Digital Commons Network^™

Disruption Of The Cerebrospinal Fluid-Plasma Protein Balance In Cognitive Impairment And Aging, Amelia Farinas, Daniel Western, Jigyasha Timsina, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their …

Benefit Of Early Oseltamivir Therapy For Adults Hospitalized With Influenza A: An Observational Study, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza.

METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during 1 October 2022-21 July 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), …

Tau Pet Positivity In Individuals With And Without Cognitive Impairment Varies With Age, Amyloid-Β Status, Apoe Genotype And Sex, Rik Ossenkoppele, Tammy L S Benzinger, Et Al.

2020-Current year OA Pubs

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU …

Validation Of The Brugia Test Plus To Detect Igg4 Antibodies In Individuals From Belitung Timur, A Brugia Malayi Endemic Area In Indonesia, Taniawati Supali, Elisa Iskandar, Noviani Sugianto, Yenny Djuardi, Katherine Gass, Jean M. Saunders, Peter U. Fischer, Marco A. Biamonte

2020-Current year OA Pubs

The Brugia Test Plus (BT+) is a new rapid diagnostic test for Brugia species which detects human IgG4 antibodies specific for the immunogenic Brugia protein BmR1. The aim of this study was to evaluate the BT+ assay with several types of sample-matrices: whole blood, plasma, and dried blood spots (DBS) from individuals living in Belitung Timur, a Brugia malayi endemic area in Indonesia. Night blood was collected from residents living in four presumed endemic villages, while DBS were collected from schoolchildren living in those four villages. The sensitivity of BT+ was measured by comparing the BT+ results to microscopic examination …

Domains Of Housing Instability And Intimate Partner Violence Risk Among U.S. Tenants, Anairany Zapata, Leila G Wood, Annalynn M Galvin, Wenyaw Chan, Timothy A Thomas, Jack Tsai, Heather K Way, Elizabeth J Mueller, Daphne C Hernandez

Faculty, Staff and Student Publications

While IPV is often studied as a predictor of housing insecurity, few U.S. studies explore how different forms of housing instability may contribute to intimate partner violence (IPV) risk. Using a mixed-methods approach and a cross-sectional design, this study examined the association between four housing instability domains and IPV among a sample of tenants that had either experienced eviction or were at high risk for eviction. Tenants in Harris and Travis counties (Texas, USA) completed an online survey (n = 1085; March–July 2024). Housing instability was assessed across four domains: homelessness, lease violations, utility hardship, and poor housing quality. …

Retrotransposon Methylation Profiles And Survival In Black Women With High-Grade Serous Ovarian Carcinoma., Christelle Colin-Leitzinger, Katherine A. Lawson-Michod, Courtney E. Johnson, Irma M. Vlasac, Sean Yoder, Tania Mesa, Dana Roeber, Chad Huff, Michelle A T Hildebrandt, Kristin Haller, Anthony J. Alberg, Elisa V. Bandera, Melissa Bondy, Michele L. Cote, Theresa Hastert, Edward S. Peters, Paul D. Terry, Andrew B. Lawson, Andrew Berchuck, Brooke L. Fridley, Jing-Yi Chern, Jennifer A. Doherty, Jeffrey R. Marks, Joellen M. Schildkraut, Brock C. Christensen, Lucas A. Salas, Lauren C. Peres

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

METHODS: Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters …

Retrotransposon Methylation Profiles And Survival In Black Women With High-Grade Serous Ovarian Carcinoma, Christelle Colin-Leitzinger, Katherine A Lawson-Michod, Courtney E Johnson, Irma M Vlasac, Sean Yoder, Tania Mesa, Dana Roeber, Chad Huff, Michelle A T Hildebrandt, Kristin Haller, Anthony J Alberg, Elisa V Bandera, Melissa Bondy, Michele L Cote, Theresa Hastert, Edward S Peters, Paul D Terry, Andrew B Lawson, Andrew Berchuck, Brooke L Fridley, Jing-Yi Chern, Jennifer A Doherty, Jeffrey R Marks, Joellen M Schildkraut, Brock C Christensen, Lucas A Salas, Lauren C Peres

Faculty, Staff and Student Publications

Introduction: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

Methods: Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters …

Optimal Treatment Duration In Metastatic Renal Cell Carcinoma Patients Responding To Immune Checkpoint Inhibitors: Should We Treat Beyond Two Years?, Alexander Decruyenaere, Gennigens Christine, Rottey Sylvie, Laenen Annouschka, Emmanuel Seront, Els Everaert, Philip R Debruyne, Heidi Van Den Bulck, Julie Bastin, Verbiest Annelies, Christof Vulsteke, Peter Schatteman, Daisy Luyten, Sandrine Aspeslagh, Nieves Martinez-Chanza, Marlies De Bock, Thomas Meyskens, Jolanda Verheezen, Barbara Brouwers, Benoit Beuselinck

School of Nursing and Midwifery

BACKGROUND AND PURPOSE: Optimal treatment duration is unknown in metastatic renal cell carcinoma (mRCC) responding to immune checkpoint inhibitors (ICPIs). Prolonged treatment can lead to late toxicity, burden for day clinics and financial impact.

PATIENTS AND METHODS: This multicenter retrospective study included mRCC patients responding to ipilimumab/nivolumab in first-line or nivolumab in later lines, who were treated for at least 21 months and did not stop for toxicity. Progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were modeled non- and semi-parametrically. The effect of elective ICPI discontinuation (i.e. treatment interruption at the clinician's discretion) between 21 and 25 …

Efficacy And Safety Of Dapagliflozin In Patients Hospitalized With Covid-19 With And Without Type 2 Diabetes: A Prespecified Analysis Of The Dare-19 Randomized Trial, Mohammad Abdel Jawad, Ali Javaheri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although several previous studies tested SGLT2 inhibitors in the setting of an acute, non-cardiovascular illness, detailed information on their efficacy and safety among participants with and without type 2 diabetes (T2D) from double-blind randomized trials is lacking. In this secondary prespecified analysis of the Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial, we sought to evaluate the safety and efficacy of initiating dapagliflozin during acute illness with COVID-19 in patients with and without T2D.

METHODS: The DARE-19 trial randomized 1250 patients hospitalized with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. T2D was present in 636/1250 …

Effects Of Neoadjuvant Immunotherapy On Hearing In Patients With Head And Neck Squamous Cell Carcinoma, Bryce Hambach, Anhelina Bilokon, John Lee, L. Noelle Allemang, Jennifer Chisholm, Chris K. Zalewski, Julie Christensen, Carmen C. Brewer, James L. Gulley, Clint T. Allen, Lisa L. Cunningham, Katharine A. Fernandez

SKMC Student Presentations and Publications

Immune checkpoint blockade (ICB) is a commonly used treatment modality for cancer with a growing list of oncologic indications. Ototoxicity is a potential immune-related adverse event of ICB treatment, but the risk of hearing loss after ICB remains unknown. This retrospective chart review sought to identify individuals who received ICB and had available audiometric data before and after treatment in order to identify clinically meaningful changes in hearing. This single center, institutional chart review examined hearing function data in patients who underwent audiometry before and after ICB treatment. Measures included pure tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and …

Refinement Of Hyams Grading Criteria For Olfactory Neuroblastoma In An Endoscopic Sinus Surgery Predominant Cohort With Extended Follow-Up: Worth The Effort?, Stacey Gargano, Vincent Cracolici, Carl Snyderman, Eric Wang, Garret Choby, Aron Pollack, Paul Gardner, Diana Bell, Raja Seethala

Computational Medicine Center Faculty Papers

BACKGROUND: Hyams grading is considered prognostic in olfactory neuroblastoma (ONB), but grading criteria are subjective and predate modern classification and surgical approach. We evaluate the application of granular grading criteria to an endoscopic surgery predominant cohort with extended follow-up.

METHODS: 78 ONB patients were identified (1994-2019) with original diagnoses dating to 1979. Original Hyams grade, Modified Hyams grade incorporating more detailed criteria and other histologic features (i.e. divergent differentiation, clear cell/oncocytic change, and spindling) were assessed if feasible, evaluated for distribution by grade and correlated with outcomes.

RESULTS: Original Hyams grade (n = 43) distribution was: I: 4 (9%), II: …

Epigenomic Diagnosis And Prognosis Of Acute Myeloid Leukemia., Francisco Marchi, Vivek M. Shastri, Richard J. Marrero, Nam H K Nguyen, Antonella Öttl, Ann-Kathrin Schade, Marieke Landwehr, Olga Krali, Jessica Nordlund, Matin Ghavami, Fernando Sckaff, Vikash K. Mansinghka, Xueyuan Cao, William Slayton, Petr Starostik, Christopher R. Cogle, Raul C. Ribeiro, Jeffrey E. Rubnitz, Jeffery Klco, Abdelrahman Elsayed, Alan S. Gamis, Timothy J. Triche, Rhonda Ries, E Anders Kolb, Richard Aplenc, Todd Alonzo, Stanley Pounds, Soheil Meshinchi, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

Despite the critical role of DNA methylation, clinical implementations harnessing its promise have not been described in acute myeloid leukemia. Utilizing DNA methylation from 3314 leukemia patient samples across 11 harmonized cohorts, we describe the Acute Leukemia Methylome Atlas, which includes robust models capable of accurately predicting AML subtypes. A genome-wide prognostic model as well as a targeted panel of 38 CpGs significantly predict five-year survival in our pediatric and adult test cohorts. To accelerate rapid clinical utility, we develop a specimen-to-result protocol that uses long-read nanopore sequencing and machine learning to characterize patients' whole genomes and epigenomes. Clinical validation …

Neighborhood Environment And Incident Diabetes, A Neighborhood Environment-Wide Association Study ('Ne-Was'): Results From The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol)., Cara M. Smith, Elizabeth W. Spalt, Linda C. Gallo, Jordan A. Carlson, Matthew Allison, Daniela Sotres-Alvarez, Christina Cordero, Qibin Qi, Earle C. Chambers, Martha Daviglus, Amber Pirzada, Gregory A. Talavera, Robert Kaplan, Joel D. Kaufman, Stephen J. Mooney

Manuscripts, Articles, Book Chapters and Other Papers

The prevalence of type 2 diabetes is increasing among the Hispanic/Latino population. Type 2 diabetes incidence rates vary between neighborhoods, but no single aspect of the neighborhood environment is known to cause type 2 diabetes. Using data from the Hispanic Community Health Study/Study of Latinos cohort of 16,415 Hispanic/Latino adults in four major US cities, we conducted a neighborhood environment-wide association study to identify neighborhood measures or clusters of measures associated with diabetes incidence. Two-hundred and four neighborhood measures were calculated at the census tract level or within a 1-km buffer of participants' residential addresses. Independent covariate-adjusted and survey-weighted Poisson …

Use Of A Shoulder-Mounted Wearable Sensor Prototype Designed To Detect Opioid-Related Overdose: A Qualitative User Experience Study, Alexis M. Roth, Ally K. D'Angelo, David Gordon, Benjamin Cocchiaro, Anush Lingamoorthy, Rose Laurano, Matthew Salzman, Jacob S. Brenner, Cameron Baston

SKMC Student Presentations and Publications

BACKGROUND: For over a decade, drug overdose has been the leading cause of injury and accidental death in the United States. Most fatal overdoses involve opioids and occur during solitary drug use events when no one is available to initiate lifesaving responses (eg, naloxone). While there is a growing interest in devices providing early overdose detection and automated responses, little research has engaged end users in a device design process.

OBJECTIVE: This study aimed to describe user experience, perceived harms and benefits, and the acceptability of a shoulder-mounted wearable sensor among people who inject drugs who wore a device prototype …

Pilot Study Of [11c]Hy-2-15: A Mixed Alpha-Synuclein And Tau Pet Radiotracer, Chia-Ju Hsieh, Dinahlee Saturnino Guarino, Anthony J Young, Andrew D Siderowf, Ilya Nasrallah, Alexander Schmitz, Carol Garcia, Ho Young Kim, Erin K Schubert, Hsiaoju Lee, Joel S Perlmutter, Robert H Mach

2020-Current year OA Pubs

A novel brain positron emission tomography (PET) radioligand, [

Replication Of Sensor-Based Categorization Of Upper-Limb Performance In Daily Life In People Post Stroke And Generalizability To Other Populations, Chelsea E Macpherson, Marghuretta D Bland, Christine Gordon, Allison E Miller, Caitlin Newman, Carey L Holleran, Christopher J Dy, Lindsay Peterson, Keith R Lohse, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Wearable movement sensors can measure upper limb (UL) activity, but single variables may not capture the full picture. This study aimed to replicate prior work identifying five multivariate categories of UL activity performance in people with stroke and controls and expand those findings to other UL conditions.

METHODS: Demographic, self-report, and wearable sensor-based UL activity performance variables were collected from 324 participants (stroke

RESULTS: Two PCs explained 70-90% variance: PC1 (overall UL activity performance) and PC2 (preferred-limb use). A five-variable, five-cluster model was optimal across samples. In comparison to clusters, two PCs and individual accelerometry variables showed higher convergent …

Phase 1b/2 Study Evaluating Safety, Efficacy And Immune Effects Of Tlr9 Agonist Cavrotolimod With Anti-Pd-1 Antibodies Among Patients With Advanced Solid Tumors, Mohammed M Milhem, George Ansstas, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is an unmet need for novel immunotherapies to overcome immune evasion in patients with advanced skin cancers resistant to programmed death (PD)-1 / PD-ligand 1 (PD-L1) blockade. Cavrotolimod is a novel spherical nucleic acid configuration of a toll-like receptor 9 agonist oligonucleotide, designed to trigger innate and adaptive immune responses to tumors.

PATIENTS AND METHODS: The safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of intratumoral cavrotolimod, first dosed alone and then in combination with anti-PD-1 antibodies (pembrolizumab or cemiplimab), were assessed in a combined Phase 1b/2 dose escalation/dose expansion study in patients with advanced skin cancers, including melanoma, Merkel …

Imaging Efficacy And Safety Of Low Dose Intraventricular Tissue Plasminogen Activator In Aneurysmal Subarachnoid Hemorrhage: Case Series, Collin Liu, William W Wroe, Hussein A Zeineddine, Bryden Dawes, Michael Giordano, Aaron Mccabe, Ching-Jen Chen, Devin W Mcbride, Aaron M Gusdon, Huimahn A Choi, Spiros L Blackburn

Faculty, Staff and Student Publications

Introduction: Free hemoglobin's release into CSF from blood breakdown is a primary instigator of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Early clearance of subarachnoid blood with intrathecal (IT) fibrinolytics has shown potential to decrease incidence of DCI. However, the dosage of fibrinolytic needed is not known. We investigated the ability of low dose tissue plasminogen activator (tPA) to rapidly remove subarachnoid clot.

Material and methods: We performed a single center retrospective review of aSAH patients who received IT tPA. Dosing consistent with the CLEAR III trial for IVH was utilized-tPA (1 mg) administered every 8 h via …

Machine-Learning Driven Strategies For Adapting Immunotherapy In Metastatic Nsclc, Maliazurina B Saad, Qasem Al-Tashi, Lingzhi Hong, Vivek Verma, Wentao Li, Daniel Boiarsky, Shenduo Li, Milena Petranovic, Carol C Wu, Brett W Carter, Girish S Shroff, Tina Cascone, Xiuning Le, Yasir Y Elamin, Mehmet Altan, Simon Heeke, Ajay Sheshadri, Joe Y Chang, Percy P Lee, Zhongxing Liao, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Ignacio I Wistuba, Cara Haymaker, Seyedali Mirjalili, David Jaffray, Justin F Gainor, Yanyan Lou, Alessandro Di Federico, Federica Pecci, Mark Awad, Biagio Ricciuti, John V Heymach, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs), either as monotherapy (ICI-Mono) or combined with chemotherapy (ICI-Chemo), improves survival in advanced non-small cell lung cancer (NSCLC). However, prospective guidance for choosing between these options remains limited, and single-feature biomarkers like PD-L1 prove inadequate. We develop a machine learning model using clinicogenomic data from four cohorts (MD Anderson n = 750; Mayo Clinic n = 80; Dana-Farber n = 1077; Stand Up To Cancer n = 393) to predict individual benefit from adding chemotherapy. Benefit scores are calculated using five distinct functions derived from 28 genomic and 6 clinical features. Our integrated model, A-STEP (Attention-based …

Project Evolve: An International Analysis Of Postimmunotherapy Lineage Switch, An Emergent Form Of Relapse In Leukemia, Sara K Silbert, Alexander W Rankin, Chloe N Hoang, Alexandra Semchenkova, Regina M Myers, Elena Zerkalenkova, Hao-Wei Wang, Alexandra E Kovach, Constance M Yuan, Dana Delgado Colon, Loïc Vasseur, Alex Bataller, Samuel John, Kaylyn Utley Lyons, Barbara Friedes, Anna Alonso-Saladrigues, Hisham Abdel-Azim, Estelle Balducci, Ahmed Assim Aljudi, Marie Balsat, D Nathan Biery, Aghiad Chamdin, Bill H Chang, Raymund S Cuevo, Barbara De Moerloose, David S Dickens, Ulrich Duffner, Nicolas Duployez, Firas El Chaer, Michelle Ann Elliott, Gabriele Escherich, Sneha Fernandes, Mandi R Fitzjohn, Zhubin Gahvari, Stephan A Grupp, Rui Rochelle He, Cynthia Harrison, Christopher B Hergott, Emily M Hsieh, Annette S Kim, Dennis J Kuo, Daniel P Larson, Benjamin J Lee, Thibaut Leguay, R Coleman Lindsley, Abhishek A Mangaonkar, Kerstin Mezger, Holly L Pacenta, Jing Pan, Marlie Provost, Latika Puri, Sunil S Raikar, Armando Martinez, Isabella Bristol, Kyle Murphy, Lauren Reiman, Michele Redell, Kelly Reed, Gabrielle Roth-Guepin, Jeremy Rubinstein, Süreyya Savaşan, Kristian Schafernak, Alexandra Stevens, Aimee Talleur, Naomi Torres Carapia, Jacques Vargaftig, Anant Vatsayan, Matthias Wölfl, Liping Zhao, Susana Rives, Vanessa A Fabrizio, Koji Sasaki, Ibrahim Aldoss, Nicolas Boissel, Susan R Rheingold, Kara L Davis, Sara Ghorashian, Elad Jacoby, Alexander Popov, Adam J Lamble, Nirali N Shah

Faculty, Staff and Students Publications

Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute …

Effects Of Oxygen Manipulation On Myofibroblast Phenotypic Transformation In Patients With Radiation-Induced Fibrosis, Eric Mastrolonardo, Sarah Sussman, Bo Yun, Victor Jegede, Dev Amin, Joel Rosenbloom, Andrew P. South, Voichita Bar-Ad, Peter J Wermuth, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

We tested if hyperoxic conditions can reduce the proportion of active myofibroblasts, which are assumed to be a major driver of head and neck radiation-induced fibrosis, as measured by expression levels of pro-fibrotic genes. Radiated, non-cancerous soft tissue from the head and neck and skin/soft tissue from non-radiated flap donor site were collected from each patient. Myofibroblast density was quantified using immunofluorescence staining with α-SMA and DAPI and visualisation under confocal microscopy and compared between baseline non-radiated and radiated tissue from the same patient. From each tissue specimen, fibroblast cell lines were cultured and exposed to either normoxic, hypoxic, or …

Effects Of Long Covid On Healthcare Utilization, Michael Gottlieb, Erica S. Spatz, Huihui Yu, Imtiaz Ebna Mannan, Michelle Santangelo, Caitlin Malicki, Nicole L. Gentile, Rachel E. Geyer, Alex Charlton, Jonathan W. Dyal, Joann G. Elmore, Kristyn Gatling, Mandy J. Hill, Juan Carlos C. Montoy, Kelli N. O'Laughlin, Kristin L. Rising, Sharon Saydah, Kari A. Stephens, Ralph C. Wang, Lauren E. Wisk, Arjun K. Venkatesh, Robert A. Weinstein

Jefferson Center for Connected Care Faculty Papers

BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC.

METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the …

One-Year Clinical Outcomes In Patients With Acute Coronary Syndrome Treated With Clopidogrel Versus Prasugrel Versus Ticagrelor: Results Of The Polish Registry Of Acute Coronary Syndromes (Pl-Acs), Julia M. Umińska, Michał Skrzypek, Małgorzata Ostrowska, Piotr Adamski, Aldona Kubica, Piotr Niezgoda, Robert Gajda, Marek Gierlotka, Bartosz Hudzik, Wiktor Kuliczkowski, Diana A. Gorog, Paul A. Gurbel, Jolanta Siller-Matula, Łukasz Szarpak, Michael Savage, Grzegorz Skonieczny, Udaya Tantry, Przemysław Trzeciak, Eliano P. Navarese, Jacek Kubica, Mariusz Gąsior

Division of Cardiology Faculty Papers

BACKGROUND: Efficient dual antiplatelet therapy is crucial in reducing adverse cardiovascular events in patients with acute coronary syndrome (ACS). Comparative effectiveness between clopidogrel, prasugrel, and ticagrelor remains unclear in real-world settings.

AIMS: The objective was to evaluate one-year clinical outcomes in ACS patients treated with clopidogrel, prasugrel, or ticagrelor using data from the Polish Registry of Acute Coronary Syndromes (PL-ACS).

MATERIAL AND METHODS: This retrospective cohort study analyzed 381 278 ACS patients from the PL-ACS registry from 2009 to 2022, who were treated with clopidogrel, prasugrel, or ticagrelor during hospitalization with a 12-month consistent regimen. The primary outcome was one-year …

Participant Engagement In A National Longitudinal Study Of Covid-19: Insights From The Inspire Study, Kris Pui Kwan Ma, Tracy Stober, Michael Gottlieb, Rachel E. Geyer, Kristin L. Rising, Sharon Saydah, Michelle Santangelo, Kristyn Gatling, Dylan Grau, Ralph C. Wang, Juan Carlos Montoy, Ahamed Idris, Samuel Macdonald, Mandy J. Hill, Ryan Huebinger, Maria G. Prado, Nicole L. Gentile, Erica Spatz, Caitlin Maliki, Jocelyn Dorney, Joann G. Elmore, Michelle L'Hommedieu, Robert A Weinstein, Arjun K. Venkatesh, Kari A. Stephens

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S.

METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data.

RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to …

Clinicopathologic Risk Factors For Post-Operative Complications After Enucleation Of Pancreatic Neoplasms, Isheeta Madeka, Steven Yi, Julia S. Evans, David Baek, Haresh V. Naringrekar, Harish Lavu, Charles J. Yeo, Avinoam Nevler, Wilbur B. Bowne

Kimmel Cancer Center Faculty Papers

BACKGROUND: Pancreatic enucleation is a parenchymal-sparing procedure used for highly select patients with pancreatic neoplasms. We aim to utilize a multi-institutional health research network platform (TriNetX) and a single, high-volume center to assess complications and identify risk factors associated with post-operative pancreatic fistulas (POPF) after pancreatic enucleation.

METHODS: A two-tiered retrospective study was conducted. We identified 423 patients from TriNetX, and 34 patients from a single-institution IRB-approved database who underwent pancreatic enucleation between 2004-2025 and 2012-2023, respectively. Univariate and multivariate analyses were performed to determine risk factors associated with post-operative complications and occurrence of POPFs.

RESULTS: In the TriNetX cohort, …

Experience Matters: An Application Of The Operative Value Index For Lumbar Fusions, Danyal Quraishi, Advith Sarikonda, D. Mitchell Self, Steven R. Glener, Arbaz A. Momin, Emily L. Isch, Ashmal K. Sami, Matthews Lan, Nicholas Clark, Ashwini Sharan, Srinivas Prasad, Jack Jallo, Joshua Pelta-Heller, Alex R. Vaccaro, James Harrop, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

INTRODUCTION: As healthcare systems transition to value-based care models, it is critical to understand factors influencing costs and outcomes in neurosurgery. This study utilizes Time-Driven Activity-Based Costing (TDABC) to assess the impact of surgeon experience and case volume on costs, clinical outcomes, and operative value in lumbar fusions. While TDABC has been applied in various surgical specialties, its use in neurosurgery, particularly in analyzing surgeon-specific factors, remains limited.

METHODS: A retrospective cohort study was conducted at a single center, analyzing lumbar instrumented arthrodesis procedures from 2017 to 2019. Primary variables included surgeon experience (years) and case volume (annual procedures). Confounding …

Timing Of Nodal Metastasis In Patients With Eyelid Sebaceous Carcinoma And Implications For Surveillance And Survival, Tracy Lu, Casey Anthony, Xinyang Jiang, Jing Ning, Ryan Goepfert, Bita Esmaeli

Faculty, Staff and Student Publications

Background/aims: Sebaceous carcinoma (SC) is a rare cancer with periocular predilection. Studies focused on patterns and timing of nodal metastasis are scarce.Our aim is to report patterns of regional nodal metastasis in patients with eyelid SC, including results of sentinel lymph node biopsy (SLNB).

Methods: All consecutive patients with eyelid SC treated during 1999-2023 were retrospectively reviewed.All subjects had standard of care surgery for eyelid SC and regional lymph node evaluation using physical examination and ultrasonography (US) at baseline and during the surveillance period. 38 patients with negative findings on US had SLNB to rule out microscopic metastasis.The frequency and …

Longitudinal Analysis Of Gut Microbiome And Metabolome Correlates Of Response And Toxicity With Idecabtagene Vicleucel, Satabdi Saha, Lubna Rehman, Abdur Rehman, Faezeh Darbaniyan, Donna M Weber, Melody Becnel, Mahmoud Gaballa, Sheeba K Thomas, Hans C Lee, Chia-Chi Chang, Reetakshi Arora, Meghan Menges, Salvatore Corallo, Marco L Davila, Frederick L Locke, Mark R Tanner, Sattva S Neelapu, Elizabeth J Shpall, Christopher R Flowers, Robert Z Orlowski, Robert R Jenq, Michael D Jain, Christine Peterson, Doris K Hansen, Neeraj Y Saini, Krina K Patel

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor T-cell (CAR-T) therapy. We conducted whole-genome shotgun sequencing on stool samples (N = 117) collected at various times from patients with multiple myeloma (n = 33) who underwent idecabtagene vicleucel (ide-cel) anti-B-cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity after ide-cel infusion, along with significant differences in the bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding …

Belumosudil Reduces Oral Chronic Graft-Versus-Host Disease Tissue Inflammation And Fibrosis: A Rockstar Companion Study, Rubina Sharma, Noa G Holtzman, Iskra Pusic, Corey Cutler, Nathaniel Treister, Rohtesh S Mehta, Amin S Alousi, Nadarajah Vigneswaran, Ayesha Javaid, Francis Boksa, Drashty P Mody, Ana C Costa-Da-Silva, Olivier Schueller, Sandrine Macé, Yu Yao, Ran Ji, Beifang Hu, Kathy Marshall, Bruce R Blazar, Stephanie J Lee, Steven Z Pavletic, Jacqueline W Mays

Faculty, Staff and Student Publications

Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin-17 (IL-17) activity and promotes regulatory T-cell (Treg cell) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues. This study assessed tissue-level immune dynamics in 20 patients with oral cGVHD from the phase 2 ROCKstar trial, before and after 6 months of belumosudil treatment, focusing on key effector sites (oral mucosa [OM], minor salivary glands [MSGs], and skin) and the peripheral blood. After belumosudil treatment, reduction in …

Detection Of Oncogenic Fusions In Colorectal Cancer Using A Partner-Agnostic Next-Generation Sequencing Approach, Andrew J Pellatt, Reagan M Barnett, Sante Gnerre, Kristin Edwards, Jason A Willis, Michael J Overmann, Kanwal Raghav, Christine M Parseghian, Arvind Dasari, M Pia Morelli, Alisha Bent, Madhulika Eluri, Nicholas Hornstein, Leylah M Drusbosky, Scott Kopetz, Van K Morris

Faculty, Staff and Student Publications

Background: Gene fusions exist with low prevalence in colorectal cancer (CRC), and the clinical utility of fusion testing in advanced CRC remains unclear. We sought to identify oncogenic fusions in patients with advanced CRC using a fusion partner-agnostic circulating tumor DNA (ctDNA) assay to better understand their clinical relevance.

Methods: We performed a retrospective analysis using de-identified data from 18,558 patients with advanced CRC who underwent ctDNA next-generation sequencing with Guardant360® from 2017 to 2022. These samples were subsequently reanalyzed with a partner-agnostic bioinformatics method to identify both clonal and non-clonal fusions. We analyzed for associations between fusions and MSI-H …