257 THE MEDICAL MANAGEMENT OF CERVICAL LYMPHADENITIS CAUSED BY ATYPICAL MYCOBACTERIUM
Mathias MD, Shamoun MP, Durham M. Childrens Medical Center, Dallas, TX.
Case Report: PURPOSE: To discuss the medical versus surgical management of atypical mycobacterium cervical lymphadenitis
CASE REPORT: A two year old previously healthy boy presented with seven weeks of right neck mass swelling. The mass was initially the size of an egg and had continued to grow. The mass was mobile, nontender, and nonerythematous. He had received five days of clindamycin, three days of azithromycin, and one dose of amoxicillin-clavulanate. During this time, the node had mildly decreased and then increased in size. Review of systems revealed one day of fever at presentation and non-drenching night sweats. He did have cat, dog, and cow exposure. He had no travel exposure nor incarcerated contacts. An ultrasound had shown a 4.5cm right submandibular lymph node consistent with lymphadenitis. A MRI showed a large inflammatory conglomeration of lymph nodes, some with necrotic areas, as well as, a large abscess. He went for Incision and Drainage (I&D) of the abscess and was started on trimethoprim-sulfamethoxazole for coverage of oxacillin sensitive Staphylococcus aureus, methicillin resistant Staphylococcus aureus, and Bartonella. Acid fast bacilli stains from I&D came back positive. Tuberculin sensitivity test and Quantiferon gold were negative. Cultures returned positive for Mycobacterium avium-intracellulare complex. Due to the location and size of the node and possible deformity or injury to Cranial Nerve XI, Otolaryngology elected not to excise the node. The patient was started on long-term therapy with rifampin and azithromycin
DISCUSSION: While excision of node is the classic treatment of atypical mycobacterium, there are cases where the anatomical challenges of excision make medical therapy a reasonable alternative. (1) However, as morbidity (repeat operations and sinus tract formation) is shown to increase without complete excision, close follow up is warranted. (2)
Hazra R, et al. Lymphadenitis due to nontuberculous mycobacteria in children: presentation and response to therapy. Clin Infection Dis. 1999 Jan;28(1): 123–9.
Scott CA, et al. Management of lymphadenitis due to non-tuberculosis mycobacterial infection in children. Pediatric Surg Int. 2012 May;28(5): 461–466.
258 NEONATAL SCABIES WITH THROMBOCYTOPENIA MASQUERADING AS MUCOCUTANEOUS HERPES SIMPLEX INFECTION
Melson S, DeLeon S, Yates AM. University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Rashes are a common complaint among neonates and the differential is broad. Moreover, many of the skin lesions that are common among neonates can appear as vesiculopustular lesions and the differential diagnosis for these lesions alone varies from benign conditions without long-term sequelae to infections with high rates of morbidity and mortality.
Our patient is a previously healthy 25 day-old male who presented to a tertiary children’s hospital with a diffuse rash characterized by vesicles over an erythematous base. His physical exam was strongly suspicious for herpes simplex virus (HSV), a diagnosis supported by multiple dendritic lesions on ophthalmologic exam. Laboratory studies including spinal fluid HSV PCR and skin scrapings were sent and the infant was admitted on IV acyclovir, along with erythromycin ophthalmologic ointment and polymixin/TMP-SMX eye drops. After 48 hours, HSV culture/PCR were reported as negative and at 72 hours, the rash had evolved from vesicular lesions into crusted lesions with minimal erythema. At the same time he also developed marked thrombocytopenia, raising concern for other congenital TORCH infections. An Infectious Disease consultant had suspicion for neonatal scabies. Subsequent evaluation by dermatology with skin scrapings confirmed a diagnosis of neonatal scabies. He was treated with permethrin cream and showed rapid improvement in both his rash and thrombocytopenia. Repeat ophthalmologic evaluation resulted in a revised diagnosis of corneal abrasion, likely secondary to pruritis. He was discharged home in good condition.
Neonatal scabies is a rare diagnosis that can be treated with relative ease. The common lesions are eczematous, crusted vesicles, however, our patient illustrates a case of scabies with grouped vesicles over an erythematous base, the lesion classically associated with HSV. Additionally, he also suffered from thrombocytopenia, which has previously not been reported in the setting of scabies. This case exemplifies the diagnostic dilemma faced by pediatric providers when faced with neonatal rashes and underscores the importance of maintaining a broad differential, particularly when confronted by vesiculopustular lesions.
259 AN INFANT WITH DEVELOPMENTAL DELAY AND SIGNIFICANT HEART MURMUR
Mike S. LSU Health Shreveport, Shreveport, LA.
Case Report: Children with developmental delay are frequently seen in general pediatric practice. Early identification of delay is essential, especially if delay is the result of an organic cause that affects multiple organ systems. The diagnosis becomes particularly challenging when the child does not exhibit the classically described characteristics of a known syndrome. A high index of suspicion becomes paramount to identify the correct diagnosis and initiate the appropriate health maintenance and surveillance protocols.
The patient is a two year old African American male who presented at six months of age for evaluation of a significant cardiac murmur. Echocardiogram revealed moderate pulmonic valve stenosis with otherwise normal cardiac function. At nine months of age the patient had not begun babbling, sitting or crawling. At fifteen months of age the patient was not crawling, pulling up, or walking.
On physical exam the patient had a somewhat dysmorphic appearing face, however there were no characteristic syndromic findings to suggest the cause for his developmental delay. There was no family history of mental retardation or congenital syndromes. A chromosomal microarray showed a microdeletion on chromosome 7 and the diagnosis of Williams syndrome was made.
Williams syndrome affects 1: 7500-10,000 births. Children with Williams syndrome often have cardiovascular anomalies, short stature, characteristic facies, and developmental delay or mental retardation. Because multiple organ systems are affected by the disorder, children with Williams syndrome require specially tailored health supervision. This case explores the identification of an important genetic syndrome in a child who did not fit the classically accepted phenotype.
260 HYPOPLASTIC LEFT HEART SYNDROME IN A PATIENT WITH FETAL HYDANTOIN SYNDROME
Mumphrey CG, Barkemeyer B, Zambrano RM. LSU Health Sciences Center, New Orleans, LA.
Case Report: The association between antiepileptic drugs and congenital malformations in the offspring of women with epilepsy was first discussed in the late 1960s. Women taking antiepileptic medications carry a two- to sevenfold higher risk of congenital malformations than the general population. This risk is proportional to the increase in number of pharmaceutical agents used. In 1975, Hanson and Smith proposed the name “fetal hydantoin syndrome” after identifying a special clusters of anomalies which included craniofacial features, microcephaly, intellectual disability and hypoplasia of the distal phalanges in the offspring of the women taking phenytoin. We present a newborn male with maternal exposure to both phenytoin and lamotrigine during the whole pregnancy, and born with several classic features of fetal hydantoin syndrome and also with hypoplastic left heart. Congenital heart disease is seen less frequently with fetal hydantoin syndrome. The most common defects include: pulmonary or aortic valvular stenosis, coarctation of the aorta, patent ductus arteriosus and septal defects; most commonly ventricular septal defects. To our knowledge this would be the first report of a patient with hypoplastic left heart. Unfortunately after post operative complications support was withdrawn at DOL#32 and the patient died. Interestingly, this infant had a twin sister who also exhibited the classic fetal hydantoin phenotype but without congenital heart disease, suggesting that individual genetic variation plays a role in the variability of the phenotype. Even though there has been a growing body of evidence supporting a genetic etiology for left-sided heart defects, including HLHS; not all genes involved have been identified. In addition, the teratogenic mechanisms involved in phenytoin exposure also remain unclear, and are likely to be complex. The association between fetal hydantoin syndrome and hypoplastic left heart in our patient may offer insight to their etiologies and any possible gene(s) that may be associated. Even though lamotrigine is considered one of the safest antiepileptic drugs that can be given during pregnancy, we cannot rule out that polytherapy may have played a role in our reported novel association of hypoplastic left heart syndrome with fetal hydantoin syndrome.
261 ZINC DEFICIENCY IN AN INFANT DRINKING RICE MILK
Murphy M, Carter-King L, Eggie D, Beatty K. LSUHSC, New Orleans, LA.
Case Report: An eleven-month old male presented with a progressively worsening rash over the past three months as well as a six week-history of diffuse, worsening edema. The patient also had a two-day history of fever, decreased activity level, and cold symptoms. Detailed history revealed numerous food allergies including milk, eggs, and soy as well as multiple formula changes since birth secondary to diarrhea and vomiting. Diet consists only of a rice-based, non-dairy beverage, which had been his sole source of nutrition since three months of age. Physical exam revealed weight, height, and head circumference of <3%, <3%, and 10-25% respectively. Other pertinent exam findings include a pale, irritable, afebrile infant with thin, lightly colored hair. Pitting edema was evident in all extremities with a diffuse sandpaper rash. An erythematous, maculopapular rash was present periorally with some honey-colored crusting. A brightly erythematous, sharply-demarcated diaper rash was present with a single vesicle noted on the right proximal thigh. No involvement of mucous membranes noted. His physical exam paired with his dietary history raised concern for nutritional deficiency. Laboratory results were significant for an albumin of 1.6, prealbumin of 5.5 (range: 11-23), zinc level of 22 (range: 60-120), and a 25-OH vitamin D level of 26. After admission to the hospital, the patient was started on zinc supplements and was transitioned to an appropriate formula. He tolerated the formula well, and prior to discharge the rash and edema had mostly resolved.
A rice-based, non-dairy beverage is an inadequate sole source of nutrition for a growing infant. After consumption of the rice-based, non-dairy beverage for over seven months, our patient presented with several findings consistent with zinc deficiency, including dermatitis and failure to thrive. In addition to zinc deficiency, this inappropriate nutrition source led to a protein deficiency and a Kwashiorkor-like presentation. This case reinforces the importance of obtaining a thorough dietary history in infants, as well as the importance of parent counseling.
262 A LACTING ADOLESCENT ON ATYPICAL ANTIPSYCHOTICS: A CASE REPORT OF AN EMERGING CHALLENGE
Myers WT. University of Louisville, Louisville, KY.
Case Report: The use of atypical antipsychotics for behavioral control in the pediatric population has been increasing rapidly. The advantages of these medications are thought to outweigh the risks due to a marked decrease in the extrapyrimidal effects seen with use of typical antipsychotics. With this increased pediatric patient exposure, increased scrutiny of the incidence and severity of adverse reactions in children must also occur. We describe a 17 year old female who presented to the Emergency Department with the complaint of a 3-4 day history of milky discharge from both breasts associated with some vaginal spotting and a reported increase in breast size over the course of two months. The patient had a complex history; including, PTSD, Mood Disorder NOS, and eosinophilic esophagitis. She had been taking ziprasidone until shortly before admission due to experiencing unacceptable weight gain when placed on olanzipine. Her other medications included sertraline, lamotrigine, and lansoprazole. Physical exam demonstrated an overweight adolescent with a BMI of 28.56 and milky discharge consistent with lactation. Otherwise, her complete physical exam, including visual fields and neurologic exam, was within normal limits. Laboratory analysis showed an elevated prolactin level of 30.2 ng/mL (normal 3.0-18.6 ng/mL) and negative urine and serum pregnancy tests. She was admitted, her ziprasidone was held, and over the course of two days had a head MRI w/contrast performed, coupled with serum cortisol and thyroid studies; all were within normal limits. Her lactation ceased by day 2 of hospitalization and at discharge her prolactin levels had decreased to 13.4 ng/mL. This case clearly demonstrates a classic case of drug-induced hyperprolactinemia. The patient was at risk for this condition primarily due to her exposure to atypical antipsychotics, but also due to the co-administration of an SSRI. A review of the literature associated with drug induced hyperprolactinemia demonstrates the short term and long term effects of this condition, along with potentially resource-saving information on clinical management.
263 A PATIENT WITH MICROCEPHALY AND SIMPLIFIED GYRI PATTERN- A PHENOTYPICAL VARIANT OF THE 15q24 MICRODUPLICATION SYNDROME
Patel B. University of South Alabama, Mobile, AL.
Case Report: Abstract: Duplications in the 15q24 region have been reported to be associated with neurodevelopmental disorders, however, to date, no reports of microcephaly with simplified gyri or brain malformations have been reported. Reports of 15q24 microduplication as a result of recombinant homolog of the 15q24 recurrent microdeletion syndrome have been characterized as developmental delay, microcephaly, loose connective tissues, downslanting palpebral fissures, hypertelorism, broad nasal base, broad medial eyebrows, long smooth philtrum and full lower lip. We encountered a case of a young girl with dysmorphic features including narrow bifrontal diameter and sloping forehead who presented with developmental delay and postnatal overgrowth and microcephaly. A high resolution comparative genomic hybridization (figure3) revealed a heterozygous duplication of chromosome 15 q24 of 1.26Mb. Patient had a brain MRI done which showed Group1 microcephaly with simplified appearance of the gyri and shallow sulci with too few gyri. Our case is a novelty presentation of microcephaly and simplified gyri pattern linked to microduplication of chromosome 15q 24.
264 RECURRENT PANCREATITIS WITH CONSERVATIVE MANAGEMENT OF A LARGE PSEUDOCYST
Patel B, Ponnambalam A. University of South Alabama, Mobile, AL.
Case Report: Drainage of a pseudocyst is indicated if symptomatic and for progressive enlargement. The multitude of treatments and therapies available make it a challenging choice for many physicians.
Here we discuss the case of a 9-year old female who presented with severe epigastric pain and vomiting. Review of laboratory values showed elevated amylase and lipase and a mutation in SPHINK-1-gene, rest of the tests were normal. She was managed conservately and discharged home. Patient was non-compliant with discharge recommendations and had multiple outpatient visits for continued epigastric pain. She had two more hospitalizations. On the first of the two subsequent hospitalizations, abdominal imaging showed a pseudocyst at the head of the pancreas, which initially was 4cm in size. This was treated conservatively with nasojejunal feeds, low fat diet with pancrealipase and esomeprazole. Monthly ultrasounds were done on an outpatient basis to evaluate progression of pseudocyst and for any other complications. Over next three months, though the symptoms improved, the pseudocyst increased to 6.3 cm (See image). The decision was made to continue with conservative management of this large pseudocyst. She responded well to this management and her symptoms resolved. Amylase and lipase returned to normal limits. The pseudocyst resolved with pancreas returning to its normal size.
This case illustrates that conservative medical management can be appropriate in a large pancreatic pseudocyst. Recognition of this benefit is important as it may in the future help with clinical decision making to avoid invasive procedures with complications and risks of their own.
265 INFANT WITH MRSA NECROTIZING FASCIITIS
Patel P, Yu J, Bhatia J. Children’s Hospital of Georgia, Augusta, GA.
Case Report: Case Presentation:
Infant is a 7 day old 30 week, twin B, transferred from another hospital for worsening erythema and swelling of the right hand and arm for 3 days due to phlebitis from a PICC line. Infant had RDS initially for which he required surfactant and subsequent CPAP. A PICC line was placed on day of life 3 in the right arm. On DOL 6, Infant became febrile and swellig and erythma of the PICC insertion site noted which progressed upto hand in a day. PICC line was removed and a new PICC line was inserted in the left arm. Blood culture was obtained and the infant started on Van & Gent as Infant was febrile (CBC benign, CRP- 4.2). On DOL 7, the right hand, arm became more erythematous and swollen which coincided with a positive blood culture for gram positive cocci, Clindamycin added. A Doppler showed an abscess in the right mid-arm. A Orthopedist consulted and abcess incised, drained. MRI right upper extremity concerning for necrotizing fasciitis. Infant then transferred to our institution for further management. Physical examination at our institution was notable for tense swelling proceeding from the right hand to the ipsilateral hemithorax with significant erythema and discoloration of the right forearm. Perfusion of the right hand was poor with a prolong capillary refill time and absent pulses. Diagnosis of compartment syndrome made, Infant underwent fasciotomy. Noted to have non-viable subcutaneous tissue, large amount of cloudy fluid and pale muscles intra-operatively. Antibiotics were continued and serial blood cultures obtained. MRSA(Methicillin Resistant Staphylococcus Aureus) was persistently isolated from blood cultures for 3 days necessisating the addition of Rifampin. Infant required vigourous supportive measures. Received Vancomycin for total of 3 weeks from the first negative blood culture. At the end of therapy, fasciotomy wounds healed well and infant moved fingers and arms spontaneously. This case highlights the invasive nature of this condition, the need for prompt recognition and intervention.
266 UNILATERAL TONSILLAR ENLARGEMENT: A CASE OF SPORADIC BURKITT’S LYMPHOMA
Prudhomme A1, Raulji C2, Morrison C2, Stark M3. 1 LSU-HSC Children’s Hospital, New Orleans, LA; 2 LSU-HSC Children’s Hospital, New Orleans, LA and 3 LSU-HSC Children’s Hospital, New Orleans, LA.
Case Report: Burkitt’s Lymphoma (BL) is a rare form of high-grade non-Hodgkin’s lymphoma of B-cell origin. There are three clinical subtypes: Endemic, Sporadic and Immunodeficiency-related.
The endemic subtype is seen in equatorial Africa, is associated with Epstein-Barr Virus (EBV) and involves facial bones. Immunodeficiency-associated BL occurs in immunocompromised patients such as those with HIV, congenital immunodeficiency or allograft recipients.
Sporadic BL occurs worldwide, accounting for up to 40% of lymphoma in children in the U.S. and Western Europe. It usually involves the GI tract, but may also involve the head and neck, ovary, breast, bone marrow or CNS.
We describe a case of BL in a 6-year-old Caucasian male presenting with unilateral tonsillar enlargement. He presented at his pediatrician’s office with sore throat. The right tonsil was enlarged with a small exudative lesion. A Rapid Strep test was positive. He was treated with antibiotics for 3-5 weeks for presumed tonsillitis. The tonsil enlarged further and developed a large white plaque. There was no fever, night sweats, or weight loss. He was referred for tonsillectomy. Morphologic review revealed reactive follicular hyperplasia and architectural effacement by a diffuse monomorphic infiltrate of lymphoma cells with a starry sky appearance. The left tonsil revealed reactive follicular hyperplasia. A diagnosis of stage-2 Burkitt’s Lymphoma, C-MYC positive, with an 8:14 chromosomal translocation was made. He was referred to a Hematologist/Oncologist for staging and treatment.
Sporadic non-African BL accounts for less than 1% of head and neck malignancies with an incidence of 2-3 cases per million per year in the U.S. and Europe. BL is one of the most rapidly-growing tumors. BL of the tonsils, although rare, presents with unilateral painless tonsillar enlargement and throat discomfort. Because of the aggressive nature of BL and its significant response to chemotherapy, timely diagnosis is crucial for appropriate treatment and better outcomes. The possibility of malignancy should remain in the differential for patients with these presenting signs and symptoms.
267 SUCCESSFUL CARDIOPULMONARY BYPASS WITHOUT EXCHANGE TRANSFUSION IN SICKLE CELL DISEASE
Raney L1, Gardner R1,2. 1 LSUHSC, New Orleans, LA and 2 LSUHSC, New Orleans, LA.
Case Report: Cardiopulmonary bypass presents risks for patients with sickle cell anemia (SSD) since external oxygenation of blood and intraoperative hypothermia increase the incidence of sickling and associated vaso-occlusive crisis. Currently, reduction of these risks involves exchange transfusion pre or intraoperatively in an effort to reduce hemoglobin S, with a goal HbS ranging from <5 to 30%. We present a case of successful cardiopulmonary bypass, without complication, in a patient with SSD who did not undergo exchange transfusion preoperatively. K.A. is a 14 yo F with SSD and a history of frequent pain crises requiring hydroxyurea treatment. She was found to have an aortic valve tumor on a routine echocardiogram. In preparation for surgery, a CBC, and hemoglobin electrophoresis were drawn. Her Hb was 9.5, Hct 29, and her HbS 17%. Of note, she recently had a simple transfusion during a pain crisis. During surgery, she received standard general anesthesia, was placed on bypass, and was cooled to 33°C. The tumor was excised, she was rewarmed, and then weaned from bypass. Acid-base status, core body temperature, oxygenation, and hydration status were all closely monitored. The operation was completed without complication, and without exchange transfusion. She had an uncomplicated post op course where she was extubated on POD #2, chest tubes removed on POD #3, and pain was managed on her home regimen of oral MS contin and Tylenol. The tumor was incidentally found to be an aortic valve papillary fibroelastoma. This case demonstrates not only the risks but the precautions necessary for cardiothoracic surgery in patients with SSD. It also shows that once given proper supervision and assiduous intraoperative care, SSD patients can safely undergo cardiopulmonary bypass and thermal cooling without vasoocclusion.
268 CHROMOBACTERIUM VIOLACEUM SEPSIS: COMPONENTS IN TREATMENT
Richard KR1, Lovvorn J2. 1 UAB, Birmingham, AL and 2 UAB, Birmingham, AL.
Case Report: 11 yo male with progressive buttock abscesses. He was initially given PO Clindamycin for presumed Staphylococcal infection. I&D later revealed gram-negative rods (GNRs) and the patient remained hospitalized and started on IV Ceftriaxone and Clindamycin. 24 hours after I&D, the patient’s clinical status declined and he was transferred to our tertiary care center. Upon arrival, the patient required intubation for impending respiratory failure and progressive shock. Vancomycin and Nafcillin were then added. Rapidly, the patient declined, in spite of maximal conventional ventilator settings, aggressive fluid resuscitation, large-volume transfusions and multiple vasoactive agents. Antibiotics were again expanded to include Meropenem and Gentamicin. The patient continued to have progressive multiorgan dysfunction, severe metabolic acidosis, ultimately requiring initiation of Veno-Venous (VV) ECMO, and later transitioned to Venoarterial (VA) ECMO. The preliminary results of the patient’s I&D cultures grew “brightly violet-colored gram-negative rods, consistent with Chromobacterium violaceum.” Antibiotic coverage was broadened to include Ciprofloxacin and Bactrim. The patient was without multi-agent GNR coverage for a minimum of 96 hours from the time the initial buttock lesions were first evaluated. Until C. violaceum was finalized, Vancomycin and Nafcillin were continued. Over a five-week PICU stay, 14-day course of ECMO, and ongoing multi-antibiotic therapy, the patient significantly improved. He was extubated on hospital day 19 and antimicrobials were further narrowed to Ciprofloxacin and Meropenem on which the patient still remains.
Broad-spectrum coverage with Clindamycin, Vancomycin, and Nafcillin in a patient with presumed gram-positive sepsis secondary to abscesses was not adequate to provide clinical improvement in this patient. As the patient worsened, antibiotics were than expanded to maximize gram-negative coverage. When preliminary cultures revealed chromobacterium violaceum, based on case reports, Ciprofloxacin and later Bactrim, were added. Treatment of GNR was critical to this patient’s recovery. Furthermore, the rapid initiation of ECMO was also key to this patient’s stabilization.
269 CONGENITAL CERVICAL PILOCYTIC ASTROCYTOMA PRESENTING AS HYPOTONIA IN A NEONATE
Shakir AK, Holcomb JW. Georgia Regents University, Augusta, GA.
Case Report: Astrocytomas are the second most common CNS tumors in the newborn, often presenting as hydrocephalus or macrocephaly. We are reporting a case of cervical pilocytic astrocytoma that presented as hypotonia.
A 35-week gestation infant born by C-section, to a G2P0 mother, was hypotonic since birth, with presumed bilateral plexus palsy. On admission neurological exam, he had generalized hypotonia that was worse in upper extremities (UE), spontaneous flexion of right UE and lower extremities, but no spontaneous movements of left UE, spontaneous closing of fists, but no palmar grasp, 3 beats of ankle clonus, DTRs could not be elicited. Pupils were equal and reactive, root and suck reflexes intact and Moro weak and asymmetric. Sepsis evaluation, liver and thyroid function, ammonia, CPK were normal. MRI of the brain and cervical spine (DOL 3) was suspicious for a neoplastic cystic lesion of the cervical cord. MRI with contrast showed a 5/3/16 mm intramedullary lesion at C3-C7 consistent with low grade astrocytoma or ganglioglioma. The infant underwent excisional biopsy and debulking on DOL 8. Pathology revealed pilocytic astrocytoma WHO grade I. The infant recovered well with improvement in tone. He has limited left wrist flexion on DOL 30.
We report an unusual type, location, and presentation of a congenital cervical pilocytic astrocytoma that presented with generalized hypotonia immediately after birth.
270 PANCYTOPENIA AND GELATINOUS BONE MARROW TRANSFORMATION IN ANOREXIA NERVOSA: A CASE REPORT
Shankar A1, Benjamins L2, Beyda RM2. 1 University of Texas Medical School at Houston, Houston, TX and 2 University of Texas Medical School at Houston, Houston, TX.
Case Report: Anorexia nervosa is a psychiatric, eating disorder associated with various hematologic changes such as anemia, leukopenia, and less commonly neutropenia and thrombocytopenia. Half the patients with anorexia nervosa also have bone marrow atrophy. In rare and very severe cases, severe neutropenia and gelatinous bone marrow transformation (GMT) can be seen.
In this report, we present a 17 year old Asian female with anorexia nervosa who presented with fever, streptococcal pneumonia and respiratory distress. She was found to have severe neutropenia and pancytopenia that did not improve despite daily transfusions of red blood cells, cryoprecipitate, fresh frozen plasma, and platelets. Peripheral blood smear showed normocytic, hypochromic anemia with anisocytosis, few cells, and slight polychromasia. A bone marrow biopsy was done and showed marked hypoplasia (cellularity <5%) with diffuse gelatinous transformation. These findings were due to deficiency in carbohydrates, calories and depletion of the bone marrow fat stores.
Cases of anorexia nervosa with pancytopenia, severe neutropenia and GMT are rare. These symptoms may be reversed with rapid adequate nutrition with close monitoring for refeeding syndrome. In addition, there are reports that use of hematopoietic growth factors may also be used to accelerate bone marrow recovery. However once the patient is medically stable, treatment of the underlying condition of anorexia nervosa is essential to prevent relapses.
271 RARE OVARIAN TUMOR MASQUERADING AS HEMATOMETRA
Sharma A, Northrip K. University of Kentucky, Lexington, KY.
Case Report: An 11 years old African American female presented to the afterhours clinic with the chief complaint of a vague deep intermittent lower abdominal pain since 2-3 months without any radiation. It was associated with worsening generalized abdominal distension, a 40lbs unintentional weight gain and intermittent diarrhea alternating with constipation over the previous 3 months. Her past medical history was noncontributory. She denied being sexually active or having reached menarche.
On examination, her abdomen was soft but distended without hepatosplenomegaly. A globular mass was felt rising from the pelvis. No focal tenderness or hernias were noted. Fluid thrill was appreciated. On digital rectal examination, no hard stool, palpable masses or blood were appreciated. On genital examination, she had normal-appearing external genitalia except for a slight bulge of the introitus. She was noted to have stage IV pubic hair and breast development. An abdominal radiograph revealed mild fecal burden without evidence of obstruction. The possibility of an occult malignancy was suspected but in view of her young age and absence of any B symptoms, it was considered prudent to avoid imaging radiation exposure prior to specialty consult. A presumptive diagnosis of hematometra was made based on the constellation of signs and symptoms and she was referred to OBGYN for further management.
Later, a CT scan of abdomen and pelvis revealed a 14x11x10cm cystic mass arising from the right ovary with internal septations, along with a massive ascites. She underwent laparotomy with right ovarian cystectomy, right oophorectomy and partial omentectomy. Histopathology of the ovarian mass revealed a juvenile granulosa cell tumor (JGCT) of the ovary (Stage IB).
Ovarian granulosa cell tumors (GCT) are extremely rare neoplasms arising from the sex-cord stromal cells of the ovary, representing less than 5% of all malignant ovarian tumors. JGCT represents only 5% of all GCTs and the mean age at diagnosis is 13–17 years. Most GCTs produce estradiol leading to isosexual precocious puberty. This might explain the advanced secondary sexual characters in our patient. Complete surgical resection, if achievable, is usually curative. This case highlights the importance of considering how to structure a plan so as not to miss a rare diagnosis while pursuing more common ones.
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273 TREATMENT OF PEDIATRIC CHOLINERGIC REACTION IN RURAL KENYA
Shirk AM. University of Alabama -Birmingham, Birmingham, AL.
Case Report: 15 month old male presented to rural hospital in Kijabe, Kenya with fever, seizures, and agitation. Patient was full term infant, IUTD, with motor development delay but no other significant PMH. Morning of presentation mom found him on the floor under his crib, crying and combative. He had episode of “jerking” and one episode of NBNB emesis. ROS positive for rhinorrhea, drooling, and decreased activity the previous day. He had no known trauma or new food or herbal medicine exposure. In the ER, patient had temp of 101.2, HR of 220, RR of 15 with subcostal retractions and saturation of 74% on RA. Patient was agitated with intermittent 30 second seizures with left eye deviation. Pupils were 2mm, slowly reactive and patient was drooling. Auscultation revealed tachycardia with no murmur, scattered crackles, and wheezing. Extremities were hypotonic, cool and clammy with 1+ reflexes. Electrolytes showed Na 137, K 4.7, Ca of 9.8, and Cr of 1.3. CBC WNL with WBC 12,000. CSF had 2 WBC, 0 RBC and normal protein/glucose. Chest x-ray showed no infiltrate. Head CT with mild brain atrophy but no traumatic findings. Patient was given Ceftriaxone, 50/kg NS over 6 hours, and loaded with phenobarbital. Over the next 72 hours patient developed diarrhea, bilateral infiltrates on chest x-ray, copious secretions, and required intubation. On day 4 of illness, despite no clear history of cholinergic exposure, with seizures, vomiting, bronchorrhea, diarrhea, miosis, and diaphoresis patient was empirically given Atropine 0.04 mg/kg with immediate improvement. Within 4 hours, PEEP and O2 were weaned, and he was extubated within 24 hours. With q2 hour Atropine (drip was unavailable), fever, secretions, wheezing resolved, and reflexes improved. Patient was slowly weaned to q6 hour atropine, and was discharged 2 weeks after presentation. Discussion: Cholinergic poisonings without a source are a rare, but important clinical dilemma. Cooking containers and specific endemic herbs must be considered as possible sources when the toxidrome emerges. Mom used herbal medicines with previous children, which is likely source despite multiple denials in history. In resource limited settings, atropine can be used to effectively treat symptoms with careful observation and frequent dosing.
274 INTRACARDIAC MASSES AS INITIAL FINDING IN A CHILD WITH ACUTE MYELOGENOUS LEUKEMIA
Singh M1, Cain J2, Ramji F3, Kern W4. 1 University of Oklahoma, Oklahoma City, OK; 2 University of Oklahoma, Oklahoma City, OK; 3 University of Oklahoma, Oklahoma City, OK and 4 University of Oklahoma, Oklahoma City, OK.
Case Report: We describe an 18 month old boy who presented with 4 day history of increased work of breathing, decreased oral intake, and oliguria. A chest radiograph showed cardiomegaly, which prompted an emergent echocardiogram. The echocardiogram revealed a moderate pericardial effusion with infiltrative cardiomyopathy. Tumor masses were seen in all 4 chambers with consequent decrease in ventricular filling. Cells in the pericardial fluid were identified as myeloblasts by flow cytometry. A renal ultrasound showed bilateral hydronephrosis, caused by infiltrative masses in the collecting systems of both kidneys. A bone marrow aspiration and lumbar puncture were planned for the next morning but rapid decompensation, with developing multi-organ failure, led to emergent use of extracorporeal membrane oxygenation (ECMO).
Literature review shows this to be an unusual site, especially in children. While outcome in similar reports was poor, our patient remains a long-term survivor after a challenging clinical course. Data on myeloid sarcoma was reported during later incidental reviews and is incomplete. Although myeloid sarcoma was once thought to be rare, it appears that a significant minority of pediatric AML cases present with mass lesions. Depending on anatomical site, such lesions may add to morbidity and early mortality. Our patient’s presentation in cardiogenic shock, rapidly progressing to multiorgan failure, use of pericardial fluid for diagnosis and the crucial role played by imaging is unusual. Aggressive support was started with ECMO and dialysis. Chemotherapy was also delivered but was attenuated due to hepatic compromise. In spite of this inauspicious situation, this patient is a long-term survivor-perhaps the only one reported in the pediatric literature with intra-cardiac myeloid sarcoma. The case is worth reviewing because of its unusual features. It also demonstrates the importance of pediatric subspecialty team work for children with cancer presenting with life threatening symptoms.
275 MY BELLY HURTS...AGAIN
Smith D, Mitchell H, Monroe K. UAB, Birmingham, AL.
Case Report: Introduction: Abdominal pain is one of the most common complaints in the pediatric ED. Many times this can be a result of a simple viral infection, constipation or functional abdominal pain. We must be aware though, that cases of abdominal pain that stand apart in their symptom quality or duration, require further workup and expansion of our differential. Hereditary pancreatitis is rare, but has significant sequelae, and should be suspected in children with recurrent epigastric pain associated with nausea and vomiting.
Case: The patient is a 7 year old male who presented to the ED with intermittent abdominal pain for 6 months. He has been evaluated by a pediatric GI doctor, but no etiology had yet been discovered. At the time of presentation in our ED, the patient had 3 weeks of worsening epigastric pain, and one day of rapid breathing. A chest x-ray in the ED showed a large right pleural effusion. A CT of the chest, abdomen and pelvis subsequently revealed bilateral pleural effusions, pancreatic pseudocysts with calcifications and portal-splenic vein thrombosis with collaterals. Initial lab work revealed a WBC count of 18 thous/uL and a lipase of 1553 U/L. The clinical picture was consistent with hereditary pancreatitis with acute flair and reactive pleural effusions. The patient remained clinically stable but was admitted for fluid and pain management along with therapeutic thoracocentesis.
Discussion: Hereditary pancreatitis is an autosomal dominant condition, resulting in recurrent episodes of pancreatitis. Episodes begin in late childhood and are consistent with acute pancreatitis including sharp epigastric pain, fever, nausea and vomiting. Episodes last 1-3 days and typically become more frequent as the patient ages. Recurrent pancreatitis will eventually lead to chronic pancreatitis, loss of pancreatic function, type 1 diabetes mellitus and an increased risk of pancreatic cancer. Diagnosis is made through clinical presentation, lab work consistent with pancreatitis and imaging revealing characteristic pancreatic changes.
Conclusion: Abdominal pain in children can be easily disregarded. It is important to realize that hereditary pancreatitis is rare, but has life-long implications and early diagnosis is important for proper management. A wide differential in children with atypical presentations will protect against rare diseases falling through the cracks.
276 ALL THAT HURTS IS NOT ARTHRITIS
Velayuthan S1, Gates P2, Chen H1,2, Raman V1,2. 1 Louisiana State University Health Sciences Center, Shreveport, LA and 2 Shriner’s Hospital for Children, Shreveport, LA.
Case Report: A 17- year-old Hispanic female was admitted for severe joint contractures. Symptoms started at 2 years of age with fever, joint pain and swelling. She was diagnosed with Juvenile Idiopathic Arthritis (JIA) and treated with corticosteroids, methotrexate and anti-inflammatory medications. Therapy was subsequently discontinued due to lack of response. Her symptoms progressed to joint contractures and inability to walk. Her brother had similar disease and died of respiratory complications at the age of 14 years. On examination, the patient was a small-built, wheelchair-bound teenager with severe flexion contractures in the wrists, fingers, knees, ankles and toes without synovitis or joint effusions. Laboratory studies showed no signs of inflammation and rheumatoid factor (RF) and anti-cyclic citrullinated peptide were negative. Radiographs showed generalized osteopenia with near-complete loss of carpal bones and osteolysis of the distal ulna and left femoral head.
The severity of osteolysis in the absence of erosions or signs of inflammation and similar disease in a sibling suggested a genetic etiology. Additionally, the parents were reportedly second cousins. Based on the clinical and radiographic findings, the patient was diagnosed with Winchester syndrome, an autosomal recessive disorder characterized by multicentric osteolysis, leathery skin, corneal opacities, coarse facies and renal anomalies. Our patient had coarse facies and renal utrasonography was normal. The underlying genetic defect has recently been identified in the matrix metalloproteinase-2 (MMP-2) gene. Our patient highlights the importance of considering alternative diagnoses besides JIA in patients with an atypical presentation, poor treatment response and familial disease.
277 PLASTIC BRONCHITIS PRESENTING IN A 6 YEAR OLD WITH PNEUMONIA
Walkup JD, Rincon-Subtirelu M, Johnson G. University of Tennessee at Chattanooga College of Medicine, Chattanooga, TN.
Case Report: A 6 year old female with history of Fontan procedure presented to the emergency room with worsening cough of three days duration. In addition to this, she had reports of wheezing and a prior diagnosis of asthma. The initial evaluation, including chest x-ray, was significant for right lower lobe pneumonia and elevated CRP.
Over the course of 3 days the patient had worsening hypoxemia and required increasing amounts of supplemental oxygen. Her respiratory exam was quite variable. At times she appeared to be improving in the right lung fields, but then developed diminished air movement on the left lung fields. Because of left lung involvement, post-tussive emesis, and new onset of wheezing, albuterol treatments were given which seemed to improve her status.
On the fourth day of admission her case took an unexpected turn as she began to complain of nasal congestion. During the night she began forcefully blowing her nose trying to clear it and produced a small white tissue-like substance. This “tissue” was roughly 1 cm in length and appeared to have a branching pattern to it, resembling a lung cast. It is believed with the patient’s frequent cough and post-tussive emesis that the lung cast became lodged in the nasal passage.
Based on the patient’s Fontan physiology, changing lung exam, and presence of a lung cast, a diagnosis of Plastic Bronchitis was made. Plastic Bronchitis is the development of bronchial casts that cause airway obstruction, possibly due to endobronchial lymph leakage. This case is unique because this process has been minimally described in palliated single-ventricle physiology and the presence of asthma and pneumonia confounded the diagnosis.
278 SEIZURES AND REGRESSION IN A PEDIATRIC PATIENT: A RARE DISORDER IN A FAMILIAL COHORT
West C, Dunlap M. University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Case Report: Progressive loss of milestones, cognitive function, and new onset seizure disorder is an ominous constellation of symptoms. The differential diagnosis includes neuronal ceroid lipofuscinoses (NCL), leukoencephalopathies, mitochondrial disorders, mucopolysaccharidoses, gangliosidoses, and peroxisomal disorders, a daunting list at best. We present the case of a 4 year old female who was found to have Neuronal Ceroid Lipofuscinoses, late infantile type II (CLN2) after progressively worsening seizures and loss of milestones. Diagnosis was made via lysosomal enzyme testing, with deficiency of Tripeptidyl-peptidase 1 (TPP-1) in conjunction with concomitant evaluation of a biological sibling.
Patient is a 4 year old female with complex medical history, clouded by placement in foster care at 2 years of age. At that time she had a speech delay, but normal growth and development in other domains. Her first seizure was at 32 months. Initial genetics work up was negative. She was followed by her primary care provider for progressively worsened seizures, loss of motor and speech milestones, and dysphagia with aspiration events. At 4 years she was admitted for placement of a gastrostomy tube secondary to dysphagia and aspiration. Hospital stay was extended by surgical complications. During her admission it was noted that a biological sibling, who was being cared for in a separate foster placement, was also admitted with very similar symptomatology and clinical course. Expanded genetics evaluation included lysosomal enzyme testing for our patient, and conjunctival biopsy with electron microscopy for the sibling that showed lysosomal inclusions characteristic of Neuronal Ceroid Lipofuscinosis.
Neuronal Ceroid Lipofuscinoses are a group of rare disorders. This case highlights the importance of continuity of care, particularly for children whose biological family history is incomplete. As research into this inherited genetic condition is ongoing, it is important to identify cohorts of affected families whose disease course and response to treatment provide direction for future research. Lastly, this case draws attention to consideration of NCL in the differential diagnoses when seizures and developmental regression are present.
279 GASTRIC PNEUMATOSIS
Wright L, Caudill J, Crissinger K, Gremse D. University of South Alabama, Mobile, AL.
Case Report: Gastric pneumatosis is a very rare entity. This case report highlights an unusual presentation of an infant with a past medical history of gastroschisis repair S/P primary repair after birth who developed gastric pneumatosis.
A 1 month old female presented with a 1 day history of nonbloody, nonbilious emesis, increased abdominal distention, and excessive irritability, but no history of fever, rhinorrhea, cough, or diarrhea. She had stable vital signs and her cardiopulmonary exam was normal. Her abdomen was protuberant, but soft, and nontender with good bowel sounds.
A complete blood cell count, CRP, and electrolytes were normal, but her liver tests showed total bilirubin 4.9, direct bilirubin 3.7, ALT 69, and AST 84. An acute abdominal series showed mild gaseous distension. An UGI/SBFT showed reflux to the oral cavity. Her labwork worsened over 3 days to CRP 6.6 mg/dL, total bilirubin 8.3, direct bilirubin 6.5, AST 172, ALT 144, and GGT 161 so that she underwent a percutaneous liver biopsy. On the evening of the biopsy, she developed increasing abdominal distention, tachycardia, respiratory distress, and hypotension. An abdominal x-ray showed free air. Due to concern of a liver biopsy complication, an emergent exploratory laparotomy was performed, but revealed no bleeding from the liver biopsy site or leaks in the duodenum or several bowel loops in the RUQ. The stomach was, however, noted to have pneumatosis involving the gastric wall. There appeared to be several areas of bruising or blood in the stomach wall without obvious perforation. An EGD showed severe gastritis, but no ulcerations or active bleeding. Blebs in the submucosa were observed during the EGD. Postoperatively, she remained intubated for 7 days and required a milrinone drip for 6 days to maintain her blood pressure. After 21 days of antibiotics and acid reduction therapy, there were no signs of pneumatosis on x-ray, the baby was feeding well, and she was discharged home.
Fewer than 40 cases of gastric pneumatosis have been reported, mostly in association with necrotizing enterocolitis and proximal intestinal obstruction. With a presumed infectious etiology, treatment includes broad spectrum antibiotic therapy and hemodynamic support. When a child presents with vomiting, it is important to remember this complicated gastrointestinal history.
280 EARLY INDOMETHACIN USE INCREASES NEC IN PREMATURE INFANTS
Abu El Haija M1, Rouce R2, Rassin D1, Jain SK1. 1 University of Texas Medical Branch, Galveston, TX and 2 Texas Children’s Hospital, Houston, TX.
Purpose of Study: NEC is a disease of prematurity with significant morbidity & mortality. Indomethacin (INDO) is COX-2 inhibitor used for treatment of PDA & IVH prophylaxis. INDO ↓es intestinal blood supply which may ↑risk of NEC. Premature infants (PI) often receive inotrops (DOPA) &/or steroids (HCT) for hypotension. We explored if early use of INDO alone or in combination with DOPA &/or HCT ↑es NEC.
Methods Used: In retrospective 1:1 matched case control study, medical records of infants with NEC (January 2007- March 2010) were collected. Gestational age matched controls born within 3 months of cases were included. Continuous & categorical variables were compared in NEC versus controls by using t-test & Pearson chi-square. We used multivariate regression analysis to determine the significance of receiving INDO, DOPA or HCT alone/combination in developing NEC.
Summary of Results: 64 infants with NEC were matched to 59 controls (table). 63% of the infants with NEC received early INDO (IVH prophylaxis; p0.02 figure 3) & 6% infants in NEC group developed PVL versus none in control (p 0.005). NEC group received longer duration of TPN (p 0.0001).
Conclusions: Early INDO use↑es NEC, PVL & duration of TPN use in PI.
Perinatal Medicine Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
281 TRANSCUTANEOUS BILIRUBINOMETRY DURING & AFTER PHOTOTHERAPY IN PRETERM INFANTS
Ansari S, Fonseca RA, Malloy M, Jain SK. University of Texas Medical Branch, Galveston, TX.
Purpose of Study: Jaundice (NJ) occurs in ≥2/3rd infants. Visual inspection is not accurate to evaluate NJ specially during & after phototherapy (PHT). Transcutaneous bilirubin (TcB) is accurate but PHT affects reliability. We evaluated accuracy of TcB from covered (TcB_C) & PHT exposed skin (TcB_UC) in preterm infants (PI) during & after discontinuing PHT.
Methods Used: In prospective observational study, we included PI (30-36 wks) requiring PHT. Infant’s forehead was covered by BiliEclipse & TcB_C/TcB_UC were measured on infants forhead. PHT was turned off 5 minutes before measuring TcB. Capillary blood sample was collected (within 15 minutes of TcB) for serum bilirubin (TSB). TcB_C, TcB_UC, TSB were measured before starting PHT (baseline), every 24 hours during PHT & 24 hours after discontinuing PHT. ANOVA (analysis of variance) & Bonferroni t-test were used to compare TcB_c & TcB_UC with TSB.
Summary of Results: We included 64 infants, mean gestation was 33.4 wks, birth weight 2022 grams, 62% hispanic & 17% DAT positive infants (table). Before starting PHT, TcB_C, TcB_UC & TSB were not significantly different. TcB_C correlated with TSB after 46, 65 & 89 hours of PHT exposure. TcB_UC was significantly lower than TcB_C & TSB after 46, 65 & 89 hours of PHT exposure. 24 hours after discontinuing PHT, TcB_C remained significantly higher than TSB & TcB_UC.
Conclusions: In PI, TcB_C is reliable in measuring bilirubin during PHT treatment but not after 24 hours discontinuing PHT. It may take >24 hours to equiliberate TcB_C after discontinuing PHT.
282 BENEFIT VERSUS RISK OF LUMBAR PUNCTURES IN EXTREMELY LOW BIRTH WEIGHT INFANTS
Baalbaki S, Ambalavanan. N. University of Alabama in Birmingham, Birmingham, AL.
Purpose of Study: Meningitis is diagnosed by evaluation of cerebrospinal fluid (CSF) obtained by lumbar puncture (LP). Extremely Low Birth Weight (ELBW) infants are sometimes evaluated by LP soon after birth if exposed to preterm prolonged rupture of membranes (PPROM) or chorioamnionitis, which are known risk factors for early onset neonatal sepsis. However, it is unknown if the increased venous pressure associated with infant positioning for LP increases the risk of severe intraventricular hemorrhage (IVH). We hypothesized that LPs on the first day of life (DOL) are associated with increased risk of severe IVH that may outweigh the benefits of confirming meningitis in ELBW infants.
Methods Used: Retrospective data analysis of electronic medical records of 343 ELBW infants born at the University of Alabama in Birmingham Hospital in 2010-12 was performed to quantitate the identification of meningitis and incidence of severe IVH in relation to other clinical variables. A p<0.05 was considered significant.
Summary of Results: Ninety-two of 343 neonates underwent a LP on DOL1. Infants receiving a LP were significantly heavier at birth and their first CBC had higher white blood cell counts, percentage of neutrophils, and platelet counts. Their mothers were more likely to be diagnosed with clinical chorioamnionitis and to have had longer PPROM. Only 1 CSF culture was positive, but the organism (coagulase negative staphylococcus) was considered a contaminant. Of those receiving a LP, 27.2% (25) developed severe IVH compared to 13.5% (34 of 251) of those who did not. Patients receiving a LP were 2.97 times more likely to develop severe IVH after adjustment for other important clinical variables using logistic regression.
Conclusions: A LP on DOL1 is associated with a higher risk of severe IVH in ELBW infants and a low yield of positive cultures. Clinical algorithms including LPs as part of the sepsis workup in preterm infants may need reevaluation if these findings are validated in larger or multicenter studies.
283 TOPICAL NYSTATIN FOR PREVENTION OF CATHETER ASSOCIATED CANDIDIASIS IN ELBW INFANTS
Bodin MB1,2, Godoy G2, Philips JB1. 1 Univ of AL at Birmingham, Birmingham, AL and 2 DCH Regional Medical Center, Tuscaloosa, AL.
Purpose of Study: Systemic infections with Candida species continue to be major causes of morbidity and mortality in NICUs. The incidence of such infections in ELBW infants with central catheters has been reported to be between 4% and 15%. Multiple prophylactic protocols have been developed in attempts to reduce these infections. No protocols published to date used topical therapy and instead relied on oral or systemic treatment. We initiated a topical nystatin protocol in an attempt to reduce the frequency of systemic Candidal infections in extremely low birthweight infants with central catheters while minimizing the risks associated with oral or systemic prophylaxis.
Methods Used: All infants with a central venous and/or arterial catheter had a thin layer of nystatin cream (100,000 units/gm) applied to the axillae, groin, neck, and behind the ears once daily until the access device(s) were removed. We retrospectively reviewed the electronic records of all infants <1 kg birthweight admitted to DCH Regional Medical Center between 1/1/2000 and 12/31/2010 to identify those infected with Candida species. We also reviewed the microbiology department blood and spinal fluid culture results. This sudy was approved by the IRBs at the study site and at UAB.
Summary of Results: 464 ELBW infants were admitted during the study period. All had at least one central catheter placed and all received the nystatin protocol. Of these, 3 (0.65%) developed Candida bloodstream infections.
Conclusions: Topical application of nystatin cream in ELBW infants with central catheters appears to be an effective prophylactic regimen for prevention of central catheter associated systemic Candidiasis. A larger, randomized trial is needed to confirm this observation.
284 TRANSFUSION ASSOCIATED NECROTIZING ENTEROCOLITIS (TANEC) AT KOSAIR CHILDREN’S HOSPITAL IN VERY LOW BIRTH WEIGHT INFANTS (<1500GMS)
Crabtree CD1, Pakvasa M2, Radmacher P1, Adamkin DH1. 1 University of Louisville, Louisville, KY and 2 Emory University, Atlanta, GA.
Purpose of Study: To identify recent cases of NEC and to determine if PRBC transfusions were temporally associated.
Methods Used: A five-year retrospective chart review of all very low birth weight (VLBW) infants with a diagnosis of NEC (Bell’s Stage ≥ II). Prenatal data, postnatal clinical course and NEC outcomes were reviewed.
Summary of Results: Sixty cases of NEC from 888 admissions over 5 years were identified (rate 6.8%, range 2.9% to 15.2%). TANEC occurred in 45% of cases (27/60). Neonatal profiles were similar between TANEC and non-TANEC infants. Maternal pregnancy profiles were similar except for a significant occurrence of maternal diabetes in non-TANEC infants (15% vs. 0%, p=0.035). Enteral feeding initiation was at ~4 days of life in both groups and receipt of human milk (HM) as first feeding was similar. The feeding rate at the diagnosis of NEC was significantly lower in TANEC infants (125 ± 30 mL/k/d) compared to non-TANEC infants (140 ± 24 mL/k/d, p=0.045). The age at diagnosis was similar although weight at diagnosis of NEC was lower in TANEC infants (1159 ± 284 g) compared to non-TANEC infants (1325 ± 316, p=0.038). At diagnosis of NEC, 90% of non-TANEC infants were receiving either preterm formula (PTF) or HM fortified with PTF compared to 69% of TANEC infants (p=0.044). Interestingly, 6% of non-TANEC and 4% of TANEC infants were never fed. Late onset sepsis occurred in 12 infants in each group (37% and 44%, non-TANEC and TANEC infants, respectively) and each group had a similar exposure to antibiotics prior to diagnosis. There were similar organisms recovered from blood and urine. Medical NEC occurred in 56% of TANEC infants and 61% of non-TANEC infants. Both groups experienced 18% mortality.
Conclusions: The 5-year rate of NEC for our NICU was similar to nationally reported rates. Mortality was somewhat lower than national figures. Variability in rates of NEC from year to year was seen. TANEC occurred more often than expected but at a rate similar to NEC without contemporary transfusion. The rate of late onset sepsis was higher than expected and merits further scrutiny. The role of maternal diabetes during pregnancy was an unexpected finding which requires further investigation.
285 EARLY VITAMIN D SUPPLEMENTATION FOR PREVENTION OF RESPIRATORY MORBIDITY IN EXTREMELY PRETERM INFANTS
Craig C2, Ambalavanan N1, McNair T1. 1 UAB, Birmingham, AL and 2 University of Alabama School of Medicine, Birmingham, AL.
Purpose of Study: To determine if vitamin D supplementation to extremely preterm infants reduces respiratory complications, reduces infection, and prevents bronchopulmonary dysplasia.
Methods Used: Extremely preterm infants born at 28 gestational weeks or less were randomized to receive a placebo, high dose: 800 IU/day or low dose: 200 IU/day oral vitamin D; each infant received the dose for 28 days. This project was an interim analysis of the first 25 patients enrolled in this study (planned total enrollment=100). An enzyme immunoassay (ELISA) for 25(OH) vitamin D was done on blood samples from: cord blood (day 1), postnatal day 14, and postnatal day 28.
Summary of Results: Vitamin D concentrations were compared to the number of days requiring respiratory support, defined as the need for supplemental oxygen or positive pressure ventilation to maintain oxygen saturation levels between 88-95%. The average vitamin D concentrations were 13.57ng/ml in cord blood, 29.5ng/ml in day 14 blood, and 34.14ng/ml in day 28 blood (normal range 30-50ng/ml). The rank correlation coefficient for the length of stay in the hospital was R=-0.33 for cord blood, R=-0.15 for day 14 blood, and R=-0.08 for day 28 blood, with significant p values for each day.
Conclusions: Nearly all extremely premature infants were found to be very deficient in vitamin D at birth. However, no correlation was found between serum vitamin D concentrations and respiratory morbidity. This preliminary analysis was limited due to small sample size; additional biochemical analyses will be performed after enrollment of an additional 50 infants.
286 IMMUNIZATION STATUS OF INFANTS PRIOR TO DISCHARGE FROM A LEVEL IV NICU AT A CHILDREN’S HOSPITAL
Ferguson JM1,2, Harsono M1,2, Sahni J3, Dhanireddy R1,2, Pourcyrous M1,2. 1 University of Tennessee HSC, Memphis, TN; 2 Le Bonheur Children’s Hospital, Memphis, TN and 3 Le Bonheur Children’s Hospital, Memphis, TN.
Purpose of Study: AAP recommends all infant, regardless of their BW or GA, be immunized at the recommended age. However the primary care providers and parents of NICU patients are hesitant, specifically with infants who have surgical complications and congenital anomalies, and therefore immunizations are delayed. Since a majority of these infants are still in the NICU at 2 months of age, it is important to initiate the primary immunization in the NICU. A recent article reported that only 51% of infants prior to discharge from the NICU were “up-to-date” with primary immunization. The objective of this study is to assess the immunization status of infants in the NICU at a children’s hospital where infants may have complex clinical conditions such as congenital heart disease, multiple congenital anomalies and surgical interventions.
Methods Used: This is a retrospective chart review of primary immunization status of 62 infants who were still in the level IV NICU at Le Bonheur Children’s Hospital at two months of age during the year 2011.
Summary of Results: Birth weight of 37 infants was < 1500g (VLBW) and of 25 infants was ≥ 1500g. Amongst VLBW infants, 54% needed surgical GI-interventions. In the VLBW infants, 78% (29 of 37) received primary immunization ⩽ 90 d of age, while 22% (8 of 37) received immunization after 90 d of age. Amongst infants with BW ≥ 1500g, 52% needed surgical GI-interventions and 40% needed intervention for complex congenital cardiac anomalies. Surprisingly, 100% of these infants were immunized before 70 d of age.
Conclusions: Based on the CDC criteria, 2 month old immunizations received at < 91 d of age are considered “up-to-date”. We had 100% “up-do-date” compliance in infants with BW ≥ 1500g and 78% compliance in infants < 1500g. Immunizations that are initiated in the NICU may improve compliance of subsequent immunizations in these vulnerable infants. Much of the success in this NICU can be attributed to the multidisciplinary medical team’s review of immunization needs on daily rounds.
287 BRONZE BABY SYNDROME IN A BLUE FUGATE
George A, Sharma A, Dang S. University of Kentucky, Lexington, KY.
Case Report: A term exclusively breast fed female infant born via C-section to a 24 year old Caucasian mother with gestational diabetes developed hyperbilirubinemia on third day of life. Risk factors for hyperbilirubinemia included parietal cephalohematoma, ABO setup and maternal gestational diabetes. Serum bilirubin level was 20.3mg/dL and phototherapy was started. After 8 hours of phototherapy, the infant developed a bluish-gray discoloration of skin. Parents belong to the family of “Blue Fugates of Kentucky” so the differential diagnosis included methemoglobinemia, breast feeding jaundice, ABO incompatibility and cholestasis.
The Fugates, a family that lived in the Appalachian region of Kentucky, are the most famous example of hereditary methemoglobinemia. This population is named after the family of Martin Fugate- a French native who immigrated to Kentucky in 1820. This family carries an autosomal recessive disorder, lacking the enzyme cytochrome-b5 methemoglobin reductase which reduces spontaneously formed methemoglobin in the body.
Our patient was supplemented with formula and phototherapy was continued. Initial laboratory studies ruled out methemoglobinemia as well as ABO incompatibility. Bilirubin levels started trending down but the discoloration persisted. Interestingly, when the temperature probe was removed from the trunk, the discoloration was not noticed on that area. At that point, a diagnosis of bronze baby syndrome (BBS) was entertained.
BBS as a complication of phototherapy was first described by Kopelman et al in 1972. BBS is rare and is noted in infants with elevated levels bilirubin in their blood, especially after starting phototherapy. The etiology of BBS is unknown, but it is believed to be caused by an abnormal accumulation of un-excreted photoproducts of bilirubin or an unknown pigment that has the characteristic absorbance on spectrophotometry. Liver function tests performed on the infant were normal and her discoloration resolved after discontinuation of phototherapy confirming the diagnosis.
288 DOES INTENSE LACTATION EDUCATION HELP INCREASE THE PROVISION OF BREAST MILK AT 32 WEEKS OR LESS?
Kahn L, Eichenwald E. University of Texas, Health Science Center, Houston, TX.
Purpose of Study: The purpose of this study was to determine whether more intense lactation education and ongoing maternal intervention would increase the initiation of pumping and the duration and amount of breast milk supply to preterm infants compared with standard protocols in place in the NICU.
Methods Used: After IRB approval as a quality improvement initiative, enrollment began in October, 2012. We planned to enroll 60 mothers in each group or stop enrollment by October 31, 2013 or whichever came first.
Inclusion criteria included:
32 weeks or less, inborn only
Maternal stability after delivery
English speaking
No contraindication to breast feeding
Baby expected to go home with birth mother
Intervention mothers were enrolled in months the PI was off clinical service. Infants delivered during service months served as controls and received standard lactation education. The intervention included a face to face interview within 48 hours of birth by the PI, a special pamphlet addressing the provision of breast milk to a premature infant and additional telephone contact at one week post discharge.
The primary outcome was the amount of breast milk available for each baby assessed at 48 hours, one, two and four weeks of life.
Summary of Results: Recruitment is on going. Complete analysis will be available at the time of the meeting. We expect to find increased provision of breast milk to our premature population born to mothers in the intervention group.
Conclusions: Maternal provision of breast milk to preterm babies is an important aspect of their medical care with obvious health benefits. Understanding whether different models of lactation support affect maternal decisions to provide breast milk to their vulnerable infants is essential.
289 IATROGENIC CHYLOUS ASCITES IN A FORMER PREMATURE INFANT WITH SEVERE CHRONIC LUNG DISEASE
Lee C, Makoni MM, Chaaban H. OUHSC, Oklahoma City, OK.
Case Report: Introduction: Chylous ascites in infants and neonates is rare. There is limited data on pathogenesis, diagnosis, and treatment. We present a case of iatrogenic chylothorax and ascites in a former premature infant with severe chronic lung disease (CLD).
Case Description: The patient was a 5 month old male infant who presented to our hospital for gastrostomy tube (GT) and tracheostomy tube placement. He was a former 26 week premature infant with a history of pulmonary hypertension, stage 4 bronchopulmonary dysplasia (BPD) with significant hyperexpansion and suspected blebs, TPN cholestasis, and poor growth. On arrival, he had severe respiratory acidosis requiring increasing ventilator settings resulting in worsened hyperexpansion. He improved gradually and underwent an uncomplicated tracheostomy. A few days later, he had worsening respiratory status and abdominal distention. Due to concern for pulmonary hypertension, an echocardiogram was done. There was no evidence of pulmonary hypertension but there were bilateral pleural effusions and massive abdominal ascites. An abdominal ultrasound showed normal liver architecture and blood flow. Paracentesis revealed milky white fluid significant for triglycerides >1000mg/dL, 99% lymphocytes and WBC>2000/mm3. He was treated with bowel rest, TPN, octreotide, spironolactone, and multiple paracenteses for comfort and with resolution of his pleural effusion but persistence of his ascites. Work up for chylous ascites was negative with no evidence of abdominal masses, malrotation on Upper GI, or liver dysfunction. We suspect that his chylothoax and ascites could be a result of the rapid changes in the intra-thoracic pressure secondary to his severe CLD and assisted ventilation. The patient continued to have ascites and worsening electrolyte abnormalities despite maximum medical therapy. Pediatric surgery was consulted for further evaluation and management, however due to continued deterioration in his clinical status, the parents decided to withdraw care.
Discussion: This case represents a case of chylothorax and persistent chylous ascites due to suspected rapid changes in the intra-thoracic pressure in a neonate with severe pulmonary disease. Although not a common presentation, it should be considered as an etiology when evaluating chylothorax and chylous ascites.
290 COMBINING TRANSCUTANEOUS CO2 MEASUREMENT WITH SERUM BICARBONATE TO PREDICT CAPILLARY BLOOD GASES
Lee M, Elabiad M. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Our objective was to estimate a capillary blood gas (CBG) by combining the partial pressure of carbon dioxide (PaCO2) obtained noninvasively by transcutaneous PaCO2 monitoring (TCOM) with serum bicarbonate obtained on a basic metabolic panel (BMP). The estimated CBG would be compared to the measured CBGs obtained as part of routine care.
Methods Used: A TCOM measurement was be obtained within 60 minutes of a scheduled lab collection that included a CBG and a BMP. As precision of TCOM decreases with high PaCO2 levels, levels above 55 mm Hg were excluded from the final analysis. CBG was estimated using the PaCO2 measurement on TCOM, the bicarbonate level on a BMP, and a calculated pH using the Henderson-Hasselbalch equation. The study outcome was the number of calculated CBGs that were in agreement with measured CBGs. Statistically, this was defined as a measurement within 1 standard deviation from the mean based on a Bland-Altman analysis and clinically a pH within ±0.1 units of the measured pH but not crossing a pH interval of 7.3-7.45. If calculated pH crossed the pH interval, then the clinical agreement drops to within ±0.05 units of measured CBG.
Summary of Results: Twenty seven simultaneous measurements of TCOM and blood work were obtained. Fifteen TCOM measurements were <55 mmHg. Fourteen of the 15 calculated CBG had the pH within 1 standard deviation from the mean and satisfied the clinical definition of agreement (figure).
Conclusions: Combining transcutaneous PaCO2 with serum bicarbonate is a safe and accurate method to estimate a CBG. Its use would save on blood volume and time of the procedure as well as on cost of running the CBG.
291 FIVE YEAR EXPERIENCE (2007-2011) WITH NECROTIZING ENTEROCOLITIS AT KOSAIR CHILDREN’S HOSPITAL IN VERY LOW BIRTH WEIGHT INFANTS (<1500GMS)
Pakvasa M1, Crabtree CD2, Radmacher P2, Adamkin DH2. 1 Emory University, Atlanta, GA and 2 University of Louisville, Louisville, KY.
Purpose of Study: To review the 5-year experience with necrotizing enterocolitis and transfusions.
Methods Used: A five-year retrospective chart review of all very low birthweight (VLBW) infants who developed NEC (Bell’s Stage > II). Sixty cases (6.8%) from 888 admissions were identified. Prenatal data and postnatal clinical course were reviewed as to the antecedents associated with NEC.
Summary of Results: The 5-year NEC rate for our NICU was 6.8% with annual variation from 2.9% to 15.2%. Perinatal and neonatal profiles revealed mean birthweight 983 grams and 27 weeks’ gestation. Sixty-three percent of infants were delivered by c-section and 78% of mothers had received antibiotics prior to delivery. Approximately 1 in 4 mothers admitted to smoking during the pregnancy and 15% admitted to illicit drug use. Respiratory distress syndrome was diagnosed in 98% of infants and 77% received at least 1 dose of surfactant. Forty-seven percent received pharmacologic therapy for PDA and 13% were ligated. One half of the cohort developed late onset sepsis. Eighteen percent had positive cultures at diagnosis of NEC. Enteral feeding initiation was at ~4 days of life with 62% receiving human milk as first feed. NEC was diagnosed at a mean (± SD) postnatal age of 28 ± 15 days. Forty percent of infants were receiving human milk (HM, plain or fortified) at the time of diagnosis and the feeding rate was 129 + 37 mL/kg/day. Transfusion associated NEC (NEC diagnosed within 48 hours of transfusion, TANEC) occurred in 27 infants (45%). Medical NEC occurred in 58%, and 18.3% of cases resulted in death.
Conclusions: The overall rate of NEC for our NICU was similar to nationally reported rates, while mortality in our cohort was lower than national figures. Year to year variability in rates of NEC were seen. Late onset sepsis and TANEC were more common than expected. We speculate that strategies to decrease both late-onset sepsis and transfusion exposure will improve outcomes.
292 ADDITIONAL EFFECTS OF ABSENT END-DIASTOLIC FLOW IN PREMATURE INFANTS?
Parker WJ, Ray CS, Bazacliu C, Waller J, Bhatia J. Medical College of Georgia, Georgia Regents University, Augusta, GA.
Purpose of Study: Determine the effects of fetal absent or reversed end-diastolic flow on morbidity and mortality in premature infants.
Methods Used: A 5-year retrospective study identified 58 fetuses with absent or reversed end-diastolic flow prior to delivery. Infants were grouped into those <30 [n=26] or 30 to 36 and 6/7[n=32] weeks gestation. Data collected included maternal age, gravida and parity, birth weight, 1 and 5 minute Apgar Scores, intrauterine fetal demise, death in delivery room, neonatal death, hepatic dysfunction [Alanine aminotransferase, aspartate aminotransferase, direct bilirubin], Necrotizing enterocoitis [NEC], Intraventricular hemorhage [IVH], oxygen requirement at 36 weeks post menstrual age [CLD], length of stay and malformations. Data analyzed by t-tests or Wilcoxon Rank Sum test for continuous variables and chi-square or Fisher’s Exact test for catgorical variables.
Summary of Results: Infants below 30 weeks gestation demonstrated lower median Apgar scores at 1- and 5 minutes, lower mean platelet count, higher median length of stay and higher ALT, higher incidence of NEC, Stage II or greater, chronic lung disease, death in the delivery room, and death in the neonatal period than infants greater than 30 week gestation [Chi square or Fisher’s Exact tests]. Further, incidence of chromosomal abnormalities or malformations was significantly greater in infants > 30 than < 30 weeks [p=0.0063] gestation.
Conclusions: Infants born after absent or reversed end-diastolic fetal flow born prior to 30 weeks gestation, have lower Apgar Scores, higher ALT, higher incidence of NEC, CLD and death compared to a cohort greater than 30 weeks. Incidence of congenital anomalies was greater in the larger cohort of infants. These data are similar to previous reports for major morbidity, but suggest the need for further studies based on the incidence of malformations. Limitations of our study: retrospective, small number of subjects, no comparable group of infants without aberration in umbilical flow.
293 IS RETINOPATHY OF PREMATURITY AN EMERGING PROBLEM IN INDIA?
Patel R1, Starner C1, Shah MJ2, Talati AJ1. 1 UTHSC, Memphis, TN and 2 Polio Foundation, Ahmedabad, India.
Purpose of Study: Retinopathy of prematurity (ROP) is a developmental disease of the retina in which deficient vascularization occurs. ROP is a leading cause of childhood blindness worldwide and the number one cause of childhood blindness in the U.S. The risks for ROP are multifactorial and include low birth weight and prematurity. The current screening guidelines in the United States entails that any infant, who weighs less than 1500g at birth or is born at 30 weeks or less, be screened because they are at risk for developing ROP. Since ELBW infants’ survival is poor in India, physicians do not think of ROP as a significant problem. We proposed to review the problem of ROP in an urban setting in India, and emerging nationality.
Methods Used: A prospective chart review, during a one-month duration in Ahmedabad, India. Polio Foundation’s ROP team was followed and observed the screening eye exams performed by Retcam and later reviewed by an Ophthalmologist. Retcam was used by the Polio Foundation team in several hospitals throughout the city of Ahmedabad. Clinical data was collected via examining patient charts. Preterm infants with BW ⩽ 2000 gm or ⩽ 32 weeks were screened.
Summary of Results: 67 patients who had a mean BW of 1479(SD 471) grams were screened. There were 7 (10.5%) who required treatment and this group had a mean birth weight of 1175grams (SD 445). The mean gestational age of the total population was 31.5 wk (SD 2.9). The patients requiring treatment had a mean gestational age of 29 wk (SD 1.5). There was no correlation found between gender and developing ROP. Twenty-one percent of the twin patients required treatment suggesting the possibility of it being a risk factor. Of the 7 patients requiring treatment, 6 of them had been on supplemental oxygen and 2 of them had been put on ventilation, suggesting the definite role of supplemental oxygen.
Conclusions: A large number of babies needed treatment for ROP in this cohort. The infants requiring treatment were heavier in this cohort compared to infants in United States. The data from each country should be collected and guidelines developed to screen these preterm infants as more premature babies survive in this emerging and developing nationalities.
294 PARTIALLY THROMBOSED UMBILICALVEIN VARIX WITH ASSOCIATED TETRALOGY OF FALLOT
Patrick-Esteve J, Eggie D, Buis M. LSUHSC-New Orleans/Children’s Hospital, Gretna, LA.
Case Report: Thrombosis of an umbilical vein varix (UVV) is a rare finding with unclear clinical consequences. Various outcomes depending on associated anomalies have been reported. One recent case series, of infants with UVV, found a higher incidence of associated fetal abnormalities including fetal anemia, chromosomal abnormalities and intrauterine death. We present a case of a partially thrombosed UVV with associated Tetralogy of Fallot.
Our infant, twin A, was born at 33 WGA via cesarean section secondary to oligohydramnios, non-reassuring fetal status, and breech positioning. He was born to a 32 year old, G3 P1 mom who conceived dichorionic diamniotic twin boys after a round of clomid injections. Maternal history was complicated by chronic hypertension, anti-phospholipid antibody syndrome, hypothyroidism, and a history of HSV. Maternal medications included Procardia, Lovenox, Aspirin, progesterone injections and Armour thyroid. Prenatal ultrasound showed concern for umbilical artery aneurysm. The infant was delivered at 1425 grams and immediately required resuscitation and intubation. Apgar scores at 1 and 5 minutes were 3 and 7, respectively. The infant was soon transferred to a tertiary care facility where an Echocardiogram confirmed the finding of TOF, and an abdominal ultrasound revealed a partially thrombosed UVV, without involvement of the portal vein. The UVV was initially monitored with weekly abdominal ultrasounds, followed by less frequent monitoring as the thrombosed varix remained stable.
There is still no overall consensus on management of prenatally diagnosed UVV, although, regular NST and ultrasound for monitoring has been recommended. Our infant presents with several findings known to increase the risk of morbidity and mortality associated with UVV, including abnormal NST, IUGR, TOF and oligohydramnios. Furthermore, he presents with a partially thrombosed UVV, a condition which has been associated with intrauterine fetal demise. Emergent delivery of our infant due to non-reassuring NST may have prevented a potential intra-uterine demise secondary to a partially thrombosed UVV. With close monitoring of his UVV no intervention was necessary, and the patient is doing well at home with outpatient management of his congenital heart disease.
295 INTRAVENTRICULAR HEMORRHAGE- A PREVENTABLE BAGGAGE
Ravisankar S1,2, Higginson J1,2, Stroud T2, Williford A2. 1 East Carolina University, Greenville, NC and 2 Vidant Medical Center, Greenville, NC.
Purpose of Study: We initiated a quality improvement project to decrease the incidence of Intraventricular hemorrhage (IVH) in our unit. IVH is identified as one of the major problems impacting the survival, neurodevelopment and eventual quality of life of premature neonates. We reviewed the data of all our inborn patients over the last two years to evaluate the incidence of severe IVH and all IVH (< 1500 gram patients) and were surprised by our high numbers - 12.6% for severe IVH (IQR 3.3-10.3) and 31.1% for all IVH (IQR 13.6-27.0) compared to centers within the Vermont Oxford Network. Recognizing such worrisome numbers, we scrutinized our practice to identify key variables which may have contributed to such high incidences and noticed that our admission temperatures were well below the accepted standards. Vermont Oxford data showed us with a 51.3% (IQR 8-34) rate for admission temperatures less than 36C in infants <1500 grams birth weight. Our aim in this quality initiative is to reduce our incidence rate of IVH by half and improve admission temperatures.
Methods Used: Streamlined admission protocol for all babies < 29 weeks primarily starting in the delivery room to maintain optimal admission temperatures, followed by a Golden hour rule to meet specific deadlines at the end of the first hour. In addition to ensuring that the overbed warmers are preheated to 100% we have started using a chemical warming mattress and placing all babies < 29 weeks in a polythene bag more consistently with a designated personnel from the delivery team ensuring compliance. A protocol for intravenous indomethacin for IVH prophylaxis was drafted for use in suitable patients. Other changes include maintaining neutral head position with the head end elevated at 30 degrees for the first 72 hours, clustered medical and nursing care with minimized handling, judicious use of sedation, avoiding routine suction and decreased noise and light stimulation.
Summary of Results: Preliminary data has shown improvement with our current efforts coupled with education and awareness.
Conclusions: A formalized protocol combined with collective efforts of the team can improve hypothermia and reduce IVH rates of premature neonates.
296 DOES TREATMENT WITH BEVACIZUMAB AFFECT NEURODEVELOPMENT IN INFANTS WITH RETINOPATHY OF PREMATURITY?
Shipp KE1, Huff LL1, Taylor SN1, Deacon B2, Saunders R2, Ebeling M1, Ruddy-Humphries A1, Shirer K2, Katikaneni L1. 1 Medical University of South Carolina, Charleston, SC and 2 Medical University of South Carolina, Charleston, SC.
Purpose of Study: Intravitreal bevacizumab (IVB) is rapidly replacing laser therapy as the treatment of choice for infants with retinopathy of prematurity (ROP), but its systemic effects on the developing child remain largely unknown. The purpose of this study is to determine whether infants with ROP treated with IVB have worse neurodevelopmental outcomes than infants treated with laser therapy (LT).
Methods Used: We performed a retrospective chart review of infants seen in neonatal follow-up clinic comparing infants who received IVB (with or without LT) with those treated with LT only for ROP. Infants were evaluated in cognitive, fine motor, language, and gross motor development using the Capute Scales (CAT/CLAMS) and modified Peabody Developmental Motor Scale. Developmental quotients (DQ) were calculated for prematurity-adjusted age. Parents completed Ages and Stages Questionnaires (ASQ). Data analysis was performed using Student’s t test and Fisher’s exact test.
Summary of Results: 21 infants were included in the study, with 12 in the IVB group (IVBG) and 9 in the laser group (LTG). The mean gestational age and birth weight for both groups were 24.9 wks (23-26 3/7) and 636 g (435-955) respectively, and were similar between the two groups. 86% of the subjects were ⩽26 wks. The assessments occurred between 6 and 39 months of age, with 83% of the IVBG and 78% of the LTG being >1 year old at follow up. The groups were comparable in z-scores of weight, length, and head circumference. No significant differences were noted between the IVBG and LTG in global cognitive (DQ 82 and 72, respectively, p=0.47), language (DQ 93 and 73, p=0.12), or gross motor development (DQ 78 and 66, p=0.37). The groups showed similar findings in muscle tone, with 33% normal tone in the IVBG and 22% normal in the LTG (p=0.66). No significant difference was found in ASQ pass rate between the two groups, with 50% passing in the IVBG and 33% passing in the LTG (p=0.66).
Conclusions: In our study of children with ROP followed up to 39 months of age (most >1 year old), no significant difference in neurodevelopment was detected between those treated with IVB and those who received only LT.
297 IDENTIFYING THE POSSIBLE ETIOLOGIES OF CEREBRAL PALSY IN AHMEDABAD, INDIA
Starner C1, Patel R1, Shah MJ2, Talati AJ1. 1 UTHSC, Memphis, TN and 2 Polio Foundation, Ahmedabad, India.
Purpose of Study: Cerebral palsy (CP) is a nonprogressive syndrome of neurological deficits that results in dysfunction of muscle coordination, movement, and posture. CP is caused by brain injury and can be congenital or occur later in infancy. Thesymptoms of CP depend upon the severity of brain injury. Therefore, the disease can be very mild or extremely severe. CP is classified based on the type of motor abnormality present in the patient. The three broad classifications are spastic, dyskinetic, and ataxic. Spastic CP can further be categorized by the extent of muscle paralysis in the appendicular skeleton and can range from monoplegic to quadriplegic. Dyskinetic CP can be subcategorized into chorea, dystonia, and athetosis. In the US, the prevalence of CP is about 2 to 4 in every 1000 children. The exact prevalence of CP in India is difficult to obtain. The purpose of this study was to identify preventable causes of CP in a population of patients receiving treatment at a charitable organization in Ahmedabad, India. Future guidelines can be developed to address the identifiable causes.
Methods Used: In this study we collected information on current CP patients attending the non-profit, Polio Foundation Hospital, in Ahmedabad, India. During a four week stay in Ahmedabad, we observed and interviewed the charts and parents of the children with CP. We looked at delivery mode delivery location, and closely examined the birth history to identify the cause of CP. The majority of patients were born in urban private hospitals and all but one patient were born in a hospital.
Summary of Results: A total of 43 patients were assessed with mean age of 6.9 years (SD 4.6). There were 28 males and 15 females in the cohort. Assessing the etiologies of CP from the 43 patients interviewed, we found that 25 had a birth related cause, 2 were genetic malformations, 3 were preterm, 4 were infectious, and 8 were “other”. All 43 patients in the cohort were undergoing physical therapy as treatment and 12 of them had needed at least one operation or surgery in addition to physical therapy.
Conclusions: This study showed that CP in this cohort in Ahmedabad was largely birth related. Home-delivery did not seem to be a major contributory factor. Improving care during delivery and the neonatal period can help decreasing the incidence of CP in this population.
298 RETINAL LASER ABLATION THERAPY AND CORPUS CALLOSUM GROWTH
Thekkiam, Muralidharan S, Zayek MM. USA Children and Women Hospital, Mobile, AL.
Purpose of Study: In spite of absence of major brain imaging abnormalities, extremely low birth weight infants (ELBWI) remain at risk for major disabilities at later age. Abnormal development of corpus callosum (CC) and cerebellum has been associated with adverse neurodevelopmental outcome. Our aim is to determine whether severe retinopathy requiring laser therapy may affect the development of the CC and the cerebellar vermis (VS).
Methods Used: ELBWI with severe intra-ventricular hemorrhage (Grade 3 or 4), periventricular leukomalacia or cerebellar hemorrhages were excluded from the study. We reviewed charts of 63 ELBWI with gestational age <25 weeks and divided them into 2 groups, “Laser” (n=21), and “control” (n=42). Brain MRI was performed for all babies at Term equivalent age (TEA). We measured mid-sagittal surface area of the Corpus callosum (CCSA) and the VS by Ultrasound (US) at birth, 6 weeks and 16weeks post natal age (PNA) and at TEA by MRI.
Summary of Results: There was no significant difference in head circumference, weight and VS size at birth and at 16 weeks between Laser and Control groups. However, the CCSA was significantly smaller, in the Laser group, at 16wks by US (p=0.034) (figure) and at TEA by MRI. The median (interquartile range) of CCSA by MRI was 1.02 (0.84-1.19) cm2 in the Control group at PNA 16 (15-18) weeks vs. 0.65 (0.54-0.71) cm2 in the Laser group at PNA 20 (17-22) weeks, (p<0.001). After adjusting for gestation age or birth weight, the decrease in the CCSA remained significant in the Laser group.
Conclusions: Severe retinopathy in ELBWI requiring laser therapy is associated with a reduction in CC size. Pathophysiology for these findings requires further analysis.
299 A NEWBORN PRESENTING WITH A CONSTELLATION OF SYMPTOMS DIAGNOSED WITH JOUBERT SYNDROME
Vala SK, Burns JJ. FSU College of Medicine, Pensacola, FL.
Case Report: A full term male neonate was admitted to NICU for evaluation of irregular breathing, hypotonia and stridor in the first hour of life. Mother was 31 year old AB +, serology/GBS negative, with no history of drugs, alcohol or tobacco use during pregnancy. No ultrasound was done due to inadequate prenatal care. Delivery was by repeat C-section with Apgar scores of 5/7/8; a weak cry was noted immediately after birth. Family history was significant for developmental delay of male sibling who died at 6 months of age.
On physical exam, weight was 2870 gm, length 47 cm, OFC 34 cm. There was episodic tachypnea with respiratory rate > 100/minute, inspiratory stridor and episodes of apnea lasting more than 45 seconds with central cyanosis and bradycardia. Additional findings included hypotonia, horizontal nystagmus, polydactyly and a soft globular compressible 2 cm swelling in the occipital region consistent with a cranial defect. No other dysmorphic features were noted. Patient had initial blood gas analysis indicating respiratory alkalosis, with pH-7.58, pCO2-13, pO2-160, HCO3-12.2. CBC, CRP, chemistry panel, urinalysis, lactate, pyruvate and ammonia were within normal limits. Head ultrasound found a 13mm defect in occipital skull with herniating brain matter. MRI showed a small midbrain with thickened and elongated superior cerebellar peduncle (“molar tooth sign”). The 4th ventricle appeared triangular shaped at mid level and bat-wing shaped superiorly. Cerebellar hemispheres appeared dysgenetic and triangular in shape superiorly.There was a tiny herniation of a CSF filled sac through a bony defect in the midline occipital region. Joubert syndrome was diagnosed based on collection of physical and imaging findings. Cardiac echo, ophthalmologic evaluation, ultrasound of abdomen were normal.
Interventions included intubation because of apnea episodes, orogastric tube feeding and multi-disciplinary team including neurology, neurosurgery, physical therapy, and speech therapy.
Joubert syndrome should be considered in the differential diagnosis of infants having irregular breathing, inspiratory stridor, nystagmus, occipital cranial defects and polydactyly.
300 CLINICAL FEATURES OF NEWBORNS READMITTED TO THE HOSPITAL FOR MANAGEMENT OF HYPERBILIRUBINEMIA
Waite S, Leysath A, Burns JJ. FSU, Pensacola, FL.
Purpose of Study: The purpose of this study was to determine which clinical features are present in newborns re-admitted to the hospital for management of hyperbilirubinemia.
Methods Used: A retrospective chart review was performed of newborns readmitted for management of hyperbilirubinemia over a 2-year period. Frequency data obtained included feeding method, gestational age, the category of bilirubin level per Bhutani nomogram at nursery discharge, age and percent weight loss at nursery discharge, presence of hemolysis, and age and percent weight loss at readmission.
Summary of Results: 42 infants were readmitted to the hospital for management of hyperbilirubinemia. Descriptive statistics: 81% of these infants were breast-fed, 69% were <38 weeks gestational age and 64.3% were both breastfed and <38 weeks gestational age. Hemolytic disease was present in 11.9% of infants; 16.7% had jaundice in the first 24 hours of life and 9.5% required phototherapy in the nursery. Mean age at discharge was 2.3 days (S.D. 0.46). Category of discharge bilirubin: 2.4% high risk (>95th percentile), 42.9% high-intermediate risk (75%ile-95%ile), 40.5% low-intermediate risk (40%ile-75%ile) and, 7.1% low risk (<40%ile). Average weight loss at discharge was 5.79%; 2.4% had weight loss >10%. At readmission, average age was 5.3 days (S.D. 1.07); average weight loss was 7.88% (S.D. 3.60); average bilirubin level was 18.45 mg/dL (S.D. 2.32). Infants discharged <48 hours old had higher bilirubin levels at readmission when compared to those discharged > 48 hours old with total serum bilirubin levels of 20.0 mg/dL vs 17.7 mg/dL respectively (t =3.54;p= 0.001). 31% of the infants readmitted for hyperbilirubinemia had >10% weight loss, which was statistically different from discharge. (McNemar p=0.001).
Conclusions: Babies who are readmitted for hyperbilirubinemia usually are breast fed, premature and are 5 days of age and a significant number had weight loss >10% from birth weight. Discharge from the nursery < 48 hours of life is associated with higher bilirubin levels on readmission. Babies even in the low intermediate category of bilirubin at time of discharge can comprise a significant proportion of readmissions. This study suggests that ensuring effective breastfeeding and even later discharge practices especially in preterm infants might reduce some of the readmissions for newborn jaundice.
Pulmonary and Critical Care Medicine Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
301 AN UNUSUAL PSYCHOSIS: ANTI-N-METHYL-D-ASPARTATE RECEPTOR ENCEPHALITIS: A CASE REPORT
Carthan KA, Murphy DJ. Emory University School of Medicine, Atlanta, GA.
Case Report: 28 year old female with a history of anemia presented to the emergency department from a psychiatric facility with altered mental status and seizure activity. At the psychiatric facility, she was receiving thorazine, haloperidol, and benztropine for a diagnosis of severe anxiety with psychotic features. Initial physical exam revealed a fluctuating level of consciousness (i.e. periods of orientation to time and place alternating with periods of hostility and inappropriate laughter) as well as fluid responsive hypotension and tachycardia. She was admitted to the MICU for hemodynamic instability and altered mental status. Initial differential diagnosis included neuroleptic malignant syndrome (NMS), infectious encephalitis, toxic ingestion, autoimmune disorders, and paraneoplastic syndromes. Empiric treatment with antibiotics for infectious encephalitis and bromocriptine for NMS was initiated pending the results of CT head, lumbar puncture, toxicology screen, and electroencephalogram (EEG). When initial studies were non-diagnostic, antibiotics and bromocriptine were discontinued and her symptoms were controlled with benzodiazepines and anti-epileptics. On hospital day 21, CSF fluid analysis showed anti-NMDA receptor antibodies supporting a diagnosis of anti-NMDA receptor encephalitis. Subsequent transvaginal ultrasound revealed a 3.7 cm x 3.5 cm right ovarian cyst and she later underwent salpingo-oopherectomy. Her mental status slowly improved and she was discharged home on hospital day 46.
Conclusions: Anti-NMDA receptor encephalitis is a rare cause of altered mental status with variable clinical presentations and frequent overlap with other diseases. This syndrome is frequently associated with ovarian teratomas and removal is the treatment of choice. A high index of suspicion and early lab evaluation is important for prompt diagnosis and management of this disorder.
References:
Gregory S. Day, Sasha M. High, Bianca Cot, David F. Tang-Wai. Anti- NMDA-Receptor Encephalitis: Case Report and Literature Review of an Under-Recognized Condition. JGIM 26:811-816.
302 CONGENITAL LIPOMATOUS OVERGROWTH, VASCULAR MALFORMATIONS, EPIDERMAL NEVUS, AND SCOLIOSIS SYNDROME AND PULMONARY HYPERTENSION: A CASE REPORT
Carthan KA1, Udoji TN2. 1 Emory University School of Medicine, Atlanta, GA and 2 The Ohio State University, Columbus, OH.
Case Report: 41 year-old African-American female with a history of systemic hypertension and CLOVES syndrome was evaluated for progressive dyspnea on exertion, and syncope. She was WHO functional class III and physical examination revealed loud P2 component of S2, S3 gallop and other stigmata of right heart disease. There were multiple truncal vascular malformations and upper extremity epidermal nevi consistent with a diagnosis of CLOVE syndrome. Transthoracic echocardiogram (TTE) showed a dilated right atrium with a pressure of 15 mmHg and an estimated pulmonary artery systolic pressure (PASP) of 39.2 mmHg. Ventilation Perfusion (V/Q) scans showed several matched defects. Right heart catheterization (RHC) showed a mean right ventricular systolic pressure (RVSP) of 84/5mmHg, PASP of 79/37 mmHg (mean 54 mmHg) and a Fick cardiac output of 4.20 L/min.
She was diagnosed with Group 1 PH and was started on treprostinil which improved her functional class. She was weaned off supplemental oxygen and outpatient pulmonary function test showed moderate restrictive physiology and mild reduction in diffusion capacity. She was later switched to sildenafil and ambrisentan and continued to do well. Repeat TTE one year later showed an RVSP 75.2mmHg and RHC two years following her diagnosis was similar to her initial RHC.
Conclusion: PH is an under recognized morbidity in individuals with CLOVES syndrome. Pulmonary embolism and venous thromboembolism has also been reported and if untreated can progress to chronic thromboembolic pulmonary hypertension and possibly death. This report highlights that prompt recognition of PH in patients with this rare disorder may reduce morbidity.
References:
Ahmad I Alomari. Characterization of a distinct syndrome that associates complex truncal overgrowth, vascular, and acral anomalies: a descriptive study of 18 cases of CLOVES syndrome. Clinical Dysmorphology. 2009, 18:1-7.
303 LIFE THREATENING WEGENER’S GRANULOMATOSIS: AN UNCOMMON DISEASE MASKED BY COMMON SYMPTOMS
Cohen C1, Prabhakaran P1,2, Diaz F1,2. 1 Children’s of Alabama, Birmingham, AL and 2 Children’s of Alabama, Birmingham, AL.
Case Report: Wegener’s granulomatosis (WG) is an ANCA-associated vasculitis that is progressive in nature, classically causing upper and lower airway disease with renal involvement. We report a 16 year-old previously healthy female who presented critically ill with shock and pulmonary hemorrhage. The month prior to presentation included multiple upper airway infections and cough progressing to respiratory distress with hemoptysis. Community acquired pneumonia and acute respiratory distress syndrome were suspected. She was admitted to the intensive care unit after intubation and the initiation of vasopressors. A pulmonary-renal syndrome was suspected when she was found to have oliguric renal insufficiency and hematuria. The diagnosis of WG was confirmed with the detection of an antibody to proteinase 3. Clinical improvement was noted after initiating treatment for WG including intravenous corticosteroids, plasmapheresis, rituximab, and cyclophosphamide. This report emphasizes that early recognition of symptomatology, with high index of clinical suspicion, is necessary for prompt diagnosis of WG. Often children with undiagnosed WG will present with constitutional symptoms including fever, arthralgias, recurrent sinusitis, otitis media, and stridor. The development of diffuse alveolar hemorrhage, which ultimately led to her diagnosis of WG, is the presenting feature in up to 44% of cases.
304 INTRA-ABDOMINAL CHYLOTHORAX
Dixon K, Wilhelm C, Wilhelm A. University of Mississippi Medical Center, Jackson, MS.
Case Report: A chylothorax is defined as leakage of lymphatic fluid or chyle into the pleural space, normally caused by traumatic or mechanical obstruction of the thoracic duct. Malignancy is the most common cause of non-traumatic chylothorax. Here we present an atypical presentation of chylothorax.
A 42 year old African American female with hypertension and obesity was admitted to the Gynecologic Oncology service for evaluation of an adnexal mass found on ultrasound. She complained of menorrhagia, increasing abdominal girth, twenty pound weight gain, and worsening shortness of breath with dyspnea on exertion for several months prior to admission. Physical exam findings included decreased breath sounds in the right hemithorax, and a distended, non-tender, protuberant abdomen. Computed tomography (CT) revealed massive bilateral ovarian masses (18 cm and 19 cm in diameter), abdominal ascites, and a large loculated right pleural effusion, with leftward mediastinal shift and compressive atelectasis of the right middle and lower lobes. Pleural fluid analysis from bedside thoracentesis showed an exudative effusion with chylothorax, and triglycerides of 234 mg/dL. A paracentesis was performed, and 4.5 liters of hazy, yellow fluid were drained, however fluid studies were not performed. Her dyspnea improved after a chest tube was placed, and a second CT of her chest was done after the fluid was drained. No mediastinal lymph nodes, masses, or other cause of thoracic duct disruption was identified. The patient subsequently underwent total abdominal hysterectomy and bilateral salpigo-oopherectomy. Pathology returned as metastatic carcinoma, likely breast primary. The chylothorax resolved after surgery, and the chest tube was removed prior to discharge.
Pleural fluid triglycerides > 120 mg/dL suggests lymphatic drainage out of the lymphatic system into the surrounding potential space. Because there was no intrathoracic abnormality causing thoracic duct obstruction, our differential diagnosis for the etiology of her chylothorax included chylous ascites translocating through a diaphragmatic defect, intra-abdominal lymphatic duct obstruction from massive tumor burden, and Meig’s syndrome. When confronted with a chylothorax of unknown etiology, intra-abdominal pathology should be considered as the cause.
305 CITALOPRAM OVERDOSE CAN CAUSE NONCARDIAC PULMONARY EDEMA
Edriss H Pfarr M, Nugent K. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: We report a 53-year-old man who ingested 2400 mg of citalopram and presented to emergency department three hours post-ingestion with altered mental status, somnolence, and a blood pressure of 67/45 mmHg. He failed to respond to three boluses of normal saline (1000 ml each) and required vasopressors. The patient developed serotonin syndrome with hyper-reflexia, rigidity, and ankle myoclonus. He had a tonic-clonic seizure in the ER requiring intravenous lorazepam and phenytoin. An ECG showed QT prolongation. Chest X-ray on presentation was normal. Within 32 hours the patient developed acute respiratory distress, hypoxemia, a wide A-a gradient, PaO2/FiO2 < 200, and chest X-ray changes compatible with acute respiratory distress syndrome (ARDS). He had normal central venous pressure, normal cardiac biomarkers, normal systolic and diastolic function on echocardiography, and no acute ST/T wave changes. His ABG showed a metabolic acidosis and a respiratory acidosis. The patient required intubation and ventilation but recovered within 24 hours.
Citalopram has been associated with seizures and ECG abnormalities after overdoses. The respiratory complications and metabolic acidosis have been reported only a few times in the literature. We are reporting the second case of ARDS; the respiratory failure developed during hospitalization as the neurotoxicity resolved. This man is the fifth case of metabolic acidosis due to a citalopram overdose; his metabolic acidemia may be explained by drug metabolism to propionic acid. The respiratory acidosis seen in this patient has not been reported previously.
306 ESOPHAGEAL PERFORATION AND BILATERAL EMPYEMA FOLLOWING ENDOSCOPIC ESOPHYX
Edriss H, El-Bakush A, Nugent K. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: We report a 48-year-old white man was diagnosed with GERD and hiatal hernia 15 years ago. He underwent transoral incisionless fundoplication (TIF) after failing conservative therapy. A few hours after surgery, the patient developed midsternal chest pain. Physical examination revealed decreased breath sounds on the left side, O2 saturation was 88% on a 40% Venti-mask. The next day, the patient’s respiratory status deteriorated and he was intubated for mechanical ventilation. Chest x-ray showed a large left-sided pleural effusion and bilateral pulmonary infiltrates consistent with consolidation. Laboratory studies: white blood count 16.9 × 109/L, hemoglobin 16 g/dl, Arterial blood gases revealed: pH-7.27, PaCO2-46.7mmHg, PaO2-53.2 mmHg, HCO3– 21. Computed tomography of the chest showed moderate-to-large left-sided and moderate right-sided pleural effusions with compressive atelectasis/consolidation of both lower lobes, left sided pneumothorax, and pneumomediastinum, findings consistent with distal esophageal perforation. The patient spiked a fever (101.2°F) on post-operative day two. A left-sided chest tube was inserted, and purulent, brown-greenish fluid was drained (1300 ml). Pleural fluid analysis showed an exudative effusion consistent with esophageal perforation with empyema. The patient had fever for five days and leukocytosis despite the antibiotic coverage, chest tube placement. He also developed acute kidney injury secondary to sepsis which resolved over four days. Blood cultures were negative; pleural fluid culture grew coagulase negative staphylococcus and diphtheroides. On postoperative day eight, a left side thoracotomy and decortication for non-resolving empyema was performed. The patient was able to be successfully extubated four days later. He was discharged six days after extubation.
The transoral incisionless fundoplication using the EsophyX device is relatively effective in treating GERD. However, the complications with this procedure can be life threatening.These include bleeding and esophageal perforation complicated with pneumothorax, empyema, respiratory failure, and mediastinitis. We need post marketing studies to assess the safety, efficacy, and clinical outcomes using this novel procedure, and these patients need close post procedural follow-up
306A WBC AND TEMPERATURE EVENTS DURING MECHANICAL VENTILATION
Edriss H, Whiting JW, Ngo N, Nugent K. Texas Tech University Health Science Center, Lubbock, TX.
Purpose of Study: The criteria for SIRS include changes in WBC, temperature, respiratory rate, and heart rate. Changes in WBC counts and/or temperature could have important implications in patients on ventilators, but the frequency of these changes (events) is uncertain.
Methods Used: We reviewed the electronic medical records and x-rays from 281 ventilation episodes in our medical intensive care unit from 12/1/2012 to 4/30/2013 to determine the characteristics of patients requiring ventilation, the indications for ventilation, the initial arterial blood gases, and the number of patients meeting the criteria for a ventilator-associated event. We determined the number of days during each ventilation episode in which the temperature ( <96.8°F, >100.4°F) or WBC ( <4K/μL, >12K/μL) was out of the normal range.
Summary of Results: This cohort included 257 patients who required 281 episodes of mechanical ventilation. 25.3% of patients were <50 years old, 46.3% were 50-70 yrs, and 28.4% were >70 yrs. 55.4% were men, and 66.2% were overweight or obese. The mean APACHE 2 score was 13.5±5.9. The initial PaO2/FiO2 was 210±110, the PCO2 was 45.1±22.8, and the pH was 7.3±0.1. The median number of ventilator days was 4 with an interquartile range (25%-75%) of 3-9. The overall mortality was 29.5%. 196 out of 275 eligible ventilator episodes (71.3%) had 1 temperature event; 95 had 2 temperature events and 42 had 3 temperature events. 194 out of 253 eligible ventilator episodes (76.7%) had 1 WBC count out of range; 51 had 2 WBC events and 8 had 3 WBC events. Nineteen patients (6.7% of episodes) met CDC criteria for a ventilator-associated event based on deterioration in gas exchange. Twelve of these patients with ventilator-associated events had an increased WBC count during the two days before through two days after the event. Eleven patients had an increased temperature during this period.
Conclusions: Increases in both WBC counts and temperatures occur frequently in ICU patients on ventilators and do not reliably identify patients with ventilator events defined by the new CDC criteria. These SIRS parameters need evaluation when they occur but cannot be used to identify patients with ventilator-associated complications.
307 HOSPITAL READMISSIONS FOLLOWING TRACHEOSTOMIES IN THE NEONATAL INTENSIVE CARE UNIT: A RECENT EXPERIENCE FROM ONE ACADEMIC CENTER
Hundalani S1, Arnold J1,2. 1 Baylor College of Medicine/ Texas Childrens Hospital, Houston, TX and 2 Texas Children’s Hospital, Houston, TX.
Purpose of Study: To describe the indications, surgical timing, length of stay and early readmission rates of infants discharged from the neonatal intensive care unit (NICU) with tracheostomies.
Methods Used: Retrospective chart review of infants undergoing tracheostomy placement over an 18-month period from June 2011-Dec 2012 and discharged home from the NICU in a large urban academic pediatric hospital. Data is presented as median (IQR).
Summary of Results: Of 46 infants who underwent a tracheostomy, 31(67%) met inclusion criteria. 45% were male, 35% inborn, 39% ⩽1kg at birth; Post menstrual age (PMA) at tracheostomy was 50 weeks (44-54) and total hospital stay was 162 days (109-207). While PMA at tracheostomy was similar in patients ⩽1kg and >1kg, ⩽1kg group had a longer post tracheostomy stay (p=0.02). 95% tracheostomies were elective, of which 80% were for prolonged mechanical ventilation. In 75% patients ⩽1kg, the primary indication was chronic lung disease. In >1kg, airway obstruction was the primary indication in 52 % and chronic lung disease in 16%. 22% patients were on tracheostomy collar at discharge. 26%(8/31) infants were readmitted within 1 week, 84%(26/31) readmitted within 6 months, with 16%(5/31) requiring four or more admissions. 3/8 readmissions within the first week were related to airway emergencies (1 mucus plug, 2 codes requiring CPR) and 3/8 were related to infections. The six-month mortality rate was 3%. One death within the first year post discharge was due to cardiopulmonary arrest secondary to tracheostomy dislodgement.
Conclusions: 37% readmissions in the first week post discharge were related to airway emergencies, some of which could be prevented with effective management by caregivers. Our tracheostomy education is very comprehensive including CPR education and rooming in prior to discharge. In addition, we have piloted a simulation based project to train parents in tracheostomy related airway emergencies. While hospital readmissions are to be expected in this complex population, we hope to help them be more prepared and skillful with the initial management of airway emergencies at home.
308 STATUS ASTHMATICUS IN A PATIENT WITH HYPERTROPHIC CARDIOMYOPATHY
Kallur SA1, Dahm P1, Banker A2, Yadav A3, Erikson C1. 1 University of Texas Health Science Center Medical School, Houston, TX; 2 University of Texas Health Science Center Medical School, Houston, TX and 3 University of Texas Health Science Center Medical School, Houston, TX.
Case Report:
Introduction: Asthma is a common childhood illness that presents with wheezing and affects 1 in 11 children. It is a chronic inflammatory disorder of the airways, characterized by an obstruction of the bronchial tree. Hypertrophic cardiomyopathy (HCM) is a genetic defect of the cardiac myocyte. Hypertrophic obstructive cardiomyopathy (HOCM) is HCM with obstruction of the left ventricular outflow tract. In the pediatric population the incidence of HOCM is about 4.7 cases/million. HOCM presents in 10% of children as congestive heart failure, with wheezing, cough and chest tightness. Our case describes HOCM presenting with asthma.
Case Report: This is a case of a 13 year old male with past medical history of mild intermittent asthma. He presented in respiratory failure secondary to status asthmaticus. Per family, the patient began to develop symptoms the day of admission. His typical rescue medications did not improve his symptoms. At the outside hospital, he was unresponsive, emergently intubated, and transferred for a higher level of care. On our initial exam, the patient was noted to have a harsh 2/6 systolic murmur louder at rest. The patient’s asthma was treated successfully and he was extubated the following day. Upon standing up on the day of extubation, he had a syncopal event. Cardiac enzymes were elevated. The echocardiogram from the day of admission validated the clinical suspicion of HOCM. The patient had pulmonary function tests done at the time of hospitalization confirming obstructive airway disease. He was discharged on albuterol, fluticosone, metoprolol, and montelukast,with follow up in cardiology clinic.
Conclusion: Beta-blockers are the mainstay of treatment to relieve symptoms in HOCM . The use of beta-blockers in the setting of asthma is controversial. In our search of the literature, there were no cases of HOCM and asthma reported. This case presents an interesting dilemma where treating one disease worsens the second. Further research needs to be done to provide the safest treatment for this population.
309 TRANSFORMING GROWTH FACTOR BETA 1-INDUCED EPIGENETIC MODIFICATION OF THY-1 IN PRIMARY LUNG FIBROBLASTS
Neveu W, Mills T, Sueblinvong V. Emory University School of Medicine, Atlanta, GA.
Purpose of Study: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease and its incidence increases with age. Although the causative mechanisms remain poorly understood, there is compelling experimental and clinical data implicating the pro-fibrotic cytokine transforming growth factor β1 (TGFβ1) in its pathogenesis. We previously identified in senescent mice a pro-fibrotic lung phenotype with an increase in the number of fibroblasts negative for Thy-1, a cell surface molecule associated with fibrosis. As Thy-1 acts as a fibrotic suppressor and that loss of gene expression by epigenetic modification leads to a fibrotic phenotype in lung fibroblasts, we evaluated whether TGFβ1 epigenetically regulates Thy-1 differentially in primary lung fibroblasts from young vs. old mice.
Methods Used: Primary lung fibroblasts harvested from young (3 month) and old (24 month) mice were treated with TGFβ1 ± the DNA methyltransferase (DNMT) inhibitor 5-Azacytidine (5-AZA) for 72 hrs and analyzed for Thy-1 gene expression by quantitative RT-PCR. DNMT gene expression (e.g. DNMT 1, DNMT3a, and DNMT3b) were analyzed by quantitative RT-PCR in cells at baseline and following TGFβ1 treatment at 24 and 72 hrs.
Summary of Results: TGFβ1 treatment for 72 hrs decreased Thy-1 gene expression in fibroblasts from young mice. In contrast, TGFβ1 treatment in the presence of increasing doses of 5-AZA had a minimal impact on Thy-1 expression. As lung fibroblasts from old mice express higher levels of TGFβ1 and lower levels of Thy-1 at baseline, we treated them with 5-AZA alone and identified an increase in Thy-1 gene expression relative to untreated cells. Interestingly, no significant difference was observed in DNMT expression in response to TGFβ1 treatment in fibroblasts from young or old mice, but this is in fact consistent with previous studies showing dissociation between DNMT mRNA levels and protein activity.
Conclusions: TGFβ1 appears to induce Thy-1 methylation in lung fibroblasts, and the decreased expression of Thy-1 in fibroblasts from old mice may be a consequence of elevated TGFβ1 and activation of the DNMT pathway. Future studies to determine how Thy-1 is regulated as fibroblasts age may identify therapeutic targets in IPF.
310 HIV-RELATED PROTEINS INHIBIT THE NRF2/ARE SIGNALING PATHWAY IN ALVEOLAR MACROPHAGES
Singh M, Fan X, Guidot D. Emory University and the Atlanta VA, Atlanta, GA.
Purpose of Study: Infection with the human immunodeficiency virus (HIV) causes oxidative stress within the airways, as best reflected by glutathione depletion within the alveolar space, and induces alveolar macrophage dysfunction; however, the mechanism(s) are poorly understood. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive master transcription factor that regulates the activation of the anti-oxidant response element (ARE), a group of anti-oxidant gene targets that have a significant role in cellular responses to oxidative stress. We hypothesized that HIV- related proteins (Tat and gp120), independent of HIV infection, decrease Nrf2 expression in alveolar macrophages and thereby impair activation of the ARE, ultimately leading to oxidative stress and macrophage dysfunction.
Methods Used: A rat alveolar macrophage cell line (NR8383 cells) and a human alveolar macrophage cell line (THP-1 cells) were incubated with either recombinant gp120 (100ng/ml) or Tat (10ng/ml) for 24 hrs (at which time gene expression was assessed) or 72 hrs (at which time protein expression was assessed). The relative gene and protein expression of Nrf2 and the Nrf2/ARE-dependent genes glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) were quantified by QRT PCR and western blot analyses, respectively.
Summary of Results: Treatment with either gp120 or Tat decreased Nrf2 and NQO1 gene and protein expression in both cell lines. In parallel, THP-1 cells treated with either GP-120 or Tat had decreased gene expression of GCLC, which is the rate-limiting step in glutathione synthesis.
Conclusions: Taken together, these findings suggest that HIV-1-related proteins, which are expressed and are present in relatively high concentrations in the alveolar lining fluid in chronic HIV infection, inhibit anti-oxidant defenses in the alveolar macrophage. We hypothesize that activation and/or over-expression of Nrf2 may be able to rescue the alveolar macrophage from the toxic effects of these HIV-related proteins and thereby enhance lung immune health in these vulnerable individuals.
311 EXTRA INTESTINAL MANIFESTATION OF CROHN’S DISEASE
Velayuthan S, Umer S. Louisiana State University Health Sciences Center, Shreveport, LA.
Case Report: Extra intestinal manifestations of Crohn’s disease in children are diverse and well documented. We report a case of Crohn’s disease with persistent pulmonary nodules treated as recurrent pneumonias with poor response to antibiotic therapy and responded well to oral steroids.
A 16-year-old girl with medically controlled Crohn’s disease presented to us with a foot ulcer and pleuritic chest pain. The foot ulcer was diagnosed as pyoderma gangrenosum with biopsy. The chest radiograph (CXR) at presentation revealed left lower and right middle lung lobe opacities. The previous CXR obtained a year ago showed similar opacities and further history revealed poor response to antibiotic treatment for presumed recurrent pneumonias. Serology for histoplasma, coccidioides and mycoplasma were negative. Immunoglobulins, serum angiotensin levels, anti glomerular antibodies and c ANCA were normal. Computed tomography of chest showed left lower lobe nodule with scattered multiple small nodular opacities. Gram stain from broncho alveolar lavage showed few neutrophils and the cultures were negative. Biopsy from the left lung nodule showed nodular foci with chronic non specific inflammation. Sputum and tissue cultures for mycobacterium and fungi were negative.
Due to multiple unsuccessful treatments with different antibiotics and unrevealing laboratory evidence for infection, pulmonary manifestation of Crohn’s disease was suspected. Treatment with oral steroids was initiated and the lung opacities and pyoderma gangrenosum on foot slowly disappeared. The recent CXR shows some scars and no nodules or opacities. This case implies the importance of awareness among clinicians about the uncommon manifestation of Crohn’s disease.
312 THE FREQUENCY OF VENTILATOR-ASSOCIATED EVENTS IN A MEDICAL INTENSIVE CARE UNIT
Whiting JW, Edriss H, Ngo N, Nugent K. Texas Tech University Health Sciences Center, Lubbock, TX.
Purpose of Study: The CDC has developed new criteria to identify ventilator-associated complications, including pneumonia. These criteria require an increase in FiO2 by at least 20% or an increase in PEEP by 3 cm H2O for at least two days after a period of improving or stable gas exchange. We wanted to determine how frequently this happened and what caused the deterioration in gas exchange.
Methods Used: We reviewed the electronic medical records and x-rays from 281 ventilation episodes in our medical intensive care unit from 12/1/2012 to 4/30/2013 to determine the characteristics of patients requiring ventilation, the indications for ventilation, the initial arterial blood gases, and the number of patients meeting the criteria for a ventilator-associated event.
Summary of Results: This cohort included 257 patients who required 281 episodes of mechanical ventilation. 25.3% of patients were <50 years old, 46.3% were 50-70 yrs, and 28.4% were >70 yrs. 55.4% were men, and 66.2% were overweight or obese. The mean APACHE 2 score was 13.5±5.9. The initial mean PaO2/FiO2 was 210±110, the PCO2 was 45.1±22.8, and the pH was 7.3±0.1. The median number of ventilator days was 4 with an interquartile range (25%-75%) of 3-9.The overall mortality was 29.5%. Nineteen patients (6.7% of all episodes) met CDC criteria for a ventilator-associated event; 6 met FiO2 criteria (31.6%) and 13 met PEEP criteria (68.4%). Twelve of these patients (63.2%) had an increased WBC count (> 12K/μL) during the two days before through two days after the event. Eleven patients had an increase in temperature (> 100.4°F) during this period. Based on review of the medical records, cultures, changes in antibiotics, and changes in chest x-ray, we identified the following explanations for the change in gas exchange parameters. Four had pneumonia, 4 had atelectasis, 5 had CHF, 2 had ARDS, and 3 had miscellaneous reasons.
Conclusions: Approximately 7% of the patients in this cohort had a ventilator-associated event. Most of these events represented PEEP changes. The clinical diagnoses varied and included pneumonia, ARDS, atelectasis, and CHF. Only 4 patients appeared to have a ventilator-associated pneumonia. These new CDC criteria may not identify most ventilator-associated complications.
313 THE UTILITY OF TRACHEAL ASPIRATES IN THE MANAGEMENT OF PATIENTS WITH VENTILATOR-ASSOCIATED EVENTS
Whiting JW, Edriss H, Ngo N, Nugent K. Texas Tech University Health Sciences Center, Lubbock, TX.
Purpose of Study: The Clinical Pulmonary Infection Score uses the presence of purulent secretions to help make the diagnosis of ventilator-associated pneumonia. It is unclear whether information recorded in the medical record about sputum collected by tracheal suctioning provides useful information.
Methods Used: We reviewed the electronic medical records and x-rays from 281 ventilation episodes in our medical intensive care unit from 12/1/2012 to 4/30/2013 to determine the characteristics of patients requiring ventilation and the number of patients meeting the criteria for a ventilator-associated event identified by new CDC criteria. We analyzed information in the records about tracheal aspirates on the event day using a semi-quantitative scoring method to characterize the sputum recovered.
Summary of Results: This cohort included 257 patients who required 281 episodes of mechanical ventilation. 74.7% were older than 50 yrs, 55.4% were men, and 66.2% were overweight or obese. The mean APACHE 2 score was 13.5±5.9. The initial PaO2/FiO2 was 210±110, and the PCO2 was 45.1±22.8. The median number of ventilator days was 4 (interquartile range: 3-9).The overall mortality was 29.5%. 19 patients (6.7% of episodes) met CDC criteria for a ventilator-associated event. Patients with purulent, thick sputum in larger quantities had the same temperature, WBC, and number of ventilator days as patients with less abnormal sputum (Table).
Conclusions: There is significant variability in the quantity and characteristics of the sputum aspirated from patients with ventilator-associated events. The information collected during routine care does not help with the clinical diagnosis in these patients.
314 WHAT PATIENTS WITH NEWLY DIAGNOSED PULMONARY HYPERTENSION WANT TO HEAR FROM PHYSICIANS: A DESIRE FOR HONEST, CLEAR AND HOPEFUL COMMUNICATION WITH CONCERN FOR NEED OF IMPROVED PHYSICIAN EDUCATION
Yandle G, Grewal H, Erbil J, Lauto P, Smart F, DeBoisblanc B, Lammi MR, Saketkoo LA. LSU Health Sciences Center, New Orleans, LA.
Purpose of Study: To broadly understand the health-related communication needs of patients with pulmonary hypertension (PH). To collect qualitative data from PH patients that will guide investigations development of communication protocols and self-efficacy strategies.
Methods Used: Patients from a sequential convenience sample at a national PH patient conference were asked the following question: ‘For a patient with a new diagnosis of PH, is there anything a doctor could say that would be helpful? For example, what would you have liked to know when you were first diagnosed with PH?’. Written responses were coded by 4 independent investigators utilizing inductive analysis. Fisher’s Exact test was used to compare differences between groups.
Summary of Results: 72 patients (mean age 54 yrs) participated (Table 1). Patients responded that optimism was important and that available treatment options justified physician communication of hopefulness. Patients conveyed that receiving compassionate, clear and honest knowledge about PH was vital. Discussions of disease mechanisms and treatment were rated as important to patients at time of diagnosis. Guidance on external sources of knowledge was desired. Patients often volunteered that primary care and pulmonary physicians needed heightened education on PH. When comparing iPAH to non-iPAH, significantly more iPAH patients responded that “Expected Disease Impact” (p=0.02,OR=8.8), “Web-Site Guidance” (p=0.04,OR=3.3), and “Support Organizations” (p=0.01,OR=4.7) were needed at time of PH diagnosis; but otherwise there were no significant differences amongst groups.
Conclusions: This examination provides important insight into desired patient-physician communication at time of PH diagnosis. These results suggest that the development of physician communication protocols that include information on PH resources may support a stronger sense of patient well-being and promote better health outcomes. Importantly, the frequency of patient expressions of medical ignorance of PH (information not asked for) warrants efforts to educate community physicians.
315 FATIGUE MAY PARALLEL DSYPNEA IN IMPACT ON FUNCTIONING AND QUALITY OF LIFE IN PATIENTS WITH PULMONARY HYPERTENSION
Yandle G, Grewal H, Erbil J, Lammi MR, Lauto P, Smart F, DeBoisblanc B. Saketkoo LA. LSU Health Sciences Center, New Orleans, LA.
Purpose of Study: To take inventory of the most concerning symptoms of patients with PH.
Methods Used: A convenience sample of patients attending a national PH patient conference, independently completed a questionnaire designed for this investigation to capture patients’ concerns in an unbiased manner. The patients registered their personal and disease demographics with the research division of the conference. Questions were open-ended, non-leading, non-specific and inquired about patient experiences with regard to disease impact, disability, access to health care, health provider communication and coping. Surveys were analyzed by inductive methodology whereby data were deconstructed to single concepts from which a coding system was allowed to emerge. Fatigue was assigned to phraseology referencing energy, exhaustion, tiredness, or fatigue; while dyspnea was assigned to phraseology describing breathing, shortness, difficulty walking, or desaturation. Depression and anxiety were identified with similar inscrutable terms. Statistical comparisons of dichotomous categorical variables utilized Fisher’s Exact test. Comparisons across patient groupings of age and medication utilized Chi square analysis. Non-parametric variables were compared using Mann Whitney U.
Summary of Results: 71 patients completed the survey. Median age was 54 years (range 15-77). NYHA Functional Class (FC) assignments were I (8%), II (51%), III (31%) and IV (3%). 82% of respondents supplied fatigue as an unsolicited symptom while 84% supplied dyspnea. Anxiety, depression, memory loss and pain were each experienced by <20% of the group. There were 161 occurrences of fatigue phraseology within the questionnaires compared to 122 occurrences of dyspnea (p=0.1). Dyspnea (p=0.004) but not fatigue was correlated with NYHA FC. Neither dyspnea nor fatigue correlated with age or type of medication used.
Conclusions: An unbiased survey of PH patients revealed fatigue as a central experience with high impact on patients’ quality of life and function. Fatigue rivaled dyspnea across all PH groups. Further investigations to measure fatigue as a potential metric of residual disease activity and to examine strategies that manage fatigue in PH patients are warranted.
Renal, Electrolyte and Hypertension Joint Plenary Poster Session and Reception
5:00 PM
Thursday, February 20, 2014
316 SPINAL EPIDURAL ABSCESS IN HEMODIALYSIS PATIENTS
Afzal U1, White JM1, Jin C1, Baer S2, Huber L1,2, Colombo R1, Kintziger K1, Kheda MF1, Nahman NS1. 1 Georgia Regents University/Medical College of Georgia., Augusta, GA and 2 VAMC, Augusta, GA.
Purpose of Study: Spinal epidural abscess (SEA) may be a serious infectious comorbidity in hemodialysis (HD) patients. SEA may be the result of bacteremia (BAC), but other factors are possible. We have previously shown that BAC occurs in over 20% of incident HD patients, suggesting a significant risk for this condition (Chebrolu, IDSA, 2012). To more fully address the role of BAC and other co-morbidities associated with SEA, we queried the United States Renal Data System (USRDS).
Methods Used: All incident HD cases from the USRDS for calendar years 2005-2008 were queried for a diagnosis of SEA, BAC and several potential clinical covariates using ICD-9 diagnosis codes submitted for Medicare billing. Descriptive statistics and log-binomial regression analysis were performed.
Summary of Results: For the 4-year period of study, 355,084 patients were available for analysis. The median age was 65 years. SEA was identified in 660 (0.19%) patients. Vascular access type at the initiation of HD included AVF in 47,732 (13.4%), AVG in 14,179 (4.0%) and vascular catheter in 293,173 (82.6%) patients. Of the demographic variables, black race [relative risk (RR) 1.218, 95% confidence interval (CI) 1.025- 1.447] and female sex [RR 1.179, 95% CI 1.009-1.379] carried significant risks for SEA. Infectious comorbidities, including diagnosis of BAC [RR 7.757, 95% CI 6.432-9.355], MRSA infection [RR 2.684, 95% CI 2.192-3.286] and hepatitis C [RR 1.660, 95% CI 1.223-2.253] were associated with the highest risk. Of the non-infectious factors, diabetes mellitus [RR 1.515, 95% CI 1.278-1.797] and vascular catheters [RR 1.347, 95% CI 1.008-1.800] carried an increased risk of SEA.
Conclusions: Spinal Epidural Abscess is an uncommon but serious complication of HD. The risk of spinal epidural abscess is highest in patients with infectious co-morbidities, especially bactremia, but diabetes and the presence of a central vascular catheter are also significant risk factors.
317 EMERGENCE OF ATYPICAL MYCOBACTERIAL EXIT SITE INFECTION IN CURRENT ERA OF USE OF TOPICAL GENTAMICIN FOR INFECTION PROPHYLAXIS IN PERITONEAL DIALYSIS PATIENTS
Ahmad M1, Bansal S1, Paolo F2,1, Salazar M3. 1 University of Texas Health Sciences Center at San Antonio, San Antonio, TX; 2 South Texas VA Medical Center, San Antonio, TX and 3 University Hospital, San Antonio, TX.
Case Report: Peritoneal catheter-related peritonitis and exit site infections (ESIs) are associated with significant morbidity in peritoneal dialysis (PD) patients. Topical Gentamicin has been widely used for prevention of such infections. Recently, there have been reports of atypical mycobacterial ESIs from outside US and Gentamicin cream is postulated to be one of the potential risks because of selective pressure on other micro-organisms. Here, we report a series of 3 patients who had Mycobacterium Fortuitum ESIs on prophylactic exit-site Gentamicin cream from our center.
Three patients, all male, average age of 30 yrs, on PD for 1-8 months, presented with exit site pain, redness and exudate. They were started on empirical Cephalexin at the time of presentation. Initial culture reported gram positive diphtheroid-like organisms. However, in 5-7 days laboratory identified organisms as M fortuitum sensitive to Azithromycin, Ciprofloxacin and Doxycycline in each patient. Patients were switched to combination of either of two of these antibiotics. Since atypical mycobacteria are ubiquitous in the environment, cultures were taken from water supply, PD fluids and contact surfaces from patient’s home and dialysis center to find the source, however, these remained negative. First patient required removal of PD catheter for non-resolving infection. Second patient had resolution of ESI but required catheter removal for ESI and concomitant peritonitis from coagulase negative staphylococcus after 4 months of initial presentation. Third patient recovered completely. All 3 patients were able to stay on chronic PD after brief discontinuation in 2 patients.
There is emergence of atypical mycobacterial ESI in recent years internationally. The clinical presentation is similar to other bacterial ESIs, therefore, diagnosis requires high vigilance since the treatment involves prolonged use of dual antibiotics. Topical gentamicin use is a possible risk factor but needs confirmation in large studies. For now, use of Mupirocin and Gentamicin on alternative basis is an option to avoid these infections.
318 WHEN COKE IS NOT HYDRATING: COCAINE INDUCED ACUTE INTERSTITIAL NEPHROSIS
Bahaa Aldeen M, Talibmamury NB, Ismaael T, Adenwala YE, Smalligan RD. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: A 47yo African American (AA) man was admitted with 4 days of back pain, N/V and low urine output. There was no h/o fever, dysuria, frequency, hesitancy, viral symptoms, trauma, rash, or constipation. Despite his PMH of HTN, DM, and hyperlipidemia he denied taking any meds for 18 months including NSAIDs, acetaminophen or antacids. He denied smoking and alcohol but admitted to cocaine use. No significant FH. PE: BP 235/125, HR 90, T98, O2 sats nl. Lungs and heart normal, abd soft but bilat CVAT. Neuro exam normal. Labs: Cr 10.5 (1.2 in 2010), BUN 63, Gluc 151, Ca 9.4, PO4 6.1, Hgb 15, WBC 9.1, platelets 167k, amylase/lipase nl, AST/ALT nl, bili 1.4, AP 39, CPK 127. Hep panel, C&P-ANCA, anti-GBM, anti-myeloperoxidase, ANA and H. pylori were all negative. C3, C4 nl. UA: 2+ blood, no WBCs or eos, no casts, no albumin, neg for nitrate/LE and bacteria. Imaging: CXR, abd x-rays, CT abd, EKG and TTE all normal.
Course: Pts urine output declined from 700cc/d to 400cc/d and the third day he required hemodialysis with Cr 14. Renal biopsy showed typical findings of interstitial nephritis. The patient was dialyzed for 10 days and responded to steroids and went home with an improving Cr of 3.5.
Discussion: Internists encounter patients with acute kidney injury (AKI) on a daily basis, most of which can be explained by prerenal azotemia, ATN, obstruction, or rhabdo among other etiologies. Cocaine is only rarely implicated as an etiology of AKI and if it is, usually the injury is due to ATN or pigment effects. Acute interstitial nephritis (AIN) caused by cocaine, on the other hand, has only been described in a handful of cases. AIN is a renal lesion that causes a decline in creatinine clearance and is characterized by an inflammatory infiltrate in the kidney interstitium and is most often associated with drug therapy. AIN can also be seen in autoimmune disorders like SLE, Sjögren’s, or sarcoidosis; or with infections remote to the kidney like Legionella, leptospirosis and streptococcal disease. Our case was very similar to the other reported cases of AIN due to cocaine in that all have occurred in middle-aged AA males and all have responded to steroids. This case reminds clinicians to consider AIN in patients with AKI and a history of cocaine abuse.
320 A HEAVY HEART ON DIALYSIS
Baudy AJ, Ibie NC, Simon EE. Tulane Medical Center, New Orleans, LA.
Case Report:
Introduction: Pericarditis is the inflammation of the pericardium and was first described by Richard Bright in 1836 in the context of uremic pericarditis with renal failure. Since then two main types of pericarditis have been described: uremic pericarditis, which develops prior to renal replacement therapy or within 8 weeks of initiation of therapy; and dialysis-associated pericarditis, which develops after being stabilized on dialysis. Our case describes a patient who presented with dialysis-associated pericarditis with large pericardial effusion after being on dialysis for several years.
Case Description: A 62 year old female with a past medical history of end stage renal disease on dialysis for several years secondary to diabetes, and recent osteomyelitis presented to the hospital with complaints of shortness of breath and wheezing that woke her up from sleep the morning of presentation. She states that she had orthopnea and PND, but denied any chest pain, palpitations, nausea, vomiting, fever chills, or recent weight loss. Echocardiogram revealed findings of a large pericardial effusion. Of note, records from the patient’s dialysis unit showed that patient has been showing up in her dialysis regularly, but signs off after about 2 hours of dialysis. Dialysis-associated pericarditis was diagnosed and dialysis was intensified. The patient was dialyzed daily for ten days with no improvement in clinical status or pericardial effusion. After extensive discussions between specialties, an anterior pericardial window was later done and the patient clinically improved. More importantly her pericardial effusion resolved and she was discharged to long term care facility.
Discussion: Dialysis-associated pericarditis occurs in 2-21% of patients on dialysis and management is different between this condition and uremic pericarditis. Both conditions can lead to increased morbidity and mortality in end-stage renal disease patients.It is very important for physicians to recognize to two conditions in order to prevent complications that may arise from delaying proper care. The current evidence supports earlier surgical intervention in patients with dialysis-associated pericarditis with large pericardial effusions, whereas patients with uremic pericarditis tend to respond to intensified dialysis.
321 SYNTHETIC CANNABINOIDS AND ACUTE KIDNEY INJURY
Berry JD, Srisung W, Prabhakar S. Texas Tech University Health Sciences Center, Lubbock, TX.
Purpose of Study: The use of cannabinoids is on the increase in the community especially in the face of changes in state regulations. The use of several synthetic cannabinoids (SCs) has also been on the rise but the full spectrum of their adverse effects is unknown. Most reports of adverse events related to SCs have been neurologic, cardiovascular, or sympathomimetic. We describe here a case of acute kidney injury as a result of “Spice”, a popular synthetic cannabinoid.
Methods Used: Case report with review of literature.
Summary of Results: A 31-year-old Hispanic male with no history of previous medical illness except for hypertension for a few years, was admitted from the emergency room two days after a physical assault due to worsening renal function. No external or bony injuries were detected. The patient admitted to abusing IV methamphetamine and smoking “Spice”, synthetic marijuana, a SC daily. On admission, patient was oliguric with his serum creatinine was 2.6 mg/dL, and his BUN was 26 mg/dL. Urine analysis was unremarkable except for trace protein and was negative for blood or hyaline casts. The following day, the patient’s serum creatinine rose to 3.0 mg/dL, and his BUN was measured to be 24 mg/dL. The patient had no prior history of kidney injury or disease. An ultrasound of abdomen showed slightly enlarged kidneys with increased echogenicity and no hydronephrosis or mass. From day 3, the urine output began to increase with gradual decline in serum creatinine levels. On day 6, the Scr was 1.4 mg/dL and BUN had dropped to 18 mg/dL. A week later patient was found be asymptomatic with with return of normal renal function. The course and recovery were compatible with acute tubular necrosis (ATN).
Conclusions: Although a definitive association between the use of synthetic cannabinoids and acute kidney injury has not yet been established, a causal link has been proposed previously by the Center for Disease Control [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6206a1.htm, Feb 2013] and in a recently published study [Clin J Am Soc Nephrol 8, 523-526,2013]. Renal biopsies done in such cases (3 out of 4) revealed ATN. The clinical course of our patient with history of SCs abuse together with recently published reports warrants more awareness of this clinical syndrome in the medical community.
322 SEVERE HYPOCALCEMIA DUE TO DENOSUMAB IN METASTATIC PROSTATE CANCER
Bhutta U1,2, Iqbal T2, Haragsim L1. 1 OUHSC, Oklahoma City, OK and 2 OUHSC, Oklahoma City, OK.
Case Report: Denosumab, a human monoclonal antibody that neutralizes receptor activator of NF-kB ligand (RANKL) has been shown to decrease the incidence of skeletal-related events in metastatic bone disease. We report a case of severe hypocalcemia following a single dose of Denosumab.
We were asked to see a 45-year-old gentleman with a 3-year history of
metastatic (bone, liver & lymph nodes) prostate cancer for which he had been treated with androgen deprivation therapy in the past, along with zoledronic acid for bone metastases.
He had issues with the zoledronate, mainly pains & he was switched to Denosumab. He was seen in the ER a week after his first Denosumab injection for worsening leg swelling and hematuria. His calcium level was found to be low at 0.65 mmol/L and he was admitted to the hospital for IV and PO calcium supplementation. On physical exam, Chvostek and Trousseau’s signs were negative and the EKG was normal. His vitamin D levels were low and PTH was inappropriately normal. He had not been on vitamin D supplementation at the time of admission. He was started on ergocalciferol, calcitriol and high doses of IV and PO calcium for around 12-13 days but his calcium levels never came up to more than 1 mmol/L. He also developed severe hydronephrosis due to his underlying malignancy and his renal function kept worsening. It was decided to start him on dialysis for his renal failure and persistent severe hypocalcemia. His calcium levels finally normalized after a few sessions of dialysis and he was sent home on outpatient dialysis since he did not want placement of nephrostomy tubes for his hydronephrosis.
Denosumab use has been associated with mild hypocalcemia in clinical trial but not to the extent that was seen in our patient. Our patient had been treated with bisphosphonate as well as Denosumab, and had osteoblastic mets, all of which are risk factors for hypocalcemia. To prevent the cardiac and neurological complications associated with hypocalcemia it has been advised to check and supplement vitamin D levels, and periodically monitor calcium levels prior to starting therapy.
323 RITUXIMAB FOR HEPATITIS C - ASSOCIATED CRYOGLOBULINEMIA
Desai J1,2, Saith S1,2, Afzal U1,2, Diamond M1,2, Nahman NS1,2. 1 Georgia Regents University, Augusta, GA and 2 Charlie Norwood Veterens Association Center, Augusta, GA.
Case Report: Case Presentation: A 56 year old white male presented with worsening edema for 3 months and orthopnea and pigmented patches on both lower extremities for 1 year. 12 years prior, he was diagnosed with hepatitis C (HCV), cryoglobulinemia, biopsy proven MPGN and treated with cyclophosphamide and prednisone. The creatinine over the next several years was reportedly 1.1 - 1.4 mg/dl. 7 years prior to this evaluation he developed purpura and skin ulcers. His HCV viral titers were increased and he was treated with ribavirin and interferon for 6 weeks, followed by peginterferon for 48 weeks. At the most recent visit, creatinine was 2.7 mg/dl, 6 gm proteinuria, C3 low at 81 mg/dl and C4 low at 1 mg/dl. Rheumatoid factor was 20 times normal at 234, and cryoglobulins were present. Repeat renal biopsy reportedly showed type I MPGN with possible microtubular structures consistent with cryoglobulins. He was treated with plasmapheresis (PP) and prednisone over the next several months with recurrent symptoms whenever PP was stopped. HCV treatment was restarted but was stopped due to renal impairment. Rituximab 600 mg weekly was started when serum creatinine was 2 and proteinuria of 7 gm/day. The course was complicated by transient thrombocytopenia but 8 weeks following 4 doses of rituximab the creatinine was 1.3 mg/dl, RF normal, cryogloblulins were not present.
Discussion: This patient had HCV-associated cryoglobulinemia with biopsy proven type 1 MPGN. His disease was resistant to prednisone and PP. Rituximab, a monoclonal antibody to CD 20 present on B cells, was started and followed by recovery of renal function sufficient to allow continued therapy for HCV. His course was complicated by thrombocytopenia which may have been due to his underlying HCV versus a side effect of rituximab. This case was similar to a few recent reports on the use of rituximab in resistant HCV- associated cryoglobulinemia. There have also been some small studies suggesting rituximab may be more efficacious than conventional therapy for cryoglobulinemia.
Conclusions: Rituximab is effective and safe in treating HCV-associated cryogloblulinemia and should be considered in patients resistant to prednisone and PP.
324 SIADH SECONDARY TO INTRACRANIAL PATHOLOGY: FLUID RESTRICTION MAY NOT CUT IT
DiSalvo N, Engel LS, Martinez J. LSU Health Sciences Center, New Orleans, LA.
Case Report: A 45 year old male with a history of lung adenocarcinoma with metastases to the brain and L3-L5 and C5 vertebrae presented to emergency department with a two day history bizarre behavior and increased agitation. He had received whole brain radiation 5 months prior as well as chemotherapy with carboplatin, pemetrexed, cisplatin, and temozolamide started 3 months ago. On exam he was moving all extremities continuously without purpose and mumbling incoherent sounds. He was found to have a serum sodium level of 125mmol/l, which was 135mmol/l 3 weeks prior. After about 1 liter of fluids from antibiotics and various medications his sodium decreased to 120mmol/l. Strict fluid restriction was initiated and his sodium responded minimally to 122mmol/l. His neurological exam remained unchanged. After 100cc and two 50cc boluses of 3% normal saline his sodium rose to 128mmol/l over the next 24 hours and his symptoms completely resolved. With continued fluid restriction his sodium and neurological status normalized.
Discussion: The mainstay of treatment for most patients with SIADH is fluid restriction. However, this treatment plan is frequently ineffective in raising sodium levels when patients have severe symptoms and intracranial disease. Lack of well controlled studies comparing therapies for symptomatic hypontremia make us rely on case series and expert opinion to determine therapeutic plan. Based on current recommendations, hypertonic saline should be reserved for previously well individuals who are symptomatic with seizures, coma, or new focal neurologic findings and whose serum sodium levels are less than 120 mEq/L.
325 EARLY LINEZOLID-INDUCED LACTIC ACIDOSIS IN END STAGE RENAL DISEASE PATIENT ON STATIN THERAPY
Gharaibeh K, Brewer M, Sandhu N, Juncos L. University of Mississippi Medical Center, Jackson, MS.
Case Report: Lactic acidosis (LA) may be caused by drug-induced impairment of cellular respiration. Linezolid is used for bacterial infections due to gram-positive cocci, including strains resistant to methicillin and vancomycin. Statins are commonly used lipid-lowering agents. We present a case of significant LA secondary to linezolid toxicity in a patient with end-stage renal disease (ESRD) while taking a statin.
A 32-year-old male with ESRD, systemic lupus erythromatous, Evan’s Syndrome (autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura), and history of thrombocytopenia-induced mucosal bleeding presented to our hospital complaining of a one-day history of hematochezia. He was discharged 3 days earlier on linezolid for urinary Enterococcus faecium. The remaining review of systems was negative. Vital signs were: BP 115/65, pulse 98, afebrile. Physical exam revealed clear lungs, normal abdominal exam, and no signs of hypoperfusion. Laboratory findings included bicarbonate 17 mmol/L, blood pH 7.37, and lactate 6.5 mmol/L. The serum bicarbonate continued to trend downward and lactate continued to trend upward, peaking at 9.9 mmol/L despite no signs of hypoperfusion or other obvious causes of LA and continued high-bicarbonate hemodialysis. Upon review of medications, the patient was noted to have received linezolid for nearly one week in addition to long-term simvastatin therapy, both of which have been separately reported to induce mitochondrial dysfunction. The decision was made to discontinue both medications in favor of alternative treatment as linezolid could induce asymptomatic LA. After 48 hours following discontinuation, the patient’s lactate level started to trend downward and normalized after 5 days.
LA is a toxic effect reported with prolonged linezolid therapy and is purported to be caused by inhibition of mitochondrial protein synthesis. Our patient presented with early linezolid-induced LA likely secondary to decreased renal clearance while also receiving simvastatin, which is reported to inhibit mitochondrial function that could accentuate mitochondrial toxicity leading to significant LA. Concluding that administration of linezolid and statin simultaneously could exaggerate mitochondrial dysfunction leading to rapid LA in the presence of risk factors.
326 TUNNELED DIALYSIS CATHETER REMOVALS BY NON-INTERVENTIONAL NEPHROLOGISTS: THE UNIVERSITY OF MISSISSIPPI EXPERIENCE
Gharaibeh K1, Csongrádi 1,2, Saleh N1, Dreisbach A1, Tapolyai M3, Fülöp T1. 1 University of Mississippi Medical Center, Jackson, MS; 2 University of Debrecen, Debrecen, Hungary and 3 University of South Carolina, Columbia, SC.
Purpose of Study: Tunneled (or cuffed) hemodialysis catheters (TDC) have been in use since 1987. The prevalence of TDC use in the United States is 24%, the vast majority (83%) of patients with end-stage renal disease (ESRD) in the United States initiate hemodialysis with a TDC. Bedside removal of TDC by non-interventional Nephrologist is not commonly performed or studied.
Methods Used: We performed a retrospective cohort review of our mixed in and outpatient experience at the University of Mississippi Medical Center between January 2010 and June of 2013. We collected data on patients and procedure-related variables, success and complications rates. The study was reviewed and approved by the University of Mississippi Human Research Office and data analyzed with SPSS v.19.
Summary of Results: Of the 138 subjects, mean age was 50 (+/−15.9) years, 49.3% were female, 88.2% African-American and 41% diabetics. Site of removal were the right internal jugular (IJ) in 75.4%, left IJ 14.5% and femoral vein 10.2%; 45.7% took place in an outpatient setting. Main indications at the time of removal were proven bacteremia in 32.8%, clinical septic or infected state in 14.6%, along with “TDC no longer necessary” in 55.8% due to either recovery of renal function or maturation of permanent dialysis access. Trainees under supervision removed 78 (56.5%) of the TDCs; of these, 5 cases (6.4%) needed hands-on assistance from Attending. All removal has been technically successful and well tolerated without TDC tear or soft tissue injury (bleeding) but we observed Dacron “cuff” separation and subcutaneous retention in 6.5% cases. Most of the outpatient removals took place due to access maturations (p<0.0001). There was a significant association between outpatient removal and cuff retention (p=0.007) but not with level of training or site of removal.
Conclusions: In this relatively large cohort of mixed inpatient and outpatient bedside TDC removals, the procedure was well-tolerated with minimal complication rate.
327 PARTIAL BOWEL OBSTRUCTION IN PERITONEAL DIALYSIS: THINK ENCAPSULATING PERITONEAL SCLEROSIS
Grewal RK, Krane K, Paramesh A. Tulane School of Medicine, New Orleans, LA.
Purpose of Study: Introduction: Encapsulating Peritoneal Sclerosis (EPS) is a rare yet serious cause of peritoneal dialysis (PD) failure. The diagnosis is based on clinical suspicion of clinical findings and confirmed with radiological and/or pathological findings. We describe a case of EPS in a PD patient without sign of inflammation or radiological findings, diagnosed at laparoscopy and biopsy findings.
Methods Used: Not applicable.
Summary of Results: Case: A 56 year old male with a history of end stage renal disease (ESRD) due to diabetic nephropathy on peritoneal dialysis presented to an outside hospital with generalized abdominal pain and nausea. The patient denied fever, chills, vomiting, diarrhea or dizziness, but had developed abdominal discomfort and inability to drain his peritoneal fluid. He was diagnosed with partial small bowel obstruction based on clinical exam and a CT scan. His symptoms did not improve with nasogastric suction and he was transferred to Tulane Medical Center. At this time, his physical examination was significant only for generalized abdominal tenderness with a clean PD catheter exit site. Though PD fluid cell count showed: WBC of 4177/mm3, RBC of 13713/mm3 and a culture was negative, the catheter would not drain any fluid. The CT scan was reviewed which confirmed the findings of partial small bowel obstruction without any peritoneal enhancement or calcifications. Because of the non-functioning catheter, the patient underwent laparoscopy which showed significant adhesions and dense thickened peritoneal cavity consistent with EPS. The PD catheter was removed and hemodialysis was begun.
Conclusions: Though EPS is not a common condition, it should always be part of the differential diagnosis in patients on PD presenting with symptoms or signs of small bowel obstruction. In particular, this case illustrates the importance of clinical symptoms in patients on PD in considering a diagnosis of EPS.
328 SHE IS ALL “DRESSED” UP: A CASE OF ALLOPURINOL DEADLY COMPLICATION
Ibie NC, Alper AB. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: 1) To help with early diagnosis of Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome as a complication of Allopurinol
2) To increase awareness and prompt initiation of appropriate management for DRESS syndrome
Methods Used: NA.
Summary of Results: A 45-year-old woman with history of chronic kidney disease stage 4, most recent creatinine of 2.7 mg/dL, hypertension, and recent diagnosis of gout presented with a diffuse rash for 4 days starting from her low back and progressing to include her entire body. The patient had been started on allopurinol 100 mg daily 2 months prior. The patient’s development of erythroderma, fever, facial swelling, acute kidney injury (Cr. 8.9 mg/dL), elevation in liver enzymes (AST 183 units/L; ALT 143 units/L; Alkaline phosphatase 91 units/L), and marked peripheral eosinophilia (Eosinophils 15.4%) were consistent with a diagnosis of DRESS syndrome. Steroids were started for the treatment of DRESS and allopurinol was held. The punch biopsy was done which was consistent with a diagnosis of DRESS syndrome. The patient was initially treated with 40 mg intravenous methylprednisolone every 8 hours for 2 days and later switched to prednisone by mouth with improving clinical symptoms. Laboratory values prior to discharge were- Eosinophils 1%; Creatinine 6.0 mg/dL; AST 145 units/L; ALT 173 units/L, Alkaline phosphatase 153 units/L. The patient was discharged with 40 mg of prednisone daily for 7 days, then 30 mg by mouth daily thereafter until her follow-up with dermatology. She presented back to the hospital 3 days after discharge with difficulty swallowing and shortness of breath requiring intubation. Laboratory values were mostly improved (Eosinophils 0%, Creatinine 3.8 mg/dL; AST 79 units/L; ALT 153 units/L; Alkaline phosphatase 266 units/L). CT of the brain revealed large intraparenchymal hemorrhage with subfalcine and uncal herniation. Care was withdrawn per the family’s request the following day and the patient subsequently died.
Conclusions: Up to two percent of patients taking Allopurinol develop DRESS. Though rare, DRESS syndrome is a side effect of allopurinol that physicians should be aware of and about which they need to educate their patients, prior to prescribing Allopurinol therapy, due to the significant mortality (10%) rate of this complication.
329 HEAD-TO-HEAD COMPARISON OF SAFETY PROFILES OF INTRAVENOUS IRON SUCROSE, FERRIC GLUCONATE AND TOTAL DOSE IRON DEXTRAN IN CHRONIC KIDNEY DISEASE PATIENTS
Khan S1,2, Dossabhoy N1,2, Brignac2, Kallam A1,2. 1 LSU Health Sciences Centre, LA and 2 Overton Brooks VA Medical Centre, Shreveport, LA.
Purpose of Study: There are multiple intravenous (IV) iron formulations available today, but very few studies have made a head-to-head comparison. The purpose of this pilot study is to compare the safety profiles of various IV iron formulations in patients with chronic kidney disease (CKD) and iron deficiency anemia (IDA).
Methods Used: This is a retrospective chart review of patients receiving various IV iron formulations at a single center, the VA Medical Center, Shreveport, LA. We included patients with IDA and CKD stages 3 and higher for our analysis. As per prevailing clinical practice, K-DOQI criteria guided the need and usage of IV iron in these CKD patients. Data was collected regarding patient demographics and comorbities, baseline renal and hematological parameters, and adverse events noted with drug administration. Iron sucrose (IS) and ferric gluconate (FG) were given in doses used routinely in clinical practice; whereas iron dextran (ID) at our center was given as a total dose infusion (TDI) of 1000 mg administered IV over 4–6 hours (if negative reaction to an initial test dose).
Summary of Results: This pilot study examined the records of patients administered 609 doses of IV iron - 28% were white, 67% AA, 98% male, 49% had DM, 73% had HTN; age 61+13 years. CKD stage 3 = 29%, stage 4 = 10%, stage 5 = 59%; 33% were on dialysis. Baseline lab values: Creat 4.7+3.2 mg/dL; eGFR 25+19 mL/min; Hgb 9.6+1.7 g/dL; iron 36+21 mcg/dL; T-sat 14+7%. Adverse events (AE) were noted in 8 out of 261 administered doses (3.1%) with ID - commonest being itching, chills and back pain. No AE was noted with either IS or FG. No anaphylactic reaction was noted with any product.
Conclusions: Iron dextran given as total dose infusion has a higher rate of AE’s than routine doses of IS or FG. This may be explained by the much higher dose used for ID; or by the relatively small sample size. However, all of the AE’s were minor, and none were life-threatening.
330 NORMAL KIDNEY PARAMETERS IN PATIENT WITH RENAL FAILURE
Klomjit S, Hosiriluck N, Sutamtewagul G, Rassameehiran S, Phisitkul S. Texas Tech Health Science Center, Lubbock, TX.
Case Report: Serum creatinine and urine output are long known to be parameters for assessment of kidney injury. They have not been established as the best parameters for kidney function evaluation.
75-year-old female with past medical history of dementia, hypertension, and right nephrolithiasis, was admitted to the hospital for shortness of breath and hypoxemia. She was diagnosed with aspiration pneumonia. During hospitalization, she was found to have progressive bilateral pleural effusion from serial chest radiographs. Her urine output was adequate, ranging from 0.6 to 2 liters per day. Her daily fluid balance was positive about one liter every day. Vital signs were within normal limit. Her weight was 45.5 kg. Physical examination was significant for decreased breath sound both lower lungs and peripheral edema. Echocardiogram showed normal systolic function with ejection fraction of 60-64% and normal diastolic function. Pleural fluid analysis showed transudative profile. Serum creatinine was stable at 0.7-0.9 mg/dL. Estimated glomerular filtration rate (eGFR) by MDRD formula was 97 ml/min/1.73m2. Complete metabolic panel was unremarkable. Urinalysis was unremarkable. Fractional excretion of sodium was 1.22% and urea was 48.35%. 24-hour urine protein was 182 mg. Creatinine clearance was 11 ml/min. Serum cystatin C was 2.73 mg/L (normal values 0.5-1 mg/L). She was diagnosed with end stage kidney disease. Conventional hemodialysis was started. Her pleural effusion and fluid retention reduced and she was discharged home with outpatient hemodialysis.
This case illustrates common pitfall when physicians only rely on serum creatinine and eGFR from MDRD formula. Patient underwent several therapeutic thoracocentesis for idiopathic pleural effusion before end stage kidney disease was diagnosed. MDRD formula has limitation in low-body-weight patient to correctly assess renal function. Clinical vigilance is very important to diagnose renal failure in this case. Serum cystatin C may help, as it is not affected by gender, age, race, protein intake, and muscle mass, unlike serum creatinine. Calculated eGFR from CKD-EPI Cystatin C Equation is 18 ml/min/1.73m2. The sensitivity and specificity of serum cystatin C to predict acute kidney injury are 0.86 and 0.82.
331 OVARIAN SEROUS CARCINOMA: A RARE CAUSE OF SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION
Klomjit S, Mankongpaisarnrung C, Dumrongmongcolgul N, Srisung W, Gadwala S, Nugent K. Texas Tech Health Sciences Center, Lubbock, TX.
Case Report:Background: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with malignancy is relatively common. More than 75% of these patients have small cell lung cancer. Ovarian tumors associated with SIADH are extremely rare.
Case description: A 57-year-old postmenopausal woman presented with confusion and new-onset seizures. She had a past history of hypertension, hypothyroidism, and unknown gynecologic malignancy treated with transvaginal hysterectomy 40 years ago. She was on hydrochlorothiazide and levothyroxine. Physical examination revealed clinical euvolemia and no detectable focal neurological deficits. Admission laboratory showed serum Na 110 mmol/L, glucose 84 mg/dL, serum osmolality 234 mOsm/kg, uric acid 5.6 mg/dl, urine sodium 147 mmol/L, and urine osmolality 442 mOsm/kg. Fractional excretions of sodium and urea were 0.7% and 56%. Her serum cortisol and TSH were within normal limits. Computed tomography (CT) of the head and chest was unremarkable. CT of abdomen and pelvic showed bilateral complex adnexal masses; CA-125 was 241 units/ml. An ovarian tumor in conjunction with SIADH was diagnosed.
On admission, she was given hypertonic saline, and hydrochlorothiazide was discontinued. Her serum sodium increased gradually to 115 mmol/L. Her mental status was improved, but her serum sodium values remained low. She then was treated with fluid restriction (1000 ml/day) and demeclocycline. Her serum sodium increased slowly to 125 mmol/L. She underwent surgery with bilateral ovarian mass removal, peritoneal washing, and intra-abdominal tissue sampling. The pathology report showed serous carcinoma of ovaries with mesenteric metastasis.
Conclusion: SIADH is a common cause of hyponatremia. Malignancy-associated SIADH needs to be excluded when patients present with severe hyponatremia, even when a possible culprit medication, such as hydrochlorothiazide, is present. Pulmonary tumors, gastrointestinal tumors, and lymphoma are common causes of malignancy-associated SIADH. Rare intra-abdominal tumors, particularly ovarian cancer, may need to be considered. Our literature review identified three cases of ovarian teratoma and one case of ovarian serous adenocarcinoma.
332 CASE OF ACUTE KIDNEY INJURY, LARGE KIDNEYS, MEDIASTINAL LYMPHADENOPATHY DUE TO IgG4RELATED DISEASE- TUBULOINTERSTITIAL NEPHRITIS
Mohare K, Roberts S, Bodana S. Ochsner Clinic Foundation, New Orleans, LA.
Case Report:Abstract: IgG4 related disease is a relatively new entity. IgG4RD is characterized by systemic involvement, dense infiltration of affected organs with IgG4 positive plasma cells and characteristic storiform fibrosis on histopathology. Kidney involvement commonly causes tubulointerstitial nephritis, shows good response to steroids and often has elevated IgG4 levels. As this is a novel entity, it is still not highly suspected clinically, although once histologic diagnosis is established, it correlates clinically. Different measures are ongoing to establish the diagnostic criteria.
A 50 year old African American man presented with acute kidney injury on underlying chronic kidney disease. He had 40 lbs weight loss, fatigue, shoulder pain, fever and altered behavior. On presentation he had creatinine of 9, non-nephrotic range proteinuria, elevated total protein, mild hypercalcemia with a negative ANA screen. On imaging, kidneys were enlarged with Right kidney at 14.8 cm and Left kidney at 13.7 cm. He also had mediastinal lymphadenopathy. Serum ACE levels were normal. Clinically malignancy was highly suspected. SPEP, UPEP were negative. A kidney biopsy was performed which showed characteristic whorling dense fibrosis involving 90% of the tissue with polyclonal granular deposits in the tubular basement membrane. Patient was started on systemic steroids and had a good response.
Discussion: IgG4 related disease is a recently recognized systemic immune-mediated disease. IgG4-TIN is the most common renal manifestation which can present as acute or chronic renal insufficiency, renal mass lesions, or both. Histologically, plasma cell rich inflammatory infiltrate, storiform fibrosis, tubular basement membrane immune complex deposits are common. Other lesions like membranous glomerulonephritis, IgA nephropathy, membranoproliferative glomerulonephritis were not observed in the biopsy. IgG4 levels were not obtained initially as the diagnosis was not suspected. Proposed diagnostic criteria for IgG4-TIN by Raissian et al and Japanese Society of Nephrology criteria for IgG4-RKD will help diagnose more cases. As noted in this case, malignancy is highly suspected at the time of presentation due to similarities in signs and symptoms but biopsy helps solve the puzzle.
333 CASE OF ACUTE KIDNEY INJURY ALONG WITH SEVERE THROMBOCYTOPENIA, HYPERBILIRUBINEMIA DUE TO LEPTOSPIROSIS INFECTION IN NEW ORLEANS AREA
Mohare K, Bodana S, Blemur P. Ochsner Clinic Foundation, New Orleans, LA.
Case Report: 27 years old man without any significant past medical history presented with acute illness. He had high grade fever associated with severe myalgia, nausea, vomiting, headache and poor oral intake. During his almost a week long illness, he developed jaundice, cough, rusty sputum production. His admission labs were remarkable for creatinine of 4.5, Total bilirubin 22, Direct bilirubin 15, normal liver enzymes, LDH 343. Remarkably he had serum potassium of 2.6. Also, of note he had severe thrombocytopenia of 22,000. He was still holding his blood pressure without any episode of hypotension. Peripheral smear was negative for schistocytes although clinically he was strongly suspected to have thrombotic thrombocytopenic purpura. Urine analysis was negative for any hematuria. Initially plasmapheresis was offered till other results became available. However, peripheral smear continued to remain clear of any schistocytes. ADAMTS13 assay came back normal. Hence other etiologies were considered. Infectious disease work up was sent for various possible differential diagnoses including Brucellosis, Rickettsial disease, Ehrlichiosis, leptospirosis. Diagnosis was not very obvious as thrombocytopenia was severe and is not classic feature of leptospirosis. Finally diagnosis became clear when serology for leptospirosis came back positive at 1:100.
Patient was a resident of New Orleans. He was a wildlife game inspector. His work involved working in the marshy swamp areas with close contact with various wild life creatures including alligators. Plus he had been hunting ducks and fishing in Buras, LA the week prior to this presentation. This also involved wading in the pond water.
Discussion: Leptospirosis is a zoonosis with protean clinical manifestations caused by pathogenic spirochetes of the genus Leptospira. Here it was considered as one of the differential diagnoses however severe thrombocytopenia is not a typical feature of the disease. Severe hypokalemia could have been from tubular dysfunction. Patient responded appropriately once started on Doxycycline. Overall it is felt this diagnosis should be considered more often in the appropriate setting as it can be potentially fatal. But with the correct use of antibiotic in time mostly there is recovery.
334 UNEXPLAINED HYPOTENSION: A CASE OF SEVERE HYPOCALCAEMIA
Paccione R, Khalique S, Nimkevych O, Fremin K, Soltani Z. LSU Health Sciences Center, New Orleans, LA.
Case Report: Hypocalcaemia after thyroidectomy is a common finding. It may be transient or a permanent post-operative complication if removal of the parathyroid occurred incidentally during thyroidectomy. Hypocalcaemia should be considered as a cause of hypotension in these patients. Here we discuss a case of severe hypotension secondary to hypocalcaemia.
Case Report: A 72 year old Caucasian female with a history of hypertension, hypothyroidism status post thyroidectomy two months prior, chronic alcohol abuse and depression was found down in her home. On physical exam vitals: HR 96 bpm, respirations 21 breaths/min on mechanical ventilation, BP 71/31 mmHg, temperature 98.6 F. Of note, she was sedated at the time of the physical exam, but bilateral upper extremity twitching was present. The remainder of the physical exam was unremarkable. Pertinent laboratory findings included ionized Ca 0.65 mmol/L, calcium 3.6 mg/dl, magnesium 1.6 mg/dl, phosphorus 10.2 mg/dl, potassium 2.5 mmol/L, BUN 68 mg/dl, creatinine 5.3 mg/dl with baseline normal kidney function. PTH <5.0 pg/ml, cortisol WNL and the remainder of the work up was normal. Blood and urine cultures were negative. Due to profound hypocalcaemia, the patient was placed on continuous renal replacement therapy. After three days, the calcium normalized and the patient no longer required vasopressor support. Her mental status and kidney function improved. The patient was sent home off dialysis and on vitamin D and calcium supplements.
Discussion: Hypocalcaemia following near total of total thyroidectomy is a common complication. It can be a result of a disruption of the blood supply to the parathyroid gland or total removal of the parathyroid. The hypocalcaemia can range from asymptomatic to severely symptomatic. Hypocalcaemia traditionally manifests as tetany, seizures, altered mental status and/or arrhythmias. However, it can also present as refractory hypotension, as was the case in our patient. Once traditional calcium supplementation has been implemented and fails to adequately replace the calcium, dialysis should be considered.
Conclusion: Hypocalcaemia should be considered among the differential as the cause of severe hypotension.
335 DEVELOPMENT OF A CLINICAL PRACTICE GUIDELINE FOR VANCOMYCIN DOSING AND MONITORING
Palm S1, Belt E1, DeLeon S1, Balan A2, Hagemann T3. 1 University of Oklahoma Health Sciences Center, Oklahoma City, OK; 2 University of Okahoma Health Sciences Center, Oklahoma City, OK and 3 University of Okahoma Health Sciences Center, Oklahoma City, OK.
Purpose of Study: Over the course of a 2-month period in the summer of 2012 at The Children’s Hospital at OU Medical Center (TCH), three patients receiving vancomycin experienced drug-induced acute kidney injury (AKI). Subsequently, a chart review of patients on vancomycin at TCH revealed inconsistent dosing and laboratory monitoring of levels and renal function. Vancomycin-induced AKI is becoming an important topic on a national scale due to increasing trough goals, although no official pediatric dosing or monitoring guidelines were found when contacting other major children’s hospitals. This project aims to develop a clinical practice guideline to assist medical care providers and pharmacists in making decisions regarding vancomycin dosing and monitoring to prevent drug-induced AKI.
Methods Used: A multidisciplinary team was assembled, including General Pediatrics and Infectious Disease faculty, pediatric residents, clinical pharmacy, hospital nursing, laboratory staff, and TCH’s Senior Quality Coordinator. Collaboratively we established cost effective dosing and vancomycin trough/serum creatinine monitoring guidelines, which should either eliminate or allow early identification of patients with vancomycin-induced AKI. The guidelines include monitoring for patients receiving additional nephrotoxic medications and for pharmacy or infectious disease consults to guide physicians in appropriate dosing and monitoring in more complicated cases.
Summary of Results: The Clinical Practice Guidelines are currently being distributed to physicians, residents, nurses, and pharmacists via email, educational meetings, and postings in work areas. A comparison study to evaluate the incidence of drug-induced AKI before and after the implementation of the guidelines will then be completed.
Conclusions: With close, consistent monitoring of vancomycin troughs and serum creatinine in patients on vancomycin, the incidence of AKI should significantly decrease after guideline implementation. As vancomycin is not the only nephrotoxic drug used regularly, an expansion of AKI prevention is also in development process.
336 METABOLIC HEALTH MODIFIES THE ASSOCIATION OF BODY MASS INDEX AND RISK OF END-STAGE RENAL DISEASE
Panwar B1, Hanks LJ1, Tanner RM1, Muntner P1, Kramer H2, McClellan W3, Warnock DG1, Judd SE1, Gutiérrez OM1. 1 University of Alabama, Birmingham, AL; 2 Loyola, Chicago, IL and 3 Emory, Atlanta, GA.
Purpose of Study: Obesity has been associated with poor outcomes in the general population. However, recent studies have demonstrated that the association of body mass index (BMI) with outcomes depends in part on clustering of metabolic risk factors. We examined whether metabolic health modifies the association of BMI with end-stage renal disease (ESRD) within the REGARDS study, a cohort of 30,239 black and white adults.
Methods Used: The primary exposures were BMI and metabolic health. Metabolic health was defined according to the harmonized criteria for metabolic syndrome - persons with ≥3 metabolic syndrome factors were categorized as metabolically unhealthy and those with <3 as metabolically healthy. The outcome was ESRD. Cox models were used to estimate the hazard ratio of ESRD as a function of BMI and metabolic health, separately. We tested for effect modification of metabolic health on the association between BMI and ESRD.
Summary of Results: We excluded participants with missing data, who did not fast for the study visit, or were on dialysis, leaving 21,840 persons in analyzed sample. 218 participants developed ESRD over <6 years of follow-up. Metabolic health modified the association of BMI with incident ESRD (P-interaction=0.004). When we stratified the analysis according to categories of weight and metabolic subtype, as compared to metabolically healthy normal weight persons, higher BMI was associated with lower risk of ESRD in those who were metabolically healthy, whereas higher BMI was associated with higher risk of ESRD in those who were metabolically unhealthy in analyses adjusted for demographic variables, lifestyle factors, and co-morbidities. (Table).
Conclusions: Metabolic risk factors modify the association of BMI with risk of incident ESRD. BMI alone is a poor marker of future risk of ESRD. Elevated BMI may be protective against the development of ESRD among metabolically healthy individuals.
337 CALCIPHYLAXIS IN END STAGE RENAL DISEASE PATIENTS FROM THE UNITED STATES RENAL DATA SYSTEM
Saith S1,2, Huber L1,2, Nahman NS1,2, Kheda M1,2, Baer S1,2, Colombo R1,2, Kintziger K1. 1 Georgia Regents University, Augusta, GA and 2 Charlie Norwood VA Medical Center, Augusta, GA.
Purpose of Study: Calciphylaxis (CPX) is a rare condition usually seen in ESRD patients and is associated with significant mortality. It is characterized by subcutaneous vascular calcification and cutaneous necrosis. Its etiology is thought to be multifactorial but unclear. Given its low prevalence, few studies are available investigating CPX. Our study queried the United States Renal Data System (USRDS) to investigate the co-morbidities and outcomes associated with CPX.
Methods Used: All prevalent ESRD patients in the USRDS were queried. CPX was defined using the ICD-9 diagnosis code 275.49 (other disorders of calcium metabolism) plus at least one of 7 additional relevant diagnosis codes identifying skin lesions common to the disease (i.e. nodules, ulcers, skin necrosis, etc) during the same inpatient visit as the CPX diagnosis. Basic descriptive statistics were used to assess frequencies and percentages for categorical variables and mean and standard deviation (SD) for continuous variables.
Summary of Results: A total of 2,133,440 individuals with ESRD diagnosed between 1963 and 2009 were identified and 13,560,760 hospital records from 1977 through 2008 analyzed. 459 (0.02%) patients met the criteria for CPX. For this group: mean age was 50.4 years (SD 15.7) with 20.3% > 65 years, 71.0% female, 59.0% Caucasian and 37.3% African-American. Treatment modality at the time of CPX diagnosis: center-based hemodialysis (HD) (78.7%), peritoneal dialysis (14.8%) and transplant (2.4%). Comorbidities associated with CPX included obesity (79.1%), diabetes mellitus (65.8%), coronary artery disease (47.7%), bacteremia (43.1%) and history of parathyroidectomy (28.1%). The median survival time for individuals with CPX was 1.1 years and 50% of the deaths were within 87 days of their CPX diagnosis. Most common causes of death were cardiac arrest (23.9%), septicemia (20.6%), other identified causes (19.9%), withdrawal from dialysis/uremia (5.7%) and MI (3.3%).
Conclusions: Although rare, CPX is associated with a high mortality. It is more common in obese, diabetic, female and in-center HD patients. Cardiovascular disease and severe mineral bone disorders may also be present. Bacteremia is a common complication and may contribute to the high mortality.
338 PERSISTENT METABOLIC ACIDOSIS IN DIALYSIS PATIENT AFTER UNINTENTIONAL SALICYLATE OVERDOSING
Schwartz DW. University of Tennessee, Memphis, TN.
Case Report: Metabolic acidosis is a common and important complication of Chronic Kidney Disease and End Stage Renal Disease. Correcting the acidosis in CKD patients has been shown to slow progression of kidney disease. It must be monitored and managed appropriately. There are numerous causes of both non anion gap and anion gap acidosis. We present a case where a dialysis patient was found to have an anion gap acidosis of unknown cause, that when resolved, persisted due to a second cause. Patient is a 63yo M with h/o ESRD who had been having persistent diarrhea that had been refractory to medications. Patient has a h/o chronic pancreatic insufficiency and has been on pancrelipase. Patient denied blood in stool, F/C, abdominal pain. He was noted on monthly lab work to have a serum bicarbonate of 10 with an anion gap of 20. Pt was otherwise at baseline and the thought was the diarrhea was causing the AG, and we did not believe he was taking heavy amounts of salicyaltes or ingesting methanol. Patient relates on next HD session that he has been taking several packets of BC Powders every day. It was explained to him that this contains too much aspirin to safely take. He also noted mild tinnitus when questioned about it. Patient told to stop BC powders and was indeed found to have elevated salicylate levels. Patient was no longer taking BC powers but diarrhea has persisted. Regardless, the patient continued to have a significant acidosis. Bicarbonate increased in HD to 34, and he is told he cannot miss HD for now (he has a h/o of mild noncompliance). The acidosis persisted secondary to the diarrhea. A thorough evaluation of acidosis is often required to come to the etiology, as there are often several causes of an acid-base disorder present at the same time that can cloud the evaluation. Preventing chronic acidosis in renal patients is important given the long-term complications of acidosis, such as decreased cardiac output and renal disease progression.
339 IV HYDRALAZINE FOR TREATMENT OF HOSPITALIZED HYPERTENSIVE CHILDREN: HOW EFFECTIVE ?
Shatat I1, Ostrye J2, Jones J1, Hailpern S3, Egan B4, Chessman K2. 1 MUSC Children’s Hospital, Charleston, SC; 2 Medical University of South Carolina, Charleston, SC; 3Independent Consultant, Palo Alto, CA and 4MUSC, Charleston, SC.
Purpose of Study: IV hydralazine is frequently used for treatment of hypertension in the hospitalized child. it’s safety and efficacy in treating hypertension in hospitalized children has not been examined.. The objective of this study was to determine the efficacy and safety of the first dose of intravenous hydralazine at the Medical University of South Carolina Children’s Hospital.
Methods Used: A retrospective chart review was conducted to evaluate the efficacy, safety, and appropriate use of intravenous hydralazine in hospitalized children over a 3-year period. The patient population included children ages birth to ∼ 18 years admitted to one of the non-critical care areas of the hospital. patient’s blood pressure and heart rate prior to and up to 8 hours after each dose was given were collected. Other admission-specific and patient demographic data were also collected, along with documented adverse effects.
Summary of Results: 110 hospital admissions were included in this review. The mean age was 8.65 years, 57.3% were male, and 35.5% were white. Pre dose systolic and diastolic BPs were 146.4 and 92.0, respectively. Almost one-third (30.0%) of patients received an inappropriate dose of hydralazine (∼ 0.1 mg per kg per dose). All patients received intravenous hydralazine appropriately. Only 8 patients (7.3%) achieved BP control after one hydralazine dose, with 9.1% of patients having documented adverse effects. In a multivariate regression models examining percent change in systolic and diastolic BP, younger age, appropriate dose, and receiving two or more concurrent antihypertensive agents were significantly associated with decreases in diastolic, but not systolic BP.
Conclusions: In hospitalized children, younger age, appropriate dose, and receiving hydralazine in addition to chronic hypertensive management is associated with a significant percent decrease in diastolic, but not systolic BP. Intravenous hydralazine is well tolerated in children.
340 A RARE CASE OF LOW-SOLUTE HYPONATREMIA IN A NON-ALCOHOLIC: A CASE REPORT AND LITERATURE REVIEW
Srisung W, Mankongpaisarnrung C, Anaele C, Dumrongmongcolgul N, Ahmed V. Texas Tech University Health Sciences Center, Lubbock, TX.
Case Report: Euvolemic hyponatremia poses a diagnostic challenge to physicians. Among this group, low-solute hyponatremia is relatively uncommon. Classic cases were described in alcoholics as beer potomania, which is characterized by hyponatremia in the setting of low-solute intake and heavy beer drinking. We report a case of low-solute hyponatremia in a non-alcoholic who was given solute load, and subsequently had excessive diuresis with resultant rapid increase in serum Na.
A 69-year-old African American man with HTN, seizure disorder but no underlying psychiatric diagnoses presented with confusion and urinary incontinence. He had a serum Na of 117 mEq/L with urine osmolality of 132 mOsm/L and plasma osmolality of 250 mOsm/L. Urine Na was not checked initially. He was given 1 L bolus of normal saline in the ER. Repeat serum Na at 12 hr was 127 mEq/L. Urine output was 8 L in this first 12 hr. 5% Dextrose water was then started at 100 ml/hr. 15 hr after bolus, his Na decreased to 123 mEq/L, urine osmolality was 315 mOsm/L and urine Na was 128 mEq/L. Further history obtained when he regained consciousness revealed inability to maintain oral intake due to poor appetite for 3 months, but he could still hydrate himself adequately. He was an occasional alcohol drinker. He has history of hospitalizations due to hyponatremia of unclear etiology. Na level was monitored and the rate of D5W was adjusted to keep the rate of increase in Na to no more than 8–10 mEq/L in 24 hr and 18 mEq/L in 48 hr. He was finally discharged at serum Na of 130 without any neurologic sequelae.
Our case highlights the importance of detection of low-solute hyponatremia. Its clinical picture can mimic SIADH as urine osmolality may exceed 100 mOsm/L and urine Na may exceed 40 mEq/L. However, low-solute hyponatremia will typically cause significant diuresis and rapid increase in Na after solute load as opposed to worsening serum Na in SIADH. Rapid correction of Na can predispose to osmotic demyelination syndrome. However, if over-correction occurs, lowering the Na with D5W is crucial. Management includes fluid restriction in mild or asymptomatic patients and finite amounts of IV fluids in symptomatic cases, and maintenance of the solute load with oral intake.
341 AN UNCOMMON CAUSE OF BILATERAL ENLARGED KIDNEYS: CASE REPORT AND LITERATURE REVIEW
Srisung W1, Mankongpaisarnrung C1, Warraich I2, Sotello D1, Yarbrough S1, Laski M1. 1 Texas Tech University Health Sciences Center, Lubbock, TX and 2 Texas Tech University Health Sciences Center, Lubbock, TX.
Case Report: Metastasis to the kidney is the most common etiology of intrarenal malignancy, but it remains uncommon (12.6% in malignancy of epithelial origin). Lung cancer is the most common primary lesion (19.8-23.3%), but only 22.5% of lung cancer spreads to kidneys. It can present unilaterally (46%) or bilaterally (54%), and either as an isolated mass or infiltrative disease. We report a case of squamous cell lung carcinoma causing bilateral infiltrative kidney metastasis.
A 67-year-old White woman presented with a 6-month history of chronic productive cough, abdominal bloating, and weight loss. Diminished breath sounds were noted at the right lung base. Basal metabolic panel revealed Na 127 mEq/L, BUN 32 mg/dl, and creatinine 2.4 mg/dl. Chest x-ray showed a right lower lobe cavitary lesion with air-fluid level. Computed tomography (CT) of the lungs showed 8.6x6.2 cm and 1.6x1.4 cm cavities in the right lower lung, multiple pulmonary nodules, and right-sided pleural effusion. Abdominal CT scan showed right adrenal mass and sclerotic changes of T12 and L2 bony metastases, bilateral enlarged kidneys (right 8.7x12.5 cm and left 8.1x13 cm) with multiple small hypodense lesions, and retroperitoneal lymphadenopathy. Urinalysis showed RBC >20 and WBC 5-10. The 24-hour urine protein was 310 mg. Renal ultrasound showed an infiltrating process without hydronephrosis. Renal biopsy showed squamous carcinoma cells among a normal appearing glomerulus and atrophic tubules. Stains were negative for CK7 and CK20. Transbronchial biopsy revealed squamous cell carcinoma. The definite diagnosis was thus squamous cell carcinoma of the lung with infiltrative renal metastasis.
In this case, the microscopic hematuria, azotemia, and non-nephrotic range proteinuria resulted from metastatic lung cancer that diffusely infiltrated both kidneys. Enlarged kidneys in patients with suspected cancer elsewhere should raise concern for metastasis. Kidney biopsy remains the gold standard for diagnostic workup for renal metastasis.
342 THE LONG-TERM OUTCOME OF KETOCONAZOLE AND TACROLIMUS CO-ADMINISTRATION IN KIDNEY TRANSPLANT PATIENTS
Umber A. Tulane, Metairie, LA.
Purpose of Study: To report our experience of combined use of Ketoconazole & Tacrolimus in kidney transplant recipients.
To study the effect of combination therapy on rate of rejection in Kidney Transplant recipients.
Methods Used: From 2006 to 2012, there were 450 adult patients who received a primary kidney transplant in our center. Among them, ketoconazole was given in 199 patients after transplant surgery and was continued for at least 1 year or until graft failure (group 1), while 149 patients did not receive any ketoconazole (group 2).
The combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. Basic demographic data were similar between the 2 groups.
Summary of Results: The cumulative incidence of biopsy-confirmed and clinically-treated acute rejection over 5 years was significantly higher in group 1 than in group 2 (34% vs. 18%, p<0.001). The 5-year Kaplan-Meier estimated patient and graft survival were not statistically different between the 2 groups. Multivariable logistic regression analyses identified ketoconazole usage as an independent risk of acute rejection (OR 2.35, 95% Cl 1.41-3.90; p=0.001). Delayed graft function (OR 2.1, 95% Cl 1.15-3.68; p=0.015) and infectious complication (OR 1.8, 95% Cl 1.05-3.10; p=0.031) were also found to be significant risks of acute rejection.
Conclusions: Our study suggests that co-administration of Ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.
343 TOO MUCH OF A GOOD THING: WHEN PREGABALIN MAKES YOU JERK
Wang HT1, Yu S2, Smalligan RD1. 1 Texas Tech Univ HSC, Amarillo, TX and 2 Texas Tech Univ SOP, Amarillo, TX.
Case Report: A 51yo woman on hemodialysis (HD) presented with severe leg pain that prevented her from walking. She denied trauma, heavy lifting, prolonged immobility or leg swelling. PMH: HTN, ESRD, IBS, GERD; Meds: amlodipine, aspirin, clonidine, dicyclomine, hydralazine, metoprolol, ranitidine, and sevelamer. FH neg, no smoking, alcohol or drugs. PE: T98, BP 131/76, and O2 95% on RA; alert, cardiac, pulmonary, abdominal, and neurologic exams normal except for weakness in the lower extremities with preserved reflexes. Labs: c/w her ESRD and Ca and CPK were nl.
Course: After DVT was ruled out pregabalin was given for neuropathic pain. Next day her pain and strength had improved so her dose was increased. The third day she developed choreoathetosis but no nystagmus, tremor, Chvostek or Trousseau’s sign. The pregabalin was stopped and benztropine started. HD continued on schedule. The choreoathetosis resolved over 2 days and the patient went home able to walk.
Discussion: Pain from peripheral neuropathy is a common complaint heard by internists. While gabapentin was excellent for treating it, pregabalin was later found to be even more effective. Pregabalin is an isomer of GABA which binds to Ca channels in CNS regions and increases GABA transport. It is minimally metabolized and is excreted 90% unchanged in the urine. Side effects include edema, dizziness, somnolence, ataxia, headache, and fatigue. Case reports have revealed other side effects including dysautonomia, dyskinesia, extrapyramidal syndrome, etc. Our patient had been stable on her home meds for more than 3 months making them unlikely culprits. In addition, no other meds besides pregabalin were started prior to her choreoathetosis and it faded after stopping pregabalin. This is supportive of the hypothesis that pregabalin was the cause. Pregabalin is usually dosed at 150 mg daily or divided bid or tid for neuropathy. However, dose adjustment is recommended in renal impairment. For patients with a CrCl ∼ 15 ml/minute, the recommended dose is 25-75 mg as a single daily dose. This renal adjustment was overlooked in our patient. This case reminds physicians to consider the possibility of choreoathetosis when using pregabalin and the importance of renal dose adjustment, particularly in hemodialysis patients.
344 RISK FACTORS FOR DEATH FOLLOWING A DIAGNOSIS OF SPINAL EPIDURAL ABSCESS IN HEMODIALYSIS PATIENTS
White J1, Jin C1, Colombo R1, Baer S1,2, Afzal U1, Kintziger K1, Kheda M1, Huber L1, Chebrolu P1, Nahman NS1,2. 1 Georgia Regents University, Augusta, GA and 2 Augusta VAMC, Augusta, GA.
Purpose of Study: In previous work we showed that spinal epidural abscess (SEA) is a serious infectious comorbidity in hemodialysis (HD) patients (JASN, abstract in press). SEA was significantly associated with bacteremia, MRSA infection and hepatitis C, however, the risk factors for mortality following a diagnosis of SEA remained undefined. The present study addressed these questions via queries of the United States Renal Data System (USRDS).
Methods Used: All incident HD cases from the USRDS for calendar years 2005–2008 were queried for a diagnosis of SEA. Survival and risk factors associated with mortality were also assessed. ICD-9 diagnosis codes were used to identify diagnoses. Cox regression models were used to determine the relative hazard of death associated with an SEA diagnosis compared to other known risk factors for death in ESRD patients. We used bivariate and multivariable models to assess these associations. Using backwards elimination of non-significant variables, a final model was obtained, and the hazards ratios (HR) and 95% confidence intervals (CI) determined.
Summary of Results: For the 4-year period of study, SEA was identified in 660/355,084 (0.19%) patients. The HR and 95% CI for death from SEA was HR 1.20, CI 1.085, 1.328. Demographic variables that conferred a significant risk for death included age > 65 years (HR 2.269, CI 2.243, 2.295) and the presence of a dialysis catheter (HR 1.884, CI 1.850, 1.918). The top 4 comorbid conditions significantly associated with mortality in SEA positive patients included cirrhosis (HR 1.715, CI 1.667, 1.765), decubitus ulcer (HR 1.669, CI 1.640, 1.699), bacteremia (HR 1.407, CI 1.390, 1.425) and TPN (HR 1.376, CI 1.326, 1.429). Other significant co-morbidities included pancytopenia, candidemia, hepatitis C infection and C. difficile colitis (HR range: 1.363 - 1.145).
Conclusions: SEA in HD patients is associated with an increased risk of death. Older age, the presence of dialysis catheters, cirrhosis, decubitus ulcers, bacteremia, and TPN constitute the greatest risk factors for death and thus necessitate a comprehensive approach to management.
345 IS THERE A ROLE FOR ECULIZUMAB IN THE TREATMENT OF SEVERE SHIGA TOXIN ASSOCIATED HEMOLYTIC UREMIC SYNDROME?
Yanik MV, Feig D. University of Alabama at Birmingham, Birmingham, AL.
Case Report: Background: Hemolytic uremic syndrome is a thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. A majority of pediatric cases are associated with a diarrheal illness caused by shiga toxin producing E coli (STEC-HUS). Recent evidence suggests that in addition to direct endothelial injury and inflammation, activation of the complement system may be an important mechanism of organ injury in STEC-HUS. Standard treatment of STEC-HUS is supportive care. The use of eculizumab, a monoclonal antibody that inhibits C5, for treatment of STEC-HUS remains controversial.
Case: Patient is a 6 year old Caucasian male with a severe and complicated course of STEC-HUS. Initially admitted with bloody diarrhea and dehydration, he developed thrombocytopenia and acute kidney injury within 24 hours of hospitalization. By hospital day 2 patient was anuric and dialysis was initated on hospital day 5. He developed neurologic symptoms with altered mental status and seizures, followed by shock and respiratory failure. Given his rapidly progressing course, patient was given a dose of eculizumab on hospital day 7. He continued to clinically worsen. He had a cardiac arrest and required ECMO for combined cardiac and respiratory failure on hospital days 9–20. He developed abdominal compartment syndrome and bowel infarction requiring colonic resection. He also sustained a right temporal and parietal stroke. Although over several months patient gradually improved and was able to be discharged, he continues to have stage II chronic kidney disease, cognitive deficits, and mild left hemiplegia a year later.
Discussion: In this severe case of STEC-HUS there was no benefit of the administration of eculizumab, as the patient continued to deteriorate clinically. A case series in the New England Journal of Medicine reported on 3 patients with severe STEC-HUS who were treated with eculizumab, all of which had dramatic improvement within 24 hours of the first infusion. There are conflicting reports on the effects of eculizumab use during the 2011 STEC-HUS outbreak in Germany.
Conclusion: Further studies, especially randomized controlled trials, are needed to evaluate the potential efficacy of eculizumab in the treatment of STEC-HUS.
Southern Society for Clinical Investigation and Southern American Federation for Clinical Research Plenary Session SSCI Young Investigator Award Finalists SAFMR/SSCI/ Young Faculty Award SAFMR/SSCI/ Trainee Research Award
8:00 AM
Friday, February 21, 2014
346 RECOVERY OF SMALL MYOCYTES AND REVERSE REMODELING IN HYPERTENSIVE HEART DISEASE
Al Darazi F, Zhao W, Zhao T, Sun Y, Marion TN, Ahokas RA, Bhattacharya SK, Gerling I, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Hypertensive heart disease (HHD) includes hypertrophied cardiomyocytes and widely scattered foci of microscopic scarring, which have replaced necrotic myocytes. Bordering on these microdomains of fibrosis are small myocytes that re-express β-myosin heavy chain (β-MHC), a fetal gene. We hypothesized small myocytes represent an autologous population of cells which could be recovered for reverse remodeling in HHD.
Methods Used: 8-wk-old male Sprague-Dawley rats received aldosterone/salt treatment (ALDOST) for 4 wks followed by a 4-wk period of assisted recovery when oral antioxidants (ZnSO4 and nebivolol, a β3 receptor agonist) were given.
Summary of Results: Compared to untreated age-/sex-matched controls: mean arterial pressure (MAP, 162±2 vs. 99±2 mmHg) and left ventricular (LV) mass (1043±23 vs. 883±32 g) were increased (p<0.05) while pressure-independent scarring appeared in the right and left heart at 4 wks ALDOST. Bordering on these scars were α-smooth muscle actin+ myofibroblasts (myoFb) and small myocytes revealing: i) re-expression of β-MHC and atrial natriuretic peptide (ANP); ii) increased expression of reactive oxygen species; and iii) reduced nitric oxide. Cardiac tissue 8-isoprostane and redox-sensitive ligases (atrogin-1 and MuRF1) of the ubiquitin protease system were each increased (p<0.05) while E/A ratio and LV fractional shortening were reduced (p<0.05). Assisted recovery led to normalized MAP, regression in LV mass, and reduction in small myocytes (p<0.05) with restored redox balance and NO, neutralized protein degradation, together with improved diastolic and systolic function.
Conclusions: HHD includes microdomains of fibrosis where small myocytes re-express a fetal gene program together with altered redox balance and protein degradation. Recovery of these myocytes, using neurohormonal withdrawal plus a regimen of antioxidants, is feasible and leads to reverse remodeling with improved ventricular function in HHD. Whether heterocellular signaling with myoFb exists and the potential origin of these small myocytes as progeny of bone marrow or cardiac stem cells vs. dedifferentiated myocytes remains to be determined.
347 ROLE OF ASPERGILLUS FUMIGATUS SIALIDASE IN DISRUPTION OF PULMONARY ARTERY AND PULMONARY MICROVASCULAR ENDOTHELIA
McGrath B1, Cioffi E2, Cioffi D3, Fortwendel J1. 1 University of South Alabama College of Medicine, Mobile, AL; 2 University of South Alabama College of Medicine, Mobile, AL and 3 University of South Alabama College of Medicine, Mobile, AL.
Purpose of Study: Aspergillus fumigatus (Af) is the primary causative species of invasive aspergillosis (IA), a deadly disease that affects immunocompromised patients. A better understanding of the molecular mechanisms regulating invasive growth of Af is essential to the development of novel antifungal therapies. Pulmonary artery (PA) and microvascular (MV) endothelial cells, which form important barriers to hyphal angioinvasion and subsequent bodily dissemination during IA infection, have been shown to express sialic acids that contribute to the integrity of cell-cell interactions. The current study tested the hypothesis that a sialidase enzyme secreted by Af contributes to pathogenesis by facilitating the disruption of these endothelial barriers.
Methods Used: To generate a mutant strain lacking sialidase activity, the sole Af sialidase gene, siaA, was deleted by homologous recombination in a uridine auxotrophic strain using Af protoplast transformation. Standard Aspergillus culture and microscopy techniques were employed to analyze the effect of siaA deletion on germination, hyphal growth and morphogenesis. To determine the impact of siaA deletion on host-pathogen interactions, electric cell-substrate impedance sensing (ECIS) was utilized to measure cell-cell barrier disruption in the presence of Af conidia.
Summary of Results: Deletion of siaA caused delayed germination and a statistically significant reduction in radial growth rate, as compared to wild type. However, the ΔsiaA strain developed morphologically normal hyphae. ECIS analyses indicated reduced cell-cell barrier disruptions for both PA and MV cell lines when cultured with the ΔsiaA mutant.
Conclusions: Taken together, our data suggest that siaA contributes to the timing of Af asexual development and to the disruption of endothelial barriers. Future studies will further define the role of siaA as a potential virulence determinant by delineating the individual contributions of sialidase activity to Af growth, endothelial barrier disruption and virulence in a murine model of invasive aspergillosis.
348 NOVEL PROTECTIVE EFFECT OF HISTONE DEACETYLASE 9 AS A REPRESSOR OF ANGIOTENSINOGEN EXPRESSION IN THE FEMALE RAT KIDNEY
Bourgeois C1,2, Rui P3, Sato R1,2, Prieto MC1,2. 1 Tulane University, New Orleans, LA; 2 Tulane University, New Orleans, LA and 3 Tulane University, New Orleans, LA.
Purpose of Study: Young females are protected from the development of hypertension and related end-organ damage compared to males. Inappropriate activation of intrarenal renin-angiotensin system (RAS) is a major contributor to hypertension and renal injury. During intrarenal RAS activation, upregulation of angiotensinogen (AGT) in renal proximal tubular cells (PTC) serves as a key mechanism. Females exhibit lower excretion of AGT in urine, suggesting that intrarenal AGT production in females may be a protective factor against the development of hypertension. However, whether epigenetic factors influence intrarenal AGT expression levels leading to the sex disparities has not been delineated. In this study we aimed to determine the epigenetic factors controlling AGT expression in PTC.
Methods Used: AGT mRNA and protein levels in renal cortex of male and female Sprague Dawley rats were measured by real time RT-PCR and Western blot analyses. Furthermore, we used a chromatin modification enzyme PCR array to examine if epigenetic factors which repress gene transcriptions, particularly histone deacetylases (HDAC) and co-repressors, are determinant for the low AGT expression in the kidney of females. To clarify the relationship between HDAC9 and AGT, gene silencing of HDAC9 was performed in the rat PTC.
Summary of Results: AGT mRNA and protein levels were significantly lower in renal cortex of females than males (0.15 ± 0.01 in mRNA, 0.41 ± .03 in protein, ratio to male). In the HDACs and co-repressors tested in this study, only HDAC9 exhibited higher expression in renal cortex of females than males (7.09± 0.88, ratio to male). Western blot and immunohistological analyses using rat renal cortex and cultured rat PTC revealed HDAC9 is expressed in PTC. HDAC9 with Knockdown by siRNA augmented AGT mRNA (1.92 ± 0.35, ratio to control) and protein (2.25 ± 0.50, ratio to control) levels compared to scrambled siRNA transfected cells.
Conclusions: HDAC9 is a novel suppressing factor of AGT in PTC, helping to explain the low levels of intrarenal AGT in females. These findings help to delineate the mechanisms underlying sex disparities in hypertension and renal injury associated with dysregulation of RAS.
349 ROSIGLITAZONE INCREASES CHOLESTEROL EFFLUX CAPACITY IN PATIENTS WITH TYPE 2 DIABETES
Agarwala A, Givens E, McGuire DK, De Lemos JA, Rohatgi A. UT Southwestern Medical Center, Dallas, TX.
Purpose of Study: Thiazolidinediones (TZDs) are medications used in patients with type 2 diabetes (T2DM) that activate peroxisome proliferator- activated receptors (PPAR) γ, thereby improving insulin sensitivity and glycemic control. In most patients, treatment with TZDs increases HDL-C, suggesting that TZDs may have effects on atherosclerosis via the reverse cholesterol transport (RCT) pathway. A few small reports without placebo control have shown that TZDs may increase macrophage-specific cholesterol efflux capacity (CEC), the first critical step in RCT. We tested the hypothesis that TZDs, specifically rosiglitazone (rosi), increase CEC in patients with T2DM in a placebo-controlled trial.
Methods Used: 111 patients (57 rosi, 56 placebo) with T2DM and either the presence of coronary disease or strong risk factors for coronary disease were randomized to double-blinded treatment with rosi vs. placebo for 6 months. CEC was measured at baseline and after 6 months treatment.
Summary of Results: Preliminary results from the first 65 patients (30 rosi, 35 placebo) show increased mean CEC in patients randomized to rosi vs. placebo (ΔR: 0.064 ± 0.31; ΔP: -0.045 ± 0.26, p=0.03). Paired comparisons of baseline vs. treatment show an increase in the rosi arm (0.87 ± 0.54 vs. 0.93 ± 0.51, p 0.005) but no change in the placebo arm (0.79 ± 0.51 vs. 0.74 ± 0.51, p 0.83) (Figure 1).
Conclusions: These findings from a randomized placebo-controlled trial suggest that activation of PPAR γ increased CEC and that the effect of TZDs on atherosclerosis may be mediated by their effects on cholesterol efflux.
350 THE ROLE OF LEUKOCYTE ASSOCIATED IMMUNOGLOBULIN-LIKE RECEPTOR-1 (LAIR-1) IN SUPPRESSING COLLAGEN-INDUCED ARTHRITIS
Kim S1, Price L1, Cullins D1, Park J1, Stuart JM1,2, Kang A1, Myers L3,1. 1 University of Tennessee Health Science Center, Memphis, TN; 2 Veterans Affairs, Memphis, TN and 3 Le Bonheur Children’s Hospital, Memphis, TN.
Purpose of Study: The success of Abatacept (CTLA4-Ig) in treating rheumatoid arthritis (RA) suggests that targeting T cells can be an effective therapeutic strategy for RA. A possible new therapeutic target might be the inhibitory receptor Leukocyte Associated Immunoglobulin-Like Receptor-1 (LAIR-1) which is found on peripheral mononuclear cells, including NK cells and T cells. Our hypothesis was that stimulation of LAIR-1 will suppress cell signaling and lead to inhibition of autoimmune arthritis in the collagen-induced arthritis (CIA) model.
Methods Used: DR1 transgenic mice that were LAIR-1 -/- mice (n=7) were immunized with type II collagen (CII) to induce arthritis and compared to DR1 LAIR-1 +/+ littermate controls (n=13). Each mouse was scored three times weekly beginning 2 weeks post immunization and the mean severity scores and percentage of arthritic limbs were recorded at each time point.
Summary of Results: When CII-reactive murine T cells were cultured in vitro with the immunodominant determinant of CII we found that type I collagen could suppress IL-17 responses in the presence of LAIR-1. In vivo, mice that were immunized demonstrated that the LAIR -1 -/- group developed more severe arthritis than the wild type mice (severity scores 4.3 ± 2.7 vs. 2.2 ± 1.4, p=0.03). In addition, LAIR -1 -/- mice had a greater percentage of limbs affected with arthritis than did the wild type group (33 ± 21 vs. 17 ± 10, p=0.02). Antibody titers (IgG) to CII correlated with arthritis severity.
Conclusions: We have demonstrated that LAIR-1 -/- /DR1 mice develop arthritis that is more severe, with more arthritic joints than DR1 mice alone. These data suggest that LAIR-1 stimulation is involved in the modulation of CIA and that stimulation of LAIR-1 may serve as an effective treatment for RA.
351 HEALTHY HIV-INFECTED INDIVIDUALS HARBOR HIV IN THEIR ALVEOLAR MACROPHAGES
Cribbs SK1, Lennox J2, Caliendo A4, Brown L3, Guidot D1. 1 Emory University and the Atlanta VA, Atlanta, GA; 2 Emory University, Atlanta, GA; 3 Emory University, Atlanta, GA and 4 Brown University, Providence, RI.
Purpose of Study: Alveolar macrophages (AM) are specialized innate immune cells that reside in the alveolus, a separate compartment site compared to blood. The half-life of these cells is significantly longer than that of an activated lymphocyte. AM can be infected by HIV-1 as they express CXCR4 and CCR5. However, reports quantifying the burden of HIV in AM are conflicting, and it is unclear what impact HIV infection has on AM function. We hypothesize that the AM is an important reservoir for HIV, contributing to cell-cell spread of the virus within the lung and exhibiting abnormal immune function that contributes to the increased risk of severe lung infections.
Methods Used: Healthy HIV-infected subjects underwent bronchoscopy and bronchoalveolar lavage. AM were isolated and HIV-1 RNA was quantified using the Abbott RealTime HIV-1 PCR Assay (Abbott Molecular Inc. Des Plaines, IL). Proviral DNA was qualitatively measured using a modified version of the above-mentioned HIV-1 RNA viral load assay. To measure phagocytic function, AM were isolated and incubated for 1 hour with FITC-labeled S. aureus in a 10:1 ratio. FITC-labeled bacteria containing cells were measured by flow cytometry. Phagocytic index was calculated as follows: (% positive cells x mean channel fluorescence)/100.
Summary of Results: We enrolled 22 otherwise healthy HIV-infected subjects (median CD4 count=409/μl, 82% with undetectable plasma viral load). HIV-1 proviral DNA and/or quantitative RNA were detected in 82% of the AM; 78% of this group had an undetectable plasma viral load and 94% were on anti-retroviral therapy. HIV-1 RNA levels ranged from 48 to 2305 copies/mL. Further, HIV-infected subjects with proviral DNA present had decreased AM phagocytosis of FITC-labeled S. Aureus compared to subjects without proviral DNA present [16.6 (IQR 6-45.2) vs. 33.1 (IQR12.2-172.1)].
Conclusions: Alveolar macrophages harbor HIV even in otherwise healthy subjects with undetectable plasma viral loads, representing a potential reservoir for the virus. In addition, HIV viral replication within these macrophages may impair phagocytosis and other immune functions, leading to an increased risk for lung infections.
Southern Society for Pediatric Research Plenary Session Young Investigator Award Finalists
8:00 AM
Friday, February 21, 2014
352 IMPROVING DISASTER AWARENESS AND PREPAREDNESS AMONG FAMILIES OF CHILDREN WITH SPECIAL HEALTHCARE NEEDS
Bagwell H1, Liggin R1, Thompson T1, Lyle K1, Anthony A1, Baltz M1, Melguizo-Castro M2, Nick T2, Kuo D3. 1 UAMS - ACH, Little Rock, AR; 2 UAMS - ACH, Little Rock, AR and 3 UAMS - ACH, Little Rock, AR.
Purpose of Study: Children with special healthcare needs (CSHCN) may present unique challenges for disaster preparedness, as some of these children require care such as home oxygen, multiple medications, or gastrostomy feeds that could be disrupted during a disaster. The purpose of this study is to determine the disaster preparedness of families of CSHCN and the impact of disaster preparedness education and intervention. It is anticipated that such families will be underprepared, demonstrated by not having an emergency information form (EIF) for their child or a disaster kit.
Methods Used: Families of CSHCN were consecutively enrolled between May and September of 2013 at the Medical Home Clinic of Arkansas Children’s Hospital, a comprehensive outpatient service for children with complex medical needs. Each family was given a 24 question literature-based survey about disaster preparedness. Following the survey, families received: 1) educational handouts on disaster preparedness; 2) a $15 disaster supply starter kit, a backpack containing first aid supplies and a flashlight. A follow-up phone survey was conducted 6-10 weeks later to determine changes in disaster preparedness. McNemar’s test was used to assess the differences between pre- and post-survey items.
Summary of Results: There were 250 families enrolled with 144 completing the post-survey. The median age of children was 3.1 years with a median of 4 required medications; 55% required gastrostomy tubes, 23% required home oxygen therapy, and 35% required a feeding pump. At pre-survey, 43% of families had an EIF for their child, increasing to 79% at the post-survey period (p-value <0.001). Only 18% of the participants in the pre-survey period had a disaster kit. At post-survey 143 of 144 respondents (99%) still had the starter disaster kit, and 44% had added items such as water, clothes, or additional first aid supplies.
Conclusions: Families of CSHCN are underprepared for a disaster, but a small disaster supply starter kit with education may increase disaster awareness and planning. Further investigation looking at long term improvements in disaster preparedness and dissemination to other populations is needed.
353 EFFECT OF COLON TRANSECTION ON SPONTANEOUS HIGH-AMPLITUDE-PROPAGATING CONTRACTIONS IN CHILDREN
Jacobs C1, Wolfson S2, Di Lorenzo C2, Cocjin J2, Monagas J2, Hyman P2,1. 1 Louisiana State University, New Orleans, LA and 2 Children’s Hospital, New Orleans, LA.
Purpose of Study: After Hirschsprung’s disease (HD) surgery, many children suffer fecal incontinence caused by increased high amplitude propagating contractions (HAPCs). The aim of this study was to determine whether children with HD have more HAPCs than children with colon transections for reasons other than HD.
Methods Used: We reviewed 500 colon manometries. Children (7.6±5.1 yrs; 275 male) with functional constipation (n=237; 7.4±5.0yrs; 126 male) and chronic abdominal pain (n=48; 9.8±5.8yrs; 25 male) served as controls compared to subjects with HD (n=56; 6.9±4.1yrs; 44 male) and colon transection for other reasons (n=24; 6.1±5.8yrs; 12 male). We excluded 139 subjects without HAPCs. We documented HAPCs during 1 h fasting and 1 h postprandial. Results are mean ± SD.
Summary of Results: During fasting, HD subjects had more HAPCs (2.2±3.4/h) vs. functional constipation (0.8±2.2/h, p=0.0004) and chronic pain (0.5±1.1/h, p=0.001), but not more than colon transection (1.9±3.2/h, p=1.0). HD showed more postprandial HAPCs (4.0±5.4/h) than functional constipation (1.5±2.5/h, p<0.0001) and chronic pain (0.9±1.6/h, p<0.0001), but not more than colon transection (2.4±3.0/h, p=0.6). There were more HAPCs fasting and post-prandial after colon transection (1.9 ± 3.2/h and 2.4±3.0/h) than functional constipation (0.8±2.2/h, p=0.3 and 1.5±2.5/h, p=1.0) and chronic pain (0.5±1.1/h, p=1.0 and 0.9±1.6, p=1.0). HD subjects were divided by chief complaint: fecal incontinence or constipation. HD subjects with incontinence (n=23) only had more HAPCs fasting (p=0.01) and post-prandial (p=0.01) than HD subjects with constipation (n=28) only.
Conclusions: Increased HAPCs followed colon transection, regardless of cause. HD subjects with incontinence had more HAPCs than subjects with colon transection for other reasons.
354 INCREASING ENTERAL PROTEIN INTAKE IMPROVES GROWTH IN VERY LOW BIRTH WEIGHT (VLBW) INFANTS
Maxted A1, Talati AJ1,2, Skeen A2. 1 UTHSC, Memphis, TN and 2 The Regional Medical Center, Memphis, TN.
Purpose of Study: Preterm infants are at a disadvantage of lacking adequate nutrition because of early separation from mother and difficulty in establishing adequate enteral intake after birth. Human milk (HM) is the best form of feeding for a newborn, but it may not be completely adequate for growth of VLBW infants. Several different additives including human milk fortifiers (HMF), liquid protein (LP) and medium chain triglycerides are added to HM to improve caloric intake and growth. We proposed to evaluate the role of adding LP to HM feeding and its effect on growth of VLBW infants during their NICU stay.
Methods Used: A retrospective chart review was done in the NICU after identifying VLBW infants receiving HM with fortification and added LP. A comparable cohort of VLBW infants receiving HM with fortification was identified. Data were collected for a 4 wk period after the infants were off intravenous nutrition. Daily weight and intake of protein and calories were calculated. A z score was calculated comparing the weekly weight change from start of study and the difference in z score each week was also calculated. Weekly total protein, albumin and other parameters of growth were also recorded for 4 consecutive wk and at the time of discharge.
Summary of Results: A total of 32 VLBW infants were studied. 15 VLBW infants (group 1) received LP in addition to HM +HMF while 17 infants (group 2) received only HM+HMF during the study period. The mean BW (672±148 vs 766±268g), GA (25.1±1.24 vs 25.9±2.2wk) and birth head circumference (22.1±1.14 vs 23.2± 2cm) were similar in both groups. As expected the estimated average daily protein intake was higher in LP (group 1), while caloric intake was similar. The mean growth velocity was higher in group 1 (24.3 ±12.5g vs 13.1±8.6g /d, p<.05) at the end of 4 week period. The weekly change in z-score for weight improved significantly in HM+HMF+LP group of infants by week 4 (-0.26 vs -1.4, p<.05) and at discharge (0.18 vs -0.99, p<.05). The serum BUN levels were similar between the groups each week.
Conclusions: Additional protein intake improves weight gain in VLBW infants fed exclusively with fortified HM. Longer follow up is needed to see the benefit on brain growth and neurodevelopmental outcomes.
355 P2Y2 PURINERGIC RECEPTOR FUNCTION IS ESSENTIAL FOR THE PATHOGENESIS OF POLYMICROBIAL SEPSIS
Arunachalam A1, Tackett B2, Maynard J2, Thevananther S2. 1 Baylor College of Medicine, Houston, TX and 2 Baylor College of Medicine, Houston, TX.
Purpose of Study: Severe sepsis is a major cause of morbidity and mortality. Cellular stress triggers ATP release into extracellular milieu. Extracellular ATP, via activation of P2Y2 purinergic receptors, plays a pivotal role in inflammation and immunomodulation. However, the functional significance of P2Y2 receptor activation in the modulation of inflammation, multi organ injury, and death is not well understood. The overall goal is to test the hypothesis that P2Y2 purinergic receptor activation is essential for the induction of inflammatory cascades and multi-organ injury secondary to microbial infection.
Methods Used: Sepsis was induced by cecal ligation and puncture (CLP) in adult (12-16 weeks) wild type (WT; C57BL6/J) and P2Y2-/- (KO; C57BL6/J) mice. Tissues (liver, lungs) and blood were collected at 3,6,12, 21h and 7 days after CLP. Tissues were analyzed for leukocyte infiltration, apoptosis, and pro-inflammatory cytokine/chemokine protein and RNA (quantitative RT-PCR) expression.
Summary of Results: WT mice subjected to CLP developed symptoms of severe sepsis and were moribund (100%) between 21-48 hr. However, KO mice survived longer (70% survival at 7 days). In response to CLP, induction of serum cytokines/chemokines was significantly attenuated in KO mice (IL-6, 67%; IFNγ, 91%; MCP-1, 96%; MIP-2, 75%), as compared to WT mice at 21 hr. CLP induced massive liver injury in the WT mice, with elevated serum ALT, leukocyte infiltration into the hepatic parenchyma, hepatocyte injury, and hemorrhagic necrosis at 21 hr. Liver injury was attenuated in the KO mice in response to CLP at 21 hr, with decreased induction of TNFα (58%), IL-6 (72%), IL-1β (49%) and MCP-1 (90%) mRNA expression, as compared to WT livers. Additionally, attenuation of markers of lung inflammation (TNFα, 76%) and kidney injury (blood urea nitrogen, 42%) were noted in the KO mice as compared to WT.
Conclusions: P2Y2 receptor function is critical for sepsis-induced mortality in mice. Early induction of hyper-inflammatory phase is dependent on intact P2Y2 receptor expression. These findings highlight the functional significance of purinergic signaling in the pathogenesis of sepsis and eventually will lead to development of novel therapeutics.
356 ROLE OF ENDOTHELIAL MONOCYTE ACTIVATING POLYPEPTIDE II (EMAP II) IN BRONCHOPULMONARY DYSPLASIA (BPD)
Lal CV1, Awasthi N2, Xu H1, Schwarz A1, Schwarz R2, Savani R1, Schwarz M1. 1 University of Texas Southwestern, Dallas, TX and 2 University of Texas Southwestern, Dallas, TX.
Purpose of Study: The expression of EMAP II- a potent antiangiogenic and proinflammatory factor, decreases during periods of vasculogenesis in fetal lung development and increases in emphysema and BPD. We hypothesized that exogenous EMAP II administration would cause BPD-like changes in uninjured-normoxic mice, and that the administration of EMAP II blocking antibody (EMAP II Ab) would rescue alveolar growth in mice exposed to hyperoxia.
Methods Used: 1) From postnatal days (PN) 3-15, EMAP II protein or vehicle was administered to mice in 21% oxygen (normoxia) 2) PN 3-15, mice were exposed to either 85% oxygen (hyperoxia) or normoxia and treated with either EMAP II Ab or non specific rabbit IgG control (NsIgG). Lungs were harvested on PN 15. Alveolar architecture was demonstrated by mean linear intercept (MLI), cellular proliferation by Ki67 immunofluorescence, and apoptosis by TUNEL assay. Vascular and epithelial lung markers were analysed by real time PCR. Pulmonary function testing (PFT) was performed at 6 weeks using Scireq Flexivent FX rodent ventilator.
Summary of Results: 1)Compared to vehicle-treated pups, normoxia pups treated with EMAP II protein developed alveolar simplification consistent with BPD (MLI: p<0.0001, t test), reduction in epithelial and vascular lung markers and worsening lung functions. 2)Compared to normoxia controls, mice exposed to hyperoxia between PN 3-15 demonstrated distal alveolar dysplasia (MLI p∼0.001 ANOVA), increased proliferation (p<0.01) and apoptosis (p<0.01). Compared to NsIgG-treated hyperoxia controls, hyperoxia pups treated with EMAP II Ab had a marked reduction in MLI (p<0.01), alveolar cell proliferation (p<0.01), apoptosis (p<0.01) and had improved compliance. EMAP II Ab had no difference in MLI and alveolar cell proliferation in normoxia pups as compared to NsIgG-treated normoxic controls.
Conclusions: In neonatal mice exogenous delivery of EMAP II protein induces distal alveolar dysplasia consistent with BPD, while delivery of an EMAP II function-blocking antibody rescues hyperoxia induced alveolar dysplasia, reduces cellular hyperproliferation, apoptosis and improves pulmonary functions. This suggests that EMAP II blockade may be a potential target for therapeutic intervention in BPD development.
357 GROUP B STREPTOCOCCI INDUCE PROINFLAMMATORY RESPONSES VIA A PROTEIN KINASE D1 DEPENDENT PATHWAY
Upadhyay K1, Park J1, Kim Y1, Meals E1, Talati AJ1, English B2, Yi A1. 1 CFRI, UTHSC, Memphis, TN and 2 Michigan State University, Grand Rapids, TN.
Purpose of Study: Protein kinase D1(PKD1) plays a significant role in inflammatory process mediated by MyD88 dependent toll like receptors(TLR). We proposed to study the role of PKD1 in Group B Streptococci(GBS) mediated proinflammatory responses and to determine a molecular mechanism by which GBS activates PKD1 in macrophages.
Methods Used: RAW 264.7 cells were stimulated with live GBS or penicillin G-killed GBS and activation of PKD1 was analyzed by in vitro kinase assay and phospho-specific Western blot assay. Subsequently, MyD88-/- macrophages, IRAK1-/-, or TRAF6 -/- macrophages were stimulated with GBS and activation of PKD1 was analyzed. Next, to investigate whether PKD1 plays indispensable role in GBS mediated proinflammatory responses, RAW264.7 cells and C57BL/6 mice were stimulated with GBS in the presence of PKD inhibitor Gö6976 and expression and production of the selected cytokines/chemokines were analyzed by RT-PCR and ELISA. Finally, to determine contribution of PKD1 in GBS-mediated septic shock-like death, D-galactosamine (D-GalN) sensitized mice were challenged with antibiotic killed GBS in the presence of PKD inhibitor and then viability of mice was observed.
Summary of Results: Both live and antibiotic killed GBS induced kinase activity and phosphorylation of PKD1. PKD1 activation by GBS was completely abolished in MyD88-/- macrophages and IRAK1-/- macrophages but not in TRAF6 -/-macrophages. GBS induced activation of signaling modulators (i.e., JNK, ERK, p38, or NF-κB) and expression and production of proinflammatory cytokines and chemokines (TNFα, IL-6, IL-10, IL-12p40, IP-10, MCP-1, CCL5, MIP-1α, MIP-2, LIX, and KC) were either ablated or significantly inhibited in the presence of PKD inhibitor in vitro and in vivo. Furthermore, systemic administration of PKD inhibitor protected D-GalN-sensitized mice from shock mediated death caused by GBS.
Conclusions: GBS induced activation of PKD1 via a MyD88 and IRAK1 dependent manner. PKD1 played an indispensable role in GBS-mediated activation of MAPKs and NF-κB and subsequent expression of proinflammatory cytokines and chemokines in vitro and in vivo. Furthermore, inhibition of PKD1 activation protected mice from death due to exaggerated proinflammatory response induced by antibiotic-killed GBS.
Cardiovascular Club II - Young Clinician Scientist Award Competition
11:00 AM
Friday, February 21, 2014
358 MITOCHONDRIAL DNA HAPLOTYPE CONTRIBUTES TO THE CYTOSKELETAL AND MITOCHONDRIAL RESPONSES TO CYCLICAL STRETCH IN ISOLATED CARDIOMYOCYTES
Guichard JL1, Benavides G1, Ballinger S1, Dell’Italia L1,2. 1 University of Alabama at Birmingham (UAB), Birmingham, AL and 2 Birmingham Veteran Affairs Medical Center, Birmingham, AL.
Purpose of Study: We have shown that humans with isolated mitral regurgitation and normal left ventricular systolic function have significant myofibrillar degeneration, aggregates of small mitochondria, and increased formation of reactive oxygen and nitrogen species (ROS/RNS) within the cardiomyocytes. These findings suggest an interaction between the cytoskeleton and mitochondria. To determine if differences in mtDNA haplotype can contribute to differences in VO disease susceptibility, we developed a novel mitochondria-nuclear exchange (MNX) mouse model in which the mitochondria (mt) from wild-type C57BL/6J (C57 WT) and C3H/HeN (C3H WT) mice have been exchanged onto the respective nuclear (n) backgrounds (C57n:C3Hmt or C3Hn:C57mt).
Methods Used: Cyclical stretch experiments were performed with isolated cardiomyocytes. Cardiomyocytes were exposed to stretch (60 cycles per minute with 20% stretch for 3 hours) using the Flexcell® FX-5000™ Tension System. Transmission electron microscopy (TEM) and immunohistochemistry (IHC) analyses were used for cardiomyocyte structural assessment. The XF24 Extracellular Flux Analyzer from Seahorse Bioscience (North Billerica, MA, USA) was used to measure real-time oxygen consumption and extracellular acidification rates.
Summary of Results: TEM analysis showed that control cardiomyocytes had tightly packed and electron dense subsarcolemmal, interfibrillar, and perinuclear mitochondria. C57 WT and C3H MNX stretched cardiomyocytes demonstrated extensive ultrastructure changes including mitochondrial disorganization and swelling, smaller and rounder mitochondria with a loss of electron density, and structural breakdown of the myofilaments and Z-lines. IHC analysis showed marked disruption of desmin in C57 WT and C3H MNX stretched cardiomyocytes, which were in contrast to control cardiomyocytes and C3H WT and C57 MNX stretched cardiomyocytes. Mitochondrial bioenergetic analysis associated the C57 mtDNA haplotype with bioenergetic dysfunction.
Conclusions: We have shown that mtDNA haplotype contributes to the cytoskeletal and mitochondrial responses to cyclical stretch in isolated cardiomyocytes.
359 WNK1 ATIVATES BK CHANNEL ACTIVITY THROUGH MAPK ERK1/2 SIGNALING PATHWAY
Liu Y, Shi Y, Caroti C, Bao H, Cai H. Emory University School of Medicine, Atlanta, GA.
Purpose of Study: WNK (with no lysine) kinase is one of the serine/threonine kinase family. We have previously shown that WNK4 inhibits BK channel activity through enhancing its degradation via a lysosomal pathway. WNK4 was also found to inhibit BK channel activity which is kinase-dependent and via activating MAPK ERK1/2 and p-38 signaling pathways. However, little is known on the role of WNK1 in the regulation of BK activity.
Methods Used: To determine the role of WNK1 in regulation of BK channel activity, we have investigated the effect of WNK1 on BK channel activity using cell attached single channel recording technique, cell cultures, transfection, siRNA knock-down and western blot analysis.
Summary of Results: We have found that the knock-down of WNK1 expression in HEK 293 cells stably expressing alpha subunit of BK (HEK BKα cells) channel significantly inhibited both BKα activity (NPo, 0.024 ± 0.036, n=18, compared to the control group, 0.1316 ± 0.0573, n=36, p =0.006) and open probability (Po, 0.0094 ± 0.0098, compared to the control group, 0.0512 ± 0.0573, p<0.001). Western blot analysis showed that knock-down WNK1 significantly inhibited BKα total expression in HEK BKα cells in a dose-dependent manner (1.0 ± 0, 0.848 ± 0.213, 0.422 ± 0.297, n=3, p<0.05). Over-expression of WNK1 was also shown to increase BKα protein expression in a dose-dependent manner (1.0 ± 0, 1.723 ± 0.136, 2.729 ± 0.385, n=3, p<0.05) in HEK 293 cells transiently transfected with myc-BKα and HA-WNK1. We also found that WNK1 decreased ERK1/2 phosphorylation in a dose-dependent manner.
Conclusions: These data suggest that WNK1 enhanced BKα activity and total protein through inhibiting MAPK ERK1/2 signaling pathway.
360 RECOVERY OF SMALL MYOCYTES AND REVERSE REMODELING IN HYPERTENSIVE HEART DISEASE
Al Darazi F, Zhao W, Zhao T, Sun Y, Marion TN, Ahokas RA, Bhattacharya SK, Gerling I, Weber KT. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Hypertensive heart disease (HHD) includes hypertrophied cardiomyocytes and widely scattered foci of microscopic scarring, which have replaced necrotic myocytes. Bordering on these microdomains of fibrosis are small myocytes that re-express β-myosin heavy chain (β-MHC), a fetal gene. We hypothesized small myocytes represent an autologous population of cells which could be recovered for reverse remodeling in HHD.
Methods Used: 8-wk-old male Sprague-Dawley rats received aldosterone/salt treatment (ALDOST) for 4 wks followed by a 4-wk period of assisted recovery when oral antioxidants (ZnSO4 and nebivolol, a β3 receptor agonist) were given.
Summary of Results: Compared to untreated age-/sex-matched controls: mean arterial pressure (MAP, 162±2 vs. 99±2 mmHg) and left ventricular (LV) mass (1043±23 vs. 883±32 g) were increased (p<0.05) while pressure-independent scarring appeared in the right and left heart at 4 wks ALDOST. Bordering on these scars were α-smooth muscle actin+ myofibroblasts (myoFb) and small myocytes revealing: i) re-expression of β-MHC and atrial natriuretic peptide (ANP); ii) increased expression of reactive oxygen species; and iii) reduced nitric oxide. Cardiac tissue 8-isoprostane and redox-sensitive ligases (atrogin-1 and MuRF1) of the ubiquitin protease system were each increased (p<0.05) while E/A ratio and LV fractional shortening were reduced (p<0.05). Assisted recovery led to normalized MAP, regression in LV mass, and reduction in small myocytes (p<0.05) with restored redox balance and NO, neutralized protein degradation, together with improved diastolic and systolic function.
Conclusions: HHD includes microdomains of fibrosis where small myocytes re-express a fetal gene program together with altered redox balance and protein degradation. Recovery of these myocytes, using neurohormonal withdrawal plus a regimen of antioxidants, is feasible and leads to reverse remodeling with improved ventricular function in HHD. Whether heterocellular signaling with myoFb exists and the potential origin of these small myocytes as progeny of bone marrow or cardiac stem cells vs. dedifferentiated myocytes remains to be determined.
361 URIC ACID IS ASSOCIATED WITH METABOLIC SYNDROME IN CHILDREN AND ADULTS: THE BOGALUSA HEART STUDY
Sun D1,2, Zhang X1, Li S1, Fernandez C1, Chen W1, Srinivasan SR1, Berenson GS1. 1 Tulane University, New Orleans, LA and 2 Peking University Health Science Center, Beijing, China.
Purpose of Study: This study assessed the hypothesis that uric acid (UA) is associated with metabolic syndrome (MetS) components and their clustering patterns in different age periods.
Methods Used: The study sample consisted of 2614 children (1577 whites, 1037 blacks; 1333 males; aged 4-18 years) and 2447 adults (1682 whites, 1765 blacks; 1072 males; aged 19-54 years) examined during 1987-2010. The adverse levels of MetS components, including body mass index (BMI), mean arterial pressure (MAP), triglycerides to HDL cholesterol ratio (TG/HDLC), and homeostasis model assessment of insulin resistance (HOMA), were defined as >75th percentile specific for age, race and sex. Observed/expected (O/E) ratio and intra-class correlation (ICC) were used as a measure of the degree of clustering of categorical and continuous variables, respectively.
Summary of Results: UA was significantly positively associated with only BMI in children, and with all four components in adults. Odds ratios of UA associated with MetS were 1.74 in children and 1.92 in adults (p<0.001 for both), adjusted for race, sex and age. Trends in O/E ratios with UA quartiles are shown in the figure below. ICCs of 3- and 4-component clusters increased with increasing UA quartiles in children; however, only BMI-MAP-HOMA cluster showed an increasing trend of ICC in adults.
Conclusions: The results suggest an important role of UA in the development of MetS in pediatric and adult populations. The findings provide further insights into the potential pathophysiological mechanisms of MetS and have implications for identification and treatment of high risk individuals for MetS in early life.
Adolescent Medicine and Pediatrics Concurrent Session
2:00 PM
Friday, February 21, 2014
362 PEDIATRIC EMERGENCY DEPARTMENT USE BY ADULTS WITH SPECIAL HEALTHCARE NEEDS Laura A. Wright-Sexton, MD, Rosina Connelly, MD, MPH, FAAP
Wright L1, Connelly R2. 1 University of South Alabama, Mobile, AL and 2 University of South Alabama, Mobile, AL.
Purpose of Study: To describe the use of a pediatric emergency department (PED) by patients eighteen years of age and older over a ten-year period. We hypothesized that adult patients with a special health care need (SHCN) presenting to a PED were more likely to be seen by a pediatric healthcare provider.
Methods Used: This was a retrospective chart review of emergency department encounters by individuals 18 years and older resulting in care provided by a pediatric provider at a tertiary pediatric hospital from January 1st, 2002- December 31st, 2012.
Summary of Results: There were a total of 4,987 patient encounters during the study period, 504 (10%) were by adult patients with SHCN. There were a total of 261 adult patients with SHCN seeking care in the PED in this study period. Gender was not associated with whether patients were seen (p=0.46), however, having a tracheostomy and/or G-tube was significantly associated with being seen in the PED (p=0.008). Of the 504 encounters seen by a physician in the PED, 63% of the visits were unrelated to their SHCN.
Conclusions: Pediatric patients with SHCN who transition into adulthood used the PED in substantial numbers during our study period. More than 60% of these patient visits were unrelated to their SHCN. As this group of patients continues to grow, PEDs should carefully consider their resources and how best to provide care to adults with SHCN. Unless large-scale policy decisions are made, pediatric hospitals should be prepared with adequate resources and training to deal with these complex adult patients.
363 MANAGEMENT OF FEBRILE INFANTS IN PEDIATRIC EMERGENCY DEPARTMENTS: 2004-2012
Verbrugghe DB, Goudie A, Onukwube J, Doshi P, Robbins J. Arkansas Children’s Hospital, Little Rock, AR.
Purpose of Study: Up to one-third of all presentations to pediatric emergency departments (ED) are documented with fever. Fever in young infants can be a presenting symptom of infectious diseases ranging from a simple cold to devastating meningitis. While the incidence of bacterial meningitis among young infants has significantly decreased since the introduction of the Haemophilus influenza and pneumococcal vaccines, recommendations for the management of febrile infants have not significantly changed over the past 30 years.
The purpose of this study is to evaluate variation in the management of febrile infants 0-30, 31-60, and 61-90 days of age across 35 pediatric emergency departments in the United States. Management practices are compared to evolving recommendations from a multicenter and an individual facility level perspective.
Methods Used: Data from 35 EDs participating in the Pediatric Health Information System (PHIS) for years 2004-2012 were used to identify infants less than 3 months of age with a diagnosis code of fever. Medical diagnoses, diagnostic tests performed, and medications prescribed are identified in PHIS using ICD-9-CM and/or Clinical Transaction Classification (CTC) codes.
Summary of Results: 92,428 infants ∼3 months of age were identified in PHIS with an ED diagnosis of fever. By age group, blood was drawn for lab testing among 82.4%, 82.8%, and 64.9% of infants 0-30, 31-60, and 61-90 days of age respectively; urine was obtained from 82.7%, 84.2% and 72.7%; lumbar punctures (LPs) were performed in 76.4%, 52.2%, and 16.1% of infants; respiratory syncytial virus testing was performed in 28.2%, 27.3%, and 18.9%; and chest X-rays were performed in 34.9%, 24.8%, and 31.5% of infants.
Wide variation was observed across the 35 institutions under study in the management of febrile infants. Across institutions LP rates ranged from 10.4% to 73.7%, blood samples drawn from 42.4% to 90%, and urine samples obtained from 41.9% to 90.7%.
Conclusions: There is great variability among individual institutions in how febrile infants are managed upon presentation to the emergency department. Management practices vary from evolving consensus recommendations in the United States. Our future studies will determine whether management practices are related to the outcomes of infants presenting with fever.
364 ASSESSING INTENT AND WILLINGNESS TO IMMUNIZE CHILDREN AGAINST INFLUENZA IN THE PEDIATRIC EMERGENCY DEPARTMENT
Stevenson M1, Levine A2, Bryant K1, Paul RI1. 1 University of Louisville School of Medicine, Louisville, KY and 2 University of Louisville School of Medicine, Louisville, KY.
Purpose of Study: Limited data exist regarding influenza vaccination (IV) programs in the pediatric emergency department (ED) setting. The objectives of this study were to determine rates of influenza immunization among children with a minor illness or injury treated in a pediatric emergency department (ED) and parent willingness for their child to receive influenza vaccine (IV) during future ED visits.
Methods Used: A 25-question survey was administered to parents of children aged ≥ 6 months evaluated in the ED in the summer of 2013. Exclusion criteria include temperature ≥ 103°F, communication barrier, egg or IV allergy, or evaluation for non-accidental trauma. Demographic and visit data, IV history, and intent and willingness to receive future IV were recorded. Data were analyzed using standard descriptive statistics.
Summary of Results: Of 457 families approached, 119 (26%) declined participation, 53 (12%) were ineligible, and 285 (62%) were enrolled. Mean age was 7.2 (±5) years; 46% were black; and 56% had ≥ 1 ED visit in the past year. Fifteen (3%) were too young to have received IV in the prior season. Of the remainder, 64% (95% confidence interval: 59%, 70%) reported receiving ≥ 1 dose of IV in the past year. The most common reasons for not receiving IV were concerns about side effects (31%) and lack of time or interest (24%). 85% of parents report they will probably/ definitely vaccinate their child prior to the upcoming influenza season; 83% report willingness to receive IV at a future ED visit. Children with any current chronic medical condition were more likely to report vaccination in the prior influenza season (77% vs 60%, p<0.005). Among respondents for the 88 children who were over 6 months during the previous influenza season yet not vaccinated, 55 (63%) report they would probably/definitely give IV to their child if offered in the ED. Of these, 22 (25%) children had asthma or a high risk chronic health condition.
Conclusions: Because influenza immunization rates for children are lower than desired, our data support an IV program in the pediatric ED. Parents are often concerned about side effects of influenza immunization. Primary care providers should consider targeting education in this area to impact vaccination rates.
365 PERCEIVED PAIN WITH HPV VACCINE COMPARED TO OTHER RECOMMENDED VACCINES FOR ADOLESCENTS: WHAT CAUSES THE BIGGEST “OUCH”?
Salz N1, Lopez A2, Amin R3, Burns JJ1. 1 Florida State University College of Medicine, Tallahassee, FL; 2 Sacred Heart Children’s Hospital, Pensacola, FL and 3 University of West Florida, Pensacola, FL.
Purpose of Study: The purpose of the study is to determine if the Human papillomavirus vaccine (HPV) is more painful at the time of administration than other recommended vaccines. Pain associated with the HPV vaccine may contribute to incomplete vaccination status and explain higher rates of syncope reported in some studies. No study has been done that surveys pain from the patient receiving the recommended adolescent vaccines.
Methods Used: Consecutive patient visits from 04/24/2013 to 10/04/2013 for 10-18 year olds at a predominantly Medicaid insured residency teaching clinic were assessed for pain associated with injection using the Wong-Baker FACES Pain Rating Scale. Patients needing the HPV vaccine and at least one other immunization were eligible. Patients were blinded to the administration order. The participants were asked to rate their pain immediately after each injection. The non-HPV vaccines used for comparison were Menactra, Hepatitis A, Varicella and Tdap. Wilcoxon Signed Ranks test was used in comparing the pain scores. To account for multiple analyses, a p-value of <0.01 was used for significance using the Bonferroni correction.
Summary of Results: 150 participants were included with 47.3% females and 52.7% males. A statistically greater number of HPV injections hurt more on the pain rating scales than the average of the non-HPV injections given at the same visit (p=0.000) (see Table). HPV was also found to hurt more often than Menactra (p = 0.000) and Hepatitis A (p = 0.000) individually. There were no significant differences for Tdap nor Varicella vs. HPV using predetermined cut off of p<0.01.
Conclusions: HPV vaccine was perceived as more painful than the average of 4 commonly administered vaccines and two individual vaccines.
366 ATTITUDES TOWARD HPV VACCINE: DIFFERENCES AMONG PARENTS OF MALE AND FEMALE ADOLESCENTS
Roberts J1, Hale J2, Jacobson R3, Pope C1, Thompson D2, Darden P2. 1 MUSC, Charleston, SC; 2 OUHSC, Oklahoma City, OK and 3 Mayo Clinic, Rochester, MN.
Purpose of Study: Recommendations for human papillomavirus (HPV) vaccination of adolescent males and females originated at different dates and for different reasons. The purpose of this study is to identify differences in attitudes toward HPV vaccine between the parents of adolescent males or females.
Methods Used: In 2012, parents of 11-17 year-old adolescents were surveyed at any type of visit to 6 pediatric practices in OK and SC. Attitudes were measured with an adapted Parent Attitudes about Childhood Vaccine (PACV) survey originally developed by Opel et al. The 15-item survey is not vaccine specific; it rates general vaccine hesitancy (on a scale of 0-100) with higher scores indicating greater hesitancy. Medical records were reviewed and adolescents were considered “due for HPV vaccine” if, at the end of the visit, they had received <3 doses and were eligible for an additional dose. We compared “due for HPV vaccine,” with parents’ PACV score, and with individual responses for each of the 15 items, by adolescent gender. We used χ2, and t-tests for bivariate analyses and logistic regression for multivariable analysis.
Summary of Results: Data were analyzed from 375 parents and adolescents (55% male). Adolescent males were more likely to be due for the HPV vaccine than females (65% v. 46%, p<0.001). The mean PACV score for parents of males (22.5) was lower than for parents of females (26.5), P=0.02. The PACV scale did not predict HPV vaccine status for either males (P=0.61) or females (P=0.19). When analyzing the 15 PACV scale items individually, two items differed by gender. Parents of males expressed less concern that vaccine might not prevent disease (34% v. 47%; P=.02) and less concern that vaccines might not be safe (35% v. 52%; P=.004).
Conclusions: Adolescent males were more likely to be due for HPV than females. Parents of males were less hesitant about vaccines than parents of females. The differences in attitudes found can guide strategies to improve HPV vaccine acceptance in males. However, in this analysis PACV was not associated with receipt of HPV vaccine.
367 COMPLIANCE WITH NATIONAL GUIDELINES FOR PEDIATRIC PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA AFTER EDUCATION BY AN ANTIMICROBIAL STEWARDSHIP PROGRAM
Jones P1, Stephens S1, Bagga B1,2, Lee K2,1, Arnold S1,2. 1 University of Tennessee Health Science Center, Memphis, TN and 2 Le Bonheur Children’s Hospital, Memphis, TN.
Purpose of Study: In 2011, guidelines for the management of community-acquired pneumonia (CAP) in children were published. For uncomplicated CAP, recommendations are that healthy, immunized children receive a penicillin if local pneumococcal resistance patterns permit. Third generation cephalosporins are reserved for children with moderate to severe or complicated CAP or those who are not fully immunized. The Antimicrobial Stewardship Program (ASP) at Le Bonheur Children’s Hospital conducted a baseline review to ascertain which antibiotics were being used to treat CAP. In addition, records for pneumococcal isolates from the preceding 2 years were reviewed to determine local susceptibility patterns before recommendations were issued.
Methods Used: All pneumococcal isolates from the microbiology lab from 2010-11 were reviewed and were classified as susceptible, intermediate or resistant based on pneumonia breakpoints. Recommendations CAP management were prepared in mid-2012 and were presented to hospital and emergency physicians and residents through conferences and grand rounds. The Pediatric Hospital Information Systems (PHIS) database was used to determine antibiotic use in patients diagnosed with pneumonia before and after education. The database was also used to compare our antibiotic use to other pediatric hospitals.
Summary of Results: Among pneumococcal isolates, 99% were susceptible or intermediate to penicillin (MIC ⩽ 4 mcg/ml). As a result, ampicillin was recommended for empiric therapy for uncomplicated CAP. During the three years prior to guideline education, ceftriaxone was used in 90% of children admitted for CAP and ampicillin in 1%. After education, ampicillin use increased to 50% during the 2012-13 respiratory season, and ceftriaxone use decreased to 50%. Ampicillin use increased from 8% to 20% at the other PHIS hospitals.
Conclusions: Local development of guidelines and ASP driven education of medical staff led to a substantial increase in the use of a narrow spectrum antibiotic, ampicillin, and a reduction in the unnecessary use of ceftriaxone for CAP. Daily ASP initiated monitoring will ensure further reduction in broad-spectrum antimicrobials in patients admitted to our hospital with CAP.
368 TEEN DRIVING TOOLKIT FOR PEDIATRICIANS
Woodfin T2, Irons E3, King WD1, Crew M3, Monroe K1. 1 univ of alabama, Birmingham, AL; 2 Univ of Alabama, Birmingham, AL and 3 Childrens of Alabama, Birmingham, AL.
Purpose of Study: The American Academy of Pediatrics (AAP) recommends pediatricians discuss safe passenger behavior. A convenience sample survey of teens in our state revealed only 11.5% of teens recalled their pediatrician discussing safe driving with them. Knowledge and practice of state pediatricians regarding safe teen driving laws and education were assessed in this study.
Methods Used: Funded by the Allstate Foundation, the Alabama AAP created a coalition of interested stakeholders, the Alabama Safe Teen Driving coalition. A series of Grand Rounds were conducted across the state. A pre and posttest were performed for the attendees at these conferences. A toolkit to assist pediatricians was created and distributed. A follow up survey assessed the usefulness of the toolkit. Log likelihood ratios used for evaluation.
Summary of Results: 147 pediatricians attended the sessions (only 61% aware of our state graduated drivers’ license law). Although, 35% of pediatricians surveyed see more than 70 adolescents in their practice each year, nearly half, 49.3% reported that they never have discussions with teen patients about safe driving. 42% were not familiar with driving contracts and of those who were familiar, only 15% had ever recommended one to a patient. The pre test indicated that only 21.0% of participants knew GDL components before the educational intervention compared to 98.6% of post test participants could correctly identify the GDL components (z=13.4, p<0.001). In follow up survey (n=45), toolkit use was most common in the primary care setting( 93% usage rate(G2 =7.4,p=0.007). The toolkit was also used more in practices that see 20 or more teens per week( 84.6%) (G2 = 10.1, p=0.002).
Conclusions: Many state pediatricians were unaware of our state law regarding GDL. Despite seeing a number of adolescents in their practices, many pediatricians were not familiar with driving contracts nor did they discuss safe driving with their patients. A brief educational intervention greatly improved knowledge among participants. The toolkit to assist pediatricians has been especially useful in primary care settings and in practices that see a high number of teens per week.
369 UTILITY OF THE GAPS QUESTIONNAIRE AMONG HIV INFECTED YOUTH
Benjamins L1, Beyda R1, Schulte C2, Rodriguez G3, Feldmann J4. 1 University of Texas School of Medicine, Houston, Houston, TX; 2 University of Texas School of Medicine, Houston, Houston, TX; 3 University of Texas School of Medicine, Houston, Houston, TX and 4 Baylor College of Medicine, Houston, TX.
Purpose of Study: Growing numbers of HIV positive children are surviving into adolescence. Risk taking behaviors in this population are uniquely important as they may potentiate HIV transmission. Limited data exists on the utility of screening tools specifically addressing modifiable risk behaviors in adolescents with HIV. The AMA’s Guidelines for Adolescent Preventive Services (GAPS) survey screens adolescents for social and behavioral risks including depressive symptoms. We assessed the utility of the GAPS questionnaire among youth with HIV.
Methods Used: We conducted a retrospective chart review of patients ages 10 to 21 years old seen at the University of Texas Pediatric HIV clinic. Data was collected from GAPS surveys completed routinely as part of the health maintenance exam. Viral load, CD4 count and other clinical data were also collected. We compared our results to the Youth Risk Behavior Survey.
Summary of Results: A total of 66 charts were reviewed; 92% of the youth were perinatally infected, average age 14.86. Compared to the 2011 YRBS, 8% of study subjects vs. 17% of YRBS youth report carrying a weapon and 33% vs. 47% report ever having sex. One third of the HIV+ youth had a history of an STI. A greater proportion of teens with HIV reported depressive symptoms (38% HIV+ vs. 28.5% YRBS). Comparing GAPS variables and viral load, we found greater reports of sadness (44%) in those with a detectable VL versus those who were undetectable (26%). Those with a detectable VL also had a statistically significant higher rate of suicidal ideation or suicide attempts (6%) compared to those with an undetectable VL (0%), p<0.05.
Conclusions: Our results are in keeping with previously published studies revealing increased rates of depression among HIV positive youth. Other risk behaviors were lower than national norms, but still of significance. Identifying and addressing risks enables earlier intervention and treatment. The GAPS is useful tool for risk identification among HIV positive youth.
370 USE OF THE PEDIATRIC SYMPTOM CHECKLIST TO SCREEN FOR ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
Kube DA, Whitaker TM, Palmer FB. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: This study was designed to determine if the attention subscale of the Pediatric Symptom Checklist (PSC), a screening tool used by primary care clinicians to detect possible behavioral disorders in children, correctly identified children with ADHD when compared to a measure specific for ADHD, the Vanderbilt ADHD Diagnostic Parent Rating Scales (VADPRS).
Methods Used: One hundred eleven children (ages 6 to18 years, 51% male) admitted to a children’s hospital for acute illness were selected for behavioral screening. A parent/caregiver completed the PSC and the VADPRS. The PSC consists of 35 items for behavioral problems, rated on a severity scale of 0-2. The PSC is positive for impairment if the total score is ≥28 and positive for ADHD if the five-item attention subscale score is ≥7. The VADPRS consists of the 9 criteria from the Diagnostic and Statistical Manual of Mental Disorders-IV-TR used for diagnosing ADHD, predominantly Inattentive Type (ADHD-I) and the 9 criteria for diagnosing ADHD, predominantly Hyperactive-Impulsive Type (ADHD-H), scored on a severity scale of 0-3, with ratings of 2 and 3 considered positive. The VADPRS is positive for ADHD-I if ≥6 specific criteria are met, ADHD-H if ≥6 specific criteria are met and ADHD, Combined Type (ADHD-C) if criteria are met for both.
Summary of Results: The PSC was positive for behavioral impairment in 15 subjects (13 on the attention subscale). Of the 13 subjects on the attention subscale, 4 subjects had a prior diagnosis of ADHD and 9 were newly identified. The VADPRS was positive for 14 subjects: 4 ADHD-I, 3 ADHD-H, and 7 ADHD-C. PSC sensitivity for identifying ADHD diagnosed on the VADPRS was 57.0%, specificity 94.2%, positive predictive value 61.5%, and negative predictive value 93.2%. The PSC correctly identified all 7 subjects with ADHD-C.
Conclusions: The PSC was moderately sensitive and highly specific for ADHD diagnosed by the VADPRS. The PSC correctly identified all subjects with ADHD-C, making it a useful screening tool for this subtype. The PSC can be useful as a screen for excluding ADHD due to its high specificity and negative predictive value. Nine previously undiagnosed ADHD subjects were identified by the PSC, supporting the idea that inpatient hospitalization may provide an additional opportunity for behavioral screening.
371 VALIDATION OF AN ANTIBIOTIC STEWARDSHIP PROGRAM’S NEONATAL INTENSIVE CARE UNIT ANTIBIOTIC USE GUIDELINES USING STERILE SITE CULTURE RESULTS
Phiapalath T1,2, Bagga B1,2, Talati AJ1,2, Arnold S1,2, Lee K1,2. 1 Le Bonheur Children’s Hospital, Memphis, TN and 2 The University of Tennessee Health Sciences Center, Memphis, TN.
Purpose of Study: In early 2012, the Antibiotic Stewardship Program (ASP) at Le Bonheur Children’s Hopsital created and implemented neonatal intensive care unit (NICU) empiric antibiotic guidelines for early and late onset sepsis, and necrotizing enterocolitis. Guidelines were based on extensive review of the literature, our hospital’s antibiogram, and discussion with neonatology staff. In 2013, concern was expressed that the implemented antibiotic regimens were inappropriate for more resistant pathogens potentially found in the NICU. The purpose of this study was to validate the use of the current NICU empiric antimicrobials by studying all positive sterile site cultures from our NICU over the past year.
Methods Used: Positive NICU cultures between June 2012 to May 2013 were extracted and all sterile site cultures were evaluated. Information collected included culture site, pathogen, and susceptibility. Each culture was evaluated for susceptibility to the ASP guideline antibiotics. Patients with resistant cultures were further reviewed for risks for antibiotic resistance.
Summary of Results: 100 of the 179 analyzed cultures were from sterile sites. 4% (4/100) were found to be resistant to guideline antibiotics. Two resistant cultures were E. coli in central line blood samples from one patient transferred from another hospital where the same organism had previously been cultured. Stenotrophomonas maltophilia grew in the other two samples. One was from lung tissue isolated in broth only. The other was from a peripheral blood culture in a patient with previous identification of the organism in a respiratory culture at the transferring hospital.
Conclusions: Our study demonstrates that the majority of sterile site cultures from our NICU are susceptible to the current ASP recommended empiric therapy. 96% of the positive sterile site cultures were susceptible to the ASP-selected empiric antibiotics. Three of the four cultures resistant to the recommended empiric antibiotics were from recently admitted patients with these bacteria previously cultured at their transferring hospitals. These results validate the utilization of our ASP-initiated NICU empiric antibiotic guidelines at our pediatric hospital.
372 ESOPHAGEAL BOUGIENAGE VS SURGICAL MANAGEMENT FOR ESOPHAGEAL COINS
Allie EH, Blackshaw A, Losek J, Tuuri RE. Medical University of South Carolina, Charelston, SC.
Purpose of Study: Our objective was to report our pediatric emergency department (PED) experience with esophageal bougienage (EB) versus surgical retrieval for esophageal coins with regard to clinical outcomes and costs.
Methods Used: We conducted a cross sectional observational review of all children with esophageal coins presenting to the MUSC PED from January 2004 to October 2012. The following data were abstracted: presenting symptoms, age, sex, exclusion criteria for bougienage, efficacy and complications, return visits, length of stay (LOS), and hospital charges. T-tests and 95% confidence intervals were used for comparisons of outcome measures between the group undergoing successful EB and those patients undergoing surgical retrieval.
Summary of Results: 245 patients presented to our PED with esophageal coins. 135 patients had successful EB and 109 had surgical retrieval. 1 case was excluded from the final analysis after being discharged with observation after failed EB. 165 patients were eligible for EB. Of the EB-eligible, 129 had successful EB; 7 had unsuccessful EB followed by surgical retrieval; and 29 underwent surgical retrieval first. Of the 80 ineligible for EB, 71 had surgical retrieval, and 9 had EB. Of the inappropriate EB there were 6 successful and 3 failed attempts. The mean length of stay (LOS) for successful EB was 137 minutes (SD 54) and 769 (SD 535) for the surgical cases. The difference in the means between treatment groups was 632 minutes, 95% CI for the difference was 723 to 541 (p = 0.000).
The mean hospital charges for successful EB were $984 (SD $576) and $7022 (SD $3132) for the surgical cases (p=0.000). The difference in means was $6,038, 95% CI $6,580 to $5,496 (p= 0.000). The mean age for the EB cases was 4 yrs (SD 2) versus 2 yrs (SD 3) for those undergoing surgical retrieval (p=0.000). The EB cases had 19 minor and no major complications and 5 return visits to clinics or the PED. One child who underwent EB had a failure of coin passage beyond the pylorus and subsequently underwent surgical retrieval. The surgical group had ten minor and two major complications – a traumatic esophageal diverticulum and an intra-procedural endotracheal tube dislodgement.
Conclusions: For eligible children, esophageal bougienage is a safe and more cost-effective management strategy for lodged esophageal coins.
Allergy, Immunology, and Rheumatology I Concurrent Session
2:00 PM
Friday, February 21, 2014
373 AUTOREACTIVE B CELL PHENOTYPE IN BXD2 MICE USING B CELL TETRAMERS
Hamilton JA2,1, Li J1, Wu Q1, Yang P1, Luo B1, Hsu H1, Mountz, JD1,2,3. 1 UAB, Birmingham, AL; 2 UAB, Birmingham, AL and 3 VA Medical Center, Birmingham, AL.
Purpose of Study: In patients with systemic lupus erythematous (SLE) and rheumatoid arthritis (RA), defective B cell tolerance enables the generation of pathogenic autoantibodies. BXD2 mice develop lupus and erosive arthritis characterized by production of high-affinity, class-switched autoantibodies. To facilitate study of the mechanisms preventing autoreactive B cell activation in the context of a full B cell repertoire, we have developed a B-cell tetramer-based strategy for ex vivo detection and characterization of autoreactive B cells in BXD2 mice.
Methods Used: A PEPperPRINT Autoimmunity Microarray covering 2,733 linear B-cell autoepitopes from the Immune Epitope Database (IEDB) was used to identify BXD2 autoepitopes. Tetramers were generated from top peptides. B cells were characterized by 11-parameter flow cytometry using live/dead analysis, non-specific and specific tetramer staining, and analysis of 4 parameters for follicular (CD23+CD21-), germinal center (GL-7), marginal zone (CD21+CD23-), and type I interferon (IFN) induced activation molecule (CD69).
Summary of Results: The dominant epitopes recognized by BXD2 autoantibodies are those commonly found in human SLE and RA patients, including peptides of nucleoproteins, ribonucleoproteins and heat shock proteins. The array further revealed reactivity with several citrulline-modified peptides. Tetramer studies revealed an age-dependent 5-10 fold increase in autoreactive B cells to fibromodulin-[cit] and snRNP in BXD2 compared to B6 mice. Within fibromodulin-[cit] tetramer+ cells, there was a significant increase in marginal zone (29% vs 4%) and germinal center (7.3% vs 0%) B cells in BXD2 vs B6 mice. There was also a significant increase in the % of CD69+ (99% vs 8.45%) tetramer+ B cells in BXD2 vs B6 mice.
Conclusions: Autoreactive B cells in BXD2 mice are enriched for activated B cells that are derived from either MZ or GC B cells. These results are consistent with our previous analyses indicating that type I IFNs stimulate CD69 expression on MZ B cells to induce follicular migration of MZ B cells to break immune tolerance to apoptotic self-antigens. These findings indicate that targeted depletion of this subpopulation of autoreactive B cells may be beneficial for treatment of rheumatic disease.
374 PREVELANCE OF CORONARY HEART DISEASE AND ITS RISK FACTORS IN VETERANS WITH SPONDYLOARTHRIDITIDES
Mains TB, Majithia V. University of Mississippi Medical Center, Jackson, MS.
Purpose of Study: An increased prevalence of cardiovascular disease (CVD) and coronary heart disease (CHD) has been reported in patients with Spondyloarthritides (SpA). This study investigated the prevalence of CVD risk factors, CHD and Cerebral Vascular accident in veterans with SpA (including Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), and Reactive arthritis (ReA) at the Jackson VAMC.
Methods Used: A retrospective chart review using ICD-9 codes for PsA, AS, and ReA was performed at Jackson, VAMC. Data including age, race, gender, lipid panel, HbA1c, presence of hypertension (HTN), smoking, CVD, and cerebrovascular events were tabulated. Matched Controls were selected from VA clinics and 2:1 matching was performed. A Comparison of CHD, stroke(s), and CVD risk factors (dyslipidemia (DLD), HTN, and diabetes Mellitus (DM) was made. Prevalence ration and odds ratio were calculated by standard method. Statistical significant (alpha <0.05) was calculated using Chi-square and Fisher’s exact test.
Summary of Results: There were 81 patients, 79 were male and 2 female. With a mean age of patients with PsA, AS, and ReA being 61,8, 60.4, and 56, respectively. There was a significant increase in the prevalence of CHD and its risk factors in the SpA, PsA, and AS patients when compared with the AHA data, and General Male vets from the 2003-04 control population. When compared to the matched controls the risk was increased but did not achieve statistical significance. There was an insufficient number of black patients in the cohort to assess effect of ethnicity.
Conclusions: Our results suggest that patients with SpA have an increased risk of developing CHD as well its risk factors. Our study is unique as increased risk and it quantification have not been previously reported in the U.S. veteran population. The increased CHD risk attributable to the increased prevalence of risk factors cannot be determined in this study but has been suggested to be over and above them.
375 LOSS OF SURROGATE LIGHT CHAIN PROTEINS DEREGULATES THE MATURE B CELL CDR-H3 REPERTOIRE
Khass M1, Watkins L2, Zhuang Y2, Burrows P3, Schroeder H2. 1 UAB, Birmingham, AL; 2 UAB, Birmingham, AL and 3 UAB, Birmingham, AL.
Purpose of Study: Successful association of the μ heavy chain and the surrogate light chain proteins, λ5 and VpreB, creates the pre B cell receptor (Pre BCR) and establishes a critical checkpoint in B cell development. Failure to create the Pre BCR arrests B cell development at the early PreB cell stage, a situation that has been suggested to be a factor promoting human acute lymphoblastic leukemia (ALL). We previously showed that the B cell repertoire is controlled by the sequence characteristics of the complementary determining region heavy chain (CDR-H3), which lies at the center of the antigen binding site. Using a bioinformatics system we developed for CDR-H3 analysis, we sought to examine the mature B cell CDR-H3 repertoire in mice lacking λ5 expression, to test whether absence of Pre BCR selection can affect its composition.
Methods Used: We analyzed CDR-H3 based on its length, reading frame usage and average amino acid hydrophobicity content.
Summary of Results: Our results show that λ5 knock out transitional and follicular B cells have an increase in the use of disfavored highly hydrophobic and/or charged CDR-H3 sequences with increased use of the normally underrepresented reading frame 2. Peritoneal cavity B1a cells from the λ5 KO mice showed the same features.
Conclusions: These findings suggest that a lack of control of the repertoire due to a defect at the PreB cell stage can impact the mature B cell compartments, potentially promoting abnormal autoantibody responses and contributing to the transformation of B cells. This insight may help to explain one mechanism for the pathogenesis of human ALL.
376 THE ROLE OF LEUKOCYTE ASSOCIATED IMMUNOGLOBULIN-LIKE RECEPTOR-1 (LAIR-1) IN SUPPRESSING COLLAGEN-INDUCED ARTHRITIS
Kim S1, Price L1, Cullins D1, Park J1, Stuart JM2,1, Kang A1, Myers L3,1. 1 University of Tennessee Health Science Center, Memphis, TN; 2 Veterans Affairs, Memphis, TN and 3 Le Bonheur Children’s Hospital, Memphis, TN.
Purpose of Study: The success of Abatacept (CTLA4-Ig) in treating rheumatoid arthritis (RA) suggests that targeting T cells can be an effective therapeutic strategy for RA. A possible new therapeutic target might be the inhibitory receptor Leukocyte Associated Immunoglobulin-Like Receptor-1 (LAIR-1) which is found on peripheral mononuclear cells, including NK cells and T cells. Our hypothesis was that stimulation of LAIR-1 will suppress cell signaling and lead to inhibition of autoimmune arthritis in the collagen-induced arthritis (CIA) model.
Methods Used: DR1 transgenic mice that were LAIR-1 -/- mice (n=7) were immunized with type II collagen (CII) to induce arthritis and compared to DR1 LAIR-1 +/+ littermate controls (n=13). Each mouse was scored three times weekly beginning 2 weeks post immunization and the mean severity scores and percentage of arthritic limbs were recorded at each time point.
Summary of Results: When CII-reactive murine T cells were cultured in vitro with the immunodominant determinant of CII we found that type I collagen could suppress IL-17 responses in the presence of LAIR-1. In vivo, mice that were immunized demonstrated that the LAIR -1 -/- group developed more severe arthritis than the wild type mice (severity scores 4.3 ± 2.7 vs. 2.2 ± 1.4, p=0.03). In addition, LAIR -1 -/- mice had a greater percentage of limbs affected with arthritis than did the wild type group (33 ± 21 vs. 17 ± 10, p=0.02). Antibody titers (IgG) to CII correlated with arthritis severity.
Conclusions: We have demonstrated that LAIR-1 -/- /DR1 mice develop arthritis that is more severe, with more arthritic joints than DR1 mice alone. These data suggest that LAIR-1 stimulation is involved in the modulation of CIA and that stimulation of LAIR-1 may serve as an effective treatment for RA.
377 ROLE OF DΒ GERMLINE SEQUENCE ON CONSTRAINING TCR CDRΒ3 DIVERSITY
Levinson M, Schroeder H, Silva-Sanchez A, Zhuang Y. University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: Diversity of the T cell receptor is mainly developed through V(D)J rearrangement and N addition during TCR development. The product of V(D)J rearrangement is the CDRβ3, a region of high variability that recognizes antigen and includes all of the D gene. The Dβ sequence is highly conserved across various species, from trout to mouse to humans. This suggests that there are some natural constraints on the TCR; these constraints are thought to limit deleterious T cells from reaching the periphery. We hypothesize that altering the D region will have an effect on the development of thymocytes.
Methods Used: In order to test our hypothesis, mice were generated with an alteration in their Dβ gene segments. The alterations are a Dβ2 KO (Dβ1), a replacement of the Dβ locus with a charged Dβ (DβDKRQ), and a replacement of the Dβ locus with a hydrophobic DH (DβYTL). Both developing thymocytes and mature splenic T cells were sorted from these mice by flow cytometry based on their expression of either CD44, CD25 and CD28 or CD4 and CD8. RNA from the thymocytes was extracted and the VDJ-beta genes were sequenced using primers to the VB13-1 and to the VBC1. In frame sequences were analyzed using IMGT junction analysis program.
Summary of Results: We have data comparing the T cell repertoires of WT and altered Dβ mutants. When compared to WT mice, the mutant Dβ mice have an altered T cell repertoire in both CDRβ3 amino acid composition and CDRβ3 length and these differences can be attributed to the changes in the germline sequence. Changing the Dβ also changes the total T cell number in both developing and mature T cells, with an altered Dβ being selected against. Preliminary functional data has shown that the T-dependent B cell response is diminished in the charged Dβ mice.
Conclusions: The Dβ germline sequence is clearly affecting the TCR repertoire. In DβDKRQ mice, the repertoire is skewed toward a shorter, more charged distribution. In DβYTL mice, CDRβ3 repertoire appears skewed towards a more hydrophobic, longer, BCR-like distribution. However, the altered TCR repertoire isn’t as hydrophobic as the BCR repertoire, suggesting mechanisms of somatic selection by preferring a less charged CDRβ3. Ongoing experiments using varied TCR Dβ locus mutants will elucidate the role of the germline sequence on the development of thymocytes.
378 REGIONS ON CHROMOSOME 2, 6, AND 10 MAY CONTRIBUTE TO THE SPECTRUM OF CVID
Hwangpo T1, Szymanska Mroczek E1, Brand M1, Burrows P1, Brown E2, Reynolds R1, Schroeder H1. 1 University of Alabama, Birmingham, AL and 2 University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: In our PID Clinic, we have cared for more than 400 patients with recurrent infections and depressed immunoglobulins. We have enrolled a majority of them in a protocol to identify regions within the genome that may contribute to the spectrum of their disease. We are interested in patients with CVID as well as a spectrum of patients who do not meet CVID criteria.
Methods Used: We included a total of 1,100 controls and 189 cases of European American ancestry; of which, 189 cases were either CVID, intermediate CVID (ICR), or hypogammaglobulemic (IgG ∼500) patients. Relative risk was estimated using odds ratios and corresponding 95% confidence intervals as implemented in PLINK as well as logistic regression association model with 10 principal component analysis were used in the analysis. Linkage disequilibrium was also assessed using Haploview and LocusZoom.
Summary of Results: The strongest gene associations with CVID were mapped to several loci on chromosomes 2, 6, and 10. Specifically, on chromosome 6, rs2523535, localized to HLA-B, was associated with CVID, ICR, and hypogammaglobulemia (p=6.5 × 10-6). Within chromosome 10, SNP rs110112086 lies upstream of microRNA MIR4675 (p=5.9 × 10-8). Within chromosome 2, SNP rs12998521 lies within IL1R1 gene (p=5.3 × 10-5).
Conclusions: This study exposes new and unexplored regions of interest within chromosomes 2, 6, and 10 in our CVID and CVID spectrum of patients. Further study of these areas may show new gene(s) that may contribute to their immunodeficiency.
379 DIAGNOSTIC CRITERIA FOR MUCOUS RECIRCULATION SYNDROME OF CHRONIC RHINOSINUSITIS
Patel A, DeShazo R. University of Mississippi Medical Center, Brandon, MS.
Purpose of Study: In clinical practice, nonallergic rhinosinusitis is a diagnosis of exclusion. One incompletely defined condition, masquerading as nonallergic rhinosinusitis, is characterized by persistent post nasal drip and mucoid rhinorrhea caused by abnormal mucous circulation within the nasopharynx. The underdiagnosis of this condition is due in part to a lack of diagnostic criteria. This investigation sought to better characterize mucus recirculation syndrome and to establish diagnostic criteria for it.
Methods Used: To develop a study cohort, we first established inclusion criteria and performed a computerized search of the medical literature published in English using the terms “mucous OR mucous AND recirculation” and “mucoid AND rhinitis”. Clinical data from these (8) patients were organized and then combined with that of 4 patients with mucous recirculation syndrome from our practice. Data from the cohort were analyzed to develop diagnostic criteria.
Summary of Results: The majority of the study group of 12 patients were female (58%) with an average age of 53 years. The most common presenting symptoms were persistent post nasal drip and nasal obstruction. Recirculation through the maxillary sinus occurs in the majority (83%) of the cohort. The more prevalent mechanism for mucous recirculation was a misplaced middle metal antrostomy (50%) with recirculation between the natural sinus ostium and the antrostomy. Recirculation between the natural ostium or antrostomy and an accessory ostium (25%) was the second most common mechanism. Mucous recirculation resolved when the abnormal ostium was enlarged to incorporate the natural ostium.
Conclusions: The diagnosis of mucous recirculation syndrome may be made if (1) A patient has symptoms of chronic rhinosinusitis characterized by post nasal drip and nasal obstruction that is refractory medical treatment, (2) Recirculating mucous is visualized on nasal endoscopy and (3) Symptoms resolve when the antrostomy or accessory ostea is incorporated into the natural osteum. Mucous recirculation syndrome should be differentiated from non-allergic rhinosinusitis and considered in patients with chronic nasal obstruction and mucoid post-nasal drip, especially if previous sinus surgery has been performed.
380 DEMOGRAPHIC IMPACT ON ASTHMA & HEALTH-RELATED QUALITY OF LIFE - A PILOT STUDY
Caruthers C1, Shah H1, Solanky T2, Kamboj S1, Kumar P1. 1 LSU Health Sciences Center, New Orleans, LA and 2 Univeristy of New Orleans, New Orleans, LA.
Purpose of Study: Asthma is a chronic inflammatory disorder with significant morbidity and mortality. It is a medically managed disease affected by proper medication reconciliation. Presumably, the higher the compliance, the better control of asthma and improved health-related quality of life (HRQOL). We analyzed the impact of demographic factors on a patient’s ability to access medications and disease comprehension
Methods Used: IRB approval was obtained. Adults with asthma were studied at Allergy-Immunology clinics. Informed consent was obtained from all research subjects. Asthma control test (ACT) and HRQOL, via SF-36 standard quality of life scores, were assessed and demographics collected. Compliance was determined by ascertaining proper medication usage.
Summary of Results: 49 bronchial asthmatic patients were studied - 14 in charity clinics and 35 in private clinics. Insured patients had mean SF-36 of 42.40 compared to uninsured patients who had mean of 35.94 (p=0.04). Analysis of the different income levels with ANOVA model showed statistical significance (p=0.01) for SF-36. Upon further analysis between income levels of less than $25,000 and more than $50,000, the mean was 38.66 and 47.58 (p=0.01). Analysis of clinic location, age and education level were not statistically significant, although there was a trend in SF-36 and ACT scores. In private clinics, the mean SF-36 and ACT scores were 42.27 and 16.69, while in charity clinics, 39.02 and 14.64. Older age groups had a lower SF-36 when comparing younger age group. For patients aged 18-25, mean SF-36 was 45.33, 25-50 years old was 41.73, and older than 50 was 40.69. Higher education level demonstrated improved SF-36 and ACT scores. Patients who did not complete high school had mean SF-36 and ACT scores of 37.90 and 14.14, high school graduates were 39.94 and 15.43, and college graduates were 44.31 and 17.63.
Conclusions: Patients with health insurance and higher income have an improved quality of life and better asthma control. Higher education was associated with better quality of life and asthma control, although the differences were not statistically significant.
381 CIGARETTE SMOKING, AGE, AND MALE SEX ARE INDEPENDENT RISK FACTORS FOR OCULAR SARCOIDOSIS
Walker M1, Janot A1,4, Huscher D2,3, Grewal H1, Yu M1, Lammi MR1, Saketkoo LA1. 1 LSU Health Sciences center, New Orleans, LA; 2 CGerman Rheumatism REsearch Centre, Berlin, Germany; 3 Charite University Hospital, Berlin, Germany and 4 Medical College of Virginia, Richmond, VA.
Purpose of Study: Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1-40/100,000. Ocular Sarcoidosis (OS) affects 25-50% of patients with sarcoidosis and can lead to blindness. To date, no studies have sought to determine risk factors for OS.
Methods Used: A retrospective chart review was conducted at a single institution with inclusion criteria of biopsy-proven sarcoidosis with a duration of >1 year and a documented smoking status. Variables collected were ages at time of diagnosis (of any organ) and at time of chart review, race, sex, smoking status, quantity of tobacco exposure, and presence (or history) of OS. Disease duration is defined as the difference of age at diagnosis and age time of chart review. Group comparisons were done by t-test and by Mann-Whitney tests where applicable. Univariate and multivariate regression analysis were done to identify independent risk factors.
Summary of Results: Of 269 charts reviewed, 109 patients met inclusion criteria. In the OS group, the portion of smokers (71.4%) was significantly higher than in the group without OS (42.0%, p=0.027). There was no significant difference (p=0.605) in the median number of pack years between smokers with OS (13 [7, 28]) and those without OS (16.5 [7, 25]). Furthermore, the OS group consisted of more male patients (57.1% versus 26.1%, p=0.009). Median disease duration of sarcoidosis was also higher in patients with OS (10 years versus 4 years, p=0.031). Through multivariate regression analysis, tobacco exposure (OR=5.24, p=0.007, 95% CI 1.58-17.41), male sex (OR=7.48, p=0.002, 95% CI 2.152-26.006), and age at time of chart review (OR=1.114, p=0.002, 95% CI 1.04-1.19) were found to be independent risk factors for OS.
Conclusions: Male sex, age at chart review, and tobacco exposure (regardless of pack years) were found to be independent risk factors for OS. Disease duration did not withstand multivariate analysis in this moderately sized group. However, screening for OS should not remit in patients with known sarcoidosis until defined in larger prospective populations.
382 SMOKING AND SECONDHAND SMOKE AMONG PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND CONTROLS: ASSOCIATIONS WITH DISEASE AND DISEASE DAMAGE
Minkin SJ, Slan SN, Gilkeson G, Kamen D. Medical University of South Carolina, Charleston, SC.
Purpose of Study: Previous reports suggest smoking may be a risk factor for developing systemic lupus erythematosus (SLE). This study explores the impact of tobacco smoke on SLE patients compared to controls and on disease characteristics among patients.
Methods Used: Data from a cohort of SLE patients and controls was utilized. Medical history, smoking and secondhand smoke exposure history, SLE Disease Activity Index (SLEDAI) and SLICC-Damage Index (SDI) scores were collected at an in-person enrollment visit and confirmed by chart review. Statistical analysis used chi square testing and multivariate logistic regression.
Summary of Results: There were 545 SLE patients and 386 controls with data available for analysis (Table). At enrollment, the mean age was 37.6 +/- 14.7 years for patients and 42.0 +/- 15.4 years for controls. Differences between current and never smokers (p=0.51) and ever and never smokers (p=0.70) were not significantly different between patients and controls. Compared to unrelated controls, African American patients were significantly more likely to be exposed in the home to secondhand smoke before the age of 18 (OR 1.81, 95% CI 1.13-2.89).
Damage by SDI (SDI > 0) was significantly associated with ever smoking (OR 3.08, 95% CI 1.4-6.6), current smoking (OR 3.17, 95% CI 1.1-9.1), and secondhand smoke exposure in childhood (OR 1.91, 95% CI 1.0-3.6). No significant relationship was found between smoking status and active disease at enrollment (SLEDAI ≥ 6) or dsDNA autoantibodies. Discoid rash was significantly associated with ever smoking (OR 2.74, 95% CI 1.5-5.1) and current smoking (OR 4.85, 95% CI 2.2-10.5).
Conclusions: Our study suggests that secondhand smoke during childhood may be a risk factor for SLE. Secondhand smoke during childhood, current smoking and past smoking contribute significantly to disease damage among patients with SLE.
Cardiovascular I Concurrent Session
2:00 PM
Friday, February 21, 2014
383 VARIATION IN GEOGRAPHIC DISTRIBUTION OF IN-HOSPITAL MORTALITY ASSOCIATED WITH ACUTE MYOCARDIAL INFARCTION: A NATIONWIDE ANALYSIS
Pant S1, Deshmukh A1, Mehta K2, Mehta JL1. 1 UAMS, Little Rock, AR and 2 University of Pittsburgh Medical Center, Pittsburgh, PA.
Purpose of Study: Mortality from acute myocardial infarction (AMI) has significantly declined nationwide due to various reasons. Data regarding geographic variation in mortality is however limited.
Methods Used: Using the Nationwide Inpatient Sample (NIS), we investigated the trends in in-hospital mortality, risk factors and procedures performed in different regions of the country from 2000-2010. The hospital’s census region was obtained from the AHA Annual Survey of Hospitals.
Summary of Results: There were a total of12,958,452 cases of AMI from 2000 to 2010. We noted an overall decline in mortality in all regions over this time span. However, the overall in-hospital mortality per 100,000 cases was highest in the South followed by Mid-west and North-east, with least in the West (Figure 1). Baseline characteristics analysis showed significantly higher occurrence of traditional risk factors (diabetes mellitus, hypertension, smoking, obesity and hyperlipidemia) in the South compared to other regions (Table 1). Median household income was significantly lower in this region as indicated by higher distribution of quartile 1 and quartile 2 incomes (Table 1). Finally, racial variation analysis showed higher race-specific mortality in the South compared to the rest (Figure 2). This race-wise mortality variation in the South is more pronounced among African-American and Hispanics (Figure 2).
Conclusions: Although mortality from AMI is trending down across all regions of the US, it is disproportionately higher in the South, likely due to uneven distribution of socio-economic and traditional risk factors in the South.
384 IMPACT OF LONG-TERM BURDEN OF OBESITY AND ELEVATED BLOOD PRESSURE ON LEFT VENTRICULAR REMODELING PATTERNS: THE BOGALUSA HEART STUDY
Lai C1,2, Cen R1, Li S1, Fernandez C1, Chen W1, Srinivasan SR1, Berenson GS1. 1 Tulane University, New Orleans, LA and 2 Peking Union Medical College Hospital, Beijing, China.
Purpose of Study: This study assessed the hypothesis that long-term cumulative burden and trends of obesity and elevated blood pressure (BP) from childhood are associated with adult left ventricular (LV) hypertrophy and geometric remodeling patterns.
Methods Used: The longitudinal study cohort consisted of 1061 adults (717 whites and 344 blacks, aged 24 to 46 years) who have been examined 4 or more times for BMI and BP from childhood to adulthood, with an average follow-up period of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP. Four LV geometric types were defined as normal, concentric remodeling (CR), eccentric (EH) and concentric hypertrophy (CH) using LV mass index and relative wall thickness.
Summary of Results: Compared with whites, blacks had higher prevalence of eccentric (17.7% vs 8.9%, p <0.001) and concentric (9.1% vs 3.5%, p <0.001) hypertrophy. Higher values of BMI, systolic (SBP) and diastolic (DBP) blood pressure of childhood, adulthood, total AUC and incremental AUC were all significantly associated with higher LV mass index and LV hypertrophy in linear and logistic regression analyses, respectively, when adjusted for race, sex age and lipid variables. The association of geometric remodeling patterns with BMI and SBP is shown in the table below. Of interest, all values of BMI had a consistently greater influence on EH than SBP. DBP showed similar association parameters with LV remodeling patterns.
Conclusions: The findings suggest that adverse influence of obesity and elevated BP levels on LV hypertrophy begins in childhood, and obesity is more important for EH than for CH, indicating the importance of preventive strategies for LV hypertrophy in early life.
385 THE PREVALENCE OF DIASTOLIC DYSFUNCTION AMONG PATENTS WHO UNDERGO ECHOCARDIOGRAMS AND ITS SIGNIFICANCE - DIABETES IS A STRONG CORRELATE OF DIASTOLIC DYSFUNCTION
Panikkath R, Jenkins L. Texas Tech University Health Sciences Center, Lubbock, Lubbock, TX.
Purpose of Study: The prevalence and progression of diastolic dysfunction among patients who undergo echocardiography in an echocardiographic center is not known
Methods Used: This study includes all adult patients (>20years) with diastolic dysfunction who had an echocardiogram at a university hospital echocardiographic center in January 2012. If the subject had a previous echocardiogram, the oldest one was evaluated for the presence and severity of LV diastolic dysfunction. Controls were subjects with normal systolic and diastolic function in absence of exclusion criteria.
Summary of Results: Of the 483 consecutive subjects who underwent echocardiography, 223 had LV diastolic dysfunction. Of those, 190 (39.4%) subjects met the inclusion criteria. Mean age of cases and controls was 67.7 ± 13.4 years (50.5% males) and 54 ± 15 (57% males) respectively (p=0.01 for age & 0.67 for sex). Diabetes (43.7% vs. 22.5%; p∼0.001), hypertension 85.7% vs. 70.1%; p =0.02) and coronary artery disease (44.2% vs. 35.0%; p=0.06) were the common comorbidities in cases and controls, respectively. In logistic regression, only age [odds ratio (OR) 1.05 (95% CI 1.01-1.10)] and diabetes [odds ratio (OR) 61.22 (95% CI 12.60-120.56) were significantly associated with diastolic dysfunction. Only 20 (10.5%) patients with diastolic dysfunction had been diagnosed with congestive heart failure. Seventy one subjects with diastolic dysfunction had a previous echocardiogram available. Over a mean duration of 49.5 ± 35.4 months, the diastolic dysfunction remained the same in 46 (64.8%), progressed by one grade in 17 (23.9%) and two grades in 4 (5.6%) patients. In logistic regression, hypertension [odds ratio (OR) 1.1 (95% CI 0.1-12.7)], diabetes [OR 0.45 (95% CI 0.2-1.4)] or BMI [OR 0.99 (95% CI 0.92-1.1)] were not significantly associated with progression of diastolic dysfunction.
Conclusions: Diastolic dysfunction in the presence of normal systolic function was seen in 39.4% of adult patients who underwent echocardiograms. Of those, only 10% had a diagnosis of diastolic heart failure. Diabetes is a strong correlate of diastolic dysfunction. In the subjects who had a previous echocardiogram, the majority had no progression of diastolic dysfunction over a mean duration of 4 years.
386 THE EFFECT OF KIDNEY TRANSPLANTATION ON LEFT VENTRICULAR SYSTOLIC FUNCTION AND MECHANICAL DYSSYNCHRONY BY GATED MYOCARDIAL PERFUSION IMAGING
Crosland W, Aggarwal H, Mehta S, Mannon R, Heo J, Iskandrian A, Hage F. University of Alabama-Birmingham, Birmingham, AL.
Purpose of Study: We have previously demonstrated that patients with end-stage renal disease (ESRD) and left ventricular mechanical dyssynchrony (LVD) have a worse prognosis and phase analysis readily evaluates LVD via gated SPECT myocardial perfusion imaging (MPI). Whether kidney transplantation influences mechanical function and dyssynchrony remains unclear.
Methods Used: We identified patients from the renal transplantation database maintained at the University of Alabama at Birmingham who underwent MPI for clinical indications before and after renal transplantation and who had normal perfusion on both sets of stress imaging. Patients with ESRD at time of second MPI were excluded. MPIs were reprocessed to derive LV ejection fraction (EF), and LVD indices (phase bandwidth [BW] and standard deviation [SD]). The primary outcomes were change in LVEF, BW, and SD before and after transplantation.
Summary of Results: The study population consisted of 30 patients (55% male, 51 ± 12 years, 55% African American, 61% diabetic). Of these, 12 (40%) had not initiated dialysis prior to first MPI and the rest had initiated dialysis for 2±2 years. The second MPI was performed at 3 ± 2 years after transplantation. LVEF (72 ± 10% vs. 67 ± 11%, p = 0.002) improved after transplantation but not phase SD (21.6 ± 14.3° vs. 21.5 ± 11.4°, p = 0.98) or BW (58.2 ± 36.0° vs. 57.6 ± 29.6°, p = 0.93). On pre-transplant MPI, 9 (27%), 14 (42%), and 15 (46%) had abnormal LVEF, SD, and BW, respectively. The corresponding numbers after transplantation were 3 (9%), 12 (36%), and 14 (42%), respectively.
Conclusions: This study shows that renal transplantation favorably influences LVEF but does not improve abnormal LVD indices.
387 EFFECT OF DECREASED RENAL FUNCTION ON LONG TERM SURVIVAL IN PATIENTS WITH LEFT ANTERIOR DESCENDING CORONARY DISEASE
Bissett JK. Central Ark VA Hosp, Little Rock, AR.
Purpose of Study: The study was designed to compare the results of therapy for left anterior descending disease in patients with and without renal disease. Despite the presence of stenosis of a major coronary artery these patients would usually be excluded from randomized clinical trials.
Methods Used: A computerized medical record system was used to follow the clinical course of 100 patients with left anterior descending disease form 2003-2013. The system documents and allows review from multiple hospitals throughout the United States. The patients were divided into 2 groups on the basis of a glomerular filtration rate of 60 millimeters per minute per 1.73 meters squared. Coronary angioplasty, coronary bypass surgery, and measurement of fractional flow reserve were applied when appropriate. The patients were placed on standard medications and treated by primary care, nephrology, and cardiology and offered pacemakers, defibrillators, and dialysis as needed. No patient was excluded from data collection for any reason.
Summary of Results: (1) In this pilot study of a small group of patients in a national health care system renal disease was a significant predictor of mortality with a 10 year hazard ratio of 3.39 (confidence interval 1.68-6.85, p<0.01) (2)Death occurred in 22/35 patients with a reduced glomerular filtration rate at baseline versus 19/46 patients with normal renal runction (p<0.01). (3) These results include all deaths from multiple medical conditions.
Conclusions: (1) Patients with coronary disease with left anterior descending stenosis can experience increased mortality from renal disease despite medical and interventional cardiac therapy (2) Additional studies are needed to design methods for preservation of renal function in patients with vascular disease.
388 DISRUPTION OF GUANYLYL CYCLASE/NATRIURETIC PEPTIDE RECEPTOR-A GENE INDUCES CARDIAC FIBROSIS THROUGH TGF-β/SMAD DEPENDENT PATHWAY
Subramanian U, Gogulamudi V, Pandey KN. Tulane University, New Orleans, LA.
Purpose of Study: Targeted-disruption of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) in mice provokes high blood pressure, cardiac hypertrophy, fibrosis, and remodeling associated with congestive heart failure. The objective of this study was to determine the mechanisms regulating the development of fibrosis in Npr1 gene-disrupted mice hearts.
Methods Used: The Npr1 null mutant (Npr1-/-, 0-copy), heterozygous (Npr1+/-, 1-copy), and wild-type (Npr1+/+, 2-copy) mice were orally administered with transforming growth factor-β1 receptor inhibitor GW788388 (2 mg/kg/day) for 28 days, the hearts were isolated and used for quantification of fibrotic markers using real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses. Together, systolic blood pressure (SBP), heart weight-to-body weight (HW/BW) ratio, left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVEDS), and percent fractional shortening (FS) were analyzed.
Summary of Results: The Npr1-/- null mutant mice showed 6-fold induction of fibrosis in the hearts. The expression of a number of fibrotic markers was markedly induced, including connective tissue growth factor (CTGF, 5-fold), α-smooth muscle actin (α-SMA, 4-fold) and TGF-βRI (4-fold), TGF-βRII (3.5-fold) and SMAD proteins (SMAD-2, 5-fold; SMAD-3, 3-fold) in Npr1-/- mice hearts compared with wild-type control mice. The treatment with TGF-β inhibitor, GW788388, significantly prevented the development of cardiac fibrosis and potentially down-regulated the expression of fibrotic markers and SMAD proteins in Npr1-/- mice compared to vehicle-treated wild-type animals.
Conclusions: The results of the present study suggest that the development of cardiac fibrosis in Npr1-/- gene-disrupted mice might be regulated through TGF-β mediated SMAD-dependent pathways.
389 ADVANCED GLYCATION END PRODUCTS (AGES) AND ASSOCIATIONS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Toney MM, Kamen D. Medical University of South Carolina, Charleston, SC.
Purpose of Study: Oxidative stress plays a role in disease activity and premature atherosclerosis seen in patients with systemic lupus erythematosus (SLE). Advanced glycation end products (AGEs) are prevalent in the Western diet. The accumulation of serum AGEs disrupts protein function, and interaction with its receptor induces production of reactive oxygen species and activation of vascular endothelial cells, leading to increased oxidative stress. Our hypothesis is that serum AGE levels, indicators of dietary habits, correlate with inflammation and potentially impact autoimmunity.
Methods Used: Serum samples from 80 Gullah African American participants recruited prospectively into the SLE in Gullah Health (SLEIGH) study were assayed with AGE Competitive ELISA kit from Cell Bio Labs. The cohort consisted of 50 patients (25 with no history of cardiovascular disease, and 25 with history of cardiovascular disease or renal disease) and 30 controls (15 related controls, 15 unrelated healthy controls). Student’s T-test was used to compare AGE levels among SLE patients to controls. We used logistic regression models to examine predictors of autoantibody status and a nested case-control design to compare AGE levels between different disease subsets of patients.
Summary of Results: As shown Table 1, mean AGE levels were higher in the control group than the patient group. Interestingly, among controls, ANA positivity significantly correlated with higher AGE levels (p=0.0008), even when adjusted for age (years) (OR 1.09, 95% CI 1.02-1.17, p=0.011). Among patients, smoking status (p=0.004) and hydroxychloroquine (p=0.016) use were consistent with higher AGE levels and statistically significant. Though not statistically significant, history of stroke among patients correlated with higher AGE levels (p= 0.08).
Conclusions: Although there was not a statistically significant difference in AGE levels between SLE patients and controls, the AGE levels were significantly higher with ANA positivity among controls. This finding suggests that serum AGE levels may play a significant role in autoimmunity and warrants further study.
390 INSULIN-LIKE GROWTH FACTOR 1 REGULATES LIPID ACCUMULATION IN MACROPHAGES - A POTENTIAL MECHANISM FOR INSULIN-LIKE GROWTH FACTOR 1 MEDIATED ATHEROPROTECTION
Higashi Y, Shai S, Sukhanov S, Kim C, Snarski P, Delafontaine P. Tulane University, New Orleans, LA.
Purpose of Study: Lipid accumulation and foam cell formation is a hallmark of atherogenesis, whereas apoptosis of foam cells leads to necrotic core formation and plaque vulnerability. Insulin-like growth factor-1 (IGF-1) is anti-atherogenic, and loss of IGF-1 signaling in macrophages not only increases plaque burden, but also induces a vulnerable plaque phenotype with enlarged necrotic cores and thin fibrous caps. We investigated potential mechanisms for accelerated atherosclerosis in macrophage specific IGF-1R knockout mice (MΦIgf1rKO).
Methods Used: MΦIgf1rKO was created on Apoe-deficient background. Animals were fed on a high-fat diet for 8 wks, and atherosclerotic burden and aortic gene expressions were assessed. Peritoneal macrophages were isolated and assessed for lipid transport activities.
Summary of Results: MΦIgf1rKO had an increase in atherosclerotic burden (57±15% increase by aortic sinus cross-section analysis vs. Igf1r floxed mice, n=8, p<0.05), and plaque composition was altered: MΦIgf1rKO had an increased macrophage content (Mac3 staining, by 39±13%, P<0.05) and a decrease in smooth muscle cell content (α-smooth muscle actin staining, by 34±17%, P<0.05). Aortic gene expression analysis showed that MΦIgf1rKO downregulated ABCA1 and ABCG1 (by 32±14% and 45±19%, P<0.05, n=10), transporters responsible for lipid efflux from macrophages, and upregulated ACAT-1 and DGAT-2 (by 58±16% and 115±55%, P<0.05, n=10), lipid metabolism enzymes responsible for lipid storage; however MΦIgf1rKO did not alter Msr1, CD36, or LOX-1 expression. Furthermore, MΦIgf1rKO suppressed PPARγ and LXRβ (by 47.6±2.5% and 43.0±10.8%, P<0.01), consistent with changes in expression of lipid transport and lipid metabolism related genes. In cultured macrophages we assessed the effect of IGF-1 on lipid transport and found that MΦIgf1rKO-macrophage shows reduced lipid efflux to apolipoprotein A1 and HDL (P<0.01).
Conclusions: Our findings suggest that loss of IGF-1 signaling in macrophages promotes lipid accumulation, thereby enhancing foam cell formation and necrotic core enlargement, which account for a vulnerable plaque phenotype. IGF-1 regulation of lipid accumulation provides a novel therapeutic strategy to treat atherosclerotic lesions and to promote plaque stabilization.
391 ROSIGLITAZONE INCREASES CHOLESTEROL EFFLUX CAPACITY IN PATIENTS WITH TYPE 2 DIABETES
Agarwala A, Givens E, McGuire DK, De Lemos JA, Rohatgi A. UT Southwestern Medical Center, Dallas, TX.
Purpose of Study: Thiazolidinediones (TZDs) are medications used in patients with type 2 diabetes (T2DM) that activate peroxisome proliferator- activated receptors (PPAR) γ, thereby improving insulin sensitivity and glycemic control. In most patients, treatment with TZDs increases HDL-C, suggesting that TZDs may have effects on atherosclerosis via the reverse cholesterol transport (RCT) pathway. A few small reports without placebo control have shown that TZDs may increase macrophage-specific cholesterol efflux capacity (CEC), the first critical step in RCT. We tested the hypothesis that TZDs, specifically rosiglitazone (rosi), increase CEC in patients with T2DM in a placebo-controlled trial.
Methods Used: 111 patients (57 rosi, 56 placebo) with T2DM and either the presence of coronary disease or strong risk factors for coronary disease were randomized to double-blinded treatment with rosi vs. placebo for 6 months. CEC was measured at baseline and after 6 months treatment.
Summary of Results: Preliminary results from the first 65 patients (30 rosi, 35 placebo) show increased mean CEC in patients randomized to rosi vs. placebo (ΔR: 0.064 ± 0.31; ΔP: -0.045 ± 0.26, p=0.03). Paired comparisons of baseline vs. treatment show an increase in the rosi arm (0.87 ± 0.54 vs. 0.93 ± 0.51, p 0.005) but no change in the placebo arm (0.79 ± 0.51 vs. 0.74 ± 0.51, p 0.83) (Figure 1).
Conclusions: These findings from a randomized placebo-controlled trial suggest that activation of PPAR γ increased CEC and that the effect of TZDs on atherosclerosis may be mediated by their effects on cholesterol efflux.
FIGURE 1 Normalized cholesterol efflux at baseline and after 6 months of treatment
392 HIGH-SENSITIVITY TROPONIN FOR DIAGNOSIS OF OBSTRUCTIVE CORONARY ARTERY DISEASE
Siegfried JS, Panagopoulos G, Garratt KN, Coplan NL. Lenox Hill Hospital, New York, NY.
Purpose of Study: Small elevations in troponin values may be caused by several clinical conditions. In urgent care settings such elevations often lead to a presumptive diagnosis of active coronary artery disease (CAD). We sought to determine the relationship between small troponin elevations and presence of significant CAD.
Methods Used: Records were reviewed for 250 consecutive patients admitted from the ED with suspected cardiac ischemia who underwent cardiac catheterization during hospitalization. Unstable patients and those with STEMI or creatinine >2.0 were excluded. Data collected included high sensitivity troponin I level and presence of significant obstructive CAD (defined as ≥70% stenosis in an epicardial vessel or equivalent criteria), as well as data regarding cardiac function and risk factors. Quantitative assessment was performed using computerized quantitative coronary angiography (QCA). The data were used to generate a receiver operating curve (ROC) for use of troponin to diagnose obstructive CAD.
Summary of Results: A troponin above the lowest detectable level, 0.015 ng/mL, had a sensitivity of 71.3% and specificity of 45.8% for detection of an obstructive coronary lesion. Specificity of 80.4%, 89.7% and 95.3% was achieved at troponin 0.075, 0.437 and 4.485 with sensitivity of 44.8%, 30.8% and 19.6% respectively. The area under the ROC was 0.67. Presence of obstructive CAD, increasing age, left ventricular end diastolic pressure, lower ejection fraction, and degree of stenosis by QCA were all significantly correlated with elevated troponin. Logistic regression analysis showed that when adjusted for risk factors and cardiac function, troponin remained a weak but significant predictor of obstructive CAD (OR 1.146, 95% CI [1.021-1.287], p=0.021).
Conclusions: Troponin is a relatively sensitive marker for the presence of obstructive CAD and is fairly specific at low levels of elevation. An undetectable troponin does not rule out the presence of a significant coronary lesion and further testing may be required to delineate disease. Patients being evaluated for suspected cardiac ischemia, even with very small troponin elevations, should be evaluated thoroughly and effectively for active CAD.
393 THE PROGNOSTIC VALUE OF TRANSIENT ISCHEMIC DILATION OF THE LEFT VENTRICLE WITH REGADENOSON MYOCARDIAL PERFUSION IMAGING
Lester D, Bleich S, El-Hajj S, Heo J, Iskandrian A, Hage F. University of Alabama School of Medicine, Birmingham, AL.
Purpose of Study: Transient ischemic dilation (TID) of the left ventricle on myocardial perfusion imaging (MPI) is generally considered a sensitive and specific marker of severe and extensive coronary artery disease and is thought to provide important prognostic information. The prognostic value of TID obtained using regadenoson, a selective adenosine A2A receptor agonist, as a stress agent for MPI has not been well studied.
Methods Used: An automated software program was used to measure TID on consecutive patients with normal and abnormal perfusion pattern who underwent regadenoson MPI at our institution. The primary outcome was all-cause death.
Summary of Results: The study population consisted of 199 patients (44% male, 59±12 years, 37% diabetes, 13% with coronary revascularization) with normal and 688 patients (65%, 63±12 years, 51%, 53%) with abnormal perfusion pattern. TID was not different between the 2 groups (1.04±0.15 vs. 1.06±0.01, p=NS). None of the patients with normal perfusion pattern underwent revascularization within 90 days of index MPI. The proportion of patients with abnormal perfusion that underwent early revascularization increased with increasing quartiles of TID (11%, 13%, 16%, 23%, p=0.02). During a follow-up of 44±17 months, there were 51 (26%) and 229 (33%) deaths among patients with normal and abnormal perfusion, respectively. In patients that did not undergo early revascularization TID was not associated with overall mortality whether perfusion was normal or abnormal (Figure). These findings were unchanged in patients with diabetes or history of coronary revascularization.
Conclusions: TID to regadenoson is associated with early referral to coronary revascularization but not with long-term mortality.
Gastroenterology I Concurrent Session
2:00 PM
Friday, February 21, 2014
394 EFFECT OF COLON TRANSECTION ON SPONTANEOUS HIGH-AMPLITUDE-PROPAGATING CONTRACTIONS IN CHILDREN
Jacobs C1, Wolfson S2, Di Lorenzo C2, Cocjin J2, Monagas J2, Hyman P2,1. 1 Louisiana State University, New Orleans, LA and 2 Children’s Hospital, New Orleans, LA.
Purpose of Study: After Hirschsprung’s disease (HD) surgery, many children suffer fecal incontinence caused by increased high amplitude propagating contractions (HAPCs). The aim of this study was to determine whether children with HD have more HAPCs than children with colon transections for reasons other than HD.
Methods Used: We reviewed 500 colon manometries. Children (7.6±5.1 yrs; 275 male) with functional constipation (n=237; 7.4±5.0yrs; 126 male) and chronic abdominal pain (n=48; 9.8±5.8yrs; 25 male) served as controls compared to subjects with HD (n=56; 6.9±4.1yrs; 44 male) and colon transection for other reasons (n=24; 6.1±5.8yrs; 12 male). We excluded 139 subjects without HAPCs. We documented HAPCs during 1 h fasting and 1 h postprandial. Results are mean ± SD.
Summary of Results: During fasting, HD subjects had more HAPCs (2.2±3.4/h) vs. functional constipation (0.8±2.2/h, p=0.0004) and chronic pain (0.5±1.1/h, p=0.001), but not more than colon transection (1.9±3.2/h, p=1.0). HD showed more postprandial HAPCs (4.0±5.4/h) than functional constipation (1.5±2.5/h, p<0.0001) and chronic pain (0.9±1.6/h, p<0.0001), but not more than colon transection (2.4±3.0/h, p=0.6). There were more HAPCs fasting and post-prandial after colon transection (1.9 ± 3.2/h and 2.4±3.0/h) than functional constipation (0.8±2.2/h, p=0.3 and 1.5±2.5/h, p=1.0) and chronic pain (0.5±1.1/h, p=1.0 and 0.9±1.6, p=1.0). HD subjects were divided by chief complaint: fecal incontinence or constipation. HD subjects with incontinence (n=23) only had more HAPCs fasting (p=0.01) and post-prandial (p=0.01) than HD subjects with constipation (n=28) only.
Conclusions: Increased HAPCs followed colon transection, regardless of cause. HD subjects with incontinence had more HAPCs than subjects with colon transection for other reasons.
395 INCREASED RATE OF GASTRIC EMPTYING AFTER PYLOROPLASTY CORRELATES WITH REDUCTION OF GASTROPARETIC SYMPTOMS
Onate EJ1, Sarosiek I1, Liu K2, Dwivedi AK2, McCallum R1. 1 Texas Tech University Health Sciences Center, El Paso, TX and 2 Texas Tech University Health Sciences Center, El Paso, TX.
Purpose of Study: It is suggested that there is a poor correlation between gastroparetic (GP) symptoms and gastric emptying time (GET). Gastric Electrical Stimulation (GES) improves GP symptoms, but there is a minimal or no effect on acceleration of GET. Hence we have added pyloroplasty (PP) as a surgical procedure in GP patients receiving GES. Our Aim was to assess the correlation of changes in GET in GES patients after PP with improvement of GP symptoms.
Methods Used: Seventeen (13F) drug refractory GP patients (13- Post-Surgical, 4-Idipoathic) received PP with GES. Total GP symptoms scores (TSS) assessing severity (S) and frequency (F) of nausea, early satiety, bloating, vomiting, postprandial fullness, epigastric pain and burning were obtained by using a 5-point Likert scale at baseline and at last follow up visit, a mean of 6 months (3–18). The GET was conducted before and after surgery with GP defined as > 60% retention of isotope at 2 hrs and >10% at 4 hrs. Paired t-test, one-way ANOVA and Pearson correlation coefficient was used to analyze data.
Summary of Results: GES & PP improved severity of TSS from 20 to 11points and frequency from 21 to 12 (P<0.001). GET retention was reduced from 75% to 39% at 2hrs and from 47% to 12 at 4hrs (P<0.001). There was a significant correlation between reduction in severity and frequency of postprandial fullness with acceleration in GET: (p=0.032) and (p=0.022) respectively. There was also a strong correlation between reduction in frequency of vomiting, epigastric pain, and epigastric burning and faster 2 hrs GET: (p=0.051), (p=0.024), (p=0.040) respectively. Additionally, there was a significant correlation of improvement in S and F of nausea and early satiety with changes in GET at 4 hrs: nausea- S (p=0.043), F (p=0.067); early satiety-S (p=0.03) and F (p=0.031).
Conclusions: 1) Overall, in drug-refractory GP the addition of PP to GES markedly accelerated gastric emptying, while also significantly improving GP symptoms; 2) The increased rate of gastric emptying after PP correlated with improvements in many GP symptoms. 3) GET remains a valuable marker for diagnosis and management of GP patients.
396 HISTOLOGICAL EVIDENCE OF INFLAMMATORY CHANGES IN THE MUSCULARIS PROPRIA OF GASTRIC SMOOTH MUSCLE IN IDIOPATHIC GASTROPARESIS PATIENTS
Saadi M1, Torabi A2, Sunny J1, Sarosiek I1, Davis BR3, Moraveji S1, McCallum R1. 1 TTUHSC- El Paso, El Paso, TX; 2 TTUHSC- El Paso, El Paso, TX and 3 TTUHSC- El Paso, El Paso, TX.
Purpose of Study: Idiopathic gastroparesis (ID-GP) patients are thought to represent a heterogenous population. Recent data indicating structural changes in their gastric smooth muscle with reduced numbers of interstitial cells of Cajal (ICC) and enteric neurons as well as increased immune infiltrates in the myenteric plexus suggest a gastroenteritis-infection based etiology. Our aim was to investigate inflammatory cell markers on full thickness surgical biopsies of the antrum in ID-GP patients.
Methods Used: Five female patients, aged 19 to 58 years, with ID-GP who underwent full thickness gastric (antrum) biopsy during surgery to place the gastric electrical stimulation system and pyloroplasty. Similar biopsies were obtained at surgery from 4 female non-gastroparetic chronically vomiting patients (“vomiting controls”), aged 19 to 61 years, with superior mesenteric artery syndrome (3) and Rumination Syndrome (1). The biopsy samples were stained with H&E, trichrome for fibrosis, S100 for myenteric plexus, and C- Kit (CD117) for ICC and examined under light microscopy for the presence of inflammatory infiltrate, macrophages or fibrosis in the myenteric plexus.
Summary of Results: See Table:
Two out of the five ID-GP patients (40%) had reduced ICC numbers, and two had an infiltrate of neutrophils in and around the nerve bundles. One had evidence of apoptotic neuronal changes. There were no inflammatory cells identified in the biopsies from the “vomiting control” patients.
Conclusions: 1) This study shows that cellular abnormalities are found in the gastric muscularis propria in most ID-GP patients (4 out of 5). 2) The neutrophil infiltrates in the myenteric plexus observed in two patients have not been previously described and provide more support for the concept that post-infection neural injury could be the underlying pathophysiology in patients termed as “idiopathic” gastroparetics.
397 CORRELATION OF SIGMOIDOSCOPY FINDINGS IN CHILDREN WITH MILK PROTEIN ALLERGY
Patel B. University of South Alabama, Mobile, AL.
Purpose of Study: Milk protein allergy, an immunologic reaction to cow’s milk proteins, is becoming a chronic problem in children upto one year of age. It affects up to 3% of children in the United States of America. It can cause skin, lung, and gastrointestinal manifestations via IgE or non-IgE mediated response. The objective of this study was to determine if children less than one year of age who presented with symptoms of milk protein allergy had positive sigmoidoscopy findings. In addition, we sought to correlate the symptoms of milk protein allergy with sigmoidoscopy findings of lymphonodular hyperplasia (LNH) and eosinophils count per high power field (eosinophils/hpf) in the rectosigmoid.
Methods Used: This was a retrospective chart review of patients referred to the University of South Alabama Pediatric Gastroenterology clinic from outlying clinics with symptoms of milk protein allergy including blood per rectum, fussiness, vomiting, gas/constipation, poor weight gain, wheezing and rash.
Summary of Results: Most children were less than six months old and there was an even distribution of males and females included in this study. The commonly reported symptoms were fussiness, vomiting, constipation and rectal bleeding. Our study was divided into two groups, those with microscopic or macroscopic rectal bleeding and those without. The LNH and eosinophil/hpf were analyzed in these two groups. It was found that patients with rectal bleeding had the highest number of eosinophils/hpf. However, there was no statistical significance between the number of eosinophils/hpf or presence of LNH in either group.
Conclusions: Vomiting was the most common symptom associated with eosinophil/hpf and wheezing was the least. While 63% of the patients in both the rectal bleeding and non rectal bleeding groups were on a protein hydrolysate formula prior to their sigmoidoscopy, they had lower eosinophils/hpf, and the other 37% of patients who were on non protein hydrolysate formulas (excluding amino acid formulas) had higher eosinophils/hpf. Thus we conclude that sigmoidoscopy may not be useful in infants who have already been on protein hydrolysate formulas. Further studies are needed to look for causes of LNH, as it may be due to other cells involved such as T-cells. Future studies may show that these cells instead of eosinophils/hpf in food hypersensitivity reactions may be of better diagnostic value.
398 SIGNIFICANT GASTROESOPHAGEAL REFLUX DISEASE IN INFANCY IS ASSOCIATED WITH ESOPHAGEAL REFLUX IN CHILDHOOD
Ramasamy P, Gremse D. University of South Alabama Children’s & Women’s Hospital, Mobile, AL.
Purpose of Study: Limited available evidence suggests that presence of gastroesophageal reflux disease (GERD) in infancy may be associated with GERD symptoms later in life (Winter et al., Scand J Gastroenterol 2011;46:1157-68). Our aim is to determine the incidence of GERD in children who had GERD during infancy confirmed by esophageal pH monitoring.
Methods Used: Infants born between 1990 through 2008 who underwent esophageal pH study were followed for GERD symptoms during childhood. Infants with GERD who had no follow up records or who had co-morbidities were excluded from further analysis. Data were collected from query of electronic patient database. The presence of GERD in children who had an abnormal pH study in infancy was compared to those with normal pH study results. Continuous variables were compared using student’s t-test & discrete variables were analyzed by chi-square with Yates’ correction.
Summary of Results: Examination of patient records identified 371 infants with abnormal pH studies (positive group) & 394 infants with normal pH studies (control group). 241 infants in positive group & 256 infants in negative group were excluded from further analysis due to lack of follow up records. In addition, 9 infants in the positive group & 14 infants in the negative group were removed due to co-morbid conditions like genetic syndromes or previous gastrointestinal surgery. Of the 206 patients in the final analysis, 38/105 subjects in the positive group & 20/101 subjects in the control group were found to have GERD in childhood (36% vs. 20%, p=0.0139). The 2 groups were similar in terms of age at follow up (9.2 ± 5.2 vs. 9.7 ± 5.34 yr., x ± SD, p=0.14), gender (55% vs. 46% male, p=0.16) & race (60%/40% vs. 38%/60%/2%, Caucasian/African-American/Asian).
Conclusions: We conclude that children who have significant GERD in infancy are more likely to experience GER symptoms during childhood. We speculate that abnormal esophageal pH study results in infancy may be prognostic of an increased risk of GERD later in childhood.
399 A HEALTHIER BODY FAT DISTRIBUTION AFTER GASTRIC BYPASS SURGERY IS ASSOCIATED WITH IMPROVEMENTS IN INSULIN SENSITIVITY AND ADIPOKINE LEVELS
Mitchell PW1,2, Marks-Shulman P2, Shang M2, Tyree R2, Tamboli R2, Abumrad N2. 1 LSUHSC New Orleans School of Medicine, New Orleans, LA and 2 Vanderbilt University School of Medicine, Nashville, TN.
Purpose of Study: Body fat distribution is an important determinant of health risks, and is dependent upon hereditary factors and hormones. Android obesity (central or “apple-shaped”), which includes visceral fat, is correlated with increased risk of cardiovascular disease and type 2 diabetes, whereas gynoid obesity (lower body or “pear-shaped”), is associated with lower disease risk and may even be protective. Roux-en-Y gastric bypass (RYGB) is to most effective means to achieve massive weight loss and improvements in metabolic diseases. We hypothesized that an improved body fat distribution after RYGB would be associated with improvements in insulin sensitivity and metabolic hormone profiles.
Methods Used: To test this hypothesis, we utilized data from our cohort of 42 RYGB subjects (all females) collected prospectively up to 2 years after RYGB. Body fat distribution was assessed by waist and hip circumferences and dual-energy x-ray absorptiometry (DXA), which measured percent fat in the android and gynoid regions.
Summary of Results: Body fat distribution improved after RYGB to a more gynoid fat distribution. A decrease in the ratio of android-to-gynoid percent fat (AGR) after RYGB had a significant effect on improvements in hepatic and peripheral insulin sensitivity and leptin levels after RYGB in addition to weight loss. The increase in adiponectin after RYGB was associated with a decrease in AGR but was not associated with weight loss. Body fat distribution before RYGB had no effect on changes in body weight, insulin sensitivity, or metabolic hormones after RYGB. Additionally, our data indicate that waist-to-hip ratio is not a precise substitute for AGR in obese and post-RYGB subjects.
Conclusions: This data suggests that individuals with android and gynoid obesity experience the same weight loss and metabolic benefits after RYGB; however, the location of fat mass loss is a determinant of the degree of metabolic improvements after RYGB.
400 CONSTIPATION DIAGNOSIS AND MANAGEMENT: What are our practices?
Lowry M, Lukens E, Monroe K, Hitch M, Morris J, Pruitt C, Nichols MH. University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: The purpose of this study was to investigate the diagnostic techniques and management used to assess a pediatric patient with suspected constipation by Pediatric Emergency Medicine (PEM) and Pediatric Gastroenterology (GI) Health Care Providers (HCP) and Pediatric Residents. This study follows another study examining 621 ED patients with discharge diagnosis of constipation where 72% of patients had x-rays, 35% treated with enemas, 51% with ED intervention (19% no documented treatment results), and 36% with dietary recommendations.
Methods Used: A survey was emailed to 125 physicians and nurse practitioners regarding their individual practice in the diagnosis and management of abdominal pain related to constipation. This survey questioned their use of imaging, digital rectal exams, enemas, oral laxatives and patient counseling. The study was approved by our Institutional Review Board.
Summary of Results: 95 HCP completed the survey: 17 PEM Attendings, 8 PEM Fellows, 2 PEM Nurse Practitioners, 6 GI Attendings, 3 GI Fellows, 59 Pediatric Residents. When HCP were asked if they obtain x-rays in patients with abdominal pain, 16% HCP responded usually, 44% sometimes, 24% occasionally, 15% rarely. Main reasons for x-rays included suspicion of obstruction (86%) or intussusception (57%), persistent vomiting (44%), or generalized pain with negative workup (54%). Digital rectal exams were usually performed by 32% of HCP, 24% sometimes, 19% occasionally, 20% rarely. Preferred treatment for constipation included enema 56%, Miralax 90%, dietary recommendations 49%. GI HCP were more likely than PEM HCP to administer an enema and counsel on structured toileting. When asked if results were documented if ED intervention, 31% responded always, 33% usually, 14% sometimes, 7% occasionally, 11% rarely. HCP believed an ED discharge order set (95%) and prompts to document results if rectal or treatment performed (77%) would be beneficial.
Conclusions: When comparing the practices of HCP with an ED retrospective study of patients with discharge diagnosis of constipation, x-rays were obtained more frequently than reported practice by HCP. Enemas are a common treatment practice of HCPs. Documentation of treatment results and discharge recommendations could possibly be improved with HCP education and ED chart prompts and discharge order sets.
401 THERE’S NO PREDICTING! NATURAL HISTORY OF IRRITABLE BOWEL SYNDROME IN CHILDREN
Lee ES2, Hyman P1,2,3. 1 Children’s Hospital New Orleans, New Orleans, LA; 2 LSU Health Sciences Center - New Orleans, New Orleans, LA and 3 Digestive Health Alliance Children’s GI Research Network, Milwaukee, WI.
Purpose of Study: The purpose of this study was to prospectively gather information concerning symptoms, treatment, and school absence in a cohort of children with IBS.
Methods Used: We enrolled 144 subjects (97 female) aged 4-17 years. All met symptom based Rome criteria for IBS on the QPGS-RIII questionnaire.
Summary of Results: We found subtypes: constipation predominant-IBS (c-IBS) in 43, diarrhea-predominant IBS (d-IBS) in 60, alternating IBS (a-IBS) in 31, and no subtype in 10. BMI was >85% in 36%. We found dyspepsia, defined by frequent upper abdominal discomfort, in 71 IBS subjects. Pain exacerbations lasting hours to days resulted in an abdominal migraine diagnosis in 39 subjects. At the initial visit 64% had missed school within the past month because of abdominal pain. Physicians prescribed medicine in 90%, cognitive behavioral therapy in 18%, and no treatment in 9%. The most frequently prescribed medicines were laxatives in 42% and gastric acid suppressants in 27% of the sample. Other medicines included anticholinergics, antidepressants, prokinetics, appetite stimulants, peppermint oil, fiber, and probiotics.
Follow-up visits varied in number and chronology, from one to 9 visits, based on clinical status. Five subjects (3%) withdrew because their diagnosis changed: 2 Crohn’s disease, 2 celiac disease. Forty-four subjects were lost to follow -up. One year after the initial visit, we interviewed 95 subjects. Twenty-one subjects (22%) were asymptomatic, 37 (39%) were improved, 26 (27%) were unchanged, and 6 (6%) were worse. (No response from 5). Age, sex (regardless of the onset of puberty), IBS subtype, BMI, and co-morbid functional disorders did not predict outcome.
Conclusions: We conclude that there was no consensus treatment for IBS. The relatively common use of acid inhibitors may reflect attempts to treat co-morbid dyspepsia, or treat IBS with a safe placebo. A majority of IBS children attending GI clinic miss school because of symptoms. The natural history of IBS is uncertain, and it is unclear whether treatment alters outcome. The absence of consensus about drug treatment casts doubt on drug efficacy.
402 CHRONIC USE OF ADVIL CAUSING COLLAGENOUS COLITIS
Moti D, Ahmed M. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: Collagenous colitis is characterized by chronic watery diarrhea which typically occurs in middle aged patients. Several etiologies have been suggested, one of them to be NSAIDs. In this report, we present case of chronic diarrhea due to collagenous colitis associated with a long term use of Advil.
An 83 year old white female presented with diarrhea of 2 months duration. The diarrhea was watery and non-bloody. The daily frequency was 9-12 motion per daily. The diarrhea was mostly post-prandial. There was no abdominal pain, fever or chills. Patient denied any nausea or vomiting and any significant weight loss. No recent history of travel. Patient had history of chronic arthritis and was taking at least 800 mg of Advil daily for more than 5 years. At presentation, patient showed signs of dehydration. The stool examination was non-revealing. A colonoscopy with biopsy revealed chronic colitis consistent with Collagenous Colitis. Patient was rehydrated, and was advised to discontinue the Advil. She was started on budesonide. Within a short period of time, her symptoms ceased, and she remained disease free on subsequent follow up.
Collagenous Colitis is one of the two different types of microscopic colitis which typically occurs with middle aged patients. It is characterized by chronic, watery diarrhea associated with fecal urgency. Several theories on the etiology of collagenous colitis have been suggested. It is possible that the underlying causes may differ among patients. Collagenous colitis may represent one clinical presentation of a group of collagenous mucosal inflammatory diseases of the gastrointestinal tract that affect not only the colon but also the small intestine and stomach. The diagnosis of Collagenous Colitis is established by biopsy of the colonic Mucosa. Therapy should consist of stopping NSAIDs and other drugs that have been associated with these disorders. Steroid is the mainstay of treatment.
403 IMPACT OF SOCIAL MEDIA ON GASTROENTEROLOGISTS IN THE UNITED STATES
Davis ED1, Tang S1, Zebedee Z1, Glover P1, Wu R2, Wang A2. 1 University of Mississippi, Flowood, MS and 2 UT Southwestern, Dallas, TX.
Case Report: Social media is pervasive in the mobile and connected world. As of 2012, Facebook® has more than one billion users and Twitter® has about 300 million users.
Major academic gastroenterological societies in the US; such as the AGA, ASGE, ACG, and their affiliatedscientific publications all have active pages among social media.
To assess the current impact of social media on healthcare and gastroenterology in the US and the attitude of gastroenterologists toward social media.
We sent web-based invitations to all 183 gastroenterology fellowship program directors and 6,600 practicing gastroenterologists in the US. 265 invitees completed the survey. We were interested in areas such as: the amount of time physicians spent on social media, which medium, and how much of their supplemental educational material was derived from these sources.
The majority of study participants were not interested in social media as a way to obtain continuing medical education. 82.1% of respondents did not access AGA, ASGE, ACG social media pages for educational materials. 47.7% of gastroenterologists never utilized any form of social media. In addition, most respondents thought that social media will not positively impact medicine, with respect to the accurate dissemination of medical information. Smart phones are the most popular device used for e-mails and web browsing. In 2013, the majority of American gastroenterologists were not interested in social-media-based medical education and did not believe social media would positively impact medicine.
404 CORRELATION BETWEEN ENDOSCOPIC FINDINGS AND CLINICAL SYMPTOMATOLOGY IN TODDLERS WITH REFRACTORY CONSTIPATION AND MILK PROTEIN INTOLERANCE
Alkilani A, Connelly R, Crissinger K. University of South Alabama Children’s and Women's Hospital, Mobile, AL.
Purpose of Study: Refractory constipation in toddlers may be due to milk protein intolerance (MPI) that is diagnosed by increased eosinophils in the duodenum &/or colon. The purpose of the study was to determine wherher intestinal eosinophilia correlates with the severity of constipation and associated clinical symptoms.
Methods Used: Retrospective chart review.
Summary of Results: Results: All patients presented with refractory constipation between 1-3 years. Group 1 included 65 patients, 52% male, diagnosed via endoscopy in infancy with MPI (>10 eos/hpf in duodenum (ED) &/or >5 eos/hpf in rectosigmoid colon (ERS)) with lymphonodular hyperplasia (LNH), a frequent endoscopic finding in MPI, present in 65%, ED in 64%, and ERS in 97%. There was no association between the presence of ED or ERS and symptoms of hard stools, fecal occult blood (FOB), visible blood, visible mucus, abdominal pain, abdominal distention, bloating, vomiting, straining with defecation or the presence of more than two symptoms (>2SS). There was a significant association between LNH and hard stools (p<0.046). Of note, 22% were already on, or asked to be on a cow’s milk-free diet (CMFD) due to the severity of the constipation and 17% were asked to be on a soy protein-free diet (SPFD). Our second group included 27 patients, 55% male, who were scoped due to refractory constipation and were diagnosed with MPI between 1 & 3 years of age with LNH in 85%, ED in 68%, and ERS in 100%. There were significant correlations between ED and FOB (p< 0.037) and ED and the presence of >2SS (p<0.004). In this group, all patients were asked to be on a CMFD and in 26% the constipation resolved, 48% didn’t improve, and 26% had no follow-up or compliance with the CMFD. Lastly, 44% of patients were asked to be on a SPFD and in 50% of them the constipation resolved, 33% didn’t improve, and 16% had no follow-up or non-compliance with the SPFD.
Conclusions: Although intestinal eosinophilia is used for the diagnosis of MPI, few correlations with symptomatology exist in patients with refractory constipation and MPI in the toddler age group whether diagnosed as infants or toddlers, but at least 50% improved on a CMFD or CMFD plus SPFD. The primary limitations were the small numbers and the variability in dietary compliance.
Hematology and Oncology I Concurrent Session
2:00 PM
Friday, February 21, 2014
405 T(8;9)(P22;P24): A SIMPLE TRANSLOCATION OR A NEW DISEASE?
Bitar C1, Saba J2, Safah H3. 1 University of Balamand, Beirut, Lebanon; 2 Lebanese University, Beirut, Lebanon and 3 Tulane University, New Orleans, LA.
Purpose of Study: Janus kinase 2 (JAK2) gain of function mutation is a well-known genetic anomaly in myeloproliferative neoplasms (MPN). Recently, t(8;9)(p22;p24) has been described to activate JAK2 resulting in a variety of diseases that surpasses MPN to include cases of acute leukemia, lymphoma, and myelofibrosis. At the molecular level, t(8;9)(p22;p24) results in new fusion gene product, putting pericentriolar material 1 (PCM1) gene located on 8p22 and JAK-2 located on 9p24 together. This leads to continuous activation of JAK2 tyrosine kinase, with subsequent hematological malignant effects. PCM1-JAK2 positive diseases are characterized by an aggressive disease course and resistance to most available therapies. In this study, we review all reported cases of t(8;9)(p22;p24) and discuss issues related to diagnosis and therapy.
Methods Used: An extensive literature search on PubMed/MEDLINE was conducted using the keywords “PCM1” and “JAK2”. 27 published articles with a confirmed t(8;9)(p22;p24) were identified. Data were gathered and tabulated regarding the following 10 variables: age, gender, presentation, diagnosis, peripheral blood, bone marrow, cytogenetics, FISH, therapy, and outcomes.
Summary of Results: 27 cases were identified. Median age was 47 years (range, 12-75 years), with a striking male predominance (M:F =4.4; M=22, F=5). Myeloid neoplasm was by far the most common diagnostic entity (24/27), this includes atypical CML n=6; AML n=5; CEL n=5; MDS n=4; MPN- unclassified n=3; acute erythroid leukemia n=1. The rest was lymphoid malignancies (3/27): one pre-B-ALL, one Burkitt’s leukemia, and one T-cell lymphoma. The choice of therapy was based on disease entity, and can be divided into 3 categories: cytotoxic chemotherapy, allogeneic stem cell transplant, and tyrosine kinase inhibitors. The latter was a well-tolerated therapy and induced favorable responses. Long follow-ups were unavailable in most cases, and death was reported in12 cases secondary to disease progression or complications of therapy.
Conclusions: t(8;9)(p22;p24) remains a rare translocation resulting in an aggressive disease. Emerging tyrosine kinase inhibitors have promising roles, but need to be validated in the context clinical trials.
406 PRIMARY TREATMENT FOR CLINICALLY LOCALIZED PROSTATE CANCER: DOES AGE OR RACE MATTER?
Saltzman A1,2, Luo S3,4, Hudson M1. 1 Ochsner Clinic Foundation, New Orleans, LA; 2 Louisiana State University, New Orleans, LA; 3 Washington University School of Medicine, St. Louis, MO and 4 John Cochran Veterans Affairs Medical Center, St. Louis, MO.
Purpose of Study: To determine whether racial and/or age differences exist for the primary treatment type received by veterans with equal insurance access for prostate cancer detected by PSA > 4 mg/mL.
Methods Used: We identified a cohort of 20,694 African American (AA) and white veterans aged 40-70 years with PSA >4 ng/mL between 10/1/2000 and 9/30/2007 within VHA. 6,223 underwent prostate biopsy and 3,030 veterans were diagnosed with prostate cancer. We performed a retrospective chart review and/or obtained data from the Veterans Administration Central Cancer Registry on patients with clinically localized disease. We report the primary treatment received, stratifying by age and race. Treatment categories included active surveillance, surgery, radiation, androgen-deprivation therapy alone, other (photon beam, cryotherapy), and refused/no treatment.
Summary of Results: 2479 veterans with clinically localized prostate cancer were analyzed. Overall, AA veterans were most likely to undergo radiation therapy (p<0.0001) while whites were most likely to undergo surgery (p<0.0001). When stratifying by age alone, veterans aged 40-49 and 50-59 were most likely to undergo surgery (p<0.0001) while veterans ages 60-69 were most likely to undergo radiation (p<0.0001). When stratifying by age and race, only the 50-59 age group showed racial differences, with AA veterans most commonly treated with radiation and white veterans most commonly treated with surgery (p<0.001). Comorbidity indices, using the Romano adaptation of the Charlson comorbidity index, were significantly higher in the 50-59 year old AA veterans than their white counterparts (p=0.0017), but D’Amico risk status and Gleason score were not significantly different (p=0.1245 and p=0.0877 respectively).
Conclusions: Age and comorbidities are associated with primary treatment type for localized prostate cancer, and may in part explain observed racial differences in primary treatment type received for clinically localized prostate in veterans.
407 RED BLOOD CELL TRANSFUSION AND RED BLOOD CELL EXCHANGE IN SICKLE CELL DISEASE
McNaughton J, Mayhall G, Schmid J. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Red blood cell (RBC) transfusion and RBC exchange are procedures used to treat sickle cell disease (SCD). Information was gathered on each to educate sickle cell patients and families.
Methods Used: A literature review was performed to examine aspects of sickle cell disease and transfusion therapy, including the history of SCD and therapeutic apheresis, the effects of transfusion on hemoglobin S, the risks and benefits of RBC transfusion and RBC exchange, and transfusion reactions, including alloantibody formation.
Summary of Results: Sickle cell crises often occur due to occlusion of blood vessels by high levels of Hemoglobin (Hb) S cells. RBC transfusion helps improve blood flow and preserve oxygen delivery to tissues by increasing the amount of normal HbA, which decreases the proportion of HbS. Transfusion and exchange are indicated to treat and prevent many of the serious events that can occur in SCD, including stroke and acute chest syndrome. Simple transfusion is the receipt of a unit of healthy donor RBCs. Exchange is the separation of a patient’s whole blood by an apheresis machine. The RBCs are removed with subsequent return of the remaining blood and donor RBCs. There are benefits and risks to both. Transfusion and exchange transfusion decrease the levels of HbS and provide HbA, although transfusion can lead to iron overload. Exchange prevents iron overload, but exposes the patient to more donor RBC units. When a marked reduction of HbS is needed, exchange will be more effective than transfusion. Transfusion reactions rarely occur and are most commonly hives or fever. More serious reactions can happen, such as hemolytic transfusion reactions, although transfusion services have many steps in place to prevent these. Alloantibody formation is common in sickle cell patients. Many transfusion services provide extended phenotype matching for RBC antigens to prevent antibody formation and all provide antigen negative blood in cases where an antibody has been made.
Conclusions: Transfusion and exchange provide excellent results in the treatment and prevention of vaso-occlusive crises in SCD. There are risks to each, although transfusion services work to prevent serious events, so that the benefits of transfusion and exchange in SCD outweigh the risks.
408 STROMAL CELLS PROVIDE SUPPORTVE NICHE FOR TUMORIGENESIS AND METASTASIS IN ESOPHAGEAL ADENOCARCINOMA
Zhang X1, Myers T2, Cordova J2, Green H2, Davis N3, Bolton J2, Margolin D2, Li L1. 1 Ochsner Clinic Foundation, New Orleans, LA; 2 Ochsner Clinic Foundation, New Orleans, LA and 3 Ochsner Clinic Foundation, New Orleans, LA.
Purpose of Study: The incident of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. The 5-year survival rate is about 15%. Lymph node (LN) is the first metastatic site for EAC. Positive LN involvement in EAC is one of the strongest negative indicators for patient outcome. It is known that LN stromal cells not only physically construct the LN architecture but also are essential for regulating cell migration and recruiting. To elucidate the molecular mechanism underlying EAC metastasis, we investigated the role of stromal cell in EAC growth and metastasis using noninvasive imaging approaches in a human-in-mouse xenograft model.
Methods Used: EAC tissue samples were obtained from 8 consented patients undergoing esophageal resection and digested using collagenase for single cell suspension. The characteristics of EAC patient cancer cells and human EAC cell line OE33 were compared by flow cytometry and immunohistochemistry. Luciferase-tagged OE33 or patient cancer cells were subcutaneously implanted in the flanks of NOD/SCID mice. EAC tumorigenesis and/or metastasis in the absence or presence of stromal cell HK or HK cell conditioned-media were monitored by bioluminescence imaging system.
Summary of Results: We established a reproducible human-in-mouse xenograft models that developed spontaneous metastasis. The xenografts from OE33 cells and EAC patients’ cancer cells share similar architecture, biomarkers, and histopathologic morphology with primary tumor in EAC patients. Addition of HK cells or HK cell conditioned-media not only significantly facilitates the EAC cell growth in vitro, but also supports primary tumor growth and mouse liver and lung metastasis.
Conclusions: We have developed a robust approach for imaging of EAC growth and dissemination, permitting both macroscopic and microscopic analysis of EAC progress. Our data suggested that LN stromal cells provide a direct support to EAC development and metastasis. Targeting signals from stromal cells in combination with chemotherapy may provide a promising therapeutic strategy for EAC.
409 PULMONARY EMBOLISM IN A PREVIOUSLY HEALTHY YOUNG WOMAN
Wallis NK1,2, Northrip K1, Radulescu VC1. 1 University of Kentucky, Lexington, KY and 2 University of Kentucky, Lexington, KY.
Case Report: An obese 16 year-old female presented in severe respiratory distress that developed over the course of 5 days. She complained that her heart was “racing” and her throat “throbbed” and was unable to speak full sentences or walk even a few steps. A CT scan of the chest revealed large bilateral pulmonary emboli and significant right heart strain. ECHO verified RV dilation with systolic dysfunction and tricuspid regurgitation. Right heart catheterization confirmed elevated right heart filling pressures and she was successfully treated with ultrasound-enhanced thrombolysis. Coagulopathy work-up included Factor V Leiden, Factor VIII, protein C and S, prothrombin, homocystine, Beta-2 glycoprotein and anticardiolipin. All were within normal limits except the lupus anticoagulant (LA), which was strongly positive. Upper and lower extremity ultrasound did not show evidence of DVT. The patient was treated with Lovenox as a bridge to Coumadin and was discharged home after 9 days. Her only medical problem prior was menorrhagia for which she was started on the OCP, Tri-Previfem, 3 months prior. Her family history was negative for significant blood clots or pregnancy losses.
Pulmonary embolization has become more common in the adolescent population over the past couple of years. Possible causes include the increased use of oral contraceptives, the obesity epidemic, and improved diagnostics. Obesity and OCPs independently increase the risk of thrombosis and the combination of both lead to a 24-fold higher risk. Our patient had these risk factors plus a positive test for LA, an antiphospholipid antibody. Persistent antiphospholipid antibodies further increase the risk of both arterial and venous thrombosis. After diagnosis, the patient was counseled to avoid all estrogen-containing contraceptives. She will remain on life-long anticoagulation if repeat testing reveals persistent LA as she would then meet the diagnostic criteria for antiphospholipid antibody syndrome. This case highlights the need to carefully consider the risks and benefits prior to starting a patient on OCPs and reminds clinicians of the complex set of factors in determining a patient’s risk for thrombosis.
410 ACUTE PROMYELOCYTIC LEUKEMIA PRESENTING WITH GINGIVAL HYPERPLASIA
Eubanks J, Herrin V. University of Mississippi Medical Center, Jackson, MS.
Case Report: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia resulting from the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene that typically presents with pancytopenia, bleeding, and coagulopathy. We report a case of an unusual presentation of APL involving gingival infiltration.
A 43 year old man with a history of pulmonary embolism, non-compliant with warfarin, presented with a four day history of progressive gum swelling, bleeding and tenderness with associated difficulty speaking. Examination showed pronounced gingival hyperplasia and bleeding. A complete blood count showed a white blood count of 57 × 109/L, anemia, and thrombocytopenia with a peripheral blood smear showing promyelocytes and blasts. No coagulopathy was present. Bone marrow biopsy showed hypercellularity with promyelocytes comprising >80% of the marrow cells. Cytogenetics revealed t(15;17)(q24;q21) and fluorescence in situ hybridization showed the PML-RARα gene fusion, establishing the diagnosis of APL. He was treated with all-trans-retinoic acid (ATRA) plus cytarabine and idarubicin. Aminocaproic acid solution improved the gingival bleeding. His course was complicated by differentiation syndrome treated with dexamethasone and a brief interruption in ATRA therapy. At completion of induction, there was vast improvement in gingival hyperplasia.
While oral bleeding is often present at diagnosis of APL, leukemic infiltration of the gingival tissue is rare. This is more commonly seen with monocytic variants of acute myeloid leukemia and cases reported of gingival involvement in APL have been associated with relapse rather than initial diagnosis. This case underscores the potential for a gingival manifestation of APL at presentation.
411 ANALYSIS OF EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) MUTATIONS AND ECHINODERM MICROTUBULE-ASSOCIATED PROTEIN-LIKE 4-ANAPLASTIC LYMPHOMA KINASE (EML4-ALK) GENE REARRANGEMENT IN LUNG ADENOCARCINOMA PATIENTS: A 3-YEAR EXPERIENCE OF THE LOUISIANA STATE UNIVERSITY (LSU) PUBLIC HOSPITAL IN NEW ORLEANS
Narmala SK, Puligothram S, Jahangir SZ, Boulmay B. LSU - New Orleans, New Orleans, LA.
Purpose of Study: The National Comprehensive Cancer Network recommends that all patients with lung adenocarcinoma (LA) be tested for EGFR mutation and EML4-ALK gene rearrangement (EGFR/ALK). EGFR mutations are found in approximately 10% of white patients and up to 50% of Asian patients with LA. The prevalence of EML4-ALK gene rearrangement is between 2-7% in LA patients. Both are more common in non-smokers. We analyzed the frequency of EGFR mutations and EML4-ALK gene rearrangements from the biopsy samples submitted for these analyses.
Methods Used: We identified patients from LSU diagnosed with metastatic LA whose specimens were sent for EGFR/ALK from January 1, 2009 to June 30, 2013. Data collected included number of specimens sent for EGFR/ALK, number of samples with inadequate tumor, biopsy technique utilized and number of re-biopsy attempts for EGFR/ALK.
Summary of Results: 54 patients were evaluated in the study time period: 58 individual biopsy specimens were sent for EGFR/ALK. 34/58 (58%) of specimens were found to be adequate for EGFR and/or ALK. 6/34 samples were inadequate for EGFR, but adequate for ALK, 2/34 were inadequate for ALK, but adequate for EGFR. In 12/34 samples only EFGR was tested, ALK was not tested. Only 1 of the 28 samples tested for EGFR had the mutation and none of the 22 samples tested for EML4-ALK had the gene rearrangement.
Conclusions: A substantial proportion of initial LA diagnostic biopsies were inadequate for EGFR/ALK analysis. EGFR mutations and EML4-ALK rearrangement are rare in LA patients seen at LSU public hospital. Most of patients in the analyzed tend to be black and almost all had an extensive smoking history which could explain the low frequency of EGFR mutations and EML4-ALK rearrangement.
412 INTERIM LSU HOSPITAL (ILH) STUDY 2012: EVALUATING ADHERENCE TO SUPPORTIVE CARE GUIDELINES FOR PATIENTS ADMITTED TO ILH FOR NEUTROPENIC FEVER
Castillo E, Dhillon N, Puligothram S, Boulmay B. LSUHSC, New Orleans, LA.
Purpose of Study: The purpose of this quality improvement project was to identify if growth factors and prophylactic antibiotics had been included in the treatment plan of the patients admitted with neutropenic fever in 2012.
Methods Used: At LSU Interim Hospital in New Orleans, the Hematology/Oncology team evaluated the number of neutropenic fever admissions and whether growth factors and antibiotics had been administered per guidelines. A chart review of these admissions was performed in order to give recommendations to the cancer committee as applicable.
Summary of Results: A total of 21 charts of patients admitted for neutropenic fever as a primary diagnosis were reviewed.
- Eleven patients (six on hyper-CVAD and five on 7+3) received prophylactic antibiotics; they all had an indication for antibiotic prophylaxis according to commonly accepted guidelines.
- Fourteen patients (6 on hyper-CVAD, 3 on R-CHOP, 3 on 7+3 and 2 of DCF) received growth factor as part of their treatment. Per guidelines, it was only indicated in 11 of them.
- Seven patients (1 on FOLFOX, 1 on weekly Cisplatin + radiotherapy, 2 on DCF, and 2 on Cisplatin + Etoposide) did not receive prophylactic antibiotics or growth factors, also consistent with commonly accepted treatment guidelines.
Conclusions: After evaluating the characteristics of chemotherapy related neutropenic fever admissions to the LSU Interim Hospital, we have come to the conclusion that guidelines for prophylactic antibiotics and growth factors use were followed. Based on this data, we have no recommendations to the cancer committee, other than to encourage clinicians to use the treatment templates provided in EPIC, which are built with commonly accepted supportive care agents.
413 HODGKIN’S LYMPHOMA PRESENTING WITH EPIDURAL SPINAL INVOLVEMENT
Evans J, Herrin V. University of Mississippi Medical Center, Jackson, MS.
Case Report: Hodgkin’s lymphoma typically presents with painless lymphadenopathy, however in minority of cases can have extranodal spread of disease. We report a case of newly diagnosed classical Hodgkin’s lymphoma with epidural spinal involvement resulting in severe lumbar spinal canal stenosis.
A 32yo female presented with complaints of shortness of breath, palpitations, subjective fevers, night sweats, and unintentional weight loss over the past several weeks. Initial CT scan of chest showed extensive lymphadenopathy in supraclavicular, hilar, and mediastinal lymph nodes, therefore patient was transferred to our institution. On physical exam patient was found to have large palpable soft tissue mass at base of left neck with normal neurological exam. Initial labs were significant for leukocytosis of 12,000, hemoglobin of 6.5 g/dL, and platelet count of 207,000. Patient was admitted to the hospital and underwent subsequent CT imaging of her neck and abdomen that revealed wide spread lymphadenopathy, as well as L5 vertebral lesion. She then underwent a MRI of her lumbar spine confirming involvement of L5 vertebra as well as an epidural mass extending from L3-4 to S2-3 that resulted in severe lumbar spinal canal stenosis. Surgery was consulted and performed excisional biopsy of cervical lymph node that was consistent with classical Hodgkin’s lymphoma, nodular sclerosis subtype. While in the hospital patient had recurrent fevers up to 103 degrees Fahrenheit with complaints of pain in lower back requiring intravenous narcotics, but did not express signs of spinal cord compression. She also received 2 units of packed red blood cells for treatment on anemia with improvement in shortness of breath and palpitations. After results of biopsy patient was discharged from the hospital with plans to undergo outpatient bone marrow biopsy for staging purposes prior to initiation of chemotherapy.
Epidural spinal involvement of Hodgkin’s lymphoma is a relatively rare phenomenon found most often in disseminated advanced stage disease. Its occurrence has been described between 0.5 and 3%. Unless it causes signs of cord compression, treatment typically involves systemic chemotherapy without surgical intervention.
Infectious Diseases I Concurrent Session
2:00 PM
Friday, February 21, 2014
414 GROUP B STREPTOCOCCI INDUCE PROINFLAMMATORY RESPONSES VIA A PROTEIN KINASE D1 DEPENDENT PATHWAY
Upadhyay K1, Park J1, Kim Y1, Meals E1, Talati AJ1, English B2, Yi A1. 1 CFRI, UTHSC, Memphis, TN and 2 Michigan State University, Grand Rapids, TN.
Purpose of Study: Protein kinase D1(PKD1) plays a significant role in inflammatory process mediated by MyD88 dependent toll like receptors(TLR). We proposed to study the role of PKD1 in Group B Streptococci(GBS) mediated proinflammatory responses and to determine a molecular mechanism by which GBS activates PKD1 in macrophages.
Methods Used: RAW 264.7 cells were stimulated with live GBS or penicillin G-killed GBS and activation of PKD1 was analyzed by in vitro kinase assay and phospho-specific Western blot assay. Subsequently, MyD88-/- macrophages, IRAK1-/-, or TRAF6 -/- macrophages were stimulated with GBS and activation of PKD1 was analyzed. Next, to investigate whether PKD1 plays indispensable role in GBS mediated proinflammatory responses, RAW264.7 cells and C57BL/6 mice were stimulated with GBS in the presence of PKD inhibitor Gö6976 and expression and production of the selected cytokines/chemokines were analyzed by RT-PCR and ELISA. Finally, to determine contribution of PKD1 in GBS-mediated septic shock-like death, D-galactosamine (D-GalN) sensitized mice were challenged with antibiotic killed GBS in the presence of PKD inhibitor and then viability of mice was observed.
Summary of Results: Both live and antibiotic killed GBS induced kinase activity and phosphorylation of PKD1. PKD1 activation by GBS was completely abolished in MyD88-/- macrophages and IRAK1-/- macrophages but not in TRAF6 -/-macrophages. GBS induced activation of signaling modulators (i.e., JNK, ERK, p38, or NF-κB) and expression and production of proinflammatory cytokines and chemokines (TNFα, IL-6, IL-10, IL-12p40, IP-10, MCP-1, CCL5, MIP-1α, MIP-2, LIX, and KC) were either ablated or significantly inhibited in the presence of PKD inhibitor in vitro and in vivo. Furthermore, systemic administration of PKD inhibitor protected D-GalN-sensitized mice from shock mediated death caused by GBS.
Conclusions: GBS induced activation of PKD1 via a MyD88 and IRAK1 dependent manner. PKD1 played an indispensable role in GBS-mediated activation of MAPKs and NF-κB and subsequent expression of proinflammatory cytokines and chemokines in vitro and in vivo. Furthermore, inhibition of PKD1 activation protected mice from death due to exaggerated proinflammatory response induced by antibiotic-killed GBS.
415 PREVALENCE AND AGE-RELATED ACQUISITION OF ANTIBODIES AGAINST GROUP A STREPTOCOCCAL M-RELATED PROTEINS
Agbaosi T1,2, Niedermeyer SE1,2, Penfound TA1,2, Dale JB1,2. 1 University of Tennessee Health Science Center, Memphis, TN and 2 Veterans Affairs Medical Center, Memphis, TN.
Purpose of Study: Group A streptococcal (GAS) infections are common in children but less common in adults. Immunity against type-specific M proteins of GAS protects against subsequent infection with the same M type. The relative resistance of adults to infection has been attributed to immunity to multiple M types, among other factors. An additional explanation is immunity to shared, cross-protective GAS antigens that provides broader protection later in life. M-related proteins (Mrp) of GAS are expressed by 83% of GAS isolates and contain opsonic epitopes,. Unlike M proteins, Mrp’s are highly conserved and are grouped into three structurally related families represented by Mrp2, Mrp4, and Mrp49. In the current study we evaluated the prevalence and age-related acquisition of Mrp antibodies in children.
Methods Used: Serum samples from 88 subjects (ages 1-19) were obtained from the clinical laboratories of a pediatric hospital. Purified, recombinant N-terminal peptides of Mrp2, 4, and 49 were used to assess Mrp antibody levels by ELISA.
Summary of Results: Significant levels of antibodies against any of the three Mrp’s were observed in 49/88 serum samples (56%). Mrp4 antibodies were the most prevalent (37/88), followed by Mrp 2 (29/88) and Mrp49 (12/88). 25% of serum samples contained antibodies against one Mrp, 17% against two and 14% against all three. There was a clear association between the subjects’ age and prevalence of antibodies against Mrp’s (r=0.32, p<0.05). Significant age-related trends were also observed with Mrp4 and Mrp2. Additional studies are underway to examine the type-specific M antibody levels in the same cohort to assess the spectrum of GAS infections in relation to age.
Conclusions: Mrp antibodies are prevalent and are acquired in an age-related manner. Taken together with our recent studies showing that N-terminal peptides of Mrp’s contain opsonic epitopes, these results suggest that Mrp antibodies in combination with M antibodies may contribute to the relative resistance to GAS infections later in life. These findings also have implications for the development of broadly protective GAS vaccines.
416 M-RELATED PROTEINS AND M PROTEINS OF GROUP A STREPTOCOCCI EVOKE BACTERICIDAL ANTIBODIES AGAINST GROUP C AND G STREPTOCOCCI
Niedermeyer SE1,2, Penfound TA1,2, Hysmith ND1,2,3, Dale JB1,2. 1 University of Tennessee Health Science Center, Memphis, TN; 2 Veterans Affairs Medical Center, Memphis, TN and 3 St. Jude Children’s Research Hospital, Memphis, TN.
Purpose of Study: Non-group A β-hemolytic streptococcal infections have emerged as prominent causes of invasive disease. In recent studies, the incidence of serious infections involving group C and G streptococci belonging to the species Streptococcus dysgalactiae subspecies equisimilus (SDSE) exceeds that of group A streptococci (GAS). Efforts to develop safe and effective streptococcal vaccines have virtually ignored the significant global burden of disease caused by SDSE. In the current study, we evaluated the bactericidal activity of antisera raised against protective antigens of GAS, M-related proteins (Mrp) and M proteins, against various SDSE emm types.
Methods Used: BLAST analysis was used to identify sequence homologies among GAS and SDSE surface proteins. Rabbit antisera were raised against Mrp and the 30-valent M protein-based vaccine and used in whole-cell ELISA and bactericidal tests with various SDSE representing multiple emm types.
Summary of Results: Significant sequence homologies were identified between some M proteins of SDSE and GAS Mrp’s and M peptides contained in the 30-valent vaccine. Mrp and 30-valent vaccine antisera reacted with multiple emm types of SDSE in whole-cell ELISA. In bactericidal tests, 5/5 SDSE tested to date were opsonized and killed in human blood containing either Mrp or 30-valent vaccine antisera. Studies are in progress to assess the extent of potential cross-protection between GAS vaccine antigens and clinical isolates of SDSE.
Conclusions: The observation that antisera raised against protective antigens of GAS promote bactericidal killing of SDSE suggests that vaccines originally designed to prevent GAS infections could potentially elicit broader immunity against serious invasive streptococcal diseases. These results are consistent with previous observations of lateral exchange of genetic material between GAS and SDSE. Future studies will be designed to test combination vaccines containing GAS antigens to determine the breadth of potential coverage against SDSE.
417 THE INCIDENCE OF HERPES ZOSTER AMONG VETERANS
Moanna A1,2, Rentsch C1, Rimland D1,2. 1 Veterans Affairs Medical Center, Decatur, GA and2 Emory University School of Medicine, Atlanta, GA.
Purpose of Study: The incidence of herpes zoster (HZ) in the U.S. has been estimated to be 1 million cases or more annually with a higher rate in adults older than 60 years of age. The morbidity of the disease including post-herpetic neuralgia imposes significant impacts on quality of life. Previously, we found that the incidence of HZ had increased from 3.10 episodes per 1000 veterans in 2000 to 5.22 in 2007. Here, we present a follow-up study to evaluate the incidence of HZ in veterans after the introduction of the zoster vaccine in late 2007.
Methods Used: To evaluate the continuing trend in the annual incidence of herpes zoster since 2007, we derived incidence rates using the Veterans Health System (VHA) Decision Support System (DSS) reports of HZ by ICD-9 codes and the corresponding denominator data for all veterans in care. The annual rates of HZ were calculated by dividing unique patients with HZ by the total number of veterans seen that year. The same method was used to calculate the rate by age groups. Chi square for trend was calculated for the total and age specific rates over the entire time period. We used data from DSS to present the use of zoster vaccine nationally.
Summary of Results: The total number of veterans seen increased from 5,292,175 in 2007 to 5,919,203 in 2012. The number of zoster episodes increased from 28,529 episodes in 2007 to 39,503 in 2012. Since 2007, the annual incidence of HZ increased from 5.39 per 1000 veterans to 6.67 in 2012 (R2 =0.6510, p=0.0524) .This increasing rate was seen in both men and women for all age groups. There were 114,126 doses of the zoster vaccine administered at the VA between 2007 and 2012. The estimated coverage for veterans 50 years or older was 2.49% and that for veterans 60 or older was 3.14%.
Conclusions: The incidence of HZ continues to increase in our veteran population despite the introduction of the zoster vaccine in 2007. The uptake of this vaccine remains low in the population age 50 and older.
418 ANTIBIOTICS FOR EARLY ONSET SEPSIS PROPHYLAXIS- TIME FOR STEWARDSHIP?
Rampon K1, Gaston K2, Talati AJ1,2. 1 UTHSC, Memphis, TN and 2 The Regional Medical Center, Memphis, TN.
Purpose of Study: Recent advances in prenatal care and maternal prophylaxis for GBS colonization have decreased the incidence of group B streptococcal (GBS) infection and early-onset sepsis (EOS), yet it remains a feared complication of birth. Prophylactic antibiotics (abx) are justified in some situations. Neonates with clinical symptoms of sepsis and/or abnormal laboratory values may be continued on abx beyond the empirical 48-hour mark of sterile cultures. However, antimicrobial therapy in infants without other indications should be promptly discontinued. Various maternal indications have been used in the past to predict risk for the infant of developing EOS. Likewise, clinical symptoms and lab tests of the infant appropriately increase the suspicion of infection. We proposed to evaluate the reasons for starting abx in a neonate immediately after birth and duration/reasons of prolonging abx in event of a sterile blood culture in an asymptomatic infant.
Methods Used: Retrospective chart review of all neonates born during the 4 mths prior to June 2013 was done in a level 3 NICU. Infants with positive blood culture were excluded. Medical records were reviewed after IRB approval and data collected from neonates who were started on abx included demographics, maternal history, duration and type of abx, laboratory values and clinical symptoms.
Summary of Results: 218 infants received abx soon after birth. Mean birth weight was 2666 gm with gest. age 35 wk. Mean duration of abx therapy was 88:52 ±19:57 h. For infants ⩽ 1500gm the mean duration was longer 95±20 h compared to infants >1500 gm 87±20h. Maternal risks included chorioamnionitis (27%), positive GBS status (16.5%), UTI (10%) and PROM (15%). 184/218 (85%) received abx for >48h. Of these 184 infants 110 (59%) had normal lab values. A reason was not documented for continuing abx for 64 (30%) patients. 84(45%) had reason documented as elevated CRP and 24(13%) as maternal chorioamnionitis.
Conclusions: Several asymptomatic infants continue to receive abx beyond 48 h in spite of no obvious reason. A “hardstop” by pharmacy at 48h may prevent unnecessary additional doses of abx. This could save exposure to infants of hundreds of doses of abx/year with significant cost savings. Continuation of abx in face of abnormal lab values in asymptomatic infants should also be re-evaluated.
419 A POPULATION-BASED INVESTIGATION OF OUTCOMES OF CANDIDEMIA
Kabbani S1,2, Stein B1,2, Hollick R4, Harrison LH4, Farley M1,2,3. 1 Emory University School of Medicine, Atlanta, GA; 2 GA Emerging Infections Program (EIP), Atlanta, GA; 3 VA Medical Center, Atlanta, GA and 4 Maryland Active Bacterial Core surveillance (EIP), Baltimore, MD.
Purpose of Study: Describe risk factors associated with mortality from candidemia.
Methods Used: Demographic and clinical data were collected prospectively between 3/1/08 and 2/28/13 for candidemia cases identified through active, population-based, laboratory surveillance in Georgia and Maryland EIP. Univariate analysis of risk factors associated with mortality at 30 days in children and adults was performed; p<0.05 was significant.
Summary of Results: Overall, 3,782 candidemia cases were identified with a mean annual incidence of 14.5/100,000 population. While only 64.9% of cases were hospital-onset (HO), 93.1% had at least one of the following risk factors: use of central venous catheter (CVC) (84.6%), total parenteral nutrition (TPN) (34%), or antibiotics within 14 day (78.8%). Death occurred in 917 (26.4%) adults and 32 (13.8%) children. Fluconazole resistance was found in 7.2% of cases and was not associated with mortality. Among adults, mortality was significantly higher with age ≥45 (OR 2.28 CI 1.82-2.84), HO (OR 1.86, CI 1.57-2.21), antibiotics(OR 1.6, CI 1.31-1.97), CVC (OR 1.46, CI 1.17-1.83), ICU stay (OR 3.85, CI 3.18-4.65), renal disease (OR 1.72, CI 1.43-2.06), liver disease (OR 1.74, CI 1.42-2.13), malignancy (OR 1.43, CI 1.18-1.72), prior antifungal use (OR 1.37, CI 1.11-1.69), and infection with Candida krusei (OR 2.21, CI 1.3-3.76) or C. tropicalis (OR 1.38, CI 1.08-1.75). Black race (OR 0.8, CI 0.69-0.94), TPN administration (OR 0.84, CI 0.72-0.99), CVC removal within 7days (OR 0.25, CI 0.21-0.3), antifungal treatment (OR 0.2 CI 0.16-0.25) and C. parapsilosis (OR 0.54, CI 0.43-0.69) were associated with lower odds of death. In children, death was significantly associated with male gender, CVC, antibiotics, ICU stay, and malignancy; antifungal treatment and CVC removal were associated with lower odds of death.
Conclusions: Candidemia was strongly associated with use of CVCs, TPN, and systemic antibiotics. Mortality from candidemia was higher in older adults, those with underlying diseases or on systemic antibiotics, and infection with C. krusei or C. tropicalis. Multivariable analysis will be conducted to determine independent risk factors for mortality associated with candidemia.
420 PREVALENCE OF STREPTOCOCCAL SKIN INFECTIONS IN AMERICAN SAMOAN CHILDREN WITH RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE
Broge T1, Gorman S1, Marrone J2, Burns JJ1. 1 Florida State University Pediatric Residency Program and Sacred Heart Hospital, Pensacola, FL and 2 Lyndon B. Johnson Tropical Medical Center, Pago Pago, American Samoa.
Purpose of Study: Our study sought to identify a link between cutaneous GAS infections and acute rheumatic fever (ARF) in American Samoa. ARF and rheumatic heart disease (RHD) are considered endemic in the South Pacific, particularly among indigenous populations. RHD is a known sequelae of untreated group A streptococcal (GAS) pharyngitis, however, there is increasing evidence implicating GAS skin infections in the pathogenesis of ARF and RHD in impetigo-endemic populations.
Methods Used: Electronic medical records of 115 American Samoan children with a history of ARF were analyzed retrospectively. Records were analyzed for history of a clinic visit in which the patients were noted to have impetigo or sore throat prior to diagnosis with ARF. The proportion of children with ARF with history of skin infections were compared to the proportion of children with ARF with history of sore throat using McNemar’s test.
Summary of Results: 24.3% of patients were found to have had a clinic visit for sore throat prior to being diagnosed with ARF. 47.8% of patients were noted to have a clinic visit for impetigo prior to being diagnosed with ARF. These were statistically different: McNemar test p value = 0.000.
Conclusions: Our findings suggest that GAS skin infections should be considered in the pathogenesis of ARF. Our data suggests that a history of symptomatic GAS pharyngitis is less common than cutaneous infections in children with ARF. A defined link between GAS skin infections and rheumatic heart disease would have potentially significant implications for the treatment and prevention of this disease in endemic populations.
421 ENGAGEMENT IN HIV PRIMARY CARE, USE OF ANTIRETROVIRAL THERAPY, AND UNPROTECTED SEX AMONG HOSPITALIZED HIV-INFECTED PATIENTS
Chang AG1, Bednarczyk R2, Cardenas G3, Metsch L4, del Rio C1,2. 1 Emory University School of Medicine, Atlanta, GA; 2 Emory University Rollins School of Public Health, Atlanta, GA; 3 University of Miami Miller School of Medicine, Miami, FL and 4 Columbia University Mailman School of Public Health, New York, NY.
Purpose of Study: HIV-infected drug users are less likely to be engaged in HIV primary care and be on antiretroviral therapy (ART). They are also more likely to have high-risk sexual behaviors. We examined factors associated with engagement in care, use of ART, and unprotected sex among hospitalized HIV-infected patients in two inner-city hospitals.
Methods Used: We performed cross-sectional analysis on screening interviews from Project HOPE, a randomized controlled trial testing a behavioral intervention among hospitalized HIV-infected crack cocaine users in Atlanta, GA and Miami, FL. We used bivariate analyses and multivariate logistic regression models to identify factors associated with currently or previously having an HIV care provider, currently taking ART, and having unprotected sex with an HIV-negative or status unknown partner.
Summary of Results: Among 3,121 HIV-infected screener interviews, 75% reported having ever used drugs, and 58% of them reported using non-injection drugs in last 6 months and/or injection drugs in the last 12 months. Currently having an HIV care provider and being on ART were associated with older age, higher income, stable housing, lack of recent incarceration, absence of alcohol and recent drug use, and having been in substance abuse treatment. Having unprotected sex with an HIV-negative or status unknown partner was associated with female gender, recent crack cocaine use, and recent diagnosis of a STI. Among recent crack cocaine users, having ever been in substance abuse treatment was associated with currently having an HIV care provider (AOR 3.03, CI 1.80-5.09), currently taking ART (AOR 2.18, CI 1.31-3.64), but also with having unprotected sex with an HIV-negative or status unknown partner (AOR 1.83, CI 1.01-3.31) after adjusting for gender, age, income, education, housing, and incarceration.
Conclusions: These data suggest that substance abuse treatment is important for engagement in HIV care and use of ART but does not appear to decrease high-risk sexual behavior among HIV-positive drug users.
422 IS AZITHROMYCIN MODULATING INFLAMMATION VIA TOLL LIKE RECEPTOR (TLR) PATHWAYS IN GROUP B STREPTOCOCCUS (GBS) SEPSIS ?
Upadhyay K1, Meals E1, English B2, Talati AJ1. 1 CFRI, UTHSC, Memphis, TN and 2 Michigan State University, Grand Rapids, MI.
Purpose of Study: Combination of ampicillin(AMP) and azithromycin(AZM) improved clinical signs, mortality and cytokine levels in our mouse model of GBS sepsis. We proposed to study if the effect of AZM in modulation of inflammation is secondary to bacterial factors[using AZM resistant strain(AZR) of GBS] or host factors[using MyD88-/-, TLR9-/-, TLR2-/-mice].
Methods Used: Swiss Webster mice (wt 18g, age 3 wks) were injected intraperitoneally (IP) with AZR GBS Ia (log 7-8 cfu/ml) and MyD88-/-, TLR9-/- mice (wt 15 gm, age 3 wks) were injected with GBS Ia (log6 cfu/ml). Mice were divided in 4 groups(grp). Grp 1 -no antibiotics, grp 2- treated with AMP(100mg/kg/d; MIC ⩽0.25 mcg/ml), grp 3- treated with AZM (10 or 50mg/kg/d; MIC 16ug/ml for AZR GBS and MIC ⩽0.125ug/ml for AZM sensitive strain ) and grp 4- treated with AMP+AZM. Antibiotics were administered q24h IP. Mice were monitored using “clinical sepsis score (CSS)”. Mice were sacrificed at 120h and blood was obtained for later cytokine assay.
Summary of Results: For AZR GBS experiment; case fatality rate was found to be 100% in grp 1 and grp 3; 50% in grp 2 and 0% in grp 4. Mean serum TNF-α was lower in grp IV(246±67 pg/ml) compared to grp 1 (6952±701 pg/ml), grp 2 (7209±1826 pg/ml) and grp 3 (5980±626 pg/ml) (p⩽0.05) The CSS was significantly lower in grp 4 compared to other grps (fig). Also the case fatality rate was 100% in grp 1; 50% in grp 2 and 0% in grp 3 and 4 using MyD88-/- mice. However, no difference was seen in mortality among TLR9-/- mice. Similarly, the CSS was significantly lower in grp 3 and grp 4 compared to grp 1 and grp 2 in MyD88-/- mice but no significant difference was seen in TLR9-/- mice.
Conclusions: The effect of AZM in modulation of inflammation may be related to TLR9 and is seen even in mice infected with AZR GBS.
Medical Education, Medical Ethics, and Advocacy Concurrent Session
2:00 PM
Friday, February 21, 2014
423 INTEGRATED HANDS-ON COOKING AND CLINICAL NUTRITION CURRICULUM IMPROVES PEDIATRIC RESIDENTS’ COMPETENCIES AND ATTITUDES TOWARD NUTRITION EDUCATION FOR PATIENTS
Urday P, Monlezun DJ, Harlan T. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Recent studies demonstrate how multiple competing education objectives within residency programs and medical schools often complicate sufficient training in nutrition education as a hallmark of preventative medicine competencies. As a response, Tulane University School of Medicine created The Goldring Center for Culinary Medicine. We sought to adopt this curriculum, originally designed for medical students, for pediatric residents.
Methods Used: The Goldring Center for Culinary Medicine launched the first two modules in its seven-module series spanning a 21-hour multidisciplinary curriculum over 3 years with integrated nutrition education and hands-on cooking classes, guided by a professional chef and physician. Residents’ survey responses (n=28) after the first year of curriculum participation including the first two modules were compared to baseline responses prior to the first module. Mean scores for competencies and attitudes according to dietary habits were analyzed using chi-square tests and non-parametric McNemar’s tests, followed by logistic regression models.
Summary of Results: Compared to responses prior to curriculum participation, more residents reported strong agreement that nutritional education should be routine patient care (41.4% vs. 36.7%) and that physicians can influence patients’ dietary habits (41.4% vs. 37.5%). Fewer residents reported less than suboptimal competencies in patient education on the health effects of a low fat diet (82.1% vs. 93.9%) and assessing total calories and saturated fat by food labels (57.1% vs. 63.3%) after their first two modules. With adequate personal daily intake of vegetables such as carrots and squash, they were 85% less likely (versus 76% pre-curriculum) to report deficits in daily hydration education for patients (OR=0.15, CI 0.0254-0.9517, p=0.044).
Conclusions: Our first year results indicate that The Goldring Center for Culinary Medicine’s integrated nutrition curriculum can improve resident competencies and attitudes in providing patients nutrition education. Ongoing monitoring is underway to determine the longitudinal impact of the curriculum on residents.
424 COMPARISON OF LGBT CULTURAL SENSITIVITY TEACHING METHODS USING THE VIRTUAL REALITY WORLD OF SECOND LIFE VERSUS A TRADITIONAL WORKSHOP FORMAT
Jones VF1, Rowland ML2, Brueckner-Collins J3, Mack A3, Gault S3, Richardson A4, Hazard M5. 1 University of Louisville, Louisville, KY; 2 University of Louisville, Louisville, KY; 3 University of Louisville, Louisville, KY; 4 University of Kentucky, Lexington, KY and 5 University of Kentucky, Lexington, KY.
Purpose of Study: The researchers sought to determine if the use of technology in the form of the virtual world of Second Life (SL) enhanced learners’ perceptions of knowledge and attitudes of Lesbian, Gay, Bisexual and Transgender (LGBT) healthcare issues.
Methods Used: Sixty-five health professional students attended a one hour presentation designed to provide fundamental knowledge and skills in working with LGBT youths. These students were randomly allocated to receive either a traditional workshop or a workshop using a standardized patient encounter in the virtual world of SL. A post-workshop survey gauged students’ interest in and satisfaction with the traditional versus SL workshop formats.
Summary of Results: The SL group’s clinical scenarios were ranked as the most effective component of that workshop, whereas the traditional control group rated their paper-based scenarios as the third most effective component. The SL group felt more strongly that the session enhanced knowledge of LGBTQ identities and community (rating of 1.9/5, with 1 as excellent and 5 as poor) than control (2.1/5). The SL group (1.6) was more convinced than control (2.2) that the session increased their awareness of disparate health problems within this population. Not only did Second Life enhance students’ self-perceived knowledge of barriers to healthcare specific to this population (1.67), as compared to control (1.9), but it also increased their perceived sensitivity and compassion for LGBTQ patients (1.3), as compared to control (1.9).
Conclusions: This study provided preliminary evidence that use of virtual world technology enhances student interest in and satisfaction with LGBT instructional programming.
425 PRE-CLINICAL MEDICAL SCHOOL ELECTIVE TEACHING END-OF-LIFE COMPETENCIES IMPROVES STUDENT PREPAREDNESS IN CLINICAL ROTATIONS
Schwab Keeport ML, Cruz B. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Medical education in the U.S. inadequately addresses end-of-life (EOL) and palliative care (1). We previously reported that a pre-clinical elective increased students’ self-perception of readiness to discuss EOL-related issues at the end of the class (2). This study aims to determine if their preparedness to address these topics persists beyond completion of the course and following a year of clinical education.
Methods Used: We designed an elective taken by twenty-five first-year medical students for ten total course hours. We have implemented it for three consecutive years starting with the Class of 2014, in their MS-1 year. This cohort has now completed its first and main clinical year of medical school. A survey assessing self-perception of EOL competencies was administered to students in the class of 2014. Results from those who completed the elective were compared with control students who had routine pre-clinical medical education. Survey data was collected using online survey instruments and analyzed using chi-square tests via SPSS statistical software.
Summary of Results: Medical students who completed the elective in their MS-1 year said they felt more prepared to speak to patients and/or patient families about EOL issues than their counterparts when assessed shortly after completion of the course (78% of elective students responding “Prepared” compared to only 32% of controls; p < 0.001). These responses persisted two years later into the clinical training years, where 70% of MS-3 students who had taken the elective responded “Prepared” compared to only 36% of students who had not taken the elective(p < 0.05).
Conclusions: The increased comfort and ability to speak about EOL-related issues to patients and their families that students achieved following their participation in the MS-1 elective has persisted into their clinical years. This student-initiated elective exemplifies the usefulness and impact of teaching EOL core competencies early in the pre-clinical curriculum.
(1) Hesselink, B. et al. (2010). Education on end-of-life care in the medical curriculum: Students’ opinions and knowledge. Journal of Palliative Medicine, 13(4), 381-387.
(2) Azevedo BM, Keeport MS, Anwar DM. “Teaching End of Life Care to 1st Year Medical Students,” AAHPM Poster March 2013.
426 A NOVEL TEACHING MECHANISM IN NEPHROLOGY OF THE DANGERS OF HYPOCALCEMIA IN CHRONIC RENAL FAILURE
Sims N1,2, Dietiker K1,2, Feig D1, White M1,2, Peterson D2, Parks D2, Youngblood A2, Zinkan L2, Tofil N1,2. 1 UAB, Birmingham, AL and 2 COA, Birmingham, AL.
Purpose of Study: To standardize exposure and enhance learning.
Methods Used: We designed a simulation case to illustrate the interaction of NaHCO3 and iCa levels in a hyperkalemic patient. Monthly simulations were conducted with residents on the renal rotation. Residents completed a pre and post test. Scenario: 6 y/o with FSGS presents with vomiting, HA, and abdominal pain. HR 92, BP 192/135, RR 26, O2 95% on RA. Physical exam shows edema. Significant labs: Na130, K5.9 without hemolysis, HCO3 15, BUN 83, Cr 3.5, Ca 5.5, Phos 7.8, Alb 2.1. VBG: 7.23/35/45/15. iCa 0.8. Peaked T waves on EKG.
Summary of Results: Twenty-one residents participated in the simulation. Mean percentage of correct responses increased from pretest (66% +/− 24%) to posttest (97% +/− 7%), p <0.0001.Comparisons between pretest performance and year in residency did not demonstrate a significant difference (62% +/− 22% vs. 70% +/− 26%, p=0.4). Comparison between pretest performance and number of times on nephrology service also failed to reveal a significant difference (64% +/− 24% vs. 70% +/− 24%, p=0.5).
Conclusions: Administration of NaHCO3 and removal of hydrogen ions from albumin causes calcium to rapidly bind to albumin resulting in abrupt hypocalcemia leading to cardiac arrest. Residents are unaware of this physiologic mechanism regardless of year in residency or number of times on the renal service. 40% of teams who were aware that NaHCO3 should not be given to hypocalcemic patients gave NaHCO3 during the simulation indicating they did not understand why NaHCO3 was dangerous. This simulation taught the physiologic interaction between NaHCO3 administration and hypocalcemia.
427 DIFFICULT PEDIATRIC AIRWAY SIMULATION MODEL DEVELOPMENT FOR STUDY EXAMINING EFFICACY OF VIDEOLARYNGOSCOPY
Burhop J, Poirier MP, Clingenpeel J. Eastern Virginia Medical Center, Children’s Hospital of the King’s Daughters, Norfolk, VA.
Case Report: It has been established that the videolaryngoscope is a valuable tool in securing the successful tracheal intubation of difficult airways in adult patients. However, there is minimal available evidence to gauge its efficacy within the infant, child and adolescent populations with anatomically difficult airways. Furthermore, the literature is virtually devoid of simulation studies in individuals with specific syndromes such as trisomy 21. The purpose of our study is two-fold; first to develop an anatomically challenging model followed by comparison of video vs. direct laryngoscopic techniques to secure a tracheal intubation. Additionally our study looks to enhance safety and improve patient outcome through simulation of difficult pediatric airway scenarios with an emphasis on laryngoscopic technology, curriculum development and education.Anthropometric data regarding anatomical features and measurements of children with trisomy 21 was employed during the model modification process. The starting point was a standard newborn airway model. Macroglossia was achieved with tongue modification and decreased oral cavity size. The mentum was retracted, along with atlantoaxial instability through neck rivet alterations. Vocal cord anatomy was retained to provide the intubation participant with a standard point of completion for securing the tracheal airway. The second phase of our project involves putting the airway to test with direct and videolaryngoscopic intubating techniques and is currently underway.
428 SHOULD PHYSICIANS TREAT THEIR RELATIVES OR THEMSELVES? DeChant RD, Goebel LJ, Mufson MA. Marshall University Joan C. Edwards School of Medicine, Huntington, WV
DeChant R, Goebel L, Mufson M, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV.
Purpose of Study: We hypothesized that some physicians treat their relatives for minor illnesses even though this practice is discouraged. The AMA agrees that treatment of relatives has the potential for compromised objectivity, incomplete evaluation and interpersonal problems in the face of bad outcomes. To assess this issue at our university-based practice we conducted a survey of faculty and resident physicians regarding their attitudes and practices of treating relatives and themselves.
Methods Used: We surveyed physicians who attended one Grand Rounds in Internal Medicine, Family Practice, OB/GYN or Pediatrics during the summer of 2013. Data was entered into an Excel spreadsheet for analysis and statistical tests applied as appropriate using the website Vassarstats.
Summary of Results: he study group comprised 30 faculty physicians and 51 residents and fellows. The response rate was 93%. Sixty-nine percent of respondents were men, and the overall median age of respondents was 30-39 years old and the median age of faculty was older, 50-59 years. One-half of physicians felt it was “okay” to treat relatives at least sometimes. Women physicians less often than men physicians agreed that they should treat their relatives (p=0.004). Seventy-five percent of respondents had treated a relative for a minor illness, while 6% had treated a relative for a serious illness (p<0.0001). Over one-third prescribed medications for family members without examining them. More than one-half treated themselves for minor illnesses, with 21% prescribing their own medications. Two-thirds of respondents had a primary care physician; significantly more women than men had a primary care physician (88% vs 56%, p=0.01).
Conclusions: Our faculty and residents treated relatives and themselves often. Respondents to our survey often treated their relatives without an examination, risking all the pitfalls this lack of care incurs. Although many physicians in our study had their own physicians, they treated themselves, which was contrary to their best interest. More education is needed to discourage physicians from treating relatives and themselves, as optimal care derives from your own impartial physician.
429 AN INVESTIGATION OF THE STATISTICAL METHODS USED IN THE CURRENT MEDICAL LITERATURE
Narayanan R1, Nugent R2, Nugent K1. 1 Texas Tech University Health Science Center, Lubbock, TX and 2 Carnegie Mellon University, Pittsburgh, PA.
Purpose of Study: Current ACGME guidelines require internal medicine residents to develop skills in the interpretation of medical literature and to understand principles of research. The statistical foundation and education necessary to understand the current medical literature are uncertain.
Methods Used: We reviewed the statistical methods and terms used in 49 articles discussed at our Internal Medicine Journal Club between 1/1/2013 and 6/30/2013. We collected information on study type and on the statistical methods used for summarizing and comparing samples, determining the relationships between independent variables and dependent variables, and estimating models.
Summary of Results: Fourteen articles came from JAMA-IM, 11 from the NEJM, 6 from The Annals of IM, 5 from JAMA, and 13 from other journals. Twenty reported randomized controlled trials. Summary statistics included mean values (39 articles), category counts (38), and medians (28). Group comparisons were based on t-tests (14 articles), χ2 tests (21), and nonparametric ranking tests (10). The relationships between dependent and independent variables were analyzed with simple regression (6 articles), multivariate regression (11), and logistic regression (8). Fourteen studies used sensitivity analysis. Nine studies reported odds ratios with 95% confidence intervals, and seven analyzed test performance using sensitivity and specificity calculations. These papers used 128 statistical terms and context-defined concepts, including some from epidemiology-biostatistics (31), data collection (12), data analysis (56), modeling (24), and meta-analysis (5). Based on usual undergraduate and graduate statistics curricula, 64.8% of the concepts and methods used in these papers required at least a master’s level statistics education. Ten software programs were used in these articles.
Conclusions: The interpretation of the current medical literature requires a significant background in statistical methods, and the methods used exceed the education provided to students and residents. Given the complexity of medical education, these deficiencies will be hard to fix, but this project provides the basis for a curriculum in study design and statistical methods needed by physicians.
430 INTERNAL MEDICINE RESIDENT CASE REPORT PUBLICATIONS AND RELATED CITATIONS
Argueta E1, Nugent K2, Buscemi D1. 1 Texas Tech University HSC, Lubbock, TX and 2 Texas Tech University HSC, Lubbock, TX.
Purpose of Study: Current guidelines require internal medicine residents to participate in scholarly activity. Case report publications often provide residents entry into the medical literature. However, journals limit the number of case reports, in part, because the citation frequency is low, and this reduces journal impact factors. We tried to determine if this was a valid concern by reviewing publications by our residents.
Methods Used: We searched for all case report publications by internal medicine residents from Texas Tech HSC in Lubbock from 2008 through 2013. We determined the journal impact factor using Journal Citations Reports. We then identified all citations of articles published through 2014 using Google Scholar and Scopus and the impact factors of the citing journal. We also collected information on resident attitudes about case report publications using an anonymous questionnaire.
Summary of Results: This study involved 61 residents who published 56 case reports/letters. Thirty-nine journals (69.6%) had impact factors; the median was 1.87 with an interquartile range (25%-75%) of 1.32-4.38. Twenty-five articles had 86 citations. The types of articles citing the case reports included 36 case reports (41.8%), 24 review articles (27.9%), 10 letters (11.6%), 9 clinical series (10.5%), 3 research studies (3.5%), 2 book chapters (2.3%), 1 image (1.2%), and 1 editorial (1.2%). Fifty citing journals had impact factors; the median was 1.97 with an interquartile range of 1.29-3.90. There was no difference in impact factors between the publishing journals and the citing journals based on a ranking test (P= 0.40). Thirty-one residents responded to a questionnaire on case reports. Twenty-five (80.6%) thought that the skills involved in writing a case report would improve their core competencies. Six residents thought completing a case report should be a mandatory requirement, 17 were neutral, and 9 disagreed/strongly disagreed.
Conclusions: Many residents can successfully publish case reports, and these reports are frequently cited. Case reports provide the basis for clinical reviews for uncommon medical problems and can stimulate clinical studies. Residents provide a critical work force for this activity; journals do benefit through citations and increases in impact factors.
431 PHYSICIAN SPECIALISTS AND THE NRMP MATCHES
Ruiz MA. Louisiana State University Health Sciences Center, New Orleans, LA.
Case Report: Introduction The need for physician specialists is rising faster than the modest increases in production. Supply is not keeping pace with demand, a situation already recognized in primary care. The same situation applies to medical subespecialities.
Methods Used: This study uses data obtained from the 2010-12 GME Census of the AAMC and AMA. To illustrate the changing dynamics of the growth of US medical schools on the access to GME positions, we conducted a trend analysis of the data using SPSS.
Results: The results show a modest, steady increase of both medical students and GME. The total medical school increase (‘04-‘11) is about 1005 per year on average (1.5%/year). The total GME positions increase in the same period is 1583 per year on average (1.7%/year). The match gap between PGY-1 positions and the medical school senior class size is approximately 6000 to 8000 per year for IMGs and others. The number of fellows matched in the U.S. in 2012 is 6138 of 6799, about 90%2 filled. There is a relatively brief “scramble” for the unfilled slots, and most are utilized each year. Most of these positions are in Internal Medicine and Pediatric specialties; there are a number of others in specialty training that do not use the fellowship title or recognition.
Discussion: Thus, while increased numbers of at least some specialty GME programs are underway and will help keep up with demand, further expansion is essentially prohibited by a congressional act in 1997. The supply therefore has been “plateaued”. As reform is implemented, ever more patients will need physicians, not only in primary care assuredly, but also a variety of specialists.
Conclusions: While the results show that the number of medical students are increasing, these trends indicate that an increase in GME positions is required to accommodate the expanding medical school class size. For example in 2004, there were 1.53 PGY-1 positions per active US Senior compared to 1.45 positions in 2012. The current unfilled positions after the annual NRMP match are mostly in primary care. Since the physician shortage is and will be both in specialty and primary care, more GME positions will be necessary.
432 THE CONTEXT OF ADOLESCENT HOPE
Bennett A1, Wood DL1,2, Goldhagen J1, Butterfield RC2, Kraemer D2. 1 University of Florida-Jacksonville, Jacksonville, FL and 2 UF Health at Jacksonville, Jacksonville, FL.
Purpose of Study: Hope, reflected in one’s beliefs about the future, motivates goal-directed behavior and facilitates positive youth development. Adolescents’ future expectations of life expectancy and educational attainment predict risk-taking behaviors, educational achievements, and health outcomes. Previous studies have used these proxy measurements of hope to characterize high-risk youth and their hopeless environments. The objective of this study was to use a human capital investment framework to investigate the individual and contextual assets of hopeful adolescents.
Methods Used: The public-use data (n=6,504) from Wave I of the National Longitudinal Study of Adolescent Health was used for this analysis. Adolescents made predictions about their chances of living to age 35 and attending college. Their predictions were assigned a numerical value and summed to create a Hope Scale from 1-10. Those who were “almost certain” of both were considered to have high hope. Multivariable logistic regression compared the most hopeful, or those with a score of 10 on the Hope Scale, to all others and identified variables that were significantly associated with higher hope. The odds ratios for the unique contributions of each independent variable was determined by controlling for all other variables.
Summary of Results: Statistically significant (p<0.0001) relationships were found between the highest sense of hope and social capital (family, neighborhood, school, and general connectedness), financial capital (household income and neighborhood poverty concentration), educational capital (parent education), and environmental capital (connectedness scales, breastfeeding, gender). Hope had stronger associations with social and educational capital measurements than with financial capital measurements. Race and family structure failed to remain significant when controlling for the other variables.
Conclusions: Hope, as a form of personal capital serves as a priceless asset in the face of adversity. Identifying the human capital assets that serve as major determinants of health is crucial in order to guide the design of policy and social interventions to optimize child health and well-being.
Neurology and Neurobiology Concurrent Session
2:00 PM
Friday, February 21, 2014
433 SHAKE AND BAKE
Yu M1, Tadin D1, Engel LS1, Lopez FA1, Conrad EJ2. 1 LSU Health Sciences Center, New Orleans, LA and 2 LSU Health Sciences Center, New Orleans, LA.
Case Report: Neuroleptic malignant syndrome (NMS) was first described by the symptoms of pallor, hyperthermia, and respiratory and psychomotor abnormalities in association with haloperidol.
Case: A 48-year-old male mental health resident with a history of schizoaffective disorder was noted by facility staff to have a stooped posture, a mild temperature elevation and abdominal rigidity on exam. The patient was given two doses of benztropine prior to transfer to our hospital. His mediations included clonazepam, divalproex sodium, olanzapine, and risperidone. At the time of admission his rectal temperature was 103.1οF, heart rate 108 beats/min, blood pressure 134/99, respiratory rate 43, and oxygen saturation 100% on room air. He appeared distressed and tremulous. He was alert and oriented to person, place, and time but required frequent re-direction. He was tachypneic with decreased breath sounds at the bases but without crackles or wheezes. Bowel sounds were absent and his abdominal muscles were visibly contracting. He had increased muscle tone and was hyperreflexic throughout. His laboratory findings revealed a white blood cell count of 10,800/ul with bandemia of 19% and mild thrombocytopenia of 112,000/ul. He had rhabdomyolysis with creatinine kinase level of 103,275 u/l causing acute kidney injury and myoglobinuria. He also had transaminitis (AST 1660 u/l and ALT 356u/l). All of his medications were stopped. Cooling blankets, fans, and ice packs were used for his hyperthermia. He was given aggressive IV fluid repletion, placed on bromocriptine, valium as needed for agitation, and given one dose of dantrolene. Per psychiatry, he was restarted on his home dose of divalproex sodium. His muscle rigidity improved.
Discussion: NMS is classically associated with high potency first generation antipsychotics. However newer atypical agents, as well as other classes of anti-dopaminergic drugs are recognized causes. As soon as NMS is suspected, the offending agent must be discontinued. Respiratory and circulatory systems should be monitored closely while intravenous fluids and treatment of fever are undertaken. Treatment consists of conservative therapy, benzodiapines, dantrolene, and dopamine agonists, with electroconvulsive therapy used for refractory cases.
434 DILATED CARDIOMYOPATHY SECONDARY TO MITOCHONDRIAL ENCEPHALOPATHY WITH LACTIC ACIDOSIS AND STROKE-LIKE EPISODES
Graebert A, Engel LS, Lo B. LSU Health Sciences Center, New Orleans, LA.
Case Report: Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes (MELAS) is a maternally inherited mitochondrial syndrome typically diagnosed in childhood or early teenage years. The stroke-like episodes typically present in a relapsing-remitting manner with gradual neurological decline leading to dementia.
Case: A 32 year old African American male with a diagnosis of MELAS, confirmed by muscle biopsy 8 years prior, presented with a 2 month history of shortness of breath, dyspnea on exertion, and lower extremity edema. The patient was afebrile with a blood pressure of 108/90, heart rate of 103, respiratory rate of 20, and a room air oxygen saturation of 100%. Cardiac exam revealed a III/VI holosystolic murmur heard best at the apex and an S3. Lung exam was unremarkable. He had bilateral lower extremity pitting edema extending to his hips. Laboratory studies showed a WBC count of 5.7 K/uL with 71% neutrophils. His complete metabolic profile revealed a HCO3 18 mmol/L, BUN 38 mg/dL, creatinine 1.67 mg/dL, bilirubin 3 mg/dL, AST 92 U/L, ALP 213 U/L, and ALT 100 U/L. BNP was greatly elevated at >5000 pg/mL. Initial troponin was elevated at 0.14 ng/mL and peaked at 0.17 ng/mL. Lactic acid was also elevated at 3.9 mmol/L. Urinalysis did not contain any protein. Urine electrolytes revealed a fractional excretion of sodium of 6.7%; no urine eosinophils were present. EKG demonstrted normal sinus rhythm with evidence of left atrial enlargement, and chest x-ray revealed mildly increased pulmonary vasculature. The patient was found to have 4 chamber enlargement, moderate to severe tricuspid regurgitation, and an ejection fraction < 20% by echocardiogram. Diuresis with IV furosemide provided improvement in his respiratory status and edema; however, he continued to be oxygen dependent at the time of discharge.
Discussion: MELAS is a rare mitochondrial disorder that not only affects the nervous system, but can also have cardiac, renal, and endocrine manifestations, as were seen in this patient with a dilated cardiomyopathy, renal insufficiency, and diabetes mellitus. A hypertrophic cardiomyopathy is more commonly associated with MELAS, but a dilated cardiomyopathy has also been described.
435 ISCHEMIC BRAIN INJURY SECONDARY TO SEVERE SYSTEMIC LOXOSCELISM
Soape M, Swaminath D, Whealy M, Desai V, Nugent K. Texas Tech University Health Sciences Center, Lubbock, TX.
Case Report: Rhabdomyolysis (RM), acute renal failure (ARF), and disseminated intravascular coagulation (DIC) have been frequently associated with systemic loxoscelism. The case presented herein demonstrates these findings plus bilateral globus pallidus lesions.
A 47 year old man was found unresponsive in a hotel and intubated at the scene. His labs showed RM (CK 57,125 IU/L), ARF (BUN 37 mg/dL; Cr 4.1 mg/dL), hepatitis (ALT 5,721; AST 12,831) and coagulopathy (PT 20.9; INR 2.02; PTT 35.5). He also had a high LDH (5,372) and developed a mild anemia which would be consistent with hemolysis. A necrotic lesion formed on his head with a raised edge and surrounding erythema. A dermatology consult concluded the lesion was most likely secondary to a spider bite. After successful extubation, he had weakness of his right upper extremity. A MRI demonstrated ischemia in the bilateral globus pallidi. His labs and symptoms improved over his remaining hospital stay with supportive care. He was discharged home on day 12 of hospitalization.
Systemic loxoscelism is a rare complication of the bite from the spider Loxoceles recluse or Brown Recluse. Diagnosed clinically, the lesion was consistent with a brown recluse bite, endemic to the area of the incident. With only speculation linking the lesion to a bite, a literature review found only 2 confirmed bites. Understanding this diagnosis is one of exclusion, a differential diagnoses was evaluated. Causes for RM such as illicit drug and statin use were disproved with a negative urine drug screen and statin therapy only started a few days prior to the event. DIC was investigated, but blood cultures taken on admission showed no growth. This case also demonstrates CNS injury likely due to loxosceles envenomization. The injury could be secondary to hypoxia; however, the CNS involvement would be more diffuse. It is possible the event was secondary to thrombosis formation and DIC. A likely mechanism is a microvascular thrombosis induced by the loxosceles venom sphingomyelinase D (SD). Also, it has been shown that loxosceles venom has cytotoxic effects on the endothelial cells. This case gives a unique presentation of brain involvement due to possible, but well documented, pathological processes.
436 SEVERE HEADACHE AFTER A PAIN INJECTION IN THE BACK - PNEUMOCEPHALUS AFTER EPIDURAL STEROID INJECTION
Panikkath R, Aly M, Umezurike IC, Nugent K, Panikkath D. Texas Tech University Health Sciences Center, Lubbock, Lubbock, TX.
Case Report: Introduction: Epidural steroid injections are commonly performed for pain relief. However, they can uncommonly cause significant complications, such as pneumocephalus.
Methods: This is a case analysis and review of literature.
Results: A 78-year-old woman with chronic back pain, arthritis, and chronic kidney disease was scheduled for an epidural steroid injection for severe back pain. She received a steroid injection in her lower back and another one in her neck from a pain specialist. However, as soon as she sat up after the procedure, she developed excruciating headache. The headache was bi-frontal, throbbing, 8/10 in intensity and was associated with vomiting. She noted slight relief with lying down. There were no neurological deficits. A CT scan of her head showed a rounded shaped hypodensities in her both lateral ventricles consistent with free air. She was admitted to the hospital, and neurosurgery was consulted. They advised conservative management and assumption of supine position for 48 hours. She was treated with narcotics due to the intensity of the headache. Her headache gradually resolved in 2 days. A CT head performed after 2 days showed significant reduction in the amount of air in the lateral ventricles. She was discharged home with advice to report to the emergency room in the event of clinical deterioration. She did not have any events on follow up.
Conclusion: Pneumocephalus, although is a very rare complication after epidural steroid injection, can manifest as severe excruciating headache. In contrast to the post dural puncture headache, this manifests immediately and becomes aggravated by motion with little relief on supine position. Accidental puncture of the dura with introduction of air into the subdural space during epidural injection is believed to be the reason for this complication. The mechanical effect of the air in the ventricle is believed to be the reason for the headache. As little as 2ml of air can result in headache. Pneumocephalus can often be managed with conservative management.
437 CARDIOVASCULAR RISK FACTORS PREDICT THE SPATIAL DISTRIBUTION OF BRAIN WHITE MATTER HYPERINTENSITIES
Banerjee S, King K, McColl R, Peshock R. * UT Southwestern Medical Center, Dallas, TX.
Purpose of Study: Increased volume of white matter hyperintensities (WMH) are associated with cardiovascular risk factors; however, WMH are also prevalent with normal aging. Recent studies have suggested that some brain regions are more strongly associated with specific risk factors. The purpose of this study was to create a map of every individual brain voxel that was significantly associated with a risk factor (hypertension, diabetes, hypercholesterolemia) as compared to the control population. Furthermore, the study aims to create a predictive model to diagnose and prognosticate brain injury secondary to these risk factors, based on a patient’s WMH distribution.
Methods Used: The 2066 study participants were sampled from the Dallas Heart Study, a population based study. The participants’ WMH distributions were generated from their MRIs using an automated algorithm developed by Hulsey et al. (2012). For each risk factor, the subjects were divided into a case group and a control group. Every voxel of WMH was compared between the two groups using a two tailed nonparametric permutation test.
For each risk factor, an algorithm was created that calculated the Bayesian odds ratio of having risk factor associated damage at each voxel. For every patient, the average Bayesian odds ratio was determined and this odds ratio approximates the likelihood of having risk factor associated damage given a patient’s WMH distribution.
Summary of Results: Of the total of 431891 voxels that comprise the distribution of WMH over the entire population, 64998 voxels (15%) were significantly more prevalent in hypertensives compared to the controls. Similarly, 59592 voxels (14%) were more prevalent in diabetics, and 34201 voxels (8%) were more prevalent in participants with hypercholesterolemia.
Conclusions: For hypertension, diabetes, and hypercholesterolemia, certain voxels were significantly associated with a risk factor, and maps of these voxels were created. Knowing the WMH distribution significantly associated with each risk factor will improve the specificity for evaluating patients for risk factor associated white matter injury. Additionally, a Bayesian predictive model was developed for each risk factor that assigns an odds ratio which evaluates an individual patient’s probability of having risk factor associated injury.
438 CEREBRALVASCULAR CYTOPROTECTIVE EFFECTS OF HEAD COOLING DURING SEIZURES IN NEWBORN PIGLETS: ROLE OF HEME OXYGENASE PATHWAY
Harsono M1, Parfenova H2, Leffler CW2,1, Pourcyrous M1,2. 1 University of Tennessee HSC, Memphis, TN and 2 University of Tennessee HSC, Memphis, TN.
Purpose of Study: Cerebral vascular function is damaged in postictal period. Activation of Heme Oxygenase (HO) pathway during seizures protects postictal cerebral vascular function. Selective head cooling in neonatal hypoxic ischemic encephalopathy has promising neuro cytoprotective effects. However the role of HO pathway during head cooling is unclear. We hypothesized that cerebral vascular cytoprotective effects of head cooling in epileptic seizures are via HO pathway.
Methods Used: Cerebrovascular reactivity (CVR) was tested in: 1) Intact control (no seizures, no head cooling, no SnPP/CrMP); 2) Normothermic seizures (only seizures induction); 3) Head cooling (only head cooling); 4) Head cooling-Seizures (no SnPP/CrMP); 5) SnPP-Seizures (no head cooling); 6) SnPP-Head cooling-Seizures; and 7) CrMP-Head cooling-Seizures. Newborn piglets were anesthetized with ketamine+xylazine. Intubated, ventilated and paralyzed with pancuronium bromide. Bicuculline was used for seizures induction. Tin protoporphyrin (SnPP) or chromium mesoporphyrin (CrMP) were used to block HO activity. In head cooling groups, ice pads were placed around the head 30 mins prior to seizures induction and kept during seizures. When fully conscious, piglets were extubated and placed at animal care facility. 48h later, CVR to physiologically relevant vasodilators was tested using closed cranial window methodology. CVR was tested using endothelium-dependent (bradykinin; hemin), astrocyte-dependent (glutamate) and smooth-muscle-dependent (sodium nitroprusside; isoproterenol) vasodilators.
Summary of Results: In normothermic seizures group (37-38C), postictal CVR to endothelium- and astrocyte-dependent vasodilators were reduced compared to intact control group. In head cooling seizures group (34-35C), postictal CVR to endothelium- and astrocyte-dependent vasodilators were completely preserved. HO inhibitors, SnPP or CrMP, attenuated or blocked protective effects of head cooling on postictal CVR to endothelium- and astrocyte-dependent vasodilators.
Conclusions: Selective head cooling during seizures has protective effects on postictal endothelium-dependent cerebral blood flow regulation. HO pathway is involved in cerebral vasoprotection of head cooling during seizures.
439 ISCHEMIC STROKE FOLLOWING SPONTANEOUS INTERNAL CAROTID DISSECTION IN A YOUNG PATIENT WITH HISTORY OF MIGRAINES
Rivas AM, Sotello D, Copeland S, Orellana-Barrios M, Suarez J. Texas Tech University Health Science Center, Lubbock, TX.
Case Report: Spontaneous dissection of the carotid or vertebral arteries is a recognized cause of cerebral ischemia and stroke. An association between spontaneous dissections and migraine has been suggested but not proven. We present the case of a young, healthy patient with history of migraines who developed a right middle cerebral artery ischemic stroke and was found to have a dissection of the internal carotid artery (ICA).
A 31-year-old male patient with past medical history of migraines presented to the emergency room with left-sided weakness preceded by “the worse headache of my life”. Head CT scan and MRI showed acute ischemic injury involving the right middle cerebral artery distribution. Neck and head CT angiogram showed total occlusion of the mid and proximal right internal carotid artery up to C1 level with reconstitution of flow above C1 likely due to patent anterior communicating artery with low flow to the ICA and low flow to the right MCA. Arterial Doppler of the extracranial carotid arteries showed mild plaque in the right common, internal and external carotid arteries without stenosis but with high resistive flow noted in the right internal carotid artery. Transthoracic echocardiogram was unremarkable as well as workup for hypercoagulable conditions. LDL cholesterol was found to be 103mg/dL. The patient had significant left-sided weakness, which resolved almost completely with 3 months of physical therapy.
Most ischemic events related to internal carotid artery dissection arise from thromboembolic events due to narrowing of the arterial lumen. The exact mechanism by which spontaneous carotid artery dissection develop is not clear yet and literature on this subject is mostly limited to case reports. Inflammatory conditions affecting the vessels have been proposed as risk factors, more specifically altered vascular reactivity during migraine has been thought to contribute to the development of cervical artery dissection in isolated cases. Interestingly our patient’s symptoms of stroke were preceded by a severe headache which he thought was a migraine attack, in fact past medical history of migraine was the only risk factor we found on this patient for arterial dissection.
440 FIRST USE OF K2, FIRST SEIZURE
Moti D, Ahmed M. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: “K2”, “Spice”, Incense” is one of the synthetic, legal, intoxicating drugs (SLIDS) which is sold over the counter as bath salts and incense with a label “not for human consumption” simply to avoid regulation by the FDA.
A 17 yr old male with no PMH was brought to the hospital by his family after he presented with seizure-like activity. Pt was at a party when he suddenly started to have tonic clonic movement of the upper and lower extremities with rolling of the eyes, and drooling of saliva and being incontinent to urine. The event lasted for about 2 minutes and thereafter patient was confused for about 20 minutes. Prior to this event, pt was not having any headache, nor blurring of vision, nor fever, nor chills. There is no family history of seizure and patient, himself, had no prior history of seizure. Pt claims he has never smoked or consumed alcohol in the past. Urine tox test was neg for any illegal substance. Upon repeated questioning, he admitted that he used K2 in the party for the first time. SLIDS are increasingly used in USA by young generation. A survey of youths at a rave party indicated that 21% had used one of them on at least one occasion. These drugs are relatively cheap and are not detected on a standard urine screen. It can produce a sympathomimetic syndrome with features that range from pure adrenergic stimulation to a mixed picture of stimulant and hallucinogenic effects. K2 contains a synthetic cannabinoids which has full agonist mechanism of action with variable concentration and potency. Physicians need to be aware of SLIDS in order to recognize and manage the intoxication syndrome associated with these substances when encountered in clinical practice.
441 A HAND NOT UNDER CONTROL OF THE MIND - THE ALIEN LIMB
Panikkath R, Nugent K, Yik Lim S, Panikkath D. Texas Tech University Health Sciences Center, Lubbock, Lubbock, TX.
Case Report: Introduction: Alien limb is a phenomenon in which a limb is not under control of the mind. The person loses control of the limb, and it acts as if it had a mind of its own.
Methods: This is a case analysis and literature review.
Case Report: A 77-year-old woman with chronic atrial fibrillation had her anticoagulation stopped temporarily for spine surgery. No bridging with low molecular weight heparin was done. Two days later while watching television, she noted an arm flinging across her visual field. She got terrified when she realized that this was her left hand. She did not have any control of the left arm for almost 30 minutes, and it continued to move doing purposeful movements. She later noted that her left arm was numb and slightly weak after she regained control over it. Her husband helped her to the car to take her to the hospital and noted that she was dragging he left lower limb while walking. In the hospital, a CT and MRI of the brain, showed an acute infarct in the right parietal lobe. Transthoracic and transesophageal echocardiograms did not show any evidence of clots. She gradually regained normal power on the left side. A diagnosis of transient ischemic attack possibly due to cardioembolic stroke was made. She was discharged home with instructions to not to stop anticoagulation without bridging with low molecular weight heparin.
Conclusion: Alien limb syndrome or Dr Strangelove syndrome is an interesting situation in which a person loses control of his limb which starts to act as if it had a mind of its own. It has been reported after brain surgery, brain tumor, aneurysms, degenerative conditions of the brain, and uncommonly after stroke. Alien limb as a manifestation of cardioembolic TIA is extremely rare with only few cases reported in the literature. Alien limb persists for variable duration of time depending on the etiology of causation. Although self-injurious behaviors like slapping and choking have been reported in patients with alien limb syndrome, it rarely leads to significant injury. There is no well-established drug therapy for this syndrome, although in one case report clonazepam was been reported to be beneficial.
Perinatal Medicine I Concurrent Session
2:00 PM
Friday, February 21, 2014
442 GENETIC ASSOCIATION OF FOLATE RECEPTOR GENES (FOLR2, FOLR3) AND MYELOMENINGOCELE
Tenpenny JC1, Kit Sing Au P2, Northrup H2. 1 University of Texas-Houston, Houston, TX and 2 University of Texas-Houston, Houston, TX.
Purpose of Study: To identify single nucleotide polymorphisms (SNPs) and mutations within coding regions of genes involved in folate transport, specifically FOLR2 and FOLR3 genes, and determine whether these SNPs are associated with increased risk for myelomeningocele (MM).
Methods Used: A total of 96 patients with MM (48 Hispanic, 48 Caucasian) were selected from a biobank of subjects with MM. Subjects were primarily recruited from three sites (Houston, TX, Toronto, Canada, and Los Angeles, CA). Their DNA was sequenced to identify variants across ten exons of the FOLR2 and FOLR3 genes. Forward and reverse primers were designed for PCR amplification of each of the five exons identified on the FOLR2 gene, as well as for the five exons on the FOLR3 gene. These were downloaded from NCBI website. Gel electrophoresis was used to verify exon size for each pair of primers. Sequences of amplified products were obtained by the Sanger sequencing method and compared to the published reference sequence. Sequences that differed from the reference sequences were considered variants. SNPs are variants previously reported in dbSNP databases, while novel mutations are those not previously reported. Frequencies of SNPs in MM subjects were compared to ethnically matched controls in dbSNP. We used 2-sided Fisher’s exact method to test for association.
Summary of Results: We identified three novel and six previously described SNPs. Of these novel variations, we found a single, large insertion variant of 173 bp in the 5′-untranslated region of FOLR2. We also identified two novel variants in FOLR3 not previously described. Two of the six previously described SNPs, both in FOLR2, demonstrated significant association with MM.
Conclusions: We identified three previously undescribed variations including one insertion variant involving exon 1 of FOLR2 and two substitutions near exon 2 of FOLR3 that may be associated with MM. We also demonstrated association of two SNPs in FOLR2 gene with MM. One of the variants we described appears to involve important splicing regions of the FOLR3 gene that may alter the transport of folate and thus contribute to the development of MM.
443 GENETIC ASSOCIATION OF THE GLUT2 GENE AND MYELOMENINGOCELE (MM)
Ruggiero J1,2, Northrup H2, Kit Sing Au P2. 1 University of Texas - Houston, Houston, TX and 2 University of Texas - Houston, Houston, TX.
Purpose of Study: Single nucleotide polymorphisms (SNPs) within coding regions of genes involved in glucose metabolism, specifically the GLUT2 gene, are associated with increased risk for MM.
Methods Used: We selected 96 patients (48 Caucasian, 48 Hispanic) with MM from a cohort of subjects recruited primarily from three sites (Houston, TX, Toronto, Canada, and Los Angeles, CA). Patient DNA was amplified with Genomiphi and PCR reactions were completed following primer design for each of the 11 exons of GLUT2 (RefSeq NM_000340 downloaded from UCSC Genome Browser). Exon products of PCR reactions were verified by gel electrophoresis for predicted sizes. Sequences of PCR products generated by the Sanger sequencing method were compared to the GLUT2 RefSeq. Variants not reported in the public single nucleotide polymorphisms database (dbSNP) are considered novel variants. Novel variants will be verified by reverse sequencing. Parents’ DNA will be sequenced to determine whether the variant is inherited or de novo. Statistical analysis with Fisher’s exact test has been performed to compare allele frequencies between MM subjects and ethnically matched reference populations found in public databases (dbSNPs, 1000Genomes, NHLBI ESP) to evaluate association with MM.
Summary of Results: Analysis of sequencing data revealed a single base pair deletion within the coding region of exon 11 of the GLUT2 gene in one Hispanic study patient. A total of 8 known SNPs within the coding and non-coding regions of GLUT2 were also identified and allele frequencies are significant for 4 SNPs in our study population.
Conclusions: We found a novel single base pair deletion that results in truncation of the GLUT2 protein at the C-terminus. The observed deletion alters the coding frame and is predicted to alter the function of the GLUT2 protein. We also found four SNPs that are significantly associated with risk for MM. These variants may disrupt glucose metabolism and influence susceptibility to MM. Glucose homeostasis is critical to embryogenesis, suggesting that altered pathways may be associated with MM. The anticipated results of this study will warrant further investigation of the GLUT2 gene and its association with MM.
444 HYPOGLYCEMIA AND/OR HYPERGLYCEMIA IN INFANTS WITH HYPOXIC ISCHEMIC ENCEPHALOPATHY IN THE COOLCAP TRIAL WERE ASSOCIATED WITH POOR OUTCOME
Basu SK1, Kaiser JR1, Gunn AJ2. 1 Baylor College of Medicine, Houston, TX and 2 Auckland University, Auckland, New Zealand.
Purpose of Study: Deranged glucose homeostasis is common in infants with hypoxic ischemic encephalopathy (HIE). Our study investigates whether hypoglycemia and/or hyperglycemia during the first 48 hrs after randomization in infants with HIE in the CoolCap Trial was associated with poor outcome.
Methods Used: We performed secondary analysis of data from the CoolCap Trial involving 234 infants with HIE with gestational age >36 wks. Plasma glucose data from 211(90%) infants up to 48 hrs after study randomization were analyzed for associations with the CoolCap Trial poor primary outcome of either death and/or severe neurodevelopmental disability at 18 months of age. Glucose concentrations were not available in 7 (3%) infants and 16 (7%) infants were lost to follow-up. Hypoglycemia (⩽40 mg/dL) and hyperglycemia (>150mg/dL) were analyzed for their association with poor outcome by chi-square and logistic multivariate regression.
Summary of Results: Of the 211 infants, 126 (60%) had a poor outcome and 125 (59%) had deranged glucose homeostasis. The strongest association between outcome and abnormal glucose concentrations were noted within 12 hrs after randomization. Poor outcome was associated with hypoglycemia (in 21 of 26 [81%] infants, p=0.019), hyperglycemia (67%, p=0.046), occurrence of either hypoglycemia or hyperglycemia (67%, p=0.001) and recurrent values of glucose derangement (79%, p∼0.001) within 12 hrs of randomization. Logistic multivariate regression analysis revealed that the association remained significant even after accounting for birth weight, Sarnat stage, and randomization to cooling or standard therapy.
Conclusions: We observed that infants with HIE with hypoglycemia and/or hyperglycemia within the first 12 hrs after randomization to the CoolCap Trial were associated with poor outcome and may be an important prognostic factor in infants with HIE.
445 HYDROCORTISONE PRE-TREATMENT REDUCES HYPOXIC ISCHEMIC BRAIN INJURY IN NEONATAL RATS
Bhatt A, Feng Y, Kumar P. University of Mississippi Medical Center, Jackson, MS.
Purpose of Study: Corticosteroid, like dexamethasone (Dex) is used as a neuroprotective agent against the hypoxic-ischemic (HI) brain injury in infants undergoing surgical repair of congenital heart disease. But, Dex causes neurodegeneration in developing brain while hydrocortisone (HC) use is safer. The purpose of our current project was to evaluate whether HC provides neuroprotection against the subsequent HI brain injury in newborns rats.
Methods Used: Seven-day-old rat pups had the right carotid artery permanently ligated followed by 140 min of hypoxia (8% oxygen). Rat pups received two i.p. injections of either saline or HC, 20 and 10 mg/kg at 24 and 4 h before the HI exposure, respectively. For the comparison, some rat pups at the corresponding age were treated similarly to the operated ones, except no carotid artery ligation or hypoxia or drug exposure. (sham). Brain damage was evaluated by weight loss of the right hemisphere at 22 days after hypoxia. Additionally, caspase-3 activities, cleaved caspase-3 and TUNEL cells were measured at 24 h after hypoxia by the enzyme activity and fluorescence microscopy analysis, respectively.
Summary of Results: There was no difference in right (RH) and left hemisphere (LH) weight in sham group (-0.8 ± 0.6%, n=6). LH weight was not affected by the HI in this model. HC reduced the weight loss in RH from -31.9 ± 5.7% in vehicle-treated pups (n=10) to -3.3 ± 1.8% in HC-treated pups (n=12, P∼0.01). Additionally, it also decreased HI induced increase of caspase-3 activity in right cortex (94.4 ± 2.5 pmol/mg, sham; 432.5 ± 117.3 pmol/mg, vehicle and 176.3 ± 54.4 pmol/mg, HC, P∼0.01) and in right hippocampus (93.0 ± 14.7 pmol/mg, sham; 508.5± 161.1 pmol/mg, vehicle and 198.6 ± 83.9 pmol/mg, HC, P∼0.01), TUNEL positive cells in right cortex (4.7± 0.1/field, sham; 72.5± 16.4/field, vehicle and 5.1± 0.3/field, HC, P∼0.01) and in right hippocampus (5.8 ± 0.1/field, sham; 62.5 ± 19.1/field, vehicle and 5.3 ± 0.4/field, HC, P∼0.01), as well as cleaved caspase-3 positive cells in right cortex (7.9± 3.8, sham; 71.1± 18.1, vehicle and 13.6± 5.5, HC, P∼0.01) and in right hippocampus (3.4 ± 0.6/field, sham; 60.6 ± 9.5/field, vehicle and 7.6 ± 0.9/field, HC, P∼0.01) in neonatal rat brains.
Conclusions: HC provides robust neuroprotection against subsequent HI in newborn rats.
446 DEFICIENCY OF SURFACTANT PROTEIN A LEADS TO INCREASED NEOVASCULARIZATION IN A MOUSE MODEL OF OXYGEN INDUCED RETINOPATHY
Bhatti F, Ball G, Edwards M. OU Children’s Hospital, Oklahoma City, OK.
Purpose of Study: Surfactant protein A (SP-A) is expressed in the mouse retina and is up regulated by toll-like receptor stimulation. SP-A also modulates human retinal endothelial cell function in vitro. We therefore hypothesized that SP-A signaling alters vascular development in the preterm neonate to impact retinopathy of prematurity (ROP). This was tested using an in vivo oxygen-induced retinopathy (OIR) model with Wild Type (WT) and SP-A null (SP-A-/-) mice. In this model hyperoxia induces a primary retinal vascular obliteration, followed by neovascularization (NV) when the mouse pups return to room air. In the first experiment the pups were exposed to hyperoxia alone to induce only vasoobliteration (VO) and in the second the pups were exposed to hyperoxia and then room air to induce VO and NV.
Methods Used: In the first experiment, WT and SP-A-/- mice were exposed to 75% hyperoxia from P5 to P10. The animals were sacrificed on P10 and retinas flat mounted after immunostaining with cd31 to visualize blood vessels. To study the complete OIR model, WT and SP-A-/- litters were kept in room air until P7 and 75% hyperoxia from P7 to P12. The animals were sacrificed on P17 and Retinas were analyzed for total area, area with VO, and area with NV. VO and NV areas were expressed as a percentage of total retinal area and compared using Student’s t-test. p∼0.05 was considered significant.
Summary of Results: In mice exposed to 75% O2 from P5 to P10, WT mice had increased VO% compared to SP-A-/- (WT 40% vs SP-A-/- 32% p=0.006). In the second experiment on mice with completely developed OIR, SP-A-/- mice had increased VO compared to WT (30.1% vs 23.6% p=0.13), but had decreased NV (14.4% vs 30% p=0.001).
Conclusions: Although SP-A-/- mice exposed to hyperoxia alone had decreased VO, they had a slight increase in VO when placed in hyperoxia at P7-P12. This may be a result of regression of normally growing vessels when exposed to hyperoxia. The decrease in NV in SP-A-/- mice suggests that the absence of SP-A may lead to a decrease in inflammatory cytokines, impacting blood vessel growth in the second phase of ROP. Thus SP-A may be protective in maintaining vascular growth in the first phase of ROP, but overexpression (due to inflammation) may impact the second phase of vascular neoproliferation.
447 IMPACT OF HIGH PARENTERAL PROTEIN ON THE GROWTH OF THE CORPUS CALLOSUM AND THE VERMIS IN EXTREMELY LOW BIRTH WEIGHT (ELBW) INFANTS
Najjar M, Zayek MM. Children and Women’s Hospital, Mobile, AL.
Purpose of Study: Background: Adverse neurodevelopmental outcome may occur in ELBW infants without major brain imaging abnormalities. Hypoplastic brain structures, such as thin corpus callosum (CC) and hypoplastic vermis (V), have been associated with cognitive, socio-emotional, and psychiatric disorders as well as learning disabilities in toddlers, adolescents, and adults, born extremely premature. While aggressive parenteral protein intake in ELBW infants may improve somatic growth, its effects on brain structural growth remain unknown.
Objective: Our aim is to evaluate the effects of high parenteral protein intake on the growth of corpus callosum and cerebellar vermis in ELBW infants.
Methods Used: Charts of 237 ELBW infants (born ∼28 weeks gestation and birth weight ∼1000 g) were reviewed from 2 different time periods, 2007-2009 in which 132 infants received old standard parenteral protein intake of 0-3.5 g/Kg.d (LOW group), and 2010-2012 during which 105 infants received parenteral protein intake of 3-4 g/Kg.d from day 1 (HIGH group). We measured -using cranial ultrasound at birth and at 10-12 weeks of life - the absolute values and the percent of change from birth in mid sagittal surface area of the corpus callosum (CC) and the cerebellar vermis (V).
Summary of Results: Overall, there was no difference between HIGH and LOW protein groups in weight gain, or in head, CC, or V growth. However, in the subpopulation of infants who received >28 days of parenteral nutrition (PN) (n=130), the HIGH protein group (n=78) enhanced weight gain and CC growth when compared to the Low group (n=52). However, head or vermis growth were not different. The median (interquartile range) values at a postnatal age of 10-12 weeks for body weight were 1286 (978-1555) vs. 1081 (849-1491) g, p=0.04, and for CC size were 1.09 (0.9, 1.38) vs. 0.93 (0.78, 1.20) cm2, p= 0.014, respectively in High vs. Low protein groups. After adjusting for significant confounders for CC growth such as gestational age, hydrocortisone days, and TPN days, High protein intake remained a significant factor (p= 0.034).
Conclusions: The period of high parenteral protein was associated with improved CC growth, mainly in ELBW infants who needed prolonged PN. To validate our findings, further detailed nutritional analyses are currently being performed.
448 IMPACT OF LOW GRADE INTRAVENTRICULAR HEMORRHAGE ON COGNITIVE AND BEHAVIORAL OUTCOMES TO 18 YEARS OF AGE IN LOW BIRTH WEIGHT PRETERM INFANTS
Wy P1,2, Rettiganti M1,2, Li J1,2, Yap V1,2, Barrett K1,2, Whiteside- Mansell L1,2, Casey P1,2. 1 University of Arkansas for Medical Sciences, Little Rock, AR and 2 Arkansas Children’s Hospital, Little Rock, AR.
Purpose of Study: To determine the link between the occurrence of low grade IVH in low birth weight (Birth weight ∼=2500 grams) infants born prematurely (Gestational age ∼37weeks) and intellectual function, academic achievement, and behavioral problems to the age of 18 years.
Methods Used: A total of 985 infants were enrolled in a multisite interventional research program. Of the 462 infants tested for IVH, 99 demonstrated sonographic evidence of low grade IVH while 291 showed no sonographic evidence of IVH. Several outcomes were compared between these two groups. Intelligence was assessed using Stanford-Binet Intelligence scales at age 3 years, Wechsler Intelligence Scale for Children (WISC-III) at age 8, Wechsler Abbreviated Scale of Intelligence (WASI) at age 18 years, and Woodcock Johnson Tests of Achievement at age 8 and 18 years. Behavior was measured using the Achenbach Behavior Checklist at age 3 and Child Behavior Checklist (CBCL) at age 8 & 18 years. Outcomes were compared between the IVH positive and IVH negative groups using analysis of covariance (ANCOVA) after adjusting for the presence or absence of intervention, birth weight, gestational age, gender, severity of neonatal course, race, and maternal education.
Summary of Results: No statistically significant difference in intelligence as measured by Stanford-Binet Intelligence scales, Wechsler Intelligence Scale for Children (WISC-III), Wechsler Abbreviated Scale of Intelligence (WASI) and Woodcock Johnson Tests of Achievement could be appreciated between IVH positive patients and controls at any age group (36months, 8 years and 18 years of age). Additionally, there was no significant difference in problem behavior as assessed by the Achenbach Behavior Checklist and Child Behavior Checklist (CBCL) comparing IVH patients with controls.
Conclusions: Low grade IVH was not demonstrated in our study to be an independent risk factor associated with lower outcomes in intelligence, academic achievement or problem behavior at age 3, 8, and 18 years.
449 CLONIDINE AS A SINGLE DRUG THERAPY IN NEONATAL ABSTINENCE: A PILOT STUDY
Bada H1, Sithisarn T1, Caldwell R1, Gibson J2, Whitehead V1, Grider D1, Li Y3, Breheny P3. 1 College of Medicine University of Kentucky, Lexington, KY; 2 Kentucky Children’s Hospital, Lexington, KY and 3 College of Public Health University of Kentucky, Lexington, KY.
Purpose of Study: To compare neurobehavior performance between infants treated with morphine (M) and clonidine (C) for neonatal abstinence syndrome (NAS).
Methods Used: This randomized clinical trial compared opiate and non-opiate treatment (Rx) for NAS. We enrolled neonates needing Rx for NAS, with gestational age (GA) =>35wk and ∼=7d postnatal age, and no other medical complications. After informed consent, infants were randomized to receive either M 0.4 mg/kg/d or C 5 mcg/kg/d, divided into q 3h dose, p. o. A 25% dose escalation q 12 to 24h was made if no Rx response (maximum: 1 mg/kg/d for M; 12 mcg/kg/d for C). When symptoms were controlled, dose was decreased by 10% of the maximum dose q other d. Clinical and research staff were masked to Rx assignment. Clinical staff monitored Rx response by Finnegan scores. Neurobehavior was assessed using the NICU Network Neurobehavioral scales (NNNS) within 1wk of Rx and a follow-up 2-3wk later or at discharge. Repeated Measures ANOVA and Wicoxon rank sum tests were used for hypothesis testing.
Summary of Results: M treated infants (n=15) did not differ from those given C (n=16) as to birth weight, GA, 1 and 5 min Apgar scores, or post natal age at Rx. Duration of Rx was significantly lower (p=0.02) for patients treated with C (median 28 days) than M (median 39 days). NNNS summary scores improved with C but no significant change with M. Compared to M, the C group had significantly lower arousal and excitability, with a trend toward better regulation and lesser handling, hypertonicity, and asymmetric reflexes during follow-up NNNS (Table).
Conclusions: Our results show that C was associated with better neurobehavioral performance and a shorter duration of Rx compared to M. Larger studies are warranted to determine if C can be an alternative single drug Rx for NAS.
450 NEONATAL SCREENING FOR ILLICIT DRUG EXPOSURE: EVALUATING EFFICACY OF UMBILICAL CORD TISSUE DRUG SCREEN
Shah SD1, Pourcyrous M1, Flax S2, Talati AJ1. 1 University of Tennessee Health Science Center, Memphis, TN and 2 The Regional Medical Center at Memphis, Memphis, TN.
Purpose of Study: According to 2011 National survey on drug use and health, nearly 5% of American women reported using an illicit drug during pregnancy. However, these data may not be accurate and incidence may be underestimated. Not all women report illicit drug use during pregnancy and a positive urine drug screen (UDS) reflects only recent drug use in pregnancy. To identify neonates at risk, accurate diagnosis is required in neonatal period. We aimed to evaluate efficacy of umbilical cord tissue drug screen (UCDS) with other means of testing illicit drug exposure in neonate and mother.
Methods Used: In a retrospective study, neonates who had UCDS were identified from May 2013 to October 2013. Data were collected from the chart review. We gathered relevant information from the mother’s chart including maternal history of illicit drug use and UDS. We also collected demographic data such as sex, birth weight (BW), mode of delivery, 5 minutes Apgar score and gestational age (GA).
Summary of Results: A total of 40 neonates (male 14 and female 22) were identified who had UCDS, of these 4 neonates were excluded due to incomplete data. Illicit drug testing was performed as per attending physician discretion. The mean ± standard deviation BW was 3003 ± 705 grams and GA was 37 ± 3.5 weeks, and median (range) 5 minutes Apgar score was 8 (0-9). Of the 36 neonates with UCDS, 23 also had UDS. Of these 23, only 16 (69.5%) were positive compared to UCDS (82.5%). 10 neonates (25%) exposed to multiple illicit drugs. Positive illicit drugs were tetrahydrocannabinol (n = 16, 44.4%), cocaine (n = 11, 30.5%), benzodiazepine (n = 6, 16.6%), opiates (n = 5, 14%), and barbiturates (n = 1, 2.7%). Table reflects the test results from different sources.
Conclusions: Umbilical cord tissue drug screen is more reliable then urine drug screen in neonatal period. It also quantifies the amount of exposure and could be used for future studies to correlate symptoms with amount of exposure.
Pulmonary and Critical Care
Concurrent Session
2:00 PM
Friday, February 21, 2014
451 HEALTHY HIV-INFECTED INDIVIDUALS HARBOR HIV IN THEIR ALVEOLAR MACROPHAGES
Cribbs SK1, Lennox J2, Caliendo A4, Brown L3, Guidot D1. 1 Emory University and the Atlanta VA, Atlanta, GA; 2 Emory University, Atlanta, GA; 3 Emory University, Atlanta, GA and 4 Brown University, Providence, RI.
Purpose of Study: Alveolar macrophages (AM) are specialized innate immune cells that reside in the alveolus, a separate compartment site compared to blood. The half-life of these cells is significantly longer than that of an activated lymphocyte. AM can be infected by HIV-1 as they express CXCR4 and CCR5. However, reports quantifying the burden of HIV in AM are conflicting, and it is unclear what impact HIV infection has on AM function. We hypothesize that the AM is an important reservoir for HIV, contributing to cell-cell spread of the virus within the lung and exhibiting abnormal immune function that contributes to the increased risk of severe lung infections.
Methods Used: Healthy HIV-infected subjects underwent bronchoscopy and bronchoalveolar lavage. AM were isolated and HIV-1 RNA was quantified using the Abbott RealTime HIV-1 PCR Assay (Abbott Molecular Inc. Des Plaines, IL). Proviral DNA was qualitatively measured using a modified version of the above-mentioned HIV-1 RNA viral load assay. To measure phagocytic function, AM were isolated and incubated for 1 hour with FITC-labeled S. aureus in a 10:1 ratio. FITC-labeled bacteria containing cells were measured by flow cytometry. Phagocytic index was calculated as follows: (% positive cells x mean channel fluorescence)/100.
Summary of Results: We enrolled 22 otherwise healthy HIV-infected subjects (median CD4 count=409/μl, 82% with undetectable plasma viral load). HIV-1 proviral DNA and/or quantitative RNA were detected in 82% of the AM; 78% of this group had an undetectable plasma viral load and 94% were on anti-retroviral therapy. HIV-1 RNA levels ranged from 48 to 2305 copies/mL. Further, HIV-infected subjects with proviral DNA present had decreased AM phagocytosis of FITC-labeled S. Aureus compared to subjects without proviral DNA present [16.6 (IQR 6-45.2) vs. 33.1 (IQR12.2-172.1)].
Conclusions: Alveolar macrophages harbor HIV even in otherwise healthy subjects with undetectable plasma viral loads, representing a potential reservoir for the virus. In addition, HIV viral replication within these macrophages may impair phagocytosis and other immune functions, leading to an increased risk for lung infections.
452 NRF2 FUNCTION IN ALVEOLAR MACROPHAGES IS DECREASED BY HIV-1 VIRAL PROTEINS AND ZINC DEPLETION
Purcell M, Staitieh B, Fan X, Cribbs SK. Atlanta VAMC and Emory University, Atlanta, GA.
Purpose of Study: Nuclear factor erythroid 2-related factor 2 (Nrf2) is the master transcription factor responsible for the activation of the antioxidant response element (ARE). Nrf2-ARE binding is a zinc-dependent process that results in the transcription of a wide range of genes that protect the cell from oxidative stress. Prior studies by our group link zinc bioavailability to oxidative stress and decreased phagocytic function in alveolar macrophages in HIV-1 transgenic rats. In this study we examined how zinc modulates Nrf2-ARE activity in human macrophages exposed to the HIV-related protein Tat in vitro.
Methods Used: The human monocyte THP-1 cell line was cultured for 2 hrs ± the zinc chelator TPEN (5 μM) and then treated with recombinant Tat (10 ng/mL) ± zinc acetate (1 μM). 24 hrs after the initial treatment, cells were lysed and the expression of Nrf2 and two key ARE-dependent genes, glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H dehydrogenase [quinone] 1 (NQO1), were quantified by real time PCR.
Summary of Results: Tat treatment, with or without zinc, significantly decreased Nrf2 and GCLC expression. In contrast, although Tat treatment actually increased Nrf2 expression in zinc-depleted cells, ARE activity was nevertheless inhibited, as reflected by a significant decrease in both GCLC and NQO1 expression. Interestingly, zinc treatment restored Nrf2 and GCLC expression to control levels in zinc-depleted, Tat-treated cells.
Conclusions: Tat decreased gene expression of Nrf2 and the Nrf2-ARE-dependent anti-oxidant GCLC in human macrophages. This effect may explain in part how HIV-1 infection causes oxidative stress and macrophage dysfunction even in the absence of an impaired CD4 response. Further, zinc bioavailability appears to be critical to an effective response to Tat-induced oxidative stress, as the zinc-finger transcription factor Nrf2 cannot activate the ARE when the macrophage is relatively zinc deficient. As even relatively healthy individuals living with HIV have evidence of oxidative stress, zinc deficiency and alveolar macrophage immune dysfunction, these findings support the hypothesis that dietary zinc supplements could improve lung health in this vulnerable population.
453 TREATMENT WITH S-ADENOSYLMETHIONINE AND ZINC RESTORES NRF2 AND NRF2-ANTIOXIDANT RESPONSE ELEMENT DEPENDENT GENE EXPRESSION IN ALCOHOL-TREATED ALVEOLAR MACROPHAGES IN VITRO
Middour T, Fan X, Mehta A. The Atlanta VA and Emory University, Atlanta, GA.
Purpose of Study: Alcohol abuse induces oxidative stress and alveolar macrophage immune dysfunction. We determined that dietary supplementation with zinc and/or the thiol anti-oxidant S-adenosylmethionine (SAMe) reverses these effects in an experimental animal model. Alcohol inhibits the transcription factor Nrf2, which is critical to activate the anti-oxidant response element (ARE) that programmatically regulates the expression of anti-oxidant genes. We tested if these nutritional supplements could reverse alcohol-induced aberrations in the Nrf2/ARE signaling pathway in alveolar macrophages.
Methods Used: A rat alveolar macrophage cell line, NR8383, was cultured in alcohol (60 mM or ∼ 0.24%) for 72 hrs and then assessed for Nrf2 gene and protein expression; in parallel, expression of the ARE-dependent genes glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) were quantified. In separate experiments, zinc deficiency was induced with the zinc chelator TPEN and zinc-deficient cells were exposed to alcohol ± treatment with zinc (10 μM) and SAMe (500 μM) for 72 hrs and then assessed for the relative expression of Nrf2, GCLC and NQO1.
Summary of Results: Alcohol exposure significantly decreased Nrf2 gene and protein expression by ∼ 40%, GCLC gene expression by ∼ 50%, and NQO1 gene and protein expression by ∼ 60%. Alcohol-induced inhibition of Nrf2 and GCLC gene expression were exacerbated by zinc depletion. Interestingly, treatment with zinc and SAMe increased the gene expression of Nrf2, GCLC and NQO1 in zinc-depleted, alcohol-treated cells to levels that were significantly higher than in control cells.
Conclusions: Alcohol decreases expression of Nrf2 and Nrf2/ARE-dependent genes in alveolar macrophages. Importantly, these effects are exacerbated by zinc depletion, which correlates to the relative zinc deficiency we recently identified in the alveolar macrophages of otherwise healthy alcoholics. In contrast, zinc and SAMe restore the expression of Nrf2 and Nrf2/ARE-dependent genes. Taken together, these findings suggest that these dietary supplements could enhance alveolar macrophage function in alcoholics, and we have begun a clinical trial at the Atlanta VA to test this hypothesis.
454 THE DEFENSE PATHWAYS ACTIVATED BY THE TRANSCRIPTION FACTORS NRF2 AND PU.1 APPEAR TO BE COORDINATELY REGULATED IN THE ALVEOLAR MACROPHAGE
Staitieh B, Fan X, Guidot D. *Emory University and the Atlanta VA, Atlanta, GA.
Purpose of Study: In response to diverse stresses, the transcription factors Nrf2 and PU.1 activate anti-oxidant and immune defenses, respectively, within the alveolar macrophage. Signaling through each of these essential pathways is dampened by chronic alcohol abuse and/or HIV infection. Previously we determined that Nrf2 and PU.1 may bind DNA in an interactive fashion, suggesting that these fundamental defense pathways are coordinately regulated. We sought to test this hypothesis and elucidate the nature of those interactions.
Methods Used: We used RNA silencing vectors to either Nrf2 or PU.1 and transfected them into NR8383 cells (a rat alveolar macrophage cell line) in parallel experiments. After 24 hrs, we quantified the gene expression of both targets using RT-PCR. At 48 hrs, we assessed the effect of silencing RNA of Nrf2 on PU.1 protein expression by western blot analyses. In addition, we used sulforophane (SFN, a potent stimulator of Nrf2 activity) and assessed its effects on PU.1 gene and protein expression by RT-PCR and western blot analyses, respectively.
Summary of Results: Nrf2 RNA silencing significantly decreased PU.1 gene expression by 24 hrs and PU.1 protein expression by 48 hrs. Conversely, PU.1 RNA silencing significantly decreased Nrf2 gene expression by 24 hrs. In contrast, treatment with SFN significantly increased gene and protein expression of NAD(P)H dehydrogenase [quinone] 1 (NQO1; a downstream effector of Nrf2) but decreased gene and protein expression of PU.1.
Conclusions: This study provides further evidence linking the regulation of the fundamental defense pathways activated by Nrf2 and PU.1. Specifically, decreasing proximal gene expression of either transcription factor inhibits the gene expression of the other, whereas activating the Nrf2 pathway directly at a more distal step in the signaling pathway also leads to a commensurate decrease in PU.1 expression. The precise nature of their coordinated regulation is as yet unclear in light of the mutual suppression of both targets at the mRNA level and the discordant effects of stimulation at the protein level. Further experiments are necessary to determine which intermediaries, if any, may play a role in linking these two fundamental defense mechanisms.
455 DECREASED PHAGOCYTOSIS IS ASSOCIATED WITH IMPAIRED LC3 EXPRESSION IN NICOTINE EXPOSED MURINE ALVEOLAR MACROPHAGES
McCabe CF1, Grooms K1, Hart M2,1, Gauthier T3, Wongtrakool C2,1. 1 Emory University, Atlanta, GA; 2 Atlanta VA Medical Center, Decatur, GA and 3 Emory University, Atlanta, GA.
Purpose of Study: Cigarette smoke exposure is associated with a number of deleterious health effects, including increased risk of lower respiratory tract infections. Nicotine, the addictive constituent in tobacco smoke, has been implicated in mediating the effects of cigarette smoke in the lung through α7 nicotinic acetylcholine receptor (nAChR) mediated signaling. We hypothesized that nicotine reduces phagocytic function in alveolar macrophages through impaired LC3 dependent autophagic mechanisms.
Methods Used: MH-S murine alveolar macrophages were cultured and treated with 50 μg/ml of nicotine for 24 hours for all experiments. To assess phagocytosis, MH-S cells were incubated with Staphylococcus aureus particles labeled with dye that fluoresces upon phagocytosis. Hydrogen peroxide production was measured by detecting Amplex Red oxidation. mRNA expression of LC3A, LC3B and Myd88 were measured by quantitative real time PCR. Using Western blot analysis, protein expression of the autophagy markers beclin-1, LC3A, LC3B, Atg5, Atg12 and Atg7 were measured in cellular lysates. In some experiments, cells were pre-treated with 5 nM α-bungarotoxin, a selective α7 nAChR inhibitor, for 1 hour prior to nicotine treatment.
Summary of Results: Nicotine exposure significantly decreased phagocytic function and hydrogen peroxide production by 3 fold, and significantly decreased mRNA expression of LC3A, LC3B and Myd88 in MH-S cells. Compared to untreated controls, nicotine significantly decreased expression of LC3B by 20% in both 16kD and 14kD isoforms, and decreased expression of beclin-1 by 10%. Pre-treatment with α-bungarotoxin abrogated the effects of nicotine. LC3A, Atg5 and Atg7 expression were unchanged with nicotine exposure.
Conclusions: Decreased phagocytosis in nicotine exposed murine alveolar macrophages was associated with impaired LC3B and beclin-1 expression through α7 nAChR dependent signaling. Although Myd88 mRNA expression was reduced, expression of other autophagy markers were unchanged, suggesting the reduction in phagocytosis in nicotine exposed macrophages may reflect impaired LC3 associated phagocytic mechanisms.
456 THE EFFECT OF VITAMIN D DEFICIENCY DURING PREGNANCY ON PULMONARY DEVELOPMENT USING NOVEL TRACHEAL ULTRASOUND AND TRACHEO-BRONCHIAL CAST IN MOUSE MODEL
Saadoon A1, Harris WT1, Ambalavanan N2. 1 University of Alabama at Birmingham, Birmingham, AL and 2 University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: To investigate the effect of vitamin D deficiency during pregnancy on airway structure in a mouse model. As the trachea and major bronchi share similar cartilaginous structure of joint, vitamin D deficiency during airway development may have deleterious effects on the supportive structures of these airways.
Methods Used: Development of Vitamin D deficiency model: Mice kept in ultraviolet UV light-free surroundings using UV blocking film and they received vitamin D-depleted diet after weaning. Tracheal Ultrasound: Visual-sonic radial probe and used to measure tracheal diameter at 4 and 8 weeks. Pulmonary Function Test: Performed at the ages of 4 and 8 weeks using FlexiVent apparatus. Histologic studies: Cross section of mid-trachea was done for one-week old pupsDigital images were analyzed using BioImageXD to evaluate tracheal cartilage total area and thickness. Airway casting: Lungs were fixed using Karnovsky’s fixative then hung inside a vacuum chamber. A syringe containing mixture of silicone is connected to the lung. The casts are then left to cure overnight then the tissue is dissolved.
Summary of Results: Vitamin D3 level at 7 weeks was below the detection limit (<2.5 ng/ml) in the vitamin D deficient mice. Tracheal diameter measured with ultrasound is well correlated with that of tracheo-bronchial cast (Pearson Correlation Coefficient of 0.753, p 0.031). Tracheal diameter in vitamin D sufficient group is significantly larger than the vitamin D deficient group (0.8 mm vs 0.65 mm, p 0.007). When stratified by age there was a significant difference at 8 weeks (0.90 mm vs 0.81, p 0.047) but not at 4 weeks (0.67 mm vs 0.57 mm, p 0.074). On histology we documented decreased cartilaginous width in the vitamin D deficient pups (0.44 mm vs 0.68 mm, p 0.027)
Conclusions: We established a standard way of tracheal ultrasound. Tracheal diameter is smaller in pups born to vitamin D deficient mice with thinner tracheal ring cartilage. This protocol can be used to study different congenital and acquired airway diseases and therapeutic interventions
457 A POTENTIAL ROLE FOR HDAC6 IN PULMONARY FIBROSIS
Saito S, Zhuang Y, Luo F, Sanchez C, Lasky J. Tulane University, New Orleans, LA.
Purpose of Study: Idiopathic pulmonary fibrosis (IPF) is a devastating disease. Histone deacetylase 6 (HDAC6) has been implicated in EMT (epithelial-mesenchymal transition) and FMD (fibroblast-myofibroblast differentiation). This study investigates a role for HDAC6 in pulmonary fibrosis.
Methods Used: HDAC6 expression in IPF lungs and control lungs was assessed by qRT-PCR and immunoblots. HPL1D cells (immortalized human lung epithelial cells) and normal human lung fibroblasts (NHLFs) were treated with recombinant human TGF-β1 ± Tubastatin (HDAC6 inhibitor). Markers for EMT and FMD were assessed using qRT-PCR and immunoblots. Wild-type C57BL/6 mice were given adenovirus expressing TGF-β1 (Adv-TGF-β1) or GFP (Adv-GFP) on Day 0, followed by treatment with Tubastatin on Day 1-10. Collagen-1(Col-1) and α-smooth muscle actin (α-SMA) expression levels were assessed using qRT-PCR and immunoblots of lung homogenates. Collagen expression was also assessed using trichrome stain of lung sections.
Summary of Results: HDAC6 protein expression is altered in IPF lungs and murine lungs treated with Adv-TGF-β1. In HPL1D cells, Tubastatin ameliorated the decrease of E-cadherin and increase of Col-1 expression induced by TGF-β1. In NHLFs, Tubastatin repressed TGF-β1-induced expression of Col-1 and α-SMA. Tubastatin also reduced the TGF-β1-induced expression of Col-1 in mouse lungs.
Conclusions: Increased HDAC6 expression is associated with, and likely contributes to, the pathology of pulmonary fibrosis. The effectiveness of Tubastatin, an HDAC6 selective inhibitor, in reducing fibrosis in an animal model supports a therapeutic strategy to employ HDAC6 inhibitors to treat IPF.
458 COLLECTION OF EXHALED BREATH CONDENSATE AND DETECTION OF ARACHIDONIC ACID METABOLITES AFTER CARDIOPULMONARY BYPASS IN CHILDREN
Sandhu HS1,2, Heidemann S3. 1 Le Bonheur Children’s Hospital, Memphis, TN; 2 University of Tennessee Health Science Center, Memphis, TN and 3 Children’s Hospital of Michigan, Detroit, MI.
Purpose of Study: Exhaled breath condensate (EBC) has been used to detect oxidative injury and inflammation in the lungs of non-intubated patients. After cardiopulmonary bypass, infants may develop lung injury as shown by increased concentrations of arachidonic acid metabolites such as leukotriene (LT)B4 and 8-isoprostane (IP). The objectives of this study were 1) to develop a method of collecting EBC in mechanically ventilated infants and 2) to determine if LTB4 and 8-IP can be detected in the EBC.
Methods Used: Infants < 2 yrs of age, expected to need CPB and mechanical ventilation for 24 hrs had EBC and mini lavage samples collected pre CPB, 4 hours post bypass and 24 hours post bypass. A cooled RTubeTM with a one-way valve was placed in the exhalation tubing of the ventilator system and EBC was collected for 15 mins. LTB4 and 8 IP were measured by EIA.
Summary of Results: The EBC volume ranged from 110ul to 350ul except for one sample of 1265 ml. Inadvertent dilution of this sample may have been from condensation left in the in-line suction tubing. LTB4 was detected in all samples of EBC and lavage while 8 IP was detected in 9 of EBC and 15 lavage samples (fig)
Conclusions: EBC can be collected in mechanically ventilated infants in sufficient quantities for measurement of arachidonic acid metabolites when a commercially available device is used without humidification. Improvement of this methodology would include consideration of total exhaled volume during the collection period. Ultrasensitive methods of analysis of LTB4 and 8-IP such as Luminex bioassays might lead to more accurate measurements.
459 AN EMERGING LANGUAGE FOR PULMONARY HYPERTENSION WITHIN THE WORLD HEALTH ORGANIZATION’S (WHO) INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH (ICF)
Yandle G1, Grewal H1, Erbil J1, Lauto P1, Escorpizo R2, Lammi MR1, DeBoisblanc B1, Saketkoo LA1. 1 LSU Health Sciences Center, New Orleans, LA and 2 LSU Health Sciences Center, New Orleans, LA.
Purpose of Study: To collect data from pulmonary hypertension (PH) patients and from PH validated instruments necessary to build a WHO ICF Core Set relevant to functioning and accommodations PH.
Methods Used: 1) Patients were invited by a national PH patient organization on behalf of the investigators to attend focus groups and interviews. During these sessions they answered open-ended questionnaires in brief essay format. Questions remained general: ‘How has PH affected or changed your life?’, ‘What are your most disabling symptoms?’, ‘How has your ability changed?’, ‘If you could change 3 things about having PH what would they be? 2) A literature review was performed to identify and extract all validated PH outcome measures/instruments (both traditional and patient-reported) utilized in clinical investigations. 3) Data from both sources were deconstructed to the most basic meaningful concepts, and linked to ICF by the investigators who had established a prior proportion of agreement of 0.94 (adjusted for chance was 0.72).
Summary of Results: The initial item collection resulted in 149 preliminary categories and populated categories in all ICF domains with 9 in Body Structure, 58 in Body Function, 62 in Activities and Participation and 20 in Environmental. Tables highlight differences in data collection strategies.
Conclusions: These are the founding steps in the development of a PH-ICF Core Set. Except for ‘Body Structure’, PH patient collection consistently provides a significantly greater quantity of information; while the deconstruction of validated instruments in PH supplied lesser but different information - validating importance of both methods. Additional phases of item collection will continue with PH specialists and patients, then undergoing item reduction with assessment for differences between WHO PH groups potentially necessitating WHO Group specific PH-Core Sets.
460 GAIT CHARACTERISTICS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Nantsupawat N1,3, Lane AP2, Siangpraipunt O1, Gadwala S1, Nugent K1. 1 Texas Tech University Health Sciences Center, Lubbock, TX; 2 Texas Tech University, Lubbock, TX and 3 Chiang Mai University, Muang, Thailand.
Purpose of Study: Patients with COPD have reduced gait speed and more frequent falls. Multiple factors potentially influence gait speed and the risk for falls. We analyzed gait characteristics in these patients using video recordings and fall risk using questionnaires.
Methods Used: Patients completed a short history about comorbidities and falls and the Activities Specific Balance Confidence (ABC) Scale questionnaire. They performed the Get Up and Go Test which also included the Tinetti balance and gait assessments. Their typical gait was video recorded and analyzed with Dartfish (Fribourg, Switzerland) video analysis software.
Summary of Results: Fourteen patients completed in this study. The mean age was 69.7±6 years, the mean FEV1 was 1.01±0.38 L (36.9 ±15.6 percent predicted), and the mean 6 minute walk distance was 320±102 meters with a calculated gait speed of 0.9 ±0.3 meters/seconds. Three patients had a history of falls without significant injury. The mean ABC scale score was 91.8±14.9, but the scores ranged from 10 to 100. Patients reported decreased balance confidence when “stepping onto or off an escalator while holding onto parcels” and when “walking outside on icy sidewalk”. The mean time in the Get Up and Go Test was 11.9±2.0 seconds. Temporospatial parameters of gait included mean step length of 0.65±0.06 meters, mean double support time of 0.36±0.05 seconds, mean double support time ratio of 30.4±3.1 percent, average free walking speed of 65.3±6.9 meters/minute, and number of steps per minute of 100.4±8.8.
Conclusions: These patients had a reduced step length and a reduced gait speed. They had an increased time spent in double support. Their gait and balance were qualitatively normal using the Tinetti tools for assessment. Most but not all patients had good balance confidence scores. This study suggests that patients with COPD do not have grossly abnormal gait characteristics; the time spent in the double stance phase may help protect them from falls.
461 MARINOBUFAGENIN IDENTIFIES PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME
Farjo B1, Abbas K2, Morin K1, Patel B1, Puschett JB2. 1 University of Texas, Houston, TX and 2 Texas A&M College of Veterinary Medicine and Biosciences, College Station, TX.
Purpose of Study: Acute respiratory distress syndrome (ARDS) is a serious medical complication often associated with sepsis,shock, trauma, pneumonia and other predisposing conditions. Despite improvements in care, principally in the ICU setting, mortality rates currently range from 41-58% in most series. The pathophysiology includes the development of pulmonary edema and increase vascular permeability . Marinobufagenin (MBG) is a member of a group of agents called the bufodienolides which, along with the cardenolides, represent the families of agents called the cardiotonic steroids or cardiac glycosides. They act principally by virtue of their ability to inhibit the ubiquitous enzyme, Na/K ATPase. Studies performed in this laboratory in endothelial monolayers obtained from rat lung demonstrate that MBG causes vascular “leak” by interfering with the function of the adherens proteins.
Methods Used: We obtained urine specimens from patients with documented ARDS for the determination of MBG, comparing these values to ICU patients without ARDS utilized as “controls” (C).
Summary of Results: The mean excretion of MBG in 14 ARDS patients was 753 +/- 285 (SE) pg/mg creatinine and in 10 C patients was 306+/- 170 pg/mg creatinine (P< 0.05).
Conclusions: We conclude that MBG may prove to be valuable in diagnosing patients with ARDS in the ICU setting.
Renal, Electrolyte and Hypertension I
Concurrent Session
2:00 PM
Friday, February 21, 2014
462 DOT1/H3K79 PATHWAY MEDIATES DEFECTIVE URETERIC BUD BRANCHING LEADING TO RENAL HYPODYSPLASIA IN PRORENIN RECEPTOR PRRUB-/- MICE
Song R, Riedl L, Yospiv I. Tulane University, New Orleans, LA.
Purpose of Study: Dot1 is histone methyltransferase specific for Histone 3 lysine 79 (H3K79) that is important for differentiation of collecting duct (CD) cells. Targeted deletion of the Dot1 in the CD principal cells (PCs) in mice represses the acquisition of PC phenotype resulting in polyuria (Wu. JASN, 2013). We tested the hypothesis that renal hypodysplasia(RHD) and polyuria observed in mice that lack the prorenin receptor(PRR) in the ureteric bud(UB) lineage (PRRUB-/-) (Song. PLoS ONE, 2013) is due to reduced Dot1/H3 dimethyl K79 (H3m2K79) expression.
Methods Used: Mutant [Hoxb7Cre+/PRRflox/flox (PRRUB-/-), n=3] and control (PRRUB+/+, n=3) mice were studied on embryonic (E) day E17.5. Dot1 mRNA and protein expression in the kidney was studied by real-time qRT-PCR and immunohistochemistry, respectively. H3m2K79 protein expression was determined by immunohistochemistry and Western blot analysis. The intensity of H3m2K79 and Dot1 immunoreactivity, normalized for surface area of the kidney section, was examined by Slidebook 4.1 software.
Summary of Results: Kidney section surface area was smaller in the mutant compared to control mice (220600±20120 vs.533800±72170 pixels, p<0.05). Dot1 mRNA levels were decreased in mutant compared to control mice (0.68±0.06 vs. 1.0±0.01, p<0.01). Dot1 and H3m2K79 immunostaining was reduced in the mutant vs. control kidneys (Dot1: 0.62±0.03 vs. 1.0±0.01, p<0.05; H3m2K79: 0.64±0.04 vs.1.1±0.01. p<0.05.). Western blot analysis revealed decreased H3m2K79 protein levels in mutant compared to control kidneys (1.0±0.06 vs. 1.5±0.02, p<0.05).
Conclusions: We conclude that reduced H3m2K79 methylation by Dot1 in the UB of PRRUB-/- mice contributes, in part, to RHD and polyuria observed in these mice.
463 MACROPHAGES CONTRIBUTE TO ANGIOTENSIN II MEDIATED ANGIOTENSINOGEN STIMULATION IN RENAL PROXIMAL TUBULAR CELLS
Sato R, Miyata K, Navar L. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Chronic angiotensin II (Ang II) elevation leads to the development of hypertension accompanied by the intrarenal renin-angiotensin system (RAS) activation including stimulation of proximal tubular angiotensinogen (AGT) and associated accumulation of macrophages (MΦ) in the kidney. Treatment with immunosuppressive drugs reduces the Mφs infiltration, the intrarenal Ang II elevation and the blood pressure in hypertensive animal models. These findings suggest that the accumulated MΦ play crucial roles in the intrarenal RAS activation and the development of hypertension. However, the contribution of MΦ to the intrarenal AGT augmentation and the cellular mechanisms have not been delineated. This study was performed to elucidate the role of MΦ in AGT expression and its mechanisms.
Methods Used: Cultured rat MΦ were treated with 0.05-5 μM Ang II up to 48 h, and the culture medium was collected. After removal of Mφ by centrifugation, the separated culture medium was transferred and incubated with rat renal proximal tubular cells (RPTC) for 24 h. mRNA levels of interleukin 6 (IL-6) in MΦ and AGT in RPTC were evaluated by real-time RT-PCR.
Summary of Results: Treatment with 5 μM Ang II activated p38 MAP kinase and increased IL-6 expression (2.65 ± 0.11, ratio to control) at 48 h. The IL-6 augmentation was attenuated by an Ang II receptor antagonist, olmesartan. After incubation of RPTC with the culture medium of Ang II-stimulated Mφ, AGT expression in RPTC was augmented in dose-dependent manner based on Ang II exposure in MΦ (1.12 ± 0.24 by 50 nM, 1.36 ± 0.28 by 500 nM and 1.71 ± 0.49 by 5 μM Ang II, ratio to control). Addition of neutralizing IL-6 antibody to the collected culture medium of Ang II-stimulated MΦ attenuated the AGT augmentation in RPTC (1.52 ± 0.10-fold change without IL-6 antibody and 1.17 ± 0.27-fold change with IL-6 antibody).
Conclusions: These results demonstrate that Ang II increases IL-6 production in MΦ, and the augmented IL-6 increases AGT expression in RPTC. In vivo implications are that elevated intrarenal Ang II enhances the accumulation of MΦ in the kidney and stimulates then IL-6 production in the MΦ, which augments intrarenal AGT expression during the development of Ang II-dependent hypertension.
464 ALDOSTERONE MODULATES NCC VIA ALTERING ITS INTERACTION WITH 14-3-3 GAMMA
Feng X1,2, Zhang Y1, Lee M1, Caroti C1,2, Cai H1,2. 1 Emory University, Atlanta, GA and 2 Atlanta VA Medical Center, Decatur, GA.
Purpose of Study: To determine whether 14-3-3 is involved in aldosterone-mediated regulation of NCC.
Methods Used: Cell cultures, transfection, immunoprecipitation and western blot analysis were used in the study.
Summary of Results: 14-3-3 gamma down-regulated total NCC and membrane NCC protein expressions in a dose-dependent manner in HEK293 cells transiently transfected with GFP-NCC and 14-3-3 gamma plasmids. Aldosterone treatment (10 μM, for 3 hours) increased both total and membrane NCC protein expression in HEK293 cells transfected by GFP-NCC and 14-3-3 gamma, while decreasing interaction of NCC with 14-3-3 gamma. We also found that aldosterone increased both total and membrane NCC expression via decreasing NCC ubiquitination
Conclusions: These data suggest that aldosterone increases NCC expression through deceasing binding of 14-3-3 gamma to NCC, and therefore decreasing NCC ubiquitination.
465 CO-LOCALIZATION AND FLUORESCENCE RESONANCE ENERGY TRANSFER DEMONSTRATE INTERACTION BETWEEN THE SODIUM CHLORIDE COTRANSPORTER AND THE EPITHELIAL SODIUM CHANNEL
Wynne BM1, Mattheyses AL2, Mistry A1, Mallick R1, Hoover R1. 1 Emory University, Atlanta, GA and 2 Emory University, Atlanta, GA.
Purpose of Study: Regulation of systemic blood pressure occurs predominately via renal maintenance of sodium and water balance. The sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are both primary mechanisms for sodium reabsorption and are expressed apically in the late distal convoluted tubule (DCT2). Hyperactivity of sodium reabsorption by either can produce increases in blood pressure. These transporters are thought to work independently; however, regulatory systems such as aldosterone and angiotensin II for both NCC and ENaC contain appreciable overlap. Data from this laboratory suggests an interaction as shown by co-immunoprecipitation. Thus, we hypothesized that NCC and ENaC may be co-localized, as well as interacting with each other.
Methods Used: COS-7 cells were co-transfected with vectors containing: GFP-tagged NCC and/or mCherry-tagged subunits of ENaC α, β or γ. Co-localization experiments were performed along with fluorescence resonance energy transfer (FRET) acceptor photobleaching. Western blot analysis was performed after blue native polyacrylamide gel electrophoresis (BN-PAGE) on non-denatured cell lysate from mouse DCT cells.
Summary of Results: Transfection of COS-7 cells with GFP-tagged NCC and a subunit of mCherry-tagged ENaC (α, β or γ) revealed significant co-localization of NCC with ENaC subunits. Furthermore, using FRET acceptor photobleaching technology in the dually transfected (NCC+ENaC α, β or γ) cells, we observed a significant increase (p<0.0001, ANOVA) in EGFP fluorescence following mCherry photobleaching as compared to fluorescent-only vector controls (NCC+Cherry or ENaC β or γ+EGFP). Cells co-transfected with NCC and ENaC α or β exhibited more than a 28% increase in EGFP fluorescence, as compared to NCC+mCherry vector only expressing (9.7% ± 1.9) cells. Furthermore, BN-PAGE revealed a similar pattern of interaction; IP for NCC and ENaC α were found localized to approximately 720kDa.
Conclusions: These novel data suggest an intimate association and possible interaction between NCC and the α and β subunits of ENaC, which may influence our understanding of salt transport in the distal nephron.
466 NOVEL PROTECTIVE EFFECT OF HISTONE DEACETYLASE 9 AS A REPRESSOR OF ANGIOTENSINOGEN EXPRESSION IN THE FEMALE RAT KIDNEY
Bourgeois C1,2, Rui P3, Sato R1,2, Prieto MC1,2. 1 Tulane University, New Orleans, LA; 2 Tulane University, New Orleans, LA and 3 Tulane University, New Orleans, LA.
Purpose of Study: Young females are protected from the development of hypertension and related end-organ damage compared to males. Inappropriate activation of intrarenal renin-angiotensin system (RAS) is a major contributor to hypertension and renal injury. During intrarenal RAS activation, upregulation of angiotensinogen (AGT) in renal proximal tubular cells (PTC) serves as a key mechanism. Females exhibit lower excretion of AGT in urine, suggesting that intrarenal AGT production in females may be a protective factor against the development of hypertension. However, whether epigenetic factors influence intrarenal AGT expression levels leading to the sex disparities has not been delineated. In this study we aimed to determine the epigenetic factors controlling AGT expression in PTC.
Methods Used: AGT mRNA and protein levels in renal cortex of male and female Sprague Dawley rats were measured by real time RT-PCR and Western blot analyses. Furthermore, we used a chromatin modification enzyme PCR array to examine if epigenetic factors which repress gene transcriptions, particularly histone deacetylases (HDAC) and co-repressors, are determinant for the low AGT expression in the kidney of females. To clarify the relationship between HDAC9 and AGT, gene silencing of HDAC9 was performed in the rat PTC.
Summary of Results: AGT mRNA and protein levels were significantly lower in renal cortex of females than males (0.15 ± 0.01 in mRNA, 0.41 ± .03 in protein, ratio to male). In the HDACs and co-repressors tested in this study, only HDAC9 exhibited higher expression in renal cortex of females than males (7.09± 0.88, ratio to male). Western blot and immunohistological analyses using rat renal cortex and cultured rat PTC revealed HDAC9 is expressed in PTC. HDAC9 with Knockdown by siRNA augmented AGT mRNA (1.92 ± 0.35, ratio to control) and protein (2.25 ± 0.50, ratio to control) levels compared to scrambled siRNA transfected cells.
Conclusions: HDAC9 is a novel suppressing factor of AGT in PTC, helping to explain the low levels of intrarenal AGT in females. These findings help to delineate the mechanisms underlying sex disparities in hypertension and renal injury associated with dysregulation of RAS.
467 EFFECTS OF ATENOLOL AND HYDROCHLOROTHIAZIDE ON 24-HOUR HEART RATE AND RATE-PRESSURE PRODUCT IN BLACK AND WHITE PATIENTS WITH ESSENTIAL HYPERTENSION
Yang Z, Cotsonis G, Chapman A. Emory University School of Medicine, Atlanta, GA.
Purpose of Study: Hypertension is the most common chronic disease and leading cause of morbidity and mortality. β-blockers and diuretics are two most recommended first-line drugs, blood pressure control is achieved in only 40%, particularly lower response in blacks. Our recent study of 24-hr ambulatory blood pressure (ABP) monitoring showed that blacks are more responsive to hydrochlorothiazide (HCTZ), less responsive to atenolol (ATEN) than whites, particularly at night. Heart rate (HR) and rate-pressure product (RPP, systolic BP x HR) are independent predictors of cardiovascular events. The present study investigated the effects of HCTZ and ATEN on 24hr HR and RPP in blacks and whites.
Methods Used: 485 (60%) grade 1-2 hypertensive patients (42% black) were eligible for the study analysis. Subjects were randomized to receive either HCTZ 12.5 mg or ATEN 50 mg daily. After three weeks, the initial dose was doubled in individuals with an average home or office blood pressure >120/70 mm Hg (92.7% at maximal dose). They were maintained on this dose for at least six more weeks. ABP monitors were used to record 24hr BP and HR at baseline and at the end of drug treatment; q15 min from 6AM to 10PM (daytime) and q30 min from 10PM to 6AM (nighttime). RPP is calculated as HR x SBP.
Summary of Results: Baseline nighttime HR and RPP were significantly higher in blacks than whites. HCTZ didn’t cause HR change, but moderate reduction of 24hr RPP by 713, no difference between 2 races or day vs nighttime. ATEN caused significant reduction of 24hr HR and RPP in both races, but greater at daytime with whites (3366) higher than blacks (2582). 24hr HR and RPP were significantly lower in whites than blacks after ATEN therapy. Regression analysis showed that these responses were associated with race, baseline HR and RPP, and renin activity.
Conclusions: Nighttime HR and RPP of blacks were higher than whites, maybe due to increased sympathetic and renin activity. ATEN caused more significant reduction of 24hr HR and RPP than HCTZ in both races, specifically at daytime in whites. Therefore, ATEN seems to provide more cardioprotection than HCTZ. If HCTZ is used in high risk cardiovascular patients, combination with beta-blocker would be appropriate.
468 ACUTE KIDNEY INJURY ASSOCIATED WITH LINAGLIPTIN
Nandikanti DK, Gosmanov A, Gosmanova E. University of Tennessee Health Science Center, Memphis, TN.
Case Report: Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is an oral hypoglycemic drug which is thought to be well tolerated in diabetic patients with chronic kidney disease (CKD). Here, we report a case of acute kidney injury (AKI) after initiation of linagliptin in a CKD patient receiving lisinopril.
A 54 year-old male with hypertension on lisinopril 80mg daily, amlodipine 10mg daily, hydralazine 50 mg tid, and clonidine 0.2mg bid, type 2 diabetes on glimepiride 2mg daily, and stage 4 CKD complained on recurrent hypoglycemia during routine follow-up. He had blood pressure (BP) of 156/70mmHg and unremarkable physical exam. At baseline, serum creatinine (SCr) was 4.3mg/dL, BUN 64mg/dL, and HbA1c 5.5%. Glimepiride was stopped and linagliptin 5mg daily was initiated to reduce the incidence of hypoglycemia. In one week, the patient developed asymptomatic increase in SCr and BUN to 7.0mg/dL and 101mg/dL, respectively. His weight decreased by 2.5kg and BP was 120/57mmHg. Skin turgor was mildly decreased; otherwise, physical exam was normal. Urine sediment was bland. Fractional excretion of sodium (FENa) was 3.4%. Linagliptin was discontinued as the onset of AKI coincided with its initiation. Due to BP and weight being lower than usual, it was suspected that patient had mild volume depletion. He received 2L of normal saline over 24 hours and lisinopril was held. SCr started to improve and returned to the baseline 3.4mg/dL 10 days later. Lisinopril was restarted as the patient had proteinuria. Repeat SCr remained stable at 3.5mg/dL 4 weeks later.
In animal models, DDP-4 inhibition downregulates Na+/H+ exchanger in the proximal renal tubule leading to diuresis and BP reduction. In the present case, we also observed mild BP and weight decrease at the time of AKI. Normal kidney response during hypotension is to preserve sodium. In this case FENa, was increased and consistent with the proposed mild diuretic effect of linagliptin. We hypothesize that the patient developed AKI due to renal hypoperfusion from linagliptin-induced natriuresis in the setting of concomitant lisinopril use which is known to impair autoregulation. It may be prudent to closely monitor kidney function after the initiation of linagliptin in patients with advanced CKD treated with ACE-inhibitors.
469 ULTRAFILTRATION RATE IN HEMODIALYSIS PATIENTS. CLINICAL CORRELATIONS
Hannan E, Navarrete JE. Emory University, Atlanta, GA.
Purpose of Study: Study the realtion between weight (Wt) and ultrafiltration rate (UFR) in hemodialysis (HD). Correlate UFR with intradialytic hypotension.
Methods Used: Records of patients admitted to Emory Northside Dialysis Center in 2011 were reviewed, and included if they received more than 3 months of HD. Every HD was analyzed for changes in weight (ultrafiltration-UF) and treatment time. UFR was determined as UF(ml)/Wt(kg)/HD time(hr) and presented in ml/kg/hr. A UFR >12 was considered high. HD hypotension was defined as a drop in mean arterial pressure (MAP) of more than 20mmHg or a MAP of less than 65mmHg during HD. The pre-dialysis weight was used for UFR calculations
Summary of Results: Of 183 patients, 134 were included, representing 15389 dialysis. 57% were males and 43% were females. Age was 55±15(21-91), Weight was 81±23(36-141). 47% were diabetics, 11% had documented coronary artery disease (prior angioplasty or CABG) and 22% had CHF. 13% were HIV positive and 8% had a history of malignancy. The average UFR for the entire cohort was 8.6±3.6 ml/kg/hr (1.9-19.2). Figure 1A represents the relation between patient weight and UFR, were patients with lower weight had significantly higher UFR. 23% of HD were associated with a UFR >12ml/kg/hr. Patients with more frequents UFR>12 had similar calcium, phosphorus, hemoglobin and albumin, and higher iPTH and Kt/V than those with less frequent episodes of high UFR. The frequency of these events was inversely correlated with patient weight (Figure 1B). UFR was inversely correlated with HD time. There was no association between UFR or prescribed/achieved dialysis time and the risk of dialysis related hypotension, independent of diabetic status of the patient.
Conclusions: Patients with lower weight had significantly higher UFR, a factor that should be considered when analyzing the relation between UFR and outcomes. We found no association between UFR and risk of dialysis related hypotension.
470 HEALTH CARE CLIMATE IS RELATED TO PHOSPHORUS CONTROL IN END STAGE RENAL DISEASE
Umeukeje EM, Wallston K, Lewis J, Cavanaugh K. Vanderbilt University, Nashville, TN.
Purpose of Study: Hyperphosphatemia is a mortality risk factor in End Stage Renal Disease (ESRD). We aimed to analyze the influence of ESRD patients’ perception of providers’ autonomy support (i.e., patient centeredness) on phosphorus management.
Methods Used: In a cross-sectional study of 100 dialysis patients, phosphate binder medication adherence was assessed by the Morisky Medication Adherence Scale (MMAS) (low 0-5; high 6-8), and compared to serum phosphorus. The Health Care Climate (HCC) Questionnaire (range:1-7) assessed patients’ perception of their providers’ autonomy support for phosphate binder use. The CESD10 characterized depressive symptoms. Regression models were used to examine independent factors of medication adherence, phosphorus control and differences by race.
Summary of Results: Subjects were mean age of 51 years (SD 15), 53% male, 72% non-white, 89% hemodialysis and 11% peritoneal dialysis, with a mean serum phosphorus of 5.7mg/dl (1.6). Medication adherence was associated with phosphorus (High 5.2 (1.5) vs. Low 6.3 (1.5); p=0.0008). Higher HCC correlated with high MMAS (High 5.9 (1.8) vs. 4.9 (2.1); p=0.017), even in analyses adjusting for demographics (β [95% CI]: 0.30 [−.02 - 0.62]; p=0.066). Higher CESD10 was associated with lower HCC (80% vs. 60%; p=0.033). This differed by race (p-int=0.12), and among non-whites adjusting for age and gender, patients with higher CESD10 were more likely to have low HCC (OR [95% CI]: 4.51 [1.31 - 15.47]; p=0.017).
Conclusions: Our findings support the association between binder adherence and phosphorus control and also an association with HCC score. Depressive symptoms may be important in the perception of the health climate especially among non-whites. No significant correlation was found between HCC scores and serum phosphorus levels but this may be due to the limited sample size and the relatively small variation in the serum phosphorus levels. The influence of patient’s perceptions of the autonomy by their provider may perhaps directly affect medication adherence, and only indirectly affect serum phosphorus levels.The development of strategies targeting this perception especially through depression management in non-white ESRD patients may be critical to the optimization of mineral bone health in ESRD. Additional research in larger, more diverse dialysis samples is warranted.
471 REGULATION OF NOVEL CALCIUM-SENSITIVE DICARBOXYLATE TRANSPORT PROCESS
Walker R2,1, Coleman-Barnett JA1,3, Hamm LL1,3,2, Hering-Smith K1,3,2. 1 Tulane University, New Orleans, LA; 2 Tulane University, New Orleans, LA and 3 SLVHCS, New Orleans, LA.
Purpose of Study: Citrate is a potent inhibitor of nephrolithiasis. Urinary citrate prevents the formation of insoluble complexes between calcium and oxalate and other anions by complexation of calcium (Ca2+). The concentration of citrate in the urine is determined by proximal tubule reabsorption; most of which is thought to be facilitated by the Na+ dicarboxylate cotransporter (NaDC1). We previously demonstrated a novel calcium-sensitive dicarboxylate transport process in an opossum kidney proximal tubule cell line (OK). Reducing extracellular Ca2+ from 1.2 mM to <60 μM results in an increase in citrate and succinate transport in OK cells. This process has not yet been characterized but is likely not NaDC1 since we have previously determined that NaDC1 is not calcium-sensitive. The purpose of this study is to further elucidate the mechanisms of this novel calcium-sensitive transport process.
Methods Used: To further elucidate the regulation of this novel calcium-sensitive transport process, radioisotope uptake assays using14C-citrate (Cit) or 14C-succinate (Suc) were performed in OK cells in normal (1.2 mM) and low (<60 μM) Ca2+ conditions.
Summary of Results: To further elucidate the regulation of this novel calcium-sensitive transport process, radioisotope uptake assays using14C-citrate (Cit) or 14C-succinate (Suc) were performed in OK cells in normal (1.2 mM) and low (<60 μM) Ca2+ conditions.
Conclusions: Our data suggests that stimulation of the PKC pathway and CaSR leads to inhibition of calcium-sensitive dicarboxylate transport thus likely indicating CaSR involvement in calcium-sensitive citrate transport regulation.
472 THE RATE OF RENAL FUNCTION DECLINE IN NON PROTEINURIC DIABETICS WITH CHRONIC KIDNEY DISEASE
Hobeika L, Hunt K, Neely B, Arthur J. Medical University of South Carolina, Charleston, SC.
Purpose of Study: Patients with DM and CKD without albuminuria or proteinuria are often thought to have a cause of CKD other than DM but this has not been demonstrated. We hypothesized that if this is true, the rate of decline of renal function should be similar among non proteinuric patients with and without DM. We compared the rate of decline of renal function over a 5 year period between patients with HTN with or without DM.
Methods Used: We reviewed a database of 5035 patients from nephrology, endocrinology and general internal medicine clinics between 2008 and 2012, with an initial mean eGFR > 35ml/min/1.73m2. We used ICD9 diagnosis codes to identify patients with HTN without autosomal dominant polycystic kidney disease. We excluded patients with less than 2 measures of serum creatinine (Cr) and without urine studies over 5-year period. We calculated the yearly eGFR for each patient from the lowest serum Cr in each year using CKD-EPI formula. 856 patients had an initial eGFR between 35 and 80ml/min/1.73m2. Patients with eGFR >80 ml/min/1.73m2 were excluded. Patients with proteinuria were excluded. We defined proteinuria as positive dipstick without pyuria (wbc ≥5), or urine protein to Cr ratio ≥0.2, or 24hr urine protein ≥0.2g. Patients with microalbuminuria were included. Annual rate of decline in eGFR was estimated by fitting a regression model with random intercept and slope.
Summary of Results: Data from 370 patients without proteinuria are included in this analysis. 40.8% were male, 63.0% white and 63.8% had DM. Of those tested for microalbuminuria (n=138, 37.3%), 22.5% (n=31) were positive all of whom had DM. In unadjusted analyses the rate of eGFR decline across 5-year period was greater in patients with DM than without DM (0.87 vs. 0.12ml/min/year, p=0.0015). After adjusting for age, race, gender, baseline eGFR and use of ACE inhibitors, ARB and spironolactone, the rate of eGFR decline was greater among diabetics than non diabetics (0.80 vs. 0.26ml/min/year, p=0.0082). This association held when patients with microalbuminuria were excluded (0.74 vs 0.25ml/min/year, p=0.0209).
Conclusions: Our study showed more rapid decline in kidney function in non proteinuric CKD with DM compared to the general population. These results suggest that even in the absence of albuminuria or proteinuria DM may be the cause of loss of renal function.
Cardiovascular Club II
9:00 AM
Saturday, February 22, 2014
473 ANGIOTENSIN II TYPE 2 RECEPTOR REGULATES SKELETAL MUSCLE STEM CELL DIFFERENTIATION: IMPLICATIONS FOR TREATMENT OF CACHEXIA AND SKELETAL MUSCLE WASTING
Yoshida T, Delafontaine P. Tulane Heart and Vascular Institure, New Orleans, LA.
Purpose of Study: Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Patients with advanced CHF or CKD often have increased angiotensin II (Ang II) levels and cachexia, and Ang II causes skeletal muscle wasting and prevents muscle regeneration through Ang II type 1 receptor (AT1R) signaling. However, the function of Ang II type 2 receptor (AT2R) in skeletal muscle physiology is completely unknown. We aimed to analyze the function of AT2R in skeletal muscle regeneration.
Methods Used: Cardiotoxin (CTX) was injected into hindlimb muscles of C57BL/6 mice and the effect of AT2R suppression (AT2R antagonist PD123319 [30 mg/kg/d]) and activation (AT2R agonist CGP42112 [1 μg/kg/min]) was analyzed by quantitative RT-PCR of muscle stem cell (MuSC) differentiation markers (myogenin and eMyHC) and H/E staining. Signaling pathways downstream of AT2R in MuSC were analyzed in primary culture of MuSC by western blotting.
Summary of Results: We found that AT2R was barely detectable in mouse muscle and MuSC, but AT2R expression was robustly increased in regenerating skeletal muscle after CTX injury or cultured MuSC induced for differentiation. PD123319 infusion significantly suppressed myogenin and eMyHC expression during regeneration (56.9% and 40.2% decrease in PD, respectively. p<0.01), and reduced regenerating myofiber size (727.5±54.6 and 516.0±37.0 μm2 in sham and PD, respectively, p<0.05). On the other hand, CGP42112 infusion increased myogenin and eMyHC expression (44.5% and 79.1% increase in CGP, respectively, p<0.05), and the size of regenerating myofibers (784.3±32.1 and 981.1±65.2 μm2 in sham and CGP, respectively. p<0.05). In cultured MuSC, AT2R knockdown by siRNA suppressed myogenin and eMyHC expression and MuSC differentiation via upregulation of phospho-ERK, and ERK inhibitor U0126 treatment completely blocked the effect of AT2R knockdown.
Conclusions: These data indicate that the increase in AT2R played an important role in regulating MuSC differentiation and muscle regeneration. During MuSC differentiation, AT2R signaling positively regulates MuSC differentiation and potentiates skeletal muscle regenerative potential, providing a new therapeutic target in wasting disorders such as CHF and CKD.
474 POSTOPERATIVE CATION DYSHOMEOSTASIS WITH ARRHYTHMIAS FOLLOWING CARDIOVASCULAR SURGERY
Efeovbokhan N1, Shahbaz AU1, Atta ur Rehman B1, Weiman DS2, McGee JE3,1, Ramanathan KB3,1. 1University of Tennessee Health Science Center, Memphis, TN; 2University of Tennessee Health Science Center, Memphis, TN and 3Department of Veterans Affairs, Memphis, TN.
Purpose of Study: An acute stressor state, such as accompanies cardiovascular surgery, provokes neurohormonal activation. Ensuing elevations in plasma catecholamines promote the translocation of circulating cations (i.e., K+, Mg2+ and Ca2+) to systemic tissues. The resultant dyshomeostasis of extra- and intracellular cation concentrations in the heart leads to prolongation of myocardial repolarization and the QTc interval of the electrocardiogram, together with a greater propensity for supra- and ventricular arrhythmias. Herein we hypothesized cationic dyshomeostasis and resultant cardiac effects with arrhythmias would be found in patients having cardiovascular-related surgery, including coronary artery bypass.
Methods Used: A prospective assessment of serum K+, Mg2+ and Ca2+, together with QTc interval of the electrocardiogram, were monitored in 20 male patients (69.9±0.8 yrs) having supra- and ventricular arrhythmias within 24h of cardiovascular-related surgery at the VAMC in Memphis. The majority of these patients were receiving intravenous norepinephrine postoperatively.
Summary of Results: Hypokalemia (3.52±0.10 mmol/L) was found in 80% of these patients while 60% had hypomagnesemia (1.77±0.10 mg/dL) and 75% hypocalcemia (7.85±0.20 mg/dL). QTc prolongation (>440 ms) was seen in 95% (491±11 ms), together with 7 having new-onset atrial fibrillation, 3 with ventricular tachycardia, and the remainder having premature atrial or ventricular beats or both.
Conclusions: In patients having cardiovascular surgery, hypokalemia, hypomagnesemia and hypocalcemia, together with prolonged QTc interval, commonly appear during the immediate postoperative period. A dyshomeostasis of these cations is frequently accompanied by new onset supra- and ventricular arrhythmias, including atrial fibrillation. Serial surveillance and maintenance of these cations within narrowly defined limits (i.e., K+ >4.0 and Mg2+ >2.0) is necessary to avoid arrhythmias in this setting.
475 IGF-1 REDUCES MONOCYTES RECRUITMENT INTO THE ATHEROSCLEROTIC PLAQUE AND SUPPRESSES CHEMOKINES: POTENTIAL MECHANISM MEDIATING IGF-1-INDUCED ATHEROPROTECTION
Sukhanov S, Snarski P, Shai S, Higashi Y, Delafontaine P. Tulane University, New Orleans, LA.
Purpose of Study: We have shown that insulin-like growth factor I (IGF-1) decreases atherosclerosis in Apoe-null mice and this effect was associated with reduction in plaque macrophages. We hypothesized that IGF-1 suppresses circulating monocytes recruitment into the plaque and tested this hypothesis in the present study.
Methods Used: To assess monocytes recruitment into the plaque we feed Apoe-null mice with high fat diet for 8 wks followed by IGF-1 administration (1.5 mg/kg/d) and injection of red latex beads which are specifically taken up by monocytes. Chemokines/chemokine receptors were quantified by RT arrays and RT-PCR and protein profiling was performed with Milliplex ELISA.
Summary of Results: Acute IGF-1 administration (i.p.,1 wk) reduces red-labeled cells in the plaque (1.05±0.3, IGF-1 vs.1.8±0.2 cells/plaque, saline, control) without changes in labeled monocytes in mouse spleens. Chronic IGF-1 delivery (osmotic mini-pumps, 4 wks) also decreased labeled monocytes in the plaque (1.3±0.3, IGF-1 vs. 2.6±0.4 cells/plaque, saline) suggesting that IGF-1 reduces monocytes recruitment into atherosclerotic lesions. Since chemokines/chemokine receptors are a key regulator of monocytes chemotaxis toward atherosclerotic lesions, we quantified chemokines in mice with a 20% decline in circulating IGF-I (6T/E mice). We found that chemokines mRNA levels were upregulated in aortas of 6T/E mice vs. control mice: MCP-1, 185%; CCR1, 118%; and CCR2, 99% increase. Protein levels of circulating chemokines were also increased in 6T/E mice vs. control: MCP-1 (19.7 vs.7.6 pg/ml); CXCL1 (74.4 vs.24.9 pg/ml) and e-selectin (70.1 vs.48.9 pg/ml) showing activation of the chemokines/chemokine receptors by low serum IGF-1. To further confirm these findings we quantified IGF-1 effect on chemokines in cultured THP-1 monocytes. IGF-1 (50 ng/ml) decreased MCP-1 (43±6% decrease), CCR1(40±4% decrease) and CCR2 (38±5% decrease) mRNA in THP-1 cells.
Conclusions: We demonstrated that IGF-I reduces monocytes recruitment into the plaque. Low serum IGF-1 upregulates chemokines in vivo and IGF-1 suppresses chemokines in cultured monocytes. Taken together these data suggest that downregulation of chemokine system is the potential mechanism mediating anti-atherosclerotic effect of IGF-1.
476 LOWER CHOLESTEROL LEVELS DO NOT CONFER PROTECTION FROM CORONARY ARTERY DISEASE IN HEPATITIS C
Pothineni NK, Vallurupalli S, Mehta JL. University of Arkansas for Medical Sciences, Little Rock, AR.
Purpose of Study: Hepatitis C and Coronary artery disease post huge healthcare burdens. With advent of the inflammation hypothesis in atherosclerosis, there is increased interest in chronic infections being pro-atherosclerotic. However, limited data regarding the pro-atherosclerotic effect of hepatitis C exists. The current study was done to estimate the risk of developing CAD in patients with Hepatitis C and to see if traditional risk factors can predict the risk of CAD in this hepatitis C patients.
Methods Used: We conducted a retrospective database study using the Translational Research Institute database at the University of Arkansas for Medical Sciences. Validated International classification of diseases 9th edition (ICD 9 CM) diagnosis codes were used to identify patients with Hepatitis C and CAD. Age and sex matched controls without hepatitis C were identified for comparison. Univariate and multivariate logistic regression analysis was performed using SPSS version 21.0.
Summary of Results: Hepatitis C patients tend to have a higher incidence of CAD (4.86% vs. 3.24%, p=0.17). Traditional risk factors like hypertension, diabetes, smoking and obesity were more common in hepatitis C group. Hepatitis C patients have lower levels of total and HDL-cholesterol (p<0.05). LDL cholesterol levels were also lower in the Hepatitis C group (P<0.07).
Conclusions: Patients with hepatitis C appear to have a higher risk of developing CAD. Lipid profile does not appear to be an optimal risk stratification tool in these patients. This may be due to decreased hepatic synthetic and metabolic function. Traditional CAD risk factors also appear to be higher in this group. Hepatitis C represents a high risk group for CAD warranting closer screening and follow up for primary prevention of cardiac events.
477 MOLECULAR PREDICTORS OF STATIN INTOLERANCE
Fish H1, Elam MB2, Majumdar G2, Raghow R2. 1University of Tennessee Health Sciences Center College of Medicine, Memphis, TN and 2Memphis VA Medical Center, Memphis, TN.
Purpose of Study: The current obesity epidemic has many Americans on statin drugs. Up to 10% of these patients experience muscle pain in response to these statin drugs and are left with less effective cholesterol management therapies. Recent studies suggest an association of statin-induced myalgia and low serum levels of vitamin D. We rechallenged statin-tolerant and statin-intolerant subjects with statin drugs, and compared vitamin D levels, as well as gene expression in muscle biopsy and peripheral blood mononuclear cells (PBMC’s). Another question we sought to answer was whether any changes in gene expression seen in the muscle are reflected in PBMC’s. If so, this would allow future use of PBMC’s as a sentinel for muscle.
Methods Used: Biopsy samples and PBMC’s were collected through the Hypertension/Lipid Research Clinic at the VA. RNA was isolated using the TRIzol method, converted to cRNA, and hybridized to microarray beads using Illumina Human Expression BeadChip Kits. Microarray gene expression analysis was performed in a specialized lab and the microarray data was processed with Illumina BeadStudio GX Module (3.4.0). We used GeneSpring software to identify genes that are differentially expressed between the statin-tolerant and statin-intolerant subjects and input these candidate genes into Ingenuity Pathway Analysis, to identify any common pathways.
Summary of Results: Vitamin D levels were in fact found to be significantly higher (p=0.025) in the cases group, however 7 of 16 cases, versus 0 of 10 controls, were on a vitamin D supplement at the time of the study. A trend was seen between intolerance and a positive family history of intolerance (p=0.09), suggesting a genetic component of statin-induced myalgia. A psychological component may also be at play, with an association (p=0.028) between patient-reported concerns regarding statin drugs and the incidence of myalgia. RNA microarray do not seem to indicate that gene expression changes seen in the muscle are reflected in PBMC’s, indicating that PBMC’s may not be a sentinel for muscle tissue.
Conclusions: Vitamin D deficiency alone may not precipitate adverse muscle symptoms in response to statins. However, there seems to be a genetic component to statin-induced myalgia and further pathway analysis should illuminate some of the mechanisms involved.
478 GUANYLYL CYCLASE/NATRIURETIC PEPTIDE RECEPTOR-A GENE-DISRUPTION INDUCES CARDAIC FIBROSIS THROUGH CANONICAL SMAD-DEPENDENT MECHANISM
Chen D, Subramanian U, Pandey KN. Tulane University, New Orleans, LA.
Purpose of Study: Disruption of the guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) gene leads to elevated arterial blood pressure, progressive cardiac fibrosis and congestive heart failure in mice similar to untreated human hypertensive patients. The objective of this study was to illuminate the mechanisms of cardiac fibrosis in mice carrying permanent ablation of NPRA signaling.
Methods Used: Heart tissues of gene-disrupted (Npr1-/-, 0-copy), and wild-type (Npr1+/+, 2-copy) mice were used for the analysis of cardiac hypertrophy and fibrosis using Masson’s trichrome staining. Western blot and immunohistochemistry analyses were performed to elucidate the cardiac levels of fibrotic markers and SMAD proteins in Npr1-/- mice hearts.
Summary of Results: Significant increases in the expression levels of fibrotic markers such as connective tissue growth factor (5-fold), alpha-smooth muscle actin (3.5-fold), and transforming growth factor-β (TGF-β, 4.5-fold) were observed in 0-copy (Npr1-/-) mice hearts compared to 2-copy (Npr1+/+) mice. Likewise, the expression levels of TGF-β1 receptor I (TGF-βRI) and TGF-β1 receptor II (TGF-βRII) were induced by 4-fold and 3.5-fold, respectively, in gene-disrupted Npr1-/- mice hearts. Furthermore, the expression levels of SMAD proteins were also measured to delineate the role in fibrosis. The results demonstrated that the expression levels of pSMAD2, pSMAD3, and SMAD4 were increased by 3-fold, 2-fold, and 3-fold, respectively, in the Npr1-/- mice hearts compared to age-matched wild-type mice.
Conclusions: The results of the present study suggest that the development of cardiac fibrosis in Npr1 knockout mice might be regulated through the canonical SMAD-dependent pathway.
479 ANGIOTENSIN II SUPPRESSES MUSCLE REGENERATION IN THE MURINE MODEL OF MUSCULAR DYSTROPHY
Galvez S, Yoshida T, Sukhanov S Delafontaine P. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: We have previously shown that Ang II induces skeletal muscle wasting and suppresses skeletal muscle regeneration in the cardiotoxin-induced injury model in mice. We hypothesized that Ang II would suppress skeletal muscle regeneration contributing to muscle wasting in mice with muscular dystrophy.
Methods Used: To test this hypothesis, we used C57BL/10ScSn-Dmdmdx/J (mdx) mice and measured levels of regeneration markers (Pax7, Myod, and myogenin) and histologically quantified the percent regeneration of muscle cross sections. We infused 8-10 week old female mdx mice with 500 ng/kg/d Ang II for 7 days via osmotic minipumps.
Summary of Results: In H&E staining of cross sections of gastrocnemius muscles, the percentage of total CSA with centronucleated myofibers was significantly reduced in Ang II infused mice (21.7% decrease, n= 6 in both groups, p = 0.0087). RNA from quadriceps muscles was analyzed by qPCR of the myogenic regulatory factors Myod, myogenin, and Pax7. While Ang II caused an insignificant decrease in the mRNA expression of Pax7, there was a significant increase in Myod mRNA expression (3 fold increase, Saline n = 7, Ang II n = 6, p = 0.0012) and an insignificant increased trend in myogenin mRNA expression.
Conclusions: Our data suggests that Ang II suppresses muscle regeneration by inhibiting the activation of satellite cells and delaying the process of regeneration. This finding is likely important for the understanding of mechanisms of muscle degeneration in muscular dystrophy. In future studies, we will attempt to further elucidate mechanism(s) by which the renin-angiotensin system modulates muscle degeneration/regeneration in muscular dystrophy.
Allergy, Immunology, and Rheumatology II
Concurrent Session
1:00 PM
Saturday, February 22, 2014
480 LOW BONE MINERAL DENSITY IN AFRICAN-AMERICAN MALES MAY BE MORE PREVALENT THAN PREVIOUSLY REPORTED
Aujla KS, Majithia V. U.M.M.C., Jackson, MS.
Purpose of Study: Osteoporosis (OP) in Males is prevalent and frequently under-recognized. There are a number of known demographic factors such as age, race and BMI as well as secondary causes of low bone mineral density (BMD). This study aims to describe the prevalence of the demographic factors and SC in men with low BMD and also assess their impact on the prevalence.
Methods Used: Retrospective chart review of men who underwent DEXA scan performed at UMC from 2005-2012 was done. Data regarding BMD, demographics i.e. age, race, height, BMI, secondary medical causes, medications, social factors was analyzed.
Summary of Results: 585 charts were analyzed. There were 410 whites (W), 175 African-Americans (AA). Low bone density was prevalent in 437 patients (74.7%). Amongst these 143 (24.4%) had T-score < -2.5 (osteoporosis) BMD. In this cohort, osteoporosis was seen more commonly in 53/175 AA males (30.28%) versus 90/410 W males (21.95%). These AA males were younger (Mean age 56.04) as compared to W (Mean age 62.64). Low BMI seemed to be the major contributor to low BMD.
Conclusions: In this cohort osteoporosis was seen in a higher % of AA males as compared to W males and at a younger age but no racial differences were found in the prevalence of known risk factors. Also found was that Low BMI, smoking and overall medication use may be better associated with low BMD and potentially better predictors than older age and secondary medical disorders. These results highlight that the racial differences in prevalence and effect of underlying factors needs to be better quantified in the epidemiology of male osteoporosis
481 CRYOGLOBULINEMIA WITH DEPOSITION MEDIATED DYSFUNCTION
Googe A, Grover I. University of Mississippi, Jackson, MS.
Case Report: A 48 year old white female with cryoglobulinemia presented with non-tender, non-pruritic, non-palpable purpura up to 4 cm in diameter. Upon admission, dopplers were positive for DVT, and we initiated anticoagulation. Next, we obtained a biopsy of the purpura. Hepatitis C, hepatitis B, ANA, ANCA, RPR, and HIV antibodies were negative. However, RF was >700 units/mL, and a polyclonal gammopathy was present. Skin biopsy studies revealed deposition of IgM and C3 in the vessel subepithelium, and a neutrophilic infiltrate with necrosis of the dermis and epidermis suggestive of deposition mediated leukocytoclastic vasculitis. Following admission, the patient’s status deteriorated and by day 3, the serum creatinine had risen from 0.73 mg/dL to 2.19 mg/dL with urinary red blood cell casts. A normocytic anemia developed with hemoglobin of 6 g/dL from 12 g/dL. TTE estimated an EF of 30%, reduced from ≥60% just 3 months prior to admission. With plasmapheresis, high dose prednisone, and azathioprine, the purpura and mulit-system dysfunction resolved within 2 weeks.
482 JUVENILE IDIOPATHIC ARTHRITIS IN MINORITIES PROPORTIONAL TO DEMOGRAPHIC
Hundley K1, Brown AG2,1. 1LSUHSC, NEW ORLEANS, LA and 2Children’s Hospital, New Orleans, LA.
Purpose of Study: JIA is a rare autoimmune disease that causes inflammation and damage in the joints of children. This is a descriptive study of JIA patients enrolled in a mult-center CARRA study at Children’s Hospital of New Orleans.
Methods Used: Patients diagnosed before 16 who met JIA criteria were recruited from the Rheumatology clinic. Baseline data recorded includes: demographic information; medical and family history; JIA classification; physician assessment; medication exposures; CHAQ and Health, quality of life, disease activity and pain assessments. All information collected was de-identified and shared with the CARRA registry.
Summary of Results: This cohort of 14 JIA patients includes 3 males, 4 African-Americans and 10 Caucasians; 29% were African-American. Age range is 1 to 18 with an average age of 10 years. The average disease duration is 5 years. Subtypes included are oligoarticular, pauciarticular, RF negative polyarticular and systemic. Nine patients have been exposed to corticosteroids, and 8 to DMARDs and biologics. Of these 8 patients, 6 were polyarticular, 1 was oligoarticular and 1 was systemic JIA. Six oligoarticular or systemic JIA patients used systemic or intra-articular steroid injections alone. The average CHAQ is 0.77; the average disease activity score is 3.5; and the average pain score is 5. The average current functional class is I, and worst ever functional class is II. The most common subtype was RF negative polyarticular JIA, which differs from the most common reported subtype of oligoarticular JIA. Subtype was associated with type of treatments; over half required biologics or DMARDs for their JIA. The average CHAQ was 0.77.
Conclusions: Our study shows that African-Americans are proportionally represented in our population, while other studies have demonstrated that they are underrepresented. The average CHAQ corresponds with mild to moderate disability, in contrast to the average functional class of I. The majority of patients function well in daily life. A worst functional class ever of II suggests JIA can affect functional ability. The average disease activity score and the average pain score suggest that JIA is difficult to control. This small cohort added to the national CARRA database can improve treatment and outcomes JIA paitents.
483 CAT SCRATCHES PATIENT; I SCRATCH MY HEAD
Compton S, Maher L, Majithia V. University of Mississippi Medical Center, Jackson, MS.
Purpose of Study: Patients with systemic lupus erythematosus (SLE) frequently present with fever. Determining if the fever is a reflection of active lupus, infection, or other cause can be clinically challenging. Establishing the correct diagnosis is crucial as therapies can be markedly different. While immunosuppressive agents are helpful in active lupus, they could worsen symptoms if used in the wrong setting.
Methods Used: Case Presentation.
Summary of Results: A 22 year old white female with SLE was seen in clinic for a seven-day history of intermittent fevers up to 102 Fahrenheit. Other than myalgias, she was relatively asymptomatic without sick contacts or signs of active lupus. At evaluation, she had been afebrile for 24 hours; physical exam was unremarkable other than a cushingoid appearance. Inflammatory markers and complements were normal, and a viral etiology was suspected. We continued her prednisone and hydroxychloroquine; however, her azathioprine was held for one week. A few days later, her fever returned; labs showed marked increases in her inflammatory markers with decreasing complements. Exam was largely unchanged other than scratches on the bilateral forearms from a recently purchased cat. Bartonella titers for cat scratch disease returned strongly positive, and treatment with azithromycin was started. Her fever resolved after treatment, and repeat bartonella serologies trended downward. Her azathioprine was resumed shortly thereafter given concerns that her recent infection placed her at high risk for a lupus flare. At follow up, her complements had returned to baseline, and there were no clinical signs of active lupus.
Conclusions: Cat scratch disease is caused by the gram negative bacteria Bartonella henselae and typically presents with self-limited adenopathy, fever, myalgias/arthralgias and occasionally visceral organ involvement. Diagnosis is made by clinical impression plus serologic testing. Although it more commonly affects children, our patient was likely more susceptible given her SLE and use of immunosuppressive medications. The lack of adenopathy may be explained by her cushingoid appearance or a compromised peripheral lymphatic tissue reaction due to immunosuppression. Since infections can cause symptoms similar to active lupus, clinicians must remain vigilant when assessing SLE patients with fever to ensure proper therapy is initiated.
484 PRESCRIBING PATTERNS OF MYCOPHENOLATE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Varadarajan R, Morella K, Gilkeson G, Oates J, Kamen D. Medical University of South Carolina, Charleston, SC.
Purpose of Study: Lupus nephritis (LN) is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). Several studies have demonstrated favorable efficacy and safety for mycophenolate mofetil (MMF) in LN, and these reports have led to increasing use of MMF for patients with SLE and LN, particularly in African Americans (AA). Use of MMF for extra-renal manifestations of SLE has not been as well-described.
The aim of this study is to compare prescribing patterns of MMF with other therapies for SLE and examine whether use of MMF for extra-renal manifestations of SLE protects against development of LN.
Methods Used: Retrospective data from 562 patients with SLE enrolled in the longitudinal MUSC Lupus Database were included in this study. Patients with LN were compared to SLE patients without renal involvement. Demographic and medication use categories were compared using Chi-square testing. Two-sided p-values <0.05 were considered significant.
Summary of Results: Comparison of patients with and without LN is shown in Table 1. Of the 235 patients who have ever taken MMF, 100 patients had no LN within 90 days of starting, and 11 of the 100 (11%) subsequently developed LN. A similar proportion (11%) of the 141 patients started on AZA with no LN within 90 days of starting subsequently developed LN.
Conclusions: MMF use is growing for both LN and now extra-renal manifestations of SLE. Of interest, we found that MMF is more commonly prescribed than azathioprine, long considered the first-line steroid-sparing immunosuppressant for SLE. This study confirms the trend towards using MMF for extra-renal manifestations of SLE at our institution. Although patients taking MMF and AZA for extra-renal manifestations of SLE had the same likelihood of subsequently developing LN, MMF was prescribed to patients at higher risk of LN suggesting a possible protective effect which should be explored in prospective studies.
485 CHALLENGE OF DIAGNOSING AVARIANT OF SWEET SYNDROME IN AMYOPATHIC DERMATOMYOSITIS
Chiang EP, Leblanc S, Majithia V, Johnson D. University of Mississippi Medical Center, Division Rheumatology, Jackson, MS.
Case Report: Sweet syndrome is a rare skin disease known as acute febrile neutrophilic dermatosis, characterized with abrupt fever, neutrophilia, and painful skin lesions of the face, neck, trunk, and extremities. Neutrophilic dermatosis (pustular vasculitis) of the dorsal hands is a localized variant involving dorsal hands. Sweet syndrome maybe associated with leukemia, malignancy, inflammatory bowel disease or medications. It is challenging to diagnose and evaluate the etiology in a patient with auto-immune disease such as amyopathic dermatomyositis.
We report a case of a 64-year-old woman with amyopathic dermatomyositis treated with hydroxychloroquine and azathioprine. Two and half weeks after initiation of azathioprine, she presented with fever, hypotension, generalized weakness, and cutaneous eruption of tender pustules, confluent raised plaques, and vesicular lesions mostly on dorsal hands and mildly forearms, face, and legs. Laboratory evaluation noted leukocytosis, neutrophilia, CRP 14.5mg/dl, ESR 45mm/hr, positive urinalysis with urinary tract infection. Due to atypical presentation of her rash and CPK of 141 U/L, alternative etiologies were considered. Subsequent histopathology of a skin biopsy supported neutrophilic dermatosis of dorsal hands. Azathioprine, felt to be her trigger, was discontinued and IV fluid, broad spectrum antibiotics, and methylprednisolone 125 mg IV daily were given resulting in rapid resolution of majority of the cutaneous eruptions and residual healing of plaques. At follow-up, she is doing well with continued resolution of eruptions.
Sweet syndrome associated with azathioprine is uncommon and challenging to diagnose. It can resemble azathioprine hypersensitivity syndrome due to overlapping features and necessitate histopathology to tell apart. In addition, the initial cutaneous manifestation of neutrophilic dermatosis of dorsal hands can mimic dermatomyositis, wherein the cutaneous lesion distribution could lead to confusion as to cause of the skin lesions. In our patient, skin biopsy was required in finalizing diagnosis. Most patients with drug-induced Sweet syndrome have dramatic response with systemic corticosteroid as shown here.
486 NOW YOU SEE IT! NOW YOU DON’T!! A CASE OF FALSE POSITIVE HIV TEST IN LUPUS
Bhawal J, Lirio E, Majithia V. UMMC, Jackson MS.
Case Report: Introduction: Lupus is autoimmune disease, which has a variable and extremely heterogeneous presentation and has a number of auto-antibodies. Due to lupus patient’s propensity to form antibodies, they may have a variety of false positive test-results. ANA, Ant-smith, dsDNA, SSA and SSB are usually positive in lupus and in HIV patient
Case: A 56-year-old female with history of HTN and anemia presented with acute renal failure and a creatinine of 9. She was hospitalized and work up showed anemia, leucopenia, thrombocytopenia, UA showed 4+ protein, and she had 4 gram proteinuria on 24 hr-urine. results showed high positive ANA, SSA, SSB, Ds DNA, HIV, and anti-smooth muscle antibodies.
She had no other S/S of lupus (no hair loss, no oral sores, alopecia, malar rash, arthritis), her sexual and social history put her low risk for HIV. Confirmatory tests for HIV, western blot and high sensitivity PCR were negative. A renal biopsy was not performed due to thrombocytopenia and elevated creatinine of 4.
During hospital course she was started on hemodialysis, hydroxycholoroquine 200 mg daily, and prednisone 60 mg daily for 3 weeks . She was discharged. On follow up in 3 weeks she continued to have no lupus related symptoms, and azathioprine 150 mg/day was started.
Discussion and Conclusion: Two tests usually performed for screening and confirmation of HIV are ELISA and Western Blot. HIV PCR testing is the most sensitive and specific test for presence of the infection. Both antibody tests can be falsely positive in normal patients and particularly in patients with auto-immune diseases. Patients with out any medical history and especially those with previous blood transfusions, prior pregnancies or an organ transplant will make HLA antibodies. Test kits for HIV (both for ELISA and Western Blot Test) will be contaminated with HLA antigens to which these antibodies can react causing positive tests. patients with HIV may also present with positive ANA, ANCA, Anti-GBM antibodies without any clinical manifestation.
487 DEADLY DERMATOMYOSITIS: A CASE OF RAPID DECOMPENSATION
Wright A, Engel LS McKay M. LSU Health Sciences Center, New Orleans, LA.
Case Report: Dermatomyositis is an uncommon inflammatory disease marked by muscle weakness and characteristic cutaneous findings. In recent years, a subset of patients with polymyositis and dermatomyositis has been found to have antisynthetase syndrome which is now recognized as an important cause of autoimmune inflammatory myopathy.
CASE: A 54 year old white male diagnosed with dermatomyositis and interstitial lung disease within the past month presented complaining of worsening generalized weakness and difficulty breathing. The patient received a dose of methotrexate and was told to resume prednisone prior to his presentation. Physical exam showed mild hypoxia, mild tachypnea and fine posterior rhonchi. A cat scan of his chest revealed drastic worsening of the interstitial lung disease previously noted. He was started on high dose steroids as antisynthetase syndrome and acute alveolitis was suspected. The patient continued to have hypoxia and unpredictable variations in his respiratory status and developed new-onset systolic heart failure. On day 19 of his admission, he had rapid decline in his blood pressure and oxygen saturation requiring intubation and treatment with pressers. Unfortunately he progressed to multi-organ failure with marked metabolic and respiratory acidosis as well as bilateral pneumothoraces and pneumomediastinum. His DNR status was discussed with his family and care was withdrawn.
DISCUSSION: Dermatomyositis is typically a disorder of residual weakness and disability whereby the great majority of patients affected do not die from the disease process itself. However, ∼5% have a fulminant progressive course with eventual death, mostly from muscle weakness or cardiopulmonary involvement. Antisynthetase syndrome, a rare medical syndrome caused by antisynthetase antibodies that manifests as interstitial lung disease, inflammatory polyarthritis or myopathy, may be associated with rapid progression of dermatomyositis. There is limited treatment available for antisynthetase syndrome.
Clinical Epidemiology and Preventive Medicine
Concurrent Session
1:00 PM
Saturday, February 22, 2014
488 A COMMUNITY HEALTH WORKER HOME VISITATION PROJECT IN KENYA
Garcia B, Mascarenas D, Wurzburger R, Tomedi A. The University of New Mexico School of Medicine, Albuquerque, NM.
Purpose of Study: Four million children die globally each year. Most of these deaths occur in developing countries and are due to preventable disease. Sub-Saharan Africa has disproportionately high neonatal mortality. Community Health Worker (CHW) programs are a promising intervention to reduce this high mortality rate. This research evaluates a CHW Program in rural Kenya. We assessed frequency of utilization of health care facilities and overnight hospitalizations in families who are participants in the CHW program versus families who did not participate.
Methods Used: This quasi-experimental study encompassed two consecutive years and compared the rate of utilization of medical facilities for neonatal illness in an intervention group with the rate in a control group. The control group was a random sample of 176 infants born during the same year and in the same villages as the intervention group, but who did not receive home visits by CHWs. The intervention group was a random sample of 326 infants who received home visits. CHWs taught mothers healthy newborn care and breastfeeding practices and assessed infants for signs of illness. Utilization of medical services was measured using a household survey. Severity of neonatal illness was assessed by need for overnight hospitalization. Household, maternal, and child characteristics were collected in the survey.
Summary of Results: Surveys were completed for 502 households with infants less than 1 year of age. Among families not visited, 36% reported taking their infant to a healthcare facility, compared with 22% of families visited by a CHW (p < .01). Rates of overnight hospitalization were 6% for not-visited infants and 1% for visited infants (p=.004). No significant differences were found in household, maternal, and child characteristics. 43% of CHW visited families were in the poorest quintiles, while 33% of not-visited families were in the poorest quintiles (p = .11).
Conclusions: This study found that a CHW newborn home visitation program in rural Kenya was able to significantly decrease rates of health care facility utilization and need for hospitalization. This study did not have the power to detect an effect on neonatal mortality, but the reduction in health care utilization and hospitalization rates suggest the potential to reduce mortality.
489 HIGH SENSITIVITY C-REACTIVE PROTEIN IS ASSOCIATED WITH CYSTATIN C IN WHITES BUT NOT IN BLACKS: THE BOGALUSA HEART STUDY
Thakkar BG, Fernandez C, Chen W, Srinivasan SR, Berenson GS. Tulane University, New Orleans, LA.
Purpose of Study: High sensitivity C-reactive protein (hsCRP) is a reliable marker for inflammation-mediated end organ damage and serum cystatin C is a reliable marker for renal function. Decreased renal function (GFR<60ml/min/1.73m2) is associated with elevated levels of inflammatory markers. Some studies have shown that hsCRP is significantly associated with cystatin C - both in elderly population with GFR<60ml/min/1.73m2 and also in elderly population with GFR>60ml/min/1.73m2. Our aim is to study racial (black-white) divergence in the association between hsCRP and cystatin C in asymptomatic young adults.
Methods Used: This is a cross-sectional analysis of 794 subjects enrolled in the Bogalusa Heart Study with mean age 43.5 years (29.4-51.2 years), 31.4% blacks, 58.3% females. Multivariable linear regression analysis was used to determine significant racial divergence in the association between hsCRP and cystatin C, after controlling for traditional cardiovascular risk factors.
Summary of Results: The mean value of cystatin C in white subjects was 0.84 mg/L (+/- 0.25), whereas in black subjects it was 0.82 mg/L (+/- 0.25); the difference was not significant (p=0.616). After accounting for the effect of multiple cardiovascular risk factors, hsCRP was a significant predictor of cystatin C in whites (β=0.157, p<0.001) but not in blacks (β=0.125, p=0.24).
Conclusions: The mechanism of inflammation-mediated end organ damage in relation to renal function is influenced by racial (black-white) phenotypes. Thus, racial divergence should be taken into account while estimating the risk of inflammation-mediated end organ damage in association with renal function.
490 COMPARISON OF CLINICAL COVARIATES IN AFRICAN AMERICANS AND CAUCASIANS WITH AND WITHOUT FAMILY HISTORY OF PROSTATE CANCER
Soodana prakash N1, Ledet E2, Dotiwala AK1, Luk EJ1, Sartor AO2. 1Tulane School of Medicine, New Orleans, LA and 2Tulane University, New Orleans, LA.
Purpose of Study: 15.33% of men born today will be diagnosed with PCa their lifetime. Older age, African Ancestry and family history are well known risk factors for PCa. For this study, patients were recruited from Louisiana, especially Southeastern Louisiana, which has been shown to have both a unique Caucasian (CA) population and a highly admixed African American (AA) population (Parra et al. 1998. Am J Hum Genet. 63(6):1839-1851). We evaluated whether having family history of PCa influenced clinical presentation, and then compared these results to published literature in order to determine if this cohort was a representative population.
Methods Used: Via the Tulane Cancer Center clinics, we identified 552 patients with a clinical and histopathological diagnosis of PCa. Among them 117 were AA and 435 were CAs; 48 AA men and 130 CA men reported to have a PCa family history (first degree relatives with PCa). We documented the following clinical factors: age of onset, metastasis, and Gleason score. Analyses were performed to identify any potential clinical correlations with regards to family history of PCa, race, and other clinical covariates
Summary of Results: In this cohort, AA men (41%) were more likely to have a family history of PCa than CA population (30%) (p=0.0295). Men with a family history of PCa had a significantly younger age at diagnosis regardless of race (p<0.0001 for both). AA men with family history had significantly younger age at diagnosis compared to their CA counterparts (p<0.0001); AA with family history were youngest at diagnosis (mean 60.58). There were no significant differences in Gleason score or metastasis with regards to family history and race
Conclusions: In this study we did not find any significant relationship between family history and Gleason score or metastasis. AA men were more likely to have a family history of PCa when compared to CAs. In both populations, family history was associated with an earlier age at diagnosis. These findings are consistent with similar cohorts reported in the literature. Continued expansion of this important cohort may yield significant insight into underlying racial and clinical disparities observed in familial PCa.
491 RISKY TEEN DRIVING BEHAVIOR TRENDS
Smola C, Woodfin T, King WD, Monroe K. UAB, Birmingham, AL.
Purpose of Study: Motor vehicle crashes are the leading cause of death for U.S. teens with Alabama ranking 4th. Many interventions, including teen driving summits, strengthened state Graduated Drivers License (GDL), public service announcements, and texting laws have been initiated. GDL laws were passed in July 2010 and advertisement started in fall, 2010. Texting laws became effective in July 2012 although passage and advertisement were started prior to that date. Our study surveyed area teens for the last four years (2009-12) to determine the prevalence of risky driving behaviors and any changes as a result of previously stated interventions.
Methods Used: A survey was given to every high school in Jefferson County, Alabama in October of the last four years. Monetary rewards were given to increase responses. Students were questioned on their knowledge of GDL laws, their driving behaviors of seatbelt use, drinking, speeding, and texting. IRB approval was obtained and data was collected anonymously. The study tested for possible correlations of selected behavioral factors over time using the Spearman Rank Correlation provided by Epi Info, Version 7.
Summary of Results: Data was trended over four years and divided into two periods (2009-10) and (2011-12) to determine if the interventions started in 2010 were making a significant change. We compared the two data groups' responses during the last 30 days. Demographics were similar between the two groups. Although some variation in the prevalence of speeding and seatbelt usage was noted, no significant correlations for any behavioral factor were detected.
Conclusions: Both strengthened GDL laws with their corresponding advertisements and texting laws have not resulted in a consistent change. The initial evaluation only spans four years, (only two years of the GDL change); so further years of observation could improve statistical power and reach a higher awareness of the new law. Obviously, the high prevalence of texting, speeding and alcohol use and the low seat belt use among teen drivers are worrisome. The decreasing prevalence of speeding may be the singular, consistent improvement over time that was observed, although not statistically significant. Continued education and awareness of the law must continue to augment the protective effects of the most recent amendments.
492 PERITONITIS IN PERITONEAL DIALYSIS PATIENTS REQUIRING HOSPITALIZATION
Falk IN1, Colombo R1, Baer S1,2, Kheda M1, Iwuagwu N1, Huber L1,2, Nahman NS1,2, Kintziger K1,2. 1 Medical College of Georgia, Augusta, GA and 2 Charlie Norwood VA Medical Center, Augusta, GA.
Purpose of Study: Peritonitis (PTN) is a common complication of peritoneal dialysis (PD). PTN is usually treated in an outpatient setting, but PTN patients with complications (septic symptoms or severe abdominal pain) may be admitted for management. By definition, this inpatient group may constitute a sicker population, raising questions of potential co-morbid conditions that may be associated with PTN requiring admission. On this basis, we queried the United States Renal Data System (USRDS) to assess the incidence of inpatient PTN and the co-morbidities that may be associated with the disease.
Methods Used: All incident PD cases from the years 2005–2008 from the USRDS were included in the analysis. PD was initially defined according to the dialysis modality indicated on the most recent form 2728. PTN and all comorbidities were defined by ICD-9 diagnosis codes. Dialysis modality at PTN diagnosis was also obtained and classified as either PD or non-PD. Descriptive statistics were performed, and chi-square test p-values were reported.
Summary of Results: The analysis included 25,292 PD patients. Inpatient PTN occurred in 17% of the group. Those who were not on PD at the time of PTN diagnosis (770 patients, 3%) were excluded from subsequent analysis. Demographics showed: 54% male, 72% Caucasian and 64% < age 65 years. When compared to PD patients without PTN, patients with PTN exhibited greater incidences of an array of significant co-morbidities, including diabetes (53 vs. 27%), bacteremia with SIRS (19.9 vs. 5.1%), bacteremia without SIRS (13.8 vs. 8.1%), PVD (11.2 vs. 7.6%), MRSA infection (2.7 vs. 0.8%), hepatitis C (2.7 vs. 1.1%) and systemic lupus erythematosus (2.4 vs. 0.9%). There were no differences in the incidence of appendicitis, decubitus ulcer, endocarditis, pancytopenia, and Wegener’s.
Conclusions: Inpatient PTN occurs in almost 20% of incident PD patients. It is associated with diabetes as well as serious infectious conditions. These results suggest that symptomatic outpatients with a possible diagnosis of PTN may be at risk for serious infectious complications, including bacteremia and sepsis, and the continued practice of admitting symptomatic patients is appropriate.
493 RELATIONSHIP BETWEEN WIND DIRECTION AND A TEMPORAL KAWASAKI DISEASE (KD) CLUSTER
Burns JJ1, Amin R2, Broge T1, Hommeida S1, Onuegbu P1, Taylor S1. 1 FSU College of Medicine, Pensacola, FL and 2 University of West Florida, Pensacola, FL.
Purpose of Study: To determine if a temporal cluster of KD cases had any relationship to wind direction as has been reported in Japan, Hawaii and San Diego (Rodo X., Ballester J., Cayan D., Melish M., Nakamura Y., Uehara R., Burns J. Association of KD with tropospheric wind patterns. Scientific Reports 2011)
Methods Used: KD cases admitted to a Northwest Florida Children's Hospital from 2/16/2008 to 9/10/2011 (42.5 months) were previously analyzed for temporal clustering using SATSCAN™. A statistically significant temporal cluster of KD cases was found between 12/11/2010 and 9/10/2011 (9.0 months). The daily measured hours of wind from eight different directions for the local area during the 42.5 months of the KD study were downloaded. (http://weathersource.com). The data was categorized into one of two groups: either in the KD time cluster or not in the KD time cluster. Statistical significance was set to p-value <0.005 to account for multiple analyses using Bonferroni correction.
Summary of Results: The non-parametric Mann-Whitney U test was used to compare the hours of wind direction coming from eight compass points for those dates in the KD cluster vs. those not. During the KD temporal cluster there was statistically higher number of hours of wind from the south-southwest (Mann Whitney: p = 0.000) and lower number of hours of wind from the reciprocal east-northeast (Mann Whitney: p = 0.002) and north-northeast directions (Mann Whitney: p = 0.001). No statistical significance was found between the KD cluster and other wind directions (Table 1).
Conclusions: There appears to be a relationship between a temporal KD cluster and the wind direction adding further evidence linking wind currents with KD.
494 NOVEL APPLICATION OF GENOMICS HEAT MAP MODEL FOR META-ANALYSIS OF CLINICAL NUTRITION CURRICULUMS TO IMPROVE PHYSICIAN-GUIDED NUTRITIONAL LIFESTYLE MANAGEMENT OF CHRONIC DISEASE
Hill K, Monlezun DJ, Harlan T. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Despite significant evidence showing that the impact of physician counseling on patient lifestyle modifications reduce the risk profile for these chronic diseases, there is no consensus on evidence-based nutrition course of study for current or future physicians. To determine which curricula have sufficient efficacy in patient outcomes and acceptance by physicians and medical students, The Goldring Center for Culinary Medicine conducted a novel application of the genomics heat map model producing a robust systematic review and meta-analysis to accelerate dissemination of evidence-based curricula to physicians and medical students.
Methods Used: Studies were clustered by similarities in impact on the American medical community (estimated by the Scimago Journal & Country Rank), type of education curriculum, and study design. Data analysis features chi-square test, McNemar test, and multivariate logistic regression to provide predictive statistical models.
Summary of Results: Retrieval included 22,408 articles, from which 13 studies were incorporated (n=1,879 subjects). Most studies (93%) relied mainly on convenience voluntary surveys for curriculum impact and acceptance, with few including such objective measures as students' national board scores and physicians' documentation prevalence in medical charts for nutrition education. No studies correlated patient outcomes with longitudinal tracking of curriculum impact on medical professionals, nor integrated cooking and clinical nutrition curricula in both classroom and community contexts.
Conclusions: This novel application of the genomic heat map model not only demonstrates the clear need for methodology improvements in promising curriculum development and dissemination, it also highlights the need for such innovated hands-on cooking and nutrition curricula as that of The Goldring Center for Culinary Medicine amid the global chronic disease epidemic.
495 A Pinch of Experience: Integrated Clinical Nutrition Curriculum as Continuing Medical Education for Practicing Physicians
Urday P, Monlezun DJ, Harlan T. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Nearly half of physicians report lack of competencies in patient nutritional education for common obesity-influenced diseases. Continuing Medical Education (CME) credits may thus be an effective opportunity for providing the most up-to-date nutritional education strategies to enhance practicing physicians' competencies and positive attitudes toward patient nutritional education
Methods Used: Tulane University School of Medicine launched the first known medical school-based teaching kitchen led by a professional chef with dedicated research capacities as The Goldring Center for Culinary Medicine. The center translated its 25-hour medical student elective curriculum over 6 modules integrating cooking skills and clinical nutrition into a CME-styled curriculum for physicians. Physicians on this pilot study (n=8) were administered a 69-question survey before and after their first two modules. Baseline analysis evaluated these metrics using chi-square test, non-parametic McNemar test, and multivariate crude and adjusted logistic regression models in comparison to medical students (n=51) and residents (n=28) who participated in their respective nutrition curriculum tracks in similar degree as the physicians.
Summary of Results: After the nutrition education intervention, the comparable majority of medical students (86.3%) and residents (85.7%) reported lack of proficiency in patient education for Type II diabetes, in contrast to the minority of CME physicians (28.6%, p = 0.001). Physicians were 94% less likely to report lack of proficiency compared to residents and medical students (OR=0.06, CI 0.0111-0.3758, p=0.002). This relationship disappeared after controlling for time in practice.
Conclusions: Our findings suggest that the competencies in nutrition education by practicing physicians is not significantly superior to residents or medical students in areas outside of education for diabetics. Integrated curriculums like that of The Goldring Center for Culinary Medicine may thus help current and future physicians fill significant gaps in their nutrition education competencies and attitudes to improve chronic disease management.
496 Recipe for Improving Chronic Disease Management: Personalized Nutrition Education for Medical Students via Predictive Multivariate Regression Models
Chen Y, Monlezun DJ, Harlan T. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Recent studies indicate that a homogenous medical education curriculum is optimal for improving medical student competencies and attitudes in nutritional education given their heterogenous backgrounds in knowledge bases and skill sets. The Goldring Center for Culinary Medicine, launched by Tulane University School of Medicine as the globe's first known teaching kitchen nested within a medical school with an accompanying research core, sought to accurately map predictive factors for competency and attitude deficits in a large cross-sectional study.
Methods Used: A 69-question survey was administered to 201 first-year medical students prior to their exposure to the center's elective curriculum. Homogenous data variables were aggregated with baseline data from the previous year's survey for a large sample analysis. Analysis features chi-square test, student t-test, and multivariate logistic regression models controlling for known covariates. Results were generated according to a five-point Lickert scale.
Summary of Results: Data from survey respondents (n=604) were categorized according to attitudes, knowledge, and dietary habits. Predictive factors in multivariate analyses for competencies and attitudes were identified from univariate analyses. Predictive factors were then ordered in logistic regression in terms of magnitude of significant association with a priori-identified individual competencies and attitudes based on national guidelines. Significant relationships respectively were: select diet (predicting 12 competencies and attitudes), past nutrition education (11), third or fourth year level (7), male gender (3), white race (2), primary care specialty (2), and over 29 years of age (1).
Conclusions: Our results indicate that nutrition education for optimal improvement in medical student competencies and attitudes in nutrition education for patients is most predicted by personal dietary habits followed by past nutrition education. These findings can help provide stratified curriculum tracks personalized for medical students with similar predictive factor profiles.
497 Will Increasing Premedical Student Exposure to Registered Dieticians in Cooking Sessions Improve Future Physicians’ Nutritional Education for Patients?
Faruqi J, Monlezun DJ, Harlan T. Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Despite recent findings supporting improved patient outcomes with coordination of patient care between physicians and registered dieticians (RDs), consultation rates lag behind the demand for nutritional education for patients amid physician time constraints. The Goldring Center for Culinary Medicine at Tulane University sought to investigate the impact of exposure of RDs on premedical students' competencies in patient nutrition education, attitudes, and dietary habits both during undergraduate schooling and into medical school and residency.
Methods Used: A pilot study was initiated to begin the multi-stage hypothesis testing that increased integrated nutrition education including via RD-led cooking sessions will lead to increased effective coordination of patient care between physicians and RDs. A baseline 52-question survey was administered before RD-led education simulations targeting pediatric obesity with survey distribution following this intervention.
Summary of Results: Among premedical student respondents (n=65) prior to the education intervention, only a minority of students strongly agree that nutritional assessment should be a routine component in patient visits (30.9%) and that physicians can impact patients’ dietary habits (40.0%). Students with recommended daily vegetable intake were 79% less likely to report proficiency deficits in patient education on identifying antioxidants in local produce (OR=0.21, CI=0.0550-0.7819, p=0.020) and 78% less likely to be competent in counseling patients on the health impact of high fat diets (OR=0.22, CI=0.0514-0.9606, p=0.044).
Conclusions: Our findings indicate that suboptimal dietary habits of premedical students may be an initial significant barrier to improving their competencies and attitudes regarding clinical nutrition and collaboration with RDs in patient care. Hands-on involvement with RDs early in their path to becoming physicians may thus improve these metrics not only on their understanding of patient education for patients’ nutrition habits, and their own.
Endocrinology and Metabolism
Concurrent Session
1:00 PM
Saturday, February 22, 2014
498 PROTEIN PHOSPHATASE 2C-ALPHA KNOCKDOWN REDUCES ANGIOTENSIN II-MEDIATED SKELETAL MUSCLE WASTING VIA RESTORATION OF MITOCHONDRIAL RECYCLING AND FUNCTION
Tabony AM, Delafontaine P. Tulane University, New Orleans, LA.
Purpose of Study: Circulating angiotensin II (AngII) is elevated in congestive heart failure (CHF), and leads to skeletal muscle wasting, which is strongly associated with poor patient outcomes. We previously found that AngII upregulates protein phosphatase 2C-alpha (PP2Cα) and dephosphorylates AMP-activated protein kinase (AMPK), a critical regulator of cellular metabolism, in skeletal muscle. To test the hypothesis that blocking AngII-upregulation of PP2Cα would prevent AngII-induced wasting, gastrocnemius (Gas) muscles of FVB mice were injected with 5μg of PP2Cα or scrambled siRNA and mice were infused with saline or AngII (1μg/kg/min) for 4 days.
Methods Used: Protein expression and phosphorylation status (SDS-PAGE/Western Blotting), mitochondrial activity (Cytochrome C Oxidase (COX) Activity) and energy availability (ATP levels) were determined.
Summary of Results: Knockdown of PP2Cα reduced AngII-induced wasting from a 26% decrease in Gas weight with scrambled siRNA to a 13% decrease with PP2Cα siRNA (p<0.001). PP2Cα knockdown blocked AngII upregulation of PP2Cα (p<0.01), increased p-T172-AMPK and inhibited AngII-mediated reductions in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α, p<0.05), in COX activity (p<0.05) and in ATP levels (p<0.05). AngII impaired autophagy as determined by a 2.6-fold increase in p62 expression (p<0.001), and this induction was reduced by PP2Cα knockdown (p<0.05). AngII reduced activating S555 phosphorylation of UNC-51-like kinase 1 (ULK1), a critical regulator of autophagosome formation (p<0.05), and increased inhibitory S757 ULK1 phosphorylation (p<0.05) and these effects were prevented by PP2Cα siRNA (p<0.05).
Conclusions: Thus AngII inhibited AMPK activity (thereby preventing mitochondrial biogenesis) and impaired autophagy (preventing clearance of damaged mitochondria), resulting in mitochondrial dysfunction, decreased ATP, and wasting. Knockdown of PP2Cα normalized AMPK activity/PGC-1α levels and blocked AngII inhibition of ULK1, leading to improved mitochondrial biogenesis/recycling, function, and energy production, and inhibition of AngII-induced wasting. These results demonstrate novel effects of Ang II on cellular metabolism that are likely critical in mediating the muscle wasting that is a hallmark of CHF.
499 TRANSCRIPTOME STUDY OF ISLETS OF LANGERHANS FROM THE PANCREAS OF NOD AND CONTROL MICE
Freeman AG1, Lenchik N1,2, Gerling I1,2, Chen H3. 1 University of Tennessee Health Science Center, Memphis, TN; 2 Veterans Administration Medical Center, Memphis, TN and 3 University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: Non-Obese Diabetic (NOD) mice are used in the study of Type 1 Diabetes (TID). New insights into the pathogenesis of T1D could be gained by obtaining comprehensive expression profiles from the Islets of Langerhans. Obtaining islet RNA with sufficient quantity and quality has been challenging because of the large amount of RNA degrading enzymes in the pancreas. We developed a new protocol using RNA-sparing techniques that solve this problem.
Methods Used: Pancreases were obtained from NOD and C57BL/6 (control) mice at 4, 6, 8, and 10 weeks of age. Islets were obtained using laser-capture microscopy (LCM). RNA was extracted from the islets, RNA integrity and quantity was determined, and expression data was collected using Affymetrix arrays.
Summary of Results: A number of changes to standard protocols were evaluated. These experiments produced a protocol that allowed us to obtain RNA of sufficient amounts and integrity to acquire expression profiles. The profiles showed that individual NOD islets had markedly different gene expression profiles compared to controls. A substantial difference was also observed between both individual islets with or without insulitis and between individual islets with insulitis at the same age. Transcriptome data from pooled islets at the different ages suggest a progressive increase in specific leukocyte subsets and cytokine/chemokines, although some appeared earlier than others and some were reduced by 10 weeks of age.
Conclusions: In this pilot study we developed a protocol that allowed extraction of RNA with sufficient quantity and quality to obtain comprehensive expression profiles. Whereas histological methods may characterize expression of a few hundred genes, this method covers over 26,000 RefSeq transcripts providing an unprecedented level of insight into the molecular pathology of NOD mice. We have demonstrated the ability of this approach to discover changes in expression of genes in NOD islets that have never before been reported.
500 COMBINATION THERAPY OF PHENTERMINE AND TOPIRAMATE FOR OBESITY; A “REAL WORLD” VIEW
Uwaifo G, Cosentino G, Varughese A, Dubin R. LSUHSC-NO, New Orleans, LA.
Purpose of Study: Obesity is prevalent in the Southern US. Weight management (Wmgt) dependent solely on lifestyle modification oft has limited success in sustaining weight (Wt) loss. While there are limited medication options for Wmgt some of the best Wt loss results other than bariatric surgery involved use of combination pharmacotherapy. Qsymia, a recently approved combination medication has shown promise for long term Wmgt in clinical trials but remains largely inaccessible for underserved, underinsured patients(pts). We report on the use of the individual components of Qsymia; phentermine (Ph) and topiramate (Tp) in combination therapy in a “real world” setting of an underserved outpatient Wmgt program.
Methods Used: The pts were seen in a Wmgt program for underserved, underinsured pts. The decision to include pharmacotherapy in the individual pts Wmgt was made on a case by case basis. As part of the Wmgt protocol all pts had serial follow up and labs every 3-4m. All pts were recommended to participate in a dietician run lifestyle and dietary counseling program.
Summary of Results: 109 pts recruited to date. 86 are female and 65% are African American, 35% Caucasian and 1% others (Hispanic and Asian). Mean duration of medication use is 6m±5.8 with a range of 1-45m. The mean initial weight(lbs) and BMI (kg/m2) are 334±110 and 53.6±14.7. This significantly reduced at final observation to 315±96 and 50.7±12.8. The Wt loss ranges from 110 to a weight gain of ~ 22 and the mean % Wt lost is 5.3±5.9 with a range of 25% loss to 5% gain. The mean Ph dose is 19.3mg with 15mg being most commonly used while the mean Tp dose is 71mg with 50mg the most common dose. Wt loss is also associated with significant reduction in blood pressure, pulse rate, triglycerides, HBA1c, fasting glucose, insulin and waist circumference. Serum uric acid, 25 OH vitamin D, urine microalbumin and other lipids werent significantly different. The medication combination is well tolerated with only 5 pts (0.05%) having adverse effects requiring discontinuation of one or both medications.
Conclusions: Combination therapy of Ph and Tp is effective in achieving robust Wt loss and associated cardiometabolic benefits in a cohort of underserved subjects with obesity. The clinical response is however quite variable and overall is not as dramatic as that reported in the certification trials for Qysmia.
501 THE EFFECT OF PAYOR SOURCE ON ACHIEVING DIABETES METRICS IN AN ENDOCRINOLOGY CLINIC
Jacovino CA, Goidel R, Gosmanov A. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: The rate of achieving diabetes management goals of hemoglobin A1c (HbA1c) <7.0%, blood pressure (BP) <140/80 mmHg, and LDL-cholesterol (LDL-C) <100 mg/dL as recommended by the American Diabetes Association (ADA) in clinical practice is suboptimal. The aim of this study was to determine if a payor source could influence meeting of diabetes care goals.
Methods Used: We performed a retrospective chart review of patients with diagnosis of diabetes mellitus that attended endocrinology clinic for 24 months under the care of a single endocrinologist in an academic medical center (n=93). We analyzed HbA1c, systolic BP, LDL-C, body mass index (BMI) and type of anti-diabetic agents used in patients having commercial insurance (n=33), Medicaid (n=13), and Medicare (n=47).
Summary of Results: Subjects in the Medicare group were older (63.6±12.9 yrs) compared with the commercial and Medicaid groups (50.6±11.6 and 48.3±13.4, respectively) (P<0.05). BMI was similar among all groups with an average of 32.3±7.1 kg/m2. During the baseline evaluation, 3% of patients in the commercial group, 0% in the Medicaid and 17% in the Medicare group have already met all 3 diabetes target goals. After 24 months of continuous clinical care, 50% of the patients in the commercial group, 25% in the Medicaid and 62% in the Medicare group achieved diabetic metrics as recommended by the ADA. Individual goals in the patients with commercial insurance, Medicaid and Medicare were achieved in 55%, 32%, and 72% for HbA1c, in 80%, 83%, 83% for systolic BP, and in 88%, 42%, 89% for LDL-C, respectively. BMI has not significantly changed in all three patient groups during the treatment. There was no statistically significant difference in age, BMI, insulin use, and incretin mimetic use between patients who achieved and did not achieve combined diabetes targets in either group.
Conclusions: Patients in the commercial insurance group and Medicare group can achieve substantial improvement in diabetes care metrics while receiving care in subspecialty clinic. We also found that glycemic goals are more difficult to achieve than control of BP or LDL-C. Other clinical and potentially therapeutic approaches must be used in patients who are not able to meet the ADA performance measures targets.
502 TRADITIONAL SCREENING MODALITIES FOR BONE HEALTH MAY NOT APPLY TO THE HIV POPULATION
Stephens KI1,2, Rimland D1,2, Tangpricha V1,2. 1 Emory University, Atlanta, GA and 2 Atlanta VA Medical Center, Decatur, GA.
Purpose of Study: Individuals with human immunodeficiency virus (HIV) are at increased risk for osteoporosis and fractures due to concomitant risk factors such as vitamin D deficiency, hypogonadism and anti-retroviral therapies. Whether traditional screening modalities for bone disease apply to the HIV infected population remains unclear. We sought to investigate the utility of DEXA and FRAX scores in identifying the prevalence of sub-clinical vertebral fractures in HIV patients with vitamin D deficiency.
Methods Used: We enrolled subjects who were HIV positive and vitamin D deficient (25-hydroxyvitamin D (25(OH)D) <30 ng/mL). Bone mineral density was assessed by DEXA and the calculated 10 year fracture risk using the World Health Organization FRAX equation. Two independent radiologists reviewed lateral chest x-rays for the presence of sub-clinical vertebral fractures.
Summary of Results: We identified 342 adult subjects with HIV (mean CD4 count: 512±256 cells/mm3) and vitamin D deficiency (mean 25(OH)D: 12.6±4.4 ng/mL). Overall 49 (14.3%) subjects met diagnostic criteria for osteoporosis per DEXA, and 178 (54.3%) had osteopenia. The mean risk of any osteoporotic and hip fracture by FRAX was 2.3±2.3% and 0.37±0.78%, respectively, well below the recommended threshold for treatment. Yet, sub-clinical vertebral fractures by lateral chest x-ray were detected in 108 (46.6%) subjects. As compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% vs. 15.7%, p=1.0 ) and osteopenia (55% vs. 61%, p=0.42), and similar FRAX major (1.3% vs. 1.5%, p=0.02) and FRAX hip (0.1% vs. 0.1%, p=0.41) scores. Finally, neither osteoporosis and osteopenia status, FRAX scores, 25(OH)D level, CD4 count, body mass index, sex, calcium and parathyroid hormone levels, smoking history, nor renal function were predictive of those with fracture after multivariable analysis.
Conclusions: We found that a significant proportion of patients with HIV and vitamin D deficiency have fragility fractures. However, traditional screening tools for bone disease such as DEXA and FRAX score failed to identify those with fractures. Whether lateral CXR should be used as a screening tool for sub-clinical fractures and to help guide appropriate therapy in this high risk population warrants further study.
503 EFFECT OF A HIGH CARBOHYDRATE DIET ON WEIGHT CHANGE AND METABOLIC PARAMETERS IN PRE-DIABETIC, OBESE SUBJECTS
Hicks S, Stentz FB, Kitabchi AE. University of Tennessee Health Science Center-College of Medicine, Memphis, TN.
Purpose of Study: This study focuses on the effects of a high carbohydrate (HC) diet on weight loss, glucose metabolism, insulin sensitivity, and body composition after 6 months on the diet. The specific aim is to determine if the HC diet will be effective in conversion of pre-diabetic subjects to normal glycemic.
Methods Used: Participants receive a HC diet (15% kcals from protein, 55% kcals from carbohydrates, and 30% kcals from fat) for 6 months. Oral glucose tolerance tests (OGTT), mixed meal tolerance tests (MTT), and DXA scans are conducted at baseline, 3 months, and 6 months.
Summary of Results: BMI, body weight, blood pressure, fat mass, fasting glucose and insulin, 2 hour OGTT glucose and insulin as well as the OGTT AUC for glucose and insulin decreased for subjects on the HC diet. The OGTT and MTT show how the glucose levels decreased over the 6 month period after exposure to the same amount of glucose, emphasizing that the body more efficiently clears glucose after being on the diet. Overall glucose levels are lower for the MTT than the OGTT, showing how the body responds differently to a meal composed of pure sugar versus a balanced diet. In regards to insulin sensitivity, the insulin levels for OGTT and MTT decreased over the 6 months. This lowering comes from the body becoming more insulin sensitive due to weight loss. Therefore, the body needs less insulin to clear the same amount of glucose. Comparing baseline to 6 months, the AUC values decrease. This decrease shows that the body is exposed to less glucose over time due to the increase in insulin sensitivity brought on by weight loss from being on the diet.
Conclusions: Weight loss on a HC diet leads to conversion from pre-diabetic glycemia to normal, increased insulin sensitivity, and a more efficient insulin response to glucose levels. By eating meals composed of a healthy balanced diet, glucose levels will be lower in the body than eating sugary, unhealthy meals.
504 CHANGES IN PATIENT OUTCOMES IN DEDICATED INTERNAL MEDICINE RESIDENT DIABETES CONTINUITY CLINIC
Caruthers C, Hebert C, Richards R, Melendez L, Yi Y, Martinez J, Engel LS, Cefalu W, Friday K. LSU Health Sciences Center, New Orleans, LA.
Purpose of Study: Most Internal Medicine (IM) Residency programs integrate diabetes care into their regularly scheduled continuity clinics. LSUHSC-New Orleans IM Residency program created a monthly Diabetes (DM) Continuity Clinic staffed by Endocrinologists. The purpose of this study was to determine if diabetic outcomes improved as a result of a specific diabetes continuity clinic.
Methods Used: We identified patients in a Monthly diabetes continueity clinic and patients with diabetes in General IM Residency clinics between 2008–2011 and at least three clinic visits. Various labs and vitals were collected and analyzed at baseline and follow-up.
Summary of Results: 1,255 patients with diabetes were identified-1,010 in the General IM Residency clinics (control group) and 245 patients in the dedicated DM Continuity clinics (test group). The gender and age distribution were similar for both. The Hemoglobin A1C (A1C) for the control group at baseline was 7.88 with follow-up value of 7.83 while test group had initial A1C of 9.54 at baseline with follow-up value of 8.53, which was statistically significant (p<0.01). There was no significant difference for the Low-Density Lipoprotein value between the two groups at baseline; however, both groups did have decreases from baseline to follow-up. Total cholesterol in control group was 172mg/dL compared to the test group at 184mg/dL. There was a statistically significant difference in the follow-up values for these two groups (p-value=0.003). The microalbumin/creatinine ratio was elevated for both groups, and there was no change in follow-up values. A blood pressure goal of 130/80 was identified. 26% of control group were at goal initially with improvement to 30% at follow-up. 36% of test group were at goal with improvement to 50% at follow-up.
Conclusions: The dedicated DM Continuity Clinic demonstrates an improvement in patient outcomes in regards to Hemoglobin A1C, total cholesterol and blood pressure management compared to patients with diabetes treated in the General IM Residency clinics. Extending this novel concept to other IM Residency programs could strengthen the training of Internists to better treat and manage patients with diabetes.
504A TNF-α INDUCED INSULIN RESISTANCE: USE OF SIRNA TO DEMONSTRATE ROLE OF PTEN
Bulger D1,2, Conley J2, Conner S1,2, Majumdar G1,2, Solomon S1,2. 1 University of Tennessee Health Science Center, Memphis, TN and 2 Veterans Association Medical Center, Memphis, TN.
Purpose of Study: The incidence of Type 2 Diabetes Mellitus (DM2) has sharply increased, primarily due to obesity. Adipose tissue in obesity produces higher amounts of TNF-α, which leads to chronic low-grade inflammation and insulin resistance (IR). The mechanism is still unclear. Previous genomic and proteomic studies by us on this IR have revealed significant differences in PTEN. PTEN dephosphorylates PIP3 and induces IR. Herein we utilize siRNA knockdown of PTEN to elucidate its role in TNF-α induced IR.
Methods Used: With and without PTEN siRNA (25 nM)/Dharmafect 1, H411E rat hepatoma cells were treated with insulin (10,000 μU/ml), TNF-α (1.0 nM), and insulin + TNF-α. We also tested 3-hydroxypicolinate vanadium (IV) complex (VO-OHpic) (37.5 nM) and metformin (10 μM). Protein and mRNA were extracted from the cells and analyzed by Western blot (Wb) and Real Time RT-PCR. Levels of PTEN in treated cells were compared to untreated control. Sensitivity or resistance to insulin were reflected by results of p-Akt Wb.
Summary of Results: PTEN/β-actin protein levels as measured by quantitation of Wb bands are calculated as percentages of control: insulin (80%, ↓); TNF-α (197%, ↑↑, p < 0.05); and insulin + TNF-α (122%, ↑). For PTEN/β-actin mRNA levels as measured by Real Time RT-PCR, percentages of control were the following: insulin (65.8%, ↓↓); TNF-α (198%, ↑↑); and insulin + TNF-α (98%, ↓). Insulin inhibited and TNF-α stimulated PTEN levels. Phospho-Akt/Total-Akt protein levels: insulin (230%, ↑↑, p < 0.05); TNF-α (95%, ↓); and insulin + TNF-α (300%, ↑↑↑, P < 0.05). Both insulin and VO-OHpic each prevented TNF-α induced stimulation of PTEN (p < 0.05), and the combination was additive (p < 0.05). Metformin, previously shown to inhibit TNF-α, showed no significant effects in the current experiments.
Conclusions: Use of siRNA PTEN provides proof of concept of a critical role of this phosphatase in insulin signaling. Insulin inhibits and TNF-α stimulates PTEN. An increase in PTEN inhibits insulin signaling. Unexpectedly, TNF-α stimulation of PTEN did not alleviate IR (p-Akt). Despite this last inconsistency, our overall data supports a central role for PTEN in IR, making it a potential therapeutic target in DM2.
505 Conversion from Prediabetes to Normal with Weight loss in Obese Subjects on a High Protein Diet
Bruno E, Kitabchi AE, Stentz FB. University of Tennessee Health Science Center, Memphis, TN.
Purpose of Study: To assess the effects of a high-protein (HP) diet on weight loss, metabolic parameters and conversion from pre-diabetic glycemia to normoglycemia after six months on the diet.
Methods Used: Upon screening and enrollment in the study, participants received weekly HP meals, comprising 30% kcals from protein, 40% kcals from carbohydrates and 30% kcals from fat. Participants were weighed at meal pick-up; oral glucose tolerance tests (OGTT) and mixed meal tolerance tests (MTT) were performed at baseline, 12 weeks and 24 weeks; and DXA scans were performed at baseline and 24 weeks.
Summary of Results: All participants assigned to the HP diet experienced weight loss on their diets, with an average percent body weight loss of 6.6% (±2) and an average BMI decrease from 41.1 (±3) at baseline to 38.8 (±3) at 24 weeks. In terms of conversion to normal glycemia from a pre-diabetic state, as indicated by their 24-week measured glucose OGTT results, subjects were successful in returning to normal glycemia ( less than 140 mg/dL at the 120-minute measurement of a glucose OGTT). Patients also experienced an average decrease in their glucose MTT, insulin OGTT and insulin MTT values from baseline to 24 weeks, as well as in their AUC values over the same period.
Conclusions: Based on the results shown by those patients who completed the study, weight loss leads to conversion from pre-diabetic glycemia to normal glycemia, as well as to increased insulin sensitivity relative to previous insulin resistance, as evidenced by the decrease in patients' glucose MTT and insulin MTT values from baseline to 24 weeks. The study's results revealed that a healthy, reduced-calorie, HP diet is a major contributing factor to a more efficient insulin response to glucose in the body. As evidenced by the decrease in AUC values from baseline to 24 weeks, weight loss due to an HP diet results in less exposure to glucose over time and accordingly in increased insulin sensitivity, with a corresponding decreased activity of beta cells in the pancreas.
506 LEPTIN DEFICIENCY PRESENTING AS NEW ONSET DIABETES MELLITUS IN AN 11 YEAR OLD BOY WITH PROGEROID APPEARANCE
Stender SR1, Brown RJ2, Cochran E2, Baez E1, Gumus P1, Lacassie Y1. 1 LSU Health Sciences Center, New Orleans, LA and 2 NIH/NIDDK/DEOB, Bethesda, MD.
Case Report: A previously healthy 11 6/12 year old AA boy, height 153 cm (80%),weight 34 kg (25%), BMI 14.5(<5%), presented with abdominal pain, hyperglycemia, HbA1C 12.5%, normal blood gas, glucose 166 mg/dL, Insulin 8.4 uIU/ml, C-Peptide 2.6 ng/mL, anti GAD 65 antibodies <0.5 U/ml, IA-2 autoantibodies 0.8 U/mL, Insulin autoantibodies <2uU/mL. Subsequent labs: leptin < 0.6 ng/mL, triglycerides 2590 (30-149) mg/dL, cholesterol 246 (<169) mg/dL, HDL 17 ( 40-59) mg/dL, ALT 140 (7-56) U/L,GGT 102 (6-66)U/L. Because of lipodystrophy, hypo and hyperpigmentary abnormalities, evident progeroid features, Genetics was consulted. Hypertelorism and telecanthus, long neck with prominent cervical spine, minor syndactyly toes 2-3, extra finger flexion creases and other findings were described. Although a single gene defect was suspected,aCGH was performed.Only a dup1p36.23 of unknown clinical significance was reported. Review of pictures from infancy revealed slow progression from normal habitus and facies to his current distinctive appearance.
Extreme insulin resistance necessitated total daily insulin up 5.0 u/kg/day, treated with insulin lispro CSII therapy with minimal success (HbA1c 9.3). Oral medicines included Metformin, Lipitor, and Fish oil. Dietary advisement addressed decreasing concentrated sweets, salt, HFCS and saturated fats.
He was referred to the NIH Clinical Center for evaluation under research protocol 02-DK-0022,“Long-Term Efficacy of Leptin Replacement in Treatment of Lipodystrophy.” Studies revealed: DEXA: 8.3% total body fat, BMD 1.08 gr/cm squared (z-score +2.2); transthoracic cardiac ECHO: prominent trabeculations in LV apex wall suggestive of noncompaction cardiomyopathy, EF 60%; liver biopsy: steatohepatitis with moderate steatosis, no fibrosis; Renal: 24 hr urine macroproteinuria (2.1 gm/24 hr) with hypertension (systolic up to 140’s). Enalapril was begun. No kidney biopsy was recommended. One month after beginning subcutaneous metreleptin, the patient was no longer insulin dependent, HbA1c 6.7, later 5.5%.
Dyslipidemia has resolved and Lipitor discontinued with normalized triglycerides and total cholesterol. Metreleptin dose is being titrated down in order to facilitate weight gain.
507 EFFECTS OF INSULIN AND METFORMIN THERAPY ON BONE MINERAL DENSITY IN DM 2 PATIENTS
Conner SH1,2, Awoniyi O1,2, Solomon S1,2. 1 University of Tennessee Health Science Center, Memphis, TN and 2 Veterans Association Medical Center, Memphis, TN.
Purpose of Study: Type 2 diabetes (DM2) and osteoporosis are two major diseases that affect our aging population. Wnt signaling is active in both bone remineralization and insulin action and diabetes. We propose to test the hypothesis that treatment of diabetes mellitus with a combination of insulin and metformin affects bone density in a positive way. This could prevent progression of osteopenia to osteoporosis in DM2 patients; delay the need for additional treatment for osteoporosis; and result in significant health care cost savings in these patients.
Methods Used: The bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DXA) was compared between osteopenic metformin and insulin treated DM2 patients and age, sex, and race matched control diabetic patients not on insulin or metformin. We also compared bone density in the same patient, before and after (while still on) metformin and insulin therapy. Hemoglobin A1c (HbA1c) values were tabulated and compared between groups. Inclusion and exclusion criteria were identified. Appropriate statistical analysis included paired and unpaired student's t-test and ANOVA.
Summary of Results: Paired and unpaired student’s t-test and ANOVA were performed on the BMD data as measured by DXA. We found no significant change between our treatment group (BMD= −1.10±0.28) and control group (BMD = −1.17±0.38, P=0.172, NS). Comparison of HbA1C values demonstrated significantly higher values in the treated (7.81±1.45) than the control (5.89±0.71) diabetic groups (p<0.01).
Conclusions: In a retrospective chart review in the Memphis VAMC, our data shows that we are not able to demonstrate a significant improvement of bone mineral density in both osteopenic patients with Type 2 diabetes on insulin and metformin after 10 years of therapy, and also when comparing them to osteopenic patients with DM2, not on insulin and metformin. Furthermore, significantly worse HbA1C values in the treatment group suggest that suboptimal control of the diabetes may have played a role, diminishing improvement in BMD. Although we were unable to demonstrate an improvement in BMD with this study, the concept remains worthy and should be followed up with a prospective study.
Gastroenterology II
Concurrent Session
1:00 PM
Saturday, February 22, 2014
508 EOSINOPHILIC GASTROINTESTINAL DISEASE: AN IN-DEPTH ANALYSIS OF THE SIMILARITIES AND DIFFERENCES BETWEEN RACE AND SEX
Smith E1, Dimmitt R1, Atkinson P2. 1 UAB, Birmingham, AL and 2 UAB, Birmingham, AL.
Purpose of Study: Eosinophilic gastrointestinal diseases occur when eosinophils selectively accumulate along the intestinal tract in response to an antigen stimulus. Disease processes included under this term are eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis and colitis. We know there are both environmental and genetic factors that play a role in the phenotypic presentation of EoE. The complete pathophysiology of this disease, however, has yet to be elucidated. There is a clear predisposition of white males with EoE. Less has been studied regarding the demographics of eosinophilic gastroenteritis and colitis. At Children’s of Alabama, we have identified over 300 patients with eosinophilic gastrointestinal diseases. We are enrolling these patients into our registry to compare and contrast their disease onset and progression. In particular, we are evaluating the various presentations between African Americans and Caucasians and between males and females.
Methods Used: While our patient population is predominantly white males, we have seen an increased percentage of African Americans compared to other EoE studies. We plan to investigate potential reasons for this discrepancy. Possible factors include differences in genetics, environment or geographical location. We will attempt to answer these questions by evaluating the demographics of Alabama compared to states where other studies were done. We will look at the percentage of African Americans living in Alabama, the percentage of allergies and atopic disease among Alabama’s general population and African Americans. We will also review any differences between males and females with eosinophilic gastrointestinal disease. We will compare age of onset, symptoms, severity of disease and atopic diseases.
Summary of Results: Alabama has an increased number of African American children with EoE (24%) compared to other studies (most ~12%). We will provide potential confounding factors to explain this variation. We will also result any distinctions seen among males and females with eosinophilic gastrointestinal disease.
Conclusions: The goal of our analysis is to increase our understanding of different factors that may play a role in the underlying pathogenesis of eosinophilic gastrointestinal diseases.
509 Ethnic Disparities in the Risk of Colorectal Adenomas associated with lipid levels: A Retrospective Multiethnic Study
Rabbanifard R1, Lipka S1, Gowda S1, Shen H2, Devanney V1, Davis-Yadley A1, Patel S2, Viswanathan P3. 1 University of South Florida, Tampa, FL; 2 Nassau University Medical Center, East Meadow, NY and 3 Nassau University Medical Center, East Meadow, NY.
Purpose of Study: Although previous data exists showing uncontrolled lipid levels in white and black patients is associated with colorectal adenoma, there is scarce data on the association of cholesterol levels and colorectal adenomas in Hispanic patients. With the rapid projected increase in the Hispanic population, we set out to see if a significant association exists between cholesterol levels and colorectal adenomas.
Methods Used: The sample included 1473 consecutive patients who underwent screening and diagnostic colonoscopies from 2009 to 2011 at a community hospital in East Meadow, NY, after excluding those with colon cancer, inflammatory bowel disease, or incomplete colonoscopies. Statistical analysis was performed using Chi squared for categorical variables and t-test for continuous variables with age-,gender-and race-adjusted odds ratios. 95% confidence intervals between lipid levels with the presence of colonic adenomas were estimated using unconditional logistic regression model. SAS 9.3 software was used to perform all statistical analysis.
Summary of Results: When looking at combined data of both diagnostic and screening colonoscopy findings of general population, there was an association with elevated triglyceride levels greater than 150 and presence of multiple colorectal adenomas OR 1.60 (1.03, 2.48). Further studies showed association with adenomas found in the proximal colon and cholesterol levels between 200–239 with OR 1.57 (1.07, 2.30) and LDL levels of 130–159 with OR 1.54 (1.04, 2.30)and increasing with LDL >160 1.82(1.20,2.75). In comparison, when focusing on the Hispanic population, neither elevated triglycerides, cholesterol, nor LDL showed statistical correlation with the presence, size, location or multiplicity of colorectal adenomas.
Conclusions: Although there appears to be significant correlation between elevated lipid levels and colorectal adenoma in white and black patients, we could not find such association in the Hispanic population. This finding can possibly be due to environmental factors such as dietary, colonic flora, or genetic susceptibility, which fosters further investigation and research.
510 Ransomed from Ranson: Acute Infective Necrotizing Pancreatitis Patient Survives
Adenwala YE1, Nazim MH2, Smalligan RD1. 1 Texas Tech Univ Health Sciences Center, Amarillo, TX and 2 Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: A 28yo woman with epigastric pain radiating to the back with N/V was admitted. PMHx: Cholelithiasis and alcohol abuse; no previous abdominal surgery. Meds: acetamin., ASA. PE: T 98.9, BP 101/41, HR 157, RR 32. Acute distress, diaphoretic, no scleral icterus. Lungs clear; heart regular; abdomen distended and tender in epigastrium, absent BS; neuro nl. Labs: Ca < 5, AG 27, gluc 201, Cr 1.6, LDH 755, WBC 19k, amylase 15k, lipase 1181, AST 98, ALT 34, AP 84, TB 0.8. CT: severe pancreatitis. Within 48 hours the patient had satisfied 8 Ranson’s Criteria, predictive of 100% mortality. By day 8 she required mechanical ventilation and paracentesis, showing cloudy fluid with Gram positive cocci. Exploratory lap showed necrosis of the head of the pancreas and necrosectomy was done daily 5 times. The patient survived and went home on day 60.
Discussion: Internists are confronted with patients with abdominal pain daily. Acute pancreatitis is a common etiology and is typically at the top of the differential. The dx is confirmed by finding two of the following: tender epigastrium; elevated amylase/lipase; and/or typical findings on imaging. While gallstones and alcohol abuse are the most common culprits, followed by high TG and post-ERCP; the vast majority of these can be managed with bowel rest, IV fluid administration, pain control and meticulous attention to VS, electrolytes and urine output. In patients with high predictors of mortality (Ranson’s criteria) and deteriorating condition, as in our case, a repeat contrast CT showing non-enhancement of >30% of the pancreas indicates necrosis. Immediate sampling of peripancreatic fluid for Gram stain and culture helps distinguish infection from sterile necrosis. Though controversy exists, broad spectrum antibiotics with surgical exploration and necrosectomy is an accepted alternative. Some experts propose a stepwise, minimally invasive approach and only a head to head trial will be able to determine the best approach to this uncommon complication. Regardless of approach, internists need to be aware that prompt action to control sepsis and prevent multi-organ failure when possible can reduce the mortality of this dangerous medical condition.
511 CLARITHROMYCIN ASSOCIATED HEPATOTOXICITY
Khalique S, Paccione R, Lo B. LSU Health Sciences Center, New Orleans, LA.
Case Report: Clarithromycin hepatotoxicity is an uncommon adverse effect that has been documented in a few cases. Macrolide-induced hepatotoxicity is likely due to its inhibitory effect on Cytochrome P450 3A4 (CYP3A4). We describe a case of clarithromycin-associated hepatotoxocity in a patient with no known liver disease.
Case Report: Our patient, a 45 y/o Filipino man with a PMH of hypertension, hyperlipidemia, iron deficiency anemia, diabetes mellitus type II, presented with acute jaundice, abdominal pain and hyperbilirubinemia (T. bili 22 mg/dL). On admission, he had just completed a 7-day course of clarithromycin 250 mg bid along with Tylenol 1000 mg daily for a URI. His physical exam was pertinent for sclera icterus and jaundice. Abnormal labs included Total bilirubin 22 mg/dL, AST 225 U/L, ALP 128 U/L, ALT 310 U/L, lipase 75 U/L, ammonia 45 umol/L, albumin 3.1 g/dL, INR 1.4 sec. HIV, RPR, and hepatitis serology were negative. Abdominal ultrasound was unremarkable. He was treated with N-Acetylcysteine for three days for presumed acetaminophen toxicity and then discharged.
One month later, he returned with worsening jaundice, abdominal distention consistent with ascites, sclera icterus, sublingual and skin jaundice. Labs included: Total bilirubin 19.8 mg/dL, AST 80 U/L, ALP 104 U/L, ALT 55 U/L, INR 1.5 sec, albumin 1.9 g/dL, lipase 49 U/L. EGD showed portal hypertension, gastropathy, and esophageal varices. Liver biopsy revealed chronic liver disease of unknown etiology and bridging fibrosis and inflammation consistent with acute toxic drug insult. Autoimmune work up was inconclusive. Paracentesis showed portal hypertension. He was discharged home on Lasix, aldactone, and lactulose. Repeat liver biopsy after discharge confirmed the initial biopsy results of fibrosis consistent with acute hepatotoxicity. Clinic labs five months later revealed complete resolution of both symptoms and LFTs and liver chemistries.
Discussion: Hepatotoxicity is a known but less common adverse reaction of macrolides. Physicians should be aware of risk factors that may increase the risk of macrolide-induced hepatotoxicity: age > 55 y/o, female gender, multiple medical problems (chronic renal insufficiency), polypharmacy, prior macrolide use. Awareness of these risk factors prior to prescribing macrolides can help prevent irreversible liver damage.
512 ISOLATED SMALL INTESTINAL METASTATIC DISEASE AS A HERALD OF RECURRENT NSCLC
Miller E, Caruthers C, Engel LS, Sanne S. LSU Health Sciences Center, New Orleans, LA.
Case Report: The small bowel is a very rare location of metastatic deposits of non-small cell lung cancer (NSCLC).
Case: A 58 year old patient with a history of Stage III (T2N2M0) NSCLC treated with chemotherapy and radiation presented to the hospital with a one week of shortness of breath and chest discomfort. The patient's NSCLC had been considered to be in virtual remission based a PET scan following his treatment. At presentation the patient was found to have a severe microcytic anemia. Initial workup for a source for the patient's blood loss was negative. A review of the patient's medical record suggested a suspicious finding on a surveillance CT involving the small bowel. The patient underwent CT enterography to and was found to have a partially obstructing mass located on the mesenteric side of the small bowel. Laparoscopic exploration of his abdomen was performed with resection of the mass with re-anastamosis of the small bowel; no signs of other masses or metastatic deposits were evident. Gross pathology revealed an 8cm lesion fixed on the mesenteric side of the bowel serosa eroding into the bowel lumen which was determined to be a poorly differentiated carcinoma invading through both the mucosal and serosal surfaces. Immunostaining of the sample revealed CK-7 and TTF-1 staining characteristics in line with the biopsy from the patient's primary lesion in the lung and a diagnosis of NSCLC metastatic to the early ileum was made. The patient was considered to have a solitary metastatic event to the small bowel and was discharged with plans to undergo salvage therapy. Several weeks later the patient returned to the Emergency Room with nausea, weight loss, melena, and decreased appetite and on CT scanning was found to have widespread carcinomatosis with implants throughout his large and small bowel along with nodules in his liver, adrenal glands, and kidneys.
Discussion: While an extremely rare location for isolated metastasis in patients with NSCLC, metastatic disease to the small bowel may be associated with mild and non-specific symptoms that may not be immediately recognized as metastatic disease. While these lesions generally portray a very poor prognosis; early and aggressive therapy may improve time to further relapse and quality of life.
513 Too Acute An Angle: A Case of Superior Mesenteric Artery Syndrome
Kanji A, Begum T, Smalligan RD. Texas Tech Univ HSC, Amarillo, TX.
Case Report: A 43yo man presented with nausea, vomiting, and epigastric pain of 10/10. He had vomited ten times in 24 hours. BMs were regular with no hematochezia or melena. No NSAID or ETOH use but he smoked 1 ppd. PMH: esophagitis, gastritis, Mallory Weis tear, duodenal ulcer and repeated similar episodes since age 17. Meds: none. PE: T 98.4°F, BP 158/94 mmHg, HR 62, RR 20, BMI 18. Heart and lungs normal, abdomen soft, non-distended but with hypoactive bowel sounds and tender to deep palpation of all quadrants but without rebound. Labs: Hgb 16, WBC 15k, 86% segs, plt 245k, K 3.2, HCO3 20, BUN 11, Cr 0.8. LFTs normal, Alb 4.3. Abd CT: distended stomach and duodenum to the level of the superior mesenteric artery (SMA). SMA syndrome was diagnosed and patient kept NPO, NG tube placed, IVF given along with IV PPI, anti-emetics and pain control. He improved and went home 48 hours later.
Discussion: Most patients admitted with abdominal pain, nausea and vomiting have small bowel obstruction due to adhesions. The SMA syndrome is an uncommon disorder that can look similar but results from compression of the third part of the duodenum between the SMA and abdominal aorta. The main anatomical feature is narrowing of the angle between the SMA and the aorta which is 38° to 65° normally but between 9° and 22° in patients with the syndrome; our patient's angle was 20°. The cause of this narrowing is believed to be related to the loss of intra-abdominal adipose tissue after extreme dieting or illness. A retrospective study by Lee found a median BMI of 17.4 at the time of diagnosis. In one series, all patients were asymptomatic until an initial significant weight loss occurred. Another etiology is post surgical correction of scoliosis or other condition that altered the relationship between the SMA and aorta. Clinical features include food intolerance, nausea, vomiting, weight loss and epigastric pain. The diagnosis of SMA syndrome is most commonly confirmed by CT although ultrasound can be used. Treatment is either conservative as in our case or surgical by various techniques including gastrojejunostomy, duodojejunostomy, or section of the Ligament of Treitz (Strong's operation). Unfortunately, not all patients who undergo surgery for this condition have resolution of their symptoms.
514 SEVERE ACUTE PANCREATITIS: A COMMON YET NOT SO COMMON PRESENTATION
Childers K, Goldberg R, Ismail K. University of Tennessee Health Sciences Center, Memphis, TN.
Case Report: Acute pancreatitis commonly encountered in the practice of medicine and gastroenterology. All too often, we see heavy and chronic alcohol abuse as the contributing underlying etiology. However uncommon, severely elevated triglycerides are an important etiology of acute pancreatitis that must always be screened for on presentation. A 53 year old white female with past medical history of hypertension, diabetes mellitus, Crohn’s disease, hypothyroidism, gastroesophageal reflux, and dyslipidemia presented with severe epigastric abdominal pain of 3 days duration. Remainder of her triage and review of symptoms were largely unremarkable aside from abdominal pain and fever. A careful social history revealed no prior alcohol abuse. Physical examination revealed fever of 101.5F, severe intravascular depletion, with tachycardia—clearly in a systemic inflammatory response state. Abdominal examination revealed significant distention with right upper quadrant and epigastric pain. No signs of acute abdomen were present. An initial CT scan revealed a possible necrotic region in the pancreatic head. Further laboratory investigation revealed a lipase level of 5402 and triglyceride level of 6097. Emergent ultrasonography of the abdomen revealed no gallstones and a normal biliary system. The patient's diagnoses included severe hypertriglyceridemia and pancreatitis with bedside index of severity in acute pancreatitis (BISAP) score of 3. Initial high volume isotonic saline infusion and meropenem was begun. After aggressive volume replacement, slow transition to dextrose fluids and insulin infusion was begun, as was atorvastatin and gemfibrozil therapy. Heparin infusion was started. Initial concern for slow response to triglyceride lowering approach gave way to possible need for plasma exchange therapy, however, triglyceride levels began to improve—ultimately reaching 284 without exchange therapy. Symptoms improved and patient was discharged home. Consideration was given for possible primary lipoprotein metabolism disorder versus secondary lipoprotein elevation, and current outpatient genetics testing is planned. This case illustrates the importance of lipid profile evaluation in the setting of severe acute pancreatitis.
515 IDIOSYNCRATIC REACTION OF CLOPIDOGREL
Kapila A1, Locke A1, Khanna A2, Reddy CM2, Young M2. 1 East Tennessee State University, Johnson City, TN and 2 East Tennessee State University, Johnson City, TN.
Case Report: Introduction: Clopidogrel is a widely used irreversible antiplatelet agent belonging to thienopyridine group. It is associated with a wide spectrum of adverse effects ranging from rash, thrombotic thrombocytopenic purpura, neutropenia, aplastic anemia, serum sickness, systemic inflammatory response syndrome and hepatotoxicity. We report an interesting case of hepatotoxicity in a patient who was recently started on clopidogrel.
Case report: A 75 year old female with past medical history significant for hypertension, dyslipidemia, hypothyroidism, osteoporosis, degenerative joint disease, presented to the hospital with nausea, vomiting and fever of 100.8 °F of one day duration. One day prior she underwent elective cerebral anterior communicating artery aneurysm coiling. Her only new medication was clopidogrel which was started 5 days prior to elective surgery and discontinued post procedure. Home medications were esomeprazole, rosuvastatin, levothyroxine, lortab, pregabalin and risedronate. Lab work was significant for hepatotoxic and cholestatic pattern, anemia and thrombocytopenia. Total bilirubin of 1.6 mg/dL, AST/ALT- 1362/716 IU/L, ALP-160 IU/L. All laboratory values were within normal limits 5 days prior to her admission. Hepatitis panel and acetaminophen level were unremarkable. Ultrasound of right upper quadrant and HIDA scan were normal. MRCP could not be performed because of the recent coil placed. Clopidogrel continued to be withheld along with lortab and rosuvastatin. Patient improved clinically and was discharged in a stable condition with total bilirubin decreased to 1 mg/dL and AST/ALT- 162/310 IU/L.
Discussion: Clopidogrel is metabolized primarily in the liver. To the best of our knowledge there are 15 cases described in the literature of clopidogrel hepatotoxicity. The most common pattern of injury is mixed hepatocellular and cholestatic pattern. Mechanism of clopidogrel induced liver injury is either direct dose dependent toxicity or acute hypersensitivity reaction. Our patient had onset of symptoms within 5 days of initiation of the medication indicating the latter. Even though liver injury is uncommonly associated with clopidogrel, it is important for clinicians to recognize the hepatotoxic potential of the same.
517 INFLAMMATORY FIBROID POLYP
Chauhan A1, Engel LS1, Joshi V2. 1 LSU Health Sciences Center, New Orleans, LA and 2 Ochsner Medical Center, New Orleans, LA.
Case Report: A 62 year old male presented with 3 month history of intermittent painless rectal bleeding. He denied weight loss, loss of appetite, abdominal pain or any other pertinent symptoms. He had never had a colonoscopy and there was no family history of cancers in close relatives. Past medical history is significant only for hypertension. Physical exam only revealed mild pallor and lab studies confirmed normocytic normochromic. An abdominal CT scan with PO and IV contrast revealed two areas of suspected colonic wall thickening, one within the hepatic flexure of the colon and the other within the ascending colon in the region of the ileocecal valve. Colonoscopy revealed a pedunculated, recently bleeding polyp at the hepatic flexure. The polyp was 40 mm in size and was removed with a saline injection-lift technique using a hot snare. Histopathology confirmed inflammatory fibroid polyp.
DISCUSSSION: Inflammatory fibroid polyp (IFP) is a relatively rare, benign lesion of gastrointestinal tract. IFP can be found in any part of GI tract but gastric antrum and rectosigmoid are the most predominant sites of involvement. IFP is found in both males and females with minor female preponderance. IFP has been described as inflammatory pseudotumor, neurofibroma and eosinophilic granuloma. IFP can occasionally pose a diagnostic dilemma and it has been sometimes mistaken for a sarcoma. Current literature supports benign nature of the lesion and post resection recurrence has not been reported.
518 METFORMIN INDUCED LATE CHRONIC DIARRHEA
Nadhem O, Bahaa Aldeen M, Ahmed M, Al-Janabi M. Texas Tech Univ Health Sciences Center, Amarillo, TX.
Case Report: A 57 yr-old Caucasian female, with past med history of DM type 2 diagnosed in 2002 on Metformin 500mg BID since then, referred to the hospital due to abnormal electrolytes after a routine workup. She was admitted with chronic diarrhea of 3 months duration,10-15 bowel movements/day and generalized weakness. She denied fever, weight loss, abd pain, nausea, vomiting, or recent travels. On exam: postural hypotension, abdomen was soft, non-tender, and otherwise normal exam.
Labs: WBC 25,200, Na 119, K 3.5, Cl 87, Mg 1.4, Bicarb 22, and lactic acid 1.5.
Hospital Course: Metformin was stopped on admission and substituted with insulin, she was resuscitated with IV NS 0.9%, and the electrolytes were replaced. A stool sample was sent for analysis which showed neg lactoferrin, neg C.diff. toxin and eventual neg culture. Gastroenterology was consulted and colonoscopy and EGD were done with multiple biopsies taken. The colon was normal with trivial gastritis. By the third day the diarrhea had resolved with only 1-2 bowel movements/day, WBC and electrolytes were normal. The patient was discharged on insulin. Pathology Report; Colon: mild non-specific chronic colitis. Stomach: mild chronic inactive gastritis. The patient was followed up few days later with complete resolution of the diarrhea.
Discussion: Metformin is an agent of the biguanide class. It reduces hepatic glucose production and improves peripheral glucose utilization. It is effective as monotherapy or in combination with other agents. The most common adverse effect is GI including diarrhea, commonly when it is first administered or when the dose is increased.
This side effect can sometimes lead to stop an effective treatment of DM. It is a rare to occur years after the initiation of Metformin. Different pathophysiological hypotheses have been proposed to explain it, however, none of them can be considered adequate. Electrolyte abnormalities are still a concern which may raise morbidity/mortality. Diagnosis can be challenging. Colonoscopy may be used to exclude other causes. A trial of stopping Metformin is the mainstay of treatment.
Internists should remember to suspect Metformin as the cause of late chronic diarrhea since its recognition can lead to successful treatment. The patient described here showed a favorable response to stopping Metformin.
Health Care Research and Quality Improvement
Concurrent Session
1:00 PM
Saturday, February 22, 2014
519 RISK FACTORS FOR PORT-ASSOCIATED BLOODSTREAM INFECTIONS (PA-BSI) IN TWO LARGE TEACHING HOSPITALS
Dariushnia SR1, Jacob JT1, Chunduri KV1, Dai T2, Easley KA2, Applegate KE1. 1 Emory University, Atlanta, GA and 2 Emory University, Atlanta, GA.
Purpose of Study: To evaluate the association of port, procedure and physician experience and PA-BSI rates.
Methods Used: All internal jugular vein chest ports that were both implanted and explanted by interventional radiology from August 2009 to December 2012 were reviewed. Dwell time, indication for placement (malignancy vs. non-malignancy), number of lumens (double lumen [DL] vs. single lumen [SL]), power vs. non-power port, use of peri-procedure cefazolin (IV vs. IV plus pocket irrigation), and operator (fellow) experience (quarter of calendar year) were assessed. PA-BSI rates were determined using standard CDC definitions for the numerator and dwell time (time in days from implantation to explantation) for the denominator, and compared using Poisson regression.
Summary of Results: 274 patients were included, 50% Caucasian and 58% female. Most ports were placed in patients with solid organ (71%) or hematologic (20%) malignancies, with 64% being SL. There were 79 PA-BSI for an overall infection rate of 1.11/1000 port-days (95% confidence interval, 0.88 - 1.41). Median dwell time of the infected ports was 213 days. There were no significant differences in PA-BSI rates per 1000 port-days between placement of power vs. non-power ports (1.1 vs. 1.3), addition of pocket irrigation compared to IV cefazolin alone (1.3 vs. 1.0), or quarter of placement. DL ports had a significantly higher PA-BSI rate per 1000 port-days compared to SL ports (1.5 vs. 0.9, p=0.03). PA-BSI rate per 1000 port-days was highest in ports placed for patients without malignancy, followed by hematologic and solid organ malignancies (2.1, 1.8 and 0.8, respectively; p=0.003).
Conclusions: The extended median dwell time of 213 days indicates that in our population, port maintenance is a greater issue for infection than insertion. Port pocket irrigation with cefazolin, in addition to IV peri-procedure cefazolin, did not decrease infection rate but increased procedure cost. Patient selection for port placement and the decision to use DL ports should be done judiciously. Additionally, since no increased risk of infection was seen, we now consider a power port the standard port for our patients.
520 SERIAL COMPLETE BLOOD COUNTS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXACERBATION: MEDICAL NECESSITY OR EXPENSIVE HABIT?
Kauffmann S, Kubiak N, Mitchell C. University of Louisville, Louisville, KY.
Purpose of Study: Chronic obstructive pulmonary disease (COPD) exacerbations are one of the largest financial burdens to our notoriously expensive US healthcare system. We hypothesize that serial complete blood counts (CBCs) in uncomplicated COPD exacerbations contribute to cost but are not associated with change in management or length of stay.
Methods Used: This observational, retrospective chart review was performed on patients with COPD discharged from medicine ward teams July 2010 through June 2012, identified by MS-DRG diagnoses 190-191. Demographic information, number of CBCs ordered, white blood cell (WBC) and platelet counts, hemoglobin, blood gas, length of stay (LOS), antibiotic and steroid use, were recorded. Analysis with Chi-Square or Fischer Exact testing, the Student t-test and Pearson correlation coefficient tests was performed.
Summary of Results: Of the 71 subjects, the mean age was 58.9y; 34 (48%) were African American and 30 (43%) white; 41 (58%) were female. Home nebulizers and oxygen use were reported by 18.3% and 40.8%, respectively. Sixty percent were current and 35% were former smokers. The mean WBC on admission was 9.11 (SD 3.34). Steroids and antibiotics were prescribed in 90% and 89% of the cases, respectively. There was no statistical difference in the WBC for those treated or not treated with antibiotics or steroids, nor between those with normal or abnormal chest radiographs. The number of CBCs ordered (3.07, SD 1.112) was positively correlated with the mean LOS (2.282, SD 1.244d) (0.811, p < 0.001), though there was no correlation between any component of the CBC and LOS. There was a significant correlation between PaCO2 with LOS (p = 0.004).
Conclusions: Much research has been done on implementing reductions in unnecessary laboratory testing, however no method has consistently been proven superior or sustainable over time. We evaluated COPD admissions to determine the frequency of ordering CBCs, and whether the results were associated with LOS or treatment. We found that CBCs were performed almost daily, yet the individual results had no correlation with LOS, treatment with antibiotics or steroids, or with chest radiograph findings. Further research should target interventions to reduce excess phlebotomy and therefore cost in COPD admissions.
521 EVALUATION OF VANCOMYCIN DOSING IN THE PEDIATRIC POPULATION: A QUALITY IMPROVEMENT PROJECT
Jones M1, Bolton M2, Mathews R3. 1 Our Lady of the Lake Regional Medical Center, Baton Rouge, LA; 2 Our Lady of the Lake Regional Medical Center, Baton Rouge, LA and 3 Our Lady of the Lake Regional Medical Center, Baton Rouge, LA.
Purpose of Study: Vancomycin has a narrow therapeutic window and often requires multiple dose adjustments to obtain effective serum concentrations. This seems to be especially true in the pediatric population whose renal excretion of vancomycin often produces subtherapeutic levels. The objective of this study is to evaluate the effectiveness of standard vancomycin dosing in the pediatric population at a children’s hospital located in the South.
Methods Used: Standardized forms utilized by pharmacy in tracking vancomycin usage allowed a retrospective medical chart review of all pediatric patients receiving vancomycin from May 2011 to July 2012. After excluding patients with documented renal dysfunction and those who never had a vancomycin level drawn, data regarding patient's age, associated diagnoses, vancomycin dosing and trough levels, and laboratory results were analyzed.
Summary of Results: Approximately 947 dosing intervals were analyzed. Out of these, 640 had trough levels associated with them. Overall, there were 35 (5%) trough levels that were considered to be supratherapeutic and 311 (49%) that were considered to be subtherapeutic. At a dosage of 15 milligram/kilogram (mg/kg), there were 137 patients who were subtherapeutic and only 44 patients were subtherapeutic at a dosage of 17.5 mg/kg. In contrast, 18 patients reached supratherapeutic levels at a dosing of 15 mg/kg while no patients were found to be supratherapeutic with dosing of 17.5 mg/kg. Only 24% of all the patients analyzed reached therapeutic levels by the time the first trough was measured prior to the 4th dose.
Conclusions: The majority of the patient population studied is not reaching therapeutic vancomycin levels with a starting dose of 15 mg/kg every 6 hours. In addition, the patient population is not reaching therapeutic ranges in a timely fashion. We are currently in the process of changing the standardized dosing of vancomycin to 17.5 mg/kg every 6 hours. We will collect data for a minimum of 3 months with a goal that 80% of our patient population will reach therapeutic levels by the first trough measurement.
522 TARGETED ELECTRONIC ALERT DECREASES INPATIENT SULFONYLUREA-ASSOCIATED HYPOGLYCEMIA
Land AM1, Griffin RL2, Taylor BB3. 1 University of Alabama at Birmingham Hospital, Birmingham, AL; 2 University of Alabama at Birmingham, Birmingham, AL and 3 University of Alabama at Birmingham Hospital, Birmingham, AL.
Purpose of Study: The safety of sulfonylureas in inpatients is unclear. We developed a targeted electronic alert to identify those most at risk for sulfonylurea-associated hypoglycemia and then examined the effect of this alert on hypoglycemia in this population.
Methods Used: Setting: A 1,100-bed tertiary care academic medical center using computerized physician order entry (CPOE). There were two phases, development (phase 1; retrospective) and intervention (phase 2; prospective).
Phase 1: We characterized patients with hypoglycemia on sulfonylureas (chart review, Oct 2010-Sep 2011). From this, we developed a CPOE-triggered alert that fired upon order of a sulfonylurea.
Phase 2: An electronic alert fired for patients at increased risk of hypoglycemia with sulfonylureas; patients >50 years of age with an estimated GFR of <60mg/dL (began Feb 2013). We included options to override the alert. The main outcome was the proportion of patients with the alert overridden (Mar-Jul 2013). The secondary outcome was the number of hypoglycemic episodes, defined as blood glucose <70mg/dL. We excluded alerts for outpatient therapy.
Summary of Results: During five months, the alert fired 230 times during 117 patient hospitalizations. The alert was overridden during 73 hospitalizations (62.4%) and the order was canceled in 44 (37.6%). Among the 73 patients where the alert was overridden, 10 (13.7%) experienced 28 hypoglycemic episodes (2.8 episodes/patient). Among the 44 patients where the order was canceled, 5 (11.4%) experienced 7 hypoglycemic episodes (1.4 episodes/patient). Patients with an overridden alert had a 2.5-fold increase in the frequency of hypoglycemic events compared to patients where the order was canceled (Relative Risk 2.45, 95% Confidence Interval 1.07-5.59).
Conclusions: After deploying a CPOE alert targeting patients at higher risk of hypoglycemia while on sulfonylureas, the alert was overridden over 60% of the time. Among patients where the alert was overridden, more hypoglycemic events occurred. Our findings support the development and use of targeted alerts based upon institution-specific data.
523 COMPARISON OF METHODS FOR THE ISOLATION OF EXOSOMAL RNA FROM PROSTATE CANCER PATIENTS
Dotiwala AK1,2, Ledet E1,2, Sartor AO1,2, Luk EJ2. 1 Tulane University Cancer Center, New Orleans, LA and 2 Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Exosomes potentially aid cancer growth and metastases via transportation of their RNA-enriched cargo. Preliminary data suggest that that exosomes make distant sites in the body hospitable for metastasis. The nature of exosomal RNA (exoRNA) is currently poorly described. To verify the integrity and character of extracted RNA, proper quality measures are required to ensure that the exoRNA is appropriate for downstream applications such as sequencing.
Methods Used: 10-20 ml of plasma were collected from PCa patients at Tulane Clinics in New Orleans, LA. Exosomes were isolated from plasma by ultracentrifugation. To select an optimal and reliable method for exoRNA isolation, three methods for RNA extraction were chosen: 1) Qiagen RNeasy™, 2) Exiqon miRCURY™, and 3) Invitrogen TRIzol™. Samples were analyzed with Nanodrop 2000 Spectrophotometer and Agilent Bioanalyzer 2100. Column-based methods, RNeasy and miRCURY, yield longer strands of exoRNA, which are more informative for sequencing (Eldh et al. 2012. Mol Immunol. 50(4):278-86).
Summary of Results: Concentrations of exoRNA isolated with RNeasy (mean 8.21 ng/μl) and miRCURY (mean 14.37 ng/μl) were low with no significant difference in average yield. The TRIzol method produced significantly higher average yields (178.97 ng/μl, p<0.0001). There was significant difference in RNA concentrations between patients (p=0.0164), but no significance in 260/280 ratios between patients or methods. Bioanalyzer results indicated that the nucleic acids were highly fragmented (<150 nt) and there was no cellular contamination (RIN=1).
Conclusions: The TRIzol method produced the greatest yield of high-quality exoRNA suitable for downstream applications. The differences in concentration between samples are within expected parameters given the extensive heterogeneity associated with PCa. The lack of significance in 260/280 ratio between patients or methods suggests that each method yielded exoRNA of sufficient quality. exoRNA quality was confirmed by Bioanalyzer results which indicated no cellular contamination. As expected, exoRNA was highly fragmented. The TRIzol method is superior to column-based methods in recovering RNA from plasma-derived exosomes.
524 PHARMACOEPIDEMIOLOGY OF ACETAMINOPHEN-OPIOID PRESCRIBING IN YOUNG INFANTS
Basco W1, Roberts J1, Ebeling M1, Garner S2, Hulsey T1, Simpson K1. 1 Medical University of South Carolina, Charleston, SC and 2 South Carolina College of Pharmacy, Charleston, SC.
Purpose of Study: We evaluated the indications for combination acetaminophen - opioid prescribing to young infants and compared whether potential opioid overdose prescriptions varied by indication.
Methods Used: Using 2011-2012 SC Medicaid claims data, we identified infants < 6 months old who received combination acetaminophen -opioid drugs, linked prescriptions to diagnoses (indications for the drug), and classified the diagnoses as appropriate or not (91% raw agreement, with differences resolved by consensus). We compared whether the frequency of potential opioid overdose errors varied by indication, grouped into “appropriate indications” (surgical procedures and trauma/pain) and “inappropriate indications” (respiratory complaints or “other”). We used logistic regression to assess the relationship between indication groups and potential opioid overdoses, controlling for demographic variables. The Institutional Review Board of MUSC approved this study.
Summary of Results: 67 infants < 6 months old received either acetaminophencodeine (97%) or acetaminophen-hydrocodone (3%). Median age was 4.0 months, 79% were male, and they had a reasonable race/ethnic distribution. 79% percent of the indications were appropriate (surgical 73% or trauma/pain 6%) and 21% inappropriate (respiratory 9% or other 12%). Urological diagnoses were very common, representing 42% of the indications among all acetaminophen -opioids. Overall, 3/67 (4.4%) of the prescriptions represented potential opioid overdoses. The frequency of potential opioid overdose was 7.1% among subjects prescribed for inappropriate indications vs 3.8% among subjects prescribed for appropriate indications, but this difference was not statistically significant (Fisher's exact p =0.50). In logistic regression analyses, controlling for age, gender, and race/ethnicity, there were no significant differences in the frequencies of potential opioid overdoses between inappropriate and appropriate drugs.
Conclusions: Surgical diagnoses comprise the majority of indications for acetaminophen -opioid drugs prescribed to infants < 6 months old. Acetaminophen -opioid drugs dispensed for inappropriate conditions may have higher frequencies of potential overdose, but additional subjects will be needed to further evaluate this question.
525 EPIDEMIOLOGIC DESCRIPTION OF EMERGENCY DEPARTMENT BASED EXPRESS ADMIT UNIT
Shirk AM, Monroe K, Whitley J. University of Alabama -Birmingham, Birmingham, AL.
Purpose of Study: The Express Admit Unit (EAU) was created at Children’s of Alabama to care for patients arriving from outside healthcare facilities or private offices for admission. The EAU was physically based in the Emergency Department (ED) with the goals of increasing patient safety with decrease in unplanned transfers, utilizing ED nurse expertise in screening of direct admits to ensure patient level of care is appropriate and divert unstable patients to ED care, and facilitate rapid flow of patients through EAU to assigned unit (goal is within 1 hour).
Methods Used: A chart review of all 761 patients that were admitted through the EAU from August 2012 to January 2013 was performed recording admit diagnoses, admitting team, source of admission, length of stay in EAU, and unplanned transfer within 24 hours as well as diversion to ER care because of unstable status, patient safety reports, and patient complaints within the first 6 months of operation.
Summary of Results: An average of 127 (96–148) patients were admitted through the EAU every month. 51% came from outside hospitals, 36% came from a clinic, and 13% were admitted from home. 47% were admitted to the general pediatrics team, 41% to various subspecialties, and 11% were admitted to surgical services. Average length of stay was 77 minutes. In 6 mo period, 23 patients required higher level of care than initially requested. For 19 of those patients, deterioration was identified in the EAU by ER nurses and they received appropriate, timely resuscitation and were admitted to proper level of care. Only 4 of 761 patients had unplanned transfer within 24 hours of admission. Over first six months, only two patient safety reports were filed (both relating to registration), and no patient complaints were registered regarding the EAU.
Conclusions: Establishing an EAU in the Emergency Department facility provides efficient and safe care, allows rapid and effective escalation of care in cases of clinical deterioration, and appears to decrease unplanned transfers.
526 Practice Level Factors Affecting Vaccination Rates
Zweigoron R1, Binns H2, Ebeling M1, Roberts J1. 1 MUSC, Charleston, SC and 2 Lurie Children’s Hospital, Chicago, IL.
Purpose of Study: Multiple factors influence vaccination up-to-date (UTD) rates, including patient, family, and provider differences. This study seeks to better understand the impact of practice-level factors on UTD rates.
Methods Used: The Illinois Department of Public Health provided practice-level vaccination rates by auditing the vaccination status of 50 random pediatric patients in 54 Chicago practices who received vaccines from the Vaccines for Children program. A questionnaire was developed to collect information about practice-level patient demographics, staffing, protocols around vaccine delivery, reminder-recall, quality improvement and electronic resources. Vaccination rates were compared to these components of care delivery to find significant associations. Chi-square, T-test, ANOVA and correlation analyses were done of practice-level factors and UTD rates at 24 and 35 months respectively.
Summary of Results: Of the 54 practices included, 41% were private, 46% were Federally Qualified Health Centers, 4% were city health department practices, and 9% were academic centers. Pediatricians staffed 33% of practices, family medicine (FM) doctors staffed 18.5% and the rest were staffed by a combination. Private practices and practices using standing orders had a higher percent of UTD patients at 24 months (p=0.01; p=0.03), but not at 35 months. Having a practice of only pediatricians was associated with higher UTD rates at both 24 and 35 months (76%, 84% respectively), compared to a combination of pediatrician/FM office (63%, 74%) and FM (59%, 66%), (p<0.01). Being part of an umbrella organization and taking walk-in patients were associated with lower UTD rates (p=0.03; p=0.03). Private practices differed from the other practices in that they were more likely to have privately insured patients and less likely to have FM doctors or nurse practitioners, evening hours, take walk-ins, or be part of an umbrella organization. As a practice's percent of publicly insured patients decreased, the UTD rate rose at both 24 and 35 months (r=−0.43, p=0.001; r=−.037, p=0.007).
Conclusions: Having pediatricians on staff, being privately owned, using standing orders and having more privately insured patients was associated with a higher UTD rate. The latter three factors remained significant when controlling for physician type.
527 VACCINATION RATES FOLLOWING SICK DAY CATCH-UP IMMUNIZATION: A PILOT QUALITY IMPROVEMENT INVESTIGATION
Ford S, DeLoach L, Rozema T, Thomas R, Cameron-Guy L, Northrip K. University of Kentucky College of Medicine, Lexington, KY.
Purpose of Study: To determine the effect of reviewing immunization records for all same-day sick visits and offering catch up vaccines on the immunization rates of children presenting to our clinic for acute illnesses.
Methods Used: Vaccine records of children presenting to our clinic for same-day call in visits during a one week period were obtained retrospectively and analyzed to determine the total number and percentage of patients who were missing recommended vaccinations. We then instituted a policy in our clinic of reviewing immunization records and offering catch-up shots during sick visits. Records of all patients presenting for sick visits during a subsequent one week period were similarly analyzed to determine the number and percentage of delayed vaccinations, as well as the number and percentage of catch up vaccines that were given during the visit. Vaccination rates pre- and post-implementation of the policy were compared. Results were compared via Chi-square or Z test analysis where appropriate.
Summary of Results: See Table 1.
Conclusions: Conclusions: Reviewing immunization records of children at sick visits and offering catch-up vaccinations significantly reduces unvaccinated rates in this population.
528 THE EXPERIENCE OF MEDICALLY AND SOCIALLY COMPLEX PATIENTS WITH HIGH READMISSION RATES
Nault J1, Speck P2, Scroggins M3, Bell P3, Bailey JE1,4. 1 University of Tennessee Health Science Center, Memphis, TN; 2 UTHSC, Memphis, TN; 3 Methodist Le Bonheur Healthcare, Memphis, TN and 4 UTHSC, Memphis, TN.
Purpose of Study: Building evidence suggests that members of vulnerable populations disproportionately experience frequent readmissions and struggle from complex social problems. But little data is available documenting their experience of care and the particular challenges they face. This study documents the experience and challenges faced by superutilizing patients enrolled in the SafeMed Program, a care transitions program with an emphasis in medication management funded through the Center for Medicare and Medicaid Innovation.
Methods Used: Two focus groups were conducted with participants in order to learn about their challenges, needs, experiences of care, and how peer group sessions could support them best. Facilitators used a semi-structured interview guide. Approximately 20 patients and caregivers participated. A co-facilitator took notes during sessions followed by debriefing of results. Data were analyzed manually to identify major themes that emerged from the focus groups. Findings were reviewed by all key program staff in attendance for concurrence.
Summary of Results: Five major themes emerged: 1) Patients have very high levels of fear, anxiety, and depression about health outcomes, life in general, 2) Patients have chronic pain that is not well managed and makes it hard to focus on self-management behaviors, 3) Patients lack support even from friends and family members, 4) Patients want information that is individualized and consistent, 5) Patients want to discuss their health and healthcare in a trusted environment.
Conclusions: Re-designing care processes to be more patient-centered must not only address the physical needs of patients but also the social and emotional needs. Providers need to understand patient culture, family situations, and lifestyles in order to individualize care plans. Support group sessions that integrate knowledge about disease management with interactive discussion between peers about what makes it hard to change health behaviors can fill an important gap in access to high-quality, cost effective, patient-centered care.
529 IMPROVING DISASTER AWARENESS AND PREPAREDNESS AMONG FAMILIES OF CHILDREN WITH SPECIAL HEALTHCARE NEEDS
Bagwell H1, Liggin R1, Thompson T1, Lyle K1, Anthony A1, Baltz M1, Melguizo-Castro M2, Nick T2, Kuo D3. 1 UAMS - ACH, Little Rock, AR; 2 UAMS - ACH, Little Rock, AR and 3 UAMS - ACH, Little Rock, AR.
Purpose of Study: Children with special healthcare needs (CSHCN) may present unique challenges for disaster preparedness, as some of these children require care such as home oxygen, multiple medications, or gastrostomy feeds that could be disrupted during a disaster. The purpose of this study is to determine the disaster preparedness of families of CSHCN and the impact of disaster preparedness education and intervention. It is anticipated that such families will be underprepared, demonstrated by not having an emergency information form (EIF) for their child or a disaster kit.
Methods Used: Families of CSHCN were consecutively enrolled between May and September of 2013 at the Medical Home Clinic of Arkansas Children’s Hospital, a comprehensive outpatient service for children with complex medical needs. Each family was given a 24 question literature-based survey about disaster preparedness. Following the survey, families received: 1) educational handouts on disaster preparedness; 2) a $15 disaster supply starter kit, a backpack containing first aid supplies and a flashlight. A follow-up phone survey was conducted 6–10 weeks later to determine changes in disaster preparedness. McNemar's test was used to assess the differences between pre- and post-survey items.
Summary of Results: There were 250 families enrolled with 144 completing the post-survey. The median age of children was 3.1 years with a median of 4 required medications; 55% required gastrostomy tubes, 23% required home oxygen therapy, and 35% required a feeding pump. At pre-survey, 43% of families had an EIF for their child, increasing to 79% at the post-survey period (p-value <0.001). Only 18% of the participants in the pre-survey period had a disaster kit. At post-survey 143 of 144 respondents (99%) still had the starter disaster kit, and 44% had added items such as water, clothes, or additional first aid supplies.
Conclusions: Families of CSHCN are underprepared for a disaster, but a small disaster supply starter kit with education may increase disaster awareness and planning. Further investigation looking at long term improvements in disaster preparedness and dissemination to other populations is needed.
Hematology and Oncology II
Concurrent Session
1:00 PM
Saturday, February 22, 2014
530 Analysis of Thromboleastometry Findings in Adults With Sickle Cell Disease and Controls
Janbain M, Leissinger CA, Kruse-Jarres R. Tulane School of Medicine, New Orleans, LA.
Purpose of Study: Vaso-occlusive phenomena are a clinical hallmark of sickle cell disease (SCD). Knowing that these events may be related to the activation of the hemostatic system that is assessed from a global standpoint by thromboelastometry (TEM), it is challenging to characterize TEM findings in patients with SCD, to differentiate their clinical phenotype upon presentation, and predict their prognosis.
Therefore, we aim to characterize the TEM findings in both whole blood (WB) and plasma (PL) in patients with SCD during periods of steady state and acute illness, and compare them with those of healthy controls and sickle cell trait (SCT).
Methods Used: In a cross-sectional study, we obtained TEM and other hemostatic data on 24 adult patients with SCD (16 in steady state and 8 in acute illness); and 13 race and age matched controls (6 with sickle cell trait (SCT) and 7 with no trait). We looked at coagulation time (CT) as a function of coagulation factors; clot firmness time (CFT) and alpha angle(α) assessing platelet and fibrinogen function; and maximum clot firmness (MCF) evaluating the mechanical clot quality (plt, fibrinogen and factorXIII) and thrombodynamic potential index (TPI) looking at the global coagulation.
Summary of Results: Overall, patients with SCD had higher TPI in WB (p=0.23;=0.25) and lower TPI in PL (p<0.0001;=0.47) compared to controls and SCT respectively. Also, patients with SCD had lower CT (p=0.02), lower CFT (p<0.0001) higher MCF; α and TPI (p<0.0001;=0.051; <0.0001) in WB compared to PL.
SCT patients had lower CT, CFT, alpha with higher MCF in WB compared to PL. While healthy controls had higher CT; MCF and TPI (p=0.01; <0.0001; <0.0001) and lower CFT, α (p=0.16; <0.0001) in WB compared to PL.
Conclusions: Whole blood of SCD patients seems to be hypercoagulable in comparison to WB of controls and SCT. While the plasma of SCD patients was hypocoagulable when compared to PL of healthy controls. Overall, TEM profiles of WB were different than PL. This was more obvious in SCD patients reinforcing the contribution of the cellular component to the pathophysiology of the disease and the possible compensatory hypocoagulable status of the plasma in these patients. Further studies of larger, more homogeneous patient groups, are required to adequately assess the clinical utility of TEM in patients with SCD.
531 Skin manifestations of metastatic lung cancer: Case reports
Ruiz MA. Louisiana State University Health Sciences Center, New Orleans, LA.
Case Report: Background: Lung cancer is one of the most common cancers in the US. Skin manifestations of metastatic lung cancer including nodules, ulcers, and other skin lesions have been scarcely reported in the literature. All histologic types of lung cancer have been related to skin metastases but in recent series squamous cell carcinoma and small cell lung cancers appear to predominate
Case: We report the cases of 2 patients who presented to our Oncology clinic referred from the hospital after being evaluated for skin nodules; one with diagnosed with squamous lung cell carcinoma, and the other with small cell lung cancer.
The first patient a 57 year old male patient presented with cough, and shortness of breath. Incidentally, patient was found to have two right-sided thoracic lesions one of 3 X 5 cms and the other of abut 4 X 5 cms. The second patient a 64 year old male patient was admitted with recurrent pneumonia. On physical examination, he was found to have one 2 × 2 cms right ear, and another 1 × 2 cms right-sided mandibular lesion. The first patient was diagnosed with small cell lung carcinoma and the second with squamous cell carcinoma. Both presented with advance stage (IVB). Laboratory values were within normal range and CT scan of chest showed a 4X5 cms right upper lobe lesion with mediastinal lymphadenopathy; and in the second case a 4 × 7 cms left middle lobe lesion with local and mediastinal lymphadenopathy.
Discussion: Skin manifestations are not infrequent in advanced stages of all histologic types of lung cancer. There is a trend to overlook the correlation between skin lesions and lung cancer in the acute hospital setting. One of the reasons may be the failure to recognize the association between lung cancer and skin metastatic pathways. The scarce available literature may also contribute to obscure this association.
Conclusion: Lung cancer metastasizes to the skin. It is important to recognize this association in view of the possibility of less invasive testing procedures available for these patients including skin biopsies and such. Health care providers need to be aware of this association that even though it is not common is seen in advanced lung cancer patients.
532 INAPPROPRIATE IMAGING OF MEN DIAGNOSED WITH LOW RISK PROSTATE CANCER
Luk EJ2, Wang J2, Ledet E1, Stolten M2, Dotiwala AK1, Silberstein J2, Sartor AO1. 1 Tulane University School of Medicine, New Orleans, LA and 2 Tulane University School of Medicine, New Orleans, LA.
Purpose of Study: Utilization of imaging in men diagnosed with low risk prostate cancer (LRPC) has been recognized as both a cost and quality issue. Reduction in inappropriate imaging is an opportunity to improve care while reducing costs. This study aims to better characterize patterns of inappropriate imaging in men with LRPC evaluated at Tulane University Medical Center (TUMC).
Methods Used: Using our TUMC database of prostate cancer patients, we identified 69 patients with LRPC (per National Comprehensive Cancer Network guidelines). After classifying patients as imaged or not, we then used Fisher's exact test to compare the groups according to various referral, demographic, and oncologic characteristics. A chi-squared goodness of fit test was used to compare patients that were evaluated at an outside hospital and at TUMC.
Summary of Results: While most patients (n=57) with LRPC were not imaged, too many received unnecessary imaging (n=12). When comparing TUMC to outside providers, patients were much less likely to receive inappropriate imaging at TUMC (χ2 = 10.9, p=0.01). There were no significant differences found based on age (<65 n=46, ≥65 n=23), race (African American n=17, non-African American n=52), treatment (prostatectomy n=49, no prostatectomy n=20; radiation n=8, no radiation n=20), clinical stage (T1 n=61, T2 n=8), prostate specific antigen (PSA) (<4 ng/ml n=18, ≥4 ng/ml n=51), location of referring health care providers (urban n=62, rural n=7), referral type (self-referred n=23, physician n=46), or insurance type (public n=19, private n=46).
Conclusions: Some LRPC patients continue to receive imaging that offers little benefit. In this analysis, patients managed by academic physicians were less likely to receive inappropriate imaging compared to patients initially evaluated at non-academic sites.
533 SURVIVORSHIP ANALYSIS FOR ADOLESCENTS & YOUNG ADULTS WITH CANCER: A SINGLE INSTITUTION REVIEW
Raulji C, Glinky A, Gardner R, Prasad P. LSUHSC/Children's Hospital, New Orlenas, LA.
Purpose of Study: The 5-year relative survival for the most common cancers for adolescents and young adults (AYA) aged 15-19 has changed from 68.7% in the past to 84.5% in recent years. This improvement is only a fraction of that seen in childhood and adults. Various authors have noted that AYAs treated by pediatric oncologists have better outcomes. We examined cases of cancer in AYA treated at Children's Hospital New Orleans (CHNOLA) from 2003 to 2012, and compared treatment and outcomes from 2010 Survival, Epidemiological and End Results (SEER) data. Our goal was to demonstrate differences in survival of the AYA population treated at a pediatric center compared to national data.
Methods Used: After IRB approval a 10 year retrospective analysis of medical records of patients 14-21 years was performed. We collected patient data on age, race, gender, diagnosis, insurance, treatment and outcome. Statistical analysis was performed to determine if these clinical variables correlated with survival. Institutional survival of AYA patients was compared to SEER data.
Summary of Results: We identified 105 patients. Distribution of cancers differed from the national averages (Table 1), and overall survival of 80% in our patient cohort was comparable to SEER survival of 84.5% for years 2003-2009. Patient survival was not affected by gender, ethnicity, clinical trial enrollment, insurance at diagnosis, compliance to clinic visits or receipt of radiation therapy. Adverse outcome was associated with relapse of primary disease (p<0.001) and stem cell transplant (p<0.001).
Conclusions: Overall survival of AYA patients was comparable to national averages. The difference in distribution of diagnoses may be a result of inclusion of younger adolescents in our cohort and multicultural population. Adverse factors were relapse of disease and bone marrow transplant, presumably because they signified advanced disease.
534 SURVIVORSHIP ANALYSIS FOR OSTEOSARCOMA AND EWING’S SARCOMA: A SINGLE INSTITUTION REVIEW
Raulji C, Pritchett H, Morales-Arias J. LSUHSC/Children's Hospital, New Orleans, LA.
Purpose of Study: Primary malignant bone tumors account for approximately 6% of all childhood malignancies. Of these, osteosarcoma (OS) and Ewing's sarcoma (ES) are the most common and have an annual incidence of 8.7 per million under the age of 20 years. The mean 5 year survival for OS and ES is 61% and 60% respectively. We examined the cases of OS and ES, treated at Children's Hospital of New Orleans (CHNOLA) from 1999-2012. Comparison to national survival data from the Survival, Epidemiological and End Results (SEER) study was done. The goal of our study was to demonstrate any difference in survival of our patient population compared to national data.
Methods Used: After IRB approval a retrospective analysis of medical records for all patients diagnosed with OS or ES and treated at CHNOLA was performed. Statistical analysis was performed to determine correlation between clinical variables and survival. Institutional survival was compared to national data.
Summary of Results: Of the 44 patients diagnosed and treated as either OS or ES, 25 (57%) were OS and 19 (43%) were ES. The mean age of diagnoses for OS was 14 years and for ES was 12 years. Overall survival for these patients was 79.5 %. This was comparable to SEER survival of 78.8% for the year 2005.
Furthermore, survival was not affected by patients' age, gender, race or timing of surgery for removal of primary tumor. All non-survivors had metastatic disease at presentation, which was an adverse prognostic factor (p=0.002). Additionally, positive tumor margins at time of surgery (p=0.008) and decreased amount of tumor necrosis post chemotherapy (p=0.001) negatively affected survival.
Conclusions: Overall survival of pediatric patients with bone tumors was comparable to that of SEER data. Presence of metastatic disease and poor response to chemotherapy based on tumor necrosis and positive margins were found to be adverse prognostic factors.
535 Alternative digit ratios: a non-invasive indicator of prostate cancer aggressiveness in African Americans
Stolten M1, Ledet E2, Dotiwala AK2, Luk EJ1, Wood B2, Sartor AO1,2. 1 Tulane School of Medicine, New Orleans, LA and 2 Tulane University, New Orleans, LA.
Purpose of Study: Prenatal androgen exposure has been correlated with a range of diseases including prostate cancer (PCa). The ratio of the second to the fourth digit (2D:4D) has been linked to prenatal androgen exposure; however, use of alternate finger ratios have been shown to be a better indicator of prenatal androgen exposure than traditional 2D:4D ratio. Studies have shown that the distal fingertip extent of the second digit (2T:2D) was also associated with prenatal androgens. Since alternative finger ratios may be more sensitive to prenatal androgen levels, this study aims to use alternative digit ratio measurements to better determine aggressiveness of PCa with emphasis on racial disparities.
Methods Used: Digital hand measurements were made from images of hand scans of PCa patients. All fingers on the right hand were measured from the bottom crease at the center of the finger to the fingertip. The length of the distal fingertip of the second digit was also measured. Race, family history (FH) (first degree relatives with PCa), and age at diagnosis were recorded. These clinical covariates were then compared to the finger length ratios which were dichotomized and analyzed for possible correlations between racial subsets.
Summary of Results: Hand measurements were taken on 350 Caucasian (CA) and 100 African American (AA) PCa patients. AA men were more likely to have a smaller 2D:3D (P < 0.0001) and 2D:4D digit ratio (P < 0.0001), and larger 3D:5D (P = 0.0002) and 4D:5D (P = 0.0125) when compared to CA men. AA men with a smaller 2T:2D ratio were younger at the time of diagnosis (P = 0.0446). Additionally, AA men with a larger 2D:5D ratio were more likely to have a FH of PCa (P= 0.0238).
Conclusions: Alternative finger length ratios show differences between AA and CA men. In AA men, alternative digit ratios are associated with age of PCa diagnosis and FH of PCa. These results require validation in a larger AA subset, but may provide insight to the underlying racial disparity observed in PCa. Finger length may represent a novel, non-invasive indicator of PCa in AA men with respect to age of onset and FH.
536 Duodenal Adenocarcinoma Incognito as a Psoas Abscess
Gharaibeh K, Saleh N, Yousuf T. University of Mississippi Medical Center, Jackson, MS.
Case Report: Malignancies involving the small intestine are uncommon; adenocarcinoma is the most common malignancy affecting the duodenum. Metastasis to the psoas muscle is rare. We report a case presentation that clinically and radiographically mimicked psoas abscess, that was subsequently proven to be from metastatic disease secondary to adenocarcinoma of the duodenum, up to our knowledge, this is the first case in the literature to be reported.
62-year-old male presented with 7-month history of right lower quadrant abdominal pain radiating to the right anterior thigh and dysphagia. Three months prior to admission, the patient underwent cholecystectomy which was thought to be the etiology of his intractable pain without improvement. A CT abdomen was performed at the outside hospital 3 weeks prior to this presentation which revealed a right psoas abscess not amenable to surgical drainage. Patient was started on oral antibiotics for approximately 3 weeks with no improvement. Physical examination revealed elderly, cachectic appearing man who complained of pain with flexion of the right hip and right lower quadrant tenderness. A CT of the abdomen and pelvis showed ill-defined areas of low density involving the right psoas muscle from origin to insertion, inflammatory changes along the right psoas muscle and right iliacus muscle. Using CT guidance, a fine needle aspiration biopsy of the right psoas mass was performed, revealing a metastatic undifferentiated adenocarcinoma. Patient underwent endoscopy to work up the dysphagia, which discovered a duodenal mass; biopsy came back consistent with same pathology.
Iliopsoas metastases may mimic psoas abscess (phlegmon) both clinically as well as on radiographic imaging. Our patient had metastatic duodenal adenocarcinoma that was not obvious on the CT scan, but given his presentation and unresponsive to antibiotic therapy, further investigation was necessary. This case presentation warrants considering other differential diagnosis in the future cases of Psoas abscess especially those failed Antibiotic therapy, including malignancy especially small intestine adenocarcinoma, leading to early diagnosis, which may improve prognosis. Metastasis to psoas muscle from duodenal adenocarcinoma is extremely unheard off and this is the first case to be reported up to our knowledge.
537 OLD DRUGS - NEW ROLE
Devarakonda SS, Mills G. LSU Health, Shreveport, LA.
Case Report: CASE REPORT: We report the case of a medullary renal cell carcinoma, which showed significant response to fourth line treatment with Adriamycin and Docetaxel combination.
A 44 year old African American female was diagnosed with stage III medullary renal cell carcinoma 3 years ago. She underwent radical nephrectomy with retroperitoneal lymph node dissection. She received no adjuvant therapy and was in remission for one year. The cancer recurred with bone and liver metastases. Temsirolimus was started and she had stable disease for 2 months. At progression she was given Carboplatin and Gemcitabine doublet based on available case reports and her disease responded with no growth for 4 months. At progression, Bortezomib stabilized her disease for 2 months. None of these regimens decreased the size or number of metastatic lesions and they only halted the growth of the lesions for a short time.
She was then treated with a combination of Adriamycin and Docetaxel (Docetaxel at a dose of 75 mg/m2 and Adriamycin at a dose of 50 mg/m2 repeated every 3 weeks). Imaging repeated after treatment with four cycles of this regimen showed dramatic response with fewer pulmonary metastases and a 70% reduction in their size as per the RECIST criteria. Dose of Docetaxel had to be reduced by 20% after two cycles, due to grade 3 neutropenia and Adriamycin was stopped due to reduction in the ejection fraction after a cumulative dose of 300 mg/m2, although she was asymptomatic.
DISCUSSION: Medullary renal cell carcinoma is an aggressive malignancy known to occur in patient with sickle cell trait, and is usually resistant to chemotherapy. Response to various chemotherapeutic agents has not been consistent. Adriamycin, Vinblastine, Methotrexate, Cisplatin and paclitaxel have been used in case reports with mixed results. Our patient responded dramatically to a fourth line chemotherapeutic regimen that consisted of Docetaxel and Adriamycin. To our knowledge, this is the first case of metastatic medullary carcinoma to be treated with this particular regimen with a significant response.
538 CENTRAL DIABETES INSIPIDUS: AN UNCOMMON COMPLICATION OF INVASIVE RHINO-CEREBRAL ZYGOMYCOSIS
Carter C, Wilhelm A. University of Mississippi School of Medicine, Jackson, MS.
Case Report: Rhino-cerebral zygomycosis is a rapidly progressive form of invasive fungal sinusitis that rarely is associated with development of severe central diabetes insipidus (DI). We present a patient with steroid-induced diabetic ketoacidosis and underlying acute myeloid leukemia in remission after allogeneic stem cell transplant who developed severe central DI secondary to invasive Rhizopus infection.
A 58 year-old female with acute myeloid leukemia in remission after allogeneic stem cell transplant and recently diagnosed diabetes mellitus secondary to long-term prednisone therapy for graft versus host disease presented with a one week history of fatigue and headaches. Her physical exam was significant for a fixed and dilated left pupil, while her laboratory studies showed evidence of diabetic ketoacidosis. An initial CT of the head showed inflammatory sinus disease for which broad spectrum antimicrobial therapy including amphotericin was initiated. Over the next 12 hours she developed altered mental status, fevers, and polyuria. Her sodium level increased from 140 to 162 mmol/L during this period. She was started on IV desmopressin therapy for central diabetes insipidus. A MRI of the brain showed invasive fungal sinusitis infiltrating the left optic nerve, pituitary gland, and bilateral internal carotid arteries resulting in bilateral frontal lobe infarcts. Neurosurgery and otolaryngology specialists determined the patient’s disease was too extensive for surgical debridement. A biopsy of the left middle turbinate confirmed Rhizopus infection. Despite aggressive antifungal therapy, the patient continued to deteriorate and died several days later.
Rhino-cerebral zygomycosis is a well-described but relatively uncommon invasive fungal infection that presents with fever, headache, and rhinorrhea in patients with hematologic malignancy, uncontrolled diabetes, or receiving immunosuppressive therapy. In rare cases the infection can spread to the adjacent cavernous sinus or involve the carotid arteries. A small number of case reports studying invasive Rhizopus infection document severe central diabetes insipidus as a sequela indicative of rapid, life-threatening progression. This case highlights the need to aggressively treat sinusitis in patients with significant immunocompromise.
539 OUTCOME DATABASE FOR HIGH-THROUGHPUT SCREENING OF FOLLICULAR LYMPHOMA PROGNOSTIC MARKERS
Borgovan T1,2, Zhang X2, Huang L3, Li L2. 1 University of Queensland School of Medicine - Ochsner Clinical School, New Orleans, LA; 2 Ochsner Laboratory of Transnational Cancer Research, New Orleans, LA and 3 Pathology Department, Ochsner Clinic Foundation, New Orleans, LA.
Purpose of Study: The indolent disease course of Follicular lymphoma (FL) is marked by a relapsing and remitting pattern, partly due to the intrinsic resistance of a cell subset termed cancer stem cells. The objective is to develop a FL patient database sorted according to survival time, in preparation of high-throughput screening for prognostic biomarkers.
Methods Used: Pathology reports, and electronic records were queried to tabulate information on diagnosis, biopsies, and current health. Tissue microarray (TMA) was constructed with selected biopsies, and sections were prepared for immunohistochemistry staining using selected biomarkers. Quantification of reactivates was achieved via electronic high magnification “montage” images using a programmable deconvoluting microscope, and digital batch quantification of the amount of color designated in each image.
Summary of Results: After filtering, our list of 75 FL diagnoses was subsequently partitioned into 2 cohorts: survival ≥15 and ⩽5 years from diagnosis (n=24 and n=51, respectively. Table 1). Survival cut-offs were selected to maximize study power. The finalized database serves as an easily adaptable blueprint for scrutinizing survival and for high-throughput screening of prognostic biomarkers such as TMA.
Conclusions: Qualified prognostic markers will direct clinical decision paradigms on which FL patients are favorable candidates for early therapy, and will obviate additional insight in the development of targeted regiments and treatment protocols to ameliorate outcomes.
540 POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME MIMICKING HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN BRAIN
Alkilani A, Imran H, Wilson F, Siddiqui A. University of South Alabama Children’s and Women’s Hospital, Mobile, AL.
Case Report: We are reporting a case of Hemophagocytic lymphohistiocytosis (HLH) with suspected central nervous system (CNS) involvement that turned out to be cyclosporine (CSA) induced posterior reversible encephalopathy syndrome (PRES). A 16 year old female with spina bifida occulta, meningocoele and Chiari II malformation was diagnosed with secondary HLH after a urinary tract infection. Initial brain computerized tomography (CT) scan was normal. Due to spina bifida and a normal neurologic examination, diagnostic lumbar puncture (LP) was deferred. She was started on HLH-2004 protocol but CSA was held until day 4 due to concerns of hypertension. Once blood pressure improved with therapeutic intervention, CSA was added maintaining therapeutic levels. On day 6, her blood pressure rose to 160/110 followed by a seizure like activity. CT brain and electroencephalogram were normal. However, magnetic resonance imaging (MRI) showed multiple cortical & subcortical T2/FLAIR hyperintense foci in bilateral occipital, parietal and temporal lobes. These findings at that time were best interpreted as CNS HLH. She received 5 weekly doses of intrathecal (IT) prednisone and methotrexate via fluoroscopy guided cervical taps. She had a good response with continued therapy per protocol. Repeat MRI at 3 and 6 months showed resolution of CNS lesions. Since CNS HLH is rarely cured without a hematopoietic stem cell transplantation (HSCT), a discussion with the HSCT center raised the possibility of PRES in the differential diagnosis. Consensus on the diagnosis of PRES was reached due to the fact that her CNS symptoms started only after CSA introduction and the rapid resolution of radiologic findings was not typical of HLH. The HSCT was deferred and CSA was eventually tapered. She finished a total of 40 weeks of therapy per HLH-2004 protocol and remains symptoms free 2 months post therapy. In conclusion, neurologic symptoms should be carefully attributed to HLH if they occur after initiating the treatment, as this may inadvertently lead to IT therapy and HSCT. Hypertension crises and early resolution of MRI lesions favored the diagnosis of PRES in our patient.
Infectious Diseases II
Concurrent Session
1:00 PM
Saturday, February 22, 2014
541 POINT OF CARE SCREENING FOR CRYPTOCOCCAL DISEASE AMONG HOSPITALIZED HIV INFECTED ADULTS IN ETHIOPIA
Bornstein E1, Tenna A2, Temesgen O2, Blumberg HM1, Kempker R1. 1 Emory University, Atlanta, GA and 2 Addis Ababa University, Addis Ababa, Ethiopia.
Purpose of Study: Cryptococcal disease is responsible for significant morbidity and mortality among HIV+ patients in Sub Saharan Africa. New screening strategies are needed to increase case detection. We determined the utility of a FDA-approved point of care (POC) cryptococcal antigen screening test (IMMY Lateral Flow Assay [LFA]) among HIV+ adults admitted to Tikur Anbessa Hospital in Addis Ababa, Ethiopia.
Methods Used: HIV+ adults admitted to general medicine or medical ICU were eligible for enrollment. Study patients had venous blood, finger-stick blood, and a urine specimen collected for LFA testing. Tests were performed according to manufacturer instructions. Serum LFA results were provided to the treating physician and management decisions were at their discretion. Further clinical data were collected through interviews and medical chart abstraction. The agreement of LFA results among different sample types and characteristics associated with positive serum LFA were evaluated.
Summary of Results: 80 HIV+ patients (45% male) with a mean age of 38 were enrolled. The mean CD4 was 197 cells/μL and 64% of patients were receiving ART. Common admission diagnoses included infection (60%) and pulmonary syndrome (30%). The prevalence of serum cryptococcal antigenemia was 10% (8/80). Among the 8 patients with positive LFA, 7 had CD4 count < 100 cells/μL and 5 of 8 were receiving ART. Of the 8 patients with serum antigenemia, 7 had a positive finger stick LFA and 6 had positive urine LFA. 7 patients had LP performed and 6 had positive CSF LFA. The concordance between serum and urine LFA results (kappa (K) = 0.78, 95% CI 0.47-1.00) and serum and finger stick blood LFA results (K = 0.93 (95% CI 0.75-1.00) was high. Patients with positive serum cryptococcal LFA were more likely to have headache (88% vs. 28%), meningismus (50% vs. 6%), and fever (63% vs. 16%), than patients with negative LFA test and also had a lower mean CD4 count (73 vs. 216) (all p < 0.05).
Conclusions: Universal screening for cryptococcal disease with a low cost POC test among HIV+ inpatients in Ethiopia demonstrated a high prevalence of cryptococcemia. This screening strategy increased case detection of cryptococcal disease. LFA testing may also be performed on less invasive finger stick blood and urine samples.
542 CORRELATION OF HUMAN PAPILLOMAVIRUS AND EPSTEIN-BARR VIRUS DETECTION IN ANAL VERSUS CERVICAL SAMPLES IN A COHORT OF HIV+ WOMEN
Oddo H, Sutton K, Nelson N, Meyaski-Schluter M, Hagensee M. LSU Health Sciences Center, New Orleans, LA.
Purpose of Study: Human papillomavirus (HPV) is the most common viral sexually transmitted disease and is the causative agent of cervical cancer. We have previously identified Epstein-Barr Virus (EBV) as a possible cofactor when coupled with HPV in increasing rates of cervical dysplasia by two- to four-fold in an HIV+ population. Furthermore, HPV-related cervical dysplasia puts these individuals at a greater risk of developing similar pathology of the anus. With a marked increase in incidence of anal cancer seen in HIV+ individuals, we have begun to look at possible correlations between the co-shedding of HPV and EBV in increased anal dysplasia and pre-cancerous lesions.
Methods Used: Subjects are HIV+ women currently enrolled in a longitudinal study examining the interaction of HPV and EBV in the development of anogenital lesions. Participants are followed every three months over the course of five years, with cervical and anal Pap smears and swabs collected at each visit. Cervical and anal swabs are DNA-extracted using a Qiagen kit. HPV is detected using Roche linear array targeting the L1 gene. To test for the presence of EBV, a PCR assay is run to detect the BamH1-W gene. These results are correlated with concomitantly obtained cervical and anal Pap smears.
Summary of Results: Data was obtained for seventy-two HIV+ women who had utilizable results for all samples obtained. HPV was detected in anal swabs of 54 (75%) subjects, as well as in the cervix of 54 (75%) subjects. Among these individuals, 43 (59.7%) were concordant. Of those samples from which HPV was detected, mean = 4.8 types were found in anal samples compared with mean =3.2 types from cervical swabs. Furthermore, EBV was detected in anal swabs of 27 (51.4%) subjects, as well as in the cervix of 33 (45.8%) subjects. Among these individuals, concordance was found in 18 (25%).
Conclusions: In this cohort of HIV+ women, HPV was found commonly in both anal and cervical samples. HPV discordance between the two sites was approximately equal (anal+/cx- vs. anal-/cx+). More types of HPV were found in the anus. EBV was approximately equal in all categories. Future plans include analyzing individual viral types and persistence of HPV and EBV shedding in the anus and cervix of these subjects over multiple visits.
543 CHARACTERISTICS OF USA500/IBERIAN METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) INVASIVE DISEASE
Melendez A1, Satola S1,2, Crispell E1, Farley M1,2. 1 Emory University, Atlanta, GA and 2 Atlanta VA Medical Center, Atlanta, GA.
Purpose of Study: Describe the clinical and epidemiologic characteristics of invasive USA500/Iberian MRSA infections and compare to USA300 and USA100 disease.
Methods Used: Population-based surveillance for invasive MRSA disease was conducted in 8-county Metro Atlanta from 12-1-05 to 12-31-11. Isolates were typed by pulse-field gel electrophoresis (PFGE) and/or screened for SCCmec (SM) types II and IV and categorized as non-USA300 with SM IV, USA300, USA100 or other. SM IV isolates were subtyped and spa typed; clonal complex (CC) was inferred by spa type. CC8, non-USA300s that were SM IV but not IVa, were classified as USA500/Iberian and tested for staphylococcal enterotoxin A and B (SEA/SEB) by PCR; SEA/SEB toxin(+): Iberian, and SEA/SEB(-): USA500. Medical records were reviewed.
Summary of Results: Among a total of 2,006 invasive MRSA infections, 36% were due to USA300, 31% USA 100, and 27% (540/2,006) were USA500/Iberian of which 430 were Iberian and 110 USA500. Most invasive USA500/Iberian (99%) cases were bacteremias. Clinical syndromes included: bacteremia without focus (38%), central line-associated (24%), pneumonia/empyema (12%), skin and soft tissue (9%), urinary tract (9%), bone or joint infections (7%), and endocarditis (3%). Most were healthcare-associated community-onset (72%), in men (63%) of black race (73%); 24% were in persons with HIV/AIDS. Bactrim resistance was high (97%). In-hospital mortality was 21% (110/532). Attributable mortality, defined as death ⩽7 days of culture, MRSA + culture from other sterile site ⩽ 7-days of death, or MRSA + at autopsy, was 14%. On univariate analysis, invasive USA500/Iberian infections had greater risk of in-hospital mortality (OR 1.63; 95% CI 1.21-2.20) and attributable mortality (OR 1.44; 95% CI 1.1.01-2.03) than USA300 and similar in-hospital and attributable mortality to USA100 (OR 0.98; [95% CI 0.75-1.33]; OR 1.08 [95% CI 0.77-1.52], respectively).
Conclusions: USA500/Iberian MRSA is a common cause of invasive disease in Atlanta. The association with healthcare exposure, HIV/AIDS and bactrim resistance was strong. Mortality was similar to that with USA100 and higher than USA300 disease. A multivariate logistic regression is needed to better assess the association of USA500/Iberian MRSA with patient outcomes.
544 ENHANCED ACTIVE TB CASE FINDING AMONG PEOPLE LIVING WITH HIV: IMPACT OF A RAPID MOLECULAR TEST (XPERT MTB/RIF)
Adelman MW1, Tsegaye M2, Kempker R1, Abeje T3, Tesfaye A3, Aseffa A4, Blumberg HM1. 1 Emory University School of Medicine, Atlanta, GA; 2 ALERT Hospital, Addis Ababa, Ethiopia; 3 Regional Health Research Laboratory, Addis Ababa, Ethiopia and 4 Aramuer Hansen Research Institute, Addis Ababa, Ethiopia.
Purpose of Study: The World Health Organization (WHO) recommends active tuberculosis (TB) case finding among people living with HIV (PLHIV) in low-income, high TB-burden countries. WHO guidelines include asking PLHIV about the presence of 4 symptoms (cough, fever, night sweats, weight loss) and if any are present pursuing further evaluation. In most low income countries only smear microscopy is available for TB diagnosis; this has low sensitivity among PLHIV. Our prospective study evaluated the utility of combining the WHO symptom screen with a rapid molecular diagnostic assay (Xpert MTB/RIF) for enhancing TB case detection at an HIV clinic in Addis Ababa, Ethiopia.
Methods Used: PLHIV seen at the ALERT Hospital HIV clinic were screened for TB. Presence of the 4 symptoms, demographic, medical and laboratory data were abstracted from the medical record. For patients with a positive symptom screen, sputum was collected for smear microscopy and Xpert.
Summary of Results: 607 PLHIV were screened for TB. Mean age was 38 years, 35% were male, mean CD4 count was 416, and 89% were on antiretroviral therapy (ART). Of 607 screened, 228 (37.6%) screened positive. Those on ART were significantly less likely to screen positive (OR=0.48, 95% CI 0.29-0.79, p<0.01). Among the 228 screen positives, 126 (55.2%) provided sputum samples. 4/126 (3.2%) had pulmonary TB based on a positive Xpert test compared to 1/126 (0.8%) using smear microscopy (p=0.38). Among TB cases there was a trend towards younger age (mean 31 vs. 40, p=0.09) and lower mean CD4 count (296 vs. 426; p=0.39); neither difference was statistically significant.
Conclusions: A high proportion of PLHIV had a positive TB symptom screen; those on ART were less likely to screen positive. The 3% TB prevalence was less than the 7% reported among all PLHIV in Addis Ababa in the pre-ART era. The Xpert appeared to have a higher sensitivity than did smear microscopy but the difference did not reach statistical significance due to low TB prevalence. This pilot study emphasizes the need for larger studies and cost/benefit analyses to assess the impact of new molecular diagnostics on TB case detection among PLHIV.
545 COMPARISON OF HIV RISKY BEHAVIORS AND KNOWLEDGE OF ADOLESCENTS AND PARENTS PRESENTING TO A PEDIATRIC E.D
Barbour W1,2, Galbraith J2, Rodgers J2. 1 UAB, Birmingham, AL and 2 UAB, Birmingham, AL.
Purpose of Study: A comparison of adolescents and parents on adolescent HIV risky behaviors, knowledge of the disease, HIV testing and follow up preferences.
Methods Used: Adolescents ages 14 to 18 presenting to the pediatric E.D. were recruited to participate in a survey designed to elicit knowledge of HIV infection and engagement in HIV-related risky behaviors. Parent/legal guardian of adolescent participants was also recruited to participate. Trained research assistants posed interview questions to consenting adolescents and parents in seperate rooms. Interview responses were analyzed using basic frequency statistics.
Summary of Results: We enrolled 102 adolescents 66 males and 36 females. 19% of participants reported utilizing the pediatric E.D. for routine healthcare. Between adolescents and parents there was a 62% agreement regarding use of tobacco and 49% concerning the use of street drugs. 67% agreed on whether or not the adolescent had been in a physical fight in the past six months. Of 66 participants that reported ever having sex, 32% reported they always practice safe sex. 9% reported not using a condom during last sexual encounter. The max amount of sexual partners reported was 11 and the minimum was 1 with a mean of 3. There was 86% agreement with regards to having sexual intercourse without a condom and the risk of becoming infected with HIV but, only 46% agreement on whether or not a person can be infected with HIV by having unprotected oral sex. 86% agreed that the parent would support the teen’s decision to get tested for HIV. 66% were in agreement that the teen should be tested for HIV if a confidential, rapid test were available.
Conclusions: Our study demonstrates broad engagement in HIV risky behaviors amongst adolescents. It also highlights that parents/legal guardians poorly recognize risky behaviors. There appears to be a large knowledge gap between adolescent and parents regarding basic principles of HIV. This likely contributes to disease transmission and increased morbidity/mortality. Adolescent study participants utilize the ED for primary healthcare needs, which further supports assertions that pediatric E.D.’s are uniquely positioned to screen adolescents for HIV. Early detection will help decrease transmission rates and improve the course of the disease.
546 Impact of drug-drug interactions in first generation protease inhibitors for genotype 1 hepatitis C virus (HCV) infection
Brock JB1,2, Sunesara I1, Burton M1,2. 1 University of Mississippi Medical Center, Jackson, MS and 2 Jackson VAMC, Jackson, MS.
Purpose of Study: In 2011, FDA approved 2 novel serine protease inhibitors (PI), boceprevir and telaprevir, for treatment of chronic genotype-1 hepatitis C virus (HCV) infection in combination with pegylated interferon and ribavirin. As cytochrome P450 3A4 inhibitors, boceprevir and telaprevir are known to interact with many commonly-prescribed medications. Our aim was to determine clinically-relevant drug interactions and their impact on virologic suppression.
Methods Used: A retrospective chart review was performed on patients attending the Jackson VAMC HCV clinic between August 1, 2012 and May 1, 2013. Inclusion criteria included initiation of 3-drug therapy with interferon/ribavirin/PI. Exclusion criteria included co-infection with human immunodeficiency virus or hepatitis B virus. Medical records were reviewed at weeks 0, 4, 8, 12, and 24 of HCV treatment. The primary outcome was the relationship of drug-drug interactions at week 4 of treatment with detectable HCV RNA at week 24.
Summary of Results: A total of 40 patients met inclusion criteria. The majority of patients were male (90%). One-third of patients were cirrhotic . The average number of drug-drug interactions observed was 2.1, ranging from 0-8. Omeprazole (28%), sildenafil (23%), trazodone (20%), citalopram (20%), and loratadine (20%) were the most commonly-encountered drug-drug interactions. The majority of drug interactions were managed by observation (>85%), with the exception of sildenafil, which was managed by dose reduction or discontinuation in over half of cases. The relative risk of a detectable HCV RNA at week 24 was 2.88 (1.58 - 5.22) per additional drug interaction.
Conclusions: This data demonstrates the most commonly-encountered drug-drug interactions for HCV-infected veterans receiving triple therapy with telaprevir/boceprevir. Multiple common drug-drug interactions were observed during anti-HCV therapy with first-generation protease inhibitors. Increased numbers of drug-drug interactions may be detrimental to successful therapy for HCV. Potential explanations for the association of drug interactions and detectable viremia at week 24 include difficulty of adherence related to polypharmacy itself and medical co-morbidities associated with those on multiple medications.
547 PROTECTIVE IMMUNOGENICITY OF VACCINES CONTAINING M-RELATED PROTEINS OF GROUP A STREPTOCOCCI
Shenep LE1,2, Niedermeyer SE1,2, Penfound TA1,2, Dale JB1,2. 1 University of Tennessee Health Science Center, Memphis, TN and 2 Veterans Affairs Medical Center, Memphis, TN.
Purpose of Study: Group A streptococcal (GAS) infections are important causes of significant morbidity and mortality throughout the world. The type-specific M protein has been considered the leading vaccine candidate. M-related protein (Mrp) is another surface protein that is expressed by 83% of clinical isolates of GAS. In contrast to M proteins, the NH2-terminal sequences of Mrp's are highly conserved and are grouped into three structurally related families represented by Mrp2, Mrp4, and Mrp49. In the current study we evaluated the protective immunogenicity of Mrp in mice.
Methods Used: Four groups of 25 Swiss white mice each were immunized with four injections of 30μg of either Mrp2, Mrp4 or Mrp49 or alum alone. Immunogenicity was determined by ELISA and bactericidal tests. Protective efficacy and LD50 were assessed after i.p. challenge infections with 10-fold increasing doses of M2 GAS.
Summary of Results: Recombinant Mrp peptides were immunogenic in mice and evoked high levels of antibodies against the immunizing antigen as well as variable levels of antibodies that cross-reacted with heterologous Mrp’s. Indirect bactericidal tests of pooled immune sera and type 2 GAS resulted in 30-40% killing. The mice were challenged i.p. with 10-fold increasing doses virulent type 2 GAS. The LD50 of the M2 strain seven days post-challenge was not significantly different between immunized and control mice. However, all three Mrp vaccines showed a protective effect as determined by improved survival and delayed deaths. Statistical significance was achieved only on day one post-challenge in the Mrp2 immunized groups.
Conclusions: These results indicate that Mrp is highly immunogenic in mice and evokes bactericidal antibodies against GAS. The level of protective efficacy of Mrp suggests that they may not be effective stand-alone vaccines but may be important additions to multivalent vaccines composed of M peptides and that a combination vaccine may provide broader coverage against a range of GAS serotypes prevalent in regions of the world where rheumatic heart disease and invasive infections cause tremendous morbidity and mortality.
548 ROLE OF ASPERGILLUS FUMIGATUS SIALIDASE IN DISRUPTION OF PULMONARY ARTERY AND PULMONARY MICROVASCULAR ENDOTHELIA
McGrath B1, Cioffi E2, Cioffi D3, Fortwendel J1. 1 University of South Alabama College of Medicine, Mobile, AL; 2 University of South Alabama College of Medicine, Mobile, AL and 3 University of South Alabama College of Medicine, Mobile, AL.
Purpose of Study: Aspergillus fumigatus (Af) is the primary causative species of invasive aspergillosis (IA), a deadly disease that affects immunocompromised patients. A better understanding of the molecular mechanisms regulating invasive growth of Af is essential to the development of novel antifungal therapies. Pulmonary artery (PA) and microvascular (MV) endothelial cells, which form important barriers to hyphal angioinvasion and subsequent bodily dissemination during IA infection, have been shown to express sialic acids that contribute to the integrity of cell-cell interactions. The current study tested the hypothesis that a sialidase enzyme secreted by Af contributes to pathogenesis by facilitating the disruption of these endothelial barriers.
Methods Used: To generate a mutant strain lacking sialidase activity, the sole Af sialidase gene, siaA, was deleted by homologous recombination in a uridine auxotrophic strain using Af protoplast transformation. Standard Aspergillus culture and microscopy techniques were employed to analyze the effect of siaA deletion on germination, hyphal growth and morphogenesis. To determine the impact of siaA deletion on host-pathogen interactions, electric cell-substrate impedance sensing (ECIS) was utilized to measure cell-cell barrier disruption in the presence of Af conidia.
Summary of Results: Deletion of siaA caused delayed germination and a statistically significant reduction in radial growth rate, as compared to wild type. However, the ΔsiaA strain developed morphologically normal hyphae. ECIS analyses indicated reduced cell-cell barrier disruptions for both PA and MV cell lines when cultured with the ΔsiaA mutant.
Conclusions: Taken together, our data suggest that siaA contributes to the timing of Af asexual development and to the disruption of endothelial barriers. Future studies will further define the role of siaA as a potential virulence determinant by delineating the individual contributions of sialidase activity to Af growth, endothelial barrier disruption and virulence in a murine model of invasive aspergillosis.
549 ACCEPTABILITY OF A NEW MODEL OF ETHANOL LOCK THERAPY/PROPHYLAXIS IN CHILDREN WITH CANCER: PRELIMINARY DATA FROM THE ETHEL STUDY
Allison KJ, Branum KC, Wolf J, Flynn PM. St. Jude Childrenr’s Research Hospital, Memphis, TN.
Purpose of Study: Central line associated bloodstream infection (CLABSI) is a serious complication of central venous catheter (CVC) use. Failure of salvage therapy occurs in at least 23% of patients and risk of new infection is high. We studied a new model of ethanol lock therapy/prophylaxis (T/P) to treat CLABSI and prevent reinfection.
Methods Used: This randomized, double-blind study was approved by the St. Jude Institutional Review Board. Children and adolescents with CLABSI who consented to participate were randomized to receive CVC locks with 70% ethanol or placebo for 2 hours to each lumen. Locks were given daily for 5 days, and then on 3 non-consecutive days per week for up to 24 weeks. Participants with ports received locks only when the CVC was accessed.
Satisfaction questionnaires were collected on day 12 (D12) and at end of therapy (EOT) to assess acceptability. Responses of ‘Satisfied’ or higher were included as satisfied. Fisher's exact test was used to determine significance of differences in proportions.
Summary of Results: 51 patients were enrolled between December 16, 2011 and October 10, 2013. Satisfaction data were available at D12 for 32 patients and at EOT for 28 patients.
Most respondents were satisfied with: ease of use (93%), ease of planning (92%) and frequency of use (92%). Most respondents felt that “the good things outweigh the bad things” [GOWB] (85%) and were satisfied “taking all things into account” [OS] (86%). Satisfaction fell between D12 and EOT for OS (96.8% vs 78.6%; p = 0.07) and GOWB (93.8% vs 74.0%; p = 0.04).
Participants with implantable ports had similar satisfaction to tunneled lines for OS (88.9% vs 88.1%; p = 1.0) and GOWB (88.9% vs 83.3%; p = 0.71). At end of therapy, participants who experienced treatment failure had lower satisfaction for both OS (70.0% vs 83.3%; p = 0.63) and GOWB (60% vs 83.3%; p = 0.21) but this was not statistically significant.
Conclusions: Prolonged lock therapy for treatment and secondary prevention of CLABSI is feasible and acceptable in pediatric oncology patients. Patients or caregivers show signs of decreasing satisfaction over time and with treatment failure. These data do not include tolerability or efficacy as the study is ongoing and intervention groups are blinded.
Nutrition
Concurrent Session
1:00 PM
Saturday, February 22, 2014
550 RACIAL AND ETHNIC DIFFERENCES IN CONTEMPORARY INFANT FEEDING PRACTICES: DIRECT BREASTFEEDING AND MILK EXPRESSION
Keim S1,3, McNamara K1, Strafford K3, Dillon C1, Ronau R1, Geraghty S2. 1 Nationwide Children's Hospital, Columbus, OH; 2 Cincinnati Children's Hospital Medical Center, Cincinnati, OH and 3 Ohio State University, Columbus, OH.
Purpose of Study: The definition of breastfeeding is evolving as most mothers now bottle feed infants expressed breast milk in addition to feeding at the breast. How these behaviors differ by race/ethnicity has not been thoroughly examined. Our objective was to examine these practices in a diverse sample of Ohio women and infants to inform clinicians about prevalence and racial/ethnic differences.
Methods Used: Women who delivered a singleton, liveborn infant at >24 weeks’ gestation at Ohio State University Medical Center in mid-2011 and intended to breastfeed were invited to complete a postal questionnaire. Women reported the timing of starting/stopping direct breastfeeding, maternal expressed milk production (pumping), and infant consumption of expressed milk.
Summary of Results: Of 499 respondents (62% response proportion), 457 identified as either non-Hispanic white (378), non-Hispanic African-American/black (55), or Hispanic (24). Overall 96% ever fed their child human milk by any method: 90% directly breastfed, 88% ever fed pumped milk. Some infants were fed expressed milk but never directly at the breast (6.7%). Differences in direct breastfeeding by race/ethnicity did not reach statistical significance (p=0.06). Hispanic women were the least likely to feed their child expressed milk (57%), followed by African-American/black women (76%), and white women (91%). African-American/black women were more likely than white women to have stopped direct breastfeeding (HR=2.05, 95% CI: 1.39, 3.02) or feeding pumped milk (HR=1.84, 95% CI: 1.22, 2.79) by 6 months (too few Hispanic women to estimate). Average durations of all behaviors were longer for white women than African-American/black women (differences ranged 46-74d; durations truncated at 365d). Point estimates for Hispanic women were similar as for white women for feeding any milk and direct breastfeeding and were significantly greater than for African-American/black women (72-76 days longer).
Conclusions: Expressed milk feeding is common but is predominantly practiced by white women. All feeding behaviors were pursued for longer duration by white women than African-American/black women. Fewer differences existed between white and Hispanic women.
551 INCREASING ENTERAL PROTEIN INTAKE IMPROVES GROWTH IN VERY LOW BIRTH WEIGHT (VLBW) INFANTS
Maxted A1, Talati AJ1,2, Skeen A2. 1 UTHSC, Memphis, TN and 2 The Regional Medical Center, Memphis, TN.
Purpose of Study: Preterm infants are at a disadvantage of lacking adequate nutrition because of early separation from mother and difficulty in establishing adequate enteral intake after birth. Human milk (HM) is the best form of feeding for a newborn, but it may not be completely adequate for growth of VLBW infants. Several different additives including human milk fortifiers (HMF), liquid protein (LP) and medium chain triglycerides are added to HM to improve caloric intake and growth. We proposed to evaluate the role of adding LP to HM feeding and its effect on growth of VLBW infants during their NICU stay.
Methods Used: A retrospective chart review was done in the NICU after identifying VLBW infants receiving HM with fortification and added LP. A comparable cohort of VLBW infants receiving HM with fortification was identified. Data were collected for a 4 wk period after the infants were off intravenous nutrition. Daily weight and intake of protein and calories were calculated. A z score was calculated comparing the weekly weight change from start of study and the difference in z score each week was also calculated. Weekly total protein, albumin and other parameters of growth were also recorded for 4 consecutive wk and at the time of discharge.
Summary of Results: A total of 32 VLBW infants were studied. 15 VLBW infants (group 1) received LP in addition to HM +HMF while 17 infants (group 2) received only HM+HMF during the study period. The mean BW (672±148 vs 766±268g), GA (25.1±1.24 vs 25.9±2.2wk) and birth head circumference (22.1±1.14 vs 23.2± 2cm) were similar in both groups. As expected the estimated average daily protein intake was higher in LP (group 1), while caloric intake was similar. The mean growth velocity was higher in group 1 (24.3 ±12.5g vs 13.1±8.6g /d, p<.05) at the end of 4 week period. The weekly change in z-score for weight improved significantly in HM+HMF+LP group of infants by week 4 (-0.26 vs -1.4, p<.05) and at discharge (0.18 vs -0.99, p<.05). The serum BUN levels were similar between the groups each week.
Conclusions: Additional protein intake improves weight gain in VLBW infants fed exclusively with fortified HM. Longer follow up is needed to see the benefit on brain growth and neurodevelopmental outcomes.
552 PREVALENCE OF WEIGHT FOR AGE > 90TH PERCENTILE AND Z-SCORE > 2 FOR HEALTHY CHILDREN AGES 6 MONTHS TO 2 YEARS IN A PEDIATRIC CLINIC
Petty M, Vashishtha N, Higginbottom L, Preudhomme D. University of South Alabama, Mobile, AL.
Purpose of Study: Rising prevalence of overweight U.S. children is concerning due to negative health outcomes. Prevalence of obesity is known in 2-19 years old bracket, but weight prevalence data under the age of 2 is scarce. This age group may be a target for primordial obesity prevention because of controlled environment and intuitive activity. We sought to identify prevalence of weight for age >90th %tile and Z-scores >2 for healthy children ages 6 to 24 months.
Methods Used: A retrospective EHR review of children coming for health maintenance at our pediatric clinic was performed during May-July 2011. Data consisted of age, race, gender and low socioeconomic status (SES) identified by insurance coverage. Data was divided into 2 cohorts with self-identified race being black versus nonblack and low versus high SES. Weight for age >90th %tile and Z-score >2 were identified from the CDC. Descriptive and Chi-square analyses were performed.
Summary of Results: 1,840 patients’ records were reviewed; 1,741(95%) had complete data. There were 869(50%) females; 1,238(71%) blacks; 1,237(71%) low SES; 337(19%) weight for age %ile >90th; 101(6%) weight Z-score >2. In 6, 12, 15, 18, 24 months old cohorts, the respective prevalence of weight >90th %ile was 116(27%), 56(14%), 33(12%), 46(16%) and 86(24%). Prevalence of weight > Z-score of 2 was respectively 35(8%), 11(3%), 11(4%), 16(6%) and 28(8%). There were no statistical differences within each cohort when race, gender or SES were analyzed, except for the 6 months cohort where prevalence of weight >90th and Z-score in females was statistically higher. No statistical difference was found for prevalence of weight >90th and Z-score >2 between 6 and 24 months cohorts.
Conclusions: Prevalence of weight >90th %ile ranged from 12% to 27% between the ages of 6 months to 2 years. No difference was seen according to race, gender or sex. High prevalence of weight >90th %ile or Z-score >2 at 6 months is likely influenced by maternal factors. The 12 months prevalence is the lowest. This may be the result of transition to solid food, controlled food portions and increased activity. Rebound at 15-24 months mirrors exposure to adult food, no portion control and added calories. This finding represents a promising target for decreasing caloric intake.
553 VERY LOW BIRTH WEIGHT INFANT MINERAL AND BONE HEALTH OUTCOMES WITH VITAMIN D SUPPLEMENTATION: DOUBLE-BLIND, RANDOMIZED CLINICAL EFFICACY TRIAL
Finch C, Hollis BW, Wagner CL, Ebeling M, Taylor SN. Medical University of South Carolina, Charleston, SC.
Purpose of Study: The vitamin D (vitD) dose to optimize preterm infant health is unknown. Currently, AAP recommends 400 IU/day. This study evaluated whether infants receiving a supplemental 400 IU/day above standard preterm infant vitD supplementation differed in mineral and bone health from infants receiving placebo.
Methods Used: Appropriate weight for age, black and white, very low birth weight (VLBW) infants with plasma 25-hydroxyvitamin D [25(OH)D] < 20 ng/ml (vitD deficiency) were enrolled within 3 days of birth and randomized to active (400 IU/day supplemental vitD) or placebo group until term age equivalent (TAE). At TAE, plasma 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, urinary calcium and phosphorus excretion, and femur and spine bone mineral content (BMC) and bone mineral density (BMD) were measured. Study powered for difference in vitD sufficiency and outcomes between groups. Statistical analysis was by Chi-square, Fisher exact, and Wilcoxon Rank Sum.
Summary of Results: Forty-seven, vitD-deficient infants were enrolled with 9 lost prior to TAE, and, therefore, 19 analyzed in each group. Active and control groups did not significantly differ in gender, race, birth gestational age, days from birth to TAE visit, or 25(OH)D at entry (13.6 and 11.8 ng/ml). From birth to TAE, median total vitD intake was significantly different between active and placebo groups (942 IU/day and 525 IU/day) (p<0.0001). At TAE, active and placebo groups were not statistically different in vitD deficiency, 25(OH)D status (32.9 and 28.9 ng/ml), calcium, phosphorus, PTH, urinary calcium excretion, urinary phosphorus excretion, and femur and spine BMC and BMD. Four subjects with 25(OH)D<20 ng/ml at TAE when compared to other infants at TAE had significantly lower 25(OH)D (17.4 and 36.7 ng/ml) and higher PTH (68.1 and 38.5 pg/ml), clinically but not statistically lower vitD intake (472 and 826 IU/day) and higher urinary phosphorus excretion (10.7 and 5.2 mg/mg), and no difference in bone mineralization when compared to non-deficient infants at TAE.
Conclusions: VLBW infants receiving an additional 400 IU/day vitD received significantly higher vitD intake, but had no difference in vitD status, mineral homeostasis, or bone mineralization at term age.
554 THE EFFECT OF SLEEP COUNSELING IN WOMEN WANTING TO LOSE WEIGHT: A PILOT STUDY
Limas N, Nantsupawat N, Nugent K, Buscemi D. Texas Tech University Health Sciences Center, Lubbock, TX.
Purpose of Study: Sleep restriction is associated with weight gain and chronic medical disorders, such as hypertension and diabetes. Some patients referred to dietitians have poor sleep patterns, and sleep counseling with routine weight loss counseling might facilitate weight loss in these patients.
Methods Used: We randomized women with BMIs between 25 and 49 kg/m2 into two counseling groups- dietary advice with exercise and dietary advice with exercise and sleep counseling. We met with subjects monthly for six months and collected information on blood pressure, weight, BMI, HbA1C, LDL, HDL, on quality of life using WHO questionnaires, on sleep quality using the Pittsburgh Sleep Quality Index, and from sleep diaries.
Summary of Results: Forty subjects have entered the study. The mean age was 43.0±10.4 years, the mean weight was 187.5±29.4 lbs., and the mean BMI was 33.4±4.3 kg/m2. Six subjects had hypertension, 5 had DM, and 13 were on antidepressant medications. The mean WHO (Five) Well Being Index was 13.2±4.7 (possible score range 0-25), and the numbers of hours of sleep based on the Pittsburgh Sleep Quality Index was 6.9±1.1 hours. Twenty subjects (from both study arms) have completed 6 month follow-ups. In these subjects the BMI decreased from 31.2kg/m2 to 30.5 kg/m2 (p< 0.002) with a change in BMI ranging from -2.60 to +0.97 kg/m2. The number of hours of sleep increased from 7.55±1.1 to 7.85 ±1.0 (p=ns). The WHO Q of L-100 score (possible score range 8-40) was 20.2±4.6 at baseline and 19.8±5.8 at the 6 month follow-up (p=ns). The LDL decreased from 117.9 mg/dl to 109.9 mg/dl (p=0.046), and the HbA1c decreased from 5.65% to 5.22% (p< 0.001).
Conclusions: This pilot study will try to determine whether sleep counseling facilitates weight loss when added to standard counseling based on calorie restriction and exercise. Subjects have lost a modest amount of weight. Sleep duration and quality of life have not changed. Lipid and glucose metabolism parameters have improved which suggest that long term health benefits may occur without large changes in weight. Our final analysis will compare the weight loss in the group with sleep counseling with the group without this counseling.
555 ASSOCIATION BETWEEN BMI AND BIOMEDICAL MARKERS IN OBESE CHILDREN
Radulescu A1, Wallace C1, Li Y2, Anderson A1, Bada H1. 1 University of Kentucky, Lexington, KY and 2University of Kentucky, Lexington, KY.
Purpose of Study: To determine the association between BMI and metabolic abnormalities in children with obesity.
Methods Used: We reviewed the records of pediatric patients evaluated for obesity in the Pediatric High BMI Diagnostic Clinic. Variables collected included demographics, BMI, and laboratory data. For statistical analysis we used descriptive statistics, T-tests, and nonparametric comparisons. A p value <0.05 was considered significant.
Summary of Results: 403 pediatric patients, 2-18 yrs of age were evaluated. 298 had lipid profile, fasting blood glucose level, and HbA1c determinations; a smaller number of patients had vitamine D level measured (n=145). Patients were categorized in two age groups:191 (47.4 %) were 2-10 yrs of age (median, 7 yrs) and the remaining 212 (52.6%) were between 11 to18 yrs old (median, 13 yrs). The children in older group were heavier and had a higher BMI for both boys and girls and all races. The table compares the two groups of children by their biochemical markers. The younger children had higher total cholesterol, LDL, HDL, and vitamin D level but lower HbA1c compared to the older obese children. In a selected number of patients (n=60) insulin level was measured; levels were significantly higher in the older children than in the younger group (p<0.002).
Conclusions: Older obese children have higher BMI and are at the high risk of developing type 2 diabetes, vitamin D deficiency, and cardiovascular disese. Abnormal lipid profile is noted even in younger obese children and screening for cardiovascular risk factors should start at an earlier age.
556 CHARACTERISTICS OF OBESE CHILDREN FROM URBAN AND RURAL AREAS
Radulescu A1, Wallace C1, Li Y2, Anderson A1, Bada H1. 1 University of Kentucky, Lexington, KY and 2 University of Kentucky, Lexington, KY.
Purpose of Study: To compare the characteristics of obese children from urban versus rural areas as to their BMI, weight status and biomedical abnormalities.
Methods Used: The Pediatric High BMI Diagnostic Clinic serves obese children 2-18 years old residing in urban and rural Kentucky counties. We analyzed the medical records of these children for their weight, BMI and laboratory data. For analysis we used descriptive statistics and analysis of variance. A p value <0.05 was considered statistically significant.
Summary of Results: 403 obese patients between 2-18 yrs old were evaluated. Based on their county of residence, the patients were classified into 3 groups, urban and 2 rural areas: rural adjacent to urban location (RA) and remote rural setting (RR). Urban children were referred for evaluation at a younger age, mean (SD) of 9.9 (3) yrs, compared to the children in the rural areas (p=0.02). Mean (SD) weight of children from urban location was lower, 72.6 (28) Kg compared to 88 (34) and 84 (36) kg respectively for children in RA and RR (P=0.0013). Means of calculated BMI of children from rural groups were significantly higher than urban children (p<0.0001). Biochemical data were available in 297 children. There were no differences among groups as to fasting glucose, HbA1c, total cholesterol and LDL. Mean (SD) triglycerides, mg/dLwere 111 (76), 130 (69), and 120 (60) respectively for the urban, RA, and RR groups, p=0.02. Urban children had significantly higher HDL than rural children (p=0.001). Vitamin D levels (ng/mL) were insufficient or deficient in children across 3 groups with mean (SD) levels of 23.6 (8), 24.8 (8.9) and 27. 5 (9) for urban, RA, and RR respectively. ALT levels (U/L) were higher in rural children, mean (SD) of 29 (20) and 33 (17) for RA and RR compared to 26.6 (18) in urban children.
Conclusions: The obese children from rural areas are referred for evaluation at older ages, having worse lipid profile and with elevated ALT suggestive of associated fatty liver. In addition to screening for diabetes, dyslipidemia, and fatty liver, obese children should also be assessed for Vitamin D deficiency. Our experience suggests the need not only for early screening for obesity and co-morbid conditions, but also for improving access to medical care.
557 CAREGIVER AND CHILD PERCEPTION OF WEIGHT
Burgess K1, Tucker M2, Johnson P1. 1 University of Alabama, College of Community Health Sciences, Tuscaloosa, AL and 2 University of Alabama, College of Community Health Sciences, Tuscaloosa, AL.
Purpose of Study: Education efforts to reverse increasing pediatric obesity should be optimized. A pilot study was conducted to determine whether caregivers and children correctly perceive the healthiness of the child’s weight.
Methods Used: A survey was given to 107 caregivers of children aged 2-18 years old during an office visit. Caregiver's perception of their child’s weight (healthy weight, weighs too much, does not weigh enough) was compared to the child’s body mass index (BMI) percentile category (healthy, overweight, obese, underweight). Also, children aged 6-18 were asked their perception of their own weights for comparison to their BMI percentile category.
Summary of Results: 69% of caregivers correctly perceived their child’s weight, and 59% of children correctly perceived their weight.
When children were overweight/obese, caregivers correctly categorized them 46% of the time. Caregivers were more likely to recognize weighing too much when the child was obese rather than overweight, having a correct perception in 68% of the obese children and in 8% of the overweight children. Caregivers were least likely to detect overweight/obesity in 2-5 year olds. Caregivers failed to recognize weighing too much in 80% of overweight/obese children in this age group and recognized it only in obese children.
When asked to identify their own weight category, 52% of the obese/overweight children correctly categorized themselves. Obese children were more likely to correctly identify themselves as weighing too much when compared to overweight children (61% and 29% respectively). The child and caregiver pairs both correctly identified the child as weighing too much 40% of the time, and of those children, 90% were obese.
When caregivers made an incorrect categorization, 94% underestimated the child’s weight. When children incorrectly categorized themselves, 81% underestimated their weight.
Conclusions: This study shows children are not perceived as weighing too much until they are actually obese. The underestimation of a child’s weight leads to inaction. Education should focus on caregivers’ and children’s recognition of an unhealthy weight. If the caregiver is not aware that their child is an unhealthy weight then behavior change programs will have limited success.
558 OBESITY: DOES YOUR ZIP CODE MATTER?
Burgess K1, Tucker M2, Mouton C1, Henson D1. 1 University of Alabama, College of Community Health Sciences, Tuscaloosa, AL and 2 University of Alabama, College of Community Health Sciences, Tuscaloosa, AL.
Purpose of Study: Pediatric obesity has increased over the past decade, especially in Alabama. Obesity has been linked to individual income and education. Less is known if living in a specific community affects a child’s weight. Some research indicates obesity rates are similar in some neighborhoods. Determining the obesity rate in local neighborhoods and counties will assist in determining areas to concentrate research and interventions. This study determined whether obesity rates among pediatric patients at University Medical Center (UMC), Tuscaloosa, AL were associated with area-based measures of socioeconomic status and location.
Methods Used: This study was a retrospective chart review of 1,983 pediatric patients, aged 2-19 years, receiving care at UMC over a 6 month period. Patients were categorized as either child (2-10 years old) or adolescent (11-19 years old) and as being underweight, healthy weight, overweight or obese based on body mass index (BMI) percentile for age. Address data for each patient was plotted using geo-mapping software to identify obesity clusters. Insurance information was used to indicate socioeconomic status.
Summary of Results: Review found 81% had Medicaid and 19% had private insurance. The average pediatric patients’ BMI was in the 67th percentile; however, 20.4% of the children and 28.7% of the adolescent patients were obese, compared to the state average of 14.1% and 13.5% respectively.
There was no statistical difference in obesity prevalence between rural and urban areas, between various zip codes, or between low or high socioeconomic status. However, childhood obesity is clearly a significant issue at UMC and in the community.
Conclusions: Pediatric obesity is a ubiquitous problem in this community and region. Its prevalence crosses socioeconomic boundaries. Education efforts should be broad to reach all areas and groups.
To better understand the obesity epidemic and related social determinants of health in Tuscaloosa, more must be learned about community-level risk factors, especially how built environment and social norms operate within communities and across racial/ethnic groups. More research is needed to identify commonalities within residents of this region and to identify significant contributing factors.
559 MALNUTRITION ASSESSMENT IN CHILDREN UNDER FIVE YEARS OF AGE IN THE MEGHNA RIVER ISLANDS OF NARSINGDI, BANGLADESH
Siraj S1, Patel R2. 1 USF, Tampa, FL and 2 Mount Sinai, new york, NY.
Purpose of Study: One of the most significant threats to the South Asian nation of Bangladesh is the historically high rate of childhood malnutrition. Despite the United Nations’ Millennium Development Goal of eradicating world hunger, roughly 36% of Bengali children under 5 years of age are still underweight.
The Char Islands are an archipelago of small sand islands surrounded by Bangladesh’s massive Meghna River. During Bangladesh's six-month monsoon season, the Char Island communities become virtually inaccessible to healthcare workers due to its challenging geography and harsh flood conditions. This study hypothesizes that because of the relative inaccessibility of the Char Islands communities to basic healthcare, this population will have higher rates of malnutrition than other rural communities of Bangladesh.
This study’s primary objective is to assess the prevalence of malnutrition in children under 5 years of age in three Char Island communities in Narsinghdi, Bangladesh using the Mid-Upper Arm Circumference technique. The second objective is to assess any factors in the communities which might predict the presence of childhood malnutrition. This objective was accomplished by conducting brief health surveys with mothers in the community
Methods Used: Trained non-governmental organization staff members conducted door-to-door interviews and study participants were chosen based on convenience sampling. After obtaining verbal consent, the survey was administered in the native language and Mid-Upper Arm Circumference was measured by the NGO staff member. Simple logistic regression and descriptive analysis were performed on the data.
Summary of Results: The rate of malnutrition in the Char population was 17%. The health surveys revealed that food and education were the most important perceived predictors of health status. Mothers identified malnutrition as the most serious health threat to their children. Fifty-eight percent of mothers believed that their child was subjectively underweight when compared to others.
Conclusions: According to our study, the malnutrition rate in the three sampled Char River Islands was 17%. Although this rate is lower than the rest of rural Bangladesh, we propose the need for larger studies to include more island communities, focusing particularly on the innermost islands as they are the most difficult to access.
560 URINARY ELCTROLYTE EXCRETION AND SERUM POTASSIUM AMONG AFRICAN-AMERICANS; THE JACKSON HEART STUDY
Fülöp T1, Tapolyai M2, Zsom L1, Hickson DA1,3,4, Lirette S5, Flessner MF6, Griswold M1,3,5. 1 University of Mississippi Medical Center, Jackson, MS; 2 WJB Dorn VA Medical Center - University of South Carolina, Columbia, SC; 3 Jackson Heart Study, Jackson, MS; 4 Jackson State University, Jackson, MS; 5 University of Mississippi Medical Center, Jackson, MS and 6 NIDDK, Bethesda, MD.
Purpose of Study: The relationship between serum and urine electrolytes is not well studied in contemporaneous large African-American cohorts.
Methods Used: We performed a cross-sectional analysis of serum potassium levels in relation to serum aldosterone and urinary excretion of sodium and potassium from Jackson Heart Study (JHS) participants, 1,024 of whom submitted valid 24-hour urine collections. Medical history, including drug therapy, anthropometric measurements, serum and urine samples were obtained from JHS participants at the baseline visit.
Summary of Results: Participants with 24-hour urine collections were predominantly female (68%), obese (average BMI: 31.9±6.9 kg/m2) and older (average age: 58.4±11.3 years), with a high prevalence of hypertension (70%). The average serum potassium level was 4.2±0.4 mEq/L. Urine potassium excretion (average: 48.4±21.8 mEq/24 hour) and urine sodium excretion (average: 160.6±70.8 mEq/24 hour) were strongly correlated with each other (r=0.37, p<0.001). However, in the cohort as a whole, serum potassium levels were not correlated with urine excretion of sodium or potassium. The subcohort (n=500) not on medications potentially interfering with potassium balance showed a marginal increase in serum potassium levels 0.05 mEq/L (95% CI: 0.02; 0.09) for each 20 mEq hour rise of urinary potassium excretion in 24 hours (p=0.005). The subgroup on medication potentially interfering with potassium balance (n=524) showed no significant association between serum potassium levels and urine sodium or potassium excretion.
Conclusions: In this community-dwelling cohort of middle-aged African Americans, serum potassium levels showed no correlation with urine sodium and potassium excretions. Among participants not on medications potentially interfering with potassium, there was a suggestion of a marginal increase in serum potassium levels with increases in urinary potassium excretion.
Perinatal Medicine II
Concurrent Session
1:00 PM
Saturday, February 22, 2014
561 HOMOCYSTEINE SUPPRESSES PLACENTAL EXPRESSION OF THE CREATINE TRANSPORTER SLC6A8: ROLE OF DNA METHYLATION
Cash L1,2, Sonne S2, Bhatia J1, Ganapathy V2. 1 Georgia Regents University, Augusta, GA and 2 Georgia Regents University, Augusta, GA.
Purpose of Study: SLC6A8 mediates cellular uptake of creatine. Mutations in SLC6A8 lead to severe neurological deficits; such as intellectual and developmental disabilities. Here we studied the role of SLC6A8 in the maternal-fetal transfer of creatine across the placenta. We also investigated the influence of homocysteine on the expression and function of Slc6a8 in mouse placenta.
Methods Used: Knockout mice with deletion of methylene tetrahydrofolate reductase (Mthfr) were used as a model for hyperhomocysteinemia. Placental expression of Slc6a8 in wild type and Mthfr-null mice was investigated by real-time qPCR and immunofluorescence. DNA methylation was examined using an antibody specific for 5′-methylcytosine. These studies were complemented with a human trophoblast cell line (BeWo) with and without exposure to homocysteine for 5-7 passages. Activity of SLC6A8 in cells was monitored by [14C]-creatine uptake. Influence of DNA methylation on Slc6a8 expression was evaluated using DNA methylation inhibitors.
Summary of Results: Slc6a8 expression (mRNA and protein) was lower in Mthfr-/- placentas than in wild type placentas. DNA methylation inhibitors re-activated Slc6a8 in Mthfr-/- placentas. 5′-Methylcytosine was significantly higher in Mthfr-/- placentas than in wild type placentas. BeWo cells showed saturable Na+-coupled creatine uptake activity (Michaelis constant, 43 ± 8 μM). Chronic exposure of BeWo cells to homocysteine decreased the expression and activity of SLC6A8. Uptake of creatine in brush-border membrane vesicles from human term placenta provided evidence of SLC6A8 function.
Conclusions: Placenta expresses the creatine transporter SLC6A8 and exhibits Na+-coupled creatine transport activity. Hyperhomocysteinemia in mice decreases placental Slc6a8 expression, probably via promoter methylation. Homocysteine suppresses SLC6A8 expression in BeWo cells. Human placental brush-border membrane expresses SLC6A8. These data show that placenta possesses mechanisms to transfer maternal creatine to the fetus and that homocysteine suppresses this transport function. Since creatine is critical for energy homeostasis, maternal hyperhomocysteinemia might decrease the availability of maternal creatine to the developing fetus, potentially affecting development.
562 NEONATAL NEUTROPHIL COMPOSITION AND FUNCTION BY GESTATIONAL AGE
Makoni MM, Eckert J, Lawrence SM. Oklahoma University Health Science Center, Oklahoma City, OK.
Purpose of Study: Neonatal neutrophils have quantitative and qualitative defects including impaired chemotaxis, rolling, adhesion, and margination. Analysis of RNA markers has shown that following delivery, neonates have more immature circulating neutrophils than adults. We wanted to determine if gestational age (GA) affects neutrophil composition thus altering: (1) neutrophil microbicidal protein production; (2) phagocytosis and chemotaxis; and (3) serum chemokine and cytokine concentrations in cord blood.
Methods Used: We isolated neonatal neutrophils from cord blood of inborn infants 23-40 weeks GA. We labeled the cells as per Fujimoto et al (Cytometry 2000) and determined the percentage of immature to mature cells via flow cytometry. We then sorted based on maturational stage which was verified by determining neutrophil granule RNA production via Luminex QuantiGene Plex Assays. Serum cytokine/chemokine levels were determined via 54-plex Procarta Cytokine Assay kit, neutrophil phagocytosis was measured by flow cytometry of labeled E.coli, and chemotaxis evaluated via Transwell methods.
Summary of Results: Flow cytometry shows no difference the neutrophil composition based on gestational age. However, exposure to a full course of betamethasone resulted in a more mature neutrophil population at birth (p<0.03). Initial phagocytosis experiments show that neonatal immature neutrophils do not phagocytose E.coli as compared to neonatal mature cells, which appear to phagocytose similar to adult cells. Microbicidal protein concentration, chemokine/cytokine, and chemotaxis are currently ongoing.
Conclusions: We have shown that neonates have more circulating immature neutrophils as compared to adults, but this difference does not appear to differ based on GA of the infant. New findings are that betamethasone significantly increases the percentage of mature neutrophils in newborn infants that receive a full course of treatment. Presumably, this should improve their ability to respond to infection in the initial newborn period. Neonatal neutrophil function appears to differ based on developmental stage since immature cells are unable to phagocytose, however chemotaxis, microbicidal protein production, and chemokine/cytokine response remains to determined.
563 DOES LIBERAL SIBLING VISITATION INCREASE THE RATE OF NOSOCOMIAL INFECTIONS IN THE NICU?
Bedwell S1, Corff K2, Anderson M2, Sekar K2. 1 The Children’s Hospital at OU Medical Center, Oklahoma City, OK and 2 University of Oklahoma Health Science Center, Oklahoma City, OK.
Purpose of Study: Sibling visitation in the NICU varies across the country. Some NICUs place severe restrictions on sibling visitations particularly for children less than <3 years of age with the aim of preventing nosocomial infections. However, no study to date has linked sibling age or frequency of visits to increased infections in the NICU. Our NICU has adopted a liberal sibling visitation policy irrespective of age (ages 0-16) with strict screening procedures and documentation of current immunizations. This study evaluates whether a liberal sibling visitation policy increased the incidence of nosocomial infections in our tertiary care level IV NICU.
Methods Used: We reviewed sibling visitation records of patients admitted and discharged from our NICU between January 1, 2012 and December 31, 2012. A total of 1107 admissions and 26,433 hospital days occurred during this period. Data was analyzed to determine the correlation between visits and the incidence of any nosocomial infections. Any sibling visitation regardless of age was considered in the analysis.
Summary of Results: Bivariate analysis showed a significant correlation between any sibling visitation and any nosocomial infection (p=0.0214) but no correlation between any sibling visitation and presence of a specific nosocomial infection (late onset sepsis, ventilator associated pneumonia, central line associated bacteremia, urinary tract infection and clinical sepsis without positive culture). Multivariable logistic regression models exploring the independent effect of any sibling visitation on any nosocomial infection controlling for gestational age, chronic lung disease, necrotizing enterocolitis, intraventricular hemorrhage and patent ductus arteriosus, catheter and ventilator days show sibling visitation (aOR=1.154, CI=0.649, 2.051) did not have a significant independent effect. The incidence of infection did, however, increase significantly in all models as catheter and vent days increased.
Conclusions: While increased nosocomial infections were seen among infants with sibling visitation in the bivariate analyses, this increase was not significant when adjusting for catheter days, ventilator days and other covariates.
564 ELEVATED MATERNAL WEIGHT AND WEIGHT GAIN ON OUTCOMES IN TWIN PREGNANCIES
Halloran DR1, Marshall N2, Guild C1, Caughey A2. 1 Saint Louis University, St Louis, MO and 2 Oregon Health Science University, Portland, OR.
Purpose of Study: Determine effect of elevated prepregnacy weight and weight gain on maternal/infant outcomes in twin pregnancies.
Methods Used: This is a retrospective cohort study of birth records for twin pregnancies delivered between 1993 and 2008 to Missouri residents (N=33,272). Using 2009 IOM guidelines, prepregnancy weight was underweight (body mass index (BMI) <18.5 kg/m2), normal (BMI 18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2) and weight gain was below, within, or above the recommendations. Outcomes included gestational hypertension, method of delivery, preterm delivery (<37 weeks), and infant complication (composite of outcomes such as low Apgar score and respiratory distress syndrome). Regression models were run stratified by prepregnancy BMI for each outcome and then with both prepregnancy BMI and weight gain in the model.
Summary of Results: The sample included 1448 (4.4%) underweight women, 17,079 (51.3%) normal weight, 7555 (22.7%) overweight, and 7190 (21.6%) obese. The percent of women who gained above the recommendation increased with increasing prepregnancy weight: underweight 17.1%, normal 18.4%, overweight 20.1%, and obese 23.9%. After adjusting for confounders, regression analyses stratified by BMI found that excess weight gain increased the risk of gestational hypertension and cesarean delivery but decreased the risk of preterm delivery and did not affect infant complications. Insufficient weight gain reduced the risk of gestational hypertension and cesarean delivery but increased the risk of preterm delivery and infant complications.
Conclusions: Although elevated prepregnancy BMI increased the risk of adverse outcomes in twin pregnancies regardless of weight gain, excess weight gain increased the risk of hypertension and cesarean delivery but decreased the risk of preterm birth. Further work in twin pregnancies needs to identify optimal weight gain to minimize adverse outcomes.
565 HEALTH CARE UTILIZATION IN EARLY CHILDHOOD FOLLOWING LATE PRETERM DELIVERY
Halloran DR1, Kunovich R2, Guild C1, Caughey A3. 1 SLU, St Louis, MO; 2 UT Arlington, Arlington, TX and 3 OHSU, Portland, OR.
Purpose of Study: Determine effect of late preterm birth on health care utilization during early childhood.
Methods Used: A retrospective cohort study of birth records linked to Missouri Medicaid claims data (2000-2005). Inclusion: >=10 months of continuous coverage and 3 to 8 years of age. Health care utilization categorized as office (general and subspecialty), hospitalizations, ER, and other (eg. therapy services). Gestational age categorized as term (37-40 weeks), late preterm (34-36 weeks), and preterm (<34 weeks). Analyses included Poisson and generalized estimating equations adjusted for maternal demographics and health behaviors.
Summary of Results: There were 174,366 children in the claims data including 145,922 (83.7%) term, 20,441 (11.7%) late preterm, and 8003 (4.6%) preterm. There were a total of 2,975,025 visits between 3 and 8 years of age. The majority were office visits 1,682,952 (56.6%) along with hospital admissions 627,181 (21.1%), emergency room visits 274,959 (9.2%), and other services 389,933 (13.1%). After adjusting, children born late preterm were more likely to be hospitalized, have ER visits, and other services than term (p<0.001). Children born late preterm were less likely to have all visit types than preterm (p<0.001). Based on GEE, for every additional week of gestation, the total number of visits decreased 0.3% including a 21.8% decrease in office visits, 4.3% in hospitalizations, 1.6% in ER visits, and 1.4% in other services (p<0.001).
Conclusions: There is increased health care utilization for children between 3 and 8 years of age who were born late preterm including hospitalizations, ER visits, and other services. The impact of a late preterm delivery extends well beyond the newborn period and is likely, therefore, to be associated with increased cost.
566 KEY GLUCONEOGENIC MOLECULES ARE DEVELOPMENTALLY REGULATED IN NON-HUMAN PRIMATES
McGill-Vargas L1, Johnson-Pais T1, Gastaldelli A2, Johnson M1, DeFronzo R2, Musi N2, Blanco C1. 1 UTHSCSA, San Antonio, TX and 2 UTHSCSA, San Antonio, TX.
Purpose of Study: Hyperglycemia is a highly prevalent condition in premature infants and has been associated with significant morbidity and death. Human and animal studies have shown that premature infants have persistent hepatic glucose production despite hyperglycemia. The purpose of this project is to examine developmental differences in hepatic gluconeogenic molecules in fetal/newborn baboons.
Methods Used: Eighteen fetal baboons were delivered at 125 day (d) gestational age (GA), 140d GA and 175d GA (term=185dGA) via C-section and sacrificed immediately after birth. Eight baboons delivered at term and healthy adults were used as controls. Protein content and gene expression of key gluconeogenic/insulin signaling molecules were measured: cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), mitochondrial PEPCK (PEPCK-M), glucose-6-phosphatase-alpha (G6Pase-α), G6Pase-β, fructose-1,6-bisphosphatase, and transcription factor forkhead box-01 (FOXO1). Statistical Calculations were performed utilizing SPSS 17.0.
Summary of Results: The protein content of PEPCK-M increased as gestational age increased (9.6 fold increase from 125dGA to 175dGA, p<0.001). PEPCK-C gene expression was consistent with these developmental differences. Gene expression of PEPCK-C continued to increase into adulthood (>2000 fold increase from 125d GA to adult and 40 fold increase from term to adult, p<0.001). In contrast, G6Pase-α transiently decreased at 140dGA (p<0.01) and then returned to baseline; G6Pase gene expression was higher in preterm animals compared to term (p=0.02). FoxO1 mRNA content was higher in adults compared to neonates (p=0.02).
Conclusions: Gestational differences are seen in hepatic gluconeogenic molecules in fetal, neonatal and adult baboons. In particular, fetal PEPCK protein and gene expression increases with advancing gestational age and continues to increase with maturation into adulthood whereas G6Pase was higher in the most immature animals. PEPCK and G6Pase may play an important role in glucose metabolism during the perinatal period and could be the key molecules for glucose regulation and innovative therapies.
567 IDENTIFICATION OF HYPEROXIA RESPONSIVE ELEMENT IN PROMOTER REGION OF CYTOCHROME P450 1A1 GENE REGULATING ITS INDUCTION IN RESPONSE TO HYPEROXIA IN HUMAN LUNG CELL CULTURE
Basu SK, Chu C, Couroucli X, Weiwu J, Moorthy B. Baylor College of Medicine, Houston, TX.
Purpose of Study: Cytochrome P450 1A1(CYP1A1) family of enzymes metabolize reactive oxygen species(ROS) and are protective against oxygen mediated lung injury in animal studies. Oxygen mediated injury plays a role in bronchopulmonary dysplasia(BPD) in neonates. CYP1A1 expression is proposed to be regulated by hyperoxia (or aryl hydrocarbon) responsive elements (HREs or AhREs) in the promoter region of the gene. Our study aims to identify these HRE regions in the promoter gene regulating CYP1A1 expression.
Methods Used: We used human lung cell culture (H441) to study effect of hyperoxia, known inducer 3-methylcholanthrene (MC) and inhibitor alpha-Naphthoflavone (AN). A CYP1A1 promoter was constructed in a pGL4 luciferase reporter plasmid and the DNA sequences in several specific regions suspected to function as HRE were mutated. H441 cell lines were co-transfected by mutated promoter plasmids (e.g. pGL4-Δ974, pGL4-Δ1373) with renilla luciferase construction (pGL-Rluc) and intact wild type promoter plasmids (pGL4-WT) with firefly luciferase construction (pGL-Fluc).
We grew the cells in room air vs. hyperoxia (95% O2, 5% CO2) for 0-72 hrs and treated with AN (30 μM) and MC (1 μM) in various combinations. We measured luciferase expression by Dual Luciferase (renilla and firefly) assay as indicator of CYP1A1 promoter gene induction. Endogenous CYP1A1 expression at the RNA, protein and enzyme levels was determined using RT-PCR, Western Blot and ethoxyresorufin O-deethylase assay respectively.
Summary of Results: Our results reveal induction of endogenous and pGL4-WT CYP1A1 in response to hyperoxia and MC, and inhibition on exposure to AN. Dual luciferase assays with the mutated plasmid transfections indicate that the pGL4-Δ974 mutation blocks CYP1A1 induction in response to hyperoxia. The pGL4-Δ974 mutation also blocks the CYP1A1 induction by MC.
Conclusions: Our experiments indicate that CYP1A1 promoter gene region at (-Δ974) is involved in regulation of CYP1A1 in response to hyperoxia and known inducer/inhibitors and is a likely candidate for the proposed HRE/AhRE regulatory segment. Further studies are needed for defining the regulatory pathway and may lead to new interventions for BPD in preterm neonates.
568 DELETION OF ARYL HYDROCARBON RECEPTOR GENE POTENTIATES HYPEROXIC INJURY IN NEONATAL HUMAN PULMONARY MICROVASCULAR ENDOTHELIAL CELLS
Shivanna B, Chu C, Jiang W, Moorthy B. Baylor College of Medicine,Texas Children’s Hospital, Houston, TX.
Purpose of Study: Hyperoxia contributes to bronchopulmonary dysplasia (BPD) in preterm infants. We showed that newborn aryl hydrocarbon receptor (AhR) dysfunctional mice are more susceptible to hyperoxia-induced lung inflammation and alveolar simplification than wild type (WT) controls due to decreases in the expression of phase I (cytochrome P450 (CYP) 1A) and phase II (NADP(H) quinone oxidoreductase and microsomal glutathione S-transferase 1) detoxifying enzymes. Whether AhR protects newborn human lung cells against hyperoxic injury is unknown. Therefore, we tested the hypothesis that AhR deficient neonatal human pulmonary microvascular endothelial cells (HPMEC) will have increased oxidative stress and cell death compared to AhR sufficient HPMEC upon exposure to hyperoxia.
Methods Used: We knocked down AhR gene in HPMEC by small interfering RNA (siRNA) transfection and validated the results by western blotting and real-time RT-PCR analysis. Twenty-four hours after transfection, the HPMEC were exposed to room air (95% air and 5% CO2 at 370C) or hyperoxia (95% O2 and 5% CO2 at 370C) for upto 48 h. Following exposure, the cells were harvested to determine viability (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay), necrosis and apoptosis (Annexin V staining and flow cytometry), reactive oxygen species (ROS) generation (2′-7′- dichorodihyrofluorecein diacetate staining and flow cytometry), and AhR expression (western blotting and real-time RT-PCR analysis).
Summary of Results: Interestingly, exposure to hyperoxia decreased AhR expression in HPMEC. In both AhR sufficient and deficient HPMEC, exposure to hyperoxia increased ROS generation and cell necrosis, and decreased cell viability. However, hyperoxia-induced ROS generation and cell death was significantly increased in AhR deficient cells compared to AhR sufficient cells.
Conclusions: AhR deficient HPMEC have increased oxidative stress and cell death compared to AhR sufficient HPMEC upon exposure to hyperoxia. Our data suggest that strategies directed towards increasing AhR activation would be effective in the prevention and treatment of BPD in preterm infants.
569 B-TYPE NATRIURETIC PEPTIDE AND MORTALITY IN PRETERM INFANTS WITH PULMONARY HYPERTENSION
Cuna A, Kandasamy J, Sims B. University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: B-type natriuretic peptide (BNP) is a strong predictor of mortality in adult patients with various forms of pulmonary hypertension (PH) and may be a strong prognostic marker in preterm infants with bronchopulmonary dysplasia (BPD) associated PH as well. We sought to assess the relationship between peak BNP levels and all-cause mortality in a cohort of preterm infants with BPD and PH.
Methods Used: We retrospectively identified preterm infants with BPD and PH who had serum BNP levels measured as part of routine clinical care in the neonatal intensive care unit. Peak serum BNP level was correlated with survival to discharge or death.
Summary of Results: 36 infants (mean gestational age 26.0 ± 1.9 weeks and mean birth weight 740 ± 290 grams) with BPD and PH had available survival data and had serial serum BNP levels measured. Peak BNP level was significantly lower among infants who survived than among those who died (128 pg/ml, [IQR 23 to 463] vs. 997 pg/ml, [IQR 278 to 1770], P<0.004). On multivariate Cox proportional hazard analysis, BNP predicted survival independent of age, gender, and BPD severity. Area under receiver operator characteristic analysis identified a BNP value of 220 pg/ml to have 90% sensitivity and 65% specificity in predicting mortality.
Conclusions: BNP estimation may be useful as a prognostic marker of all-cause mortality in preterm infants with BPD associated PH.
570 REGULATION OF GENE EXPRESSION BY DNA METHYLATION DURING MURINE ALVEOLAR SEPTATION
Cuna A1, Halloran B1, Pandit K2, Kaminski N3, Ambalavanan N1. 1 Univ of AL at Birmingham, Birmingham, AL; 2 Univ of Pittsburgh, Pittsburgh, PA and 3 Yale Univ, New Haven, CT.
Purpose of Study: Lung development is a complex process involving tight regulation of multiple genes in a temporally and spatially controlled manner. DNA methylation, a major epigenetic mechanism that regulates gene expression, is vital in organ development and likely plays an important role in lung development. The aim of this study was to identify genes regulated by DNA methylation during normal alveolar septation in mice.
Methods Used: Newborn mouse lungs before start of alveolar septation and adult mouse lungs after completion of alveolar development were evaluated by microarray analysis of gene expression and chromatin immunoprecipitation followed by sequencing of methylated DNA. Genes with reciprocal changes in expression and methylation, suggesting regulation of gene expression by DNA methylation, were identified. Selected genes were further validated by real-time reverse transcriptase polymerase chain reaction, analysis of promoter methylation, and Western blotting.
Summary of Results: 210 genes were both differentially expressed and differentially methylated in adult versus newborn mouse lungs. Of these, 90 had an inverse correlation between DNA methylation and gene expression. 52 genes were methylated with decreased mRNA expression in newborn compared to adult lung; and 43 genes were methylated with decreased mRNA expression in adult compared to newborn lung. We selected MMP3, TNC, and ZNF536 for further validation.
Conclusions: Changes in DNA methylation correspond to altered gene expression of a number of genes known to be associated with organ development, suggesting that DNA methylation regulates alveolar septation in lung development.
571 THE USE OF GENTLE VENTILATION STRATEGIES FOR LUNG RECRUITMENT IN PRETERM PIGLETS
Arrindell E1, Krishnan R1, Talati AJ1, Buddington R2. 1 University of Tennessee HSC, Memphis, TN and 2 University of Memphis, Memphis, TN.
Purpose of Study: Lung recruitment and airway clearance after birth is crucial for neonatal transition to extrauterine life and the start of pulmonary gas exchange. This process is compromised after preterm birth due to surfactant deficiency, excess lung water and structural immaturity of the preterm lung, often leading to significant morbidity. This study compares lung recruitment and lung injury after 24 hours of ventilation in a preterm piglet model of respiratory distress syndrome. We hypothesized that Airway Pressure Release Ventilation (APRV) will result in improved lung recruitment and less lung injury than Assist-Control+Volume Guarantee (AC+VG), Nasal cannula (NC) & Bubble Continuous Positive Airway Pressure (bCPAP) by allowing higher mean airway pressure with high inspiratory time, maintaining lower peak pressures and maintaining airway patency with gradual lung recruitment for gas exchange. APRV may reduce lung injury by reduction of stretch and shear forces that occur with AC+VG.
Methods Used: Day 102 piglets were delivered via cesarean section from 3 sows and received either APRV (n=6) or AC+VG with tidal volume of 5cc/kg, (n= 8) for 24 hours. Piglets were intubated in the first hour of life. Control piglets received either NC (n=11) or Bubble CPAP 5cm H2O (n=6) for 24 hours. Piglets were allowed to spontaneously breathe and all received parenteral nutrition. Serial arterial blood gases were followed and x-rays were obtained. Necropsy was performed at 24 hours and lung histopathology, bronchoalveolar lavage fluid, measurements of wet/dry lung mass and surfactant expression were obtained.
Summary of Results: At 24 hours there were no significant differences in wet/dry lung mass or lung physiology data between ventilated groups. Ventilated groups had higher surfactant levels than control groups. Unventilated control pigs experienced ~50% mortality. All ventilated pigs survived 24 hours. APRV pigs exhibited improved lung aeration and recruitment, with decreased signs of lung injury by radiography and qualitative histopathology.
Conclusions: APRV is more effective than AC+VG for proactive recruitment of the preterm lung, while maintaining comparable lung physiology without increased evidence of lung injury. The long-term consequences of early lung recruitment using APRV need to be evaluated.
Renal, Electrolyte and Hypertension II
Concurrent Session
1:00 PM
Saturday, February 22, 2014
572 PDGF RECEPTOR ANTAGONISM PREVENTS THE INCREASE IN KIDNEY ANGIOTENSIN II LEVELS IN CYP1A1-REN2 TRANSGENIC RATS WITH ANGIOTENSIN II-DEPENDENT MALIGNANT HYPERTENSION
Thompson DA, Seth DM, Davis PD, Mitchell KD. Tulane University, New Orleans, LA.
Purpose of Study: Previous studies demonstrated that chronic administration of the PDGF receptor kinase inhibitor, imatinib mesylate, ameliorates the renal injury, improves renal hemodynamics, and prevents the augmented urinary angiotensin II (ANG II) excretion in transgenic rats [TGR(Cyp1a1Ren2)] with angiotensin (ANG) II-dependent malignant hypertension. The present study was performed to determine if chronic PDGF receptor blockade prevents the augmentation of intrarenal ANG II levels that occurs in Cyp1a1-Ren2 transgenic rats with ANG II-dependent malignant hypertension.
Methods Used: Male Cyp1a1-Ren2 rats (n=5/group) were induced to develop malignant hypertension by dietary administration of indole-3-carbinol (I3C, 0.3% wt/wt) for 10 days. One group was chronically treated with imatinib mesylate by oral gavage (60 mg/kg/d) starting 3 days before initiating I3C induction and maintained on imatinib for the duration of the study. Systolic blood pressures (SBP) were measured daily by tail-cuff plethysmography. On day 10 of I3C administration, rats were subjected to conscious decapitation and trunk blood was collected for measurement of plasma renin activity (PRA) and plasma ANG II levels. The kidneys were harvested for determination of total kidney ANG II levels.
Summary of Results: Dietary I3C resulted in pronounced increases in SBP (130±5 to 171±9 mmHg, P<0.05), PRA (64±6 vs. 5±1 ng ANG I/ml/hr, P<0.001), plasma ANG II levels (186±26 vs. 139±10 fmol/ml, P<0.05), and augmented total kidney ANG II content (550±31 vs. 253±24 fmol/g, P<0.001). Chronic imatinib administration did not prevent the development of hypertension (187±10 vs. 141±2 mmHg, P<0.001) or the increase in PRA (72±6 vs. 5±1 ng ANG I/ml/hr, P<0.001), but prevented the I3C-induced augmentation of intrarenal ANG II levels (285±128 vs. 253±24 fmol/g).
Conclusions: The present findings demonstrate that PDGF receptor antagonism prevents the marked increase in intrarenal ANG II levels independent of changes in blood pressure that occur in ANG II-dependent malignant hypertension. The data also indicate that chronic elevations of intrarenal ANG II levels are not required for the maintenance of the elevated arterial blood pressure in ANG II-dependent malignant hypertension.
573 DIDS INHIBITS AMMONIA TRANSPORT BY RH GLYCOPROTEINS
Caner T1, Abdulnour-Nakhoul S1,2, Brown K1,2, Hamm LL1,2, Nakhoul N1,2. 1 Tulane Medical School, New Orleans, LA and 2 Southeast Louisiana VA System, New Orleans, LA.
Purpose of Study: Acid–base disturbances have serious clinical consequences and are particularly critical in patients whose cardiopulmonary function is compromised. In the kidney, production and excretion of NH3/NH4+ is critical for net acid excretion and the regulation of acid–base balance. Recently, two non-erythroid Rh glycoproteins (Rhbg & Rhcg) were suggested to be involved in NH3/NH4+ transport. In our previous studies, we demonstrated that Rhbg transported both NH4+ and NH3. As such, the Rh transporters are unique in being able to transport both the ionic and the neutral gaseous components of ammonia. Previous studies have shown that DIDS, a known inhibitor of anion exchangers, was shown to inhibit CO2 transport by AQP1. This led us to hypothesize that DIDS might also inhibit transport of other gases such as NH3 by Rh proteins. We therefore conducted the present study to test this hypothesis.
Methods Used: We used ion-selective microelectrodes and two-electrode voltage clamp to measure changes in surface pH (pHs) and whole cell currents (I) induced by NH3/NH4+. All experiments were conducted on Xenopus oocytes expressing Rhbg. Control oocytes were injected with H2O.
Summary of Results: Our results indicate that in oocytes expressing Rhbg, exposure to 5mM NH4Cl (NH3/NH4+) caused a decrease in pHs by 0.85±0.12 and a ΔI of -58±10nA. The decrease in pHs is caused by NH3 influx whereas the inward current is due to electrogenic NH4+ influx. In the presence of DIDS, exposure to NH4Cl caused a significantly smaller decrease in pHs (0.57±0.07) and ΔI (-29±5nA). The %inhibition of pHs and ΔI were 33% & 49%, respectively (P<0.05). Similarly, exposing oocytes expressing Rhbg to 5mM MA/MA+ (a substitute to NH3/NH4+) caused a decrease in pHs of 0.27±0.04 and a ΔI of -29±6nA. In the presence of DIDS, the MA/MA+ induced changes in pHs (0.17±0.03) and ΔI (-11±2nA) were also inhibited (37% & 63%, P<0.05). DIDS had no effect on NH3/NH4+ transport in H2O-injected oocytes.
Conclusions: Our data indicate that 1)DIDS partially inhibits the transport of NH3 and MA by Rhbg without affecting endogenous NH3 and MA transport. 2)DIDS also inhibits the electrogenic transport of NH4+ and MA+ by Rhbg. 3)DIDS is the only inhibitor shown to block both gas (NH3) & ionic (NH4+) transport by Rhbg.
574 ENDOTHERIAL CELLS CONTRIBUTE TO ANGIOTENSINOGEN AUGMENTATION IN VASCULAR SMOOTH MUSCLE CELLS OF AFFERENT ARTERIOLES
Miyata K, Sato R, Navar L. Tulane University, New Orleans, LA.
Purpose of Study: Increases in renal vascular resistance play an important role in the pathogenesis of hypertension. The resistance of the afferent arterioles determine blood flow and glomerular filtration rate in the kidney. Angiotensin II (Ang II), a major endogenous vasoconstrictor, increases in some models of hypertension and contributes to impaired renal hemodynamics. We previously demonstrated that Ang II augments angiotensinogen (AGT) expression in primary cultures of preglomerular vascular smooth muscle cells (VSMCs). However, it is unclear if preglomerular endothelial cells (ECs) are involved in the augmentation of AGT in renal afferent arterioles. Therefore, this study was performed to assess the hypothesis that the ECs respond to Ang II and contribute to AGT augmentation in VSMCs in afferent arterioles.
Methods Used: We made primary cultures of preglomerular VSMCs, ECs and jaxtaglomerular cells (JGCs) isolated from afferent arterioles of Sprague–Dawley rats. The cells were identified as ECs by being positive for a marker, CD34 and endothelial NOS and negative for alpha-SMA (a marker for VSMCs) and P4H-b (a marker for Fibroblasts) by immnostaining.
Summary of Results: Ang II (100 pmol/L) suppressed renin mRNA and increased (pro) renin receptor mRNA expression with no change in AGT mRNA expression in JGCs. Interestingly, the same dose of Ang II increased the expression levels of AGT mRNA and renin mRNA in preglomerular ECs; AGT mRNA levels (1.34 +/- 0.16, N=4) and renin mRNA levels (6.16 +/- 0.96, N=4). Culture medium from ECs without Ang II treatment increased AGT mRNA expression (1.62 +/- 0.13, N=4) in preglomerular VSMCs. AGT mRNA expression was further augmented when preglomerular VSMCs were treated with culture medium of Ang II-treated preglomerular ECs (2.39 +/- 0.41, N=4). The synergistic effects of Ang II and preglomerular ECs were also observed in PAI-1, MCP-1 and TGF-β expression in preglomerular VSMCs.
Conclusions: These data demonstrate that preglomerular ECs contribute to Ang II-induced upregulation of AGT in renal afferent arterioles leading to further Ang II augmentation.
575 LACK OF THE PRORENIN RECEPTOR (PRR) IN THE URETERIC BUD (UB) DISRUPTS DEVELOPMENTAL PROGRAMMING OF NEPHROGENESIS
Riedl L, Song R, Yospiv I. Tulane University, New Orleans, LA.
Purpose of Study: Severe reductions in nephron number that are characteristic of renal hypodysplasia (RHD) are the leading cause of childhood end-stage kidney disease. Mice that lack the PRR in the UB lineage (PRRUB-/-) exhibit reduced UB branching, resulting in decreased nephron endowment and RHD (Song. PLoS ONE, 2013). In this study, we tested the hypothesis that decreased nephron endowment in PRRUB-/- mice is due to defects in molecular pathways and cellular mechanisms that control nephrogenesis.
Methods Used: PRRUB-/- (n=3) and control (n=3) mice were studied. Mesenchymal cell proliferation and apoptosis was assessed on kidney sections (3 sections/kidney) using anti-phosphohistone H3 (pH3) and -cleaved caspase 3 (Ca3) antibodies on embryonic (E) days E12.5 and E18.5. Data were normalized to the total number of DAPI-positive cells (Image J). Expression of key genes that control nephrogenesis was studied by real-time qRT-PCR on E12.5. The intensity of Six2 immunostaining (Abcam, 1:200), normalized for the surface area of the kidney section, was quantitated by Slidebook 4.1 software.
Summary of Results: The number of Ca3-positive apoptotic cells was higher (E12.5:20.7±2.5 vs.4.0±1.4 p<0.001; E18.5:10.4±3.8 vs. 2.5±1.2, p<0.05) whereas the number of pH3-positive cells did not differ on E12.5 (56.7±6.8 vs. 61.250±9.674,p=0.5) and was reduced on E18.5(18.9±2.7 vs. 38.7±3.4,p<0.001) in the mesenchyme of mutant compared with control kidneys. qRT-PCR demonstrated decreased Pax2(0.64±0.04vs.1,p<0.005), Pax8(0.73±0.01vs.1,p<0.001), FGF8(0.68±0.15vs.1,p<0.05), Lhx1(0.76±0.07vs.1,p<0.05) and Wnt4(0.43±0.2242vs.1,p<0.005), and increased Six2(5.5±0.44vs. 1, p<0.005), Bmp7 (1.44±0.1vs.1,p<0.001), Cited1(1.5±0.23vs.1,p<0.05), β-catenin(1.7±0.03vs.1,p<0.001), and Wnt9b(13.4±1.1vs.1,p<0.001) mRNA levels in mutant compared to control kidneys. Six2 immunostaining was increased in the mutant vs. control kidneys(2664000±309400vs.1030000±145200 pixels,p<0.05).
Conclusions: We conclude that lack of the UB PRR disrupts nephrogenesis via: 1) Induction of mesenchymal cell apoptosis, 2) Inhibition of mesenchymal cell survival and 3) Aberrant expression of key genes that direct nephrogenesis. These findings are consistent with the concept that branching UB provides survival and proliferation signals to the cap mesenchyme, which ultimately gives rise to nephrons.
576 PROXIMAL TUBULE TRANSPORT SYSTEMS FOR CITRATE: CELL CULTURE HETEROGENEITY
Zhang S1, Coleman-Barnett JA1,3, Sato R2, Hamm LL1,3,2, Hering-Smith K1,2,3. 1 Tulane University School of Medicine, New Orleans, LA; 2 Tulane University School of Medicine, New Orleans, LA and 3 SLVHCS, New Orleans, LA.
Purpose of Study: Purpose: Citrate is an important inhibitor of calcium nephrolithiasis and its urinary excretion has been thought to be controlled by NaDC1 on the apical membrane of the proximal tubule. However, we have recently identified a novel citrate transport system and also have found citrate transport in proximal tubule cells grown from NaDC1 knockout mice.
To further characterize the identity and nature of other citrate transport processes we utilized established cell lines from S1, S2 and S3 segments of the proximal tubule and the mouse proximal tubule cell line BUMPT-306.
Methods Used: The present studies address the gene expression profiles in these cells. RNA was isolated from S1, S2, S3 and BUMPT-306 cell lines, and cDNA was then synthesized. Real-time RT-PCR was utilized to quantify the expression of a variety of transporter genes.
Summary of Results: NaDC1 exhibited expression in BUMPT > S1 >> S2, S3 (P < 0.05); in contrast, the presumed basolateral transporter NaDC3 exhibited expression in S3 > S1 > BUMPT, S2 (P < 0.05). Other transporters that may be involved in citrate transport or its regulation (PAT1, DRA, mINDY) exhibited different patterns of expression that diverged from either NaDC1 or NaDC3.
Other transport gene products were studied for comparison and confirmation of origin of the cell lines: SLC5A2 (SGLT2) expression was higher in S1, BUMPT > S2 > S3 (P < 0.05); while GGT expression levels in S3 >>> BUMPT, S1, S2 (P < 0.05). These patterns correspond to known patterns of expression in S1, S2, and S3.
Conclusions: In conclusion the expression patterns of transporters in cultured proximal tubule cells correspond with some of the known physiological properties of these nephron segments in vivo. However, the correspondence between the in vivo physiology and cultured cell lines needs to be carefully characterized further.
577 CHANGES IN GENE EXPRESSION PROFILES IN CHRONIC KIDNEY DISEASE PATIENTS TREATED WITH TETRAHYDROBIOPTERIN VERSUS PLACEBO: A RANDOMIZED CONTROLLED TRIAL
Deveaux DD1, Gibson G3, Quyyumi A2, Jefferson M1, Park J1. 1 Emory University School of Medicine, Atlanta, GA; 2 Emory University, Atlanta, GA and 3 Georgia Tech, Atlanta, GA.
Purpose of Study: Chronic kidney disease (CKD) patients are at significantly higher risk of cardiovascular mortality. One major contributor of increased risk is decreased nitric oxide (NO) bioavailability, which in turn leads to endothelial dysfunction and sympathetic nervous system (SNS) overactivity. Tetrahydrobiopterin (BH4) is a cofactor for endothelial NO synthase activity that improves NO bioavailability in animal models of CKD; however, BH4 treatment has never before been tested in humans with CKD. The purpose of this study was to test the hypothesis that chronic BH4 treatment alters the RNA activity of genes involved in the regulation of NO and SNS activity in hypertensive patients with CKD.
Methods Used: We conducted a randomized, double-masked, placebo-controlled trial in 30 hypertensive patients with CKD Stage III, randomized to 12 weeks of: a) BH4 200 mg twice daily + folic acid 1 mg daily; versus b) identical placebo pills twice daily + folic acid 1 mg daily. Physiologic measures obtained before and after treatment included: endothelial function via brachial artery flow-mediated dilatation, SNS activity via microneurography, oxidative stress biomarkers, 24-hour ambulatory blood pressure, and RNA profiling. Specifically for this study, total RNA will be extracted from tempus tubes, and gene expression profiling will be performed on the 60 samples using the Illumina HT12 BeadChip technology at the Emory Integrative Genomics Core laboratory.
Summary of Results: We hypothesize that 12 weeks of BH4 treatment will change gene expression profiles in hypertensive patients with CKD. The current protocol using microarray technology allows for the survey of thousands of genes in a single experiment. The parent trial will be unmasked in October 2013, and thereafter, high level computational analysis on RNA data will be performed in collaboration with the Georgia Tech Integrative Genomics Center.
Conclusions: We predict that BH4 treatment in hypertensive CKD patients may improve physiologic measures, and alter total gene expression profiles. We anticipate that expression of candidate genes involved in NO and SNS regulation may be altered with time in patients treated with BH4.
578 CHANGES IN FGF-23 LEVELS MAY DETERMINE OPTIMAL 25-HYDROXYVITAMIN D LEVELS IN VITAMIN D DEFICIENT SUBJECTS WITH NORMAL RENAL FUNCTION
Alshayeb HM1, Showkat A2, Gyamlani G3,2, Quarles L2, Wall BM2,3. 1 Marshall University, Huntington, WV; 2 UTHSC, Memphis, TN and 3 VAMC, Memphis, TN.
Purpose of Study: Both vitamin D deficiency and supra-therapeutic 25(OH)D have been associated with increased mortality and morbidity, and there is lack of consensus on the optimal 25(OH)D concentration. The current study was designed to determine if changes in anabolic and catabolic vitamin D metabolites and counter -regulatory hormones (FGF-23 and PTH) occurring during treatment of vitamin D deficiency could be used to better define the optimal 25(OH)D concentration.
Methods Used: Subjects with 25(OH)D level < 20 ng/ml and normal GFR (n=25) had measurement of serum FGF-23, 25(OH)D, 1,25(OH) D2, PTH, calcium, phosphorus, and creatinine at baseline and after 8 weeks of 10,000 IU weekly cholecalciferol supplementation. 24,25(OH)D2 levels were measured in a subset of patients (n=13).
Summary of Results: Cholecalciferol treatment resulted in significant increments in serum 25 (OH)D (12 ± 4.1 to 31.1 ± 8.4 ng/ml, P <0.0001), serum 1,25(OH)D2 level (42.2 ± 22.7 to 59.0 ± 26.2 pg/ml, P<0.007) and serum 24,25(OH)D2 level (from 1.19 ± 1 to 2.33 ± 0.60 ng/ml, P<0.002) with no significant change in serum calcium or phosphorus concentrations. The increment in 25(OH)D levels to a range of 23-39.5 ng/mL (mean of 31.1 ± 8.4 ng/ml) was associated with a significant increase in FGF23 levels (74.9 ± 32.3 to 119.9 ± 37.7 ng/ml, P<0.0001) and a significant decrease in PTH (54.8 ± 24.1 to 43.8 ± 27.3 pg/ml, P <0.03). Higher FGF23 levels were associated with higher 25(OH)D concentrations (r = 0.38, p< 0.01) and higher PTH levels were associated with lower 25(OH)D concentrations (r = -0.31, p< 0.03).
Conclusions: Correction of vitamin D deficiency with a moderate dosage of cholecalciferol resulted in increased production of both anabolic and catabolic vitamin D metabolites, 1,25(OH)D2 and 24,25(OH)D2, respectively. Activation of Cyp24 A1 by increased FGF23 and decreased PTH may be protective against vitamin D intoxication and suggests that targeting 25(OH)D levels greater than the current recommended level of 30 ng/dl may have potential adverse long term effects related to chronically higher FGF23 concentrations.
579 BARRIERS TO TIMELY DIALYSIS ACCESS CREATION: A SOUTH TEXAS UNIVERSITY HEALTH SYSTEM EXPERIENCE
Aderinto O, Khan F, Mehanni C, Hirachan P, Gelfond J, Bansal S. University of Texas Health Science Center San Antonio, San Antonio, TX.
Purpose of Study: An arteriovenous fistula (AVF), graft (AVG) and peritoneal dialysis catheter are the recommended accesses to start dialysis therapy, however, about 80% patients in the US start dialysis using a catheter. We assessed the rate of suboptimal dialysis start (defined as initiation of dialysis with a catheter) with the aim to identify barriers to timely access creation at the University Health System in San Antonio.
Methods Used: Charts of consecutive incident dialysis patients were reviewed from January 2010 to December 2012. A total of 154 patients were identified.
Summary of Results: Mean age ± SD of study population was 52.4 ± 13 years, 47% were males and 82% were Hispanics. End stage renal disease was attributed to diabetic nephropathy in 75% of patients. Suboptimal starts occurred in 80% of the patients (19% had an immature AVF or AVG at the time of initiation). Patient's demographics, medical history and lab parameters were not different between the suboptimal and optimal start groups. Ninety-two percent of patients in the optimal group were seen by a nephrologist for >6 months compared to 66% patients in the suboptimal group (p=0.003). Physician and nurse pre-dialysis education was noted for 86% and 84% patients, respectively in optimal starts versus 33% and 28%, respectively in the suboptimal starts (p<0.001). Among the suboptimal starts, lack of regular health care prior to initiation (40%) and patient related delays (36%) were major barriers to timely access creation. Wait times (median [IQR] in days) to nephrology consult (90[48, 169]), vascular mapping (23[12, 49]), surgery consult (41[27, 62]) and access creation (44[23, 106]) were same between the two groups. On multivariate regression analysis, care by a nephrologist for > 6 months was the only predictor for an optimal start (OR=13, 95% CI 2.3-72).
Conclusions: Initiation of dialysis with suboptimal access is common in our system. Lack of regular health care prior to initiation and patient related delays were the major barriers to timely access creation, which are partly modifiable. This study provides the opportunity to test methods to prevent suboptimal starts.
580 PORT CATHETER PLACEMENT:SUCCESS AND COMPLICATIONS UNDER INTERVENTIONAL NEPHROLOGY
Patil S, Masri K, Sachdeva B. LSU-HSC Shreveport, Shreveport, LA.
Purpose of Study: Vascular access centers continue to expand scope of practice with addition of non-dialysis related procedures. Port-a-catheter (PC), a tunneled central venous catheter with subcutaneous port, bears several similarities to the tunneled dialysis catheter.
Methods Used: We retrospectively reviewed 523 PC placed by interventional nephrologists (IN) in an outpatient hospital academic interventional nephrology program between Jan 2001 to Dec 2011, using the prospective electronic database. Complete data was available in 521 procedures that were included in analysis. Technical success, intra-procedural, early (<2days) and late (3-15 days) complications were recorded from a chart review of each case performed.
Summary of Results: All PC placements were done by IN staff with or without a fellow, using fluoroscopy/Ultrasound guidance under procedure sedation analgesia (PSA). Demographics and clinical characteristics of the patients included are listed in table 1.
Technical success rate was 100% with 81.38% placed in the right internal jugular (IJ) and 17.66% in the left IJ. Complications are noted in table 2. 11 catheters were removed during the first 21 days post placement, 9 because of infection, one for catheter migration, one for thrombosis. 18 (0.038%) complications were seen in 467(89.4%) of cases performed with fellow as assistant compared to 4 (0.08%) in 50(9.6%) cases performed by staff independently (p value >0.05). There was no statistical difference in complications whether catheter was placed on left versus right IJ (p Value >0.05).
Conclusions: Interventional nephrologists with adequate training in placement of central venous- tunneled cuff catheters can successfully place port catheters with excellent success and minimal complication rate.
581 LONG-TERM METABOLIC CONTROL AFTER TARGETED SURGICAL PARATHYROIDECTOMY IN END-STAGE RENAL DISEASE PATIENTS
Farah Musa AR1, Clarke D1, Gharaibeh K1, Tapolyai M2, Csongrádi3, Pitman K4, Fülöp T1. 1 School of Medicine, University of Mississippi, Jackson, MS; 2 University of South Carolina, Columbia, SC; 3 Banner MD Anderson Cancer Center, Gilbert, AZ and 4 University of Debrecen, Debrecen, Hungary.
Purpose of Study: The long-term results of surgical parathyroidectomy (PTX) in end-stage renal disease patients are less well known in the modern era of newer vitamin-D analogs, calcimimetics and intra-operative monitoring of parathyroid hormone (PTH).
Methods Used: We performed a retrospective chart review of all ESRD patients undergoing PTX with one dedicated parathyroid surgeon (KTP) during index period of 08/2006 - 08/2011, with follow-up data up till 3 years. All PTX were performed by a single surgeon with intra-operative PTH monitoring and targeted gland size reduction.
Summary of Results: The cohort (N=37) was relatively young with a mean age 48.4 ±13.9 years, 94.6% African-American and 59.5% females. Preoperatively, 51.4% received cinacalcet (CNC) at a mean dose 63.5 (20.9) mg. Largest gland size removed measured 1.7 (0.8) cm and almost all (94.6%) had hyperplasia on histology. Mean length of inpatient stay was 5.5 ±2.4 days. Preoperative calcium/phosphorus measured 9.6 ±1.2/6.6 ±1.7 mg/dL with PTH of 1,589.1 ±827 pg/mL. Stabilized PTH values (4-8 days after PTX) measured 145.4 ±119.2 pg/mL. Pre-operative PTH strongly correlated (p<0.0001) with both Alkaline Phosphatase (ALP) (r 0.587) and length of inpatient days (r 0.545), but not with CNC administration. Long-term follow-up results were available for close to half of the cohort and shown in Table 1. At 24 months, 5 of the 21 subjects received CNC (23.8%). No clinical fractures were observed.
Conclusions: Gland sparing PTX improved PTH control with marked reduction of subsequent CNC utilization. While hyperphosphatemia may be a persisting problem in these patients, ALP and calcium levels remained normalized up to 3 years.
582 RETROSPECTIVE ANALYSIS OF PATIENTS WITH RENAL INVOLVEMENT IN MULTIPLE MYELOMA
Johnson SS1, Khan A1, Simon EE1,2, Safah H3, Batuman V1,2. 1 Tulane University, School of Medicine, New Orleans, LA; 2 Southeast Louisiana Veterans Health Care System, New Orleans, LA and 3 Tulane University, School of Medicine, New Orleans, LA.
Purpose of Study: In this study, we evaluated the clinical spectrum of patients with renal involvement in our multiple myeloma program.
Methods Used: A retrospective chart review was conducted at the Tulane University Cancer Center in New Orleans, Louisiana. Patients older than 18 years both male and female were included. Data on demographics, renal function, type of myeloma, treatment regimens and outcomes were recorded. The primary objective was to assess the effect of chemotherapy on renal function recovery and survival.
Summary of Results: Thirty one patients were included in the analysis. Age range was 27-76 years (average 58 years), 58% male and 42% female. Fifty-eight percent of patients received a combined therapy including thalidomide or revlimid (TR group) and 35% received a regimen including velcade (V group). Forty-five percent had IgG-κ type myeloma followed by IgG-λ and IgA-κ (16% each) myeloma. After six months of follow up, there was a notable improvement in eGFR in both TR and V groups compared to their level at presentation. There was a significant decrease in total protein at follow up in TR group. In IgG-κ and IgA-κ groups, serum creatinine was reduced and eGFR was improved; although not statistically significant at follow up, there was no notable improvement in the IgG-λ group. Total protein in IgG-κ group and calcium level in IgG-λ group were significantly decreased at follow up. No patient required dialysis.
Conclusions: (1) Both therapeutic groups (TR and V) showed improvement in renal function and TR group was more effective to reduce total protein. (2) IgG-κ is the more common type of myeloma in patients with kidney involvement. (3) Renal outcomes were generally good in patients treated with these newer regimens.
Southern Society of General Internal Medicine
Research Abstract Session A
8:30 AM
Friday, February 21, 2014
583 USING A POSITIVE APPROACH TO IMPROVE PATIENT SATISFACTION IN PRIMARY CARE
Fenner B, Jackson N, Capel BJ, Rose S, Rudy D. University of Kentucky, Lexington, KY.
Purpose of Study: Optimizing patient satisfaction is an important goal in healthcare today. Patient satisfaction is measured in several domains and results are utilized to develop strategies for improvement. These commonly involve quality improvement methods where deficits are identified and interventions for correction are initiated. Another method is to discover positive aspects of patient satisfaction and build upon these strengths. To this end we used Appreciative Inquiry to identify positive aspects of patient care in our university-based internal medicine primary care clinic.
Methods Used: We conducted appreciative interviews of 50 patients or their family members in our clinic. Subjects were asked to tell a story of a time in their clinic experience that stood out for them when they received, saw, or were part of excellent patient care, who were the individuals involved, what were the positive characteristics of those individuals, and the aspects of the clinic that contributed to this experience Responses were recorded on a response form. The texts were analyzed for thematic categories independently through qualitative methods by three reviewers. Discrepancies were resolved via consensus.
Summary of Results: The predominant themes were: personal attention given by the staff, superior bedside manner, efficient care, patient-staff relationship, consistency in care, and educational environment. Personal attention and bedside manner were overwhelmingly the most common responses, with approximately 60% of patients citing each of these aspects and every patient mentioning at least one of these two themes.
Conclusions: Patient responses parallel domains commonly utilized to measure patient satisfaction. Improvements in patient satisfaction me be frame in a positive light such as in the present study or deficits in patient satisfaction may be presented in a “blame and shame” fashion. We believe that presenting providers, staff, and administration with what patients value in their interactions with the health care system and asking for mechanisms to propagate these positive aspects may be an effective means of increasing patient satisfaction. We plan to present our data to all involved in the clinic and seek their input on how to accentuate these positive aspects. Patient satisfaction data will be followed longitudinally.
584 PROMOTING POSITIVE CHANGE IN THE RESIDENCY EXPERIENCE THOUGH DISCOVERY OF RESIDENT VALUES
Jackson N, Fenner B, Capel BJ, Rose S, Rudy D. University of Kentucky, Lexington, KY.
Purpose of Study: Residency is a trying experience. This study aims to find constructive means of improving of our Internal Medicine Residency program. Previous attempts to improve our residency program focused on eliminating negative aspects. This study utilized Appreciative Inquiry to identify positive aspects of the current program with the aim to expand upon those ideas and incorporate new suggestions.
Methods Used: We conducted appreciative interviews on 27 current Internal Medicine residents. Subjects were asked to answer a series of questions while reflecting on their time as a resident. The questions focused on points such as what he/she expected upon beginning residency, what was his/her high point in residency, what fosters a collaborative and engaged work environment and what actions can be taken to achieve a more engaged staff. The answers were analyzed for thematic categories independently through qualitative methods by three reviewers. Discrepancies were resolved via consensus.
Summary of Results: Residents initially sought to improve their medical knowledge, work towards autonomy and gain experience. However, as residents continued in their training they valued the support and respect of their superiors and peers while working as part of a collaborative unit. Residents shifted their focus from academic improvement to fostering better patient relationships and seeing results of the care they provided. When asked what they would do to improve the program, many responded with improving team dedication and communication as well as a more open academic environment.
Conclusions: While very important, knowledge acquisition may not be what residents' value most in their training. In fact, it was discovered that residents desired to improve their ability to work as part of a medical team, in both leadership and subordinate roles. Residents feel the program is most effective when support, communication and respect as part of a collaborative environment are held at highest regard. Helping resident accomplish these positive aspirations may help make residency a positive experience.
585 PRIORITIZING DOMAINS OF CLINICAL REASONING TO INCLUDE IN A CURRICULUM
Musgrove JL, Estrada C, Morris J, Kraemer R. Birmingham VAMC, Birmingham, AL.
Purpose of Study: The field of cognitive psychology has informed our understanding of how physicians think and make decisions. However, little is known about prioritizing clinical reasoning concepts for teaching. We aim to prioritize commonly described clinical reasoning concepts to facilitate the teaching of clinical problem solving skills.
Methods Used: Consensus development. First, two authors compiled an extensive list of clinical reasoning concepts from seminal narrative reviews. Second, seven clinical educators reviewed the list for additions and voted items for inclusion; items with <5 votes were excluded. Third, eight clinical educators ranked the remaining items (most important concept first, least important concept last) using a card-sort method. This technique represents a robust means of measuring opinion enhanced by a visual-motor cognitive dimension. For analysis we used the rank-order centroid method for assigning weights based on ordinal preference (order in card sort). The main outcome was the sum of weights assigned to each clinical reasoning concept by each clinical educator.
Summary of Results: Of 49 clinical reasoning concepts identified, 24 received <5 votes and five were deemed synonyms. The remaining 20 clinical reasoning concepts and the percent of total weight assigned to each concept are shown in the Table. The top four concepts were problem representation, diagnosis, dual-process thinking, and illness scripts.
Conclusions: Through a systematic consensus development, we prioritized a list of commonly described clinical reasoning concepts for teaching clinical problem solving skills.
586 UTILIZING ITERATIVE CASE PRESENTATION TO DEMONSTRATE CONCEPTS OF CLINICAL REASONING
Musgrove JL, Kraemer R, Estrada C, Morris J. UAB Division of General Internal Medicine, Birmingham, AL.
Purpose of Study: Clinical problem solving (CPS) exercises have emerged as a means of exploring the nuances of clinical reasoning. In this format, a case is iteratively presented with interposed commentary from an expert clinician. We aim to characterize the clinical reasoning concepts of published CPS exercises as an initial step towards incorporating such exercises into clinical reasoning curricula.
Methods Used: Literature review and text analysis in three steps: 1) Identified CPS exercises (table of contents review, 4 journals; Jan 2010 - May 2013). 2) Compiled a list of clinical reasoning concepts from seminal narrative reviews (seven educators voted from a list of 49 concepts; items with <5 votes were excluded). 3) Utilized a regular expression search engine to identify specific mentions of clinical reasoning concepts (including synonyms) in each CPS exercise via automated, batched searches. Search engine compatible text files created using a custom JavaScript function in Acrobat® X. Superfluous text (titles and references) was redacted with regular expression text editing software. Electronic search results concordant with word-by-word article reviews. The primary outcome was the presence of each clinical reasoning concept in each article. Differences between journals were examined with the Chi-square test.
Summary of Results: We identified 79 CPS exercises: 41 (52%) in the N Engl J Med, 22 (28%) J Hosp Med, 11 (14%) J Gen Int Med, and 5 (6%) Am J Med Sci.
Six concepts were mentioned in >10% of the articles: diagnosis 79 (100%), context 20 (25.3%), bias 13 (16.5%), illness script 11 (13.9%), problem representation 10 (12.7%), hypothesis 9 (11.4%). Concepts mentioned in ⩽ 5% of the articles were cognitive error, framing, dual process, flexibility, metacognition, system error, overconfidence, and naturalistic decision making. Differences between journals observed on all but five concepts (all p ⩽ 0.005, not shown).
Conclusions: CPS exercises represent an accessible learning tool capable of detailing expert clinical reasoning while simultaneously addressing the nuances of core clinical reasoning concepts. This study helps to characterize relevant clinical reasoning concepts which have been discussed in CPS exercises.
587 UNDERSTANDING CHANGE: FINANCIAL MODELING IN A COMMUNITY CLINIC
Guitard J, Chakraborti C. Tulane, New Orleans, LA.
Purpose of Study: To devise a basic financial model that predicts the profitability of pending organizational changes, the addition of Group Medical Visits to a standard outpatient clinic.
Methods Used: We used a break-even analysis to model moving diabetic patients from traditional 1:1 office visits into monthly group visits. Prototype group visits were defined by hypothesizing shifting of resources, such as moving certain staff from full-time to part-time, required to move from 1:1 visits to group visits were included in anticipated costs. Reimbursement rates for shared medical visits (CPT Code 99213) at FQHCs as of February 2013 were used. Future projections of costs and revenues were modeled with variable operational requirements using a break-even profitability analysis. Results of this analysis according to hypothesized changes in variables were reported as clinic profit calculated on a quarterly basis. Break-even point was defined as the number of group visit patients required to achieve a $0 profit. Clinic variables were then isolated, adjusted, and plotted to determine their relative degree of effect on the break-even point.
Summary of Results: Out of a total of 800 diabetic patients, the model identified that moving 341.6 patients (42.7%) into group visits would result in the break-even point, translating to 3.3 group visits/week with a total of 26.3 unique patients/week. For comparison, if all 800 diabetic patients were moved to group visits, 7.7 group visits/week would be required achieving a maximum profit of $33,546/quarter. The analysis also revealed that shifting payers from uninsured to Medicaid showed a roughly linear decrease in the break-even number, i.e., fewer patients would be required for the clinic to break-even.
Conclusions: Given existing clinic assumptions, the financial model was able to determine that group visits can be profitable for the clinic when at least 341.6 diabetic patients are recruited. The model showed a decrease in the break-even number when patients shift from uninsured status to Medicaid. This suggests that the profitability of group medical visits for this clinic will increase once the Affordable Care Act is fully implemented, and prompted clinic manager to pursue group medical visits. Basic financial modeling tools provide information that may impact the decision-making process of community health clinics allowing for more informed operational decisions.
Southern Society of General Internal Medicine
Research Abstract Session B
10:30 AM
Friday, February 21, 2014
588 CHARACTERISTICS OF SUPERUTILIZING PATIENTS OFHOSPITALS SERVING GEOGRAPHIC HOTSPOTS FOR READMISSION
Harris LJ1, Podila P2, Waters T1, Wan J1, Bailey JE1. 1 University of Tennessee Health Science Center, Memphis, TN and 2 University of Memphis, Memphis, TN.
Purpose of Study: Previous research demonstrates patients with multiple chronic conditions (MCC) and high rates of inpatient utilization are at high risk for readmissions, emergency department (ED) utilization, and adverse outcomes. This study documents the characteristics and experience of superutilizing patients meeting eligibility criteria for the SafeMed Program, a care transitions program among high-risk patients with MCC.
Methods Used: This retrospective cohort study analyzed electronic health record data for all patients meeting eligibility criteria for the SafeMed Program seen in either of two hospitals serving geographic hotspots for readmission in Memphis, Tennessee, USA. Study patients met the following inclusion criteria: 1) an index hospitalization between January 1, 2010 - December 31, 2011 with >2 chronic health conditions (including hypertension, congestive heart failure [CHF], coronary artery disease, diabetes [DM], and chronic lung disease [CLD]), 2) high utilization defined as >2 prior hospitalizations OR > 1 prior hospitalization and >2 prior emergency visits in 6 months prior to index hospitalization in any hospital in a large regional healthcare system, and 3) Medicare and/or Medicaid insurance. Characteristics and healthcare utilization of eligible subjects were analyzed.
Summary of Results: Of 31,505 total hospital and ED encounters, 437 unique patients met full eligibility criteria. Mean age was 68 and 59% were female. Ethnicity was 54% African-American. Most were discharged home (83.5%), and 14% had a “Do Not Resuscitate” order placed during hospitalization. Mean Charlson Comorbidity Index score was 3.8. Patient utilization included an average 9 hospitalizations and 6.5 ED visits over the subsequent 12 months. The mean ED triage acuity score was high (98% had an average score of ≥3). Seventy-seven percent had a primary care provider, not including 10% listing a community health center as their provider.
Conclusions: High hospital-based healthcare utilization predicts a continuation of high healthcare utilization. The high severity of illness present upon arrival to the hospital underscores the importance of aggressive outpatient management of chronic illnesses to mitigate preventable exacerbations and unnecessary hospital and emergency care utilization.
589 INTEREST IN AND USE OF SMART PHONE TECHNOLOGY FOR DIABETES SELF-MANAGEMENT IN DIVERSE POPULATIONS
Humble J1, Debon M2, Krukowski R2, Womack C1,2, Bailey JE1,2. 1 University of Tennessee: Health Science Center, Memphis, TN and 2 University of Tennessee: Health Science Center, Memphis, TN.
Purpose of Study: This study seeks to assess patients' current cell phone usage and interest in diabetes self-management tools, and to determine whether usage and preferences vary by practice site.
Methods Used: A survey of patients in two practices was undertaken. Patients met inclusion criteria for participation: 1) Age > 18, 2) physician diagnosis of diabetes, 3) seen for an office visit during a one-week period during 2013. Patients unable to communicate their responses were excluded. Validated questions were drawn from BRFSS and NHIS; others were taken from De Reuver, et. Al. Frequencies were calculated for patients and two-sample t-tests, chi-square, and z-tests identified differences between practices using GraphPad QuickCalcs and Vassarstats online software tools with P<0.05 considered significant.
Summary of Results: During the study period 73 patients met the inclusion criteria. Sixty patients completed the survey for an 82% response rate. Patients from the 2 practices (P1 and P2) were similar in age 65 (range [r] 37-83) for P1 and 62 (r 28-87) for P2; mean years since diagnosis 14 vs. 13; on insulin 37.9% vs. 38.7%; college graduate 20.7% vs. 29% (P >0.05); and mean BMI 32.5 vs. 32.5. However, patient characteristics varied significantly as follows: female 79.3% vs. 53.3% (P<0.05); African-American 93.1% vs. 38.7% (P<0.05); computer ownership 51.7% vs. 83.9% (P<0.01); and internet usage 51.7% vs. 77.4% (P<0.05).
Interest in the in-person classes and interventions was higher than in the mobile health applications, and interest in text messages was highest of all. Fourty-four percent of respondents were extremely interested in on-site interventions, 36% in the mobile apps, and 57.6% in receiving text messages.
Conclusions: This study shows that, while the two populations in practices 1 and 2 were different demographically, both showed high interest in the use of support services for the self-management of diabetes with respondents on average rating their interest in each component between “somewhat” and very interested. Diabetes education using an app was rated highest overall for both groups. The interest in text messaging was higher than either in person services or mobile health.
590 ENDING HOMELESSNESS FOR 48,000 VETERANS: ORGANIZATIONAL AND CLINICAL CHALLENGES FOR VA MEDICAL CENTERS
Kertesz S1,2, Austin E1, Holmes S3, Van Deusen Lukas C3, Pollio D4, White B3, Schumacher J2. 1 Birmingham VA Medical Center, Birmingham, AL; 2 U Alabama Birmingham, Birmingham, AL; 3 Boston VAMC, Boston, MA and 4 U. Alabama, Tuscaloosa, AL.
Purpose of Study: The US Department of Veterans Affairs has vastly expanded permanent supportive housing in an effort to end Veteran homelessness, progressively embracing a Housing First approach (2012-2013). The approach embodies harm reduction, offering housing without precondition of treatment participation or success. It requires VA Medical Centers to advance a major social objective that extends far outside the medical center walls. This qualitative study describes clinical, organizational and contextual facilitators and challenges experienced by VA facilities advancing this effort in 2012.
Methods Used: A multidisciplinary team interviewed medical center leadership, mid-level managers, and front-line service providers at 8 VA facilities representing 4 US regions to develop a phenomenologic description of organizational and clinical factors affecting the initiative.
Summary of Results: Frontline staff accepted the goal of advancing housing without requiring treatment success. But they expressed skepticism regarding its success with risky clients, and described situations where a Harm Reduction principle of respect for client goals meant allowing them to remain homeless.
“The Secretary said Housing First, and that’s harm reduction. I would say that 5-7% of guys don’t want to live in housing..(they) want to live off the grid. There can be conflict between Housing First and harm reduction.”
Success facilitators included a forceful communication of goals by national leadership, clear performance metrics, and resource expansion. Challenges included: local geography and rental markets; coordination with Housing Authorities; move-in expenses and interim sheltering; and, a tension for staff between housing placement logistics versus offering clinical recovery support. Middle managers exerted outsized influence on program operations. These managers were reassigned or reconfigured in 5 of 8 sites we assessed.
Conclusions: VA’s path toward Housing First highlights the roles of declared goals, resource expansion, and performance metrics in advancing change. It also illustrates key clinical and organizational challenges relevant to other communities and agencies.
591 WHAT DOES INDUSTRY TELL US ABOUT TEST CHARACTERISTICS? THE RAPID ANTIGEN STREPTOCOCCUS TEST
Patel T1, Brown E2, Davis B3, Clemans-Taylor B1, Centor R1, Estrada C1. 1 University of Alabama at Birmingham, Birmingham, AL; 2 Walter Reed National Military Medical Center, Bethesda, MD and 3 UT Southwestern Medical Center, Dallas, TX.
Purpose of Study: In published studies, the sensitivity of the rapid antigen streptococcus test (RAST) to diagnose group A streptococcal (GAS) pharyngitis is ~90%. We examine the sensitivity and specificity of RAST using industry communications.
Methods Used: Systematic review of RAST package inserts. We obtained hierarchical summary receiver operating characteristic (HSROC) curve and calculated heterogeneity (Cochran-Q; inconsistency [I-square] of diagnostic odds ratio [DOR], sensitivity, and specificity). Heterogeneity is suggested by wide prediction regions of the HSROC curve, Cochran-Q p <0.05, or I-square >50%.
Summary of Results: Eight inserts did not provide data and were excluded. Twenty-eight inserts provided data for 33 groups (31 USA/ Canada, 2 Europe), describing 27 different tests. The overall prevalence of GAS was 31.7% (4,534/14,301 patients; 25th percentile [Q1], 24.8%; 75% percentile [Q3], 31.1%; range 13.7% to 86.3%). Twenty-four (72.7%) described immune-chromatographic and nine (27.3%) immunoassay methods.
The mean sensitivity of immune-chromatographic methods (96%; 95% Confidence Interval [CI], 95% - 96%) was higher than immunoassay methods (89%; 95% CI, 87% - 91%). The mean specificity for both methods was similar, immune-chromatographic (97%) and immunoassay (96%).
The sensitivity estimates of immuno-chromatographic methods were more homogeneous than immunoassay methods methods (smaller prediction region).
Conclusions: The sensitivity of immunochromatographic RAST methods reported in package inserts is greater than immunoassay methods or published literature. Clinicians are at risk of using information that may overestimate the sensitivity of the RAST.
Southern Society of General Internal Medicine
Research Abstract Session C
1:30 PM
Friday, February 21, 2014
592 IMPACT OF GEOGRAPHIC ROUNDING AND MULTI-DISCIPLINARY ROUNDS ON COORDINATION OF CARE AND DISCHARGE TIMES
Caton C1, Wise K1, Kyle R1, Curnell-Pean K2, Iverson P1. 1 Medical University of South Carolina, Charleston, SC and 2 Medical University of South Carolina, Charleston, SC.
Purpose of Study: To evaluate the effects of geographic rounding for hospitalists’ patients and multi-disciplinary rounds on coordination of care and discharge times at our academic medical center.
Methods Used: At our institution, we implemented geographic rounding for two non-teaching hospitalist teams (PHS) on a designated unit of the main hospital. We determined that 80% of all PHS patients should be located on this unit. We initiated multi-disciplinary rounds to include hospitalists, nurses, case managers, physical and occupational therapists with a goal of increasing patient discharges prior to 3pm. On a monthly basis, we tracked every aspect of the discharge process from the time orders were written to the time patients left the hospital. These discharge times were compared to those prior to project initiation. Physicians and nurses assigned to the designated unit completed a validated survey to assess their perceptions of care decisions before and 5 months after geographic rounding began.
Summary of Results: Initial and repeat survey response of physicians and nurses were similar - 98% and 93% respectively. Of respondents, 83% were female, 55% were nurses and the majority was between ages 29-46. 50% had community based practice experience. Matched analysis was performed on survey data finding improvements in 5 of 6 domains (p<0.05). Respondents agreed that there was better communication and coordination between physicians and nurses about patient care decisions and plans. The percentage of patient discharges prior to 3pm increased from 15% to 54%.
Conclusions: The initiation of geographic rounding and multi-disciplinary rounds increased communication and coordination of patient care between physicians and nurses. With the implementation of both initiatives, we increased the percentage of patients discharged prior to 3pm.
593 MULTIDISCIPLINARY APPROACH TO TREATING HYPERTENSION
Boyars M, Cave C, Davis K, Holdgate N, Richards N. MUSC, Charleston, SC.
Purpose of Study: Approximately 30% of the adult population, or 60 million people, have hypertension, and this is the most common reason non pregnant adults see physicians on an outpatient basis (1). Data from the 2005-2008 Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension show that only 46 to 51 percent of persons with hypertension have their blood pressure under control. (3). A multidisciplinary approach to the treatment of hypertension has been shown to be a more effective means of treatment (4). The purpose of this study is to assess whether co-management of hypertension by nursing, Pharm D, and clinic physicians with close 2 week follow could improve blood pressure control in difficult to treat patients.
Methods Used: Adult patients were enrolled based on UIM physicians identifying patients with difficult to control hypertension. Patients were notified of enrollment and scheduled for follow up in 2 weeks with Pharmacist and Physician. 45 UIM patients were identified and of those 43 were enrolled. In the pre enrollment period the patient was seen first by the physician and then by the Pharm D. During this visit the physician and Pharm D took an appropriate medical history, in which they confirmed medication compliance, took a detailed medication history and recorded the blood pressure. Interventions during this visit included dietary counseling (17), medication change (13), exercise counseling (10) and smoking cessation counseling (6). On return visit the blood pressure was recorded and counseling reinforced.
Summary of Results: Of the 43 enrolled patients, 27 (63%) patients kept their follow up visit with the physician and 24 (57%) kept their follow up visit with the Pharm D. Of the patients who returned for their follow up visit an average decrease in systolic blood pressure of 9.60 mm Hg compared to pre enrollment and an average decrease in diastolic blood pressure of 3.19 mm Hg compared to pre enrollment was recorded.
Conclusions: Reductions in blood pressure have been shown to improve morbidity and mortality related to cardiovascular disease and stroke. They have also been shown to reduce hospital admissions and ER visits. Co-management has been utilized in many areas of medicine to improve patient care and outcomes. Our results show that this approach is useful to the outpatient management of hypertension.
594 RELATIONSHIP BETWEEN OBESITY AND COMORBIDITIES AND WEIGHT LOSS MOTIVATION
Schuetz S, Masero C, Zephyr D, Real K, Webber K, Rose S. University of Kentucky, Lexington, KY.
Purpose of Study: Physicians perceive obese patients and those with obesity-related comorbidities as unmotivated and unable to lose weight, and cite these as obstacles to counsel patients regarding weight loss. Greater autonomous (internal), as opposed to controlled (external) motivation (AM vs. CM) is correlated with increased weight loss success. We evaluated the relationship between weight loss motivation and obesity severity and related comorbidities. We hypothesized that higher BMI and greater number of comorbidities (COM) would be associated with higher AM and lower CM to lose weight.
Methods Used: Patients and providers in a university-based internal medicine clinic were enrolled in a six-month lifestyle intervention aimed at improving patient outcomes and patient and provider self-efficacy in obesity. Baseline data included the Treatment Self-Regulation Questionnaire to assess motivation, height, weight, and obesity-related comorbidities (HTN, hyperlipidemia, DM, and CV disease). A one-way ANOVA was performed to assess the relationships between BMI and AM/CM and COM and AM/CM.
Summary of Results: 65 patients completed the survey (33 obesity class III (BMI≥40 kg/m2), 12 class II (BMI 35-39.9), 20 class I (BMI 30-34.9)). Mean AM was 5.53, (1 (low) to 7 (high)) (Class III=5.49, II=5.63, I=5.52) and mean CM was 2.20 (1 (low) to 7 (high)) (Class III=2.34, II=2.17, I= 2.15). AM and CM did not differ significantly across BMI categories (AM: F=0.06, p=0.94 and CM: F=0.21, p=0.81). 19 patients had 0-1, 17 had 2, and 28 had 3 or 4 COM related to obesity. Mean AM for 0-1 COM=5.39, 2 COM=6.02, 3-4 COM=5.34 and mean CM for 0-1 COM=2.23, 2 COM=2.34, 3-4 COM=2.09. Increasing number of COM did not have a significant association with AM or CM (AM: F=2.00, p=0.14; CM: F=0.30, p=0.74).
Conclusions: Neither increasing BMI nor increasing number of COM was correlated with increasing AM or decreasing CM. However, we found consistently high AM and consistently low CM among all BMI categories and all numbers of COM. Our findings suggest that all classes of obese patients with differing numbers of COM are consistently motivated to lose weight. Further work is needed to assess the link between increasing BMI and increasing number of COM and associated motivation. Physicians should address weight loss with all patients with all levels of obesity and its related comorbidities.
595 RISK PERCEPTION. SELF-EFFICACY, AND OBJECTIVE HEALTH RISK
Capel BJ, Kumar B, Jackson N, Fenner B, Masero C, Zephyr D, Rudy D, Real K, Rose S. University of Kentucky, Lexington, KY.
Purpose of Study: Risk perception and self-efficacy can predict success in health related changes. However, patients may not appropriately perceive their objective risk of disease. We aimed to evaluate the correlation between patient risk perception and self-efficacy and objective patient risk as defined by the Diabetes risk score developed by Bang et al. We hypothesized that higher levels of risk perception and self-efficacy would be associated with lower objective risk of disease.
Methods Used: Patients in a university-based internal medicine clinic completed a quantitative survey assessing risk perception (RP) of developing and self-efficacy (SE) of avoiding the development of diabetes (DM) using validated survey tools. We performed chart reviews to obtain laboratory, demographic, and anthropometric data to calculate each patient's diabetes risk score based on validated risk calculators.
Summary of Results: Patients (n=28) were 96.4% white, 35.7% male, mean age 54.52 years (SD 11.92), 18% were overweight (BMI 25-29.9 kg/m2), 39% were obese (BMI ≥30), and 3 patients (10%) had a diagnosis of DM. Of patients not already diagnosed with DM (n=25), mean SE for avoiding developing DM was 4.55 (SD 2.18) (range 1 low to 7 high), and mean RP of developing DM was 2.63 (SD 1.49) (range 1 low to 7 high). Mean objective health risk of developing DM was 3.33 (SD 1.98) (range 1 low to 6 high). There was a negative correlation between SE and objective risk (r=-0.507, p=0.005) and a negative correlation between RP and objective risk (r=-0.119, p=0.281).
Conclusions: We found a non-significant correlation between patient RP of developing DM and their actual risk; however, we observed a significant negative correlation between SE in stopping the development of the disease and a patient's objective risk. Although patient understanding of risk may promote an initial desire to improve one's health, self-efficacy or one's confidence in avoiding development of diabetes may play a more significant role in influencing a patient's actual risk of DM. Further goals include increasing sample size; assessing the correlation between RP, SE, and actual risk of developing heart disease and lung cancer; as well as developing tools to help physicians improve perceived risk and self-efficacy.
596 OPTIMISM, RISKS, AND PERCEPTIONS OF HEALTH FOR EVALUATION OF UNDERLYING SENTIMENT (ORPHEUS)
Kumar B, Capel BJ, Jackson N, Fenner B, Schuetz S, Zephyr D, Rudy D, Rose S. University of Kentucky, Lexington, KY.
Purpose of Study: Interest in the relationship between personality characteristics and health has increased substantially in recent years. One measure correlated with physical health is dispositional optimism, defined as the general expectation that good things will happen. However, the relationship between dispositional optimism and risk perception by patients remains largely unexamined. In this study, we aim to assess the correlation between objective disease risk and perception of disease risk in diabetes (DM). We hypothesize that increased levels of optimism are negatively correlated with perceptions of risk as well as with objectively measured risk.
Methods Used: Patients in a university-based internal medicine clinic completed a quantitative survey assessing their level of dispositional optimism via the Revised Life Orientation Test (LOT-R), and their risk perception (RP) of developing DM. We performed chart reviews to obtain laboratory, demographic, and anthropometric data to calculate each patient's diabetes risk score based on validated risk calculators.
Summary of Results: Patients (n=28) were 96.4% white, 35.7% male, mean age 54.52 years (SD 11.92), 18% were overweight (BMI 25-29.9 kg/m2), 39% were obese (BMI ≥30),and 3 patients (10%) had a diagnosis of DM. Mean LOT-R score was 16.2 (SD 5.67) (range 0 low to 24 high). Of patients not already diagnosed with DM (n=25), mean RP of developing DM was 2.63 (SD 1.49) (range 1 low to 7 high). Mean objective health risk of developing DM was 3.33 (SD 1.98) (range 1 low to 6 high). There was a positive correlation between RP of developing DM and optimism (r=0.077, p=0.354). There was a positive correlation between optimism and objective risk of developing diabetes (r=0.465, p=0.007).
Conclusions: There was no significant correlation between optimism and risk perception of developing DM. However, surprisingly, increasing optimism was significantly correlated with increasing objective risk of developing diabetes. Limitations to this analysis include small sample size. Future goals include increasing sample size and assessing the correlation between RP, optimism, and objective risk.
Southern Society of General Internal Medicine
Research Abstract Oral Plenary Session - Joint with Vignette Plenary
9:45 AM
Saturday, February 22, 2014
597 ARE PATIENTS A RELIABLE SOURCE OF ADVERSE EVENT REPORTING? SURVEY SAYS.
Minch M1, Deep K2. 1 Univ of Kentucky, Lexington, KY and 2 Univ of Kentucky, Lexington, KY.
Purpose of Study: Learning from adverse events is an important way to improve healthcare quality and safety. However events are underreported by healthcare providers. We sought to determine whether patient comments on the post-discharge Healthcare Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey reliably identify adverse events or errors that occur in the hospital stay.
Methods Used: HCAHPS surveys with negative comments returned during a 7 month period were reviewed. Comments that described a specific adverse event or error were then analyzed by two independent raters and the patient’s medical record reviewed to corroborate the event. A coding scheme was developed iteratively from the data and one comment could receive multiple codes. We assigned a harm score for each adverse event ranging from no harm to harm requiring additional treatment.
Summary of Results: Ninety comments were reviewed, 20 of which were adjudicated as complaints which did not identify quality issues, leaving 70 comments for analysis. Of these, 29 (41%) were corroborated in the medical record. An additional 35 (50%) were not corroborated by the medical record but were deemed credible based on the patient's report and when the described event was unlikely to be documented (i.e. delays in care). Communication errors were most common and found in 27 events such as a patient being taken for a procedure which they had refused. Other common types were inadequate patient education (13), delays in clinical care (13), and medication errors (8). Patient’s also identified procedural complications (3) and lapses in infection control (2).
Ten events (14.2%) resulted in significant patient harm and/or required additional treatment. An example is a failure to recognize an abscess resulting in emergent surgery. Three of these significant harm events were deemed credible but not documented in the medical record. An additional 10 described situations that were potentially harmful but the impact on the patient was unknown. The remainder of the adverse events or errors resulted in either emotional distress/inconvenience (30) or no harm (20).
Conclusions: Patient comments on the HCAHPS post-discharge survey are a reliable source for insight into the quality of care patients receive. They may also identify issues that are not captured by other safety reporting mechanisms.
598 NEIGHBORHOOD CHARACTERISTICS AND HOSPITAL READMISSION RATES: CONSIDERING NEW OPPORTUNITIES FOR INTERVENTION
Taylor BB1,2, Buys DR1, Richman J1, Cherrington A1,2. 1 UAB, Birmingham, AL and 2 School of Medicine, University of Alabama, Birmingham, AL.
Purpose of Study: Preventing hospital readmissions is a major focus of health care reform, quality measurement, and reimbursement reform. Many efforts focus on using patient level predictors for readmission to target these efforts, with mixed results. This project engages broader social determinants of health, geographically mapping highest rates of readmission and linking location to socio-economic characteristics.
Methods Used: We obtained index admission and 30 day readmission data for University of Alabama at Birmingham Hospital patients discharged with congestive heart failure (CHF), pneumonia (PNA), or acute myocardial infarction (AMI) from 2005-2012. Patients were limited to those discharged to their home in Jefferson County. We geocoded patients’ addresses at the index admission and linked demographic data from the Year 2000 Decennial United States Census to patient records using Geographic Information Systems (GIS) software. We used census variables for prevalence of poverty and prevalence of single mother households, to create the Neighborhood Disadvantage Index (NDI) and mapped readmission rates at the census-tract level with NDI tertiles.
Summary of Results: There were 3949 participants admitted at least once during the observation period. The match rate of addresses in GIS was 93-95% indicating good validity from administrative billing data and patient location. Among the 15 neighborhoods with the highest readmission rates, 8 (53%) are in the highly disadvantaged neighborhoods, 5 (33%) are in the middle NDI tertile and only 2 (17%) are in the lowest NDI tertile. This trend holds across groups of rehospitalization rates and NDI tertiles.
Conclusions: This project demonstrates the feasibility of linking administrative and census data and mapping health services outcomes. We find evidence of an association between neighborhood characteristics and rates of readmission. Future work will examine if neighborhood factors affect individual risk of readmission. This body of work may support the need to develop neighborhood interventions to improve population health and possibly decrease hospital readmissions.
599 PATIENTS UNDERGOING CHRONIC DIALYSIS HAVE A HIGH RISK OF PROSTHETIC VALVE ENDOCARDITIS (PVE) AND DEATH FOLLOWING VALVE REPLACEMENT SURGERY
Farrington D, Jacob JT, Kilgo P, Thourani V, Steinberg J. Emory Univ, Atlanta, GA.
Purpose of Study: To assess the risk of PVE and death following valve replacement surgery in patients undergoing chronic dialysis.
Methods Used: A matched retrospective cohort study was conducted comprising patients admitted for valve replacement surgery at 2 university hospitals from 2002-2011. Patients without dialysis were matched 1:1 to dialysis patients by valve(s) replaced, year of surgery, and endocarditis as the indication for valve replacement. Charts were reviewed until time of death or loss to follow-up. Patient characteristics were compared using Chi square and t-tests. Development of PVE was evaluated using the modified Duke Criteria and analyzed with logistic regression and survival analyses, as was mortality.
Summary of Results: A total of 278 patients were included with 139 patients in each group. Non-dialysis patients tended to be older and Caucasian. 18.7% of the dialysis group developed PVE compared to 5.8% of the non-dialysis group (figure A). After controlling for age and race dialysis remained a risk factor (OR: 2.93 [95% CI: 1.17-7.31], p=0.02). Overall mortality was higher (figure B) following valve replacement in the dialysis group (64.0%) compared to the non-dialysis group (23.0%, p<0.001) for the duration of follow up.
Conclusions: The risk of PVE and death following valve replacement surgery in dialysis patients is substantial and significantly higher than non-dialysis patients. These findings may have implications for the utility of valve replacement surgery in dialysis patients and underscore the need to prevent hemodialysis-related bloodstream infections.
600 IS CERVICAL CANCER KNOWLEDGE ASSOCIATED WITH PAP SMEAR SCREENING AMONG MINORITY WOMEN?
Ilangovan K1, Koru-Sengul T2,3, Kobetz-Kerman E2,3, Rodriguez B1, Miao F3, Carrasquillo O1. 1 University of Miami Miller School of Medicine, Miami, FL; 2 Sylvester Cancer Center, Miami, FL and3 University of Miami Miller School of Medicine, Miami, FL.
Purpose of Study: Minority women have higher cervical cancer incidence. Reducing this gap requires interventions addressing potentially modifiable factors, such as knowledge. However, limited evidence exists that cervical cancer knowledge is associated with increased likelihood of being screened for cervical cancer among minority women.
Methods Used: We analyzed baseline data from the first 466 women enrolled in a large NCI sponsored randomized study. We recruited minority women aged 30-65 in Miami Dade County whom had not been screened for cervical cancer in the last three years. We dichotomized this group into women whom reported never having a Pap smear versus those whom had had at least one. Cervical cancer knowledge was assessed using 8 questions from the Health Information National Trends Survey (HINTS) which we translated and back translated into Haitian Kreyol and Spanish. Knowledge scores were grouped into three categories [low (⩽ 2 correct), moderate, and high (≥5 correct)]. Multivariate logistic regression models were used to calculate odds ratio (OR) for prior Pap smear by knowledge score, adjusted for differences in age, marital status, and ethnicity.
Summary of Results: Latinas represented 59 % of our sample while 35% were Haitian and 6% were African-American; 17% of our sample had never had a Pap smear. Among women who scored lowest in the knowledge questions, 69% had a pap smear at some point in their lives vs. 97% of women who scored highest in the knowledge questions (p<.01). After controlling for the above potential confounders, we found that women with higher cervical cancer knowledge remained significantly more likely to have ever had a Pap smear vs. those with the lowest knowledge (OR 3.38, 95%CI 1.13-10.11). In subgroup analysis, Haitians had lower levels of knowledge than Latinas (65% had low scores vs. 29% of Latinas, p<0.01). However, among both Latinas and Haitians, knowledge was significantly associated with ever having had a Pap smear.
Conclusions: Our findings suggest that improving cervical cancer knowledge may lead to increased rates of screening among Latina and Haitian women. In the parent study we will be able to test this hypothesis.