Digital Commons Network^™

A Comparison Of The Diagnostic Capability Of Kato-Katz And Real-Time Pcr For The Assessment Of Treatment Efficacy Of Ivermectin And Albendazole Combination Against T Trichiura Infections, Gabriela Matamoros, Ana Sanchez, Ruben Cimino, Alejandro Krolewiecki, Rojelio Mejia

Faculty, Staff and Students Publications

BACKGROUND: Trichuris trichiura is humans' second most prevalent soil-transmitted helminth (STH) infection after Ascaris lumbricoides, affecting approximately 460 million people worldwide. Despite its sub-optimal sensitivity, especially in low prevalence and infection intensity settings, the modified Kato-Katz (K-K) is still recommended as a diagnostic method by the World Health organization (WHO) guidelines.

METHODOLOGY/PRINCIPAL FINDINGS: Within a randomized clinical trial (RCT) comprising four treatment arms with two different anthelmintics, the present study reports an important secondary research objective to determine the diagnostic agreement between K-K and real-time PCR evaluating treatment efficacy against T. trichiura. The parasitological results were analyzed, including cure rates …

Exposure To Statin Therapy Decreases The Incidence Of Venous Thromboembolism After Trauma, Kelly E Sanders, Gabrielle E Hatton, Atharwa R Mankame, Addison C Allen, Sarah Cunningham, Jan Michael Van Gent, Erin E Fox, Xu Zhang, Charles E Wade, Bryan A Cotton, Jessica C Cardenas

Faculty, Staff and Student Publications

Introduction: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE.

Methods: We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted from January 2018 to June 2022 were included. Patients on prehospital anticoagulants, had history of inherited bleeding disorder, and who died within the first 24 hours were excluded. Statin users were matched …

The Effect Of Smoking On Functional Outcomes And Implant Survival Of Anatomical Total Shoulder Arthroplasty, Isabella E Amador, Kevin A Hao, Timothy R Buchanan, Derek S Damrow, Keegan M Hones, Trevor Simcox, Bradley S Schoch, Kevin W Farmer, Thomas W Wright, Tyler J Lamonica, Joseph J King, Jonathan O Wright

Faculty, Staff and Student Publications

Aims: We sought to compare functional outcomes and survival between non-smokers, former smokers, and current smokers who underwent anatomical total shoulder arthroplasty (aTSA) in a large cohort of patients.

Methods: A retrospective review of a prospectively collected shoulder arthroplasty database was performed between August 1991 and September 2020 to identify patients who underwent primary aTSA. Patients were excluded for preoperative diagnoses of fracture, infection, or oncological disease. Three cohorts were created based on smoking status: non-smokers, former smokers, and current smokers. Outcome scores (American Shoulder and Elbow Surgeons (ASES), Constant-Murley score, Shoulder Pain and Disability Index (SPADI), Simple Shoulder Test …

Building Resilience: A Specialty Clinic Tailored To Older Adults At Risk For Violence And Abuse, Melba A Hernandez-Tejada, Deborah M Little, Madeline J Bruce, Sarly Butte, Jason Burnett, Leila Wood, Ron Acierno

Faculty, Staff and Student Publications

Objective: Both structural (e.g., ageism) and personal (e.g., stigma) barriers hinder older adults' access to and engagement with mental health care. These barriers are particularly problematic for those vulnerable to interpersonal violence and abuse (e.g., due to social isolation). This study presents a quality improvement program aimed at older adults who have experienced significant stressful events, particularly elder mistreatment, within a larger trauma specialty clinic. Leveraging home-based telemedicine, the clinic provides evidence-based psychotherapy tailored to the needs of older adults.

Methods: From 2021 through 2023, the authors retrospectively examined treatment initiation, engagement, completion, and clinical outcomes among 231 older adults …

Three-Year Outcomes Following Tavr In Younger (<75 Years) Low-Surgical-Risk Severe Aortic Stenosis Patients., Thomas Modine, Didier Tchétché, Nicolas M Van Mieghem, G Michael Deeb, Stanley J Chetcuti, Steven J Yakubov, Paul Sorajja, Hemal Gada, Mubashir Mumtaz, Basel Ramlawi, Tanvir Bajwa, John Crouch, Paul S Teirstein, Neal S Kleiman, Ayman Iskander, Rodrigo Bagur, Michael W A Chu, Pierre Berthoumieu, Arnaud Sudre, Rik Adrichem, Saki Ito, Jian Huang, Jeffrey J Popma, John K Forrest, Michael J Reardon

Heart and Vascular Articles

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis, but data are limited on younger, low-risk patients. This analysis compares outcomes in low-surgical-risk patients agedsurgery.

METHODS: The Evolut Low Risk Trial randomized 1414 low-risk patients to treatment with a supra-annular, self-expanding TAVR or surgery. We compared rates of all-cause mortality or disabling stroke, associated clinical outcomes, and bioprosthetic valve performance at 3 years between TAVR and surgery patients aged < 75 >years.

RESULTS: In patients < 75 >years, 352 were randomized to TAVR and 351 to surgery. Mean age was 69.1±4.0 years (minimum 51 and maximum …

Glymphatic Dysfunction In Multiple Sclerosis And Its Association With Disease Pathology And Disability, Ahmed Bayoumi, Khader M Hasan, Joseph A Thomas, Akram Yazdani, John A Lincoln

Faculty, Staff and Student Publications

Background: The role of the glymphatic system in multiple sclerosis (MS)-related disability remains underexplored. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a non-invasive method to assess glymphatic function.

Objective: To evaluate glymphatic function in MS patients with lower and higher disability.

Methods: This study included 118 MS patients who underwent structural, diffusion-weighted imaging, and clinical assessment. The participants were divided into lower (MS-L, n = 57) and higher disability (MS-H, n = 61) subgroups. Brain parenchymal fraction (BPF), lesion load (LL), and DTI-ALPS index were measured. Subgroup differences and correlations between DTI-ALPS index and other measures were explored. …

Effect Of Surgical Fixation Timing On In-Hospital Mortality And Morbidity Of Distal Femur Fractures, Joseph T Gutbrod, Dustin Stwalley, Anna N Miller

2020-Current year OA Pubs

INTRODUCTION: The literature lacks a large-scale study investigating the effect of surgical fixation timing on early mortality and morbidity outcomes in distal femur fractures. The aims of this study were to determine the effect of fixation timing on in-hospital mortality and morbidity outcomes for operatively treated distal femur fractures retrospectively using large database data.

METHODS: This study is a retrospective analysis using data from the National Trauma Data Bank. Patients were stratified into a fragility cohort (age ≥ 60, ISS < 16) and polytrauma cohort (age < 60, ISS ≥16), with both cohorts analyzed separately. Within each cohort, patients were split into three fixation timing groups: within 24 h, between 24 and 48 h, and greater than 48 h from presentation to the hospital. Fixation-timing groups were compared based on the primary outcome of in-hospital mortality rate. Secondary outcomes included hospital length of stay (LOS), ICU length of stay (ICU LOS), days on a ventilator, and complications.

RESULTS: The fragility and polytrauma cohorts included 22,045 and 5,905 patients, respectively. The in-hospital mortality rate was 1.23 % in …

Relationship Between Mri Brain-Age Heterogeneity, Cognition, Genetics And Alzheimer's Disease Neuropathology, Mathilde Antoniades, Pamela Lamontagne, Tammie Benzinger, Daniel S Marcus, John C Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

METHODS: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age …

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab For Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results And Correlative Analyses From Atempt, Paolo Tarantino, Ron Bose, Et Al.

2020-Current year OA Pubs

PURPOSE: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

METHODS: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. …

A Phase 1 First-In-Human Study Of The Mcl-1 Inhibitor Azd5991 In Patients With Relapsed/Refractory Hematologic Malignancies, Pinkal Desai, Amanda Cashen, Et Al.

2020-Current year OA Pubs

PURPOSE: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies.

PATIENTS AND METHODS: In the monotherapy cohort (n = 61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, during a 3-week cycle. In the combination cohort (n = 17), patients with acute myeloid leukemia and myelodysplastic syndrome received escalating doses of AZD5991 and venetoclax during either a 3- or 4-week cycle. Primary objectives were safety and maximum tolerated dose; …

Posttreatment Surveillance Intensity And Overall Survival In Prostate Cancer Survivors (Aft-30), Ronald C Chen, Ramsankar Basak, Stacie Dusetzina, Deborah S Usinger, Zahed Mohammed, Aaron D Falchook, Jessica R Schumacher, Amanda B Francescatti, Amanda Cuddy, George J Chang, Benjamin D Kozower, Caprice C Greenberg, Anne K Barber, Aaron J Katz

2020-Current year OA Pubs

BACKGROUND: Posttreatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice are lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy or radiation therapy for localized prostate cancer is associated with overall survival.

METHODS: Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent radical prostatectomy or radiation therapy at a Commission on Cancer-accredited facility were randomly sampled. Primary data collected from 10 147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of …

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel In Relapsed Or Refractory Large B-Cell Lymphoma, Frederick L Locke, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort …

Neighborhood-Level Deprivation Mediates Racial And Ethnic Disparities In Hcc Diagnosis In Texas, Itunu O Sokale, Aaron P Thrift, Hashem B El-Serag, Abiodun O Oluyomi

Faculty, Staff and Students Publications

BACKGROUND: Texas has the highest HCC rates in the United States, and the greatest burden is among Hispanics. Racial and ethnic disparities in HCC incidence have multiple underpinning factors. We conducted a mediation analysis to examine the role of neighborhood disadvantage (Area Deprivation Index) as a potential mediator of the association between neighborhood race and ethnicity distribution and neighborhood HCC case counts in Texas.

METHODS: The primary outcome measure was counts of new HCC diagnoses per census tract based on Texas Department of State Health Services Texas Cancer Registry data. The primary exposure of interest was the race and ethnicity-based …

Senescence Biomarkers And Trajectories Of Frailty And Physical Function After Kidney Transplantation, Elizabeth C Lorenz, Byron H Smith, Hani M Wadei, Girish Mour, Cassie C Kennedy, Carrie A Schinstock, Walter K Kremers, Andrea L Cheville, Latonya J Hickson, Elizabeth J Atkinson, Thomas A White, Andrew D Rule, Nathan K Lebrasseur

Faculty, Staff and Students Publications

Cellular senescence is a biological mechanism of aging and age-related diseases. The aim of this study was to examine whether senescence biomarkers are associated with frailty and physical function trajectories in patients undergoing kidney transplantation (KT). We also discussed the relationship between senescence biomarkers and KT function. In this multicenter study, we prospectively assessed plasma levels of senescence biomarkers, frailty as measured by the Physical Frailty Phenotype, and physical function as measured by the Short Physical Performance Battery prior to KT. Frailty, physical function, and KT function were also measured 1 year after KT. Variable associations were assessed using Cox …

Prognostic Stratification In Dlbcl Patients With Aberrant Myc Gene, Jian-Rong Li, Vikram R Shaw, Abi Parthasarathy, Yong Li, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic …

Covid-19 Breakthrough Infection After Vaccination And Substance Use Disorders: A Longitudinal Cohort Of People With And Without Hiv Receiving Care In The United States Veterans Health Administration, Elena M Soyer, Kathleen A Mcginnis, Amy C Justice, Evelyn Hsieh, Maria C Rodriguez-Barradas, Emily C Williams, Lesley S Park

Faculty, Staff and Students Publications

Research regarding HIV, substance use disorders (SUD), and SARS-CoV-2 infections after COVID-19 vaccination is limited. In the Veterans Aging Cohort Study (VACS)-HIV cohort, we followed vaccinated persons with HIV (PWH) and without HIV (PWoH) from 12/2020 to 3/2022 and linked SARS-CoV-2 test results for laboratory-confirmed breakthrough infection through 9/2022. We examined associations of substance use (alcohol use disorder [AUD], other SUD, smoking status) and HIV status and severity with breakthrough infections, using Cox proportional hazards regression hazard ratios (HR). To test for potential interactions between substance use and HIV, we fit survival models with a multiplicative interaction term. Among 24,253 …

Pancreatitis Pain Quality Changes At Year 1 Follow-Up, But Gp130 Remains A Biomarker For Pain, Jami L Saloman, Kristofer Jennings, Kimberly Stello, Shuang Li, Anna Evans Phillips, Kristen Hall, Evan L Fogel, Santhi Swaroop Vege, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Darwin L Conwell, Liang Li, Dhiraj Yadav

Center for Medical Ethics and Health Policy Staff Publications

Background/objectives: Debilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study.

Methods: The Neuropathic and Nociceptive PROMIS-PQ questionnaires were used to classify pain for participants with in the PROCEED study. Putative serum biomarkers were measured via immunoassay.

Results: At enrollment, 17.6 % (120/681) subjects with CP reported no pain in the previous year. Of those, 29 % experienced pain during …

Measuring Perceived Utility Of Genomic Sequencing: Development And Validation Of The Genetic Utility (Gene-U) Scale For Adult Screening, Hadley Stevens Smith, Caryn Kseniya Rubanovich, Jill Oliver Robinson, Ariel N Levchenko, Sarah A Classen, Janet Malek, Adam H Buchanan, Barbara Biesecker, Kyle B Brothers, Benjamin S Wilfond, Christine Rini, Cinnamon S Bloss, Amy L Mcguire, Sara J Knight

Center for Medical Ethics and Health Policy Staff Publications

Purpose: As population-based screening programs to identify genetic conditions in adults using genomic sequencing (GS) are increasingly available, validated patient-centered outcome measures are needed to understand participants' experience. We aimed to develop and validate an instrument to assess the perceived utility of GS in the context of adult screening.

Methods: Informed by a 5-domain conceptual model, we used a 5-step approach to instrument development and validation: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. Adults undergoing risk-based or population-based GS who had received GS results as part …

Evaluation Of Chronic Pancreatitis Prognosis Score In An American Cohort, Soo Kyung Park, Darwin L Conwell, Phil A Hart, Shuang Li, Kimberly Stello, Evan L Fogel, William E Fisher, Christopher E Forsmark, Stephen J Pandol, Walter G Park, Mark Topazian, Jose Serrano, Santhi Swaroop Vege, Stephen K Van Den Eeden, Liang Li, Dhiraj Yadav, Jami L Saloman

Faculty, Staff and Student Publications

Introduction: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort.

Methods: The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up.

Results: The mean ± SD COPPS was 8.4 ± 1.6. COPPS correlated with all primary outcomes: hospitalizations for any …

First Interim Results From Fine-Real: A Prospective, Non-Interventional, Phase 4 Study Providing Insights Into The Use And Safety Of Finerenone In A Routine Clinical Settingfirst Interim Results From Fine-Real: A Prospective, Non-Interventional, Phase 4 Study Providing Insights Into The Use And Safety Of Finerenone In A Routine Clinical Setting, Susanne B Nicholas, Ricardo Correa-Rotter, Nihar R Desai, Lixin Guo, Sankar D Navaneethan, Kevin M Pantalone, Christoph Wanner, Stefanie Hamacher, Samuel T Fatoba, Andrea Horvat-Broecker, Antonio Garreta-Rufas, Alain Gay, Martin Merz, David C Wheeler

Center for Medical Ethics and Health Policy Staff Publications

Background: Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). The FINE-REAL study (NCT05348733) aims to evaluate the characteristics and treatment patterns of participants treated with finerenone in clinical practice.

Methods: FINE-REAL is a prospective, single-arm, non-interventional study of patients initiated on finerenone as part of their routine care in accordance with country-approved labels. The study, initiated in June 2022, is expected to be completed by January 2028. The cutoff for this pre-specified interim analysis was June 13, 2023.

Results: Participants were …

National Liver Cancer Screening Trial (Tracer) Study Protocol, Amit G Singal, Neehar D Parikh, Fasiha Kanwal, Jorge A Marrero, Sneha Deodhar, Stephanie Page-Lester, Camden Lopez, Ziding Feng, Nabihah Tayob

Faculty, Staff and Students Publications

BACKGROUND: Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice. …

Pharmacogenomic Insights In Psychiatric Care: Uncovering Novel Actionability, Allele-Specific Cyp2d6 Copy Number Variation, And Phenoconversion In 15,000 Patients, Jai N Patel, Sarah A Morris, Raul Torres, Brooke Rhead, Chris Vlangos, Daniel J Mueller, Lisa C Brown, Hailey Lefkofsky, Muneer Ali, Francisco M De La Vega, Kathleen C Barnes, Anthony Zoghbi, Joseph D Stanton, Marcus A Badgeley

Faculty, Staff and Students Publications

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and …

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Diya Surie, Yuwei Zhu, Adam S Lauring, Manjusha Gaglani, Tresa Mcneal, Shekhar Ghamande, Ithan D Peltan, Samuel M Brown, Adit A Ginde, Aimee Steinwand, Nicholas M Mohr, Kevin W Gibbs, David N Hager, Harith Ali, Anne Frosch, Michelle N Gong, Amira Mohamed, Nicholas J Johnson, Vasisht Srinivasan, Jay S Steingrub, Akram Khan, Laurence W Busse, Abhijit Duggal, Jennifer G Wilson, Nida Qadir, Steven Y Chang, Christopher Mallow, Jennie H Kwon, Matthew C Exline, Nathan I Shapiro, Cristie Columbus, Ivana A Vaughn, Mayur Ramesh, Basmah Safdar, Jarrod M Mosier, Jonathan D Casey, H Keipp Talbot, Todd W Rice, Natasha Halasa, James D Chappell, Carlos G Grijalva, Adrienne Baughman, Kelsey N Womack, Jillian P Rhoads, Sydney A Swan, Cassandra Johnson, Nathaniel Lewis, Sascha Ellington, Fatimah S Dawood, Meredith Mcmorrow, Wesley H Self, Investigating Respiratory Viruses In The Acutely Ill (Ivy) Network

Faculty, Staff and Students Publications

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

Glp-1 Receptor Agonists And Risk For Cirrhosis And Related Complications In Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease, Fasiha Kanwal, Jennifer R Kramer, Liang Li, Yu-Xiao Yang, Yumei Cao, Xian Yu, Ronald Samuel, Basim Ali, Roxanne Desiderio, George Cholankeril, Mandeep Bajaj, Hashem B El-Serag, Steven M Asch

Faculty, Staff and Students Publications

IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD.

OBJECTIVE: To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health …

Age Modulates The Predictive Value Of Self-Reported Sleepiness For All-Cause Mortality Risk: Insights From A Comprehensive National Database Of Veterans, Arash Maghsoudi, Mehrnaz Azarian, Amir Sharafkhaneh, Melissa B Jones, Hoormehr Nozari, Meir Kryger, Amin Ramezani, Javad Razjouyan

Faculty, Staff and Students Publications

Study objectives: Excessive daytime sleepiness is prevalent and overwhelmingly stems from disturbed sleep. We hypothesized that age modulates the association between excessive daytime sleepiness and increased all-cause mortality.

Methods: We utilized the Veterans' Health Administration data from 1999-2022. We enrolled participants with sleep related International Classification of Diseases 9/10 codes or sleep services. A natural language processing pipeline was developed and validated to extract the Epworth Sleepiness Scale (ESS) as a self-reported tool to measure excessive daytime sleepiness from physician progress notes. The natural language processing's accuracy was assessed through manual annotation of 470 notes. Participants were categorized into normal-ESS …

Solid Tumour-Induced Systemic Immunosuppression Involves Dichotomous Myeloid-B Cell Interactions, Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T Ueno, Bora Lim, Xiang H-F Zhang

Faculty, Staff and Students Publications

Solid tumours induce systemic immunosuppression that involves myeloid and T cells. B cell-related mechanisms remain relatively understudied. Here we discover two distinct patterns of tumour-induced B cell abnormality (TiBA; TiBA-1 and TiBA-2), both associated with abnormal myelopoiesis in the bone marrow. TiBA-1 probably results from the niche competition between pre-progenitor-B cells and myeloid progenitors, leading to a global reduction in downstream B cells. TiBA-2 is characterized by systemic accumulation of a unique early B cell population, driven by interaction with excessive neutrophils. Importantly, TiBA-2-associated early B cells foster the systemic accumulation of exhaustion-like T cells. Myeloid and B cells from …

Serum Levels Of Total Bile Acids Are Associated With An Increased Risk Of Hcc In Patients With Cirrhosis, Hashem B El-Serag, Aaron P Thrift, Hao Duong, Jing Ning, Saira Khaderi, Amit G Singal, Sumeet K Asrani, Jorge A Marrero, Hannah Powell, Kinza Rizwan, Omar Najjar, Christopher I Amos, Michelle Luster, Abeer Al-Sarraj, Emad Salem, Michael E Scheurer, Jagpreet Chhatwal, Salma Kaochar, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

METHODS: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard-adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid …

Multiomic Profiling Identifies Predictors Of Survival In African American Patients With Acute Myeloid Leukemia, Andrew Stiff, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger …

Natural History Of Indeterminate Liver Nodules In Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study, Amit G Singal, Neehar D Parikh, Kirti Shetty, Steven-Huy Han, Cassie Xie, Jing Ning, Jo Ann Rinaudo, Ashwini Arvind, Anna S Lok, Fasiha Kanwal, Translational Liver Cancer Investigators

Faculty, Staff and Students Publications

Introduction: Indeterminate liver nodules (ILNs) are frequently encountered on diagnostic imaging after positive hepatocellular carcinoma (HCC) surveillance results, but their natural history remains unclear.

Methods: We conducted a multicenter retrospective cohort study among patients with ≥1 newly detected LI-RADS 3 (LR-3) lesion ≥1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019. Patients were followed with repeat imaging at each site per institutional standard of care. Multivariable Fine-Gray models were used to evaluate associations between potential risk factors and patient-level time-to-HCC diagnosis, with death and liver transplantation as competing risks.

Results: …

Biallelic Loss-Of-Function Variants In Ubap1l And Nonsyndromic Retinal Dystrophies, Ehsan Ullah, Siying Lin, Jiaxiong Lu, Chelsea Bender, Andrew R Webster, Samantha Malka, Savita Madhusudhan, Emma Rees, Denise Williams, Aime R Agather, Catherine A Cukras, Robert B Hufnagel, Rui Chen, Laryssa A Huryn, Gavin Arno, Bin Guan

Faculty, Staff and Students Publications

Importance: Inherited retinal dystrophies (IRDs) present a challenge in clinical diagnostics due to their pronounced genetic heterogeneity. Despite advances in next-generation sequencing (NGS) technologies, a substantial portion of the genetic basis underlying IRDs remains elusive. Addressing this gap seems important for gaining insights into the genetic landscape of IRDs, which may help improve diagnosis and prognosis and develop targeted therapies in the future.

Objective: To provide a clinical and molecular characterization of 6 patients with IRDs with biallelic disease-causing variants in a novel candidate IRD disease gene.

Design, setting, and participants: This multicenter case series study included 6 patients with …