Digital Commons Network^™

Loss Of Kdm6a-Mediated Genomic Instability And Metabolic Reprogramming Regulates Response To Therapeutic Perturbations In Bladder Cancer, Pratishtha Singh, Ranit D'Rozario, Bidisha Chakraborty, Swadhin Meher, Deblina Raychaudhuri, Aminah J Tannir, Yang Li, Anurag Majumdar, Jessalyn Hawkins, Yun Xiong, Philip Lorenzi, Padmanee Sharma, Kadir Akdemir, Patrick Pilie, Abhinav K Jain, Byron Hing Lung Lee, Sangeeta Goswami

Faculty, Staff and Student Publications

Mutations in epigenetic regulators are common in bladder cancer, yet their impact on therapeutic responses remains unclear. Here, we identify that loss-of-function mutations in KDM6A, a histone demethylase altered in about 26% of advanced bladder cancers, are associated with poor survival after cisplatin chemotherapy, whereas they correlate with improved outcomes with anti-PD-1 therapy. Using CRISPR-Cas9-engineered murine and human bladder cancer models, we show that KDM6A deficiency increases formation of extrachromosomal circular DNA carrying chemoresistance loci, promoting cisplatin resistance. In parallel, KDM6A loss impairs DNA repair and rewires tumor metabolism, reducing glycolysis and lactate output. This metabolic shift diminishes histone lactylation …

Assessing The Effects Of Ehealth Literacy And The Area Deprivation Index On Barriers To Electronic Patient Portal Use For Orthopedic Surgery: Cross-Sectional Observational Study, Audrey Lynn Litvak, Nicholas Lin, Kelly Hynes, Jason Strelzow, Jeffrey G Stepan

2020-Current year OA Pubs

BACKGROUND: As electronic patient portals (EPPs) continue to gain popularity and systems transition to online tools for scheduling, communication, and telehealth, patients without access or skills to use these tools may be overlooked.

OBJECTIVE: This study analyzed patient and neighborhood-level factors, including eHealth literacy level and the Area Deprivation Index (ADI), that may limit EPP access for orthopedic surgery.

METHODS: A cross-sectional, survey-based study was performed at a single urban tertiary academic medical center in the United States across foot and ankle, hand and upper extremity, and orthopedic trauma subspecialty clinics from June 21, 2022, to August 12, 2022. Survey …

N-Palmitoyl Glutamine Is A Candidate Mediator Of Cardiorespiratory Fitness, Jeremy M Robbins, Mark Benson, Anthony R P Verkerke, Gaurav Tiwari, Shuliang Deng, Prashant Rao, Usman A Tahir, Julian Avila-Pacheco, Xu Shi, Yuntian Guan, Foje-Geh Tendoh, Jacob L Barber, Patricia E Miller, Andrew S Perry, Michael E Hall, Alexis C Wood, Kent D Taylor, Wendy S Post, Stephen S Rich, Matthew Nayor, James G Wilson, Gregory D Lewis, Ravi V Shah, Jerome I Rotter, Scott A Summers, Laura M Raffield, Shingo Kajimura, Claude Bouchard, Clary B Clish, Mark A Sarzynski, Robert E Gerszten

Children’s Nutrition Research Center Staff Publications

Background: Cardiorespiratory fitness is an integrative measure of cardiometabolic health and predictor of survival, yet little is known about its molecular underpinnings. Small molecule metabolites and lipids are increasingly recognized as exercise-stimulated signaling molecules and candidate molecular transducers of cardiorespiratory fitness.

Methods: We performed nontargeted liquid chromatography mass spectrometry-based plasma metabolomics in 654 participants (mean age, 35 years; 55% women) from the HERITAGE Family Study (Health, Risk Factors, Exercise Training, and Genetics) who had cardiorespiratory fitness (maximal oxygen uptake [VO2max]) measured by cardiopulmonary exercise testing and underwent 20 weeks of supervised endurance training. Metabolite-VO2max relationships were assessed using linear regression …

Music Therapy Versus Cognitive Behavioral Therapy Via Telehealth For Anxiety In Survivors Of Cancer: A Randomized Clinical Trial, Kevin T. Liou, Joke Bradt, M. Beatriz Currier, Raymond Baser, Katherine Panageas, Jodi Macleod, Desiree Walker, Susan Q. Li, Ana Maria Lopez, Kelly Mcconnell, Jun J. Mao

Department of Medical Oncology Faculty Papers

PURPOSE: Anxiety is prevalent, disruptive, and undertreated among survivors of cancer. Cognitive behavioral therapy (CBT) is the first-line treatment, but not all individuals have access, respond to treatment, or prefer this option because of stigma. Music therapy is effective for short-term anxiety reduction, but it is unknown whether it is noninferior to first-line CBT for long-term anxiety reduction.

METHODS: This comparative effectiveness trial randomly assigned English- or Spanish-speaking survivors of cancer to seven weekly telehealth sessions of music therapy or CBT. The coprimary end points were changes in the Hospital Anxiety and Depression Scale (HADS) anxiety score at weeks 8 …

Inhibition Of Gpx4 Induces The Death Of P53-Mutant Triple-Negative Breast Cancer Cells, William M Tahaney, Amanda Lanier, Jing Qian, Cassandra L Moyer, Nghi Nguyen, Yanxia Ma, Jamal Hill, Reid T Powell, Clifford C Stephan, Peter J A Davies, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods: In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was …

Peripheral Nerve Injury Reduces Macrophage Efferocytosis To Facilitate Neuropathic Pain, Vipul K Pandey, Tusar K Acharya, Kendal F Willcox, Sandeep Dembla, Ajeena Ramanujan, Anamaria R Grieco, Younus A Zuberi, Rajasekaran Mahalingam, Andrew J Shepherd, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

For reasons not fully understood, proresolving immune processes sometimes fail to engage after peripheral nerve injury (PNI), leading to enhanced neuropathic pain and inflammation. Here, we implicate reduced efferocytosis due to proteolytic cleavage of surface MER tyrosine kinase (MERTK) from macrophages at the site of PNI. After PNI, the proportion of macrophages expressing MERTK progressively decreased, while soluble (cleaved) MER increased. Using male and female knock-in mice encoding cleavage-resistant Mertk, we demonstrated that cleavage of MERTK from macrophages at the PNI site led to exaggerated pain-related behaviors. PNI-induced hyperactivity of TRPV1+ sensory neurons and damage to myelin and myelinated …

Twin And Cotwin Predictors Of Fetal Demise After Laser Photocoagulation Therapy In Advanced Stage Twin-Twin Transfusion Syndrome: A Fetal Heart Society Research Collaborative Study, Shiraz A Maskatia, Fu-Sheng Chou, Betul Yilmaz, Lisa Howley, Vidhya Annavajjhala, Lindsay Freud, Allison Divanovic, Laxmi Ghimire, Anita J Moon-Grady

Faculty, Staff and Student Publications

Background: Current models to predict outcomes in advanced twin-twin transfusion syndrome are limited. We hypothesized that twin and cotwin echocardiographic factors would improve model performance for donor and recipient demise following laser photocoagulation therapy.

Methods: We performed a multicenter retrospective cohort study of stage 3 to 4 twin-twin transfusion syndrome referred for laser photocoagulation therapy. Fetal echocardiograms were analyzed at a core laboratory. We used multivariable logistic regression models to select variables used for generalized linear mixed-effects modeling. Separate models were developed for donor and recipient demise, using both twin and cotwin variables. Models were assessed by area under the …

Predicting Sepsis In Heart Failure Patients Supported By Left Ventricular Assist Devices: The Role Of Ve-Cadherin And Adam10, Shiyi Li, Iván Murrieta-Álvarez, Ismael Garcia, Katherine V Nordick, Rishav Bhattacharya, Shreyo Ghosh, Ronald A Shaju, Adel M Hassan, Carl P Walther, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Vascular endothelial cadherin (VE-Cadherin) is a major endothelial adhesion molecule and can be cleaved explicitly by metalloproteinase domain-containing protein 10 (ADAM10). Vascular hyperpermeability may contribute to a greater susceptibility to sepsis in left ventricular assist device (LVAD) support patients. We aim to evaluate the efficacy of VE-Cadherin and ADAM10 for predicting sepsis in LVAD patients. We prospectively recruited 50 patients with advanced heart failure receiving LVAD therapy. Baseline and weekly postoperative blood samples (weeks 1-4) were collected, and plasma VE-cadherin and ADAM10 levels were measured. Sepsis occurred in 9 of 50 patients (18.0%). Across all sampling points, plasma VE-cadherin and …

Bio-Adrenomedullin Predicts Death And Major Adverse Cardiovascular Events In Cardiac Amyloidosis: A Cross-Continental Multicenter Study, Maximilian L Müller, Fabian Knebel, Katrin Hahn, Janin Schulte, Birte Arlt, Oliver Hartmann, Kaitlin M S Moore, Seiji Takashio, Yasuhiro Izumiya, Joshua D Mitchell, Kenichi Tsujita, Ulf Landmesser, Bettina Heidecker

2020-Current year OA Pubs

BACKGROUND: Bio-ADM (bioactive adrenomedullin) is a vasoactive peptide hormone that predicts clinical outcomes in heart failure-the main driver of adverse outcomes in cardiac amyloidosis (CA). This prospective observational study sought to assess the prognostic role of bio-ADM in CA.

METHODS: Patients with CA were enrolled from amyloid centers in Germany (observation cohort), Japan, and the United States (combined validation cohort). Bio-ADM was quantified using the sphingotest bio-ADM assay. Associations of bio-ADM with all-cause death and major adverse cardiovascular events over 2 years were assessed using Kaplan-Meier and Cox regression analyses. Likelihood ratio chi-square tests for nested models evaluated whether adding …

Intravenous Thrombolysis In Patients On Direct Oral Anticoagulants: Analysis Of The Get With The Guidelines Stroke Registry, Shadi Yaghi, Opeolu Adeoye, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in patients with AIS with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded due to recent DOAC use.

METHODS: This study included patients for the GWTG (Get With The Guidelines) registry with a diagnosis of AIS within 4.5 hours from last known normal, on a DOAC, and either (1) received intravenous thrombolysis, or (2) were excluded from …

Durability Of The Benefit Of Vagus Nerve Stimulation In Markedly Treatment-Resistant Major Depression: A Recover Trial Report, Charles R Conway, Christopher L Kriedt, Charles F Zorumski, Hunter Brown, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Greater levels of treatment resistance in major depressive disorder (MDD) are associated with lower rates of initial benefit and higher rates of relapse (lower durability).

OBJECTIVE: Characterize depressive symptoms, function, and quality of life (QoL) over 24 months of adjunctive vagus nerve stimulation (VNS) in participants with markedly treatment-resistant depression.

DESIGN: Prospective, open-label, single-arm, long-term extension study (RECOVER) conducted from September 2019 to April 2025.

SETTING: Outpatient.

PARTICIPANTS: Adults with moderate-severe MDD with ≥ 4 failed antidepressant trials in the current episode, randomized to blinded, adjunctive VNS for 12 months, who subsequently received open-label, adjunctive VNS for 12 additional …

Postoperative Lymph Is A Proximal Source Of Ctdna For Detection Of Recurrence In Hpv-Independent Head And Neck Cancer, Seka Lazare, Noah Earland, Peter Harris, Ricardo Ramirez, Benjamin Wahle, Sid Puram, Doug Adkins, Wade Thorstad, Rebecca Chernock, Aadel A Chaudhuri, Et Al.

2020-Current year OA Pubs

PURPOSE: Relapse is a major cause of failure in human papillomavirus-independent head and neck squamous cell carcinoma. Clinicopathologic criteria for adjuvant treatment remain imprecise and have not changed for decades. We investigated whether ctDNA in lymphatic exudate collected via surgical drains ("lymph") 24 hours after surgery identified molecular residual disease (MRD) and compared its performance with time-matched plasma.

EXPERIMENTAL DESIGN: Using an ultra-sensitive tumor-informed sequencing approach, tumor variants were called in lymph and plasma to classify patients as ctDNA positive or ctDNA negative, trained in an initial cohort of 36 patients, and replicated in an independent cohort of 37 patients. …

What Is The Psychological And Cognitive Impact Of Returning Alzheimer Disease Dementia Research Results To Healthy Research Participants? A Delayed-Start Randomised Clinical Trial Protocol For The Weshare Study (Washington University Study Of Having Alzheimer Disease), Sarah M Hartz, Spondita Goswami, Amy Oliver, Alissa Evans, Sacha Jackson, Erin Linnenbringer, Krista M Moulder, John C Morris, Jessica Mozersky

2020-Current year OA Pubs

INTRODUCTION: Returning research results that indicate risk of Alzheimer disease (AD) dementia-a disease for which no meaningful treatments or cure exist-to cognitively normal participants is controversial. AD is thought to begin many years before clinical signs and symptoms begin. During this time, individuals are cognitively normal but have biomarkers that indicate pathophysiological changes in the brain. With this study, we aim to evaluate the impact of returning research results on cognitively normal participants recruited from a longitudinal observational cohort on ageing at the Knight Alzheimer Disease Research Centre (Knight ADRC) at Washington University in St. Louis.

METHODS AND ANALYSIS: Our …

Association Between Monoclonal Gammopathy Of Undetermined Significance And Cardiovascular Disease Risk: A Veterans Health Administration Study, Tzeyu L Michaud, Mei Wang, Daphne R Friedman, Lawrence Liu, Theodore S Thomas, Kristen M Sanfilippo, Graham A Colditz, Martin W Schoen, Su-Hsin Chang

2020-Current year OA Pubs

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease (CVD). However, its potential to provide additional prognostic information beyond traditional CVD risk assessments remains unknown. This study aimed to examine the association between MGUS and incident CVD and to determine whether MGUS status offers additional prognostic value beyond the established atherosclerotic cardiovascular disease risk calculation.

METHODS: We conducted a retrospective, matched observational study using 2010 to 2021 Veterans Health Administration data. MGUS status, confirmed through a validated natural language processing algorithm, were 1:5 matched to individuals without MGUS. The outcome of interest was …

Clinical Performance Of A Novel Point-Of-Care High-Sensitivity Cardiac Troponin I Assay, Alan H. B. Wu, Simon A. Mahler, Stacey L. House, Saeed A. Jortani, Michael H. Creer, Kristin L. Rising, Jason J. Bischof, Chad Crystal, Gary F. Headden, Fred S. Apple, Nicholas E. Harrison, Andrew C. Meltzer, Justin T. Baca, Brian Tiffany, Mark Sochor, Grace U. Pentecostes, Katrina P. Di Tullio, Manish S. Gupta, Adam J. Singer, James L. Januzzi

Department of Emergency Medicine Faculty Papers

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).

METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and >1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with …

Stakeholder Perspectives On Humanistic Implementation Of Computer Perception In Health Care: Qualitative Study, Kristin M Kostick-Quenet, Meghan E Hurley, Syed Ayaz, John D Herrington, Casey J Zampella, Julia Parish-Morris, Birkan Tunç, Gabriel Lázaro-Muñoz, Jennifer Blumenthal-Barby, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Computer perception (CP) technologies-including digital phenotyping, affective computing, and related passive sensing approaches-offer unprecedented opportunities to personalize health care, especially mental health care, yet they also provoke concerns about privacy, bias, and the erosion of empathic, relationship-centered practice. At present, it remains elusive what stakeholders who design, deploy, and experience these tools in real-world settings perceive as the risks and benefits of CP technologies.

Objective: This study aims to explore key stakeholder perspectives on the potential benefits, risks, and concerns associated with integrating CP technologies into patient care. A better understanding of these concerns is crucial for responding to …

Omg! A Proteomic Determinant Of Neurodegenerative Resiliency, Michael R Duggan, Muhammad Ali, Menghan Liu, Ying Xu, Daniel Western, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Biofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer's disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation.

METHODS: After detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG's role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, …

Clinical Performance Of A Novel Point-Of-Care High-Sensitivity Cardiac Troponin I Assay, Alan H B Wu, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).

METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and >1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with …

Environmental Enteric Dysfunction In Well-Nourished And Undernourished Women In Bangladesh, Mustafa Mahfuz, Md Shabab Hossain, Ar-Rafi Khan, Mehjabin Tishan Mahfuz, Rumana Sharmin, A H M Rezwan, Musarrat Tasnim, S M Tafsir Hasan, S M Khodeza Nahar Begum, M Masudur Rahman, Michael J Barratt, Jeffrey I Gordon, Tahmeed Ahmed

2020-Current year OA Pubs

INTRODUCTION: Environmental Enteric Dysfunction (EED) is a subacute inflammation of the small intestinal (SI) mucosa associated with undernutrition and perturbation of the SI microbiota. Its diagnosis relies on histopathological assessment of small intestinal biopsies, with a lack of validated biomarkers contributing to underdiagnosis. This study assessed the prevalence and histological features of EED in undernourished Bangladeshi women living in an urban slum in Dhaka, compared to well-nourished women from slum and non-slum areas, and examined the factors associated with histologically confirmed EED.

METHODS: This analysis included non-pregnant, non-lactating Bangladeshi women aged 18-45 years classified by location of residence and nutritional …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Deep-Learning Serial Ct Prediction Of Survival In Immunotherapy-Treated Non-Small Cell Lung Cancer., Chiharu Sako, Brenda F Kurland, Taly G Schmidt, Jing He, Marius De Groot, Arpan A Patel, Dwight H Owen, Arya Amini, Brendan D Curti, Ronan J Kelly, Ray D Page, Aurelie Swalduz, Jean-Paul Beregi, Jan Chrusciel, Stephane Sanchez, Jakob Weiss, An Liu, Olivier Gevaert, Alma Hart, George R Simon, Ravi B Parikh, Jasper Van Der Aart, Petr Jordan

Oncology Articles

IMPORTANCE: Reliable early response biomarkers for overall survival (OS) are lacking for patients receiving immune checkpoint inhibitor (ICI) therapy for advanced non-small cell lung cancer (NSCLC). Existing imaging-based measures, such as Response Evaluation Criteria in Solid Tumors (RECIST) and tumor volume change (TVC), have limited predictive value for long-term outcomes, and advanced imaging-based biomarkers may enhance decision-making in clinical practice and clinical trials.

OBJECTIVE: To develop and validate a fully automated deep-learning imaging-based biomarker using pretherapy and 12-week follow-up computed tomography (CT) scans.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used retrospectively collected HER data from routine clinical practice (RCP) …

Career Plans Among Graduating Us Emergency Medicine Residents, Dave W. Lu, Bo Gu, D. Mark Courtney, Bryan G. Kane, Michelle D. Lall, Michael Gottlieb, Yvette Calderon, Christopher Bennett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.

OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training …

Career Plans Among Graduating Us Emergency Medicine Residents, Dave W. Lu, Bo Gu, D. Mark Courtney, Bryan G. Kane, Michelle D. Lall, Michael Gottlieb, Yvette Calderon, Christopher Bennett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.

OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training …

Cost-Effectiveness Of Home-Based Self-Sampling Vs Clinician Sampling For Anal Precancer Screening, Haluk Damgacioglu, Timothy L Mcauliffe, Timothy J Ridolfi, Elizabeth Chiao, Maria E Fernandez, Vanessa Schick, Jennifer S Smith, Bridgett Brzezinski, Jenna Nitkowski, Ashish A Deshmukh, Alan G Nyitray

Faculty, Staff and Student Publications

Importance: Anal cancer screening is recommended for high-risk populations, particularly sexual and gender minority (SGM) individuals. However, the cost-effectiveness of home-based self-sampling in increasing anal cancer screening uptake has not yet been evaluated in the US.

Objective: To evaluate the cost-effectiveness of home-based anal self-sampling compared with clinic-based screening among SGM individuals.

Design, setting, and participants: This economic evaluation used data from a 2-group randomized clinical trial conducted in Milwaukee, Wisconsin, from January 2020 to August 2022, enrolling SGM individuals aged 25 years or older. Participants were randomized to home-based self-sampling or clinic-based screening. Costs for home-based screening were obtained …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Racial, Ethnic, And Socioeconomic Survival Disparities In Early-Onset Metastatic Colorectal Cancer, Jennifer S Wang, Benny Johnson, Caitlin C Murphy

Faculty, Staff and Student Publications

Importance: Rates of metastatic colorectal cancer (mCRC) are rising among young adults. Disparities by race and ethnicity and neighborhood-level socioeconomic status (SES) among this population are understudied.

Objective: To examine the association of race and ethnicity and neighborhood-level SES with mortality among a community-based sample of young adults with mCRC.

Design, setting, and participants: This cohort study used a large electronic health record-derived database of young adults with cancer treated at 280 community-based US clinics between 2013 and 2021. Eligible patients were young adults aged 18 to 49 years diagnosed with de novo or recurrent mCRC. Patients were followed up …

Prospective Audit And Feedback By Antibiotic Stewardship Teams To Reduce Antibiotic Overuse At Hospital Discharge: A Stepped-Wedge Cluster-Randomized Clinical Trial, Daniel J Livorsi, Michael Joshua Hendrix, Erin Rachmiel, Jahnavi Bongu, Alice Bewley, Kevin Hsueh, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Antibiotics prescribed at hospital discharge are frequently unnecessary or suboptimal. Strategies to improve prescribing are not well defined.

OBJECTIVE: To evaluate whether a discharge-focused prospective audit and feedback process decreases antibiotic overuse at hospital discharge.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted across participating units at 10 hospitals with antibiotic stewardship (AS) teams and supporting staff from December 5, 2022, to November 17, 2023. After a 24-week baseline period, 1 hospital crossed into the intervention arm every 2 weeks.

INTERVENTION: The intervention consisted of disseminating institutional guidelines for oral antibiotic step-down to frontline prescribers and …

Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al.

2020-Current year OA Pubs

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. …

Cumulative Lifespan Stress, Inflammation, And Racial Disparities In Mortality Between Black And White Adults, Isaiah D Spears, Aaron J Gorelik, Sara A Norton, Michael J Boudreaux, Megan W Wolk, Jayne Siudzinski, Sarah E Paul, Mary A Cox, Cynthia E Rogers, Thomas F Oltmanns, Patrick L Hill, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: In the US, Black individuals experience higher mortality risk than White individuals. Greater stress exposure and its biological sequelae are theorized to drive this heightened risk.

OBJECTIVE: To evaluate whether greater cumulative lifespan stress exposure and elevated inflammation are associated with increased mortality risk among Black compared with White US individuals.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study (St Louis Personality and Aging Network) recruited participants from 2007 to 2011 from the St Louis, Missouri, metropolitan area. Participants were required to have a mailing address to permit longitudinal follow-up and sixth grade reading level to facilitate understanding of …

White Matter Hyperintensity Burden And Decline In Driving Performance Among Older Adults, Madhur Parihar, Yasheng Chen, Byron Xu, Semere Bekena, Ramkrishna K Singh, Yiqi Zhu, Jean-Francois Trani, Jin-Moo Lee, David B Carr, Chia-Ling Phuah, Ganesh M Babulal, Driving Real-World In-Vehicle Evaluation System (Drives) Project

2020-Current year OA Pubs

IMPORTANCE: White matter hyperintensity (WMH) burden is associated with cognitive decline, but its association with driving performance among older adults and the associations of modifiable risk factors remain unclear.

OBJECTIVE: To evaluate the association of total and regional WMH burden with longitudinal naturalistic driving performance in cognitively normal older adults and evaluate moderating associations of cognitive decline and antihypertensive therapy.

DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal cohort study enrolled community-dwelling older adults (≥65 years) in the Driving Real-World In-Vehicle Evaluation System Project. Baseline 3-T brain magnetic resonance imaging (MRI) scans and data from continuous in-vehicle driving monitoring were collected …