Pediatrics Commons^™

Cytokine-Based Strategies To Improve Prognostic Enrichment Of Pediatric Ards, E Scott Halstead, Todd M Umstead, Zissis C Chroneos, Cainan Riccio-Baum, S Rameeza Allie, Daniel J Mckeone, Debbie Spear, Ryan A Nofziger, Ronald C Sanders, Danielle Ahn, Jasmine C Dowell, Asdis F Wagner, Neal J Thomas, Prithvi Sendi, W Joshua Frazier, Courtney M Rowan, Parag N Jain, Dalia A Bashir, Stuart H Friess, Brian M Varisco, Jocelyn Grunwell, Aline B Maddux, Stephen T Famularo, Nadir Yehya

Faculty, Staff and Students Publications

Background: Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS has been described in adults using IL-6, TNFR1, and bicarbonate, and has prognostic utility. We investigated the application of this traditional parsimonious signature to pediatric ARDS patients and tested whether we could improve prognostic enrichment using other cytokines.

Methods: We leveraged a prospective multicenter cohort study of 500 children with ARDS (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome [LEOPARDS]; NCT04113434) study. Plasma samples were obtained within 24 h …

Reclassifying Pediatric Nafld Using The Steatotic Liver Disease Framework: A Multicenter Retrospective Study From The Nash Crn, Tin Bo Nicholas Lam, Katherine P Yates, Sheila L Noon, Kimberly P Newton, Mark H Fishbein, Jean P Molleston, Stavra A Xanthakos, Ajay K Jain, Miriam B Vos, Niviann M Blondet, Krupa R Mysore, Cynthia A Behling, Laura A Wilson, Jeffrey B Schwimmer

Faculty, Staff and Students Publications

Background and aims: The terminology for hepatic steatosis and NAFLD was revised under the umbrella of steatotic liver disease, with metabolic dysfunction-associated steatotic liver disease (MASLD) as the primary subtype. MASLD is defined by hepatic steatosis plus at least 1 cardiometabolic risk factor. A new category, Met-ALD, describes MASLD with alcohol consumption below the defined thresholds for alcohol-associated liver disease (ALD). While adult studies have demonstrated strong concordance between NAFLD and MASLD, the applicability of this framework in children remains unclear.

Approach and results: We assessed children clinically diagnosed with NAFLD and enrolled in the NASH CRN who had available …

Quality Domains In Home-Based Pediatric Hospice And Palliative Care: Adolescent And Young Adult Perspectives, Daniel H Grossoehme, Claire A Crawford, Jhansi Chandra Ellakula, Toluwalase Ajayi, Justin N Baker, Sarah Friebert, Lisa Humphrey, Jillann Jarrell, Rachel Thienprayoon, Pamela S Hinds

Faculty, Staff and Students Publications

Background: Current United States palliative care practice guidelines are intended to cover care across all age groups. Previous research with pediatric providers and caregivers concluded that pediatric hospice and palliative care have unique attributes. Not known is how adolescent hospice and palliative care patients understand quality palliative care. The purpose of this study was to characterize and define quality of care domains as described by adolescent and young adult patients receiving home-based hospice and palliative care.

Methods: Semi-structured interviews with 10-26 year-olds who received home-based hospice and/or palliative care visits in the prior three years at six diverse sites in …

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …

Chemotherapeutic Induction Of Cytosolic Single-Stranded Dna Accumulation Sensitizes Triple-Negative Breast Cancer To Immunotherapy, Yong Du, Li Yang, Hui Dai, Jianli Zhou, Zhicheng Zhou, Ruoxi Yuan, Rui Ye, Anh Thai Quynh Nguyen, Kishor Bhatia, Shiaw-Yih Lin

Faculty, Staff and Students Publications

Background: Despite the widespread adoption of chemoimmunotherapy in triple-negative breast cancer (TNBC), the mechanisms by which cytotoxic chemotherapy engages antitumor immunity remain poorly defined. Identifying tumor-intrinsic immunogenic programs that predict and enhance responsiveness to immune checkpoint blockade (ICB) is therefore of critical clinical importance.

Methods: Transcriptomic signatures of TREX1 deficiency were generated from CRISPR-engineered TNBC models and applied to multiple independent TNBC cohorts treated with chemoimmunotherapy. Cytosolic single-stranded DNA (ssDNA) accumulation was quantified using a flow cytometry-based assay to functionally screen chemotherapeutic agents. Immune activation and therapeutic efficacy were evaluated using in vitro assays, syngeneic mouse tumor models, flow cytometry, …

Plasma Gdf15 Affects Long-Term Dementia Risk And Alters Neuroimmune Signaling, Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu, Shannon M Drouin, Cassandra M Joynes, Minhao Yao, Murat Bilgel, Abhay Moghekar, Qu Tian, Julián Candia, Mary Kaileh, Aditi Gupta, Krystyna Mazan-Mamczarz, Myriam Gorospe, Alexey Lyashkov, Yevgeniya Lukyanenko, Mika Kivimaki, Philipp Frank, Lori L Jennings, Valborg Gudmundsdottir, Vilmundur Gudnason, Lenore J Launer, Naoto Kaneko, Shintaro Kato, Makio Furuichi, Masaki Shibayama, Masahisa Katsuno, Keita Hiraga, Yukiko Nishita, Rei Otsuka, James R Pike, Mary R Rooney, Pascal Schlosser, Yuhan Cui, Guray Erus, Christos Davatzikos, Rebecca F Gottesman, Iwao Waga, Priya Palta, Christie Ballantyne, Michael Griswold, Zhonghua Liu, Luigi Ferrucci, Allison B Herman, Keenan A Walker

Faculty, Staff and Students Publications

Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. …

Adaptation Of The Transition Readiness Assessment Questionnaire For Pediatric-Onset Multiple Sclerosis: Protocol For A User-Centered Design Approach, Claudia Gambrah-Lyles, Aaron W Abrams, Sara Loud, Hollie Schmidt, Emily Blosberg, Melissa Wright, Kelsey E Poisson, Kristen S Fisher, Kimberly A O'Neill, Akash Virupakshaiah, John W Rose

Faculty, Staff and Students Publications

Background: Pediatric-onset multiple sclerosis (POMS) is a chronic, progressive neurologic condition requiring lifelong management and coordinated transition from pediatric to adult care. Evidence-based guidelines identify transition readiness assessment as a core component of successful transition; however, most POMS clinics do not formally assess readiness, and existing tools do not address POMS-specific challenges, such as fluctuating disability, complex treatment regimens, and cognitive impairment. This gap underscores the need for a transition readiness measure tailored to POMS.

Objective: This paper aims to describe a stakeholder-engaged, implementation science-guided protocol for adapting the Transition Readiness Assessment Questionnaire (TRAQ) version 6.0 to reflect the unique …

Evaluating The Reproducibility And Verifiability Of Nutrition Research: A Case Study Of Studies Assessing The Relationship Between Potatoes And Colorectal Cancer, Yasaman Jamshidi-Naeini, Colby J Vorland, Pranav Kapoor, Bailey Ortyl, Jocelyn Mineo, Luke Still, Korlu Sorsor, Shelby Rodney, Xander Tooze, Brent Flickinger, Beate Henschel, Stephanie L Dickinson, David B Allison

Faculty, Staff and Students Publications

The credibility of nutritional research is dependent on the rigor with which studies are conducted and the ability for independent assessment to be performed. Despite the importance of these, more work is needed in the field of nutrition to buttress the trustworthiness of nutrition research. To develop and apply a process for evaluating the rigor, reproducibility, and verifiability of nutritional research, using the relationship between potato consumption and Colorectal Cancer (CRC) as a case study. We updated existing systematic reviews to include studies on potatoes and CRC, assessing their design, execution, and reporting quality. We attempted to reproduce and verify …

Pancreatitis Risk Genes Play A Major Role In Pediatric Pancreatitis: Insights From The International Study Group Of Pediatric Pancreatitis: In Search For A Cure, Maisam Abu-El-Haija, Wenying Zhang, Fuchenchu Wang, Gretchen Cress, Brian Dawson, Xiaoping Su, Tyler Thompson, Nicole Kotha, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, A Jay Freeman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Phil Greer, Amit S Grover, Andrew Y J Liman, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Michael Wilschanski, Yuhua Zheng, Ying Yuan, David C Whitcomb, Aliye Uc, Mark Lowe, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Background & aims: Clinical data show that genetic variants are significant risk factors for acute recurrent pancreatitis and chronic pancreatitis. To expand the understanding of the role of genetics in acute recurrent pancreatitis and chronic pancreatitis, high-throughput next-generation sequencing of 14 genes was completed in a multicenter pediatric cohort.

Methods: A cross-sectional study involving 944 pediatric patients with acute recurrent pancreatitis or chronic pancreatitis was conducted. CASR, CEL, CFTR, CLDN2, CPA1, CTRC, GGT1, PRSS1, PRSS2, PRSS3, SBDS, SLC26A9, SPINK1, and UBR1 were sequenced. The frequencies of identified variants were compared with frequencies in the genome aggregation database. Group differences were …

Guideline On Stress Echocardiography - 2026, Ana Cristina Camarozano, Salvador Vicente Spina, José Roberto Matos Souza, Marcelo Dantas Tavares De Melo, Daniela Do Carmo Rassi Frota, Silvio Henrique Barberato, Fabio Villaça Guimarães Filho, Harry Acquatella, Vera Márcia Lopes Gimenes, Jorge Alfredo Lowenstein, Ricardo H Pignatelli, José Maria Del Castillo, Joselina Luiza Menezes Oliveira, José Sebastião De Abreu, José Luis De Castro E Silva Pretto, Issam Shehadeh, Alex Dos Santos Felix, Mercedes Maldonado Andrade, Antônio Carlos Sobral Sousa, Maria Estefânia Bosco Otto, Andrea De Andrade Vilela, Pedro Gutierrez Fajardo, Liz Andréa Villela Baroncini, Cristiano Vieira Machado, Fábio Cañellas Moreira, José María Hernández Hernández, Marco Stephan Lofrano Alves, Samira Saady Morhy, Márcio Silva Miguel Lima, Miguel Osman Dias Aguiar, Wilson Mathias Junior, Letícia Dos Santos De Oliveira Rocha, João César Nunes Sbano, Barbara Athayde Linhares Martins Vrandecic, Fabio Roston, Arnaldo Rabischoffsky, Juliana Paixão Etto Rolim, Raphael Aparecido Barreto Da Silva, Guilherme De Rossi, Kamila Fernanda Staszko, Jolie Britt, Marcelo Luiz Campos Vieira

Faculty, Staff and Students Publications

No abstract provided.

Ultrasound-Enabled Refreshable Electrochemical Sensors For Cardiac Biomarker Monitoring, Mayank Garg, Heng Guo, Myeong Namkoong, Elizabeth Zhanov, Connor Malone, Md Saifur Rahman, Ayse Akcan-Arikan, Limei Tian

Faculty, Staff and Students Publications

Cardiac troponin I (cTnI) is the gold-standard biomarker for acute myocardial infarction, yet current laboratory-based high-sensitivity assays require centralized infrastructure, trained personnel, and serial testing, limiting their suitability for real-time or continuous monitoring in resource-limited settings. Point-of-care electrochemical sensors have shown promise for rapid cTnI detection, but their reliance on antibodies as biorecognition elements and redox mediator solutions, and single-use operation restricts practical translation. Here, we report an ultrasound-enabled refreshable electrochemical biosensor for sensitive, stable, and repeatable cTnI monitoring. The device employs a cTnI-specific peptide as the biorecognition element, providing enhanced stability during storage, transport, and operation. Label-free electrochemical impedance …

Targeted Next-Generation Sequencing Implementation In Eswatini Identifies Rifampicin And Bedaquiline Resistance Undetected By Routine Diagnostic Testing, Debrah Vambe, Alexander Kay, Mangaliso Ziyane, Mdigo Thunzini, Sein Sein Thi, Leonardo De Araujo, Viola Dreyer, Tanja Niemann, Busizwe Sibandze, Sijabu Masina, Andrea Maurizio Cabibbe, Jennifer Furin, Tafadzwa Mazuruse, Lindokuhle Dlamini, Thulani Jele, Bheki Mamba, Gugu Maphalala, Makhosazana Dlamini, Mbongeni Dube, Nomthandazo Lukhele, Daniela Maria Cirillo, Anna Mandalakas, Christoph Lange, Sphiwe Ngwenya, Christian Utpatel, Sindisiwe Dlamini, Stefan Niemann

Faculty, Staff and Students Publications

In Eswatini, multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains harbouring the rifampicin-resistance (RR) rpoB I491F mutation are missed by routine diagnostics, including GeneXpert MTB/RIF Ultra (Xpert Ultra), line probe assays (LPA), and mycobacterium growth indicator tube (MGIT) phenotypic drug susceptibility testing (pDST). To address this diagnostic gap, Eswatini introduced targeted next-generation sequencing (tNGS) in 2019. We analysed 234 patient samples enrolled from June 2021 to December 2024 with isoniazid and/or rifampicin resistance detected by routine diagnostics, or suspected treatment failure, and obtained detailed clinical and outcome data from 59 patients. tNGS detected RR in 159 strains, of which 101 (64%) carried …

Rare Pediatric Venolymphatic Malformations: Pericardial Cyst Mimickers, Shelby E Walcott, Joseph Burns, Juan Pablo Sandoval Jones, Neil Cambronero, David Brennen, Thomas M Glenn, Betul Yilmaz Furtun

Faculty, Staff and Students Publications

Background: Pericardial cystic masses are rare, and exceedingly so in pediatrics. The clinical course of such masses in children is poorly described.

Case summary: We report 2 cases in 3- and 7-year-old children. Both were initially thought to represent pericardial cysts on imaging, but surgical excision and histopathology confirmed diagnoses of a venolymphatic malformation and an epicardial cyst, respectively. The first patient presented with abdominal pain, and the second patient was asymptomatic. Both recovered well after an uncomplicated surgical intervention.

Discussion: A small number of patients with pericardial masses will have symptoms thought to be related to compression of adjacent …

Rare Pediatric Venolymphatic Malformations: Pericardial Cyst Mimickers, Shelby E Walcott, Joseph Burns, Juan Pablo Sandoval Jones, Neil Cambronero, David Brennen, Thomas M Glenn, Betul Yilmaz Furtun

Faculty, Staff and Students Publications

Background: Pericardial cystic masses are rare, and exceedingly so in pediatrics. The clinical course of such masses in children is poorly described.

Case summary: We report 2 cases in 3- and 7-year-old children. Both were initially thought to represent pericardial cysts on imaging, but surgical excision and histopathology confirmed diagnoses of a venolymphatic malformation and an epicardial cyst, respectively. The first patient presented with abdominal pain, and the second patient was asymptomatic. Both recovered well after an uncomplicated surgical intervention.

Discussion: A small number of patients with pericardial masses will have symptoms thought to be related to compression of adjacent …

The Aggregated Latent Profile Index: Measuring Person Profile Differentiation Within A Bootstrap-Validated Latent Profile Space, Se-Kang Kim

Faculty, Staff and Students Publications

Multivariate assessment profiles contain two conceptually distinct sources of variation: overall level and profile shape. Existing approaches recover some aspects of this structure, but none jointly establishes the replicability of latent pattern dimensions and provides a principled, population-referenced summary of person profile differentiation independent of overall level. We introduce the Aggregated Latent Profile Index (ALPI), a variance-weighted Euclidean distance that quantifies the degree to which an individual’s profile departs from a flat population reference within a bootstrap-validated latent profile space. ALPI is derived from the Aggregated Latent Profile Space (ALPS), a framework that combines parallel analysis with bootstrap stability diagnostics …

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, …

Impact (Immune Monitoring And Phenotype Assessment Of Clinical Trajectory) For Patients With Inborn Errors Of Immunity From The Primary Immune Deficiency Treatment Consortium (Pidtc), Danielle E Arnold, Hesham Eissa, Elizabeth Dunn, Geoffrey D E Cuvelier, Nicola A M Wright, Rebecca A Marsh, Suhag Parikh, Blachy Davila Saldana, Mark T Vander Lugt, Rosa Bacchetta, Lisa Forbes Satter, Shanmuganathan Chandrakasan, Erinn Kellner, Eric J Allenspach, Erica G Schmitt, Brent Logan, Lauri Burroughs, Morton J Cowan, Linda M Griffith, Luigi Notarangelo, Sung-Yun Pai, Michael A Pulsipher, Christopher C Dvorak, Elie Haddad, Jennifer M Puck, Troy R Torgerson, Jennifer W Leiding, Jennifer Heimall, Alice Y Chan

Faculty, Staff and Students Publications

Background: Evaluating natural history and outcomes of rare inborn errors of immunity (IEIs) has been challenging due to the diverse disease manifestations and lack of standardized data.

Objective: To develop a set of standardized, quantitative, generalizable data collection modules to measure organ dysfunction in IEIs, modeled on the previously validated Common Terminology Criteria for Adverse Event system for grading treatment toxicity.

Methods: Disease conditions were organized by organ system. Experts from the Primary Immune Deficiency Treatment Consortium identified essential features of severe combined immunodeficiency, chronic granulomatous disease, Wiskott-Aldrich syndrome, and primary immune regulatory disorders and compared these to Common Terminology …

A Multi-Country Community Of Practice To Strengthen Quality Improvement In Low- And Middle-Income Countries: A Quality Improvement Program Description, Samhita Bhargava, Heather A Haq, Brodus A Franklin, Elizabeth Davis, Florence Anabwani-Richter, Thobile Bhembe, Lindokuhle P Dlamini, Makhosazana Dlamini, Andy Chapola, Nomsa Kafumba, Chisomo Mzandu Zinyemba, Menard Bvumbwe, Kyakuwa Richard Jjuuko, Jacqueline Balungi Kanywa, Dithan Kiragga, Andreas Boy Isaac, Esther Makhalanyane, Lwamba Nyembo, Retselisitoe Mahlaha, John T Farirai, Eunice W Ketang'enyi, Andrea E M Imsen, Iuliana Costas, Susan B Torrey

Faculty, Staff and Students Publications

Background/objectives: Quality improvement (QI) is widely used in global health to improve patient outcomes, reduce costs, and strengthen service delivery. The Texas Children's Global Health Network (TCGHN) includes nine independent non-governmental organizations supporting healthcare in low- and middle-income countries (LMICs), with pediatric HIV clinical centers of excellence in six countries in sub-Saharan Africa (SSA), supported technically by Baylor College of Medicine. We describe the development of a virtual QI Community of Practice (QICoP) to connect geographically dispersed teams and strengthen local QI capacity.

Methods: In 2022, QI and global health experts convened to design the QICoP and assess site readiness. …

Corrigendum To Diagnosis Of Post-Hematopoietic Stem Cell Transplant Bronchiolitis Obliterans Syndrome In Children: Time For A Rethink? Transplantation And Cellular Therapy. 2024 Aug; 30(8):760–769, Shivanthan Shanthikumar, William A Gower, Kenneth R Cooke, Anne Bergeron, Kirk R Schultz, Amisha Barochia, Maximiliano Tamae-Kakazu, Edward Charbek, Erin E Reardon, Charlotte Calvo, Alicia Casey, Pi Chun Cheng, Theresa S Cole, Stella M Davies, Shailendra Das, Aliva De, Robin R Deterding, Deborah R Liptzin, Francoise Mechinaud, Jonathan H Rayment, Paul D Robinson, Roopa Siddiah, Anne Stone, Saumini Srinivasin, Christopher T Towe, Gregory A Yanik, Narayan P Iyer, Samuel B Goldfarb

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 …

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 …

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 …

Classification Of Gck-Mody In A Child With Mild Hyperglycemia And Islet Autoantibody Positivity: A Diagnostic Challenge, Aman N Yarlagadda, Maria J Redondo, Toni I Pollin, Mustafa Tosur, Colleen O Jodarski, Jennifer J Bell

Faculty, Staff and Students Publications

We report a 9-year-old female who presented with mild, persistent hyperglycemia, with hemoglobin A1c and oral glucose tolerance test results in the prediabetes range, relatively preserved C-peptide, and mildly positive glutamate decarboxylase 65 autoantibody levels. A strong family history of lean, noninsulin-dependent diabetes suggested a possible monogenic cause. Genetic testing with a 28-gene maturity-onset diabetes of the young (MODY) panel identified a heterozygous variant of uncertain significance in GCK (NM_000162.5:c.179C>T [p.Thr60Ile]). Following review by the ClinGen Monogenic Diabetes Variant Curation Expert Panel, the GCK variant was reclassified as pathogenic, confirming a diagnosis of glucokinase (GCK)-MODY/GCK-hyperglycemia, a stable …

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: …

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 …

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 …

Associations Among Pork Intake, Weight-Loss, And Diet Quality Outcomes In A Commercial Weight-Management Program, Ana M Palacios, Grace Anderson, Beate Henschel, Alexandra M Lee, Kelli M Richardson, Chelsie Parker, Stephanie L Dickinson, Jing X Kersey, David B Allison, Gary D Foster, Michelle I Cardel

Faculty, Staff and Students Publications

Background: Pork is a common source of high-quality protein. However, it is typically recommended in moderation due to its saturated fat content, especially as its role in weight management, weight-loss (WL) programs, and overall diet quality is not well understood. This study aimed to identify associations among pork intake, WL, and diet quality among adults with overweight or obesity participating in a weight management program (WMP).

Methods: This secondary analysis used data from a 6-month randomized controlled trial (NCT05648344) evaluating the effectiveness of a WMP on diet quality. Data were collected through online surveys and the Automated Self-Administered …

A Remote Intervention To Improve Medication Nonadherence Guided By A Marker Of Risk Derived From The Electronic Health Records Of Adolescent Transplant Recipients, Eyal Shemesh, Ravinder Anand, Rachel A Annunziato, Emily M Fredericks, Jennifer Garcia, Nitika Arora Gupta, Lawrence C Kleinman, Alyssa Kriegermeier, Krupa R Mysore, Vicky L Ng, Steven J Lobritto, Shreena Patel, Emily Rothbaum Perito, Elizabeth B Rand, Rene Romero, Robert S Venick, Sarah Duncan-Park, Jeffrey Mitchell, Sarah G Anderson, Margaret L Stuber, Miguel Reyes-Múgica, George V Mazariegos, Benjamin L Shneider

Faculty, Staff and Students Publications

Improving medication adherence in adolescents who had a liver transplant (iMALT), a prospective, block-randomized, single-blind, controlled multisite study in 13 pediatric transplant centers, used the medication level variability index (MLVI) to identify nonadherent adolescents. It compared a 2-year remote behavioral telemetric intervention (TI) that focused on adherence and addressed barriers to standard of care (SOC). The primary endpoint was the composite incidence of centrally determined (3 masked pathologists) rejection, death, retransplantation, or consent withdrawal. In 148 participants (TI group, n = 72 and the SOC group, n = 76), with a mean age 15.5 years, there were twice as many …

Circulating Metabolites Associated With Protection Against Mycobacterium Tuberculosis Infection And Inhibition Of Mycobacterial Growth, Todia P Setiabudiawan, Lika Apriani, Julian Avila-Pacheco, Edwin Ardiansyah, Vinod Kumar, Bachti Alisjahbana, Ayesha J Verrall, Andrew R Dinardo, Agnes R Indrati, Vera P Mourits, L Charlotte J De Bree, Simone J C F M Moorlag, Clary B Clish, Leo A B Joosten, Arjan Van Laarhoven, Krista E Van Meijgaarden, Mihai G Netea, Simone A Joosten, Valerie A C M Koeken, Philip C Hill, Reinout Van Crevel

Faculty, Staff and Students Publications

A significant proportion of individuals who are heavily exposed to infectious tuberculosis patients do not acquire Mycobacterium tuberculosis (Mtb) infection, as detected by an interferon gamma release assay (IGRA). We examined circulating metabolite profiles and metabolic genotypes in 199 heavily exposed IGRA-negative tuberculosis household contacts in Indonesia. Based on differentially abundant metabolites, activity of several pathways including arachidonic acid, arginine and proline, glutathione, and tryptophan metabolism, correlated with a negative IGRA at three months. SNPs near PRODH (involved in arginine and proline metabolism) were associated with circulating proline concentrations and persistently negative IGRA results, while SNPstudys near AFMID (involved in …