Medical Specialties Commons^™

Simvastatin And Rifaximin In Decompensated Cirrhosis: A Randomized Clinical Trial, Elisa Pose, César Jiménez, Giacomo Zaccherini, Daniela Campion, Salvatore Piano, Frank Erhard Uschner, Koos De Wit, Olivier Roux, Kohilan Gananandan, Wim Laleman, Cristina Solé, Sonia Alonso, Berta Cuyàs, Xavier Ariza, Adrià Juanola, Ann T Ma, Laura Napoleone, Jordi Gratacós-Ginès, Marta Tonon, Enrico Pompili, Jordi Sánchez-Delgado, Andrew S Allegretti, Manuel Morales-Ruiz, Marta Carol, Martina Pérez-Guasch, Núria Fabrellas, Judit Pich, Claudia Martell, María Joyera, Gemma Domenech, José Ríos, Ferrán Torres, Miquel Serra-Burriel, Rubén Hernáez, Elsa Solà, Isabel Graupera, Hugh Watson, Germán Soriano, Rafael Bañares, Rajeshwar P Mookerjee, Claire Francoz, Ulrich Beuers, Jonel Trebicka, Paolo Angeli, Carlo Alessandria, Paolo Caraceni, Víctor M Vargas, Juan G Abraldes, Patrick S Kamath, Pere Ginès

Faculty, Staff and Students Publications

Importance: There are no useful treatments to prevent the development of severe complications of liver cirrhosis. Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis.

Objective: To assess whether simvastatin combined with rifaximin improves outcomes in patients with decompensated cirrhosis.

Design, setting, and participants: Double-blind, placebo-controlled, phase 3 trial conducted among patients with decompensated cirrhosis in 14 European hospitals between January 2019 and December 2022. The last date of follow-up was December 2022.

Interventions: Patients were randomly assigned to receive simvastatin, 20 mg/d, plus rifaximin, 1200 mg/d (n = 117), or identical-appearing placebo (n = 120) for 12 months …

Hematopoietic Cell Transplant Compared With Standard Care In Adolescents And Young Adults With Sickle Cell Disease, Mark C Walters, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K Waller, John E Levine, John J Strouse, Joseph H Antin, Suhag H Parikh, Nitya Bakshi, Carlton Dampier, Jennifer J Jaroscak, Shayla Bergmann, Trisha Wong, Vamsi Kota, Betty Pace, Lazaros J Lekakis, Premal Lulla, Robert S Nickel, Kimberly A Kasow, Uday Popat, Wally Smith, Lolie Yu, Nancy Difronzo, Nancy Geller, Naynesh Kamani, Elizabeth S Klings, Kathryn Hassell, Adam Mendizabal, Keith Sullivan, Donna Neuberg, Lakshmanan Krishnamurti

Faculty, Staff and Students Publications

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality …

Metabolic Signatures In Adipose Tissue Linking Lipophilic Persistent Organic Pollutant Mixtures To Blood Pressure Five Years After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Douglas I Walker, Brittney O Baumert, Hongxu Wang, Jesse A Goodrich, Sarah Rock, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Scott M Bartell, Stavra Xanthakos, Xiangping Lin, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Michele A La Merill, Erika Garcia, Max T Aung, Sandrah P Eckel, Rob Mcconnell, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Persistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With …

Successful Limb Salvage In A Severe Diabetic Foot Infection: A Case Study Of Aggressive Surgical Intervention And Grafting Technique, Stephanie N. Campbell, Amanda Killeen, Michael Sobolevsky

Research Symposium

Background: Severe necrotizing diabetic foot infections are known to have high morbidity, high amputation risk, and high complication rates. Efforts at preserving the limb require significant surgical efforts and lengthy wound care. This process is more complicated in patients with significant housing instability.

Case Presentation: A 53-year-old male with uncontrolled diabetes (A1c 7.9%), housing insecurity, food insecurity presented with severe necrotizing diabetic foot infection with ascending cellulitis, infectious hemorrhagic bullae, multi-compartment abscesses of the foot and anterior leg. It is known that patients with diabetes are at increased risk of both amputation and surgical interventions than patients without diabetes. This …

Changes In Matches Into Surgical Residencies And Fellowships Following The Acgme Merger., Sara S Soliman, Gabrianna Andrews, Salma Emara, Naomi Watkins-Granville, Alicia Podwójniak, Iman Hasan, Jha Stuti, Alissa Brotman

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: In 2015, a transition was initiated among the Accreditation Council for Graduate Medical Education (ACGME), American Osteopathic Association (AOA), and American Association of Colleges of Osteopathic Medicine (AACOM), resulting in a single accrediting body for residencies and fellowships as of 2020. This study aims to elucidate whether this had an impact on osteopathic students' matching into general surgery residencies, integrated surgery residencies, and surgical fellowships.

DESIGN, SETTING, AND PARTICIPANTS: Using the Results and Data Residency Match data file and the Results and Data: Specialties Matching Service data from the National Resident Matching Program from 2015 to 2024, data was …

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-Of-Life Evaluation And 2-Year Outcomes Of Bmt Ctn 1703., Shernan G Holtan, Javier Bolaños-Meade, Monzr M Al Malki, Juan Wu, Carrie L Kitko, Ran Reshef, Andrew R Rezvani, Brian C Shaffer, Melhem M Solh, Janny M Yao, Lyndsey Runaas, Hany Elmariah, Karilyn T Larkin, Najla El Jurdi, Mahasweta Gooptu, Alison W Loren, Aric C Hall, Amin M Alousi, Omer Jamy, William Clark, Leslie Kean, Ami S Bhatt, Miguel-Angel Perales, Kristy Applegate, Yvonne Adeduni Efebera, Eric Leifer, Richard J Jones, Mary M Horowitz, Deborah Mattila, Wael Saber, Mehdi Hamadani, Michael J Martens

Oncology Articles

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant. PRO scores …

A Case Of Turmeric-Induced Hepatotoxicity With Hyperferritinemia, Nina R. Spitofsky, Albert A. Huang, Aria Jalalian, Stefanie Gallagher, Scott Fink

Department of Medicine Faculty Papers

Introduction: We present the first published case of turmeric-associated drug-induced liver injury (DILI) accompanied by significant ferritin elevation. Case Presentation: Our patient, a 59-year-old female with DILI caused by long-term ingestion of oral turmeric supplements, presented with painless jaundice on an annual exam. The patient’s liver function tests exhibited a hepatocellular pattern and hyperferritinemia (>2,000 ng/dL). Additional testing was negative except for heterozygosity for the H63D allele associated with hemochromatosis. A liver biopsy indicated acute hepatitis without fibrosis or stainable iron. Conclusion: Upon discontinuation of the supplement, liver enzymes normalized within a month. This case highlights the potential for …

Spontaneous Distal Middle Cerebral Artery Aneurysm In A Young Male With Full Mutation Of The Fragile X Syndrome With A High-Functioning Phenotype: Illustrative Case, Eleni Papadopoulos, Anna Abrimian, Hekmat Zarzour, Randi J Hagerman, Richard F Schmidt

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Fragile X syndrome (FXS) is a genetic disorder that typically presents with neurodevelopmental abnormalities. Patients with FXS can present with signs and symptoms of connective tissue disorder (CTD) and occasionally with vascular disease. However, cerebrovascular disease is not well documented in these patients, and it is unknown whether there is a direct link between abnormal levels of fragile X protein (FMRP) and its mRNA.

OBSERVATIONS: Here, the authors present a rare case of an adult male with full mutation FXS of a high-functioning phenotype who presented with syncope, and on further evaluation, a fusiform dissecting aneurysm of the distal …

Serum Metal Ion Levels In Patients Undergoing Revision Should Arthroplasty, Rishi Chatterji, Brandon Fisher, Avianna Elizabeth Arapovic, Yuying Xing, J Michael Wiater

Conference Presentation Abstracts

INTRODUCTION: Shoulder arthroplasty systems are transitioning towards more modular prosthesis options with the goal of reducing complication profiles and increasing range of motion. Modularity may increase the potential for fretting, corrosion, and subsequent release of metal ions. These events have been associated with adverse reactions in hip and knee arthroplasty, but not in the setting of revision shoulder arthroplasty. The purpose of this study was to identify associations between implant designs, metallurgy, patient characteristics, and serum metal ion levels in patients undergoing revision shoulder arthroplasty. METHODS: 51 patients that underwent revision shoulder arthroplasty were retrospectively reviewed based on prospectively collected …

Comparing Outcomes After Cemented And Cementless Total Knee Arthroplasty, Phillip Vartanyan, James Feng, Ali Omari, Elijah Christian Auch, Alex Miller, Drew Douglas Moore, Hasson Alosh, Mark S. Karadsheh

Conference Presentation Abstracts

INTRODUCTION: The optimal method of fixation for primary total knee arthroplasties (TKAs) has been subject to debate. Here we compare patients who received cemented and cementless TKAs for arthritis and compared clinical outcome measures. METHODS: All primary TKAs between January 2016 and December 2022 were obtained retrospectively from a prospective institutional database utilized for contribution to a state-wide joint arthroplasty database. Prospective data includes baseline demographics, select medical comorbidities, intraoperative variables, and postoperative course/complications. Patients were split into two cohorts based on the use of cemented vs cementless TKA implants. Hybrid fixation was excluded. Groups were compared utilizing Student’s unpaired …

New-Onset Depression Following Total Shoulder Arthroplasty: The Impact Of Preoperative Patient Factors And Postoperative Complications, Kevin Xavier Farley, Robert Dean, J Michael Wiater

Conference Presentation Abstracts

INTRODUCTION: Depression has been well studied as a risk factor for postoperative complications following total shoulder arthroplasty (TSA). However, little is known about new-onset depression (NOD) following TSA. The purpose of this study is to determine the incidence of NOD following TSA and identify risk factors for its occurrence. METHODS: This was a retrospective review of patients undergoing TSA in the Truven Health MarketScan database. NOD was identified. Patients with pre-operative depression were excluded from analysis. Post-operative complications were identified, including the development of a prosthetic joint infection (PJI), need for revision surgery, and postoperative dislocation. If a complication occurred …

Uncemented Versus Cemented Humeral Fixation In Reverse Shoulder Arthroplasty For Proximal Humerus Fractures In The Elderly: A Multicenter Retrospective Cohort Study, Johnny Kasto, Thomas Ward Throckmorton, Tyler James Brolin, H Mike Kim, Curtis R. Noel, J Michael Wiater, Thomas W. Wright, Stephanie J. Muh

Conference Presentation Abstracts

INTRODUCTION: Among surgical interventions for proximal humerus fractures, RSA has been shown to have superior or noninferior outcomes to hemiarthroplasty or open reduction internal fixation. Cemented humeral fixation in RSA has been the traditional treatment method for proximal humerus fractures, however, there is a growing interest in uncemented humeral fixation. Both cemented and cementless RSA are currently used to treat proximal humerus fractures with few studies comparing postoperative outcomes of these 2 techniques. The aim of this study was to compare postoperative outcomes between cemented and uncemented humeral fixation following primary reverse total shoulder arthroplasty (RSA) for proximal humerus fractures. …

Outcomes After Total Hip Arthroplasty: Comparison Between Posterior And Anterior Approaches, Phillip Vartanyan, James Feng, Alex Miller, Ali Omari, Elijah Christian Auch, Hasson Alosh, Drew Douglas Moore, Mark S. Karadsheh

Conference Presentation Abstracts

INTRODUCTION: The effects of surgical approach in total hip arthroplasty (THA) are often debated. Here we compare patients who underwent THA through a posterior versus anterior approach and compared clinical outcomes and patient reported outcome measures (PROMs). METHODS: All primary THAs between January 2016 and December 2022 were obtained retrospectively from a prospective institutional database utilized for contribution to a state-wide joint arthroplasty database. Prospective data was abstracted including baseline demographics, select medical comorbidities, intraoperative variables, postoperative course/complications and patient reported outcomes. Two cohorts were developed based on approach: anterior (aTHA) and posterior (pTHA) THA. Cohort groups were compared utilizing …

Two-Year Follow-Up Of Additive Manufactured, Fully 3d Printed Humeral Prosthesis, Jie Jonathan Yao, Andrew Jawa, J Michael Wiater, Anand M. Murthi, Matthew J. Smith, Derek J. Cuff, Samantha Anne Riebesell, Dennis Debernardis, Luke Stanford Austin

Conference Presentation Abstracts

INTRODUCTION: A fully 3D printed prosthetic may offer numerous potential advantages including improved pore precision, overall porosity, topology optimization, spatial variability in stiffness, communication between pores, and strut size. However, there are numerous theoretical concerns surrounding inferior mechanical performance with fully 3D printed implants (e.g. potentially higher rates of fatigue, increased in vivo particle release, etc.) compared to conventionally fabricated ones. We are aware of no reports on the clinical performance of fully 3D printed, off-the-shelf, humeral prostheses. To validate fully 3D printed humeral designs, the purpose of this study was to provide minimum 2-year postoperative clinical outcomes and survivorship …

Polyethylene Wear: An Under-Recognized Cause Of Failed Shoulder Arthroplasty, Brandon Fisher, Matthew Astolfi, Justin Taylor Deslaurier, Karen Childers, James Youngjin Lee, Marisa Samani, J Michael Wiater

Conference Presentation Abstracts

INTRODUCTION: Particle-induced osteolytic and chronic inflammatory effects of polyethylene (PE) wear are a source of failure after both anatomic total shoulder arthroplasty (ATSA) and reverse total shoulder arthroplasty (RTSA). Historically, PE wear has rarely been reported as a cause of revision in the setting of prior shoulder arthroplasty, unlike hip and knee counterparts. The goal of this study was to analyze and present the clinical, radiographic, and intra-operative findings in a consecutive series of patients who presented after shoulder arthroplasty with evidence of PE wear. METHODS: This was a retrospective review of prospectively collected data on a consecutive series of …

Are Pre-Operative Falls Associated With Post-Operative Complications In Patients Undergoing Aseptic Revision Hip Or Knee Arthroplasty?, Kevin Xavier Farley, Robert Dean, Mark S. Karadsheh, Drew Douglas Moore

Conference Presentation Abstracts

INTRODUCTION: Pre-operative falls are common in patients undergoing primary hip or knee arthroplasty and pre-dispose patients to poor outcomes. However, this relationship in those undergoing revision hip and knee arthroplasty (rTHA, rTKA) is unclear. This study sought to study the relationship between a pre-operative fall history and post-operative patient complications in patients undergoing rTKA or rTHA. METHODS: The National Surgical Quality Improvement Project (NSQIP) database was used to identify all patients undergoing aseptic rTKA or rTHA. The variable for a fall history was available in 2021. Fall history was defined as a patient with a fall in the 6- months …

Prophylaxis, Clinical Management, And Monitoring Of Datopotamab Deruxtecan-Associated Oral Mucositis/Stomatitis, Funda Meric-Bernstam, Aditya Bardia, Paolo Bossi, Giampaolo Bianchini, Frances Gatlin, Rajesh V Lalla, Barbara Melosky, Naoki Niikura, Timothy A Yap, Sophie S Kim, Rachana Rajagopalan, Rick M Fairhurst, Stephanie L Graff, Hope S Rugo

Faculty, Staff and Student Publications

Oral mucositis/stomatitis (hereafter stomatitis) is a common dose-limiting toxicity seen with various classes of cancer treatment. Symptoms associated with stomatitis, primarily oral pain, may impact patient quality of life and may lead to dose delay and reduction or treatment discontinuation. Datopotamab deruxtecan (Dato-DXd) is a novel trophoblast cell surface antigen 2-directed antibody-drug conjugate undergoing clinical investigation in multiple solid tumor types. Stomatitis is among the most reported adverse events associated with Dato-DXd, with most cases being grades 1-2. This article reviews the incidence of stomatitis seen with Dato-DXd, including in the phase III pivotal studies TROPION-Lung01 and TROPION-Breast01 (in patients …

A Phase I/Ii Trial Of Avelumab Combinations With Ivuxolimab, Utomilumab, And Radiation Therapy In Patients With Advanced Gastrointestinal Malignancies, Jibran Ahmed, Anne Knisely, Carlos Torrado, Bettzy Stephen, Yali Yang, Juhee Song, Anas Alshawa, Abdulrazzak Zarifa, Anuja Jhingran, Eugene J Koay, Van Karlyle Morris, Milind Javle, Robert A Wolff, Funda Meric-Bernstam, Shubham Pant, Jordi Rodon, Aung Naing

Faculty, Staff and Student Publications

Background: Checkpoint agonists utomilumab (4-1BB agonist) and ivuxolimab (OX40 agonist) enhance Teffector cell function. Preclinical studies suggest that combining these drugs with avelumab (anti-PD-L1 antibody) can potentially synergize this effect. In addition, tissue abscopal effects of radiation therapy may improve antigen presentation, complementing PD-L1 blockade. We conducted a single institution, open-label, multi-arm, non-randomized, phase 1/2 clinical trial of avelumab in combination with ivuxolimab, with or without utomilumab, and radiation therapy in patients with advanced solid tumors. Herein, we present a subgroup analysis in patients with gastrointestinal (GI) tumors (pancreatic, colon, gastric, and hepatocellular).

Methods: The primary objectives of this study …

Suppression Of Stress Granule Formation Is A Vulnerability Imposed By Mutant P53., Elizabeth A. Thoenen, Atul Ranjan, Alejandro Parrales, Shigeto Nishikawa, Dan A. Dixon, Sugako Oka, Tomoo Iwakuma

Manuscripts, Articles, Book Chapters and Other Papers

Missense mutations in the TP53 (p53) gene have been linked to malignant progression. However, our in-silico analyses reveal that hepatocellular carcinoma (HCC) patients with mutant p53 (mutp53) have better overall survival compared to those with p53-null (p53^null) HCC, unlike other cancer types. Given the historical use of sorafenib (SOR) monotherapy for advanced HCC, we hypothesize that mutp53 increases sensitivity to SOR, a multikinase inhibitor that induces endoplasmic reticulum (ER) stress. Here we show that mutp53 inhibits stress granule (SG) formation by binding to an ER stress sensor, PKR-like ER kinase (PERK), and a key SG component, GAP SH3 …

Advances In Extracellular Matrix-Associated Diagnostics And Therapeutics, Morten Karsdal, Thomas R Cox, Amelia L Parker, Nicholas Willumsen, Jannie Marie Bülow Sand, Gisli Jenkins, Henrik H Hansen, Anouk Oldenburger, Kerstin E Geillinger-Kaestle, Anna Thorsø Larsen, Darcey Black, Federica Genovese, Alexander Eckersley, Andrea Heinz, Alexander Nyström, Signe Holm Nielsen, Lucas Bennink, Lars Johannsson, Anne-Christine Bay-Jensen, Dana E Orange, Scott Friedman, Mads Røpke, Vincent Fiore, Detlef Schuppan, Florian Rieder, Benjamin Simona, Lee Borthwick, Mark Skarsfeldt, Haakan Wennbo, Paresh Thakker, Ruedi Stoffel, Graham W Clarke, Raghu Kalluri, Darren Ruane, Faiez Zannad, Joachim Høg Mortensen, Dovile Sinkeviciute, Fred Sundberg, Molly Coseno, Christian Thudium, Adam P Croft, Dinesh Khanna, Michael Cooreman, Andre Broermann, Diana Julie Leeming, Ali Mobasheri, Sylvie Ricard-Blum

Faculty, Staff and Student Publications

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denominators and distinguishing factors in this fibroinflammatory axis, which may be used to foster new …

Incidence And Correlates Of High-Grade Chemotherapy-Induced Peripheral Neuropathy In Patients With Lung Cancer, Mitchell S Von Itzstein, Sawsan Rashdan, Suzanne E Dahlberg, David E Gerber, Alan B Sandler, Joan H Schiller, David H Johnson, Yating Wang, Zhuoxin Sun, Suresh S Ramalingam

Faculty, Staff and Student Publications

Background: High-grade chemotherapy-induced peripheral neuropathy (CIPN) represents a dreaded toxicity of cancer treatments. In some cases, it may limit activities of daily living and become permanent. Because many prior studies of CIPN were conducted in breast cancer populations, less is known about CIPN in men. We therefore determined the incidence and correlates of high-grade CIPN in a large cohort of patients with lung cancer.

Methods: We collected data from the ECOG-ACRIN E1594 (comparison of 4 chemotherapy regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, carboplatin-paclitaxel) and E4599 (carboplatin-paclitaxel ± concurrent and maintenance bevacizumab) clinical trials. We identified cases with grade ≥3 CIPN. Multivariable logistic …

Meta-Analysis On Sex Differences In Mortality And Neurodevelopment In Congenital Heart Defects, Alyssa K Crain, Zhia N Lim, Chloe J Sarfatis, Magela Arias, Travis Holder, Alvaro G Moreira, Antonio F Corno, Tina O Findley

Faculty, Staff and Student Publications

Given the increasing survival rates among congenital heart disease (CHD) patients and the growing emphasis on their quality of life, there is a need to comprehensively assess the impact of surgical interventions on neurodevelopmental outcomes. With increasing awareness in sex-related disparities in CHD, there is a need to explore potential differences in surgical mortality and neurodevelopmental outcomes between male and female patients. In this systematic review, we adhered to PRISMA guidelines and PROSPERO registration (#CRD42021225610). Articles published from 2015 to 2021 were searched using MeSH descriptors in three major databases (MEDLINE Ovid, Elsevier Embase, and Cochrane Library). Study selection criteria …

Multi-Ancestry Transcriptome-Wide Association Studies Of Cognitive Function, White Matter Hyperintensity, And Alzheimer's Disease, Dima L Chaar, Zheng Li, Lulu Shang, Scott M Ratliff, Thomas H Mosley, Sharon L R Kardia, Wei Zhao, Xiang Zhou, Jennifer A Smith

Faculty, Staff and Student Publications

Genetic variants increase the risk of neurocognitive disorders in later life, including vascular dementia (VaD) and Alzheimer's disease (AD), but the precise relationships between genetic risk factors and underlying disease etiologies are not well understood. Transcriptome-wide association studies (TWASs) can be leveraged to better characterize the genes and biological pathways underlying genetic influences on disease. To date, almost all existing TWASs on VaD and AD have been conducted using expression studies from individuals of a single genetic ancestry, primarily European. Using the joint likelihood-based inference framework in Multi-ancEstry TRanscriptOme-wide analysis (METRO), we leveraged gene expression data from European ancestry (EA) …

Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato

Kimmel Cancer Center Faculty Papers

The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression …

Condensed Low-Dose Total Skin Electron Beam Therapy For Mycosis Fungoides: An Institutional Retrospective Review And Subgroup Analysis Of Patients With Large Cell Transformation, Louis Cappelli, Megan Cappelli, Nilanjan Haldar, Tiara Paul, Jenna Mandel, Tingting Zhan, Neda Nikbakht, Wenyin Shi

Department of Dermatology and Cutaneous Biology Faculty Papers

Low-dose total skin electron beam therapy (TSEBT) is an effective treatment option for mycosis fungoides (MF) with proven palliative effects and reduced toxicity. Presented is an institutional analysis of survival/response rate and quality of life for MF patients with subgroup analysis of those possessing pathologic large cell transformation (LCT). This is a single institutional retrospective review of patients with mycosis fungicides treated from 2014 to 2023 with low-dose TSEBT. All patients received 12 Gy in 6 fractions every other day with the modified Stanford technique, with boosts to shadowed sites between treatments, completed in 2 weeks. Outcomes evaluated included clinical …

Molecular Model Of Tfiih Recruitment To The Transcription-Coupled Repair Machinery, Tanmoy Paul, Chunli Yan, Jina Yu, Susan E Tsutakawa, John A Tainer, Dong Wang, Ivaylo Ivanov

Faculty, Staff and Student Publications

Transcription-coupled repair (TCR) is a vital nucleotide excision repair sub-pathway that removes DNA lesions from actively transcribed DNA strands. Binding of CSB to lesion-stalled RNA Polymerase II (Pol II) initiates TCR by triggering the recruitment of downstream repair factors. Yet it remains unknown how transcription factor IIH (TFIIH) is recruited to the intact TCR complex. Combining existing structural data with AlphaFold predictions, we build an integrative model of the initial TFIIH-bound TCR complex. We show how TFIIH can be first recruited in an open repair-inhibited conformation, which requires subsequent CAK module removal and conformational closure to process damaged DNA. In …

Integrative Analysis Of Transcriptomics And Clinical Data Of Slc1a5 In Cervical Cancer, Veronica O'Brien, Vivek Kashyap, Bhuvnesh Sharma, Murali Yallapu, Everardo Cobos, Subhash Chuahan

Research Symposium

Background: Cervical cancer is the fourth most common cancer in adult females globally and the second most common cancer in females between the ages of 15 and 44. The alanine-serine- cysteine transporter 2, ASCT2 (solute carrier family 1 member 5, SLC1A5), is a major transporter of the amino acid, glutamine. SLC1A5 expression is associated with the progression of multiple types of tumors, including liver, lung, breast, colon and head and neck cancer. However, the biological significance of SLC1A5 cervical cancer has not been systematically and comprehensively investigated. Using deep data mining and transcriptomics analyses, in this study, we investigated the …

Long-Term Neurocognitive And Behavioral Outcomes In Survivors Of Pediatric Brain Tumors: A Systematic Review, Tori Sayers, Megan W. Szobody, Nina Mourao, Blake C. Martin, Sriya Gullapalli, Kory Punch, Tirath Patel, Murali Yallapu, Bharathi Shrikanth Gadad

Research Symposium

Background: Pediatric populations have an increased susceptibility for brain tumors and suffer from neurocognitive impairment due to the neoplasm itself, and side effect of subsequent treatments. This causes many patients to experience a subpar quality of life (QoL), affecting academic endeavors, social interaction and mental well-being. Increasing our understanding of the long-term effects associated with brain tumors and the side effects from our current treatment methodology will help us formulate better treatment protocols and improve survivors’ QoL. This review aims to investigate different long-term neurocognitive and behavioral outcomes in pediatric brain tumor survivors, as well as evaluate how various treatment …

Case Report: Oral Contraceptives-Induced Cholestasis, Aura Calderon, Taiwo Ajani, Nayiri Derian, Catherine Matos, Ivan Mogollon, Andres Suarez

Research Symposium

Background: Oral contraceptives represent one of the most prevalently utilized pharmacological interventions for contraception, renowned for their safety and efficacy. However, their advantageous safety profile, these pharmaceuticals are intermittently correlated with infrequent yet significant hepatobiliary complications, including drug-induced cholestasis and hyperbilirubinemia1. The estrogenic constituents of oral contraceptives are recognized for their capacity to disrupt bile acid transport within the hepatic system, culminating in intrahepatic cholestasis2. This phenomenon is particularly alarming in individuals possessing inherent genetic susceptibilities, such as Dubin-Johnson Syndrome, wherein bilirubin metabolism and excretion are already adversely affected3. The identification and comprehension of these adverse effects are imperative for …

Investing In Limb Preservation: A Case Report In Avoiding Bilateral Amputation In A Vasculopathy Patient, Stephanie N. Campbell, Craig J. Verdin, Heather V. Tran, Nikita Gambhir

Research Symposium

Background: Limb salvage and prosthetics play vital roles in restoring function and mobility for patients with severe injuries or metabolic conditions. Limb salvage involves surgical techniques aimed at preserving a limb rather than resorting to amputation, while prosthetics provide artificial devices to replace lost limbs. Key considerations for limb salvage include restoring a functional foot, maintaining patient independence, minimizing hospitalizations, and avoiding bilateral lower limb amputations.

Case Presentation: The patient, already at single-limb status, presented with a necrotic heel ulcer, exposed calcaneus, and necrotic Achilles tendon. After vascular optimization, the risks and benefits of final aggressive measures were discussed, leading …