Digital Commons Network^™

The Yersinia Pestis Effector Yopm Inhibits Pyrin Inflammasome Activation., Dmitry Ratner, M Pontus A Orning, Megan K. Proulx, Donghai Wang, Mikhail A. Gavrilin, Mark D. Wewers, Emad S. Alnemri, Peter F. Johnson, Bettina Lee, Joan Mecsas, Nobuhiko Kayagaki, Jon D. Goguen, Egil Lien

Department of Biochemistry and Molecular Biology Faculty Papers

Type III secretion systems (T3SS) are central virulence factors for many pathogenic Gram-negative bacteria, and secreted T3SS effectors can block key aspects of host cell signaling. To counter this, innate immune responses can also sense some T3SS components to initiate anti-bacterial mechanisms. The Yersinia pestis T3SS is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines IL-1β and IL-18, which are typically processed into their mature forms by active caspase-1 following inflammasome formation. Some effectors, like Y. pestis YopM, may block inflammasome activation. Here we show that YopM prevents Y. pestis induced activation of the Pyrin inflammasome induced …

Quality Of Care Assessment At A Resident-Based Primary Care Hiv Clinic, Amanda Lacue, Marshall Miller, Md

CwiC Posters

A quality improvement study based in a primary care resident-based HIV clinic, the Kendig Clinic, was conducted within Jefferson Family Medicine Associates. The study objectives were to

• Determine the percentage of the clinic patients meeting each quality measure

• Compare these calculated clinic measures to known national averages

• Use the data to determine areas to target for future quality improvement initiatives.

Hepatitis C Screening In The Homeless Population Of Philadelphia, Adam Zimilover

CwiC Posters

Hepatitis C is a viral infectious disease that is a major cause of liver disease around the world. By the 1970s, it was recognized that many hepatitis cases were not due to the known hepatitis A or hepatitis B viruses. It was not until 1989 when the virus, then known as non--‐A, non--‐B hepatitis, was identified as a new distinct virus, hepatitis C. The virus has seven major genotypes, with genotype 1 causing about 75% of cases in the United States. By 1990, a screening test for the virus was developed, and within a year, the first treatment for the …

Jeffhope News-Fall 2016

JeffHOPE News

This issue includes:

• Updates: HCV Testing
• From the Project Director
• New Position: Triage Director
• Clinic at a Glance
• Advocacy Spotlight
• Research at JEFFHope
• Eye screening in an urban homeless shelter
• Contraception
• Self-Reported Indicators for Hepatitis C Virus Screening in JEFFHope Patients
• EKG Study
• Assessing the Need for Dermatological Care and Prevalence of Dermatologic conditions in an urban homeless shelter
• Spotlight on the John Bell Center
• If you had to describe JEFFHope in one word...
• Reflections by Committee Members and Directors
• 2016-2017 JEFFHope Volunteers

Should Family Presence Be Allowed During Cardiopulmonary Resuscitation?, Karen J. Brasel, John W. Entwistle Iii, Md, Phd, Robert M. Sade

Department of Surgery Faculty Papers

No abstract provided.

Emerging Infectious Diseases: Global To Local Implications, Mary Lou Manning, Phd, Crnp, Cic, Faan

Department of Nursing Papers

Infectious disease remains among the leading causes of death worldwide. With easy mobility and air travel, pathogens can move quickly and silently to any place around the globe in a matter of days. The recent Ebola crises in West Africa clearly demonstrated the increased risk of emerging infections in our highly connected world. Legal nurse consultants are well-positioned to provide guidance on deciphering public health laws relevant to responding to infectious disease threats.

Post-Transplant Outcomes In High-Risk Compared With Non-High-Risk Multiple Myeloma: A Cibmtr Analysis., Emma C. Scott, Parameswaran Hari, Manish Sharma, Jennifer Le-Rademacher, Jiaxing Huang, Dan Vogl, Muneer Abidi, Amer Beitinjaneh, Henry Fung, Siddhartha Ganguly, Gerhard Hildebrandt, Leona Holmberg, Matt Kalaycio, Shaji Kumar, Robert Kyle, Hillard Lazarus, Cindy Lee, Richard T. Maziarz, Kenneth Meehan, Joseph Mikhael, Taiga Nishihori, Muthalagu Ramanathan, Saad Usmani, Jason Tay, David Vesole, Baldeep Wirk, Jean Yared, Bipin N. Savani, Cristina Gasparetto, Amrita Krishnan, Tomer Mark, Yago Nieto, Anita D'Souza

Department of Medical Oncology Faculty Papers

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (-Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher …

Systemic Inflammatory Response Syndrome (Sirs) After Extracorporeal Membrane Oxygenation (Ecmo): Incidence, Risks And Survivals., Karthik Thangappan, Nicholas C. Cavarocchi, Michael Baram, Brandi Thoma, Hitoshi Hirose

Department of Surgery Faculty Papers

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is frequently observed after extracorporeal membrane oxygenation (ECMO) decannulation; however, these issues have not been investigated well in the past.

METHODS: Retrospective chart review was performed to identify post-ECMO SIRS phenomenon, defined by exhibiting 2/3 of the following criteria: fever, leukocytosis, and escalation of vasopressors. The patients were divided into 2 groups: patients with documented infections (Group I) and patients with true SIRS (Group TS) without any evidence of infection. Survival and pre-, intra- and post-ECMO risk factors were analyzed.

RESULTS: Among 62 ECMO survivors, 37 (60%) patients developed the post-ECMO SIRS phenomenon, including …

Sarcoidosis Activates Diverse Transcriptional Programs In Bronchoalveolar Lavage Cells., Sina A. Gharib, Anagha Malur, Isham Huizar, Barbara P. Barna, Mani S. Kavuru, Lynn M. Schnapp, Mary Jane Thomassen

Division of Pulmonary, Allergy, and Critical Care Medicine Presentations and Grand Rounds

BACKGROUND: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.

METHODS: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs.

CONTROLS: To better elucidate pathways differentially activated …

What's New In Musculoskeletal Infection: Update On Biofilms., Arvind Nana, Sandra B Nelson, Alex Mclaren, Antonia F. Chen, Md, Mba

Rothman Institute Papers

No abstract provided.

Two Cases Of Vibrio Infection And Sepsis In The Delaware Estuary, René Daniel, Md, Joseph Yoo, Md, Roberto Fratamico, Md, Robert Measley, Md

The Medicine Forum

INTRODUCTION

Vibrio is a genus of Gram-negative motile rods. Several species are pathogenic, including Vibrio vulnificus and Vibrio parahaemolyticus. The interest in this genus is due to its extreme virulence and often fatal outcomes. In healthy patients, these infections are typically self-limited; however, in immunocompromised and cirrhotic patients, infections can result in bacteremia, which has a high fatality rate1. Both pathogens may cause acute gastroenteritis, necrotizing wound infections, and if severe, subsequent bacteremia. In this report, we present two cases of Vibrio infections recently identified in the Delaware River Estuary that resulted in severe sepsis and, in one case, death.

Unexplained Recurrent Fevers And The Importance Of Inquiring About Occupation: A Case Report, Zachary Reese, Ms4, Poonam Maru, Do

The Medicine Forum

INTRODUCTION

Many different tick-borne diseases are identified in various geographical areas throughout the United States. Ixodes scapularis tick-borne diseases can present unique diagnostic challenges because of their constellation of vague symptoms. The Ixodes scapularis tick, more commonly known as the blacklegged tick, is responsible for three specific tick-borne infections: Lyme disease (Borellia burgdorferii), Babesiosis (Babesia microti), and Anaplasmosis (Anaplasma phagocytophilum) also known as human granulocytic anaplasmosis. Although these three tick-borne diseases are characteristically found in the New England area, the geographical distribution of the Ixodes tick has expanded to encompass much of the northeastern United States and even states in …

Table Of Contents

The Medicine Forum

Table of Contents The Medicine Forum

The Journal of Thomas Jefferson University Hospital

Department of Internal Medicine

Volume 17, 2015-2016

Acute Post-Disaster Medical Needs Of Patients With Diabetes: Emergency Department Use In New York City By Diabetic Adults After Hurricane Sandy., David C. Lee, Vibha K. Gupta, Brendan G. Carr, Sidrah Malik, Brandy Ferguson, Stephen P. Wall, Silas W. Smith, Lewis R. Goldfrank

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To evaluate the acute impact of disasters on diabetic patients, we performed a geospatial analysis of emergency department (ED) use by New York City diabetic adults in the week after Hurricane Sandy.

RESEARCH DESIGN AND METHODS: Using an all-payer claims database, we retrospectively analyzed the demographics, insurance status, and medical comorbidities of post-disaster ED patients with diabetes who lived in the most geographically vulnerable areas. We compared the patterns of ED use among diabetic adults in the first week after Hurricane Sandy's landfall to utilization before the disaster in 2012.

RESULTS: In the highest level evacuation zone in New …

Comprehensive Refugee Health Surveillance In Philadelphia: A Combined Resettlement And Clinical Patient Registry, Colleen Payton, Mph, Ches, Brittany Divito, Mph, Bsn, Rn, Gretchen Shanfeld, Mph, Zoe Agoos, Md, Kevin Scott, Md, Marc Altshuler, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Oral presentation at the 6^th Annual North American Refugee Health Conference, Niagara Falls, New York.

Goal:

To improve the success of refugee resettlement and health outcomes in Philadelphia by establishing a multi-agency registry with social services and clinical measures.

Improving Influenza Vaccination Rates In The Hiv Population At An Academic Clinic, Anusha G. Govinda, Md, Anita Modi, Md, Emma Biegacki, Bryan Hess, Md

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

AIM:

Performance measure: Percentage of HIV-infected patients with documentation of influenza vaccination in Allscripts.

Numerator: Number of HIV-infected patients who have obtained an influenza vaccine during influenza season.

Denominator: Total number of HIV-infected patients at the Jefferson Infectious Disease (ID) Clinic

Patient exclusions: Those who are allergic to eggs or have had allergic reactions to the influenza vaccine in the past

Goal: "75% of HIV-infected patients at the Jefferson ID clinic will be vaccinated against influenza and documented in Allscripts during influenza season"

Medication Errors And Hospital Admissions, A Tale Of Woe, Allison Greco, Md, René Daniel, Md, Raymond Janowski, Md, Bracken Babula, Md

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

Goal for Improvement:

To improve proper medication regimens for patients as they transition between healthcare settings

So that patients achieve improved outcomes and reduced hospital admissions caused by medication errors

SMART aim is to decrease teh number of discrepancies between discharge medication lists and pill bottles or blister packs produced at one-week follow up with Jefferson PCP by 10% within six months.

Prolonged Morphine Exposure Induces Increased Firm Adhesion In An In Vitro Model Of The Blood-Brain Barrier., Marianne Strazza, Vanessa Pirrone, Brian Wigdahl, Will Dampier, Wei Lin, Rui Feng, Monique E Maubert, Babette Weksler, Ignacio A Romero, Pierre-Olivier Couraud, Michael R Nonnemacher

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

The blood-brain barrier (BBB) has been defined as a critically important protective barrier that is involved in providing essential biologic, physiologic, and immunologic separation between the central nervous system (CNS) and the periphery. Insults to the BBB can cause overall barrier damage or deregulation of the careful homeostasis maintained between the periphery and the CNS. These insults can, therefore, yield numerous phenotypes including increased overall permeability, interendothelial gap formation, alterations in cytokine and chemokine secretion, and accelerated cellular passage. The current studies expose the human brain microvascular endothelial cell line, hCMEC/D3, to prolonged morphine exposure and aim to uncover the …

Repurposing Atovaquone: Targeting Mitochondrial Complex Iii And Oxphos To Eradicate Cancer Stem Cells., Marco Fiorillo, Rebecca Lamb, Herbert B Tanowitz, Luciano Mutti, Marija Krstic-Demonacos, Anna Rita Cappello, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis in immune-compromised patients. Atovaquone is a hydroxy-1,4-naphthoquinone analogue of ubiquinone, also known as Co-enzyme Q10 (CoQ10). It is a well-tolerated drug that does not cause myelo-suppression. Mechanistically, it is thought to act as a potent and selective OXPHOS inhibitor, by targeting the CoQ10-dependence of mitochondrial complex III. Here, we show for the first time that atovaquone also has anti-cancer activity, directed against Cancer Stem-like Cells (CSCs). More specifically, we demonstrate that …

Cancer Stem Cell Metabolism., Maria Peiris-Pagès, Ubaldo E. Martinez-Outshoorn, Richard G. Pestell, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Determining the role of cancer stem cell metabolism in carcinogenesis has become a major focus in cancer research, and substantial efforts are conducted towards discovering clinical targets.

Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with …

Utilization Of Hiv-1 Envelope V3 To Identify X4- And R5-Specific Tat And Ltr Sequence Signatures., Gregory C Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Jeffrey M Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Gregory Schwartz, Uri Hershberg, Fred C Krebs, Brian Wigdahl

Department of Medicine Faculty Papers

BACKGROUND: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures …

Pharmacologic And Clinical Evaluation Of Posaconazole., Jason N. Moore, Jason R. Healy, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. There is evidence of efficacy in the treatment and prevention of rarer, more difficult-to-treat fungal infections. Posaconazole oral suspension solution has shown limitations with respect to fasting state absorption, elevated gastrointestinal pH and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide an attractive treatment option by reducing interpatient variability and providing flexibility in critically ill patients. On the basis of clinical experience and further clinical studies, posaconazole was found to be …

Integrating Correctional And Community Health Care: An Innovative Approach For Clinical Learning In A Baccalaureate Nursing Program., Mary T. Bouchaud, Beth Ann Swan

College of Nursing Faculty Papers & Presentations

PROBLEM: With an evolving focus on primary, community-based, and patient-centered care rather than acute, hospital-centric, disease-focused care, and recognition of the importance of coordinating care and managing transitions across providers and settings of care, registered nurses need to be prepared from a different and broader knowledge base and skills set. A culture change among nurse educators and administrators and in nursing education is needed to prepare competent registered nurses capable of practicing from a health promotion, disease prevention, community- and population-focused construct in caring for a population of patients who are presenting health problems and conditions that persist across decades …

Development Of A Temperature Sensitive Face Mask For Identification And Triage Of Febrile Patients, Annemarie Daecher, Flemming Forsberg, John R. Eisenbrey

Department of Radiology Posters

Abstract:

Many infectious diseases are most transmittable when the carrier is presenting with fever. We propose a disposable face mask that changes color as an indicator of fever to provide hospitals with a quick and inexpensive method for triaging infected patients while limiting exposure to others. Two blue thermochromatic dyes which transition to white at 89°F and 92°F were mixed with white paint and applied to 5 types of disposable face masks. During trials, a wearer either sat at rest or ran on a treadmill for 20 minutes and images were obtained every 5 minutes with a thermal camera to …

Vaccination Of Gerbils With Bm-103 And Bm-Ral-2 Concurrently Or As A Fusion Protein Confers Consistent And Improved Protection Against Brugia Malayi Infection., Sridhar Arumugam, Junfei Wei, Zhuyun Liu, David Abraham, Aaron Bell, Maria Elena Bottazzi, Peter J Hotez, Bin Zhan, Sara Lustigman, Thomas R Klei

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best candidates for the development of an O. volvulus vaccine. The B. malayi gerbil model was used to confirm the efficacy of these Ov vaccine candidates on adult worms and to determine whether their combination is more efficacious.

METHODOLOGY AND PRINCIPLE FINDINGS: Vaccine efficacy of recombinant Bm-103 and Bm-RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with Bm-103 resulted in worm reductions of 39%, 34% and 22% on …

A 22-Year-Old Man With Pleural Tuberculosis Associated Hydropneumothorax: Case Report And Literature Review., Lauren A Sharan, Thea Price, Md, Boyd Hehn, David Manoff, Md, Scott W. Cowan, Md

Department of Medicine Faculty Papers

A 22-year-old Asian male presented with fever, non-productive cough, right-sided pleuritic chest pain and was found to have a large right hydropneumothorax. A chest tube was placed. Pleural fluid analysis revealed a lymphocytic predominant exudate and he was subsequently started on four-drug daily anti-tuberculosis therapy (isoniazid, ethambutol, rifampin, pyrazinamide). Pleural biopsy revealed acid-fast bacilli. Given his persistent pleural effusion, he was given four doses of intrapleural tissue plasminogen activator (tPA) and dornase alpha (DNase) via his chest tube over a period of 6 days resulting in clinical and radiologic improvement. Pleural biopsy and pleural fluid culture specimens later revealed Mycobacterium …

Conjugate Haemophilus Influenzae Type B Vaccines For Sickle Cell Disease., Slimane Allali, Martin Chalumeau, Odile Launay, Samir K. Ballas, Mariane De Montalembert

Cardeza Foundation for Hematologic Research

BACKGROUND: People affected with sickle cell disease are at high risk of infection from Haemophilus influenzae type b. Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Haemophilus influenzae type b remains one of the most common cause of bacteraemias in children with sickle cell disease. The increased uptake of this conjugate vaccination may substantially improve the survival of children with sickle cell disease.

OBJECTIVES: The primary objective was …

Cannibalism, Kuru, And Mad Cows: Prion Disease As A "Choose-Your-Own-Experiment" Case Study To Simulate Scientific Inquiry In Large Lectures., Antonio Serrano, Jeffrey Liebner, Justin K Hines

Department of Medicine Faculty Papers

Despite significant efforts to reform undergraduate science education, students often perform worse on assessments of perceptions of science after introductory courses, demonstrating a need for new educational interventions to reverse this trend. To address this need, we created An Inexplicable Disease, an engaging, active-learning case study that is unusual because it aims to simulate scientific inquiry by allowing students to iteratively investigate the Kuru epidemic of 1957 in a choose-your-own-experiment format in large lectures. The case emphasizes the importance of specialization and communication in science and is broadly applicable to courses of any size and sub-discipline of the life sciences.

The Eff-1a Cytoplasmic Domain Influences Hypodermal Cell Fusions In C. Elegans But Is Not Dependent On 14-3-3 Proteins., Jessica H Shinn-Thomas, Jacob J Del Campo, Jianjun Wang, William A Mohler

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Regulatory and biophysical mechanisms of cell-cell fusion are largely unknown despite the fundamental requirement for fused cells in eukaryotic development. Only two cellular fusogens that are not of clear recent viral origin have been identified to date, both in nematodes. One of these, EFF-1, is necessary for most cell fusions in Caenorhabditis elegans. Unregulated EFF-1 expression causes lethality due to ectopic fusion between cells not developmentally programmed to fuse, highlighting the necessity of tight fusogen regulation for proper development. Identifying factors that regulate EFF-1 and its paralog AFF-1 could lead to discovery of molecular mechanisms that control cell fusion …