Medical Specialties Commons^™

Factors Associated With Rare Pediatric Cancer Trial Enrollment: A Report From The Children's Oncology Group Rare Tumors Committee, Brian R Englum, Jin Piao, Lindsay Younis, Reto M Baertschiger, Kenneth S Chen, Emily Christison-Lagay, Hetal Dholaria, Robyn Gartrell, M John Hicks, Junne Kamihara, Sarah G Mitchell, Manuela Orjuela-Grimm, Farzana Pashankar, Samara L Potter, Jennifer H Aldrink, Jeremy Rosenblum, Michael R Sargen, Kris Ann P Schultz, Brittani K N Seynnaeve, Mary Wedekind, Theodore W Laetsch

Faculty, Staff and Students Publications

Background: Over 90% of US children with cancer are treated at Children's Oncology Group (COG) centers, which seek to maximize enrollment in therapeutic and biobanking studies. Rare cancers have demonstrated lower than expected COG enrollment. We evaluated trends in COG rare cancer enrollment compared to US incidence from Surveillance, Epidemiology, and End Results (SEER) registries, examining the impact of COG therapeutic trials and Project:EveryChild, a cancer biobank/registry.

Procedure: COG and SEER data from 2002 to 2020 were queried for US patients younger than 18 years old with adrenocortical carcinoma (ACC), nasopharyngeal carcinoma (NPC), retinoblastoma (RB), thyroid carcinoma, and melanoma. We …

Dolichocolon Is Common In Pediatric Gastroenterology Patients With Constipation And Associated Complaints, David Simon, Donovan Berens, Raul Zambrana Valenzuela, Arvind Mohan, Partha Chakraborty, Timot Kellermayer, Eric H Chiou, Craig L Jensen, Ricardo A Arbizu, Marla B K Sammer, Richard Kellermayer

Faculty, Staff and Students Publications

Objectives: Dolichocolon (DC), classified under International Classification of Diseases, Tenth Revision (ICD-10) code Q43.8 ("Other specified congenital malformations of intestine"), refers to an elongated or redundant large intestine. Recent studies in adults indicate a role for dolichocolon in constipation and disorders of gut-brain interaction. Contrast enema (CE) imaging is commonly used to identify DC, typically defined as a sigmoid colon extending above, or a transverse colon descending below, the iliac crest line. Despite its potential relevance, the prevalence and clinical significance of DC in pediatric gastroenterology remain poorly understood.

Methods: This retrospective study assessed the prevalence of DC in pediatric …

Utility And Utilization Of Transabdominal Ultrasound In Pediatric Patients With Acute Recurrent Or Chronic Pancreatitis, Nicholas Norris, David Troendle, Michael Wilschanski, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Amit S Grover, Sohail Z Husain, 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, Zachary M Sellers, Andrew T Trout, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objectives: Transabdominal ultrasound (TAUS) is frequently utilized in pediatric acute pancreatitis, but less is known about its use in acute recurrent (ARP) or chronic pancreatitis (CP). Our aim was to describe TAUS utilization and findings from the largest multicenter cohort of pediatric ARP and CP, the International Study Group of Pediatric Pancreatitis: In Search for a CuRE-2 (INSPPIRE-2).

Methods: Demographic and imaging data from physician questionnaires were obtained for patients with available TAUS data. Utilization and findings were compared between ARP and CP groups. Kappa statistics were used to compare agreement of TAUS to computed tomography (CT), magnetic resonance imaging/cholangiopancreatography …

Diagnostic Evaluation And Treatment Of Utis In Children With Neurogenic Bladder, Jacqueline G Holden, Sowdhamini Wallace, Pearl W Chang, Stephanie Davis-Rodriguez, Rana F Hamdy, John M Morrison, Michael J Tchou, Victor Trevisanut, Vijaya Vemulakonda, Catherine S Forster

Faculty, Staff and Students Publications

Objective: Children with neurogenic bladder (NGB) are at increased risk for urinary tract infections (UTIs), but there is a lack of guidelines to assist clinicians in diagnosing and treating these children. Our objective was to describe the presentation and treatment of provider diagnosed UTIs in children with NGB compared to children with vesicoureteral reflux (VUR) and to assess the proportion of children with NGB who met a consortium definition of UTI.

Study design: We included children < 18 years old with either VUR or NGB who were diagnosed in the emergency department with a febrile UTI in our multicenter retrospective cohort study. We extracted and compared UTI symptoms and urinalysis results specific to children with NGB to children with VUR. We measured the proportion of UTI diagnoses concordant with the Urologic Management to Preserve Initial Renal Function (UMPIRE) consensus definition of UTI, defined as ≥ 100,000 CFU/mL of 1 or 2 organisms, pyuria, and ≥ two symptoms of UTI.

Results: The most common symptom among all children in the cohort was vomiting (38.8 %). Of the 215 children with NGB, 41.3 % met …

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Flare Guns And Trauma: Patterns, Severity, And Clinical Implications From Case And National Surveillance Data, Ramsay Hafer, Andrew Huff, Lara Phillips

Department of Emergency Medicine Faculty Papers

Flare guns are pyrotechnic devices capable of causing serious injury due to high-temperature combustion and projectile discharge. Though intended for signaling in maritime or wilderness settings, improper use can result in trauma patterns distinct from those seen with typical burns or fireworks. Despite their severity, flare gun injuries remain underreported and poorly characterized. We conducted a scoping review of PubMed, Scopus, and Ovid to identify 12 case reports involving 13 patients, and reviewed US National Electronic Injury Surveillance System records from 2015 to 2024, identifying 18 flare gun-specific injuries for a combined total of 31 injuries. Demographic, injury mechanism, body …

Quantitative Analysis Of Robustness-Based Versus Let-Based Optimization In Intensity-Modulated Proton Therapy For Pediatric Brain Tumors, Fariha Kabir Torsha, Gino Lim, Hadis Moazami Goudarzi, Radhe Mohan, David Grosshans, Wenhua Cao

Faculty, Staff and Student Publications

Purpose: To perform a quantitative analysis of the trade-off between robustness-based and linear energy transfer (LET)-based optimization of intensity-modulated proton therapy for anatomically challenging pediatric brain tumor cases.

Methods: Three pediatric brain tumor patients were included in this study. Three plans were generated for each case based on: (1) nominal optimization, without considering uncertainties and LET; (2) robust optimization, including proton range and patient setup uncertainties; and (3) LET optimization, considering increasing LET in the target and reducing LET in normal tissues. All plans were optimized with individually fine-tuned objective weighing to obtain highest achievable target coverage and meet dose …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Maturity-Onset Diabetes Of The Young (Mody) In A Racially/Ethnically Diverse Pediatric Population, Shilpi Relan, Guido Alarcon, Danielle Guffey, Charles G Minard, Mary E Fang, Kelly Timmons, Rona Y Sonabend, Mustafa Tosur, Maria J Redondo, Jennifer E Posey

Faculty, Staff and Students Publications

Context: Current practice guidelines recommend considering a diagnosis of maturity-onset diabetes of the young (MODY) in patients with diabetes with an affected parent but without typical features of type 1 or type 2 diabetes.

Objective: To test if these criteria apply to a real-world cohort of racially/ethnically diverse children with diabetes.

Methods: We performed a retrospective case review of electronic medical records of youth diagnosed with MODY in a large academic pediatric hospital in Southwestern United States. Cases were ascertained based on the identification of a molecular diagnosis of MODY.

Results: We studied 50 genetically confirmed cases of MODY: 60% …

The Impact Of Indigenous American-Like Ancestry On The Risk Of Acute Lymphoblastic Leukemia In Hispanic/Latino Children, Jalen Langie, Tsz Fung Chan, Wenjian Yang, Alice Y Kang, Libby Morimoto, Daniel O Stram, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Joseph L Wiemels, Jun J Yang, Adam J De Smith, Charleston W K Chiang

Faculty, Staff and Students Publications

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Among the genetic variants previously implicated in ALL risk, a number of them were found to be enriched in Indigenous American (IA)-like ancestries and inherited by many Hispanic/Latino individuals. However, due to potential confounding from environmental factors, the association between IA-like ancestry and risk for ALL has remained unclear. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and on the frequency and effect size of known risk alleles, while accounting for …

Hemispherotomy For Drug-Resistant Epilepsy In A Low-Resource Setting: Surgical Outcomes And Quality Of Life In 23 Children Treated In A Hybrid Program In Panama, Emmajane G Rhodenhiser, David Bonda, Carmen Baez, Hannah K Weiss, Yosef Dastagirzada, Guzman Aranda, Laurent Bruggeman, Ameeta Grover, Shaun D Rodgers, Ruben Kuzniecky, Yvonne Zelenka-Kuzniecky, Howard L Weiner, Eveline Teresa Hidalgo

Faculty, Staff and Students Publications

Introduction: Hemispherotomy is an effective treatment for children with drug-resistant epilepsy (DRE). While hemispherotomy techniques and indications have evolved, access remains predominantly constrained to high-resource settings.

Methods: We performed a retrospective analysis of children who underwent hemispherotomy from 2011 to 2023 by a hybrid team, including local Panamanian and US neurologists, neurosurgeons, and EEG technicians and analyzed surgical, epilepsy, and quality of life (QoL) parameters. Follow-up data were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) guidelines for children with epilepsy.

Results: Twenty-three children underwent hemispherotomy. The median age at surgery was 10 years (range 2-20). The …

Nutrition Support Adequacy In Children With Biliary Atresia After Liver Transplant, Nicole Knebusch, Manpreet Virk, Moreshwar S Desai, Marwa Mansour, Stacey Beer, Brittany Pearo, Kelby Fuller, Krupa Mysore, John Goss, Thomas Fogarty, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

No abstract provided.

Structural Birth Defects And Leukemia Risk In Children With Down Syndrome, Ching-Ju Hsu, Jeremy M Schraw, Sonja A Rasmussen, Tiffany M Chambers, Tania A Desrosiers, Chad D Huff, Amanda E Janitz, Russell S Kirby, Eirini Nestoridi, Wendy N Nembhard, Jason L Salemi, Charles Shumate, Jean Paul Tanner, Mahsa M Yazdy, Michael E Scheurer, Karen R Rabin, Philip J Lupo

Faculty, Staff and Students Publications

Birth defects are associated with increased cancer risk in the general pediatric population, yet their impact on leukemia risk in children with Down syndrome (DS) remains uncertain. We assessed this using data from 26,660 children with DS in the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study. Among them, 71.9% had at least one major birth defect, predominantly involving the cardiac (64.2%), musculoskeletal (21%), and gastrointestinal systems (6.8%). The cumulative incidence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) was comparable in children with and without co-occurring defects. Adjusted hazard ratios (aHR) for ALL and …

A Novel Maturation Equation For Hepatic Clearance Across Preterm, Term Neonates, Children, And Adults: Application To Paracetamol And Its Metabolite, Yunjiao Wu, Swantje Völler, Sebastiaan C. Goulooze, Karel Allegaert, Catherine M.T. Sherwin, Anne Van Rongen, Daniëlla W. E. Roofthooft, Sinno H.P. Simons, Dick Tibboel, Robert B. Flint, John N. Van Den Anker, Catherijne A.J. Knibbe

Pediatrics Faculty Publications

A preterm and term neonate to adult (PTNA) maturation equation was introduced recently to describe the glomerular filtration rate maturation from birth to adulthood for neonates of varying gestational age. This study aims to evaluate the newly developed PTNA equation against common maturation approaches like allometric scaling (AS0.75), the AS0.75 plus postmenstrual age (PMA)-based Emax (AS0.75 + PMA) equation, and the bodyweight dependent exponent equation (BDE) for the maturation of three hepatic pathways of paracetamol (PCM) from preterm and term neonates up to adults. A population pharmacokinetic analysis was conducted with pooled plasma and urine data of PCM, PCM-glucuronide (PCM-GLU), …

Trends In Hospital Resource Use For Children With Complex Chronic Conditions., Nathaniel D. Bayer, Matthew Hall, Maria Osipovich, John M. Morrison, Christian D. Pulcini, Jana C. Leary, Joanna E. Thomson, Tamara D. Simon, Dennis Z. Kuo, Jeffrey D. Colvin, Eyal Cohen, Jay G. Berry

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite a small prevalence, children with complex chronic conditions (CCCs) use substantial inpatient resources.

OBJECTIVE: To assess national trends in hospital discharges, bed days, and hospital charges for children with and without CCCs in the US from 2000 to 2022.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, repeated cross-sectional study used hospital discharge data from the Kids' Inpatient Database (KID) from the years 2000, 2003, 2006, 2009, 2012, 2016, 2019, and 2022 for US children aged 0 to 18 years, excluding uncomplicated newborn discharges.

EXPOSURE: Presence of 0, 1, 2, or 3 or more CCCs.

MAIN OUTCOMES AND MEASURES: Trends …

Fibroblasts Are The Primary Contributors To A Disrupted Micro-Environment In End-Stage Pediatric Hypertrophic Cardiomyopathy, Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Iki A Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.

Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.

Results: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes …

Soluble C5b-9 (Sc5b-9) In Pediatrics-A Clinical Assessment, Ridwan B Ibrahim, Radwa Almamoun, Sarah E Sartain, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The soluble C5b-9 (sC5b-9) is a soluble form of the Terminal Complement Complex (TCC) that is released into the circulation with elevated levels, associated with increased morbidity and mortality in patients with complement-mediated inflammatory conditions. With the advent of eculizumab and ravulizumab, proper testing for diagnoses and therapeutic monitoring is warranted.

Methods: We evaluated both the analytical and clinical performance of the Quidel Microvue sC5b-9 Plus enzyme immunoassay. Analytical performance was evaluated with precision, linearity, interference studies, and correlation with a reference laboratory. Reference intervals were established using control donor samples [n = 26; median age 18.5 years (range …

Standard Complete Blood Count To Predict Long-Term Outcomes In Febrile Infection-Related Epilepsy Syndrome (Fires): A Multicenter Study, Martin Guillemaud, Aurélie Hanin, James J Riviello, Mario Chavez, Ayush Batra, Megan Berry, Francesca Bisulli, Carlos Castillo-Pinto, Carla Cobos-Hernandez, Sophie Demeret, Krista Eschbach, Raquel Farias-Moeller, Madeline Fields, Nicolas Gaspard, Elizabeth E Gerard, Teneille E Gofton, Margaret T Gopaul, Matthew D Gruen, Anthony D Jimenez, Karnig Kazazian, Minjee Kim, Marwa Mansour, Lara Marcuse, Clémence Marois, Mikaela Morales, Lorenzo Muccioli, Elena Pasini, Michelle M Pham, Santiago Philibert Rosas, Aaron F Struck, Nathan Torcida, Mark S Wainwright, Ji Yeoun Yoo, Eyal Muscal, Vincent Navarro, Lawrence J Hirsch, Yichen Lai

Faculty, Staff and Students Publications

Objective: We investigated whether complete blood count (CBC) analyses during intensive care unit stay could predict 12-month outcomes in patients with cryptogenic febrile infection-related epilepsy syndrome (FIRES), a subset of new-onset refractory status epilepticus (NORSE).

Methods: Outcomes at 12 months were classified as "unfavorable" (Glasgow Outcome Score [GOS] 1-3) or "favorable" (GOS 4-5). Demographic, clinical, and serial CBC data were collected across treatment phases: (1) no immunotherapy (before initiation or no treatment), (2) first-line immunotherapy, and (3) second-line immunotherapy. For each treatment phase, predictive models stratified outcomes based on CBC features using decision tree regression, with separate models for adults …

Clinical Exome Sequencing Efficacy And Phenotypic Expansions Involving Non-Isolated Congenital Anomalies Of Kidney And Urinary Tract (Cakut+), E Andres Rivera-Munoz, Xiaonan E Zhao, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Jennifer E Posey, Daryl A Scott

Faculty, Staff and Students Publications

Congenital Anomalies of Kidney and Urinary Tract (CAKUT) can occur in isolation or in conjunction with one or more non-CAKUT associated congenital anomalies or neurodevelopmental disorders (CAKUT+). A molecular cause is not identified in most individuals with CAKUT+. This is due, in part, to uncertainty regarding the efficacy of genetic testing and an incomplete understanding of the genes that cause CAKUT+. Here, we use data from 515 individuals with CAKUT+ (n = 500) or isolated CAKUT (n = 15) to determine the efficacy of clinical exome sequencing (cES) and to identify new phenotype expansions that involve CAKUT. We determined that …

Elevated Serum Bile Acids Predict Poor Liver Outcomes In Children With Alagille Syndrome: Results From The Gala Study Group., Carla Fiorella Murillo Perez, Shannon M. Vandriel, Emmanuel M. Gonzales, Jian-She Wang, Li-Ting Li, Huiyu She, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzińska, Emmanuel Jacquemin, Jérôme Bouligand, Lorenzo D'Antiga, Emanuele Nicastro, Björn Fischler, Henrik Arnell, Susan M. Siew, Michael Stormon, Kathleen M. Loomes, David A. Piccoli, Elizabeth B. Rand, James E. Squires, Saul J. Karpen, Rene Romero, Mureo Kasahara, Zerrin Önal, Étienne Sokal, Tanguy Demaret, Sabina Wiecek, Florence Lacaille, Dominique Debray, Winita Hardikar, Sahana Shankar, Pamela L. Valentino, Shikha S. Sundaram, Noelle H. Ebel, Jeffrey A. Feinstein, Orith Waisbourd-Zinman, Henry C. Lin, Nathalie Rock, Henkjan J. Verkade, M Kyle Jensen, Catalina Jaramillo, Kyung Mo Kim, Seak Hee Oh, Jernej Brecemiclj, Seema Alam, Giuseppe Indolfi, Niviann Blondet, Rima Fawaz, Silvia Nastasio, Pier Luigi Calvo, Gabriella Nebbia, Cigdem Arikan, Catherine Larson-Nath, Andréanne N. Zizzo, Thomas Damgaard Sandahl, Christos Tzivinikos, Nehal M. El-Koofy, Mohamed A. Elmonem, Amal A. Aqul, Wikrom Karnsakul, Pinar Bulut, Nanda Kerkar, Victorien M. Wolters, Amin J. Roberts, Helen M. Evans, Maria Camila Sanchez, Maria Lorena Cavalieri, Deirdre A. Kelly, Jane Hartley, Way Seah Lee, Christina Hajinicolaou, Chatmanee Lertudomphonwanit, Ryan T. Fischer, Jesus Quintero Bernabeu, Ruben E. Quiros-Tejeira, Cristina Targa Ferreira, Elisa Carvalho, John Eshun, Aglaia Zellos, Antal Dezsőfi, Raquel Borges Pinto, Kathleen Schwarz, Maria Rogalidou, Jennifer Garcia, María Legarda Tamara, Marisa Beretta, Quais Mujawar, Ermelinda Santos-Silva, Cristina Molera Busoms, Eberhard Lurz, Cristina Gonçalves, Carolina Jimenez-Rivera, Jesus M. Banales, Richard J. Thompson, Bettina E. Hansen, Binita M. Kamath, Global Alagille Alliance (Gala) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND AIM: Alagille syndrome (ALGS) is a rare disorder characterised by cholestasis and extrahepatic manifestations. Given the current era of ileal bile acid transporter (IBAT) inhibitor therapies that reduce serum bile acid (SBA) levels, we evaluated whether SBA predicts liver disease outcomes in ALGS.

METHODS: Patients were ascertained from the Global ALagille Alliance (GALA) cohort. A prognostic threshold of SBA 102 μmol/L was assessed as a time-dependent covariate in Cox regression analyses for native liver survival (NLS) and event-free survival (EFS), while adjusting for total bilirubin (TB) levels.

RESULTS: 570 GALA patients were included (348 [61%] male). There was …

Personalized Risk Prediction For Cancer Survivors: A Generalized Bayesian Semi-Parametric Model Of Recurrent Events With Competing Outcomes, Nam Hoai Nguyen, Seung Jun Shin, Elissa Dodd-Eaton, Jing Ning, Wenyi Wang

Faculty, Staff and Student Publications

Multiple primary cancers are increasingly more frequent due to improved survival of cancer patients. Characteristics of the first primary cancer largely impact the risk of developing subsequent primary cancers. Hence, model-based risk characterization of cancer survivors that captures patient-specific variables is needed for healthcare policy making. We propose a Bayesian semi-parametric framework, where the occurrence processes of the competing cancer types follow independent non-homogeneous Poisson processes and adjust for covariates including the type and age at diagnosis of the first primary. Applying this framework to a historically collected cohort with families presenting a highly enriched history of multiple primary tumors …

Microbial Associations And Viruses On The Risk Of Celiac Disease (Mavric): A Longitudinal Post-Hoc Case-Cohort Study, Kristian F Lynch, Eric W Triplett, Heikki Hyöty, Angelica P Ahrens, Jutta E Laiho, Joseph F Petrosino, Richard E Lloyd, Daniel Agardh

Faculty, Staff and Students Publications

Celiac disease etiopathogenesis requires genetic predisposition and exposure to gluten, yet these factors alone are not sufficient. Larger longitudinal studies are needed to determine the role of time-varying infections and gut microorganisms. The aim was to design a celiac disease case-cohort longitudinal study using The Environmental Determinants of Diabetes in the Young (TEDDY) study. By age 3-years, persistent tissue transglutaminase autoantibodies (tTGA), i.e., celiac disease autoimmunity (CDA), was confirmed in 704 of the 6132 genetically at-risk TEDDY children. Celiac disease onset (CD-onset) was defined as the age CDA developed when followed by a biopsy-proven diagnosis. A competing risk analysis on …

An Analysis Of Diagnostic Metabolomic Profiles Associated With Hepatotoxicity During Childhood All Induction Therapy, Emily J Mason, Anna M Crain, Michael E Scheurer, Philip J Lupo, Karen R Rabin, Olga A Taylor, Marley Roberts, John P Woodhouse, Ashley Chavana, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, M Monica Gramatges, Joanna S Yi, Sandi L Pruitt, M Brooke Bernhardt, Hong Zhu, Steven D Mittelman, Van Huynh, Etan Orgel, Jeremy M Schraw, Austin L Brown

Faculty, Staff and Students Publications

Hepatotoxicity is a well-documented complication of induction chemotherapy for acute lymphoblastic leukemia (ALL), but our understanding of its biological mechanisms is limited. We identified 314 patients with ALL (aged 1-19 years) treated at Texas Children’s Hospital (2008-2019) with diagnostic bone marrow plasma available for metabolomic profiling: 234 for discovery and 80 for replication. Hepatotoxicity during induction was defined as follows: (1) transaminitis: grade ≥3 aspartate aminotransferase or alanine aminotransferase or (2) conjugated hyperbilirubinemia: conjugated bilirubin (c.bili) >3 mg/dL. Untargeted profiling detected 519 metabolites. Adjusted odds ratios (aORs) for each metabolite were calculated with logistic regression, accounting for sex, age, body …

Perioperative Nutrition In Pediatric Patients With Congenital Heart Disease And Heart Failure., Jaime Silva-Gburek, Kelsey May, Bailey Walvoord, Catalina Lozano, Jorge A. Coss-Bu

Manuscripts, Articles, Book Chapters and Other Papers

Optimal nutritional therapy is important for infants and children with perioperative congenital heart disease and heart failure. Medical providers face physiological and metabolic challenges when administering enteral and parenteral nutrition to these patients. Complications related to enteral nutrition can increase morbidity and mortality, although outcomes are improved in those cases in which caloric and nutrient administration can be achieved. Consensus regarding feeding strategies and timing of nutritive care is lacking. This narrative review aims to summarize, analyze and discuss the most recent literature on nutritional therapy in perioperative congenital heart disease, heart failure and pediatric patients requiring mechanical circulatory support …

Ultra-Low-Field Portable Magnetic Resonance Imaging Feasibility And Safety In Pediatric And Neonatal Extracorporeal Membrane Oxygenation: A Single-Center Year-Long Experience., Jessica S. Wallisch, Asdis Finnsdottir Wagner, John M. Daniel Iv, Allison Taber, Maura Sien, Sarah Foster, Nathan S. Artz, Timothy Zinkus, Hung-Wen Yeh, Jose A. Pineda, Patrick M. Kochanek, Sherwin S. Chan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improving outcomes, extracorporeal membrane oxygenation (ECMO) remains associated with high rates of acute brain injury, impacting survival and outcomes. Clinical imaging modalities, including computed tomography and standard-field magnetic resonance imaging (≥1.5 Tesla), have either limited early detection of ischemic-type injuries or are incompatible with ECMO, causing diagnostic delays. A Food and Drug Administration-cleared ultra-low-field portable magnetic resonance imaging (pMRI; 0.064 Tesla) has shown promise in acute brain injury detection and use with MRI-unsafe equipment, but pediatric ECMO data are limited.

METHODS: This institutional review board-approved, single-center study was conducted at a quaternary children's hospital. Neonatal and pediatric patients …

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

Real-World Outcomes Of Infections Following Tisagenlecleucel In Patients With B-Cell All: A Cibmtr Analysis, Hemalatha G Rangarajan, Prakash Satwani, Megan M Herr, Min Chen, Michael J Martens, Kitsada Wudhikarn, Samuel John, Vanessa A Fabrizio, Emily M Hsieh, Amar H Kelkar, Erin Doherty, David I Marks, Olle Ringden, Brian Friend, Matthew S Kelly, Nosha Farhadfar, Tim Prestidge, Nasheed M Hossain, Hongtao Liu, Shahrukh Hashmi, Dipenkumar Modi, Lena E Winestone, Zeinab El Boghdadly, Hemant S Murthy, Miguel-Angel Perales, Roy F Chemaly, Christopher E Dandoy, Joshua A Hill, Anna Huppler, Marcie Riches, Jeffery J Auletta

Faculty, Staff and Students Publications

Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. …

Posterior Fossa Decompression In Syndromic Children With Chiari-Like Posterior Fossa Crowding: A Nationwide Us-Based Study, Victor Gabriel El-Hajj, Josué Aganze Mwambali, Ihab Ahmad Al-Rikabi, Erik Öhlen, Maria Gharios, Victor E. Staartjes, Joanna M. Roy, Basel Musmar, Pascal Jabbour, Erik Edström, Adrian Elmi-Terander

Department of Neurosurgery Faculty Papers

INTRODUCTION: Posterior fossa crowding, due to cerebellar tonsil herniation, often requires surgery with posterior fossa decompression (PFD). Although most cases are due to a Chiari-1 malformation (CM1), some are due to concomitant congenital conditions, mimicking a radiological CM1. The aim of this study was to compare PFD outcomes between CM1 and the syndromic Chiari-like crowding of the posterior fossa. A national pediatric surgical database was used to compare baseline characteristics and short-term postoperative outcomes.

METHODS: Pediatric patients undergoing PFD (2012-2021) were identified in the ACS NSQIP-P database. Baseline characteristics and 30-day outcomes were compared between syndromic and non-syndromic cases. Multivariate …

Optimising Drowning Prevention Counselling Through A Physician Maintenance Of Certification (Moc) Quality Improvement (Qi) Initiative, Tracy E Mccallin, Anthony R Arredondo, Elizabeth A Camp, Shabana Yusuf

Faculty, Staff and Students Publications

Drowning is the leading cause of death in children 1–4 years old in the USA. Paediatricians play an important role in giving anticipatory guidance on drowning prevention. This quality improvement initiative aimed to increase the rate of drowning prevention counselling with provision of educational materials to caregivers of children aged 0–10 years during clinical encounters in an outpatient setting.

We refined a previously published Texas state educational programme that included evidence-based counselling strategies across three Plan Do Study Act (PDSA) cycles, with the addition of preintervention baseline counselling phase during expansion of the programme nationally to 17 and 21 states …

Condition-Specific Growth Charts For Children With Alagille Syndrome., Koen Huysentruyt, Shannon M. Vandriel, Mathieu Roelants, David A. Piccoli, Kathleen M. Loomes, Elizabeth B. Rand, Noelle H. Ebel, Jeffrey A. Feinstein, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzinska, Emmanuel M. Gonzales, Emmanuel Jacquemin, Jérôme Bouligand, Saul J. Karpen, Rene Romero, Henry C. Lin, Björn Fischler, Henrik Arnell, Li-Ting Li, Jian-She Wang, Rima Fawaz, Silvia Nastasio, Kyung Mo Kim, Seak Hee Oh, Lorenzo D'Antiga, Emanuele Nicastro, Ryan T. Fischer, Susan M. Siew, Michael Stormon, Chatmanee Lertudomphonwanit, Winita Hardikar, Sahana Shankar, James E. Squires, Shikha S. Sundaram, Catherine Larson-Nath, Deirdre A. Kelly, Jane Hartley, Pinar Bulut, M Kyle Jensen, Catalina Jaramillo, Amin J. Roberts, Helen M. Evans, Étienne M. Sokal, Tanguy Demaret, Henkjan J. Verkade, Richard J. Thompson, Bettina E. Hansen, Tim J. Cole, Binita M. Kamath, Dominique Debray, Florence Lacaille, Jernej Brecelj, Nehal M. El-Koofy, Mohamed A. Elmonem, Way Seah Lee, Maria Camila Sanchez, Maria Lorena Cavalieri, Christina Hajinicolaou, Kathleen B. Schwarz, Elisa Carvalho, Nathalie Rock, Wikrom Karnsakul, Ruben E. Quiros-Tejeira, Seema Alam, Gabriella Nebbia, Yael Mozer-Glassberg, Pamela L. Valentino, Ermelinda Santos-Silva, Zerrin Önal, Antal Dezsofi-Gottl, Melina Melere, María Legarda Tamara, John Eshun, Aglaia Zellos, Giuseppe Indolfi, Maria Rogalidou, Niviann Blondet, Pier Luigi Calvo, Marisa Beretta, Andréanne N. Zizzo, Cigdem Arikan, Mureo Kasahara, Nanda Kerkar, Amal A. Aqul, Victorien M. Wolters, Raquel Borges Pinto, Jesus Quintero Bernabeu, Jennifer Garcia, Sabina Wiecek, Christos Tzivinikos, Quais Mujawar, Carolina Jimenez-Rivera, Cristina Molera Busoms, Cristina Gonçalves, Luis Bujanda, Global Alagille Alliance (Gala) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.

OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches.

DESIGN, SETTING, AND PARTICIPANTS: This case series used data from the international, multicenter Global Alagille Alliance (GALA) study accrued between May 14, 2018, and March 20, 2023. Children born at full term between January 1, 1997, and August 31, 2019, with a clinically and/or genetically confirmed ALGS diagnosis and their native liver were included. Data from children with a known history of prematurity …