Digital Commons Network^™

Genetic Drivers And Tumor Milieu Analysis In Mantle Cell Lymphoma, Sunandini Sharma

Theses & Dissertations

Mantle Cell Lymphoma (MCL) is a B-cell lymphoma characterized by t(11;14) leading to CyclinD1 (CCND1) overexpression with highly variable clinical response. Although the tumor intrinsic mechanisms have been fairly studied, the role of the tumor microenvironment (TME) in survival and therapeutic responses is marginally examined. Herein, we integrated high-throughput genomics and characterized TME using a highly multiplexed, spatially resolved, single-cell digital pathology approach termed imaging mass cytometry (IMC) to delineate the tumor-immune landscape. We identified eight MCL genomic subtypes with distinct signatures and prognoses. Subsets C2, C5, and C6 had poorer outcomes with a 5-year overall survival (OS) of 33-50% …

Impact Of Nutritional Status And Placental Malaria Infection On Pregnancy Outcome In A Population Of Nigerian Maternal-Infant Dyads, Shirley F. Delair

Theses & Dissertations

Nigeria is the most populous country in Africa and accounts for one-quarter of the newborn mortality on the continent. Most newborn deaths are from prematurity (33%), infections (33%), and intrapartum complications (31%). Using an adapted analytical framework for the study of child survival in developing countries, this dissertation aimed to look at the pregnancy outcome of a population of Nigerian women and their offspring by looking at proximate determinants of health from nutritional status and environmental conditions. In Chapter 1, we characterized the micronutrients of the mother-infant dyads, looking specifically at concentrations of vitamin D and its metabolites. In Chapter …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Bridging The Information Divide: Leveraging The Learning Health System To Understand Rural-Urban Health Disparities In The Covid-19 Era, Alfred J. Anzalone

Theses & Dissertations

The examination of healthcare disparities, which the COVID-19 pandemic exacerbated, revealed a pronounced divide between rural and urban settings. This divide particularly underscored the challenges of integrating rural healthcare into the Learning Health System (LHS) and utilizing real-world data (RWD) in response to a public health emergency. Our investigation expanded the growing body of literature on the rural mortality penalty, encompassing the period following the COVID-19 pandemic. By employing an LHS-enabled centralized platform of RWD, we assessed the impact of rurality on adverse COVID-19 outcomes (Aim 1), focusing on inpatient adverse events and the effectiveness of treatments and vaccinations across …

Viral Hepatitis And Hiv Screening Amongst Inpatients With Substance Use Disorder, Christine Papastamelos, Md, Elizabeth Novick, Md, Carolyn Kramer, Md, John Zurlo,Md, Nikhil Seval, Md, Daniel Taupin, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• ~67,000 individuals in Philadelphia county are estimated to be living with opioid use disorder (OUD).¹
• Persons who inject drugs (PWID) are at disproportionately greater risk of acquiring HIV and viral hepatitis compared to the general public.²
• PWID are less likely to receive timely HIV and viral hepatitis screening in the outpatient setting given complex biopsychosocial barriers, including homelessness, mental illness, lack of insurance, incarceration, and stigma.^3,4

Medication Access Barriers To Hepatitis C Anti-Viral Therapy Following Transplantation Of Hepatitis C Positive Donors Into Hepatitis C Negative Recipients, Harry Rockower, Md, Sarah Yeager, Pharmd, Jami Schulte, Pharmd, Dagan Coppock, Md, Jonathan Fenkel, Md, Katherine Belden, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Over the past decade there has been a paradigm shift in solid organ transplantation with the use of Hepatitis C (HCV) positive donor organs for HCV negative recipients.
• This evaluation looks through the lens of insurance approval for direct acting antivirals (DAA) and the process needed for obtaining and ensuring affordability of these medications.
• While the AASLD/IDSA guidelines recommend early initiation of pangenotypic DAA therapy after organ transplant without the need to confirm recipient viral replication many centers often initiate the DAA approval process after viremia is detected due to insurance barriers.¹
• The process for obtaining insurance approval …

Streamlined Pre-Authorization Expedites Patient Discharges From Stroke Units To Rehabilitation Centers, Michael Vo, William Nguyen, Matthew Trotter, Jeffrey Zhou, Glenn A. Gonzalez, Eric Mong, Rene Daniel, Ross-Jordan Elliott, James Harrop

Health Equity and Quality Improvement (HEQI) Summit

Background

Problem statement: Patient discharge from neurosurgical stroke units to rehabilitation centers is a complex administrative and clinical endeavor involving a population often with cognitive and motor morbidity that can be intensified with extensive hospital length of stay (LOS).

Project aim: This project aims to analyze the change in LOS due to the introduction of liaisons, who advocate for and expedite pre-authorization, rounds, and plan of care establishment for patients with strokes.

Optimizing Resource Allocation Of A Covid-19 Prophylactic In Immunocompromised Hosts, Julianna Tolotta, Abigail Hoover, Michael Joseph, Angelinia Liddy, Anshel Kenkare, Dagan Coppock

Health Equity and Quality Improvement (HEQI) Summit

Introduction

• COVID-19 presented unique challenges for the care of immunocompromised individuals.
• Patients with suppressed immune systems lack the ability to mount a robust response to vaccines, leading to an increased likelihood of developing severe COVID-19 responses and increased mortality.
• Astra-Zeneca developed Evusheld, a monoclonal antibody (Tixagevimab/cilgavimab) as a COVID-19 prophylaxis to target the SARS-CoV-2 spike protein.¹
• In December 2023, the FDA enacted an Emergency Use Authorization (EUA) for Evusheld in immunocompromised individuals and TJUH developed a roll-out plan.²
• Thomas Jefferson University Health (TJUH) distributed the drug using a tiering system that ranked the degrees of immunocompromising conditions for …

Public And Community Perceptions Of Safe Injection Sites, Bahram Pashaee, Mph, Gary Kaplan, Mslis, Amy Leader, Drph, Mph

Health Equity and Quality Improvement (HEQI) Summit

Background

• The opioid epidemic began in 1999 and the number of deaths from overdoses has since quadrupled by 2019
• 50,000 deaths in the US in 2019 from opioid overdoses and the numbers increase each year
• Research Question: What are the public’s and communities' perceptions of safe injection sites?

Understanding The Non-Canonical Regulation Of Srebp In Aspergillus Fumigatus, Muhammad Abubakar Khan

Dartmouth College Ph.D Dissertations

Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive pulmonary aspergillosis (IPA), with high mortality rates in immunocompromised individuals. Adaptation to the hypoxic microenvironment of IPA is crucial for fungal virulence. The transcription factor SrbA, a Sterol Regulatory Element-Binding Protein (SREBP) homolog, plays a key role in this hypoxic response and regulates genes involved in hypoxic growth, sterol biosynthesis, and azole resistance, making it an attractive therapeutic target.

However, SrbA activation in A. fumigatus lacks critical components of the canonical SREBP pathway, such as SCAP, Site-1 protease (S1P), and Site-2 protease (S2P). Instead, the rhomboid protease RbdB, signal peptide peptidase …

Aids Associated Cryptosporidial And Cmv Cholangiopathy, Nada Alsharif, Luxhman Gunaseelan, Mamoun Souleiman, Cecilia Big

Conference Presentation Abstracts

Introduction AIDS-associated cholangiopathy is a biliary tract condition seen in AIDS patients who are severely immunosuppressed, contributing to significant mortality in this population even in developed countries with access to HAART therapy. Case Description We discuss a thirty-six-year-old HIV positive male, non-compliant with HAART therapy, who presented with a one year history of weight loss, persistent fatigue and chronic diarrhea, which had worsened significantly in the past few weeks. Routine laboratory studies on presentation indicated elevated liver enzymes and alkaline phosphatase, a CD4 count of two, and a high HIV RNA count of 8.8 million. Imaging via CT abdomen and …

Streptococcus Pneumoniae Neck Abscess In A Patient With Waldenstrom's Macroglobulnemia, Tanya Amal, Paul Johnson, Ayesha Sharif

Conference Presentation Abstracts

Patients with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma are at increased risk of sinopulmonary infections, pyelonephritis, and septicemia. The underlying etiology is assumed to be immune dysregulation. Patient's with Waldenstrom's macroglobulinemia have been shown to have somatic mutations in the "V". "D" and "J/H' segments of immunoglobulin gene. These mutations can affect affinity maturation and formation of memory B cells. Subsequently patient's with Waldenstrom's macroglobulinemia also have a suboptimal response to vaccination against Staphylococcus aureus, Streptococcus pneumoniae and Varicella, similar to those with multiple myeloma. Severe infections with gram positive organisms causing multifocal osteomyelitis, pleural effusion and sepsis have also been reported with …

Photodynamic Treatment Of Staphylococcus Aureus With Non-Iron Hemin Analogs In The Presence Of Hydrogen Peroxide, Badhu Prashanthika Sivasubramaniam, Benjamin M. Washer, Yuichiro Watanabe, Kathryn E. Ragheb, J. Paul Robinson, Alexander Wei

Department of Chemistry Faculty Publications

Bacteria subjected to antiseptic or antibiotic stress often develop tolerance, a trait that can lead to permanent resistance. To determine whether photodynamic agents could be used to counter tolerance, we evaluated three non-iron hemin analogs (M-PpIX; M = Al, Ga, In) as targeted photosensitizers for antimicrobial photodynamic inactivation (aPDI) following exposure to sublethal H2O2. Al-PpIX is an active producer of ROS whereas Ga- and In-PpIX are more efficient at generating singlet oxygen. Al- and Ga-PpIX are highly potent aPDI agents against S. aureus and methicillin-resistant strains (MRSA) with antimicrobial activity (3 log reduction in colony-forming units) at nanomolar concentrations. The …

Hepatitis C Management For Individuals In Custody, Oluronke D. Akinola

Doctor of Nursing Practice Projects

The hepatitis C virus (HCV) is a pathogen that spreads through blood and causes hepatitis C disease, a liver infection. Early infection symptoms are rare, making it a silent killer. HCV, the chronic liver disease accounts for half of all hepatocellular carcinoma cases and is the leading cause of liver transplantation in the US. This quality improvement project aimed to create an educational toolkit for the Department of Correction staff working with individuals in custody refusing HCV treatment. The education tools comprised an infographic flyer (English and Spanish) to teach individuals in custody about HCV treatment and a PowerPoint presentation …

Risk Factors For Hepatitis A Hospitalizations And Mortality In Kentucky's 2018 Hepatitis A Outbreak, Tanya Campbell

Walden Dissertations and Doctoral Studies

In 2018, the state of Kentucky faced an outbreak of Hepatitis A virus (HAV), which led to a significant increase in HAV cases, hospitalizations, and fatalities. The social-ecological model (SEM) was used in a cross-sectional design to identify the factors associated with this outbreak. This approach employed secondary data extracted from the National Notifiable Disease Surveillance System (NNDSS). Logistic regression was used to test hypotheses determining homelessness, drug use, and HAV vaccine status were related to HAV hospitalizations. There was a statistically significant association between the covariate age and HAV hospitalization (p = 0.004), and between homelessness and hospitalization (p < .001); however, associations between drug use and HAV vaccine status were not statistically. Intervention programs should target homeless populations; such targeting can lead to a reduction in HAV infections and HAV outbreaks. Implications for positive social change include motivation for policymakers and public health officials to assist in curtailing hospitalization and mortality rates caused by HAV in high-risk groups. Targeted prevention and intervention measures can mitigate the incidence of HAV in high-risk populations and enhance their health prospects.

Toxicological Impacts Of River Chemical Spills In Affected West Virginia Counties, Janice Lorraine Taylor Peters

Walden Dissertations and Doctoral Studies

Factors such as geographical location/proximity and exposure to external environmental events, as well as poor regulatory processes, are known to increase the risk for cancers among affected populations. There is still a gap in the literature related to the incidence of cancers in specific regions with heavy industrialization and environmental health hazards. In West Virginia, chemical contamination events have occurred in or near water systems. The goal of this quantitative, retrospective study was to discover whether there were any differences in the incidence of disease or adverse health effects and cancers due to chemical contamination in four counties (Kanawha, Mingo, …

Evaluating Critical Thinking In New Graduate Nurses Through Reflective Journaling, Robbin Guynn

Sigma Foundation for Nursing Research Grant Reports

The purpose of this project is to look at the development of critical thinking in newly graduated nurses to see if reflective journaling can help accelerate the process.

Expanding Complex Morpholines Using Systematic Chemical Diversity, Sunny Ann Tang, Afton Fults, Shelton R Boyd, Nikhil Gattu, Kevin A Tran, Jiayi Fan, Kevin R Mackenzie, Timothy Palzkill, Damian W Young, Srinivas Chamakuri

Faculty, Staff and Students Publications

The morpholine heterocycle is a structural unit found in many bioactive compounds and FDA-approved drugs, but the generation of more complex C-functionalized morpholine derivatives remains considerably underexplored. Using systematic chemical diversity (SCD), a concept that guides the expansion of saturated drug-like scaffolds through regiochemical and stereochemical variation, we describe the synthesis of a collection of methyl-substituted morpholine acetic acid esters starting from enantiomerically pure amino acids and amino alcohols. In total, 24 diverse substituted morpholines were produced that vary systematically in regiochemistry and stereochemistry (relative and absolute). These diverse C-substituted morpholines can be directly applied in fragment screening or incorporated …

Parental Knowledge Of Signs, Symptoms, And Risk Factors Associated With Sudden Cardiac Arrest In Adolescent Athletes, Lisa A. Lattera-Hughes

Walden Dissertations and Doctoral Studies

Exercise is associated with unmasking underlying cardiac disorders and increasing an athlete’s risk for experiencing a sudden cardiac arrest (SCA) event during sports. Parental knowledge is an important component of health education in relation to the future of their child’s health. The purpose of this quantitative research study was to assess the relationship between parental knowledge about warning signs, symptoms, and risk factors associated with SCA in adolescent athletes and parental willingness to participate in an educational intervention to learn about SCA. The theoretical framework was based on Nutbeam’s conceptual model of health literacy. Eightyone parents whose adolescent children participated …

Navigating Clinical Uncertainty: A Convergence Of Hiv, Positive Ana, And Genetic Cardiomyopathy, Ioannis Karageorgiou, Nicolaas Schimmel, Phillip Marchese, Tawhida Khatoon

Conference Presentation Abstracts

We present a case involving a 36-year-old male with a complex medical history, including hypertension, hyperlipidemia, cerebrovascular accident (CVA), and Hypertrophic Obstructive Cardiomyopathy (HOCM). The patient presented with a week-long history of chest, lower extremity, and back pain, tingling, and a history of recurrent falls. The initial presentation, combined with his history of ICD placement in 2019, led to investigations for Acute Coronary Syndrome (ACS) and ICD malfunction. The patient's initial laboratory workup, which included a comprehensive drug screen, was unremarkable except for mild normocytic anemia and elevated protein levels. CT scans of the head and spine and X-rays of …

Global Prevalence Of Aspirin Use For Primary Prevention Of Cardiovascular Disease: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Sang Gune K Yoo, Mark D Huffman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Medical School Watercooler Newsletter - May 2, 2024, Lindsey Lyle

Watercooler Newsletter

This is the May 2, 2024 edition of the Frederick P. Whiddon College of Medicine’s newsletter - Watercooler.

Contents Include

• GME coordinators establish wellness committee to address stress and burnout
• Ramani selected as CMO for Children’s & Women’s Hospital
• Six students earn travel scholarships for state pediatrics meeting
• Molecular lab launches genomic testing for personalized cancer care
• Resident and Fellow Academic Expo set for May 1

Unplanned Pregnancy As An Independent Risk Factor For Antepartum Si In A Post Roe Vs. Wade World, Rianna Mcnamee

Rowan-Virtua Research Day

Abstract: The objective of this literature review is to determine whether unplanned pregnancy is an independent risk factor for developing antepartum SI. Background: The Supreme Court of the United States of America recently ruled that the constitution of the United States does not confer a right to abortion to its citizens. As of October 2023, twenty-one states had developed full or partial bans on abortion, resulting in millions of Americans residing in areas where terminating unplanned pregnancy is not a viable option. There is evidence that indicates antepartum suicidal ideation (SI) is higher than that of the general population, however …

Lower Extremity Weakness In The Setting Of Covid Myositis, Christopher Dellmyer, Frank Wheeler

Rowan-Virtua Research Day

Bilateral lower extremity weakness has numerable causes including stroke, peripheral neuropathy, deconditioning, Guillain-Barre, Multiple Sclerosis, anterior cord syndrome, trauma, spinal epidural abscess and many more. It is imperative however, that we investigate and understand more rare causes of lower extremity weakness. Here we present the case of a 74-year-old female presented to the ED with a complaint of lower extremity weakness due to Covid myositis causing significant bilateral lower extremity weakness.

Case Report: Dysphagia In Inclusion Body Myositis Leading To Respiratory And Gastrointestinal Complications, Veroneka Mikhail, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Inclusion Body Myositis (IBM) stands as a rare and complex neuromuscular disorder (NMD) characterized by progressive muscle weakness and atrophy. Among its cardinal symptoms are dysphagia and respiratory distress, which are the most common cause of death in this disease. While the differential diagnosis of respiratory distress is vast and includes aspiration, pneumonia, acute coronary syndrome, emphysema, and congestive heart failure, a clinician should recognize that respiratory distress can also be secondary to dysphagia in NMDs like IBM and can quickly become life threating. Here we present the case of a 68-year-old female with a history of IBM who presented …

Case Report: Monkeypox Diagnosed In The Ed, Richard M. Baluyot, Joseph Pagano, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Rashes are one of the most common chief complaints we see as emergency medicine physicians on a day-to-day basis. Most of them tend to be self-limited and require very little workup and can be discharged home; however, it is our job to try to identify rashes that may require isolation in order to prevent an outbreak in our communities. Here we present a case of one such rash that has gained major media attention as of late, Monkeypox.

Rocky Mountain High Titer: An Unusual Delay In Surgical Clearance, Lisa Ting Huang, Victoria Wong Murray, Judith Anne Lightfoot

Rowan-Virtua Research Day

Rocky Mountain Spotted Fever, carried by a variety of ticks, is classically caused by Ricksettsia rickettsii, but may be clinically indistinguishable from other bacteria in the same family. A 47 year old female presented in December for presurgical clearance due to fever, petechial rash on the thighs and trunk, and ecchymoses on the forearms, gluteal region, and toes; additional symptoms included arthralgia in bilateral lower limbs. Bacterial infection was suspected and empirical doxycycline was initiated pending specific PCR testing. Patient adherence was unclear at the followup visit, so IV ceftriaxone was initiated and repeated immunoglobulin testing was ordered to …

A Case Of Hhv-6 Viral Meningitis, Mohammad A. Rattu, Wayne Tamaska

Rowan-Virtua Research Day

Meningitis is the inflammation of the meninges and associated with abnormal cell count in the cerebrospinal fluid (CSF). The lack of bacterial growth in cultures, most commonly referred to as aseptic meningitis, is frequently caused by viruses [2]. Viruses have become more common as the prevalence of bacterial meningitis has decreased secondary to vaccination use, with viral meningitis being the most common form among countries. Viral meningitis will present with fever, headache, photophobia, neck stiffness and nausea and vomiting. Younger children however may not show any signs of meningeal irritation. Viral meningitis is usually self-limiting and with good prognosis; however, …

Clostridium Perfringens Sepsis From A Hepatic Abscess With Hemolysis And Renal Failure, Requiring Hemodialysis, Joel Collins Ii, Katelyn Courtney, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

The prognosis of sepsis caused by Clostridium perfringens is extremely poor, with a mortality rate of 70%-100%. Management includes antibiotic regimens specific to toxin production as well as source control via surgical or interventional mechanisms. We report a case of a 64-year-old male who presented with right upper quadrant (RUQ) abdominal pain and was diagnosed with Clostridium perfringens bacteremia with associated acalculous cholecystitis, hepatic abscess, and acute renal failure requiring hemodialysis. It is felt that early hemodialysis was an associated factor in the patient's survival.

Investigating Risk Factors Contributing To The High Incidence Of Covid-19 Among The Diné People Of The Navajo Nation, Elizabeth Lila Reynolds

Rowan-Virtua Research Day

Background: COVID-19 became international news in December 2019 and subsequently impacted global health. The research shows that the Diné people of the Navajo Nation were one of the most severely impacted populations¹. The Navajo Nation is a region spanning Arizona, New Mexico, and Utah that is composed of North American indigenous people known as the Diné. Purpose: To explore the risk factors contributing to the increased rates of COVID-19 infection and severity of infection among the Diné people. Methods: This literature review research process utilized PubMed and JAMA to find scholarly articles on this topic. Search terms …