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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.

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 …

Extracorporeal Membrane Oxygenation, Acute Kidney Injury, Fluid Balance, And Continuous Renal Replacement Therapy: Acute Disease Quality Initiative (Adqi) And Extracorporeal Life Support Organization (Elso) Joint Consensus Conference, Katja M Gist, David T Selewski, Kianoush B Kashani, Ayse Akcan-Arikan, Gail Annich, Marta V Antonini, David Askenazi, Linda Awdishu, Brian C Bridges, Michael J Connor, Lui G Forni, Dana Y Fuhrman, Stuart L Goldstein, Stephen M Gorga, Pramod K Guru, Ahmad Kaddourah, Alex Lepage-Farrell, D Michael Mcmullan, Ravindra L Mehta, Shina Menon, Theresa Mottes, Thomas Müeller, Marlies Ostermann, Matthew L Paden, Natalie E Rintoul, Thiago Reis, Claudio Ronco, Emily See, Gurmeet Singh, Sean M Bagshaw, Graeme Maclaren

Faculty, Staff and Students Publications

Extracorporeal membrane oxygenation (ECMO) is increasingly being utilized for life-threatening cardiac and/or respiratory failure refractory to conventional treatment. Acute kidney injury (AKI) and fluid balance disorders commonly occur both before and during ECMO, with approximately half of cases receiving treatment with continuous renal replacement therapy (CRRT). Acute kidney injury, fluid balance disorders, and CRRT influence both short- and long-term outcomes in this population. The 36th Acute Disease Quality Initiative (ADQI) meeting was held in June 2025 to develop multidisciplinary international expert recommendations for AKI, fluid balance, and CRRT during ECMO across the age spectrum. This work encompassed five working groups: …

How To … Coach Problem Representation To Strengthen Diagnostic Reasoning In Trainees, Cody Clary, Adam Cohen, Satid Thammasitboon

Faculty, Staff and Students Publications

Problem representation (PR) is a concise synthesis of clinical information that captures the core diagnostic problem in a single statement, often referred to as a 'one-liner'. Although central to diagnostic reasoning, this skill is frequently underdeveloped in medical training. Many trainees struggle to transform clinical data into meaningful representations, which can hinder communication, diagnostic reasoning and patient safety. The Assessment of Reasoning Tool-Reconstructed (ART-R) provides a structured framework that educators can adapt as a coaching rubric to strengthen PR during clinical teaching. Using the ART-R, faculty can guide trainees to refine their PR by focusing on three elements: (1) clarity …

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 …

Rethinking Ethics For An Era Of Trusted Computational Tools, Kristin M Kostick-Quenet, Meghan Hurley, John Herrington, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Computer perception (CP) technologies are poised to deliver near real-time behavioral insights with high precision. As technical barriers recede, our field's ethical focus must shift from "Can we trust the data?" to "Should we use it here, and how?" We propose a contextual ethics framework that: (1) defines the appropriate scope of CP integration; (2) advocates codesigned roadmaps to manage expectations and epistemic conflict; (3) expands evaluation beyond performance metrics to humanistic outcomes; and (4) anticipates future high performance systems to safeguard dignity, empathy, and shared decision-making in clinical care.

Treatment Of Obsessive-Compulsive Disorder Via Mental Health Technology, Erika S Trent, Nisha Jagannathan, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that remains chronic unless intervened with evidence-based intervention. Cognitive behavioral therapy (CBT) with exposure and response prevention is the gold-standard psychological intervention for OCD, but many individuals do not receive this intervention due to barriers to accessing treatment. Mental health technology tools such as telehealth, computerized programs, internet-delivered CBT, and mobile applications have been adopted to expand the accessibility of CBT. An up-to-date summary of the evidence base of technology-mediated formats of CBT for OCD treatment is provided. Clinical benefits offered by such approaches, current limitations, and future research directions are discussed.

Barrett’S Esophagus-Associated Genetic Loci In African Americans: A Case-Control Study Using The All Of Us Research Program, Ashwin Rao, Jinyoung Byun, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

Background and aims: Barrett's esophagus is the only known precursor lesion to esophageal adenocarcinoma (EAC). Barrett's esophagus and EAC are less common in African Americans than in non-Hispanic Whites. Studies in European populations have identified Barrett's esophagus-associated risk loci; however, none have examined loci in African Americans cohorts. We conducted a case-control targeted replication study to investigate previously identified Barrett's esophagus risk loci in an African Americans cohort in the All of Us (AoU) Research Program.

Methods: We abstracted phenomic and genomic data from 108 African Americans with Barrett's esophagus and 778 African Americans controls in the AoU database. We …

Association Of Infection Frequency And Incident Clonal Hematopoiesis Of Indeterminant Potential, Ajibike Lapite, Vernon A Burk, James Decuir, Junichi Ishigami, Seyedmohammad Saadatagah, Pradeep Natarajan, Christie M Ballantyne, Elizabeth A Platz, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis of indeterminant potential (CHIP) is an age-related phenomenon associated with increased risk of hematologic malignancy. Preclinical studies have shown that infection is a driver of CHIP; clinical studies in people living with HIV suggest a relationship between chronic infection and CHIP, but the association between infection frequency and incident CHIP in the general population remains unknown. We leveraged the atherosclerosis risk in communities study to design a closed prospective cohort study. CHIP was determined based on whole-exome sequencing at 2 time points 20 years apart. Included were 3,367 individuals without cancer or CHIP at time 1 and without …

Comparison Of Different “Familial Chylomicronemia Syndrome” Clinical Diagnosis Scoring Systems In Patients With Persistent Chylomicronemia, Diane Brisson, Miriam Larouche, Nathalie Laflamme, Seyedmohammad Saadatagah, Jean Bergeron, Christie M Ballantyne, Daniel Gaudet

Faculty, Staff and Students Publications

Background: Chylomicronemia is associated with extreme hypertriglyceridemia and an increased risk of acute pancreatitis and cardiometabolic complications. Rarely, chylomicronemia persists despite control of secondary causes and conventional treatments. The most severe form of persistent chylomicronemia (PC) is familial chylomicronemia syndrome (FCS). Diagnosis scoring systems have been developed to help clinicians differentiate FCS from other causes of chylomicronemia.

Objective: To assess the ability of FCS diagnosis scoring systems to discriminate FCS from other forms of PC.

Methods: This study included 413 Caucasians presenting a history of chylomicronemia, among whom 65 (15.7%) met the criteria of PC. The performance of 3 FCS …

Validity And Utility Of A Single-Item Patient-Reported Measure Of Treatment-Related Bother In Rheumatoid Arthritis: A Cross-Sectional Omeract Study, Dorthe B Berthelsen, Tobias Haugegaard, Mohammed M Kamso, Peter Tugwell, Lee S Simon, John P A Ioannidis, Caroline Flurey, Maarten Boers, Marieke Voshaar, Pam Richards, Beverly Shea, Daniel E Furst, Jasvinder A Singh, Randall Stevens, Thasia Woodworth, Susan J Bartlett, Glen S Hazlewood, Robin Christensen

Faculty, Staff and Students Publications

Objectives: To assess the construct validity of a modified single-item measure of bother due to side effects (the GP5 item) from the Functional Assessment of Chronic Illness Therapy (FACIT) system by comparing it to current symptomatic side effects from the Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PROCTCAE) reported by patients with rheumatoid arthritis (RA).

Methods: Through a cross-sectional, web-based survey we collected information on the frequency of symptomatic side effects and bother from side effects related to RA medications. We applied multiple correspondence analysis (MCA) to reduce 80 symptomatic side effects into key dimensions (≥5% of …

A Trans-Omics Gene-Smoking Interaction Study Of Lung Cancer Based On Consortium Data, Ning Xie, Xiaowen Xu, Yanru Wang, Aoxuan Wang, Xiang Wang, Xuan Wang, Mengsheng Zhao, Jiacheng Zhou, Yongyue Wei, Manel Esteller, Zhibin Hu, Hongbing Shen, Rayjean J Hung, Christopher I Amos, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang

Faculty, Staff and Students Publications

Rationale: Genetically predicted molecular traits provide a cost-effective approach for identifying biomarkers and uncovering underlying biological mechanisms. We extended this framework to investigate gene-smoking interactions in lung cancer susceptibility.

Objectives: To identify trans-omics gene-smoking interactions affecting lung cancer risk and to assess how biomarkers modify effect of smoking.

Methods: We conducted the first trans-omics gene-smoking interaction study of lung cancer by integrating consortium-scale individual genotype data (27 737 cases vs 449 910 noncases) from the International Lung Cancer OncoArray Consortium (ILCCO-OncoArray), Transdisciplinary Research Into Cancer of the Lung (TRICL), Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the …

Functional Genomics Studies Of Psychiatric Disorders In Individuals Of Latin American Populations: A Scoping Review, Luz M Porras, Isabelle Rodríguez-Lausell, Gabriel Iglesias-Maldonado, Emily Val F Tuliao, Gabriela Martínez, Chelsey Leveque, Julian Tobon, Rachel Eloy, Sintia Belangero, Cynthia M Bulik, Camila M Loureiro, Carolina Muniz Carvalho, Vanessa Ota, Diego Luiz Rovaris, Eric A Storch, Eva Maria Trujillo-Chi Vacuan, Maria M Velasquez, Latin American Genomics Consortium, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Janitza L Montalvo-Ortiz, Paola Giusti-Rodríguez

Faculty, Staff and Students Publications

Over the past 15 years, genetic studies of psychiatric disorders have provided important insight into the contribution of both common variants of small effect, as well as rare exonic and copy number variants with large effect sizes. Genome-wide association studies (GWAS) allow us to understand the intricate polygenicity characteristic of many psychiatric disorders. However, a considerable proportion of single nucleotide polymorphisms (SNPs) implicated in these disorders localize to the non-coding regions of the genome. Unraveling the molecular mechanisms that underlie the etiology of psychiatric illnesses requires integration using functional genomics approaches. Functional genomics methods are critical for developing a mechanistic …

Whole Genome Sequencing Analysis Of Over 3500 Individuals Dementia-Free Over 85 Years Old, Gina M Peloso, Dongyu Wang, Sabrina M Abbruzzese, Joshua C Bis, Seung Hoan Choi, Alexa Beiser, Jan Bressler, Josée Dupuis, Alison E Fohner, Mohsen Ghanbari, Richard A Gibbs, Nancy Heard-Costa, M Arfan Ikram, Paul Lacaze, Quentin Le Grand, Oscar L Lopez, Thomas H Mosley, Moeen Riaz, Aïcha Soumaré, Amber Yaqub, Eric Boerwinkle, Bruce M Psaty, Myriam Fornage, Sudha Seshadri, Anita L Destefano

Faculty, Staff and Students Publications

BACKGROUND:

Identifying genetic variants conferring resilience to Alzheimer’s disease and related dementia (ADRD) may hold promise for developing therapeutics.

OBJECTIVE:

To determine genetic associations with being dementia-free at age 85 (DF85).

METHODS:

We examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF≤1%) coding and non-coding variants in DF85 participants (n=3,657) against individuals who were not DF85 (n=20,010). We verified associations using a stricter control set who developed dementia before age 85 (n=5,552).

RESULTS: …

Structural Determinants Of Ligand Response Specificity In The Mast Cell Activating Gpcr, Mrgprx2, Abiodun Adefola R Adeosun, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The mast cell-specific G-protein-coupled receptor (GPCR) MRGPRX2 (Mas-Related G Protein-coupled Receptor X2) has roles in itch and pain, and it mediates clinically relevant allergy-like responses to a diverse assortment of drugs. The varied responses of individuals to MRGPRX2 agonists, leading to drug hypersensitivity reactions in some cases, suggests the presence of consequential variants in the population. However, genetic associations with drug responses are poorly understood. We used heterologously-expressed MRGPRX2 to investigate the effect of 18 naturally occurring non-synonymous single nucleotide polymorphisms on activation by representative compounds from several classes, including neuropeptides, opioid agonists, antibiotics, neuromuscular blocking agents, and polycationic aromatic …

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 …

Early Neurodevelopmental Outcomes In Children With Congenital Heart Disease, Mike Seed, Cynthia Ortinau, Caroline Lee, Et Al.

2020-Current year OA Pubs

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 …

Natural History Of Limb Girdle Muscular Dystrophy R1 (Lgmdr1): A Grasp Consortium Study, Stephanie M Hunn, Andrew R Findlay, Amanda Clause, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

Identifying clinical outcome assessments (COAs) that are able to detect change in functional abilities over time in the limb girdle muscular dystrophy (LGMD) population is critical for managing disease progression in addition to determining drug efficacy in the context of anticipated therapeutic trials. Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 participants with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each participant completed a battery of COAs, including the North Star Assessment for Limb Girdle-Type Muscular Dystrophies (NSAD), 100-meter timed test (100 m), Performance of the Upper Limb (PUL), …

Initial Injury Type And Violent Reinjury, Nicholas Szoko, Daphne Lew, Taylor Kaser, Zoe M Miller, Matt Vogel, Michael A Mancini, Lindsay M Kranker, Christopher Behr, Vicki Moran, Rachel Ancona, Kristen Mueller

2020-Current year OA Pubs

IMPORTANCE: Violent injuries are the leading cause of death among children and young adults in the United States. Violent injury may increase the risk of subsequent injury (ie, violent reinjury), but it is unclear how this risk varies across different injury types (eg, blunt assault, stabbing, firearm).

OBJECTIVE: To describe patterns of violent reinjury across different injury types to inform tailored prevention strategies.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study included patients who presented with violent injuries to 2 adult and 2 pediatric level I trauma centers in St Louis, Missouri, from January 2016 to December 2023.

EXPOSURES: Violent …

Chronic Conditions And Mortality In Medicare Beneficiaries Before And After The Covid-19 Pandemic, R J Waken, Fengxian Wang, Jose F Figueroa, Rishi K Wadhera, Khavya Avula, E John Orav, Anne Mobley Butler, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: There were well-documented changes in health care use during the COVID-19 pandemic. Little is known about whether there were any associated decreases in claims-based comorbidity ascertainment that might have relevance to health services and policy research.

OBJECTIVE: To quantify differences in claims-based comorbidity assessment in Medicare beneficiaries pre- vs post-COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the 30 Chronic Conditions Warehouse 1- or 2-year lookback claims algorithms to ascertain each comorbidity with exact date ranges for all fee-for-service (FFS) and Medicare Advantage (MA) beneficiaries. Data were analyzed from April 2025 to April 2026.

EXPOSURES: The …

Prevalence And Aetiology Of Cerebral Palsy Among Nigerian Children: A Systematic Review And Meta-Analysis., Udochukwu Michael Diala, Aderonke O. Uhunmwangho-Courage, Fatima Abdullahi, Paul Ikhurionan, Caitlin Bakker, Duke Appiah, David Danjuma Shwe, Rose N. Gelineau-Morel, Kabiru Gurama, Olugbenga Akinyemi Ofakunrin, Angela Mcgillivray, Gabriel E. Ofovwe, Tina Slusher

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Nigeria is among the leading countries contributing to the burden of cerebral palsy. Cerebral palsy (CP) is the commonest physical disability in childhood, accounting for 16.2% of child neurology referrals. Many cases of CP are preventable with simple interventions such as neonatal resuscitation and effective phototherapy. Lack of reliable data on the burden of disease limits comprehensive national policy directed to the prevention, holistic care and rehabilitation of patients with cerebral palsy in Nigeria. Therefore, to effectively address this problem, this study aimed to describe the pooled prevalence of CP in Nigeria, its potential causes and types.

METHODS: This …

Practice Patterns In Pediatric Cardiothoracic Presurgical Conferences: A Multicenter Survey Study., Britney Reed, Poonam Puranik, Andrew Rodenbarger, Mira Trivedi, Dilachew A. Adebo, Gary Beasley, Louis Bezold, M Jay Campbell, Michael R. Carr, Joshua Daily, Mark Debrunner, Erica Del Grippo, Carlen G. Fifer, Timothy M. Hoffman, Susan R. Hupp, Joshua D. Kurtz, Gira Morchi, Carl Owada, Renuka Peterson, Michael D. Puchalski, Ryan Romans, Arwa Saidi, Rajesh U. Shenoy, Anoop K. Singh, Robert D. Tunks, Thomas M. Yohannan, Carolyn M. Wilhelm, Jyoti K. Patel

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric cardiothoracic surgeries are high-stakes, complex procedures, typically undergoing prior review at multidisciplinary conferences. This study evaluates practice patterns of conferences throughout the United States (US). Surveys were distributed to fellowship program directors or division directors in 124 US pediatric cardiology centers seeking information on conference logistics, fellow roles, quality improvement (QI), and satisfaction. All 47 responding centers (response rate 38%) conduct presurgical conferences, mostly on a weekly basis (92%) lasting 60-120 min (79%). The conferences are solely virtual (19%) or hybrid (81%). High-volume centers (> 300 surgical cases/year) are more likely to hold multiple conferences (13/20 vs 7/27, p <  0.01) and less likely to designate a moderator (11/20 vs 22/26, p = 0.027). Categorical pediatric cardiology fellows at 33 centers present clinical data (97%), echocardiograms (85%), catheterizations (82%), and cross-sectional imaging (39%), typically beginning in their first year. Most centers report that minor (98%) or major changes (51%) are made to patient management at least "sometimes." Responders rate conferences as very important (median 10/10 on a 10-point Likert scale, IQR 9-10), but satisfaction is more modest (median 7/10, IQR 7-9). Only 17% of centers have a formal QI process. Comments from 42 centers reveal positive themes of collaboration (68%) but also concerns about lengthy (30%) or inefficient (36%) discussion. Conclusions: This survey highlights common practices for pediatric cardiothoracic presurgical conferences. Conferences are collaborative and seen as highly impactful. However, satisfaction varies, and QI efforts are infrequent. These findings highlight opportunities for process improvement and standardization.

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 …

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 …

Incidental Colorectal Adenomas In Adolescents: Clinical Management, Genetic Evaluation, And Surveillance., Brett J. Hoskins, Shlomi Cohen, Colleen B. Flahive, Isabel Rojas, Aparajita Singh, Thomas M. Attard

Manuscripts, Articles, Book Chapters and Other Papers

The rising incidence of early-onset colorectal cancer has renewed attention to colorectal adenomas in adolescents and young adults (AYA), although these lesions remain rare and poorly characterized in adolescents. Lack of age-specific guidance creates uncertainty regarding genetic evaluation, surveillance intervals, and long-term management when these lesions are identified in adolescents. This narrative review synthesizes current evidence and expert perspective on epidemiology, evaluation, endoscopic management, surveillance, genetic considerations, and psychosocial implications of incidentally identified colorectal adenomas across the AYA spectrum, with emphasis on adolescents as a distinct clinical population. Available data largely derive from adults aged 20-49 years but suggest that …

Severe Thiopurine-Induced Myelosuppression In A Pediatric Acute Lymphoblastic Leukemia Patient With The Nudt15 *1/*6 Genotype: A Brief Report., Jillian Fry, Erin C. Boone, Wendy Y. Wang, Shobana John, Lisa A. Lansdon, Midhat S. Farooqi, Byunggil Yoo, Andrea Gaedigk, Keith August, Terrie Flatt, Laura Ramsey

Manuscripts, Articles, Book Chapters and Other Papers

Variants in TPMT and NUDT15 genes that affect thiopurine metabolism can guide personalized dosing to minimize toxicity. Decreased or no appreciable NUDT15 activity demonstrates impaired breakdown of active thiopurine metabolites which can lead to severe adverse events including potentially life-threatening myelosuppression. Recently, the NUDT15*6 allele was re-classified from having uncertain function to no function by the Clinical Pharmacogenetics Implementation Consortium. Here, we present a pediatric patient with a NUDT15*1/*6 genotype who experienced significant thiopurine-induced myelosuppression. The patient is a 4-year-old female with standard risk-average precursor B-cell acute lymphoblastic leukemia treated per AALL1731. Exome sequencing determined TPMT*1/*1 (normal metabolizer) and NUDT15*1/*6 …

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 …

Efficacy And Safety Of A Bodyweight-Adjusted Higher Dose Of Ocrelizumab In Relapsing (Musette) And Primary Progressive (Gavotte) Multiple Sclerosis: Two Multicentre, Randomised, Double-Blind, Parallel-Group Phase 3b Trials., Stephen L Hauser, Gavin Giovannoni, Xavier Montalban, Jiwon Oh, Amit Bar-Or, Maria Pia Sormani, Martin S Weber, Sharon Stoll, Jacqueline A Nicholas, Tetyana Nehrych, Robert Bonek, Krzysztof Selmaj, Maciej Maciejowski, Dusanka Zecevic, Catarina Raposo, Rebecca Owen, Ulrike Bonati, Katrin Madjar, Eva Harfst, Qing Wang, Anastasiia Raievska, Marianna Manfrini, Hans-Martin Schneble, Ludwig Kappos, Musette And Gavotte Study Groups

Neuroscience Articles

BACKGROUND: Ocrelizumab is a humanised anti-CD20 monoclonal antibody approved for people with relapsing (RMS) or primary progressive multiple sclerosis (PPMS). In a post-hoc analysis of phase 3 trials in RMS and PPMS using a 600 mg dose, higher exposure to ocrelizumab was associated with greater B-cell depletion and lower risk of confirmed disability progression. Here, we prospectively assessed the efficacy and safety of a high dose of ocrelizumab in patients with RMS or PPMS.

METHODS: Two multicentre, double-blind, phase 3 controlled trials were conducted to compare high-dose ocrelizumab with the approved 600 mg dose of the drug in patients with …

Can Behavioral Interventions Promote Health Equity In Pediatric Type 1 Diabetes? A Narrative Review Of Promising Treatments, Paul T. Enlow, Jaquelin Flores Garcia, Julia Price, Kristen A. Torres, David V. Wagner

Department of Pediatrics Faculty Papers

Purpose of review: Synthesize data on whether existing behavioral interventions can improve health equity among youth with type 1 diabetes.

Recent findings: While existing behavioral interventions demonstrated efficacy in improving health and/or psychosocial outcomes, evidence that these same interventions may improve health equity were lacking. Most interventions were evaluated using predominantly White and affluent samples and some studies did not report on racial, ethnic, or sociodemographic characteristics of their sample. Only a few interventions have been adapted for youth from minoritized backgrounds. Recent multisystemic and technology/mHealth interventions recruited samples that were sociodemographically representative of youth experiencing disparities, suggesting that these …

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 …