Digital Commons Network^™

Inhibition Of Cyclophilin D Rescues Cardiac Function And Bioenergetic Defects Caused By Neonatal Hypoxia, Jonathan R. Burris, Gisela Beutner, Min Yee, Bartholomew V. Simon, Michael F. Swartz, Kathryn B. Boudreau, Ethan D. Cohen, Chaitanya A. Kulkarni, Prottoy Hasan, Hongyue Wang, Karen L. De Mesy Bentley, György Hajnóczky, George M. Alfieris, Eric M. Small, Paul S. Brookes, Michael A. O'Reilly, George A. Porter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Increased oxygen levels at birth regulate myocyte bioenergetic and structural maturation controlled by mitochondrial cyclophilin D (CypD). We evaluated mechanisms of neonatal hypoxic cardiac dysfunction by exposing neonatal mice to 12% oxygen and studied cardiac bioenergetics, myocyte maturation, and function. Hypoxia decreased the activity/assembly of electron transport chain complex I, uncoupled oxidative phosphorylation, increased proliferation, decreased differentiation, increased ventricular mass, and decreased cardiac function. CypD inhibition rescued most hypoxia-mediated effects and increased cardiac function. In conclusion, neonatal hypoxia alters cardiac bioenergetics, myocyte maturation, and cardiac function through CypD-dependent pathways, providing potential therapeutic targets for neonatal cardiac dysfunction.

Speed Of Intravenous Fluid On Glycocalyx Integrity And Central Blood Volume In A Porcine Septic Shock Model, Yosef Levenbrown, Md Jobayer Hossain, Paul T. Fawcett, Marjorie Postell, Anne M. Hesek, Lynell S. Jones, James P. Keith, Thomas H. Shaffer

Department of Pediatrics Faculty Papers

BACKGROUND: It is unclear whether the rate of intravenous fluid (IVF) administration in sepsis influences glycocalyx breakdown. This study aimed to measure the effect of rapid versus slow fluid bolus in a septic pig model on the integrity of the glycocalyx by measuring the serum levels of heparan sulfate and syndecan-1, breakdown products of the glycocalyx. Because endothelial glycocalyx is composed of apical cell membrane-bound proteoglycans such as syndecan-1, covalently bound with long linear glycosaminoglycans such as heparan sulfate, shedding of these different glycocalyx components is closely related. Additionally, we measured central blood volume (blood volume in the heart and …

Mitochondrial Dna Replication Is Regulated By Endoplasmic Reticulum-Mitochondrial Contact Sites, The Mitochondrial Calcium Uniporter, And Manganese, Amaia Lopez De Arbina, Angelica Zamudio-Ochoa, Mikel Muñoz-Oreja, Diego Perez-Rodriguez, Laura Mosqueira-Martín, Rebecca Lasalandra, Marina Villar-Fernandez, Uxoa Fernandez-Pelayo, Laura Rodriguez-Gomez, Seungtae Lee, Francisco Gil-Bea, Nerea Osinalde, Ainara Vallejo-Illaramendi, Dmitry Temiakov, Antonella Spinazzola, Ian Holt

Department of Biochemistry and Molecular Biology Faculty Papers

Mitochondrial DNA replication occurs at contact sites between the endoplasmic reticulum (ER) and mitochondria (ERMCS). Beyond the known role of the tubular ER protein RTN4, the factors regulating this process are poorly defined. Here, we show that repressing the ER protein ERLIN2 in human fibroblasts depletes ER-mitochondrial contact sites and inhibits mitochondrial DNA replication, as does silencing RTN4 or the ER-mitochondrial tether GRP75. GRP75 or RTN4 scarcity also decreases the level of the mitochondrial calcium uniporter (MCU), whose inhibition blocks mitochondrial DNA synthesis. Because ERMCS depletion did not diminish mitochondrial calcium, and MCU complex can transport manganese, we tested whether …

Comparison Of Pfas-Free Hydrophobic Layer-By-Layer Coatings For Cellulosic Textiles: Evaluation Of Water Repellency, Mechanical Durability, And The Effects Of Fabric Construction, Elvira Isenzhulova, Radika Bhaskar

School of Design and Engineering Papers

Environmentally safe water-repellent coatings are urgently needed for the textile industry as an alternative to PFAS-based finishes. Challenges include development of coatings that are effective in imparting both water repellency and mechanical durability, with relatively simple synthesis to promote industry use. This study compared the performance and abrasion resistance of two different bio-based, layer-by-layer (LbL) self-assembled hydrophobic coatings for cellulosic fibers. Textile samples were coated with bilayers composed of negatively charged plant-derived carnauba wax and a positively charged component: either poly-L-lysine or lower-cost zinc oxide nanoparticles. To investigate the influence of surface microroughness on coating adhesion and performance, two different …

Quantifying Sleep Wake Rhythms In The Hospital Environment With Digital Technologies, Carsten Skarke, Nadim El Jamal, Michael V. Genuardi, Thomas G. Brooks, Antonijo Mrčela, Nicholas F. Lahens, Makayla Cordoza, Sean Sarles, Amarachi Mbadugha, Dineth R. Karunamuni, Shikhar Gupta, Charles J. Bae, Amita Sehgal, Thomas P. Cappola, Jacob T. Gutsche, Pavan Atluri, Nimesh D. Desai, Michael A. Acker, Gregory R. Grant, Richard J. Schwab, Ilene M. Rosen, Garret A. Fitzgerald

Division of Cardiology Faculty Papers

Postoperative clinical care is prone to circadian desynchronization that may influence health outcomes. In an exploratory, feasibility-oriented and signal-exploration effort, we collected 1.8 million data points using 11 remote sensors during preoperative, in-hospital and post-discharge settings in 13 elective cardiac surgery patients (5.2% enrolled from 252 screened). We found that room traffic continued during nighttime with ≥1 visit/h. Sound levels exceeded the recommended 45 dBA threshold (51.9 ± 3.3 vs. 48.3 ± 4.2 dBA during nighttime). Brightness dropped at night (89.9 ± 87.7 to 3.7 ± 9.8 lux), but bright light exposures occurred. Ambient room temperature lacked sleep-inducing diurnal variability. …

Out-Of-Pocket Costs And Antihypertensive Medication Use Among Veterans: A Natural Experiment, Alexander R. Zheutlin, Alexander Chaitoff, Daniel Addo, Joshua A. Jacobs, Catherine G. Derington, Eric L. Stulberg, Peter A. Glynn, Bernardo Modenesi, Jordana B. Cohen, Adam P. Bress

Department of Neurology Faculty Papers

BACKGROUND: Blood pressure (BP) control remains suboptimal in the United States despite available low-cost antihypertensive medications. Even small out-of-pocket medication costs may contribute to adherence. We determined whether $0 versus >$0 out-of-pocket costs for antihypertensive medications is associated with differences in adherence, discontinuation, BP control, and cardiovascular outcomes.

METHODS: We included veterans with newly diagnosed hypertension who initiated antihypertensive medication in the Veterans Health Administration from 2004 to 2022. A fuzzy regression discontinuity design with 2-stage residual inclusion leveraged differences in medication copay policy at a 50% service-connected disability threshold (≥50% service-connected disability: $0 out-of-pocket cost versus < 50%: $8 monthly cost). Outcomes included 1-year medication nonadherence (proportion of days covered < 80%), 1-year medication discontinuation (no medication in the final 90 days of the study year), 1-year BP control (systolic BP/diastolic BP < 140/90 mm Hg and < 130/80 mm Hg) and cardiovascular disease events (myocardial infarction, coronary revascularization, peripheral artery disease, or stroke).

RESULTS: Among 417 …

Deep Learning And Experimental Validation Of Brca1-Associated Protein-1 Missense Variant Pathogenicity In Uveal Melanoma, Nikhil Davé, David J. Taylor Gonzalez, Mak B. Djulbegovic, Linda A. Cernichiaro-Espinosa, Benjamin A. King, Carol L. Shields, Matthew W. Wilson

Wills Eye Hospital Papers

OBJECTIVE: To benchmark the pathogenicity predictions of AlphaMissense, a deep learning model, against high-throughput functional scores from saturation genome editing (SGE) for all experimentally tested BRCA1-associated protein-1 (BAP1) missense variants in uveal melanoma (UM).

DESIGN: Cross-sectional analytical study comparing computational predictions with experimentally derived functional classifications and clinical annotations.

SUBJECTS PARTICIPANTS AND/OR CONTROLS:  ClusteredAll 4619 BAP1 single amino acid substitutions profiled in a published Regularly Interspaced Short Palindromic Repeats-Cas9 SGE viability assay. No separate control cohort was required. Clinical Variant Database (ClinVar)-annotated variants within this set served as an independent reference.

METHODS: Saturation genome editing log₂-fitness …

Knowledge, Skills, And Attitudinal Gaps In Fibrodysplasia Ossificans Progressiva Diagnosis And Management In The United States, Patrice Lazure, Matthew Drake, Michelle Davis, Corrie Crowe, Zvi Grunwald, Lu Fan, Suzanne Murray

Department of Anesthesiology Faculty Papers

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and disabling disease. Preventing unnecessary and/or harmful medical procedures to patients requires early and accurate diagnosis, multidisciplinary care, and access to specialists with FOP expertise. This study aims to assess the needs of healthcare providers (HCPs) when providing care to patients with FOP. Knowledge, confidence, and management practices were measured through a short awareness survey, completed by 400 HCPs from different specialties who may encounter patients with FOP. Complementary qualitative data were obtained from a dialogue session about FOP. Quantitative data was analyzed using descriptive and inferential analysis, while qualitative data underwent thematic …

Stricturing Diseases Of The Gastrointestinal Tract—Current Clinical Practice, Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Gastrointestinal stricture can occur in the esophagus, stomach, small intestine, colon, and anorectum. Most of the strictures are benign. The prevalence of esophageal strictures (ES) secondary to eosinophilic esophagitis has increased. Pyloric stenosis (PS) is rarely seen in clinical practice. Sleeve stenosis (SS) and stomal stenosis or gastrojejunal anastomotic stricture (GJAS) are increasingly seen due to bariatric surgery. Crohn's disease (CD) remains a significant challenge even in the biologic era. The symptomatology of strictures depends on the location, severity, and underlying cause. Imaging studies and endoscopic procedures are the primary investigations to diagnose and evaluate strictures. Various treatment modalities are …

Maternal Inflammation Alters Nuclear And Mitochondrial Dna Methylation Patterns In Neonatal Brain Monocytes, Andrew Ebenezer, Jonathan Hicks, Brooke Hollander, Alexander Hone, Mona Batish, Robert Akins, Adam Marsh, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic ischemic encephalopathy (HIE) is a common birth complication that can cause death or lifelong disabling conditions like cerebral palsy, epilepsy, and autism. It is well established that maternal infection and inflammation are significant risk factors for HIE but reasons for this increase in neurological risk to the offspring remain unknown. Inflammation or infection are associated with epigenetic changes and may contribute to the increased risk of neurodevelopmental disability in exposed offspring. Here, we analyzed and compared DNA methylation patterns in brain monocytes isolated from control, maternal immune activation (MIA), and an inflammation sensitized HIE (IS-HIE) CF-1 mouse model …

Hydatid Cyst In The Right Ventricle Leading To Tricuspid Stenosis And Heart Failure: A Case Report, Muhammad Sheraz Hameed, Syed Rafay Hussain Zaidi, Shafaq Saleem, Muhammad Ahsan, Sarah Rahman, Azeen Razzaq, Ali Iqbal, Muhammad Sohaib Alvi, Muhammad Usama Naveed

Department of Medicine Faculty Papers

BACKGROUND: Cystic hydatid infection is a parasitic disease caused by the larval stages of Echinococcus granulosus, most commonly involving the liver and lungs. Cardiac involvement is rare, accounting for less than 2% of cases, with the left ventricle being the most commonly affected site. Involvement of the right ventricle is extremely uncommon and may lead to life-threatening complications such as tricuspid valve obstruction and hemodynamic compromise.

CASE PRESENTATION: We report a rare case of a 42-year-old patient who presented to the emergency department with exertional dyspnea, hemoptysis, chest pain, syncope, peripheral edema, and signs of right-sided heart failure. The patient …

Health Professional Education Associations: What Other Professions Teach Us About Building Resources, Community, And Advocacy For Midwifery Educators, Kim Q. Dau, Ms, Cnm

Doctor of Midwifery Advances in Midwifery Projects

In response to a looming health care workforce deficit, several health professions have experienced recent rapid workforce growth. These professions are supported by specialized health professional associations designed to promote educational excellence in the face of rapid growth. In contrast, the midwifery profession does not have dedicated professional organizations to support education programs. The purpose of this study is to better understand the various strategies used by selected health professional education associations and their value to the profession. This can be adapted to promote the growth and excellence of midwifery education in the United States, responding to the need for …

Assessment Of Clinical And Neuroimaging Efficacy Of Treatment Targeting Tau Pathology In Mild Cognitive Impairment And Mild To Moderate Alzheimer’S Disease With Hydromethylthionine Mesylate Using External Control Data, Bjoern O. Schelter, Helen Shiells, Serena Lo, Nafeesa Nazlee, Emily Evans, Peter Bentham, Serge Gauthier, Henrik Zetterberg, Gordon K. Wilcock, Lutz Froelich, Alistair Burns, Emer Macsweeney, Clive Ballard, Jin-Tai Yu, Tay Siew Choon, Vahe Asvatourian, Natalia Muehlemann, Jan Priel, Karin Kook, Tenecia Sullivan, Diane Downie, Sonya Miller, Carol Pringle, John M. D. Storey, Tom Baddeley, Charles R. Harrington, Roger Staff, Anca-Larisa Sandu, Claire Hull, Richard G. Stefanacci, Claude M. Wischik

College of Population Health Faculty Papers

BACKGROUND: Hydromethylthionine mesylate (HMTM) targets tau pathology and also has tau-independent symptomatic activity. A traditional randomised placebo-controlled trial (RCT) was precluded by loss of blinding due to urinary colouration and therapeutic activity at the minimum dose required to maintain blinding.

OBJECTIVE: To evaluate the efficacy of HMTM in participants with mild cognitive impairment (MCI) and mild to moderate dementia due to Alzheimer's disease (AD).

METHODS: Because a traditional RCT was not feasible without loss of blinding, we compared HMTM 16 mg/day in TRx-237-039 with propensity score matched true placebo controls from the FDA-sponsored Critical Path for AD (CPAD) database with …

Patient's Age Impact On Stroke Risk And Intracranial Aneurysm Occlusion: Scent Flow Diverter Study-A Nonrandomized Clinical Trial On Large And Giant Aneurysms, Ajay K. Wakhloo, Paul Jenkins, Philip M. Meyers, Alexander L. Coon, Peter T. Kan, Ajit S. Puri, Joost De Vries, Giuseppe Lanzino, Mark D. Bain, Koji C. Ebersole, Babu G. Welch, Aclan Dogan, Pascal Jabbour, J. Mocco, Adnan H. Siddiqui, Aquilla S. Turk, Philipp Taussky, Ricardo A. Hanel

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The prospective single-arm nonrandomized SCENT (Surpass Intracranial Aneurysm Embolization System Pivotal) trial on flow diverter treatment of large and giant intracranial aneurysms (IA) was analyzed for patients' age and IA characteristics affecting stroke and occlusion rates over 5 years (Trial registration NCT01716117).

METHODS: Impact on major ipsilateral stroke and IA occlusion was studied by stratifying age as 65 years and younger vs older than 65. Kaplan-Meier estimates of time to both endpoints, stratified by age, were created. Univariate predictors of time-to-stroke were analyzed using univariable proportional hazards regression models. Limited bivariable modeling was also attempted.

RESULTS: Of …

Ms-Gator: Multi-Scale Graph Attention With Topological Reasoning For Segmentation And Classification Of Prostate Cancer Based On Gleason Scores Using Histopathology Images, Sujata Patil, Mahadeva Swamy, Kavitha Sooda, Rajanikanth Vadigepalli, Khalid Nazim Abdul Sattar, Md Rafeeq

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Prostate cancer is one of the prevalent and potentially fatal malignancies, affecting men globally. Accurate segmentation and classification of prostate cancer in histopathology images remain challenging due to complex tissue architecture, staining variability, and high inter-observer differences in manual diagnosis. To address these challenges, this research proposes a Multi-Scale Graph Attention with Topological Reasoning (MS-GATOR) for segmentation and classification of prostate cancer based on Gleason Scores (GS). The MS-GATOR incorporates topological reasoning with hierarchical biological structures by constructing a graph-based representation among three spatial scales such as nuclei, glands, and tissues using Delaunay triangulation to capture both geometric and photometric …

Real And Perceived Barriers To Effective Use Of Cataract Surgical Supplies, Caitlin Davie, Lindsay K. Cloud, Scott Burris, Shaina Shiwdin, Brooke Sherry, Christina R. Prescott, Joel Schuman, David Palmer, David Chang, Daniel Parra, Cordelia Kwon, Margaret A. Tharp, Cassandra L. Thiel

Wills Eye Hospital Papers

INTRODUCTION: Cataract surgery, among the most common procedures worldwide, significantly contributes to climate change through both solid waste and air pollution, highlighting the urgent need for targeted interventions. Implementation faces hurdles including legal constraints and concerns about infection risks and malpractice.

METHODS: This article examines federal and state regulatory structures around two key waste reduction strategies: reduction of multidose medications and distribution of partly-used operating room medication to patients post-surgery.

RESULTS: We find little-to-no legitimate regulatory barriers to either waste reduction practice. Dispensing and redistributing partly-used medication has been codified in law in some states. Evidence-based reports indicate minimal risks …

A Scoping Review Of The Objective Structured Assessment Of Technical Surgical Skills (Osats), David J. O'Regan, Christopher Caddy, Retnagowri Rajandram, Paul Barach

College of Population Health Faculty Papers

BACKGROUND: Objective structured assessment of technical skills (OSATS) offers an objective tool for assessing bowel anastomosis on a benchtop. It was developed in 1997 to set appropriate standards and expectations for the surgical trainee. OSATS have become the gold standard of assessment across many disciplines. A global Likert rating scale, including respect for tissues, instrument handling, economy of movement, and flow of the operation predominates the literature. This has led to many questioning OSATS objectivity, claiming the process to be time-consuming, subjective, demanding human resources, and requiring extensive training of the trainer. We believe OSATS scoring has omitted the 22-point …

Lateral Minimally Invasive Si Joint Fusion Following Adult Spinal Deformity: A Case-Report And Literature Review, Basel Musmar, Hassan Saad, Joshua Pelta-Heller

Department of Neurosurgery Faculty Papers

This case report describes lateral minimally invasive sacroiliac (SI) joint fusion for SI joint–mediated pain in a patient with a history of adult spinal deformity surgery. A 48-year-old woman with multiple medical comorbidities previously underwent long thoracolumbar fusion. She subsequently had L4-S1 anterior lumbar interbody fusion and posterior L4-pelvis instrumentation in 2010. Following a ground-level fall in 05/2021, she developed new left-sided hip and sacroiliac pain with intermittent left lower-extremity numbness. Radiographs demonstrated mild hip osteoarthritis and sacroiliac joint sclerosis; spine imaging revealed discontinuity of the right iliac fixation rod without acute fracture. MRI of the hip showed bilateral sacroiliitis …

Anesthetic Management In Patients With Impella Devices: A Retrospective Review And Clinical Guide, Harrison Yang, Divakara Gouda, Kent B. Berg, Katherine Green, Suvan Sundaresh, Basavana Goudra

Department of Anesthesiology Faculty Papers

Background: The Impella family of percutaneous a left ventricular assist devices are increasingly used for hemodynamic support in patients with cardiogenic shock or advanced heart failure. However, guidance on anesthetic management for patients with Impella support undergoing noncardiac procedures remains sparse. This study reviews perioperative practices and outcomes to inform clinical management.

Methods: Following institutional review board approval, a retrospective analysis was performed of adult patients receiving an Impella device (2.5, CP, 5.0, or 5.5) at Thomas Jefferson University Hospital, Philadelphia, USA, between December 2017 and October 2024. Patients, who subsequently underwent procedures involving anesthesia care were included. Demographics, procedure …

Coverage, Traits, And Geographic Distribution Of Online Surgeon Reviews: Large-Scale Cross-Sectional Analysis, Michael Geng, Carlos Riveros, Yash B. Shah, Sanjana Ranganathan, Kai Fok, Renil Sinu Titus, Vatsala Mundra, Eusebio Luna Velasquez, Dharam Kaushik, Allan S. Detsky, Angela Jerath, Benjamin N. Breyer, Yusuke Tsugawa, Christopher J. D. Wallis, Raj Satkunasivam

Student Papers, Posters & Projects

BACKGROUND: The use of online physician rating platforms has significantly increased and has been shown to influence physician selection. There are limited data on the use of these platforms for rating surgeons.

OBJECTIVE: In this study, we sought to assess the geographic distribution of and patterns in rating scores of surgeons in the United States. Additionally, we examined rating volumes across different surgical specialties and the association between peer-nominated and patient-initiated ratings on online rating platforms in the United States.

METHODS: We conducted a cross-sectional study by identifying 201,154 surgeons in the United States via the National Plan and Provider …

Dasatinib And Quercetin Senolytic Treatment Delays Early Onset Intervertebral Disc Degeneration In Sm/J Mice, Emanuel J. Novais, Olivia K. Ottone, Sanjana Jagannath, Esther Jesutofunmi Akande, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice or senescence status, DQ-treated mice showed lower grades of degeneration and a decreased abundance of senescence markers, including p19ARF, p21, and the senescence-associated secretory phenotype (SASP). DQ improved disc cell viability and phenotype retention and retarded fibrosis …

Reirradiation Treatment Effects In The Clinic (Retec) Proposal - Proof Of Concept Based On Spinal Cord Dose Tolerance For Reirradiation With Stereotactic Body Radiotherapy, Jimm Grimm, Anand Mahadevan, Olusola Obayomi-Davies, Scott G. Soltys, Arjun Sahgal, Kristin J. Redmond, Michael T. Milano, Wolfgang A. Tomé, Kenneth Brooks, Scott Dodd, John Austin Vargo, Gopal Subedi, Jinyu Xue, Bisher Ebid, Felix Ehret, Byung-Han Andrew Rhieu, Christoph Fürweger, Rachel Grimm, Alexander Muacevic, Vitali Moiseenko, Shalom Kalnicki, Mark Mclaughlin, Lawrence R. Kleinberg, John R. Adler, Iris C. Gibbs

College of Health Professions Faculty Papers

BACKGROUND: Since the inception of spinal radiosurgery decades ago, the factors influencing spinal cord recovery have remained unclear. Elucidating these factors would aid in reirradiation planning and delivery. We describe modeling reirradiation normal tissue complication probabilities (NTCP) from compiled published data, akin to the collaborative Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC) projects.

PURPOSE: Simple dose-time recovery factors for the spinal cord serve as a basis to propose the Reirradiation Treatment Effects in the Clinic (ReTEC) project. ReTEC aims to define human organ recovery factors …

Utility Of Right Ventricular Mass Ratios In Recipients With Pulmonary Hypertension: A United Network For Organ-Sharing Database Analysis, Matthew P. Weber, Danial Ahmad, Howard J. Eisen, Eugene Storozynsky, René J. Alvarez, J. Eduardo Rame, Keshava Rajagopal, John W. Entwistle, Charles Hoopes, Vakhtang Tchantchaleishvili

Division of Cardiology Faculty Papers

PURPOSE: There is a lack of data reviewing the role of predicted cardiac mass ratio (PCMR) in transplant recipients with pulmonary hypertension (PH). In particular, the right ventricular (RV) mass ratio (RVMR) is a component of PCMR not yet studied separately for this purpose. We aimed to review the relationship of PCMR and RVMR with PH in terms of post-transplant overall survival.

METHODS: The United Network for Organ-Sharing (UNOS) database was queried for primary heart transplant (HTx) patients from 2004 to 2023. Predicted RVMR was calculated for donors and recipients. A parsimonious multivariable model Cox model was formed for risk …

Cerebellar Oligodendrocytic Α-Synuclein Pathology And Dentate Nucleus Neuronal Hypertrophy In Parkinson’S Disease, Diego Iacono, Hui Peng, John Paul Bouffard, Roger Kurlan

Department of Neurology Faculty Papers

Idiopathic Parkinson's disease (iPD) research has historically prioritized basal ganglia dysfunction and neuronal Lewy body pathology, often overlooking cerebellar and non-neuronal cells contributions. This study investigates cerebellar neuropathology in iPD, specifically focusing on neuronal and non-neuronal cells of the dentate nucleus (DN) and its adjacent white matter (DN-WM). We systematically assessed autopsy-confirmed iPD brains vs. age-matched controls using immunohistochemistry and stereology-based morphometry methods. The study evaluated α-synuclein pathology, other common age-related co-occurring pathologies (β-amyloid, Tau, neuroinflammation), myelin integrity (Luxol-Fast-Blue), and neuronal volumetric changes in the DN of the cerebellum. In iPD brains, we identified intracytoplasmic α-synuclein inclusions within oligodendrocytes across …

An Innovative Curriculum To Empower Trainees And Faculty To Address Patient-Initiated Identity-Based Misconduct In The Clinical Learning Environment, Nkanyezi Ferguson, Lauren E. Hock, Patrick Barlow, Aisha S. Jamison, Marcy E. Rosenbaum, Nicole Del Castillo

Department of Medicine Faculty Papers

Introduction: Training residents and attending physicians on effective communication strategies to manage biased patient and visitor comments is lacking. The I-RESPOND toolkit curriculum provides strategies for addressing identity-based misconduct in the clinical setting. Methods: Resident physicians and faculty in 12 departments at a single academic center participated in the workshop between June 2021 and February 2022. The workshop consisted of interactive didactics, an introduction to the I-RESPOND toolkit, and opportunities to practice communication strategies with formative feedback. Retrospective pre/postworkshop survey instruments and a follow-up survey were used to evaluate the workshop and subsequent experiences. Results: Sixty-six (32%) of 204 participants …

Costs, Demographics, And Causative Agents In Patients Hospitalized For Drug Induced Liver Injury: Trends In A Large Academic Healthcare System, Megan Kozar, Yunisse Gonzalez, Dina Halegoua-De Marzio

Department of Medicine Faculty Papers

PURPOSE: Drug-induced liver injury (DILI) is an uncommon but potentially life-threatening condition. To date, the burden of DILI on a single, large healthcare system has not been investigated, preventing adequate resource allocation. This study aims to quantify DILI-related healthcare utilization within the Jefferson Health System (JHS) and identify case-related factors associated with high resource requirements; such information is crucial to focus efforts toward resource reduction.

PATIENTS AND METHODS: This study characterizes trends of 48 DILI cases within JHS, including demographics, payer status, causative agent, and DILI pattern. These variables were correlated with length of stay (LOS) and cost relating to …

Contraception In The Ed: Understanding Education And Opportunities For Clinicians To Advise Patients, Hannah B. Lewis, Teagan R. Mccarthy, Dara Kass, Jennifer L. Kahoud

Department of Emergency Medicine Faculty Papers

Introduction: The United States faces a high rate of unwanted pregnancies. Despite this, many people continue to face barriers to accessing contraception. The emergency department (ED) can help bridge these gaps, but emergency clinicians must first feel comfortable offering contraceptive services. In this study, we sought to determine emergency clinician comfort in prescribing contraceptives and educating patients on their use. We also gauged clinician interest in receiving education specifically geared toward contraceptive care.

Methods: We conducted an online survey of ED residents, attendings, and advanced practice clinicians at Thomas Jefferson Univerity Hospital and affiliates in both the urban and suburban …

Protocol For Inducing Focal Striatal Stroke In Mice Using Photothrombosis, Bridget R. Boyle, Eileen Collyer, Andrea P. Berghella, Elena Blanco-Suarez

Department of Neuroscience Faculty Papers

Here, we present a protocol for inducing focal striatal stroke in mice using photothrombosis. We describe steps for photothrombotic striatal surgery, magnetic resonance imaging, open field behavioral assessment of stroke-induced motor deficits, and post-stroke monitoring. We then detail procedures for tissue collection and immunofluorescence. This protocol provides a standardized approach for consistently modeling striatal stroke in mice, enabling mechanistic studies and preclinical therapeutic testing.

Progesterone Receptors Drive Advanced Breast Cancer Phenotypes Including Circulating Tumor- And Stem-Like Cell Expansion In The Context Of Esr1 Mutation, Thu H. Truong, Noelle E. Gillis, Amy R. Dwyer, Rosemary J. Huggins, Kyla M. Hagen, Sai Harshita Posani, Nuri A. Temiz, Carlos Perez Kerkvliet, Ellie M. Piepgras, Julie H. Ostrander, Geoffrey L. Greene, Carol A. Lange

Department of Urology Faculty Papers

Endocrine therapy resistance remains a major challenge in the treatment of advanced estrogen receptor positive (ER+) breast cancer. This can be driven by acquired mutations in the estrogen receptor gene (ESR1), such as Y537S or D538G, that results in constitutive estrogen-independent ER activity. Progesterone receptors (PR) are important modifiers of ER activity, in part via direct binding. We previously showed that PR mediates expansion of cancer stem-like cell (CSC) populations. In this study, we sought to define whether PR function changes in the context of ESR1 mutations. PR readily interacted with wild type (WT), but not Y537S or D538G ERs. …

A Prolonged Nightly Fasting Plus Telehealth Coaching Intervention (Pnf+) For Men On Androgen Deprivation Therapy For Pca: A Pilot Feasibility Randomized Controlled Trial, Kuang-Yi Wen, Julianne Freedman, Kevin K. Zarrabi, Rachel Slamon, Rita Smith, Jessica Liang, Patrick Mille, William J. Tester, William Kevin Kelly

Department of Medical Oncology Faculty Papers

Background/Objectives: This study aimed to assess the feasibility and acceptability of a 3-month health coaching intervention to promote PNF and healthy diet for men on ADT for PCa.

Methods: The study was carried out via a two-armed randomized controlled trial including 40 patients with PCa at a medical center in Philadelphia. During the 3-month period, the intervention group (PNF+) received health coaching utilizing an interactive text message system, and the control group received healthy eating text messages for the same duration. The outcome variables were feasibility and acceptability.

Results: The PNF+ group (n = 27) had high …