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Introduction to Yash P. Kataria Internal Medicine Research Day(use your keyboard to scroll through the abstracts)
In 2008, the annual departmental research day program was dedicated and renamed the Yash P. Kataria IM Research Day to honor the many contributions of Dr. Yash P. Kataria, and to support the educational and research program in the Department of Internal Medicine at the Brody School of Medicine at ECU.
Dr. Kataria is Professor Emeritus of Medicine at BSOM and continues to contribute actively to the clinical, educational, and research mission of the pulmonary & critical care division at BSOM. He was the first pulmonologist in eastern NC and helped to establish the pulmonary specialty at BSOM 30 years ago and has been an integral force since the inception of the medical school. Yash was the first division chief of pulmonary medicine at BSOM and successfully recruited and
established a clinical and active laboratory research program. Yash was the section head of pulmonary at BSOM / PCMH from 1978-1995, Vice Chair of the Dept of Medicine 1987-1992, and Interim Chair 1986-87. Yash is of course known regionally, nationally, and internationally for his passion in translational research with a particular focus on sarcoidosis. He has authored over 70 publications, has received the Trudeau Award from the American Lung Association, lifetime achievement award by the NC Thoracic Society, on many occasions been listed on the “Best Doctors” list, has been a reviewer and/or on editorial board for numerous specialty journals.
Over his 30 year career, he has cared for thousands of patients with sarcoidosis and he arguably has one of the largest sarcoid cohorts in the US. Yash is revered by his patients and families. Yash has literally trained hundreds of medical students and housestaff and is cherished by them as a role model and outstanding teacher at the bedside and in clinics. Yash has been a fixture in the international sarcoid community and has contributed actively at a leadership level at ACCP, ATS, and WASOG. Scientifically, Yash is perhaps best known for promulgating a paradigm shift in our understanding of sarcoid immunology. While it was accepted dogma in the 70s that sarcoidosis was a disease of “depressed immunity” and anergy, Yash proposed and championed the concept that it is a pro- inflammatory disease with involvement of activated T-cells, cytokines, etc. Yash and his group also proposed that the active “sarcoid factor” was localized to the cell walls of alveolar macrophages and monocytes or an “autologous kveim” model (this remains an intriguing hypothesis!).
One of the missions of the medical school is community service in which medical school faculty plunged deeply. Yash lived in and loved Greenville where he raised two lovely children.
He was actively involved in the J. H Rose Attendance Area Foundation Advisory Committee; also served as a Member Board of Academic Boosters Club, Rose High School, Greenville, NC and President, Parent Teacher Association, Greenville Middle School, Greenville, NC. He also helped to develop support groups for patients with sarcoidosis & COPD, and played leadership roles in the local American Lung Association of NC. We are honoring Dr. Kataria by dedicating our annual Internal Medicine Research Day, which he started in 1987, to the Yash P. Kataria Internal Medicine Research Day. We will continue to build on the tradition of encouraging research by inviting leading guest speakers and facilitating scholarship and interaction by our trainees and faculty.
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PULMONARY ARTERY OCCLUSION PRESSURE MAY OVER-DIAGNOSE PULMONARY ARTERY HYPERTENSION IN SICKLE CELL DISEASE H Chohan, R Kadali, J Efird, R Daggubatti, P Boettger, M Mazer, D Liles, C Knupp, S Sharma
Background: Pulmonary hypertension has been shown to increase mortality in sickle cell disease. However most studies have utilized non-invasive echocardiogram and hemodynamic confirmation has been elusive. Recent reports of occlusion pressure misclassifying patients as pulmonary artery hypertension have further magnified the need for hemodynamic data validation. We hypothesized that the prevalence of PAH by hemodynamic criteria would be significantly less than the traditional echocardiogram based diagnosis. We also hypothesized that measuring left ventricular end diastolic pressure would help avoid over diagnosis. We also looked at factors which are associated with PAH in sickle cell disease. Methods: We reviewed hemodynamic data on 20 patients with sickle cell disease who underwent gold standard right heart catheterization for evaluation of pulmonary hypertension. Results: Out of 20 patients with echocardiogram diagnosed pulmonary hypertension 6 patients (30%) had PAH based on RHC criteria. However when LVEDP criteria was used only 2/20 (10%) patients had PAH. False positive rate using occlusion pressure was 67% ( 95% CI 0.22-0.96). Occlusion pressure consistently underestimated LVEDP (11.74 vs 16.20 ( 95% CI 10.1-13.3 Vs 14.1-17.9) with p value of 0.0002. This difference persisted even in patients with RHC proven PAH. Examining several independent factors, only low albumin was associated with PAH. Conclusions: These findings suggest the true prevalence of PAH in sickle cell disease may be much lower than originally believed. Pulmonary artery occlusion pressure consistently underestimated LVEDP and resulted in 20% of cases being misclassified.
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A SIMPLE RULE FOR PREDICTING OUTCOME IN HEART FAILURE PATIENTS MANAGED IN A COMMUNITY-BASED DISEASE MANAGEMENT PROGRAM H Alhosiani, D Torres, J Brinkley, WE Cascio
Background: Heart failure care in the community setting presents diagnostic and management challenges to primary care providers. Prognostic models that are based on data from community programs are helpful to the general practitioner managing heart failure.
Objective: To develop a simple prediction rule to guide management of heart failure patients in the community setting.
Methods: A 5-year registry of patients enrolled in a community-based heart failure disease management program. Baseline and follow-up clinical and diagnostic variables were collected. Primary endpoint was a composite of death and heart failure hospitalizations. We used multivariate analysis with logistic regression models to identify risk factors.
Results: A total of 246 patients were studied. Mean age was 66±15.5 years. Mean follow-up was 19.5±15.2 months. There were 126 (51%) female and 136 (55%) African-American patients. Heart failure etiology was non- ischemic in 177 (72%) patients. Median NYHA Class was 3±0.5. Mean Ejection Fraction (EF) was 40±18%. Mean baseline BNP and Creatinine (Cr) were 537±783.5 pg/dl and 1.5±0.57 mg/dl respectively. There were 57 patients (23%) who died, and 98 patients (43%) met the primary end point. Multivariate analysis identified the following parameters as independent predictors of the primary endpoint: HF admissions 12-month prior to enrollment OR= 1.78 (CI 1.24-2.57) p= 0.0019, baseline BNP OR= 1.43 (CI 1.12-1.82) p= 0.004, baseline Cr OR= 2.67 (CI 1.51-4.73) p= 0.0007, and ACEi use upon enrollment OR= 2.56 (CI 1.37-4.78) p=0.003. ROC of these covariates yielded an AUC of 0.7765.
Conclusion: Heart failure hospitalizations prior to enrollment and absence of ACEi therapy, and elevated BNP and Cr at enrollment predict poor outcome in heart failure patients managed in the community.
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CARDIOVASCULAR RISK IN EAST CAROLINA UNIVERSITY (ECU) UNDERGRADUATES
H Lai, R Ward, J Collins, K Parker, P Bolin
Background: The division of Nephrology & Hypertension conducted a pilot project between June and October 2010 to determine the prevalence of cardiovascular (CV) risk in entrant undergraduate students. Methods: Students participated in on-site assessment involving: brief medical history; measurement of body mass index (BMI), casual blood pressure (BP), measurement of nonfasting glucose and lipids; and survey of perceived health, healthcare access, physical activity, tobacco use and alcohol intake. Results: We captured 10% (n=420) of the class through student orientation fairs and another 100 students through the ECU Health 1000 course. This was a fairly healthy cohort. The (mean age =was 18 years and all participants accessed a health provider within 5 years). Demographics were reflective of the entry class-- with 78% White and 60.7% female participants. Main risk factors were diastolic BP ≥80 mmHg, low physical activity, low HDL, and obese or overweight BMI. Thirteen (2.5%) had 2 or more abnormal lipid measures, 32% had 2 or more CV risk factors and 35 (6.7%) satisfied criteria for metabolic syndrome. Of these, 71.4% were White and 45.7% were male. Conclusion: This study demonstrates that one-third of participants-- ―healthy‖ young adults with access to higher education and medical care -- has multiple CV risk factors. We anticipate the level of risk among young adults in the general community is even higher. We propose to focus on the highest risk sector of this screened population to test effectiveness of interventional strategies to reduce CV risk and to prevent CV and renal disease.
Risk Factor (%)
Low Activity* BMI≥25 BMI≥30 SBP≥140 DBP≥80 Blood Glucose>140 Abnormal Lipid**
18.0 32.9 25.6 33.7 24.1 24.4 8.8 6.3 24.9 14.1 3.8 6.6 38.5 22.3 26.6 11.2 6.9 9.0 24.2 31.7 29.5
33.3 27.0 44.9 27.8 20.3 7.6 11.6 7.8 42.0 28.5
2.9 8.6 24.6 28.9
*less than 20 minutes 3x/week **TC>240, LDL>160, HDL<50F, HDL<40M, Non HDL>190, TC/HDL>6
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SARCOIDOSIS AND ALVEOLAR MACROPHAGE POLARIZATION
I Huizar, A Malur, R Karnekar, I Marshall, MC Cashion, BP Barna, MS Kavuru, MJ Thomassen
Background: Alveolar macrophages are central to pulmonary pathology in sarcoidosis. High expression levels of the transcription factor PPAR in alveolar macrophages have been associated with the maintenance of normal lung homeostasis. Alveolar macrophages from sarcoidosis patients’ exhibit reduced PPAR activity with a concomitant upregulation of NF- B activity as compared to healthy control macrophages (AJRCMB 2004). NF B is upregulated during M1 (classical macrophage activation) while PPAR has been linked with macrophage polarization toward a more anti-inflammatory M2 (alternative activation) profile. Methods: Based on these observations we hypothesized alveolar macrophages from sarcoid patients would display a predominantly M1 phenotype compared to healthy controls. Microarray analyses of BAL cells from 12 symptomatic sarcoid patients (not on steroids) with pulmonary disease undergoing diagnostic bronchoscopy and 10 healthy controls were carried out with Affymetrix GeneChip U133A. Results: A total of 735 differentially regulated genes were found. Data confirmed previous reports of elevated interferon gamma (an inducer of M1 activation) and STAT-1. M1 genes upregulated >2 fold included the M1 interferon inducible chemokines CCL5, CXCL9, CXCL 10 and CXCL11 whereas no significant changes were detected in M2-associated genes IL-10, IL1RA, CD36, MMP2 and MMP7. Alveolar macrophages were further profiled by multicolor flow cytometric evaluation using an LSRII instrument for expression of CD206 (mannose receptor) to select and verify the macrophage population; M1 markers CD253 (TNFSF10) and CD80; M2 markers CD195 (CCR5) and CD36. Sarcoidosis alveolar macrophages exhibited elevated CD80 and reduced CD195 expression characteristic of a M1 profile. CD253 expression was higher on healthy control macrophages. Conclusion: (1) sarcoidosis alveolar macrophages display a marker profile clearly distinct from that of healthy controls and (2) healthy control alveolar macrophages express high levels of both M1 and M2 markers suggesting the alveolar macrophage homeostatic state may differ from other macrophage populations which is also consistent with the high constitutive expression of PPAR .
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PHASE II TRIAL WITH DAILY PULSE INTERLEUKIN-2 (IL 2) THERAPY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) MK Kamdar, PR Walker
Background: Therapeutic advances in treating AML have been limited in the past two decades. The overall five year survival rate in AML remains less than 50% in adults and is significantly lower (less than 10%) in patients over the age of 60. In an attempt to improve survival and reduce toxicity of therapy IL 2 has been studied in AML and has shown efficacy in relapsed AML and in consolidation of first remission. IL 2 a cytokine that promotes the proliferation and activity of cytotoxic T cells, natural killer cells and lymphokine activated cells has been shown to abrogate the clonogenic leukemic blasts in murine leukemias. Methods: We report preliminary results of a phase II trial which has enrolled patients with de novo or secondary AML of all ages to receive IL 2 after induction, during consolidation of first remission or in cases of relapse. Nine patients at our institution have met eligibility criteria since the inception of this trial. Two patients declined participation. Seven patients have received treatment with IL 2 within seven days of total white blood cell count recovery to above 500 cubic mm after either induction or post remission consolidation chemotherapy. IL 2 and famotidine were administered daily over five days with premedication. Dosage modifications were made if blood pressure was less than 90 and or there was rise in creatinine to greater than 2.
Results: Seven patients were treated with IL 2, two patients received IL 2 after induction and the remaining five received it after one of their consolidation treatments. Of the seven patients treated, one patient had prior myelodysplastic syndrome, one patient had a history of colon cancer and the remaining five patients had denovo leukemia. Of the seven patients who received IL 2, three patients died and four remain alive. One of the seven patients subsequently underwent a stem cell transplant within one month of completing IL 2 therapy and is alive. Three of seven patients have durable remission without transplant. Overall survival for patients who received IL 2 therapy is 57.1 percent with a median follow up of about two years (range 1-5 yrs). Conclusions: The preliminary results of this phase II trial are encouraging given the striking increase in overall survival with the administration of IL 2 therapy. Although the statistical power of this trial is low and we are comparing our data to historical controls, the results are encouraging enough to set forth the ground for a phase III trial in the future with a hope for improved survival for our AML patients.
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AN INTERVENTION TO IMPROVE CHRONIC KIDNEY DISEASE PREVENTION AND MANAGEMENT IN HIGH RISK PATIENTS SEEN AT THE BERNSTEIN CENTER IN GREENVILLE, CAROLINA: BLOOD PRESSURE OUTCOMES. C Winborne, K Parker, R Ward, C Christiano, M Hames, CS Lea, P Bolin
Background: Chronic Kidney Disease (CKD) is a growing public health concern, resulting in exorbitant health care costs, high morbidity, and premature mortality. If properly managed, however, adverse outcomes may be prevented and CKD patients may never progress to kidney failure. While most CKD patients are treated exclusively by primary care providers (PCPs), CKD management in primary care is suboptimal. Thus, we conducted an evidence-based CKD educational intervention targeting PCPs in a Community Health Care Center (CHC) to improve clinical practices related to CKD prevention and management. This setting was selected due to its large numbers of diabetic, hypertensive, low-income and racial minority patients— all of which are high risk for developing CKD. It was hypothesized that the educational intervention would result in improved blood pressure management evidenced by decreases inpatients’ mean blood pressure. Methods: Educational sessions based on evidence-based clinical guidelines for CKD prevention and management were led by a team of nephrologists. Changes in individual provider practices were assessed by stratifying a random sample of diagnosed hypertensive patients by provider and comparing blood pressures at baseline and post-intensive phase of the intervention using paired t-tests. Patients were included if they were 18 y/o and had at least two uncontrolled blood pressure readings (≥140/90) the years prior to and following the intervention. Analyses were conducted in PASW-18. Results: An average of 2749 patients was seen by the clinic each month and of these, 36% were hypertensive. Three providers worked in the CHC for the duration of the study, and 25 patients were reviewed per provider (n=75). When comparing individual provider management pre- and post- intervention, significant decreases in systolic blood pressures were observed for all providers (mean=-15.67, SD=6.32). Decreases in diastolic blood pressure were significant for all but one provider (mean = -6.64, SD=3.15). Discussion: Two providers reduced their patients' average blood pressures to recommended levels (<140/90 mmHg). Future interventions should incorporate control sites, evaluate the cost-effectiveness of the intervention, and examine the impact of coincident staff education.
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CAENORHABDITIS ELEGANS: A SIMPLE MODEL SYSTEM TO UNDERSTAND CANCER STEM CELLS MH Lee
Background: Cancer stem cells (CSCs), or tumor initiating cells, are believed to exist in multiple solid tumors. CSCs can self-renew like normal stem cells and cause tumors in immunodeficient mice. CSCs also resist chemotherapy and can regenerate all the cancer cell types, resulting in relapse of the cancer. Recently, key stem cell regulators, such as microRNAs and RNA-binding proteins, have been shown to be critical for the regulation of CSCs. These regulators induce the stem cells to become more differentiated and less tumorigenic through their abilities to switch off particular genes. In addition, extrinsic signaling pathways and epigenetic regulation are also important for the regulation of both CSCs and normal stem cells. Therefore, understanding all of the regulators and mechanisms involved in CSC control will provide an innovative approach for cancer treatment. Methods: We use the nematode Caenorhabditis elegans (C. elegans) as a model system to study in vivo cell fate reprogramming. Specifically, we focus on how stem cells are reprogrammed into CSCs genetically and how environmental factors like a temperature, can interact with genetic factors for cell fate reprogramming in vivo. Result: We demonstrated that key stem cell regulators and environmental factors are critical for establishing the totipotency of normal stem cells, and the prevention of CSC development, by inhibiting Ras-ERK/MAPK signaling in the C. elegans germline stem cells: Stem cell regulators include PUF RNA- binding protein and Ras-ERK/MAPK signaling. Although the capability for this process has been implicated in regenerative medicine and cancer biology, all previous experimental approaches were conducted in vitro. Moreover, the mechanism for cell fate reprogramming is still poorly understood. Conclusion: Therefore, our important discoveries and on-going experiments will find a novel, innovative approach for CSC treatment, and provide a paradigm that may facilitate pharmacological approaches to therapeutic cellular reprogramming in other organisms, including humans.
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NOVEL MURINE MODEL OF CHRONIC GRANULOMATOUS LUNG INFLAMMATION ELICITED BY CARBON NANOTUBES. I Huizar, A Malur, YA Midgette, C Kukoly, P Chen, P Ke, CJ Wingard, L Dobbs, BP Barna, MS Kavuru, MJ Thomassen
Background: Lung granulomas are associated with numerous conditions including: inflammatory disorders, environmental pollutant exposure, and infection. Osteopontin (OPN) is a chemotactic cytokine produced by macrophages and implicated in extracellular matrix remodeling. Furthermore, osteopontin is upregulated in granulomatous disease and osteopontin null mice have reduced granuloma formation. Animal models currently used to investigate chronic lung granulomatous inflammation have a pathological resemblance, but lack the chronic nature observed in human granulomatous disease. Carbon nanoparticles are generated as byproducts of combustion. Interestingly, experimental exposure to carbon nanoparticles induce pulmonary granuloma-like lesions, however the recruited cellular populations and extracellular matrix gene expression profiles within these lesions have not been explored. Due to rapid resolution of granulomas of current animal models, mechanisms responsible for persistence have been elusive. Methods: To overcome the limitations of existing models, we set out to investigate if a model using multiwall carbon nanoparticles (MWCNT) would resemble chronic human lung granulomatous inflammation. We hypothesized that pulmonary exposure to multiwall carbon nanoparticles would induce granulomas, elicit a macrophage and T cell response and mimic other granulomatous disorders with upregulation of osteopontin. Results: This model demonstrates: (a) granulomatous inflammation with macrophage and T cell infiltration; (b) resemblance to the chronicity of human granulomas with persistence up to 90 days; (c) marked elevation of osteopontin as well as metalloproteinases and cell adhesion molecules in granulomatous foci [granuloma (+)] versus non-granulomatous tissue from same mouse [granuloma (-)] isolated by laser capture microdissection (LCM) [see Table1]. Conclusions: The establishment of such a model provides an important platform for mechanistic studies of granuloma persistence.
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HYPOGLYCEMIA AFTER ROUX-en-Y GASTRIC BYPASS: IS EXTREME INSULIN SENSITIVITY THE CAUSE? MS Dar, CJ Tanner, W Chapman, JR Pender, AJ Drake III, JA Houmard
Background: Roux-en-Y gastric bypass (RYGB) induces euglycemia in 84% of type 2 diabetic patients but some non-diabetic patients experience hypoglycemia which is poorly understood and difficult to treat. Objective: We evaluated one previously type 2 diabetic patient experiencing post-prandial hypoglycemia 1+ year after RYGB and hypothesized enhanced insulin sensitivity or excessive insulin secretion as the cause.
Methods: A 56 year old white female with morbid obesity (BMI 46 kg/m2) and type 2 diabetes (A1C 11.4%) underwent RYGB and experienced weight loss (27 kg/m2), diabetes resolution (A1C 5.4%) and hypoglycemia over a 20 month span post-RYGB. She underwent minimal model testing to determine insulin sensitivity index (Si) and acute insulin response to glucose (AIRg). Results: The patient's insulin sensitivity index (Si) was 10.0 mU·l-1·min-1 which was elevated compared to other groups we have studied such as lean, non-diabetic women (age 42.7 + 2.9, BMI, 23.9 + 0.7 kg/m2, N=29) where mean SI was 7.4 + 0.8 and non-diabetic, overweight men/women after 6 months of exercise training (age 51.4 + 0.9 y, BMI 28.6 + 0.4 kg/m2, N=43) whose SI averaged 4.7 + 0.5. Also, patients 1 year post-RYGB (age 39.8± 3.1y, BMI 27.1±0.9 kg/m2, N=12) who had normalization of impaired fasting glucose increased Si from 1.2±0.3 to 4.1±0.5 highlighting the extreme insulin sensitivity in our hypoglycemic patient.
Using AIRg, we compared insulin secretion in our subject to obese non- diabetics before and after 6 months of exercise training and a morbidly obese type 2 diabetic pre- and post-RYGB. Our subject's AIRg was 71 mu/L·min compared to 380 mu/L·min in non-diabetic exercised trained subjects and 159 mu/L·min in a euglycemic patient 1 month post-RYGB. This data suggests that hypersecretion of insulin in response to carbohydrate did not occur in our subject. Conclusions: A previously type 2 diabetic patient experiencing hypoglycemia 1+ year post-RYGB appeared to have markedly enhanced insulin sensitivity (Si) and significantly decreased insulin secretion (AIRg) compared to several cross-sectional controls. This finding contradicts previous studies implicating excessive insulin secretion as the cause of post- RYGB hypoglycemia.
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THE EAST CAROLINA BREAST CENTER PHASE II TRIAL OF
NEOADJUVANT METRONOMIC CHEMOTHERAPY IN TRIPLE-NEGATIVE 0BREAST CANCER
RE Raab, PR Walker, L Bellin, JH Wong
Background: Triple negative (ER negative, PR negative, HER 2 negative) breast cancers (TNBC) lack effective targeted therapy limiting treatment options to cytotoxic chemotherapy alone. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients with TNBC >/= 2 cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy was performed in patients with clinically negative axilla. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Patients received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between July 2006 and December 2010, 12 patients with TNBC were enrolled, 9 are eligible for analysis. Accrual continues to date. Age ranged from 25 to 85 (mean age 46.5 + 16.3yrs), primary tumor size ranged from 2.5 cm to 12.0 cm (mean 5.8 cm + 2.9cm). Of the 8 patients who underwent sentinel node biopsy prior to systemic therapy, 4 patients were staged pN0 and 4 were staged pN positive. One patient experienced G3 thrombocytopenia, two patients G3 granulocytopenia, one patient G3 anemia and one patient G3 neuropathy. One patient died of a pulmonary embolus possibly related to therapy. Rate of clinical CR was 66%, rate of clinical PR was 33%, and one patient progressed on therapy. The rate of complete pathologic response was 66%. One patient had a 0.7 cm focus of residual invasive carcinoma. Positive nodes were identified in 22%- one patient who progressed on therapy and one who experienced a clinical PR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus oral cyclophosphamide followed by weekly paclitaxel plus carboplatin is well tolerated. These results suggest significant activity of this approach in women with triple negative breast cancer and warrants continued investigation.
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RACIAL DIFFERENCES IN THE PREDICTIVE VALUE OF MALLAMPATI SCORE FOR OBSTRUCTIVE SLEEP APNEA. OM Albustami; MM Islam; K Rahman, S Sharma
Background: Obstructive sleep apnea (OSA) affects 9% of females & 25% in males. Prevalence of OSA is even higher in obese and elderly patients. OSA is associated with serious long term health consequences including cardiovascular disease, hypertension, and stroke and a reduced quality of life. Mallampati score has been reported to be significantly associated with OSA. However, its clinical usefulness has not been addressed specifically in African American patients.
Objective: To determine if race affects the clinical usefulness of the Mallampati score in patients with OSA. Methods: The medical charts of 450 patients, who had overnight Polysomnography, were reviewed retrospectively. Three hundred and forty seven patients (n= 347, 77.1%) had OSA (Apnea Hypopnea Index (AHI) ≥ 5) and one hundred and three patients (n= 103, 22.9%) did not have OSA (AHI < 5). Student's t-test was used for data analysis. P-value <0.05 was considered significant.
Results: Compared to patients who did not have OSA, patients with OSA were more likely to have Mallampati score III/IV regardless of their race (p <0.001). However, Mallampati score III/IV was more strongly associated with OSA in African Americans than in Caucasians (p <0.001 for African Americans and p= 0.04 for Caucasians). Mallampati score I/II NPV was high across all groups: 92.4% for the whole group, 88.1% for the Caucasians and 96.1% for African Americans, while specificity was 76.7% for all groups. Mallampati score III/IV PPV was high across all groups: ~ 80.7 % and sensitivity was also high across all groups: 92.8% for the whole group, 88.8% for the Caucasians and 95.9% for the African Americans.
High Mallampati score (III/IV) has significant correlation with OSA, more so in African Americans than Caucasians. High Mallampati score has high PPV and sensitivity while low Mallampati (I/II) score has high NPV and specificity. Clinical Implications:
Mallampati score should be a part of the physical examination of patients with suspected SDB that can be applied easily and quickly in the clinical setting.
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TUBE FEEDING SYNDROME: A CASE REPORT
JA Dailey, E Cullen
Background:Tube feeding syndrome is potentially lethal yet easily correctable disturbance in a patient’s fluids and electrolytes seen in some patients receiving enteral feeds. Elaine Pardo describes Tube feeding syndrome as, ―a condition caused by a tube feeding regimen that provides too little water for the excretion of its solute load.‖ Tube feeding syndrome is an example of osmotic diereses secondary to high concentrated tube feeds. Approximately 152,000 patients in the United States receive home enteral feeding. Yet despite the wide spread use of enteral feeding, commonly referred to as tube feeding, there is a paucity of literature about Tube Feeding Syndrome.
Case Information:57 y/o schizoaffective disorder male was transferred from an outside hospital with hypernatremia (156’s), polyuria and polydipsia. Pt was in acute renal failure, with a cretinine of 2.18 and a bun of 53. The patient did not have any history of renal disease. Pts was not hyperglycemia. The patient had been diagnosed with diabetes insipidus by psychiatry 3 days ago by physical exam, hypernatremia and polyuria. At the time of admission the admitting psychologist suspected it was nephrogenic diabetes insipidux secondary to Librium use. Of not the patient had also developed an esophageal stricture and was being fed enterally. He also has a history of severe aspiration pneumonia.
Summary:Since the symptoms of hypernatremia, kidney failure etc. coincided with the increase in tube feeds on both attempts, it was then hypothesized that the high concentration tube feeds were causing an osmotic diereses. A literature search was done as above and patient was started on treatment for tube feeding syndrome (decrease concentration of tube feeds and increase fluid delivery) with resolution of symptoms.
Regardless of the situation, Tube Feeding Syndrome should be on the differential whenever a patient on tube feeds presents with dehydration and hyperosmolarity.
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PHASE II STUDY OF LOW-DOSE PACLITAXEL WITH TIMED THORACIC RADIOTHERAPY FOLLOWED BY GEMCITABINE AND CARBOPLATIN CONSOLIDATION IN PATIENTS WITH UNRESECTABLE STAGE III NON- SMALL LUNG CARCINOMA.
J Zhang, PR Walker
Background: Concurrent chemoradiotherapy (CRT) is a curative potential treatment for unresectable stage III NSCLC, yet the optimal treatment paradigm and choice of regimen is unclear. Previous phase I/II study (Chen et al Clin Can Res 9:969-975, 2003) using low-dose Paclitaxel with timed thoracic radiotherapy (TTR) has shown high local response by inducing maximum radiosensitization through G2-M cell cycle arrest. We conducted a phase II study of low-dose Paclitaxel with TTR as induction, followed by systemic adjuvant full-dosing chemotherapy for unresectable stage III NSCLC patients. Methods: From 4/2007 to 12/2009, 30 patients with unresectable stage III NSCLC and ECOG PS 0-2 were enrolled. Patients received Paclitaxel 15mg/m2 IV over 1 hour at 8am on Monday/Wednesday/Friday with total 55Gy TTR delivered at 4pm Monday/Wednesday/Friday and 8am Tuesday/Thursday over 5 weeks, followed by Carboplatin (AUC 5) day 1 and Gemcitabine 1000mg/m2 IV days 1 and 8, q21d for 4 cycles. Primary end point was overall survival (OS); secondary end points were overall response rate (ORR), progression-free survival (PFS) and toxicities. Results: 27 pts were evaluable. Patient characteristics: M 70%; median age 67 (39-82), 41% over age 70; stage IIIB 56%. 30 month OS 28% (95% CI: 15-53); 30 month PFS 20% (95% CI: 9- 44). ORR was 63%, 6 CR, 11 PR, 6 SD, 1 PD. TTR was delivered as planned in 26/27 patients (1 pt died after 3rd week TTR). TTR related grade 3 toxicities: esophagitis 2, pneumonitis 1, neutropenia 1. CT consolidation related grade 3/4 toxicities: pneumonitis 6, cytopenias 7, esophagitis 2, which limited median delivery of CT to 2 cycles. One patient died of sepsis. 2 patients developed pulmonary embolism. Conclusions: Low-dose Paclitaxel with timed thoracic radiotherapy is an effective concurrent CRT regimen with minimal toxicity in nonsurgical stage III NSCLC patients, especially the elderly population. Gemcitabine radiation recall and hematological toxicity were limiting adjuvant CT dose delivery.
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ULTRASOUND-DERIVED ESTIMATE OF RIGHT ATRIAL PRESSURE PREDICTS 30-DAY ACUTE HEART FAILURE RE-HOSPITALIZATIONS H Alhosiani, M Farooqui, A Mayo, J Brinkley, WE Cascio
Background: Acute heart failure (AHF) hospitalizations represent a major healthcare burden. Patients admitted with AHF are at risk for readmission with similar symptoms. Although pulmonary venous congestion is the main reason for heart failure hospitalization, many patients are discharged without adequate assessment and relief of congestion. The use of cardiac ultrasound and Doppler to derive hemodynamic parameters and guide HF therapy is emerging as a promising noninvasive technique. However, few data exist on the role of ultrasound-derived congestion assessment and whether it can be used to predict outcomes after AHF hospitalization.
Methods: A retrospective study of a random cohort of patients who were hospitalized at PCMH between 2007-2009 with primary diagnosis of AHF. The demographic and clinical variables were collected. Echocardiographic studies, obtained during the initial hospitalization, were reviewed including IVC size and inspiratory collapse data. Patients who were readmitted with recurrent AHF, within 30-days from the initial hospitalization, were identified. A multivariate logistic regression analysis was used to identify risk factors for 30-day readmission with AHF. A statistical model was used to determine whether Ultrasound-Derived Estimate of Right Atrial Pressure (UDERAP) during the initial hospitalization independently predicts 30-day re- hospitalization with AHF. Results: There were 355 patients, mean age 67.6
15.5 and mean left ventricular ejection fraction (EF) 42.7% 18.3. RAP as estimated by IVC data segregated patients into three groups: low-pressure (n= 138, 39%), intermediate-pressure (n= 101, 28%), and high-pressure (n= 116, 33%). A total of 75 patients (21%) were re-hospitalized with AHF within 30-days of the initial hospitalization. Echocardiographic estimates of RAP in this subset of high-risk patients were the following: low-pressure (32%, n=24), intermediate-pressure (17%, n= 13), and high-pressure (51%, n= 38) p= 0.0008. Using logistic regression analysis, it appears that RAP groups predicted AHF 30-day re-hospitalization (Chi Square 10, p= 0.006). High- pressure group conferred significantly greater risk compared to either intermediate or low pressure groups for 30-day AHF re-hospitalization (OR 3.16 and 1.89). Conclusion: Ultrasound-derived estimate of right atrial pressure might serve as a surrogate for congestion and therefore predict 30- day re-hospitalization for AHF.
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100% UNIVERSAL ADMISSION SCREENING FOR METHICILLIN- RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) PLUS ERADICATION THERAPY WITH MUPIROCIN PLUS CHLORHEXIDINE DECREASED HEALTHCARE-ASSOCIATED INFECTIONS DUE TO MRSA IN A TERTIARY CARE HOSPITAL
MK Cochran, DL Nobles, AD Bryant, MR Coogan, T Fisher, W Cleve, A Harrell, V Kinzie, C Shoup-Collins, A Blake, KM Ramsey
Background: Healthcare-associated infections (HAI) due to MRSA continue to be a major challenge for hospitals in the US. Strategies to decrease HAI- associated MRSA include hand hygiene, isolation of known and high-risk patients for carriage, selective screening and eradication, and universal surveillance plus eradication. A quality board initiative to eradicate HAI- associated infections due to MRSA was initiated in 2007. Methods: HAI- associated surveillance data from 1 year prior to and 2 years following the intervention of 100% universal admission screening and eradication therapy were collected and compared. Surveillance definitions of the National Health and Safety Network (NHSN) were utilized to determine infection rates for ventilator associated pneumonias (VAP), central line associated bacteremias (CLA-BSI), and catheter-associated urinary tract infections (CAUTI) per 1000 device days. The rates for the pre-intervention year were compared with the rates for the intervention and maintenance years, and analyzed for statistical significance using 2-tailed t-tests where significance equals p< 0.05. Results: Rates for MRSA-associated HAIs decreased for each device as listed. The VAPs per 1000 vent days decreased from 1.065-to-0.296 (p < 0.006) in the intervention year, and to 0.183 (p < 0.002) in the maintenance year. The CLA-BSIs per 1000 line days decreased 51% from 0.244-to-0.124 ( p < 0.292) in the intervention year, and to 0.111 in the maintenance year ( p < 0.196). CAUTI rates per 1000 foley days decreased 49% from 0.207-to- 0.101 (p< 0.254) in the intervention year, and to 0.099 (p < 0.266) during the maintenance year. Conclusions: 1) Decreases in all three HAI-associated device-related infections due to MRSA were observed following implementation of universal surveillance and eradication for MRSA, and were maintained during the next year. 2) Statistically significant decreases were observed among Ventilator associated pneumonias due to MRSA in both the intervention and maintenance years. 3) A Search and destroy strategy for MRSA-associated HAIs proved efficacious at this tertiary care center.
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EFFECT OF INCREASING ERTAPENEM USE ON THE SUSCEPTIBILITY OF NOSOCOMIAL PSEUDOMONAS AERUGINOSA TO IMIPENEM- A 10- YEAR STUDY PP Cook, M Gooch, S Rizzo
Background: There has been concern that the use of ertapenem may select for cross-resistance to group 2 carbapenems (imipenem, meropenem, and doripenem). We examined the effect of the addition of ertapenem to our hospital formulary on the resistance of nosocomial Pseudomonas aeruginosa to group 2 carbapenems over a 10-year period (2000-9) at a large, tertiary- care hospital. Methods: The study period was divided into two periods: 1) the10 quarters prior to, and 2) the 30 quarters following the addition of the drug to the formulary. Drug use was measured in defined daily doses per 1000 patient days (DDD/1000 PD). Resistance was expressed as a percentage of total isolates as well as the number of carbapenem-resistant Pseudomonas aeruginosa isolates per 10,000 patient days. Interrupted time- series analysis was used to compare use of ertapenem, group 2 carbapenems, tobramycin, piperacillin-tazobactam, cefepime, ciprofloxacin, number of resistant carbapenem-resistant Pseudomonas aeruginosa isolates per 10,000 patient days and percentage of isolates resistant to group 2 carbapenems with p< 0.05 considered significant. Spearman correlation was used to assess the relationship between antibiotic use and imipenem resistance. Results: Over the ten-year period, 3002 non-duplicate, nosocomial isolates of Pseudomonas aeruginosa were identified. Despite a large increase in the use of ertapenem, there was a statistically significant decrease in percentage of isolates resistant to the group 2 carbapenems (p=0.0015). Group 2 carbapenem use and the number of carbapenem- resistant Pseudomonas aeruginosa isolates per 10,000 patient days did not change significantly over the time period. There was a large decrease in the use of ciprofloxacin (p<0.0001), and there was a correlation of ciprofloxacin use with the percentage of isolates resistant to the group 2 carbapenems
( =0.45, p=0.004). Conclusion: The addition of ertapenem to our hospital formulary was associated with an improvement in susceptibility of Pseudomonas aeruginosa to group 2 carbapenems, possibly related to a decrease in ciprofloxacin use.
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DECREASED LEVELS OF DEHYDROEPIANDROSTERONE, DEHYDRO- EPIANDROSTERONE-SULFATE AND INCREASED LEVELS OF IL-2 CORRELATES WITH A PROMOTER VARIANT IN THE PROLACTIN GENE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS
EL Treadwell, K Wiley, B Word, R Patton, W Melchior, W Tolleson, N Goope, and BD Lyn-Cook.
Background and Objectives: Dehydroepiandrosterone (DHEA) and prolactin have been shown to have multiple immunodulatory effects on autoimmune diseases, aging, and certain neurodegenerative diseases. Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organ systems. SLE Prevalence is 9:1 in women vs. men and 3:1 of African American (AA) and Hispanic women to Caucasian (CC). The objective of this study was to determine the relevance of the 1149G/T functional single-nucleotide polymorphism (SNP) in the extrapituitary promoter of the prolactin gene in a cohort of AA and CC women with and without lupus. The -1149G/T functional single-nucleotide polymorphism (SNP) in the extrapituitary promoter has been associated with higher prolactin levels in a cohort of women with lupus; however, that cohort did not contain sufficient numbers of AA women. Methods: Blood samples were consecutively obtained by informed consent from patients seen in the rheumatology clinics at East Carolina University. Using RFLP and DNA sequencing, the SNP was evaluated and correlated with prolactin, DHEA, IL- 2, IL-12, and estrogen levels (levels determined by a standard commercial RIA assay). This study examined the frequency of the promoter 1149G/T SNP in both AA and CC women with (84) and without (56) lupus. The frequency of this SNP was also examined in a small cohort of men. Results of the study revealed that the TT-1149 genotype in women with lupus correlated to lower levels of DHEA and DHEA-Sulfate in serum, higher levels of IL-2 and higher levels of prolactin in serum (p<.0001). The GT-1149 and GG- 1149 and genotypes correlated to higher DHEA levels and lower prolactin levels in women with lupus in comparison to the TT-1149 genotype. Women with lupus with the TT-1149 genotype had significantly higher levels of estradiol (p<0.03) when compared to those with the GT or GG genotypes. The TT-1149 (34%) and GT (46%) genotypes were prevalent with women with lupus. Conclusion: Preliminary results suggest that low levels of DHEA, increased IL-2 and the TT-1149 genotype may be a risk factor for lupus. Also, it was noted that a higher percentage of AA women had the TT-1149 genotype.
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