Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

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, …

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) …

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 …

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 …

Cone Beam Computed Tomography For Endodontics: Incidental Findings And Respective Significance, Erin J Key, Nina K Anderson, Dan Colosi, Mina Mahdian

Faculty, Staff and Student Publications

Background: The aim of this study is to determine the prevalence, distribution, and follow-up recommendations of incidental findings in cone beam computed tomography (CBCT) scans acquired for endodontic treatment.

Methods: This was a retrospective review of limited field-of-view (FOV) CBCT images for endodontic evaluation obtained at the Stony Brook University School of Dental Medicine between 2018 and 2022. All scans were reviewed by 1 oral and maxillofacial radiology (OMR) resident and all incidental findings were corroborated with the radiology report approved by 1 of 2 board-certified OMRs. Data extracted for each case included age, gender, and reason for scan; and …

Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrews Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health-related quality of life and posing a safety hazard.

Methods

WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22-item Sino-Nasal Outcome Test (SNOT-22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 …

Association Of Valvular Disease Progression Using Echocardiographic Findings In A Large U.S. Cohort, Abes A. Bautista Neughebauer, Amin Yehya, Raymond L. Benza, Deepak Talreja

Department of Medicine Faculty Publications

Background

The prevalence of valvular disease in the US is approximately 2.5%. Given that over 5 million Americans are affected, it is crucial to find those at higher risk of progression. The goal of this paper is to uncover which patients are more likely to have valvular disease progression using demographic factors, EKG and echocardiogram (ECHO) findings.

Methods

This paper utilized the EchoNext Database, which pairs 100,000 electrocardiograms and echocardiograms based on specific structural heart disease labels. Univariate and multivariate logistic regression were used to find risk factors for progression for aortic stenosis (AS), aortic regurgitation (AR), mitral regurgitation (MR), …

Therapeutic Landscape Of Early Symptomatic Alzheimer's Disease Translated Into Everyday Practice For Geriatric Providers., Melissa J Bailey-Taylor, Paula Morrow, James Hendrix, Katherine E. Galluzzi, Golnosh Sharafsaleh

PCOM Scholarly Works

Alzheimer's disease (AD) accounts for 60-80% of all dementia cases. Recent advances in diagnostic biomarkers of early symptomatic AD (ie, mild cognitive impairment and mild dementia due to AD) and amyloid-targeting therapies (ATTs) have the potential to improve outcomes for patients with AD. Two ATTs (donanemab and lecanemab) are currently approved and available for use in the US. Both ATTs can slow disease progression as well as cognitive and functional decline in patients with early symptomatic AD. Treatment with ATTs is associated with specific safety concerns such as amyloid-related imaging abnormalities. Therefore, the benefit versus risk profile needs to be …

Assessing The Impact Of The 2021 Vwd Guidelines On The Diagnosis/Management Of Low Vwf Patients, Michael Dong, Joanna Larson, Sepideh Saroukhani, Miguel Escobar, Lakshmi Srivaths

Faculty, Staff and Student Publications

Introduction: The 2021 ASH/ISTH/NHF/WFH VWD diagnosis guidelines recommend Type 1 VWD diagnoses for patients with (a) VWF < 0.30 IU/mL or (b) 'Low VWF' 0.30-0.50 IU/mL with the presence of abnormal bleeding. This recommendation recategorizes 'Low VWF' patients with abnormal bleeding into Type 1 VWD.

Aim: To assess the impact of the 2021 VWD guidelines on the diagnosis and management of 'Low VWF' patients.

Methods: A single centre retrospective study was conducted to review all patients presenting for VWD evaluation between January 2000 to September 2024, analyzing for clinical features, ISTH-BAT scores, VWF/FVIII levels, and management of bleeding. 149 patients, totalling 305 clinical encounters, were included in the study.

Results: Seventy five percent of patient encounters had a change in diagnosis from 'Low VWF' to Type 1 VWD …

Safety And Effectiveness Of Stereotactic Radiosurgery For Larger Hemangioblastomas (>2cc): A Multi-Center Retrospective Study, Pavel S Pichardo-Rojas, Salem M Tos, Georgios Mantziaris, Ahmed Shaaban, Ahmed M Nabeel, Wael A Reda, Sameh R Tawadros, Khaled Abdelkarim, Amr M N El-Shehaby, Reem M Emad, Zhishuo Wei, Lindsay M Mckendrick, Ajay Niranjan, L Dade Lunsford, Selcuk Peker, Yavuz Samanci, Roman Liscak, Jaromir May, David Mathieu, Cheng-Chia Lee, Huai-Che Yang, Antonio Dono, Angel I Blanco, Yoshua Esquenazi, Nuria Martinez Moreno, Roberto Martinez Álvarez, Piero Picozzi, Andrea Franzini, Manjul Tripathi, Takuma Sumi, Takeo Uzuka, Hideyuki Kano, David Bailey, Brad E Zacharia, Christopher P Cifarelli, Daniel T Cifarelli, Joshua D Hack, Herwin Speckter, Erwin Lazo, Ronald E Warnick, Jonathan E Schoenhals, Joshua D Palmer, Zhiyuan Xu, Jason P Sheehan

Faculty, Staff and Student Publications

INTRODUCTION: Hemangioblastomas (HGB) are the most common primary intra-axial tumors in the posterior fossa in adults, with an overall occurrence of 7-10%. They occur sporadically or as part of von Hippel-Lindau (VHL) disease. The role of stereotactic radiosurgery (SRS) as a minimally invasive treatment in larger HGB (>2cc) has not been thoroughly investigated.

METHODS: This multi-center study retrospectively analyzed data from 91 patients with large HGB (>2cc) treated between 1993 and 2023. Patients were stratified into VHL-associated and sporadic groups, with assessments including radiosurgical parameters, tumor response, overall survival (OS), and progression-free survival (PFS).

RESULTS: Patients with VHL-associated …

Evaluation Of Interventions For Cognitive Symptoms In Long Covid: A Randomized Clinical Trial, David S Knopman, Deborah Koltai, Daniel T Laskowitz, Jacqueline Becker, Leigh Charvet, Juan Wisnivesky, Alex Federman, Adam Silverstein, Yuliya Lokhnygina, Giuseppina Pilloni, Michelle Haddad, Henry Mahncke, Tom Van Vleet, Rong Huang, Wendy Cox, Diana Terry, Jeannie Karwowski, Netia Mccray, Jenny J Lin, Grace A Mccomsey, Upinder Singh, Linda N Geng, Helen Y Chu, Rebecca Reece, James Moy, Zoe Arvanitakis, Sairam Parthasarathy, Thomas F Patterson, Aditi Gupta, Luis Ostrosky-Zeichner, Jeffrey Parsonnet, Elaine T Kiriakopoulos, Tamara G Fong, Janet Mullington, Sarah Jolley, Nirav S Shah, Sarah Shizuko Morimoto, Joyce K Lee-Iannotti, William D S Killgore, Brigid Dwyer, William Stringer, Carmen Isache, Jennifer A Frontera, Jerry A Krishnan, Ashley O'Steen, Melissa James, Barrie L Harper, Kanecia O Zimmerman

Faculty, Staff and Student Publications

Importance: Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need.

Objective: To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID.

Design, setting, and participants: This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID.

Interventions: Participants were randomized to 1 of …

Bayesian Reanalysis Of Early Remdesivir For The Treatment Of Covid-19 In Outpatients With High Risk Of Progression To Severe Disease, Mazin Abdelghany, Fang Yu, Stephen I. Rennard, Yeongjin Gwon

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Though Bayesian methods are flexible, intuitive, and readily incorporated into clinical decision-making, with particular utility when prior information is available, they remain underutilized in the analysis of clinical trials.

METHODS: In PINETREE, a Phase 3 randomized controlled trial (RCT) of remdesivir (RDV) for the treatment of outpatients with COVID-19 at high risk of severe disease, the primary outcome of COVID-19-related hospitalization or all-cause death was reanalyzed using a range of reference and data-driven priors. Posterior probability distributions were used to calculate the probability that the estimated hazard ratio (HR) was below a range of clinically meaningful specified thresholds and …

Efficacy And Safety Of Epcoritamab In Relapsed Or Refractory Large B-Cell Lymphoma: 3-Year Update From The Epcore Nhl-1 Trial, Yasmin H. Karimi, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Umar Farooq, Tatyana Feldman, Herve Ghesquieres, Wojciech Jurczak, Kim M. Linton, Tycel Phillips, Julie M. Vose, Won Seog Kim, Pegah Jafarinasabian, Barbara D'Angelo Månsson, David Soong, Andrew J. Steele, Zhu Li, Christian W. Eskelund, Martin Hutchings, Catherine Thieblemont

Journal Articles: Oncology and Hematology

Epcoritamab, a CD3xCD20 bispecific antibody, resulted in deep, durable responses with a manageable safety profile in patients with relapsed/refractory large B-cell lymphoma (LBCL) in EPCORE^® NHL-1 (NCT03625037). We report results from a 3-year follow-up. Adults with relapsed/refractory LBCL received epcoritamab until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Median age was 64.0 years, 39% of patients received prior CAR T-cell treatment, and 75% were refractory to ≥ 2 consecutive lines of treatment. As of May 3, 2024 (median follow-up 37.1 months [range, 0.3-45.5]), ORR was 59% and complete response (CR) rate …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Hungarian Validation Of The Pelvic Floor Distress Inventory - 20 (Pfdi-20) Questionnaire And The Pelvic Floor Impact Questionnaire - 7 (Pfiq - 7), Barbara Kozma, Bence Kozma, Peter Takacs, Dávid Rátonyi, Nelli Farkas, Attila G. Sipos, Balint Farkas

Department of Obstetrics & Gynecology Faculty Publications

Introduction and Hypotheses

Pelvic floor disorders (PFDs) affect women's quality of life through physical, psychological, and social domains. The Pelvic Floor Distress Inventory-20 (PFDI-20) and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) are validated tools for assessing symptom severity and quality of life impact. The current study aim to investigate the reliability and validity of the Hungarian versions of these questionnaires in women with PFD symptoms.

Methods

This validation study was carried out at the University of Debrecen among women with clinically confirmed pelvic floor disorders. The PFDI-20 and PFIQ-7 questionnaires were translated into Hungarian using independent native English speaker in …

Clinical Subtypes Of Co-Morbid Insomnia And Obstructive Sleep Apnea (Comisa): Results Of A Cluster Analysis, Yuan Shi, Xujun Feng, Fengyi Hao, Yuru Nie, Yihui Zhang, Zhaohua Chen, Siqi Guan, Larry D. Sanford, Michael V. Vitiello, Xiangdong Tang

Department of Pathology & Anatomy Faculty Publications

Background

Variations in the bidirectional relationship between obstructive sleep apnea (OSA) and insomnia in co-morbid insomnia and OSA (COMISA) may form distinct subtypes of COMISA, which have not been previously characterized. This study aims to identify and characterize subtypes of COMISA.

Methods

From a community-recruited COMISA cohort 256 individuals who met diagnosis for COMISA were used to identify subtypes using a two-step clustering methodology. Demographics and multidimension clinical characteristics were collected and compared among obtained subtypes. Logistic models were used to evaluate whether these subtypes were associated with cardiometabolic and mental disorders. A clinical cohort of 1816 COMISA patients was …

Tezepelumab's Effects On Patient-Reported Symptoms In Severe Asthma, Overall And With History Of Comorbid Chronic Rhinosinusitis With Nasal Polyps (Crswnp), Njira L. Lugogo, Joseph K. Han, Anju T. Peters, Stella E. Lee, Monica Kraft, Mary Kay Margolis, Sonia F. Shenoy, Nicole Martin, Shradha Chandarana, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Tezepelumab (an anti-thymic stromal lymphopoietin monoclonal antibody) treatment resulted in reduced exacerbations and improved sino-nasal symptoms and health-related quality of life in patients with severe uncontrolled asthma (SUA) and chronic rhinosinusitis with nasal polyps (CRSwNP) in the NAVIGATOR study.

Objective

To evaluate the effect of tezepelumab versus placebo on sleep disturbances, activity levels, and physical exertion tolerance in NAVIGATOR patients with SUA overall and in those with past medical history of comorbid CRSwNP.

Methods

Patients (12-80 years old) with SUA were randomized to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Patient responses to …

Clinical Outcomes With Perioperative Nivolumab By Nodal Status In Patients With Stage Iii Resectable Nsclc: Phase 3 Checkmate 77t Exploratory Analysis, Mariano Provencio, Mark M Awad, Jonathan D Spicer, Annelies Janssens, Fedor Moiseyenko, Yang Gao, Yasutaka Watanabe, Aurelia Alexandru, Florian Guisier, Nikolaj Frost, Fabio Franke, T Jeroen Nicolaas Hiltermann, Jie He, Fumihiro Tanaka, Shun Lu, Cinthya Coronado Erdmann, Padma Sathyanarayana, Phuong Tran, Vipul Devas, Tina Cascone

Faculty, Staff and Student Publications

Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30–0.70)) and pathological complete response rate …

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes., Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M. Starke, Marios-Nikos Psychogios, Edgar A. Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A. Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G. Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S. Park, Michael R. Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J. Altschul, Alejandro M. Spiotta, Peter Kan

Department of Medicine Faculty Papers

INTRODUCTION: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

PATIENTS AND METHODS: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Wenyi Wang, Pavithra Nagarajan, Heming Wang, Michael R Brown, Amy R Bentley, Qin Hui, Aldi T Kraja, John L Morrison, Jeffrey R O'Connel, Songmi Lee, Karen Schwander, Traci M Bartz, Lisa De Las Fuentes, Mary F Feitosa, Xiuqing Guo, Xu Hanfei, Sarah E Harris, Zhijie Huang, Mart Kals, Christophe Lefevre, Massimo Mangino, Yuri Milaneschi, Peter J Van Der Most, Natasha L Pacheco, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Quan Sun, Yasuharu Tabara, Dina Vojinovic, Yujie Wang, Stefan Weiss, Qian Yang, Wei Zhao, Wanying Zhu, Md Abu Yusuf Ansari, Hugues Aschard, Pramod Anugu, Themistocles L Assimes, John Attia, Laura D Baker, Christie Ballantyne, Lydia Bazzano, Eric Boerwinkle, Brain Cade, Hung-Hsin Chen, Wei Chen, Yii-Der Ida Chen, Zekai Chen, Kelly Cho, Ileana De Anda-Duran, Latchezar Dimitrov, Anh Do, Todd Edwards, Tariq Faquih, Aroon Hingorani, Susan P Fisher-Hoch, J Michael Gaziano, Sina A Gharib, Ayush Giri, Mohsen Ghanbari, Hans Jörgen Grabe, Mariaelisa Graff, C Charles Gu, Jiang He, Sami Heikkinen, James Hixson, Yuk-Lam Ho, Michelle M Hood, Serena C Houghton, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Tuomas O Kilpeläinen, Pirjo Komulainen, Henry J Lin, Gregorio V Linchangco, Annemarie I Luik, Jintao Ma, James B Meigs, Joseph B Mccormick, Cristina Menni, Ilja M Nolte, Jill M Norris, Lauren E Petty, Hannah G Polikowsky, Laura M Raffield, Stephen S Rich, Renata L Riha, Thomas C Russ, Edward A Ruiz-Narvaez, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, Tamar Sofer, Botong Shen, Jingxian Tang, Kent D Taylor, Maris Teder-Laving, Rima Triatin, Michael Y Tsai, Henry Völzke, Kenneth E Westerman, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Xiaofeng Zhu, Jennifer E Below, Simon R Cox, Michelle Evans, Myriam Fornage, Ervin R Fox, Nora Franceschini, Sioban D Harlow, Elizabeth Holliday, M Arfan Ikram, Tanika Kelly, Timo A Lakka, Deborah A Lawlor, Changwei Li, Ching-Ti Liu, Reedik Mägi, Alisa K Manning, Fumihiko Matsuda, Alanna C Morrison, Matthias Nauck, Kari E North, Brenda Wjh Penninx, Michael A Province, Bruce M Psaty, Jerome I Rotter, Tim D Spector, Lynne E Wagenknecht, Ko Willems Van Dijk, Lifelines Cohort Study, Million Veteran Program, Cashell E Jaquish, Peter Wf Wilson, Patricia A Peyser, Patricia B Munroe, Paul S De Vries, W James Gauderman, Yan V Sun, Han Chen, Clint L Miller, Thomas W Winkler, Dabeeru C Rao, Susan Redline, Diana Van Heemst

Faculty, Staff and Student Publications

Background and aims: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

Methods: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Autologous Multiantigen-Targeted T Cell Therapy For Pancreatic Cancer: A Phase 1/2 Trial, Benjamin L Musher, Spyridoula Vasileiou, Brandon G Smaglo, Catherine S Robertson, Mengfen Wu, Tao Wang, Ayumi Watanabe, Manik Kuvalekar, Yovana Velazquez, Shamika Ketkar, Tamadar Al Doheyan, Penelope G Papayanni, Aakash Shah, Natalia Lapteva, Bambi J Grilley, George Van Buren, Premal D Lulla, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, Ann M Leen

Faculty, Staff and Students Publications

T cell therapy has proven challenging for pancreatic ductal adenocarcinoma (PDAC), partly due to heterogeneous expression of tumor-associated antigens (TAAs). To address tumor heterogeneity and mitigate immune evasion, an ex vivo expanded, polyclonal, T helper 1 cell-polarized T cell product targeting five TAAs—PRAME, SSX2, MAGEA4, Survivin and NY-ESO-1—was developed. These antigens were chosen based on their tumor specificity, oncogenicity, immunogenicity and level of expression. In a phase 1/2 trial, this autologous nonengineered T cell product was administered (1 × 107 cells m−2 per infusion) monthly to patients with advanced PDAC responding (arm A, n = 13) or refractory (arm B, …

Phase 1 Trial Of Withania Somnifera Leaf Extract (Rh324) In Advanced Non-Small Cell Lung Cancer Including [18f]Fdg Pet/Ct As A Short-Term Metabolic Biomarker To Assess Efficacy: A Novel Model For Assessment Of Complimentary Therapies In Early Phase Human Clinical Trials, Jin Uk Heo, Santosh Rao, Herbert B Newton, Afshin Dowlati, Raymond F Muzic, Arash Kardan

Faculty, Staff and Students Publications

Background: Withania somnifera (WS), commonly known as ashwagandha, has been used in the traditional medical system of India. It has shown significant activity against numerous solid tumor varieties in pre-clinical in vitro and in vivo studies. This study focuses on RH324 (ReHeva Biosciences, Columbus, OH), a pharmaceutical-grade formulation derived from WS, which has received FDA allowance for clinical development as a botanical drug in the treatment of cancer.

Methods: A phase 1 open label dose ranging study of oral RH324 in advanced non-small cell lung cancer (NSCLC) was conducted. The primary endpoint of the study was assessment of short-term safety …

Suicidal Ideation In Spinocerebellar Ataxia, Levi Peppel, Ruo-Yah Lai, Christian Rummey, Puneet Opal, Jeremy D Schmahmann, Christopher M Gomez, Henry Paulson, Theresa A Zesiewicz, Susan Perlman, George Wilmot, Sarah H Ying, Chiadi U Onyike, Khalaf O Bushara, Michael D Geschwind, Karla P Figueroa, Stefan M Pulst, Sub H Subramony, Antoine Duquette, Tetsuo Ashizawa, Ali G Hamedani, Marie Y Davis, Sharan R Srinivasan, Matthew R Burns, Nadia Amokrane, Lauren R Moore, Vikram G Shakkottai, Liana S Rosenthal, Sheng-Han Kuo, Chi-Ying R Lin

Faculty, Staff and Students Publications

Objective: Suicidal ideation has not been extensively studied in spinocerebellar ataxias (SCAs). The authors examined whether individuals with SCAs have increased suicidal ideation and related factors.

Methods: The authors studied patients with genetically confirmed SCAs enrolled in the Clinical Research Consortium for the Study of Cerebellar Ataxia cohort, examining the percentages of patients with SCA subtypes 1, 2, 3, and 6 who reported suicidal ideation and comparing findings with nationally representative data from the National Survey on Drug Use and Health (NSDUH). Clinical characteristics that may contribute to suicidal ideation in SCAs, including age, disease duration, sex, ataxia severity, depression, …

Frontline Aspiration Versus Stent Retriever Thrombectomy For M2 Occlusions: Insights From The Star Registry, Michael Gaub, Rahim Abo Kasem, Ilko Maier, Ansaar Rai, Pascal Jabbour, Joon-Tae Kim, Brian Howard, Ali Alawieh, Stacey Quintero Wolfe, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Nitin Goyal, Justin Dye, Ali Alaraj, Mohamad Ezzeldin, Shinichi Yoshimura, David Fiorella, Omar Tanweer, Daniele G Romano, Pedro Navia, Hugo Cuellar, Isabel Fragata, Adam Polifka, Joshua Osbun, Fazeel Siddiqui, Mark Moss, Kaustubh Limaye, Maxim Mokin, Charles Matouk, Min S Park, Waleed Brinjikji, Ergun Daglioglu, Richard Williamson, David J Altschul, Christopher S Ogilvy, Roberto Crosa, Michael R Levitt, Benjamin Gory, Alexandra Paul, Peter Kan, Walter Casagrande, Shakeel Chowdhry, Michael F Stiefel, Ramesh Grandhi, Alejandro Spiotta, Justin Mascitelli

Faculty, Staff and Students Publications

Background: Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect.

Methods: Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0-2) at 90 days. Recanalization, …