Medical Specialties Commons^™

Identifying Social Determinants Of Health Subgroups And Their Associations With Health Outcomes In A Prospective Us Adult Covid-19 Cohort: An Analysis Of The Inspire Registry, Yohali Burrola-Mendez, Eugene Lin, Canada Parrish, Chialing Hsu, Mandy J. Hill, Michael Gottlieb, Kristin L. Rising, Lauren E. Wisk, Nicole L. Gentile, Rachel E. Geyer, Robert A. Weinstein, Michelle Santangelo, Kristyn Gatling, Jonathan W. Dyal, Joann G. Elmore, Robert M. Rodriguez, Phillip Watts, Ji Chen, Zihan Diao, Erica S. Spatz, Kwun Cg Chan, K A. Stephens, Kelli N. O'Laughlin, Inspire Group

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To identify subgroups with similar social determinants of health (SDOH) characteristics using latent class analysis (LCA) and examine their associations with physical and mental health, cognitive function and missed workdays at 3 and 6 months post-SARS-CoV-2 infection. We hypothesised that intersecting SDOH factors would differentially influence COVID-19-related health outcomes across subgroups.

DESIGN: Prospective cohort study from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), with longitudinal data collection and cross-sectional analyses at baseline, 3-month and 6-month follow-ups.

SETTING: Multicentre registry across eight US academic medical centres (Chicago, Dallas, Houston, Los Angeles, New Haven, Philadelphia, San Francisco and …

Long Term Evaluation Of The Safety And Efficacy Of Local Cooling Anesthesia During Intravitreal Injections: The Cool-2 Trial, Arshad M. Khanani, Samir N. Patel, Charles C. Wykoff, Gun-Ho Kim, Ajay E. Kuriyan

Wills Eye Hospital Papers

BACKGROUND/OBJECTIVE: To evaluate the safety and effectiveness of a medical device providing cooling anesthesia to the eye as local anesthesia for intravitreal (IVT) injections.

SUBJECTS/METHODS: As a multicenter, open label, dose escalation clinical trial, subjects receiving at least 3 IVT injections in the study eye were recruited to participate. All patients received subconjunctival lidocaine as their anesthesia for previous IVT injections. Subjects receiving IVT injections were assigned (non-randomized) to four groups in which the cooling device was applied to the conjunctiva at the location of the intravitreal injection: Group 1: -10˚C for 20 seconds; Group 2: -15˚C for 10 seconds; …

Recent Antibiotic Exposure And Response To Treatment Of Juvenile Idiopathic Arthritis: A Retrospective Cohort Study, Daniel Horton, Charu Verma, Sanika Rege, Stephen Crystal, Tobias Gerhard, Alicia Iizuka, Matthew Iozzio, Dawn Koffman, Lauren Parlett, Julianne Varga, Carlos Rose, Brian Strom

Department of Medicine Faculty Papers

BACKGROUND: Juvenile idiopathic arthritis (JIA) has been tied to microbiome disruption and antibiotic exposure. Gut microbiota may affect how adults with rheumatoid arthritis respond to methotrexate. We tested if exposure to antibiotics was associated with response to methotrexate for JIA.

METHODS: We conducted a retrospective cohort study using national US public and private insurance claims data (2001-2023). We included children ages 1-17 continuously enrolled for ≥ 10 months and diagnosed with JIA who initiated methotrexate monotherapy or, for comparison, tumor necrosis factor inhibitor (TNFi) monotherapy without prior disease-modifying antirheumatic drug (DMARD) exposure. Antibiotic exposure during the 10-month baseline period was …

Notch1 Acts As A Tumor Suppressor That Induces Early Differentiation In Head And Neck Cancer, Chenfei Huang, Shhyam Moorthy, Qiuli Li, Kazi M Ahmed, Kalil Saab, Defeng Deng, Jiping Wang, Xiayu Rao, Jiexin Zhang, Yuanxin Xi, Jing Wang, Zhiyi Liu, Noriaki Tanaka, David A Wheeler, Eve Shinbrot, Rami Saade, Curtis R Pickering, Tong-Xin Xie, Adel K El-Naggar, Abdullah A Osman, Kunal Rai, Patrick A Zweidler-Mckay, John V Heymach, Lauren A Byers, Faye M Johnson, Vlad C Sandulache, Jeffrey N Myers, Pedram Yadollahi, Mitchell J Frederick

Faculty, Staff and Students Publications

Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early …

Virtual Patient-Specific 3-Dimensional Specimen Maps For Adjuvant Radiation Therapy Planning In Mucosal Head And Neck Squamous Cell Carcinoma, Whitney Jin, Michael C. Topf, Marina Aweeda, Kavita Prasad, Olivia Prosak, Sindhura Sridhar, Zachary Kohutek, Sean All, D. W. Nathan Kim, Anthony Cmelak, Ryan Whitaker, Alexander Langerman, Kyle Mannion, Melanie Hicks, Sarah Rohde, Robert Sinard, Eben Rosenthal, Natalie A. Lockney

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

PURPOSE: Adjuvant radiation therapy planning for mucosal head and neck squamous cell carcinoma is challenging due to postoperative anatomic changes, contributing to variability in clinical target volume (CTV) delineation and risk of geographic miss or unnecessary dose expansion. Patient-specific 3-dimensional (3D) specimen maps may offer a novel approach to improve the localization of high-risk margins and facilitate multidisciplinary communication.

METHODS AND MATERIALS: In this prospective, noninterventional feasibility study, 3D scanning and virtual pathologic mapping of surgical specimens were performed as part of routine pathologic processing. Annotated 3D maps were integrated into the radiation therapy planning workflow and reviewed by the …

The Relationship Between Psychological Stress And Sars-Cov-2 Nucleocapsid-Antibody Response Following Natural Infection: Longitudinal Findings From The Aegis Study, Erika T Beidelman, Ashley Judge, David B Allison, Stephanie Dickinson, Lilian Golzarri Arroyo, Anna L M Macagno, Michael J Ricciardi, Jon Macy, Stanley Perlman, Christina Ludema, Kevin C Maki, Molly Rosenberg

Faculty, Staff and Students Publications

Psychological stress can cause diminished immune response to infectious challenges. The extent this holds true during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the modifying effect of vaccination status is untested. We explored these relationships in a non-random sample standardized to the US adult population. Across 2178 participants in the Aegis study (2021-2022), we identified 507 eligible laboratory-confirmed SARS-CoV-2 infections. We estimated the natural log of nucleocapsid-binding antibody absorbance (N-antibody) at study visits up to 225 days following a positive SARS-CoV-2 test. Linear mixed effects models were fit to estimate the association of baseline perceived stress and, separately, …

The Influence Of Social Media Messaging On Human Papillomavirus Vaccine Attitudes And Confidence Among Adolescent Males: Group Discussion Study, Neha Trivedi, Rachel Van Vleet, Czesia Eid, Amelia Burke-Garcia, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: Despite the human papillomavirus (HPV) vaccine being available to males for the past 12 years, adolescent males continue to lag in HPV vaccine uptake due to a variety of factors. With the ubiquitous nature of social media use among this population, further research is needed to improve HPV vaccine confidence among young adolescent males using these platforms.

OBJECTIVE: Using the Elaboration Likelihood Model (ELM), this study sought to better understand knowledge, attitudes, and beliefs about HPV and HPV vaccination among male adolescents aged 14-17 years and examine how social media messaging influences vaccine perceptions and explore the characteristics of …

Optimizing The Sensitivity Of Detection Of Respiratory Syncytial Virus Infections In Longitudinal Studies Using The Combination Of Weekly Sample Testing And Biannual Serology., Shannon C. Conrey, Daniel C. Payne, Maria Deza Leon, Monica Epperson, Melissa M. Coughlin, Allison R. Burrell, Claire P. Mattison, Rachel M. Burke, Julia M. Baker, Natalie J. Thornburg, Meredith L. Mcmorrow, Mary Allen Staat, Ardythe L. Morrow

Manuscripts, Articles, Book Chapters and Other Papers

Cohort studies are often challenged by incomplete adherence to sampling regimens, limiting the full capture of disease burden. We describe the detection of respiratory syncytial virus (RSV) infections achieved in a birth cohort using a combination of weekly nasal sample testing and serology. The Pediatric Respiratory and Enteric Viral Acquisition and Immunogenesis Longitudinal Cohort followed 245 maternal-child dyads from birth to age 18 to 24 months. Weekly mid-turbinate nasal swabs were tested for RSV using real-time polymerase chain reaction (RT-qPCR). Serum was tested for RSV pre-fusion F IgG and IgA antibody at age 6 weeks and biannually from 6 to …

Liver Injury From Medications Used For Treating Inflammatory Bowel Disease: The Drug-Induced Liver Injury Network Experience, Harish Gopalakrishna, Jiezhun Gu, Yi-Ju Li, Huiman Barnhart, Dina Halegoua-De Marzio, Herbert L. Bonkovsky, A. Sidney Barritt, Jean P. Molleston, Naga P. Chalasani, Marwan Ghabril

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: We aimed to investigate and characterise DILI due to approved therapies for inflammatory bowel disease (IBD).

METHODS: Using the Drug-Induced Liver Injury Network (DILIN) prospective study, we evaluated definite, highly likely, or probable DILI attributed to IBD therapies, including use for non-IBD indications (but excluding corticosteroids). HLA allele associations were investigated.

RESULTS: Among 1806 participants, 81 (4.5%) had IBD-agent DILI: 31 biologics (27 infliximab), 35 immunomodulators (31 azathioprine/mercaptopurine), 14 aminosalicylates (11 sulfasalazine) and 1 small molecule (tofacitinib). Median age was 45 years with 75% female and 78% White. Patients with biologic-DILI were younger, had longer latency (median 124 days), …

Genetic Ancestry-Concordant Ceramide Metabolism And Response To Androgen Receptor Pathway Inhibition In Metastatic Castration-Resistant Prostate Cancer, Sean Piwarski, Lauren Howard, Morgan Paul, Nick Bachelder, Bonnie Lacroix, Angela Clayton, Donna Allen, Julie Kephart, Andrew Armstrong, Steven Patierno, Daniel George, Terry Hyslop, Jennifer Freedman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The authors observed differences in response between Black and White patients with metastatic castration-resistant prostate cancer (mCRPC) who were treated prospectively with androgen receptor pathway inhibition (ARPI) in the Abi Race and PANTHER studies. In addition, genetic ancestry-related single nucleotide variants in ceramide metabolism genes were associated with the time to prostate-specific antigen progression in the Abi Race study. For this report, the authors analyzed ceramide metabolites and their association with response to ARPI treatment in the Abi Race and PANTHER studies.

METHODS: Fasting serum levels were obtained from 22 Black patients and 22 White patients in the Abi …

Sex-Based Disparities In Health Care Access And Utilization Among Patients With Atrial Fibrillation, Ji Mei May Wong, Peter R. Kowey

Department of Medicine Faculty Papers

IMPORTANCE: Females with atrial fibrillation (AF) experience a higher risk of stroke, myocardial infarction, and mortality than males with AF. Theories suggest that sex-based differences in hormonal, structural, and electrophysiologic factors are associated with this imbalance; we hypothesized that sex-based differences in health care access and utilization (HCAU) are also underlying factors.

OBJECTIVE: To determine whether sex-based disparities in HCAU barriers exist among individuals with AF.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data on patients with AF in the All of Us Research Program Registered Tier dataset (version 8), which contains integrated data from the electronic health record …

Silk Vista Baby Versus Pipeline Embolization Device For Unruptured Distal Anterior Cerebral Artery Aneurysms: A Multicenter Propensity-Weighted Comparative Study., Valerio Da Ros, Frédéric Clarençon, Adam A. Dmytriw, Pascal Jabbour Md, Marios Psychogios, Peter Sporns, Ajit S. Puri, Ameer E. Hassan, Oktay Algin, Markus A. Möhlenbruch, Mauro Bergui, Oded Goren, Gregoire Boulouis, Takeshi Morimoto, Raoul Pop, Joanna Wk Ho, Virginia Pujol Lereis, Jared Cooper, Giancarlo Salsano, Alessandro Sgreccia, Arturo Consoli, Eytan Raz, Julien Burel, Khawaja Muhammad Baqir Hassan, Zhe Ji, Riitta Rautio, Maria Ruggiero, Federico Sabuzi, Stefania Proietti, Joseph Domenico Gabrieli, Michael Levitt, Antonio Armando Caragliano, Christophe Cognard, Gaultier Marnat, Nicola Limbucci, Mariangela Piano, Alexis Guedon, Andrea Romi, Fortunato Di Caterino, Mykola Vyval, Adrien Guenego, Mohamad Abdalkader, Thanh Nguyen, Vitor Mendes Pereira, Ocilio Ribeiro Goncalves, Erwah Kalsoum, Alessandro Pedicelli, Andrea M Alexandre, Luca Scarcia

Department of Neurosurgery Faculty Papers

BACKGROUND: Flow diversion is effective for unruptured distal anterior cerebral artery (DACA) aneurysms, yet comparative data between the Silk Vista Baby (SVB) and Pipeline Embolization Device (PED) in this challenging territory remain scarce.

METHODS: We conducted a retrospective multicenter study using the CRETA Registry, including consecutive patients with unruptured DACA aneurysms treated with SVB or PED. The primary endpoint was complete angiographic occlusion (O'Kelly-Marotta grade D). Secondary outcomes included procedural characteristics, clinical outcome (modified Rankin Scale), and complications. Overlap weighting was applied to account for non-randomized treatment allocation. Predictors of occlusion were explored using penalized logistic regression. A sensitivity analysis …

Routine Transfusion Of Rh(D)-Positive Rbcs To Rh(D)-Negative Patients Designated As Do Not Resuscitate Conserves Rh(D)-Negative Red Blood Cell Inventory, Julie Katz Karp, Jovanna Everetts, Juliana Guarente, Angelica Vivero, Tiffany Bohr, Mary Harach

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: A minority of blood donors are Rh(D)-negative, and Rh(D)-negative red blood cell (RBC) products are often overutilized. As such, Rh(D)-negative RBCs may be difficult to maintain in blood bank inventory.

Study design and methods: We changed our blood bank laboratory policy to approve non-alloimmunized Rh(D)-negative patients to receive Rh(D)-positive RBCs for routine transfusion under defined criteria. Those criteria included Rh(D)-negative males (all ages) and females (aged >50 years) who were designated as do not resuscitate (DNR), either with or without intubation, in the electronic medical record.

Results: From August 15, 2024 through August 15, 2025, a total of 204 …

Matching-Adjusted Indirect Comparison Of Acoltremon Ophthalmic Solution 0.003% And Cyclosporine 0.05% Ophthalmic Emulsion For Increased Tear Production In Patients With Dry Eye Disease, Stephen Pflugfelder, Tony Okoro, Margaret Ainslie-Garcia, Anja Haltner, Emily K Prentiss, Elizabeth M Salvo-Halloran, Nikethana Srikanth, Michelle Senchyna, Esen K Akpek

Faculty, Staff and Students Publications

No abstract provided.

Prognostic Value Of Stress Perfusion Cardiac Magnetic Resonance Imaging In Kawasaki Disease With Coronary Artery Aneurysms: A 10-Year Retrospective Cohort Study, Alexander J Kiener, S Kristen Sexson Tejtel, Aimee Liou, Carolyn A Altman, Tam T Doan

Faculty, Staff and Students Publications

Background: Kawasaki disease (KD) with coronary artery aneurysms (CAA) places patients at risk for myocardial ischemia and major cardiac events (MCE). While stress perfusion cardiac magnetic resonance imaging (spCMR) is used for surveillance, its prognostic value has not been established.

Methods: We conducted a retrospective cohort study of KD patients (AHA risk levels 3-5) who underwent clinically indicated vasodilator spCMR at a tertiary pediatric center between October 2014 and December 2024. We evaluated inducible perfusion defects, late gadolinium enhancement (LGE), ventricular function, and MCE (myocardial infarction, ventricular dysfunction, arrhythmia, revascularization, transplant, or death). We performed Cox regression and Kaplan-Meier analyses …

Myocardial T1 And T2 Values Are Associated With Patient Age In Healthy Pediatric Heart Transplant Recipients, Andrew A Lawson, Robyn G Lottes, Defne Magnetta, Andrada Popescu, Kae Watanabe, Cynthia K Rigsby, Michael Markl, Nazia Husain

Faculty, Staff and Students Publications

Background: In pediatric heart transplant recipients (PHTR), myocardial T1 and T2 values are elevated in the setting of acute rejection and with cardiac allograft vasculopathy. In normal, healthy children, T1 and T2 values vary with patient age. Our goal was to identify associations between T1, extracellular volume fraction (ECV), and T2 values and patient- and donor-characteristics in PHTR without history of significant graft pathology.

Methods: We performed a single-center, retrospective chart review of consecutive cardiac magnetic resonance (CMR) studies in PHTR from 2017 to 2023. Exclusion criteria were a prior CMR during the study period, history of any prior antibody-mediated …

Human Neuronal Firing Varies With The Frequency Of Local Field Potential Oscillations, Zahra Jourahmad, Raissa K Mathura, Layth S Mattar, Melissa C Franch, Danika L Paulo, Mohammed Hasen, Nicole R Provenza, Benjamin Y Hayden, Sameer A Sheth, Eleonora Bartoli, Andrew J Watrous

Faculty, Staff and Students Publications

Neural oscillations play a critical role in shaping neuronal firing patterns. While phase-locked neuronal firing ("phase tuning") has been extensively studied in animal models and human invasive recordings, much less is known about whether neurons show preferential firing at specific oscillatory frequencies, termed frequency tuning. Here, we employ human intracranial recordings across several brain regions including hippocampus, entorhinal cortex, anterior and posterior cingulate cortex, and orbitofrontal cortex to test the hypothesis that neurons exhibit frequency-specific firing. We analyzed 357 single units recorded simultaneously with local field potentials in 19 neurosurgical patients during awake resting. We estimated the instantaneous frequency of …

Non-Isolated Dandy-Walker Malformation: Exome Sequencing Efficacy And Phenotypic Expansions, Sarah Araji, Xiaonan Zhao, Jill A Rosenfeld, Seema R Lalani, Daryl A Scott

Faculty, Staff and Students Publications

Dandy-Walker malformation (DWM) is a rare congenital abnormality of the posterior fossa and the cerebellum and has an incidence of 1 in 10 000 to 30 000 births. Although DWM can present in isolation, it is often associated with other central nervous system (CNS) abnormalities or extra-CNS anomalies (DWM+). A molecular cause is not identified in the majority of individuals with DWM+. This is due, in part, to uncertainty regarding optimal testing strategies and an incomplete understanding of the genetic causes of DWM+. In this study, we analyzed clinical exome sequencing (cES) data from 91 individuals with DWM+ to determine …

Investigating The Correlation Between Scleral Spur Angle And Intraocular Lens Tilt, Dylan Mcbee, Karim Kozhaya, Li Wang, Douglas D Koch, Allison J Chen, Mitchell P Weikert

Faculty, Staff and Students Publications

Purpose: To evaluate the correlation between the preoperative vertex-scleral spur angle (Vtx-SSA) and postoperative horizontal intraocular lens (IOL) tilt after routine cataract surgery.

Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.

Design: Prospective case series.

Methods: This study enrolled patients who underwent uneventful phacoemulsification cataract extraction with IOL implantation. The Anterion and Eyestar 900 swept-source optical coherence tomographers (SS-OCTs) were used to determine Vtx-SSA and lens tilt (crystalline and IOL) measurements, respectively. Tilt vectors were decomposed into orthogonal, vertical, and horizontal components to explore preoperative correlations independently. The Pearson correlation coefficient and linear regression analysis were used to …

Plasma Biomarkers Of Brain Injury In Critically Ill Children Receiving Extracorporeal Membrane Oxygenation, Matthew L Friedman, Michael J Bell, Bonnie A Brooks, Adam S Himebauch, Asavari Kamerkar, Kerri Larovere, Laura L Loftis, Jose A Pineda, Ahmed Said, Hitesh S Sandhu, Martin Stengelin, Catherine Demos, Mark S Wainwright, Alina N West, Allan Barnes, Allen D Everett, Ryan J Felling, Sue J Hong, Jennifer L Roem, Cynthia F Salorio, Derek K Ng, Melania M Bembea

Faculty, Staff and Students Publications

Importance: Timely identification of acute brain injury (ABI) in children receiving extracorporeal membrane oxygenation (ECMO) support is critical for early neuroprotective interventions.

Objectives: To determine if elevations in plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels in children receiving ECMO precede new ABI confirmed by neuroimaging, and if they are associated with mortality and functional outcomes.

Design, setting, and participants: This was a prospective observational cohort study conducted from 2019 to 2023, with 18-month follow-up completed in 2025. Children aged 2 days to younger than 18 years at ECMO cannulation were recruited from 11 US …

Polygenic Risk Scores And Hla Class Ii Variants Are Biomarkers Of Corticosteroid Response In Childhood Nephrotic Syndrome., Tiffany Tu, Alejandro Ochoa, Amika Sood, Ashley Dabrik, Megan Chryst-Stangl, Brandon Lane, Guanghong Wu, Frank Donovan, Ursula Harper, Settara Chandrasekharappa, Christopher Esezobor, Adaobi Solarin, David Hooper, Christine Sethna, Sandra Amaral, Mahmoud Kallash, Michelle Rheault, Priya Verghese, Vikas Dharnidharka, Eloise Salmon, Patricia Weng, Tarak Srivastava, Michael E Seifert, Cozumel Pruette, David Selewski, Keisha Gibson, Tracy Hunley, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arvind Bagga, Aditi Sinha, Nicholas Webb, Larry Greenbaum, Ali Gharavi, Krzysztof Kiryluk, Matthias Kretzler, Lisa Guay-Woodford, Simone Sanna-Cherchi, Agnieszka Bierzynska, Ania Koziell, Gavin Welsh, Moin Saleem, Charles Rotimi, Eileen Chambers, Cliburn Chan, Curegn Consortium, Pnrc Glomerular Disease Group, Cibmtr/Nmdp Consortium, Annette Jackson, Adebowale Adeyemo, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Nephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are no current reliable predictors of therapy response at initial clinical presentation.

METHODS: To evaluate predictors, we conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 children (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched control individuals.

RESULTS: A significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were …

A Phase 4, Open-Label, Non-Randomized, Multicenter Study To Evaluate Efficacy (And Safety) Of Intravenous Administration Of Optison For Contrast-Enhanced Echocardiography In Pediatric Patients, Arash Sabati, Shuo Wang, Pushpa Shivaram, Joshua Hawley, David Thompson, Francine Erenberg, Shelby Kutty, Aparna Kulkarni, Tam T Doan, Joshua D Robinson

Faculty, Staff and Students Publications

Contrast-enhanced echocardiography (CE-echo) is commonly used in adult patients to optimize endocardial border delineation (EBD) but there is limited experience in children. A prospective, open-label, non-randomized, multicenter study was performed to evaluate the efficacy of intravenous Optison for CE-echo in pediatric patients and determine the optimal dose of Optison. Subjects ≥ 9 and <  18 years with suboptimal echocardiograms (defined as ≥ 2 contiguous segments that could not be adequately visualized) were enrolled. After a baseline non-contrast echocardiogram (NC-echo), CE-echo was performed with 2 dose levels of Optison based on patient weight. The primary endpoint was visualization of the LV wall segments (LVWS) in apical 2- and 4-chamber views. An EBD score was calculated by assigning a value from 0 (no visualization) to 3 (optimal visualization) for 12 LVWS. 37 subjects across 8 sites completed the study. 30 had complete echocardiograms at both dose levels. 2 patients had usable images at dose 2 only. Mean age was 13.4 years (± 2.6) with 23 males (62%). Mean weight was 73.9 kg (± 36.8) with wide distribution of weight (interquartile range of 42-102 kg). There were 8 patients under 40 kg. Most subjects had a prior medical/surgical history (n = 33, 89%). Both dose levels of Optison CE-echo improved the number of LVWS visualized from 3.7 ± 1.1 on NC-echo to 10.0 ± 0.1 with dose 1 (p <  0.001) and 10.5 ± 0.1 with dose 2 (p <  0.001). EBD score also improved at both dose levels from 11.9 ± 2.5 for NC-echo to 28.5 ± 1.7 for dose 1 (p <  0.001) and 30.2 ± 8.4 for dose 2 (p <  0.001). The number of suboptimal echocardiograms improved from 92.3% ± 10.7 in NC-echo to 26.2% ± 9 with dose 1 (p <  0.001) and 30.8% ± 4.5 with dose 2 (p <  0.001). CE-echo with intravenous Optison in pediatric patients improved the number of LVWS visualized, improved EBD score, and reduced the number of suboptimal echocardiograms at both dosages used in this study. Intravenous Optison can improve LV visualization in pediatric patients with suboptimal echocardiograms.

Early Neurodevelopmental Outcomes In Children With Congenital Heart Disease., Mike Seed, Dawn Ilardi, Valerie Rofeberg, Cynthia Ortinau, Caren Goldberg, Garrett Reichle, Lauren Bush, Justin Elhoff, Amy Jo Lisanti, Jennifer Butcher, Caitlin Rollins, Andrew Van Bergen, Shabnam Peyvandi, Emily Bucholz, Stephanie Cox, Lyla Hampton, Jacqueline Sanz, Sonia Monteiro, Shruti Tewar, Kiona Allen, Caroline Lee, Kristi Glotzbach, Nneka Alexander, Laurel Bear, Corinne Anton, Renee Sananes, Linh Ly, Gina Boucher, Kelly Wolfe, Lindsay Edwards, Elizabeth J. Willen, Alexander Tan, Christina Ortega, Erica Sood, Anjali Sadhwani, Kari Crawford Plant, Lauren Quigley, Jessica Pliego, Elizabeth Valles, Abbey Hines, David Wypij, Thomas Miller

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Neurodevelopmental impairments are common in children with congenital heart disease.

OBJECTIVES: To compare neurodevelopmental outcomes by cardiac diagnosis and identify associations between medical and social factors and early neurodevelopmental outcomes among children with congenital heart disease.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used neurodevelopmental follow-up data obtained between May 1, 2019, and June 30, 2022, and entered into the Cardiac Neurodevelopmental Outcome Collaborative (CNOC) registry, with linkage to the Pediatric Cardiac Critical Care Consortium registry. Children younger than 30 months from 25 CNOC sites were studied. Data analysis was performed between January 2023 and December 2024.

EXPOSURES: Patients …

Parent Perspectives On Neonatal Research Without Prior Consent: A Mixed-Methods Interview Study., Stephanie A. Kraft, Abigail Brickler, Abril Beretta, Rishabh Jain, Andrea Kelsh, Kaashif A. Ahmad, Justin T. Clapp, Neal W. Dickert, Rebecca A. Dorner, Katherine F. Guttmann, Anup C. Katheria, Stephanie Kukora, Benjamin A. Mooso, Elliott Mark Weiss, Fam-Connect Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Recruitment for clinical research in the neonatal intensive care unit (NICU) is difficult, which may lead to low enrollment rates, systematically skewed samples, and nongeneralizable results. Research without prior consent (RWPC), defined as obtaining consent only after infants have been randomized to a treatment arm, may improve enrollment but raises ethical challenges. There is a need to better understand how parents with lived experience of having an infant in the NICU consider RWPC’s impact on critical ethical values related to informed consent, including decision-making, respect, and trust. This mixed-methods study aimed to describe parental perceptions of the acceptability and …

Lymph Node Dissection And Postoperative Complications After Lung Cancer Resection, Isheeta Madeka, Khaled Noueihed, Jacob Woodroof, Shale Mack, Hamza Rshaidat, Gregory L Whitehorn, Sneha Alaparthi, Scott H. Koeneman, Tyler R. Grenda, Nathaniel R. Evans, Iii, Olugbenga T. Okusanya

Department of Surgery Faculty Papers

Importance: Current lung cancer guidelines recommend lymph node sampling (LNS) with the 3 + 1 rule, which recommends station-based sampling with at least 3 N2 (mediastinal) and 1 N1 (hilar) nodal stations. Although there is oncologic benefit to rigorous LNS, potential negative impacts on surgical outcomes have not been well investigated. As adoption of the 3 + 1 rule increases given its formalization as guideline-concordant care, associations with adverse outcomes are crucial to characterize.

Objective: To evaluate whether satisfying the 3 + 1 rule is associated with increased postoperative complications.

Design, setting, and participants: This retrospective cohort study used the …

Coxfa4l2 Upregulation Preserves Residual Cytochrome C Oxidase Activity In Coxfa4-Related Leigh-Like Encephalopathy, Micol Falabella, Sandra Lopez Calcerrada, Jana Aref, Jiaze Gao, William L Macken, Chiara Pizzamiglio, Renata Kabiljo, Anna Lucia Francavilla, Pauline Gaignard, Antoine Pouzet, Jonathan Levy, Giulia Barcia, Jamie K Leighton, Efstathia Chronopoulou, Germaine Pierre, Riza Köksal Özgül, Ali Dursun, Rebecca Halligan, Helen Mundy, Javeria Raza Alvi, Tipu Sultan, William James Craigen, Lisa Emrick, Jill A Rosenfeld, Gehad Elmakkawy, Jihye Kim, Joseph J Gleeson, Aboulfazl Rad, Gabriela Oprea, Maqbool Hussain, Khalil Ur Rehman, Sadia Riaz, Robert W Taylor, Vincent Procaccio, Maha S Zaki, Erika Fernandez-Vizarra, Ciro Leonardo Pierri, Michael G Hanna, Henry Houlden, Reza Maroofian, Cristina Ugalde, Jan-Willem Taanman, Robert D S Pitceathly

Faculty, Staff and Students Publications

Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes. COXFA4 (cytochrome c oxidase subunit FA4), formerly NDUFA4, is a nuclear-encoded COX subunit, but its role in disease remains poorly defined. We report the largest genetically confirmed cohort of COXFA4-related PMD to date, comprising 13 individuals from 12 families with biallelic pathogenic COXFA4 variants. All present …

Gastrointestinal Symptoms After Sport-Related Concussion: Prevalence And Patterns In A Multi-Cohort Analysis, Emma Finnegan, Ed Daly, Katherine J. Hunzinger, Lisa Ryan

Department of Exercise Science Faculty Papers

Background/Objectives: Concussions occur across all sports globally; however, inconsistent symptom recognition continues to challenge diagnosis, management, and recovery. Although concussion effects extend beyond neurological dysfunction, gastrointestinal (GI) symptoms remain insufficiently captured within current assessment frameworks and may influence athletes’ fuelling choices and food tolerance during recovery. This study aimed to describe the prevalence and patterns of GI symptoms reported among athletes with a history of concussion and to explore whether symptom prevalence and burden differed by sex and country. Methods: A total of 401 adult athletes (225 males; mean age 32.4 ± 11.3 years) with a history of concussion were …

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …

Smaller Right Ventricle Results In Poorer Exercise Performance In Young Patients With Repaired Tetralogy Of Fallot, Christiane Mhanna, Katerina Kourpas, Takeshi Tsuda

Department of Pediatrics Faculty Papers

BACKGROUND: Severe right ventricular (RV) dilatation and exercise intolerance are considered indications for pulmonary valve replacement in surgically repaired tetralogy of Fallot (rTOF).

METHODS AND RESULTS: Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) were performed in rTOF patients with pulmonary insufficiency (PI). Oxygen pulse (OP), calculated as oxygen consumption (V̇O

CONCLUSIONS: A smaller RV was associated with worse exercise performance, indicating exercise intolerance is independent of RV dilatation in young rTOF with PI and represents a unique pathological entity responsible for reduced exercise performance.

International Multi-Center Study To Quantify The Effect Of Deep Venous Drainage After Surgical Resection Of Spetzler-Martin Grade Ii-Iii Brain Arteriovenous Malformations, Avi A. Gajjar, Rashad Jabarkheel, Mohamed M. Salem, Basel Musmar, Sandeep Kandregula, Hammam Abdalrazeq, Nimer Adeeb, Assala Aslan, Nathan Ramachandran, Stavropoula Tjoumakaris, Hamza Adel Salim, Adam A. Dmytriw, Christopher S. Ogilvy, Mustafa K. Baskaya, Douglas Kondziolka, Jason Sheehan, Howard Riina, Abdallah Abushehab, Kareem El Naamani, Najib Muhammad, Ahmed Abdelsalam, Natasha Ironside, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Arwin Rezai, Omar Alwakaa, Pierce Davis, Salem M. Tos, Ufuk Erginoglu, Johannes Pöppe, Rajeev D. Sen, Alan S. Boulos, John C. Dalfino, Christoph J. Griessenauer, Robert M. Starke, Laligam N. Sekhar, Michael R. Levitt, David J. Altschul, Neil Haranhalli, Malia Mcavoy, Hussein A. Zeineddine, Adib A. Abla, Saman Sizdahkhani, Sravanthi Koduri, Michael R. Gooch, Robert H. Rosenwasswer Md, Christopher Stapleton, Matthew Koch, Peng R. Chen, Spiros Blackburn, Ketan Bulsara, Louis J. Kim, Omar Choudhri, Bryan Pukenas, Joshua S. Catapano, Darren Orbach, Edward Smith, Pascal J. Mosimann, Alexandra R. Paul, Pascal Jabbour, Ali Alaraj, Mohammad A. Aziz-Sultan, Aman B. Patel, Amey Savardekar, Christina Notarianni, Hugo H. Cuellar, Bharat Guthikonda, Jacques Morcos, Michael Lawton, Jan-Karl Burkhardt, Visish M. Srinivasan

Department of Neurosurgery Faculty Papers

Deep venous drainage (DVD) is considered a negative prognostic factor in AVM surgery, yet its effect on postoperative functional decline remains incompletely defined. This study evaluates whether DVD predicts worsened functional status after surgical resection of Spetzler-Martin Grade II-III AVMs. This retrospective multicenter study analyzed 129 patients with Spetzler-Martin Grade II-III AVMs across nine centers in North America and Europe who underwent primary surgical resection. We excluded cases with prior endovascular or stereotactic interventions. The primary outcome measured was poor functional status, defined as modified Rankin Scale (mRS) score 3-6 at last follow up. Among 129 patients with Spetzler-Martin Grade …