Digital Commons Network^™

This Holiday Season Give The Gift Of Safety, Maclain Capron, Sonia Limaye, Pallavi Sindhu

Foundations of Public Health - Infographics

No abstract provided.

Mask What You Can Do For Your Country, Hanna Biedny, Tyler Caparoni, Robert Erianne, Mashaal Syed

Foundations of Public Health - Infographics

No abstract provided.

Mask Use: Pros & Cons, Megan Carty, Megan Donlick, Yuri Matsubara, Janine Tobia

Foundations of Public Health - Infographics

No abstract provided.

Is Your Mask Uncomfortable?, Jake Mulroy, W. Alan Pentecost, Chelcie Puetz, Kelsey Rowe

Foundations of Public Health - Infographics

No abstract provided.

The Evolving Pharmacotherapeutic Landscape For The Treatment Of Sickle Cell Disease., Samir K Ballas

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapies are needed. During the last five years, the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, 54 drugs have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the four drugs (Hydroxyurea, L-Glutamine, Crizanlizumab tmca and Voxelotor) that have been approved by the United States Food and Drug Administration (FDA) based on successful clinical trials. The second category includes 22 drugs that …

Covid-19, Serendipity, And Strange Interlude: Gloria In Absurdicum With An Apology To Ovid, Lawrence Charles Parish, W Clark Lambert

Department of Dermatology and Cutaneous Biology Faculty Papers

The absurd edicts initially issued by several governors, including those of Michigan and New York, prohibiting physicians from ordering hydroxychloroquine for patients suspected of or diagnosed with COV-19 are reprehensible. Their reasoning is beyond the pale.

Hydroxychloroquine was first approved by the FDA in 1955 and has a remarkable safety record in its use as a preventative for malaria and in the treatment of several immunologic and/or light induced diseases. Its use came about serendipitously, and its mechanism of action is unclear, but the fact remains that it seems to work.

Resistance To Ectromelia Virus Infection Requires Cgas In Bone Marrow-Derived Cells Which Can Be Bypassed With Cgamp Therapy., Eric B. Wong, Brian Montoya, Maria Ferez, Colby Stotesbury, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Cells sensing infection produce Type I interferons (IFN-I) to stimulate Interferon Stimulated Genes (ISGs) that confer resistance to viruses. During lympho-hematogenous spread of the mouse pathogen ectromelia virus (ECTV), the adaptor STING and the transcription factor IRF7 are required for IFN-I and ISG induction and resistance to ECTV. However, it is unknown which cells sense ECTV and which pathogen recognition receptor (PRR) upstream of STING is required for IFN-I and ISG induction. We found that cyclic-GMP-AMP (cGAMP) synthase (cGAS), a DNA-sensing PRR, is required in bone marrow-derived (BMD) but not in other cells for IFN-I and ISG induction and for …

Langerhans Cells Orchestrate The Protective Antiviral Innate Immune Response In The Lymph Node., Eric B. Wong, Brian Montoya, Colby Stotesbury, Maria Ferez, Ren-Huan Xu, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

During disseminating viral infections, a swift innate immune response (IIR) in the draining lymph node (dLN) that restricts systemic viral spread is critical for optimal resistance to disease. However, it is unclear how this IIR is orchestrated. We show that after footpad infection of mice with ectromelia virus, dendritic cells (DCs) highly expressing major histocompatibility complex class II (MHC class II^hi DCs), including CD207⁺ epidermal Langerhans cells (LCs), CD103⁺CD207⁺ double-positive dermal DCs (DP-DCs), and CD103⁻CD207⁻ double-negative dermal DCs (DN-DCs) migrate to the dLN from the skin carrying virus. MHC class II^{hi …}

Molluscum Contagiosum Infection With Features Of Primary Cutaneous Anaplastic Large Cell Lymphoma., Doaa Shalabi, John Ringe, Jason B. Lee, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

CD30+ T cell pseudolymphomas (CD30+ PSL) are a group of benign inflammatory cutaneous disorders that can develop in settings of viral infections or drug reactions. Owing to their histological similarities to malignant lymphomas, these benign infiltrates are occasionally misdiagnosed as malignant, causing significant concerns for patients and physicians. Herein, we report a patient with CD30+ PSL associated with molluscum contagiosum whose initial biopsy revealed atypical large CD30-expressing cells, leading to a misdiagnosis of primary cutaneous anaplastic large cell lymphoma and referral to our cutaneous lymphoma clinic. We report this case to demonstrate that reactive CD30+ infiltrate associated with molluscum contagiosum …

Jcph Presentations At The American Public Health Association Annual Conference 2019

JCPH at APHA 2019

No abstract provided.

Incorporating B Cell Activating Factor (Baff) Into The Membrane Of Rabies Virus (Rabv) Particles Improves The Speed And Magnitude Of Vaccine-Induced Antibody Responses., Joseph R Plummer, James P Mcgettigan

Department of Microbiology and Immunology Faculty Papers

B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that links innate with adaptive immunity. BAFF signals through receptors on B cells, making it an attractive molecule to potentiate vaccine-induced B cell responses. We hypothesized that a rabies virus (RABV)-based vaccine displaying both antigen and BAFF on the surface of the same virus particle would target antigen-specific B cells for activation and improve RABV-specific antibody responses. To test this hypothesis, we constructed a recombinant RABV-based vector expressing virus membrane-anchored murine BAFF (RABV-ED51-mBAFF). BAFF was incorporated into the RABV particle and determined to …

Twenty Novel Disease Group-Specific And 12 New Shared Macrophage Pathways In Eight Groups Of 34 Diseases Including 24 Inflammatory Organ Diseases And 10 Types Of Tumors., Bin Lai, Jiwei Wang, Alexander Fagenson, Yu Sun, Jason Saredy, Yifan Lu, Gayani Nanayakkara, William Y Yang, Daohai Yu, Ying Shao, Charles Drummer, Candice Johnson, Fatma Saaoud, Ruijing Zhang, Qian Yang, Keman Xu, Kevin Mastascusa, Ramon Cueto, Hangfei Fu, Susu Wu, Lizhe Sun, Peiqian Zhu, Xuebin Qin, Jun Yu, Daping Fan, Ying H Shen, Jianxin Sun, Thomas Rogers, Eric T Choi, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other genes in microarray data, we made the following findings. (1) When 34 inflammation diseases and tumor types were grouped into eight categories, there was differential expression of the 31 Mφ markers and 45 Mφ TFs, highlighted by 12 shared and 20 group-specific disease pathways. (2) Mφ in lung, liver, spleen, and intestine (LLSI-Mφ) express higher M1 Mφ …

Case-Based Asynchronous Interactive Modules In Undergraduate Medical Education., Tatiana Villatoro, Katherine Lackritz, Joanna S Y Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Undergraduate medical education traditionally consists of 2 years of lecture-based courses followed by 2 years of clinical clerkships. However, over the past couple decades, undergraduate medical education has been evolving toward non-lecture-based integrated curriculums, requiring a collaborative curriculum. Additionally, e-learning platforms have become efficacious and essential to delivering education asynchronously to students. At Thomas Jefferson University, the Pathology and Obstetrics and Gynecology departments collaborated to create a pilot series of case-based asynchronous interactive modules to teach gynecologic pathology in a clinical context, while interweaving other educational components, such as evidence-based medicine, clinical skills, and basic sciences. The case-based asynchronous interactive …

Changes In Body Mass Index And Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate To Tenofovir Alafenamide., Jason J. Schafer, Kaitlin N. Sassa, Jaclyn R. O'Connor, Ayako Shimada, Scott W. Keith, Joseph A. Desimone

College of Pharmacy Faculty Papers

Background: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) can improve renal function and bone mineral density in people with human immunodeficiency virus (PWH). The switch can also negatively influence cholesterol, but changes in body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk are unknown.

Methods: This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PWH who switched from TDF to TAF without switching other ART regimen components. Adults on TDF for ≥1 year with 2 consecutive HIV ribonucleic acid values/mL before a TAF switch were included. Body weight, …

Inactivated Rabies Virus-Based Ebola Vaccine Preserved By Vaporization Is Heat-Stable And Immunogenic Against Ebola And Protects Against Rabies Challenge., Drishya Kurup, Christine R. Fisher, Todd G. Smith, Tiago Abreu-Mota, Yong Yang, Felix R. Jackson, Nadia Gallardo-Romero, Richard Franka, Victor Bronshtein, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Ebola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014-2016 in West Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage.

METHODS: We used preservation by vaporization (PBV), a novel processing technology to heat-stabilize FiloRab1 (inactivated rabies-based Ebola vaccine), a candidate Ebola vaccine, and stored the vials at temperatures ranging from 4°C to 50°C for 10 days to 12 months. …

The Global Crisis Of Antibiotic Resistance, Cindy Hou, Do, Mba

Sepsis Symposium

No abstract provided.

Tracking Progress On Preventing And Treating Sepsis: Cdc's Adult Sepsis Event Surveillance Strategy, Chanu Rhee, Md

Sepsis Symposium

This presentation will discuss the differences between diagnostic and surveillance definitions of sepsis and the use and value of each in clinical settings. Specifically, Dr. Rhee will discuss the CDC’s new ‘Adult Sepsis Event’ surveillance tool to help healthcare facilities assess adult sepsis incidence within their facilities.

Endovascular Management And The Risk Of Late Failure In The Treatment Of Ureteroarterial Fistulas, George Titomihelakis, Anthony Feghali, Tuong Nguyen, Dawn Salvatore, Paul Dimuzio, Babak Abai

Department of Medicine Faculty Papers

Ureteroarterial fistula (UAF) is a rare and life-threatening source of hematuria. A high index of suspicion is warranted for early diagnosis and timely intervention. Because of high perioperative risk and comorbidities in UAF patients, the endovascular approach has become preferred for repair. Infection can complicate this mode of therapy, and treatment with antibiotics is important. Herein we present five cases of secondary UAFs treated with stent graft alone or stent graft and embolization.

Comparison Of Two Commercial Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry (Maldi-Tof Ms) Systems For Identification Of Nontuberculous Mycobacteria., Barbara A. Brown-Elliott, Thomas R. Fritsche, Brooke J. Olson, Sruthi Vasireddy, Ravikiran Vasireddy, Elena Iakhiaeva, Diana Alame, Richard J. Wallace, John A. Branda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Objectives: This multi-center study’s aim was to assess the performance of two commercially-available matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems in identifying a challenge collection of clinically-relevant nontuberculous mycobacteria (NTM).

Methods: NTM clinical isolates (N=244) belonging to 23 species/subspecies were identified by gene sequencing and analyzed using the Bruker Biotyper with Mycobacterial Library v5.0.0 and the bioMérieux VITEK MS with v3.0 database.

Results: Using the Bruker or bioMérieux systems, 92% or 95% of NTM strains, respectively, were identified at least to the complex/group level; 62% and 57%, respectively, were identified to the highest taxonomic level. Differentiation between members …

Antibody Responses Against The Vaccine Antigens Ov-103 And Ov-Ral-2 Are Associated With Protective Immunity To Onchocerca Volvulus Infection In Both Mice And Humans., Parakkal Jovvian George, Jessica A. Hess, Sonia Jain, John B. Patton, Tingting Zhan, Nancy Tricoche, Bin Zhan, Maria Elena Bottazzi, Peter J. Hotez, David Abraham, Sara Lustigman

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin. However, due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy. Additional tools are critically needed including a prophylactic vaccine. Presently Ov-103 and Ov-RAL-2 are the most promising vaccine candidates against an Onchocerca volvulus infection.

METHODOLOGY/PRINCIPAL FINDINGS: Protection induced by immunization of mice with the alum-adjuvanted Ov-103 or Ov-RAL-2 vaccines appeared to be antibody dependent since AID-/- mice that could not mount antigen-specific IgG antibody responses were not …

Pioneers In Dermatology And Venereology: An Interview With Prof. Lawrence C. Parish., Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

No Meaningful Drug Interactions With Doravirine, Lamivudine And Tenofovir Disoproxil Fumarate Co-Administration., Matt S. Anderson, Jocelyn Gilmartin, Li Fan, Ka Lai Yee, Walter K. Kraft, Ilias Triantafyllou, Christina Reitmann, Ying Guo, Rachael Liu, Marian Iwamoto

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration.

METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment …

Equine Or Porcine Synovial Fluid As A Novel Ex Vivo Model For The Study Of Bacterial Free-Floating Biofilms That Form In Human Joint Infections, Jessica M. Gilbertie, Lauren V. Schnabel, Noreen J. Hickok, Megan E. Jacob, Brian P. Conlon, Irving Shapiro, Javad Parvizi, Thomas P. Schaer

Department of Orthopaedic Surgery Faculty Papers

Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such …

Identification Of Emergency Care-Sensitive Conditions And Characteristics Of Emergency Department Utilization., Anita A. Vashi, Tracy Urech, Brendan Carr, Liberty Greene, Theodore Warsavage, Renee Hsia, Steven M. Asch

Department of Emergency Medicine Faculty Papers

Importance: Monitoring emergency care quality requires understanding which conditions benefit most from timely, quality emergency care.

Objectives: To identify a set of emergency care-sensitive conditions (ECSCs) that are treated in most emergency departments (EDs), are associated with a spectrum of adult age groups, and represent common reasons for seeking emergency care and to provide benchmark national estimates of ECSC acute care utilization.

Design, Setting, and Participants: A modified Delphi method was used to identify ECSCs. In a cross-sectional analysis, ECSC-associated visits by adults (aged ≥18 years) were identified based on International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis …

Non-Thermal Plasma-Induced Immunogenic Cell Death In Cancer: A Topical Review., Marian Khalili, Lynsey Daniels, Abraham Lin, Fred C. Krebs, Adam E. Snook, Sander Bekeschus, Wilbur B. Bowne, Vandana Miller

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational …

Bitter Taste Receptors For Asthma Therapeutics., Ajay P. Nayak, Sushrut D. Shah, James V. Michael, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions. Although these approaches provide relief from exacerbations, questions remain on their long-term efficacy and safety. Furthermore, current therapeutics do not address progressive airway remodeling (AR), a key pathological feature of severe obstructive lung disease. Strikingly, agonists of the bitter taste receptors (TAS2Rs) deliver robust bronchodilation, curtail allergen-induced inflammatory responses in the airways and regulate airway smooth muscle (ASM) cell proliferation and mitigate …

From Vaccine Vector To Oncomodulation: Understanding The Complex Interplay Between Cmv And Cancer., Nicole A. Wilski, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8+ T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the effcacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much …

When An Infected Meniscus Portends A Perforated Viscus, Michelle Hannon, Stephen Zachariah, Neha Bansal Etherington, Anusha Govind, Devin Weber, Bryan Hess

Division of Infectious Diseases and Environmental Medicine Faculty Papers

A 59-year-old woman with a status of post–renal transplant 7 years prior for autosomal dominant polycystic kidney disease on tacrolimus and mycophenolate mofetil presented with subacute left knee and right wrist pain. She received local steroid injections to both areas as an outpatient without improvement in her symptoms. She had recently traveled to India, her home country, to visit relatives. Aspiration of the knee revealed 4+ acid fast bacilli on smear, and she was taken for surgical debridement. She was started on empiric antibiotics for presumed infection with rapidly growing mycobacteria. Her course was complicated by acute onset abdominal pain …

Outcomes Of Haploidentical Vs Matched Sibling Transplantation For Acute Myeloid Leukemia In First Complete Remission., Armin Rashidi, Mehdi Hamadani, Mei-Jie Zhang, Hai-Lin Wang, Hisham Abdel-Azim, Mahmoud Aljurf, Amer Assal, Ashish Bajel, Asad Bashey, Minoo Battiwalla, Amer M. Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Javier Bolaños-Meade, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Stefan Ciurea, Edward Copelan, Corey Cutler, Andrew Daly, Miguel-Angel Diaz, Nosha Farhadfar, Robert P. Gale, Siddhartha Ganguly, Michael R. Grunwald, Theresa Hahn, Shahrukh Hashmi, Gerhard C. Hildebrandt, H. Kent Holland, Nasheed Hossain, Christopher G Kanakry, Mohamed A. Kharfan-Dabaja, Nandita Khera, Yener Koc, Hillard M. Lazarus, Jong-Wook Lee, Johan Maertens, Rodrigo Martino, Joseph Mcguirk, Reinhold Munker, Hemant S. Murthy, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Neil D. Palmisiano, Sagar Patel, Joseph Pidala, Rebecca Olin, Richard F. Olsson, Betul Oran, Olov Ringden, David Rizzieri, Jacob Rowe, Mary Lynn Savoie, Kirk R. Schultz, Sachiko Seo, Brian C. Shaffer, Anurag Singh, Melhem Solh, Keith Stockerl-Goldstein, Leo F. Verdonck, John Wagner, Edmund K. Waller, Marcos De Lima, Brenda M. Sandmaier, Mark Litzow, Dan Weisdorf, Rizwan Romee, Wael Saber

Department of Medical Oncology Faculty Papers

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs …

Table Of Contents: The Medicine Forum Volume 20, 2018-2019

The Medicine Forum

Clinical Images

Case Reports

• Cardiology
• Endocrinology
• Gastroenterology and Hepatology
• Hematology and Oncology
• Infectious Disease
• Pulmonary Medicine
• Rheumatology

Original Article

Editorial

Literature Review

Creative Writing