Digital Commons Network^™

Anti-Sars-Cov-2 Nucleoprotein Iga Is Associated With Worse Disease Severity In Critically Ill Covid-19 Pneumonia Patients, David Brett-Major, Dylan S. George, Eric D. Morrell, Carmen Mikacenic, Julie Carstens, Laura E. Evans, Mark M. Wurfel, Pavan K. Bhatraju, M. Jana Broadhurst

Journal Articles: Epidemiology

While humoral responses to vaccination and infection have largely focused on IgG, there is an evolving literature on ways in which IgA may drive neutrophil activity in lung injury secondary to viral infections, including COVID-19. We evaluated 238 immune-naïve, critically ill patients in the first year of the COVID-19 pandemic. Employing a laboratory-developed, multiplexed antibody testing, clinical history, medical record, and machine learning, we pursued relationships between systemic IgA and disease severity. Individuals with elevated anti-N IgA had 4-fold odds of more severe disease. This work emphasizes the importance of continued work to understand how different elements of the immune …

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 …

Diagnostic Persistence Uncovers Hepatic Abscesses Missed On Initial Imaging In An Elderly Immunocompromised Patient, Eva Kalra, Amy Mangla, Afzal Muhammad, Julie Worthington

South Atlantic Division GME Research Days 2026

No abstract provided.

Genetic Variants Associated With Sjögren’S Disease Subtypes Stratified By Clinical Feature, Nitesh Enduru, Chihiro Iwaya, Akiko Suzuki, Zhongming Zhao, Junichi Iwata

Faculty, Staff and Student Publications

Introduction: Sjögren's disease (SjD) is a chronic autoimmune disorder characterized by dry mouth (xerostomia) and dry eyes (xerophthalmia) due to inflammation in exocrine glands, particularly the salivary and lacrimal glands. The condition presents a wide variety of clinical features, suggesting that it may involve heterogeneous conditions without a clear boundary. Although genome-wide association studies (GWAS) have identified several genetic variants associated with SjD, their roles in SjD pathogenesis remain unclear.

Methods: In this study, we aimed to identify single-nucleotide polymorphisms (SNPs) associated with SjD by categorizing patients based on four diagnostic markers: anti-Ro/SSA and anti-La/SSB antibodies, IgG levels, and lymphocyte …

Clinical Factors And Diagnoses Associated With Inappropriate Urine Culture Ordering In Primary Care, Marissa Valentine-King, Barbara W Trautner, Michael A Hansen, Roger Zoorob, Lisa C K Danek, Kenneth Muldrew, Forrest Hudson, Robert L Atmar, Larissa Grigoryan

Faculty, Staff and Students Publications

Objective: Evaluate the prevalence and risk factors for inappropriately ordered urine cultures in primary care.

Design: Cross-sectional study using chart reviews.

Setting: Two primary care, safety-net clinics in Houston, Texas.

Patients: Non-pregnant adults without a urinary catheter who had a urine culture and a primary care visit between 11/2018 and 3/2020.

Methods: We classified patients lacking physician documentation of the following symptoms as having an inappropriately ordered urine culture: dysuria, frequency, urgency, hematuria, fever, chills, costovertebral angle tenderness, nephrolithiasis, and pain (suprapubic, pelvic, or flank). We extracted patient demographics, visit-related diagnostic codes, past medical history, and urine culture results. Diagnostic …

Evaluation Of Mycoplasma Genitalium Positivity And Co-Infection With Chlamydia Trachomatis And/Or Neisseria Gonorrhoeae At Various Care Sites Across The United States, Rebecca Lillis, Stacey House, Et Al.

2020-Current year OA Pubs

OBJECTIVES: We evaluated Mycoplasma genitalium (MG) positivity and co-infection with Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG), based on results from a trial assessing clinical performance of the Cobas® Liat CT/NG/MG point-of-care test.

METHODS: A prospective, US, multicenter, noninterventional study assessed MG positivity in prospective urine samples (male) and clinician-collected vaginal swabs (female) from symptomatic/asymptomatic patients aged ≥14 years attending various clinical settings. Participants were designated positive or negative for MG, CT, and NG based on combined results from three US Food and Drug Administration-approved assays and one laboratory-developed test. MG co-infection with CT and/or NG was assessed.

RESULTS: Among …

Updating The Epidemiology Of Blastomycosis And Histoplasmosis In The United States, Using National Electronic Health Record Data, 2013-2023., Juliana G E Bartels, Simon K. Camponuri, Theo T. Snow, Brittany L Morgan Bustamante, Natalie J. Kane, Rose Reynolds, Aidan Lee, Mark A. Hoffman, Theodore C. White, Justin V. Remais, Jennifer R. Head

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Where surveillance data are limited, nationally representative electronic health records allow for geographic, temporal, and demographic characterization of the fungal diseases blastomycosis and histoplasmosis.

METHODS: We identified incident blastomycosis and histoplasmosis cases from 2013 to 2023 within Oracle EHR Real-World Data, which comprises 1.6 billion healthcare encounters nationally. To characterize spatiotemporal incidence trends, we used generalized estimating equations weighted for nonrepresentativeness of electronic health record-reporting facilities. We computed standardized incidence rate ratios (sIRRs), which relay relative differences in standardized incidence rates between regions, race/ethnicity, gender, and age subgroups and the national population.

RESULTS: National incidence rates in 2023 were …

The Common Cold Is Associated With Protection From Sars-Cov-2 Infections, Camille M Moore, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults and children often respond differently to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses.

METHODS: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10 493 longitudinal nasal swabs from 1156 participants for 21 …

Peripheral Blood Gene Expression Profiling And Prognostic Significance For The Course Of Interstitial Lung Disease In Patients With Systemic Sclerosis, Shervin Assassi, Christopher P Denton, Matthias Zwick, Ramona Schmid, Carina Ittrich, Tobias Litzenburger, Sudha Visvanathan

Faculty, Staff and Student Publications

Objective: We used data from the placebo arm of the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial to determine the prognostic/predictive significance of peripheral blood cell (PBC) transcript modules for the course of forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without mycophenolate mofetil (MMF) treatment.

Methods: Patients had SSc-ILD with first non-Raynaud symptom within 7 years. MMF treatment was permitted if taken at a stable dose for ≥6 months. PBC RNA samples were taken at baseline. Global RNA sequencing was performed, followed by a modular analysis using 62 curated …

Evaluating Covid-19 Severity Prediction And Immune Dynamics With Nulisaseq: Insights From The Impacc Study, Koji Abe, Tyson H Holmes, Tran T Nguyen, Seunghee Kim-Schulze, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Joanna Schaenman, Elaine F Reed, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Holden T Maecker

Faculty, Staff and Students Publications

The National Institutes of Health-funded IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) evaluated longitudinal clinical and immunological features of human patients hospitalized for COVID-19. This study focuses on comparing the novel NULISAseq assay with the Olink platform using a subset of participants to assess their efficacy in predicting COVID-19 severity and understanding immune response dynamics. Our findings reveal that NULISAseq could provide superior detectability and dynamic range across various targets. Elastic net analysis demonstrated that specific proteins, including amphiregulin, effectively predict COVID-19 severity from sera at admission (samples drawn within 96 h of admission), with a test area under the …

Genetic Predisposition To Persistent Fatigue After A Diagnosis Of Colorectal Cancer, Elham Kazemian, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cancer-related fatigue (fatigue) is a common and persistent symptom after cancer treatment, yet the role of genetic susceptibility remains unclear.

METHODS: We used data from a prospective cohort study called the ColoCare Study, conducted over 5 US sites and Germany. Fatigue was assessed at 5 time points using the European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire fatigue subscale and analyzed as (1) a binary summary measure of the trajectory from diagnosis into survivorship (defined as severe: yes/no), (2) a mean score across all time points, and (3) the highest (ie, worst) score …

Long-Term Illness In Adults Hospitalized For Respiratory Syncytial Virus Disease, United States, February 2022-September 2023, Aleda M Leis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

Respiratory syncytial virus (RSV) can cause severe illness, but little is known about long-term consequences in hospitalized adults. We surveyed adults (>18 years of age) who survived hospitalization for RSV or COVID-19 during February 2022-September 2023 about physical functioning and quality of life; surveys were conducted 6-12 months after hospitalization. We compared outcomes after RSV hospitalization by age (< 60 vs. >60 years) and to those hospitalized for COVID-19 by using multivariable regression models. Among 146 adults hospitalized with RSV, 27.4% reported severe breathlessness and 21.9% poor quality of life at follow-up. Few differences were seen in posthospital illness by age. …

Intersectional Stigma And Resilience In The Uptake Of Cervical Cancer Prevention Services In Nigeria: A Qualitative Study, Agatha Eileen Wapmuk, Titilola Abike Gbaja-Biamila, Ekenechukwu Kokelu, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is one of the leading causes of death among women in Africa, but stigma often delays cervical cancer prevention. We explore the perceptions, enablers and nurturers through the lens of intersectional stigma in the uptake of cervical cancer prevention services in Nigeria.

METHOD: Indepth interviews and focus group discussions were conducted among women aged 30-65 years and girls aged 9-26 years in Lagos, Nigeria. Data were analysed thematically. Using the relationships and expectation domain of the PEN-3 cultural model, we identified perceptions, enablers and nurturers related to the uptake of primary and secondary cervical cancer prevention services …

Influenza Vaccine Effectiveness Against Medically Attended Outpatients Illness, United States, 2023-2024 Season, Jessie R Chung, Stacey L House, Tara Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 US influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with cocirculation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-2024 season.

METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction. Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus subtype/lineage and A(H1N1)pdm09 genetic subclades.

RESULTS: Among 6629 …

Large-Scale Profiling Of Antibody Reactivity To Glycolipids In Patients With Guillain-Barré Syndrome, Robin C M Thomma, Susan K Halstead, Laura C De Koning, Eveline J A Wiegers, Dawn S Gourlay, Anne P Tio-Gillen, Wouter Van Rijs, Henning Andersen, Giovanni Antonini, Samuel Arends, Shahram Attarian, Fabio A Barroso, Kathleen J Bateman, Luana Benedetti, Peter Van Den Bergh, Jan Bürmann, Mark Busby, Carlos Casasnovas, Efthimios Dardiotis, Amy Davidson, Thomas E Feasby, Janev Fehmi, Giuliana Galassi, Tania Garcia-Sobrino, Volkan Granit, Gerardo Gutiérrez-Gutiérrez, Robert D M Hadden, Thomas Harbo, Hans-Peter Hartung, Imran Hasan, James K L Holt, Zhahirul Islam, Summer Karafiath, Hans D Katzberg, Noah Kolb, Susumu Kusunoki, Satoshi Kuwabara, Motoi Kuwahara, Helmar C Lehmann, Sonja E Leonhard, Lorena Martín-Aguilar, Soledad Monges, Eduardo Nobile-Orazio, Julio Pardo, Yann Pereon, Luis Querol, Ricardo C Reisin, Simon Rinaldi, Paolo Ripellino, Rhys C Roberts, Olivier Scheidegger, Nortina Shahrizaila, Kazim A Sheikh, Nicholas J Silvestri, Soren H Sindrup, Beth Stein, Cheng Y Tan, Hatice Tankisi, Leo H Visser, Waqar Waheed, Ruth Huizinga, Bart C Jacobs, Hugh J Willison

Faculty, Staff and Student Publications

Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed. Recent research has highlighted glycolipid complexes, glycolipid combinations that may alter antibody binding, as targets. In this study, we investigated antibody reactivity patterns to glycolipids and glycolipid complexes using combinatorial array, in relation to clinical features in Guillain-Barré syndrome. In total, …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Physical Activity And Molecular Subtypes Of Colorectal Cancer: A Pooled Observational Analysis And Mendelian Randomization Study, Christos V Chalitsios, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity.

METHODS: Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes …

Vaccine Effectiveness Against Influenza A(H1n1), A(H3n2), And B-Associated Hospitalizations, United States, 1 September 2023 To 31 May 2024, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 influenza season included sustained elevated activity from December 2023 to February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season.

METHODS: During 1 September 2023 to 31 May 2024, a multistate sentinel surveillance network of 24 medical centers in 20 US states enrolled adults aged ≥18 years hospitalized with acute respiratory illness. Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccine effectiveness (VE) against influenza-associated hospitalization …

Gata2 Mutation Is Associated With Immune Dysfunction And Increased Mycobacterium Haemophilum Susceptibility In Immunocompromised Individuals, Ananya Gupta, Shail B. Mehta, Abhimanyu, Bruce A. Rosa, John Martin, Mushtaq Ahmed, Shyamala Thirunavukkarasu, Farheen Fatma, Gaya K. Amarasinghe, Makedonka Mitreva, Thomas C. Bailey, David B. Clifford, Shabaana A. Khader

2020-Current year OA Pubs

Infections with nontuberculous mycobacterium (NTM) are on the rise. Here, we investigated an uncommon NTM infection, by M. haemophilum (Mh, n = 4), from a shared geographic location in the United States. All patients had underlying immunosuppressive conditions or treatments. We identified that all these individuals had a nonsynonymous mutation in GATA2 gene, which was absent in healthy controls (HCs, n = 4) from the same geographic area (Missouri, USA). Whole blood from these individuals had attenuated cytokine responses to Mh stimulation for IL-1β, IL-6, IL-8, MIP-1α and MIP-1β, but not to phytohemagglutinin (PHA) or another NTM, M. abscessus. Impaired …

Innate And Adaptive Immune Features Associated With Immune-Related Adverse Events, Shaheen Khan, Venkat S Malladi, Mitchell S Von Itzstein, Hong Mu-Mosley, Farjana J Fattah, Yang Liu, Mary E Gwin, Jason Y Park, Suzanne M Cole, Sheena Bhalla, Jay Lohrey, David Hsiehchen, Angela Moses, Tao Wang, Yaming Xue, Angela B Mobley, J David Farrar, Marjaan Imam, Michelle Wu, Quan-Zhen Li, Edward K Wakeland, Yang Xie, Jeffrey A Sorelle, David E Gerber

Faculty, Staff and Student Publications

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and …

Scenario Projections Of Covid-19 Burden In The Us, 2024-2025, Sara L Loo, Sung-Mok Jung, Lucie Contamin, Emily Howerton, Samantha J Bents, Harry Hochheiser, Michael C Runge, Claire P Smith, Erica C Carcelén, Katie Yan, Joseph C Lemaitre, Emily Przykucki, Clifton D Mckee, Koji Sato, Allison L Hill, Matteo Chinazzi, Jessica T Davis, Clara Bay, Alessandro Vespignani, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Sean M Moore, T Alex Perkins, Ajitesh Srivastava, Majd Al Aawar, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Spencer J Fox, Lauren Ancel Meyers, Przemyslaw Porebski, Srinivasan Venkatramanan, Bryan Lewis, Jiangzhuo Chen, Madhav Marathe, Michal Ben-Nun, James Turtle, Pete Riley, Katriona Shea, Cécile Viboud, Justin Lessler, Shaun Truelove

Faculty, Staff and Student Publications

Importance: COVID-19 remains a disease with high burden in the US, prompting continued debate about optimal targets for annual vaccination.

Objective: To project COVID-19 burden in the US for April 2024 to April 2025 under 6 scenarios of immune escape (20% and 50% per year) and levels of vaccine recommendation (no recommendation, vaccination for individuals at high risk only, vaccination for all eligible groups) and to assess the potential benefit of vaccine recommendations in reducing disease burden.

Design, setting, and participants: For this decision analytical model, the US Scenario Modeling Hub, a collaborative modeling effort, convened 9 teams to provide …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …

Lipidomic And Proteomic Insights From Extracellular Vesicles In The Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes, Chioma M Okeoma, Wasifa Naushad, Bryson C Okeoma, Carlos Gartner, Yulica Santos-Ortega, Calvin Vary, Savio Lima-Bastos, Victor Corasolla Carregari, Martin R Larsen, Alessio Noghero, Consuelo Walss-Bass, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD patients by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) from postmortem subjects. We isolated BA9-derived …

Randomised, Placebo-Controlled Trial Of Oral Hymecromone In Adults With Pulmonary Hypertension, Kathryn Czepiel, Nadine Nagy, Tamera Panjalingam, Anissa Kalinowski, Adam R Frymoyer, Harry Karmouty-Quintana, Bo Gu, Haley Hedlin, Gernot Kaber, Sylvie Dobrota Lai, Joelle I Rosser, Paul L Bollyky, Vinicio De Jesus Perez, Roham T Zamanian

Faculty, Staff and Student Publications

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary condition associated with increased morbidity and mortality. The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH. We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH.

Methods: We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlled study in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD). Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks. The primary …

Variability In Long Covid Definitions And Validation Of Published Prevalence Rates, Lauren E. Wisk, Michelle L'Hommedieu, Kate Diaz Roldan, Imtiaz Ebna Mannan, Erica S. Spatz, Robert A. Weinstein, Arjun K. Venkatesh, Michael Gottlieb, Ryan Huebinger, Kristin L. Rising, Juan Carlos C. Montoy, Kari A. Stephens, Robert M. Rodriguez, Mandy J. Hill, Kelli N. O'Laughlin, Nicole L. Gentile, Ahamed H. Idris, Shu-Xia Li, Michelle Santangelo, Efrat R. Kean, Samuel A. Mcdonald, Kristyn Gatling, Joann G Elmore

Jefferson Center for Connected Care Faculty Papers

IMPORTANCE: Long COVID definitions vary widely, and no consensus exists on how to accurately measure its prevalence, complicating both clinical care and research.

OBJECTIVE: To assess long COVID prevalence using various definitions from published literature.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study used data from the longitudinal Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE). Participants aged 18 years or older with symptoms suggestive of COVID-19 illness at the time of their index SARS-CoV-2 test enrolled at 8 sites across the US from December 11, 2020, through August 29, 2022, with follow-up surveys collected through February 28, …

Micbg406a Polymorphism Reduces Risk Of Mechanical Ventilation And Death During Viral Acute Lung Injury, Harry Pickering, Narges Alipanah-Lechner, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Chris Cotsapas, Hanno Steen, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Monica Kraft, Chris Bime, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman, Steve Bosinger, Walter Eckalbar, Carolyn S Calfee, Oscar A Aguilar, Elaine F Reed, John R Greenland, Daniel R Calabrese

Faculty, Staff and Students Publications

MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between MICBG406A and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower …

Histologic And Immune Characterization Of Cutaneous Immune-Related Adverse Events Induced By Immune Checkpoint Inhibitors, Omar Pacha, Anisha B Patel, Jonathan L Curry, Cara L Haymaker, Nejla Ozirmak Lermi, Dzifa Yawa Duose, Ken Chen, Joud Hajjar, Aung Naing

Faculty, Staff and Student Publications

Background: Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.

Methods: Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE …

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

A Large-Scale Genome-Wide Study Of Gene-Sleep Duration Interactions For Blood Pressure In 811,405 Individuals From Diverse Populations, Pavithra Nagarajan, Thomas W Winkler, Amy R Bentley, Clint L Miller, Aldi T Kraja, Karen Schwander, Songmi Lee, Wenyi Wang, Michael R Brown, John L Morrison, Ayush Giri, Jeffrey R O'Connell, Traci M Bartz, Lisa De Las Fuentes, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Zhijie Huang, Mart Kals, Minjung Kho, Christophe Lefevre, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Yuri Milaneschi, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Botong Shen, Stefan Stadler, Quan Sun, Jingxian Tang, Sébastien Thériault, Adriaan Van Der Graaf, Peter J Van Der Most, Yujie Wang, Stefan Weiss, Kenneth E Westerman, Qian Yang, Tabara Yasuharu, Wei Zhao, Wanying Zhu, Drew Altschul, Md Abu Yusuf Ansari, Pramod Anugu, Anna D Argoty-Pantoja, Michael Arzt, Hugues Aschard, John R Attia, Lydia Bazzanno, Max A Breyer, Jennifer A Brody, Brian E Cade, Hung-Hsin Chen, Yii-Der Ida Chen, Zekai Chen, Paul S De Vries, Latchezar M Dimitrov, Anh Do, Jiawen Du, Charles T Dupont, Todd L Edwards, Michele K Evans, Tariq Faquih, Stephan B Felix, Susan P Fisher-Hoch, James S Floyd, Mariaelisa Graff, Charles Gu, Dongfeng Gu, Kristen G Hairston, Anthony J Hanley, Iris M Heid, Sami Heikkinen, Heather M Highland, Michelle M Hood, Mika Kähönen, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Setoh Kazuya, Tanika N Kelly, Pirjo Komulainen, Daniel Levy, Henry J Lin, Peter Y Liu, Pedro Marques-Vidal, Joseph B Mccormick, Hao Mei, James B Meigs, Cristina Menni, Kisung Nam, Ilja M Nolte, Natasha L Pacheco, Lauren E Petty, Hannah G Polikowsky, Michael A Province, Bruce M Psaty, Laura M Raffield, Olli T Raitakari, Stephen S Rich, Renata L Riha, Lorenz Risch, Martin Risch, Edward A Ruiz-Narvaez, Rodney J Scott, Colleen M Sitlani, Jennifer A Smith, Tamar Sofer, Maris Teder-Laving, Uwe Völker, Peter Vollenweider, Guanchao Wang, Ko Willems Van Dijk, Otis D Wilson, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Xiaofeng Zhu, Jennifer E Below, Carsten A Böger, David Conen, Simon R Cox, Marcus Dörr, Mary F Feitosa, Ervin R Fox, Nora Franceschini, Sina A Gharib, Vilmundur Gudnason, Sioban D Harlow, Jiang He, Elizabeth G Holliday, Zoltan Kutalik, Timo A Lakka, Deborah A Lawlor, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Reedik Mägi, Fumihiko Matsuda, Alanna C Morrison, Brenda Wjh Penninx, Patricia A Peyser, Jerome I Rotter, Harold Snieder, Tim D Spector, Lynne E Wagenknecht, Nicholas J Wareham, Alan B Zonderman, Kari E North, Myriam Fornage, Million Veteran Program, Adriana M Hung, Alisa K Manning, James Gauderman, Han Chen, Patricia B Munroe, Dabeeru C Rao, Diana Van Heemst, Susan Redline, Raymond Noordam, Heming Wang

Faculty, Staff and Student Publications

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health …

Gastrointestinal Infection Before Immune Checkpoint Inhibition Hinders Treatment Efficacy And Increases The Risk Of Colitis, Malek Shatila, Kian Abdul-Baki, Andres Urias Rivera, Kei Takigawa, Irene Jeong-Ah Lee, Andrew Sullivan, Tanvi Gupta, Linfeng Lu, Raakhi Menon, Ayesha Khan, Hamza Salim, Elliot Baerman, Carolina Colli Cruz, Cristina Natha, Varun Vemulapalli, Garrett Coleman, Krishnavathana Varatharajalu, Christopher Fan, Pablo Okhuysen, Anthony J Olszanski, Yan Zhou, Hao Chi Zhang, Mehnaz Shafi, Yinghong Wang

Faculty, Staff and Students Publications

Background: Gastrointestinal (GI) infections, which often result in or stem from intestinal dysbiosis, can affect the efficacy of immune checkpoint inhibitors (ICIs) and increase the risk of adverse effects, such as colitis. In this study, we explored the impact of GI infections before initiation of ICI therapy on the incidence and severity of immune-mediated colitis (IMC) and survival.

Methods: A single-center, retrospective review including all patients who received ICIs from January 2010 to February 2024 and subsequently developed IMC. Patients were screened for IMC and prior GI infections based on symptoms and stool tests. Patients' demographic, IMC, and GI infection-related …