Digital Commons Network^™

Low Dietary Folate Increases Developmental Delays In The Litters Of, Karen E Christensen, Marie-Lou Faquette, Vafa Keser, Alaina M Reagan, Aaron T Gebert, Teodoro Bottiglieri, Gareth R Howell, Rima Rozen

Faculty Research 2025

Background/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ Mthfr^677C>T mice to evaluate the effects of the TT genotype and low folate diets on embryonic development and MTHFR protein expression in pregnant mice. Methods: Female 677CC (mCC) and 677TT (mTT) mice were fed control (2 mg folic acid/kg (2D)), 1 mg folic acid/kg (1D) and 0.3 mg folic acid/kg (0.3D) diets before and during …

Use Of Cognitive-Behavioral Therapy In A Nation-Wide Veterans Health Administration Sample: The Role Of Clinic, Therapist, And Patient Factors., Alan Mcguire, Mindy Flanagan, Madison E Stout, Jessica Coffing, Marina Kukla, Morgan Traylor, Laura Myers, Nancy Henry, Jessica Carter, Marianne Matthias

Health Services and Informatics Research

OBJECTIVE: To examine the use of CBT-CP (Cognitive-behavioral therapy for chronic pain) by CBT-CP-trained therapists to treat patients with pain over a five-year period (October 2015-February 2020).

DATA SOURCES AND STUDY SETTING: CBT-CP is a core evidence-based practice that is central to multidisciplinary chronic pain care. However, research suggests that CBT-CP is underused. The current study used national Veterans Health Administration data to examine the use of CBT-CP by CBT-CP-trained therapists to treat patients with pain over a five-year period.

STUDY DESIGN: Multilevel modeling was used to evaluate clinic, therapist, and patient-level factors as predictors of CBT-CP receipt.

DATA COLLECTION: …

Association Of Epigenetic Aging With Plasma Cbiomarkers Of Amyloid, Tau, Neurodegeneration, And Neuroinflammation In Hispanic/Latino Adults, Myriam Fornage, Wassim Tarraf, Martha L Daviglus, Charles Decarli, Kevin A Gonzalez, Carmen R Isasi, Sayaka Kuwayama, Melissa Lamar, Bonnie E Levin, Humberto Parada, Alberto R Ramos, Tatjana Rundek, Bharat Thyagarajan, Hector M González

The Brown Foundation: Institute of Molecular Medicine

Background: Blood-based biomarkers hold significant promise for the early detection and diagnosis of Alzheimer's disease (AD) and other dementias. Age-related changes in blood levels of AD biomarkers are well-documented but poorly understood. Epigenetic clocks are mathematical models based on DNA methylation patterns that reflect various aspects of the multidimensional aging process. We investigated the associations of epigenetic aging with five blood-based AD biomarkers in 2656 Hispanic/Latino adults (mean age 62.5 years; 65% females) from the Hispanic Community Health Study/Study of Latinos. We used multivariable linear regression models to estimate the associations of acceleration in each of five epigenetic clocks with …

Biomechanical Analysis Of 3d Correction And Bone-Screw Forces As A Function Of Rod Insertion Sequence And Orientation Relative To The Sagittal Plane In Adolescent Idiopathic Scoliosis Instrumentation., Camille Pillot, Xiaoyu Wang, Alexandria Mallinos, Todd Ritzman, Lorena Floccari, Richard M. Schwend, Carl-Eric Aubin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In adolescent idiopathic scoliosis instrumentation, rods are typically aligned with the sagittal plane during the initial translation maneuver. Surgeons often empirically orient the rod slightly opposite to the scoliotic curve, but the optimal orientation and insertion sequence, as well as their influence on 3D correction and forces, remain unclear. This study investigates the biomechanical influence of these rod parameters on scoliosis correction.

METHODS: Patient-specific multi-body biomechanical models were developed for 30 adolescent idiopathic scoliosis patients (11 hypo-, 12 normo-, 7 hyper-kyphotic thoracic curves) to simulate posterior instrumentation with a primary segmental translation correction maneuver. Rod insertion was tested in …

Work Impairment And Financial Outcomes Among Adults With Vs Without Long Covid, Michael Gottlieb, Ji Chen, Huihui Yu, Michelle Santangelo, Erica S. Spatz, Nicole L. Gentile, Rachel E. Geyer, Caitlin Malicki, Kristyn Gatling, Kelli N. O'Laughlin, Kari A. Stephens, Joann G. Elmore, Lauren E. Wisk, Michelle L'Hommedieu, Robert Rodriguez, Juan Carlos C. Montoy, Ralph C. Wang, Kristin L. Rising, Efrat Kean, Jonathan W. Dyal, Mandy J. Hill, Arjun K. Venkatesh, Robert A. Weinstein

Department of Emergency Medicine Faculty Papers

IMPORTANCE: While much of the focus on long COVID (LC; defined as developing new, persistent symptoms lasting 3 months or longer after SARS-CoV-2 infection) has been on health status and quality of life, the impact on individual work productivity and financial distress are less well established.

OBJECTIVES: To assess differences in work and financial outcomes among individuals with current, resolved, and no LC up to 3 years after initial infection.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multisite, longitudinal cohort study enrolled adult participants (age ≥18 years) with at least 1 reported SARS-CoV-2 infection from December 7, 2020, to August 29, …

Summit Max: A Randomized Trial Of The Super Large Bore Hipoint Reperfusion System Versus Vecta System For Aspiration Thrombectomy., Thanh N Nguyen, Guilherme Dabus, Ben Mcguinness, James Caldwell, Ryan Priest, Ansaar T Rai, Osama O Zaidat, Bradley A Gross, Ricardo Hanel, Shane Lee, Shazam Hussain, Hamza Shaikh, Mohamad Abdalkader, Ronald Budzik, Craig Kilburg, Keith Woodward, Marco Colasurdo, Jesse Liu, Albert J Yoo, Priyank Khandelwal, Sohyun Boo, Phong Vu, Eugene Lin, Mohammad Almajali, Jasmeet Singh, Alhamza Al-Bayati, Michael J Lang, Michael Abraham, Ameer E Hassan, Peter Pema, Coleman Martin, Ramesh Grandhi, Daniel A Tonetti, Harry R Hixson, Amin Aghaebrahim, Eric Sauvageau, Santiago Ortega-Gutierrez, Dileep R Yavagal, Esteban Cheng-Ching, Jane Khalife, Italo Linfante, Volodymyr Vulkanov, Jazba Soomro, Johanna T Fifi, Lucien Maidan, Alexander Copelan, Clemens M Schirmer, Mark Bain, Gabor Toth, Mahesh Jayaraman, Roberta Novakovic-White, Sudhakar Satti, Nicolas Villelli, Pascal Jabbour, Matthew Page, Davina J Mcallister, Robert Araujo Contreras, Edgar A Samaniego, David S Liebeskind, Steven W Hetts, Raul G Nogueira, Joey English, Ajit S Puri

Neuroscience Articles

BACKGROUND: Rapid and complete recanalization is a primary goal in the endovascular treatment of large vessel occlusion stroke. The effectiveness and safety of super large bore aspiration catheters (0.088″ inner diameter) for the treatment of large vessel occlusion stroke have not been demonstrated in a randomized trial.

METHODS: SUMMIT MAX (A Prospective, Randomized, Controlled, Interventional Clinical Trial to Evaluate the Safety and Effectiveness of the Route 92 Medical MonoPoint Reperfusion System for Aspiration Embolectomy in Acute Ischemic Stroke Patients) was a prospective, randomized, controlled, open-label clinical trial of patients with internal carotid artery and middle cerebral artery M1 occlusions, comparing …

Vascular Risk Factors And 1-Year Cognitive Change Among Individuals With Traumatic Brain Injury, Andrea L. C. Schneider, Katherine Hunzinger, Benjamin L. Brett, Danielle K Sandsmark, Sonia Jain, Xiaoying Sun, Raquel C. Gardner, Geoffrey T. Manley, Ramon Diaz-Arrastia, Lindsay D. Nelson, Patrick Belton, Shawn Eagle, Shankar Gopinath, Ramesh Grandhi, C. Dirk Keene, Vijay Krishnamoorthy, Christine Mac Donald, Michael Mccrea, Randall Merchant, Pratik Mukherjee, Laura B. Ngwenya, David Okonkwo, Claudia Robertson, David Schnyer, Sabrina R. Taylor, John K. Yue, Ross Zafonte

Department of Exercise Science Faculty Papers

IMPORTANCE: Traumatic brain injury (TBI) and vascular risk factors are associated with cognitive impairment, but it is unknown if individuals with vascular risk factors experience worse cognitive outcomes after TBI.

OBJECTIVE: To evaluate cognitive function among patients with TBI with vs without comorbid preinjury vascular risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study examined individuals with TBI enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Study between February 26, 2014, and August 8, 2018, with a 1-year follow-up. Analyses were conducted February 26, 2024, to May 29, 2025.

EXPOSURES: Vascular risk factors (ie, hypertension, diabetes, …

An Electronic Trigger To Detect Telemedicine-Related Diagnostic Errors, Daniel R Murphy, Himabindu Kadiyala, Li Wei, Hardeep Singh

Faculty, Staff and Students Publications

Introduction

Methods

Screening Programmes And Breast Cancer Mortality: An Observational Study Of 194 Countries, Syed Mahfuz Al Hasan, Debbie L Bennett, Adetunji T Toriola

2020-Current year OA Pubs

OBJECTIVE: To investigate the associations between national breast cancer screening programmes and breast cancer mortality globally.

METHODS: We collected data on breast cancer screening programmes and breast cancer mortality from the World Health Organization's Global Health Observatory, the Global Burden of Diseases 2021 study and the Eurostat database. We assessed differences in breast cancer mortality between countries with regular and irregular screening programmes, adjusting for sociodemographic index. We calculated annual changes in breast cancer mortality from 2015 to 2021 and assessed differences in mortality changes between countries with regular and irregular screening programmes.

FINDINGS: Between 2015 and 2021, 94 of …

Human Thalamocortical Structural Connectivity Develops In Line With A Hierarchical Axis Of Cortical Plasticity, Valerie J Sydnor, Deanna M Barch, Et Al.

2020-Current year OA Pubs

Human cortical development follows a hierarchical, sensorimotor-to-association sequence. The brain's capacity to enact this sequence indicates that it relies on unknown mechanisms to regulate regional differences in the timing of cortical maturation. Given evidence from animal systems that thalamic axons mechanistically regulate periods of cortical plasticity, here we evaluate in humans whether the development of structural connections between the thalamus and cortex aligns with cortical maturational heterochronicity. By deriving a new tractography atlas of human thalamic connections and applying it to diffusion data from three youth samples (8-23 years; total n = 2,676), we demonstrate that thalamocortical connectivity matures in …

The Ccjr® Charles A. Engh, Sr, Md. Excellence In Hip Research Award: Pelvic Tilt And Cup Position Change Significantly In Most Young Patients 10 Years After Hip Arthroplasty, Joseph J Kromka, William A Zuke, Caroline J Granger, John C Clohisy, Robert L Barrack

2020-Current year OA Pubs

BACKGROUND: Acetabular cup position is fundamental to total hip arthroplasty (THA) and surface replacement arthroplasty (SRA). Even if initial cup placement is adequate, changes in spinopelvic relationships alter functional acetabular position over time. This can lead to late complications. The purpose of this study was to examine changes in pelvic tilt and acetabular position in patients with at least 10 years of follow-up after THA or SRA.

METHODS: A retrospective review was conducted of patients from one academic practice who underwent THA or SRA and had at least 10 years of follow-up. Pelvic ratio was measured and converted to pelvic …

Barriers And Facilitators To Accessing Healthcare For People With Parkinson's Disease In Latin America: A Qualitative Study, Christine Jeyachandran, Catherine Spooner, Ana Margarita Rodriguez Salgado, Matthew Prina, Joel Rhee, Jorge Jesus Llibre-Guerra, Dani Kim, Juan J Llibre-Rodriguez, Mark F Harris

2020-Current year OA Pubs

AIMS: The aim of the study was to identify the barriers and facilitators to healthcare access for people with Parkinson's disease (PWP) in Spanish-speaking Latin American countries (LAC) in Central and South America, to understand their drivers and consider the implications for health systems in LAC.

METHODS: Four online semi-structured focus groups were conducted with 25 PWP who provide education and/or support to PWP. The study was designed and implemented by a person with lived experience of PD. Data were mapped to an existing model of access to healthcare that incorporates provider and consumer abilities.

FINDINGS: There were multiple provider …

Characterization Of Visual Field Loss Over 4 Years In The Rate Of Progression In Ush2a-Related Retinal Degeneration (Rush2a) Study, Jacque L Duncan, Maureen G Maguire, Lee S Mcdaniel, Nicole R Doucet, Isabelle Audo, Allison R Ayala, Janet K Cheetham, Peiyao Cheng, Todd A Durham, Rachel M Huckfeldt, Robert B Hufnagel, K Thiran Jayasundera, Naheed Khan, Brett Malbin, Ramiro S Maldonado, Michel Michaelides, Mark E Pennesi, Christina Y Weng, Alex Zmejkoski, Shobana Aravind, Hiroshi Ishikawa, David G Birch

Faculty, Staff and Students Publications

Purpose: To report visual field loss using static perimetry (SP) and kinetic perimetry (KP) over 4 years in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

Design: Prospective, observational cohort study.

Subjects, participants, and/or controls: Participants had USH2A-related rod-cone degeneration, visual acuity ≥20/80, and KP III4e ≥10° at baseline in the study eye. Preserved cohorts with baseline visual fields sufficient to detect progression were identified.

Methods: Participants were examined annually through 4 years. Mixed-effects models were used to estimate the annual, standardized rate, and percentage rates of change.

Main outcome measures: SP measures included hill of vision (total: …

Relapse Patterns Among Children And Adolescents With Kaposi Sarcoma In Malawi, Toni Chanroo, Allison Silverstein, Casey L Mcatee, William Kamiyango, Jimmy Villiera, Parth S Mehta, Erin Peckham-Gregory, Mark Zobeck, Michael E Scheurer, Carl E Allen, Rizine Mzikamanda, Nmazuo W Ozuah, Nader Kim El-Mallawany

Faculty, Staff and Students Publications

Kaposi Sarcoma (KS) is a common childhood cancer in Malawi, but few studies have exploredclinical characteristicsofrelapsed disease. We aimed to characterize clinical patterns of relapse to improve treatment and, ultimately, long-term survival in patients with pediatric KS.A retrospective cohort study was conducted among patients ages < 19 years of age at time of KS diagnosis in Lilongwe, Malawi between August 1, 2010 and March 15, 2020. Specifically, emphasis was placed on patients who had relapsed disease and excluded patients with refractory disease or those who died whilst receiving front-line treatment. Salvage therapy typically involved an intensified chemotherapy regimen compared to front-line therapy—namely nonliposomaldoxorubicin plus bleomycin/vincristine or paclitaxel monotherapy.One-hundred and ninety patients with pediatric KS were included in this analysis, 50 of whom experienced relapse (26%).Older median age was associated with occurrence of relapse (10 vs 6.7 years, p-value = 0.004). Median time from diagnosis to first relapse was 10.6 months (range 2.3–49 months). Three-year post-relapse overall survival (OS) for the entire cohort was 60% with a median follow-up time of 4.7 years after relapse.Survival was significantly higher for patients who relapsed with the woody edema clinical phenotype of pediatric KS versus those with visceral/disseminated disease—3-year OS 79% (95% CI 62–100) versus 29% (14–61).These data demonstrate potential for continued survival after KS relapse in the pediatric population and identify subsets of high-risk patients. The higher mortality observed in patients with visceral/disseminated KS highlights the need for improved therapeutic strategies.

The Impact Of Gender, Training Year, Medical Specialty And The Covid-19 Pandemic On Resident Wellness, Sara Beachy, Jessica Luzier, Chantel Weisenmuller, Kathleen Bors, Mary Ann Maurer, Amna Anees, Tiffany Lasky, Lisa Calderwood

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Data are limited as to which factors most strongly impact medical trainees' well-being, and few studies have assessed trainee's wellness at multiple time points during the COVID-19 pandemic. Additionally, much research has not taken an intersectional approach to understanding the ways in which different facets of a resident's identity impact their wellness. Thus, more person-centred, probability-driven statistical approaches that can produce distinct heterogenous groups of individuals are warranted to understand the way in which different identities are associated with resident wellness scores.

METHODS: A latent profile analysis was conducted using institutional data from resident surveys administered from 2019 to …

Ruptured Arteriovenous Malformation Mortality: Incidence, Risk Factors, And Inpatient Outcome Score, Eric Feldstein, Allison Zhong, Kevin Clare, Bridget Nolan, Smit Patel, Nir Lavi-Romer, Zehavya Stadlan, Alis Dicpinigaitis, Jose Dominguez, Haris Kamal, Steven D Shapiro, Arundhati Biswas, Omar Tanweer, Ketan Bulsara, Carrie Muh, Jared Pisapia, Simon Hanft, Stephan Mayer, Chirag D Gandhi, Fawaz Al-Mufti

Faculty, Staff and Students Publications

Background

Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH.

Objective

We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score.

Methods

This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. …

High Risk Of Drug-Resistant Tuberculosis In Igra-Negative Contacts: Should Preventive Treatment Be Considered?, Thomas Theo Brehm, Niklas Köhler, Hans-Peter Grobbel, Jürgen Welling, Anna Maria Mandalakas, Vinicius Fava, Erwin Schurr, Christoph Lange

Faculty, Staff and Students Publications

Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.

Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M. tuberculosis-specific DNA from bronchopulmonary specimens using GeneXpert® MTB/RIF. M. tuberculosis infection was diagnosed by an interferon-gamma release assay (IGRA; QuantiFERON®-TB Gold Plus). Whole exome sequencing for genetic predisposition to mycobacterial infection was performed in one patient.

Results: Six of eight siblings aged 16-20 years from a migrant family of Somali …

Experiences Of The Emergency Department Environment: A Qualitative Study With Caregivers Of People With Dementia, Anita N Chary, Michelle Suh, Annika Bhananker, Norvin Hernandez, Ana Paulina Rivera, Ed Boyer, Mark E Kunik, Manish N Shah, Christine Ritchie, Aanand D Naik, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

ED crowding and boarding adversely impact older patients' care and outcomes. Little is known about how ED crowding impacts persons living with dementia, a vulnerable population. This study sought to explore ED experiences of caregivers of people with dementia during a period of ED crowding and boarding. We performed semi-structured interviews with caregivers of people with dementia with an ED visit during a period of ED crowding and boarding at two public hospitals experiencing a threefold increase in boarding from pre-pandemic levels. Participants were recruited via chart review. We coded data using an inductive approach. Three themes emerged from 29 …

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Fabian Ott, Sebastian Loens, Gamze Kilic-Berkmen, Ai Huey Tan, Shen-Yang Lim, Ebba Lohmann, Kaja M Schröder, Lea Ipsen, Lena A Nothacker, Linn Welzel, Alexandra S Rudnik, Frauke Hinrichs, Thorsten Odorfer, Kirsten E Zeuner, Friederike Schumann, Andrea A Kühn, Simone Zittel, Marius Moeller, Robert Pfister, Christoph Kamm, Anthony E Lang, Yi Wen Tay, Ana Luísa De Almeida Marcelino, Marie Vidailhet, Emmanuel Roze, Joel S Perlmutter, Jeanne S Feuerstein, Victor S C Fung, Florence Chang, Richard L Barbano, Steven Bellows, Aparna A Wagle Shukla, Alberto J Espay, Mark S Ledoux, Brian D Berman, Stephen Reich, Andres Deik, Andre Franke, Michael Wittig, Sören Franzenburg, Jens Volkmann, Norbert Brüggemann, H A Jinnah, Tobias Bäumer, Christine Klein, Hauke Busch, Katja Lohmann

Faculty, Staff and Students Publications

Objective: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

Methods: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

Results: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …

Building Capacity And Equity In Implementation Science: Evaluation Of A National Mentored Training Program, Ross C Brownson, Shelly J Kannuthurai, Rebekah R Jacob, Leopoldo J Cabassa, Lisa M Klesges, Rachel G Tabak, Debra Haire-Joshu, Et Al.

2020-Current year OA Pubs

BACKGROUND: As implementation science evolves, it is essential to expand training capacity to build intellectual capital continually. The demand for training in implementation science far outstrips the current supply. This paper presents the methods and findings from the Institute for Implementation Science Scholars (IS-2) national training program (2020-2024).

METHODS: The IS-2 was a US-based, two-year training program that provided mentored training for early- and mid-career researchers interested in applying implementation science principles to reduce the burden of chronic disease disparities. Scholars attended two annual, 2.5-day intensive training sessions, received ongoing remote and in-person mentoring, and were supported by other activities …

Association Between Nt-Probnp Changes And Clinical Outcomes In Paediatric Patients With Heart Failure: Insights From Panorama-Hf And Paradigm-Hf, Robert Shaddy, Charles Canter, Et Al.

2020-Current year OA Pubs

AIMS: The PANORAMA-HF trial demonstrated significant N-terminal pro-B-type natriuretic peptide (NT-proBNP) reductions in paediatric patients with left ventricular systolic dysfunction with sacubitril/valsartan or enalapril treatment over 52 weeks. This post hoc analysis aims to correlate changes in NT-proBNP levels with clinical outcomes in PANORAMA-HF patients receiving either sacubitril/valsartan or enalapril. Additionally, NT-proBNP reductions in the paediatric population were compared with a subset of adult heart failure with reduced ejection fraction (HFrEF) patients from the PARADIGM-HF trial.

METHODS AND RESULTS: This post hoc analysis utilized data from Part 2 of the PANORAMA-HF trial. Associations between baseline NT-proBNP levels, changes post-baseline and …

Left Bundle Branch Area Pacing Compared With Biventricular Pacing For Cardiac Resynchronization Therapy In Patients With Left Ventricular Ejection Fraction ≤50%: Results From The International Collaborative Lbbap Study (I-Clas), Ramez Morcos, Pugazhendhi Vijayaraman, Óscar Cano, Francesco Zanon, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit S Sharma, Marek Jastrzebski, Manuel Molina-Lerma, Zachary I Whinnett, Kevin Vernooy, Jiangang Zou, Girish M Nair, Rajeev K Pathak, Roderick Tung, Gaurav A Upadhyay, Karol Curila, Mihail G Chelu, Kenneth A Ellenbogen

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is an established treatment of heart failure with reduced ejection fraction and wide QRS. Left bundle branch area pacing (LBBAP) has emerged as a physiologic alternative by directly engaging the His-Purkinje system, potentially improving electrical resynchronization and clinical outcomes.

Objective: The aim of the study was to compare the clinical outcomes between BVP and LBBAP in patients with left ventricular ejection fraction (LVEF) ≤50% undergoing CRT.

Methods: This multicenter observational study included patients with LVEF ≤50% receiving CRT with either LBBAP or BVP at 18 centers from January 2018 to June …

Multicenter Span Trial Of Fasudil In Ischemic Stroke, Takahiko Imai, Andreia Lopes De Morais, Xuyan Jin, Tao Qin, Jessica Lamb, Karisma A Nagarkatti, Mu-Hsun Chen, Ligia S B Boisserand, Rakesh B Patel, Mariia Kumskova, Anjali Chauhan, Krishnan M Dhandapani, Mohammad B Khan, Pradip K Kamat, Yanrong Shi, Suyi Cao, Basavaraju G Sanganahalli, Joseph B Mandeville, Patrick D Lyden, David C Hess, Enrique C Leira, Anil K Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Raymond C Koehler, Lauren H Sansing, Márcio A Diniz, Cenk Ayata

Children’s Nutrition Research Center Staff Publications

Background: The SPAN (Stroke Preclinical Assessment Network) is a confirmatory multicenter trial network to test cerebroprotective interventions in experimental acute stroke. In a first-of-its-kind trial, SPAN tested 6 interventions in a rodent model of transient focal ischemic stroke. Here, we report the efficacy of fasudil, an isoform-nonselective rho-associated kinase inhibitor, on primary and secondary outcomes in the SPAN trial.

Methods: Fasudil was administered at 10 mg/kg intraperitoneally every 12 hours for 6 doses starting 5 minutes before reperfusion in a 60-minute endovascular filament middle cerebral artery occlusion model. The active treatment arm (n=345) was compared with the pooled intraperitoneal and …

Family-Level Factors That Influence Physical Activity Among Hispanic Adolescents At Risk For Type 2 Diabetes, Sandra Mihail, Ayleen A Hernandez, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Objective: Family-based health promotion and disease prevention strategies are recommended as best practice; however, there is limited knowledge regarding the family-level factors that influence modifiable behavior risk factors like physical activity (PA) among Latinx adolescents. This study addressed this knowledge gap by using qualitative methods to identify perceptions of family-level factors that influence PA among Hispanic youth.

Methods: We conducted semistructured, open-ended interviews with 20 Latinx adolescents (14-16 years) with obesity (body mass index ≥95th percentile) to identify their perceptions of how family influences PA. Content analysis was used to identify emergent themes, which were then compared across demographic factors, …

Genetic Study Of Von Willebrand Factor Antigen Levels ≤ 50 Iu/Dl Identifies Variants Associated With Increased Risk Of Von Willebrand Disease And Bleeding, Rachel K Friedman, Adam S Heath, Jennifer E Huffman, James T Baker, Natalie R Hasbani, Sarah A Gagliano Taliun, Ming-Huei Chen, Tom E Howard, Joshua P Lewis, Nathan Pankratz, Snehal Patil, Alex P Reiner, Florian Thibord, Lisa R Yanek, Jie Yao, Hung-Hsin Chen, Joanne E Curran, Nauder Faraday, Xiuqing Guo, Marsha M Wheeler, Kathleen A Ryan, Xiang Zhou, Kelly Cho, Laura Almasy, Paul L Auer, Lewis C Becker, Peter W F Wilson, Eric Boerwinkle, Jeffrey R O'Connell, Stephen S Rich, David C Samuels, National Heart, Lung And Blood Institute (Nhlbi) Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Hematology & Hemostasis Working Group, Va Million Veteran Program, John Blangero, Myriam Fornage, Charles Kooperberg, Rasika A Mathias, Braxton D Mitchell, Jerome I Rotter, Andrew D Johnson, Nicholas L Smith, Zeynep H Coban-Akdemir, Jennifer E Below, Alanna C Morrison, Jill M Johnsen, Paul S De Vries

Faculty, Staff and Student Publications

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (≤ 50 IU/dL) in the general population is underexplored.

Objectives: To identify genetic variants influencing VWF:Ag levels ≤ 50 IU/dL.

Methods: We performed a genome-wide association study in 926 cases with VWF:Ag levels ≤ 50 IU/dL and 12 846 controls from 7 studies from the Trans-Omics for Precision Medicine program. We then examined whether significant genome-wide findings were also associated with clinical diagnosis of VWD in 5 biobanks with …

Impaired Rest-Activity Rhythm Characteristics Predict Higher Risk Of Incident Type 2 Diabetes In Uk Biobank Participants, Chris Ho Ching Yeung, Alison K Wright, Daniel P Windred, Angus C Burns, Andrew J K Phillips, Sean W Cain, Martin K Rutter, Qian Xiao

Faculty, Staff and Student Publications

Objective: Circadian rhythms play a key role in metabolic health. Rest-activity rhythms, which are in part driven by circadian rhythms, may be associated with diabetes risk. There is a need for large prospective studies to comprehensively examine different rest-activity metrics to determine their relative strength in predicting risk of incident type 2 diabetes.

Research design and methods: In actigraphy data from 83,887 UK Biobank participants, we applied both parametric and nonparametric algorithms to derive 13 different metrics characterizing different aspects of rest-activity rhythm. Diabetes cases were identified using both self-reported data and health records. We used Cox proportional hazards models …

Linking Chronic Kidney Disease To Incident Heart Failure And Adverse Cardiac Remodeling Through The Plasma Proteome: The Aric Study, Leo F Buckley, Pranav Dorbala, Victoria Lamberson, Brian L Claggett, Yue Ren, Morgan E Grams, Josef Coresh, Kunihiro Matsushita, Ryan T Demmer, Ruth F Dubin, Rajat Deo, Peter Ganz, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Background: Investigation of circulating plasma proteins may reveal insights into molecular pathways that contribute to the development of heart failure (HF) among people with chronic kidney disease.

Objectives: The authors aimed to identify circulating kidney function-related plasma proteins that are associated with the risk of incident HF.

Methods: The authors studied participants of the ongoing longitudinal ARIC (Atherosclerosis Risk In Communities) study. Relative plasma concentrations of 4,697 unique proteins were measured with the use of an aptamer assay (Somalogic). Each protein was tested for associations with estimated glomerular filtration rate (eGFR), log-transformed urine albumin-to-creatinine ratio (UACR), and incident HF by …

Trends In Glucagon-Like Peptide 1 Receptor Agonist Prescribing Patterns, Maria Ukhanova, Joseph S Wozny, Chau N Truong, Lopita Ghosh, Trudy M Krause

Faculty, Staff and Student Publications

Objective: Obesity affects more than 40% of US adults, increasing risks for cardiovascular disease and type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), initially indicated for diabetes, show promise in weight loss but face coverage issues, high costs, and premature prescribing from physicians. Research is needed to assess prescribing patterns, especially in patients without diabetes.

Study design: We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization and expenditures. We analyzed GLP-1 RA prescribing rates from 2018 to 2023, comparing semaglutide with other …

Autoantibody Profiling To Predict Response To The Anti-Pd-1 Therapy, Pembrolizumab, In Rare Tumors, M H Derbala, J Hajjar, B Stephen, S A Gurses, E Kwiatkowski, P Budde, H-D Zucht, M Bräutigam, A-S Lindemann, B A Abhari, M A Gouda, L Castillo, A Zarifa, J A How, E Rodriguez, J T Moyers, D S Hong, S Fu, F Meric-Bernstam, A Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) have limited response rates in selected patients and can cause potentially life-threatening immune-related adverse events (irAEs). This underscores the urgent need for the development of biomarkers predictive of ICI response. Pre-existing autoantibodies (AAbs) have been linked with responses to ICIs and the development of irAEs. We conducted AAb profiling to assess associations between baseline AAbs and clinical benefit (CB) in patients with rare tumors treated with anti-programmed cell death protein 1-based therapy.

Patients and methods: We conducted AAb profiling using Oncimmune's SeroTag multiplex antibody discovery technology and immune oncology array containing 1168 antigens. The study …

Associations Between Social Support, Social Control, And Stage Of Change With Self-Reported And Objectively Assessed Physical Activity In Adult Latino Dyads, Jemima C John, Minjae Lee, Soo K Park, Lorna H Mcneill, Deanna M Hoelscher, Susan M Schembre, Belinda M Reininger, Larkin L Strong

Faculty, Staff and Student Publications

Health behaviors such as physical activity (PA) are socially influenced, such that individuals from shared social networks or living environments may exhibit similar habits. This cross-sectional study examined associations of social support, social control, and family member stage of change with moderate-to-vigorous self-reported and objective PA in dyads of adult Hispanic family members. We used the Godin Leisure-Time Physical Activity Questionnaire to assess self-reported PA and accelerometry for objective PA. Validated scales assessed social support, social control, and stage of change. We performed multivariable multilevel analysis using generalized estimating equations (GEE) to account for within-dyad correlations. We conducted multivariable negative …