Medicine and Health Sciences Commons^™

Human Brain Tissue With Moghe Carrying Somatic Slc35a2 Variants Reveal Aberrant Protein Expression And Protein Loss In The White Matter, Erica Cecchini, Simon Geffers, Roland Coras, Dorothea Schultheis, Christian Holtzhausen, Kristina Karandasheva, Harald Herrmann, Friedrich Paulsen, Christine Stadelmann, Katja Kobow, Till Hartlieb, Christian G Bien, Dennis Lal, Ingmar Blumcke, Lucas Hoffmann

Faculty, Staff and Student Publications

Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE) is a recently described disease entity primarily affecting young children with drug-resistant epilepsy, mainly affecting the frontal lobe. The condition is histopathologically defined by focal lesions with patchy areas of increased oligodendroglial cell density at the grey-white matter boundary and heterotopic neurons in the white matter. Approximately half of the individuals with MOGHE carry brain somatic variants in the SLC35A2 gene, which affects the UDP-galactose transporter and thus sphingolipid glycosylation. To investigate the impact of SLC35A2 variants on protein expression, we analysed MOGHE brain tissue with and without SLC35A2 …

External Validation Of The Phoenix Sepsis Score In Children With Suspected Community-Acquired Sepsis, Elliot Long, Meredith Borland, Shane George, Shefali Jani, Eunicia Tan, Natalie Phillips, Amit Kochar, Simon Craig, Anna Lithgow, Arjun Rao, Stuart Dalziel, Ed Oakley, Stephen Hearps, Ben Gelbart, Sarah Mcnab, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Charlotte Brad, Amanda Williams, Franz Babl

Department of Medicine Faculty Papers

IMPORTANCE: The novel Phoenix Sepsis Score and sepsis criteria were derived and validated using a multicountry dataset and proposed as a new definition for sepsis in children.

OBJECTIVE: To externally validate the Phoenix Sepsis Score and sepsis criteria in a cohort of children hospitalized with suspected community-acquired sepsis.

DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study used data from the multicenter, multicountry Sepsis Epidemiology in Australian and New Zealand Emergency Departments (SENTINEL) study, collected from 2021 to 2023 and including 90-day follow-up. Children admitted to the hospital through 11 emergency departments in Australia and New Zealand and treated with parenteral antibiotics …

Trends In Respiratory Pathogen Testing At Us Children's Hospitals., Matthew J. Molloy, Matthew Hall, Jessica L. Markham, Jillian M. Cotter, Elisha Mccoy, Michael J. Tchou, Megan E. Collins, Michael J. Steiner, John R. Stephens, Andrew G. Yu, Irma T. Ugalde, Rustin B. Morse, Monika K. Goyal, Samantha A. House

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Respiratory pathogen testing has been a common deimplementation focus. The COVID-19 pandemic brought new considerations for respiratory testing; recent trends in testing rates are not well understood.

OBJECTIVE: To measure trends in respiratory testing among encounters for acute respiratory infections among children and adolescents (agedyears) from 2016 to 2023, assess the association of COVID-19 with these trends, and describe associated cost trends.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective serial cross-sectional study included emergency department (ED) encounters and hospitalizations in US children's hospitals among children and adolescents with a primary acute infectious respiratory illness diagnosis. Data were ascertained from the …

Identifying Pregnant Women With Disabilities And Maternal And Newborn Outcomes, Alka Dev, Willi Horner-Johnson, Andrew Schaefer, Cecilia Ganduglia-Cazaban, Thérèse A Stukel, David C Goodman, Joanna K Leyenaar

Faculty, Staff and Student Publications

Importance: Pregnant women with disabilities are at higher risk of poor pregnancy and birth outcomes. Different methods for identifying disability may affect estimates of health disparities in this population.

Objective: To compare pregnancy and birth outcomes among pregnant women using different ways of identifying maternal disability.

Design, setting, and participants: Retrospective cohort study of linked vital records and maternal and newborn claims for Medicaid-insured live births from January 2010 to December 2014 in Texas. Data analysis was conducted from October 2023 to May 2024.

Exposure: Births grouped into 5 maternal cohorts: no identified disability, disability benefits enrollment only, disability diagnostic …

Nulliparous With Class Iii Obesity At Term: Labor Induction Or Cesarean Delivery Without Labor, Yossi Bart, Rachel L Wiley, Ipsita Ghose, Michal Fishel Bartal, Khalil M Chahine, Suneet P Chauhan, Sean Blackwell, Baha M Sibai

Faculty, Staff and Student Publications

Objective: This study aimed to compare maternal and neonatal outcomes between labor induction versus cesarean delivery (CD) without labor among nulliparous individuals with class III obesity (body mass index [BMI] ≥40 kg/m2).

Study design: A retrospective cohort study of all nulliparous singleton deliveries at ≥37 weeks with a BMI of ≥40 kg/m2 at delivery between March 2020 and February 2022. We excluded individuals with spontaneous labor, fetal malformations, and stillbirths. The primary outcome was a composite of maternal mortality and morbidity, including infectious and hemorrhagic morbidity. The secondary outcome was a neonatal composite. A subgroup analysis evaluated patients with a …

Care Utilization For Acute Respiratory Infections In Children Requiring Invasive Long-Term Mechanical Ventilation, Carolyn C Foster, Todd A Florin, Derek J Williams, Katherine L Freundlich, Rebecca L Steuart, Julia A Heneghan, Cara Cecil, Nathan M Pajor, Robert J Graham, Sriram Ramgopal

Faculty, Staff and Student Publications

Introduction: Children who use invasive long-term mechanical ventilation (LTMV) are a rare, clinically heterogenous population with relatively high hospitalization rates, most commonly for acute respiratory infection (ARI). We sought to describe patterns of ARI-related utilization and mortality in pediatric patients with LTMV, evaluating the association of a pre-existing neurologic diagnoses with outcomes.

Methods: We studied a longitudinal retrospective cohort across 40 U.S. children's hospital emergency department (ED) and hospital encounters for patients (< 21 years) with LTMV and an ARI diagnosis code (10/1/2016-6/30/2023). We examined mortality and ED/hospital utilization outcomes, defining short-stay hospitalizations as ≤ 2 calendar days. We stratified analyses by high intensity neurologic impairment (HINI) using a validated coding algorithm.

Results: We included 4866 patients (median age 4.5 years; 58.6% male) with LTMV and ≥ 1 ARI encounter. Most (95.1%) were hospitalized on their index encounter, and …

Infantile Myofibromatosis: Small Bumps Pose Big Problems, Hillary C Lee, Amee A Amin, Kudakwashe R Chikwava, Valeria R Smith, Caraciolo J Fernandes

Faculty, Staff and Students Publications

Background

Infantile myofibromatosis (IM) is a disorder characterized by proliferation of benign myofibroblastic tumors that typically manifest as solitary or multiple nodules in the skin, muscle, bone, subcutaneous tissues, and visceral organs and can pose significant morbidity and mortality risks, particularly in cases involving visceral organs or causing functional impairment. These soft tissue lesions are the most prevalent benign fibrous tumors that present before age two and can undergo spontaneous regression or are amenable to surgical resection.

Case

A preterm, male infant was born via Caesarean section to a mother with a trichorionic, triamniotic pregnancy following preterm labor. Within the …

The Glu86 Residue In Tbx4 Proves Critical For Human Lung Development, Przemyslaw Szafranski, Tomasz Gambin, Gail Deutsch, Salma A Nassef, Mary Clay Bailey, Debra L Kearney, Paweł Stankiewicz

Faculty, Staff and Students Publications

T-box transcription factors are a group of evolutionarily conserved T-box-containing regulators of mesoderm specification and development. Heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving dosage-sensitive TBX4 have been associated with pulmonary arterial hypertension (PAH), ischiocoxopodopatellar syndrome with or without PAH, and lethal lung developmental disorders (LLDDs), including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD), and other unspecified primary pulmonary hypoplasias. Loss- and gain-of-function variants have been proposed to cause pediatric PAH and LLDDs, and adult forms of PAH, respectively. Of more than 50 missense SNVs scattered across the entire TBX4, only three have been reported in patients …

Early Life Epigenetics And Childhood Outcomes: A Scoping Review, Srirupa Hari Gopal, Theresa Alenghat, Mohan Pammi

Faculty, Staff and Students Publications

Epigenetics is the study of changes in gene expression, without a change in the DNA sequence that are potentially heritable. Epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNA (sncRNA) changes have been studied in various childhood disorders. Causal links to maternal health and toxin exposures can introduce epigenetic modifications to the fetal DNA, which can be detected in the cord blood. Cord blood epigenetic modifications provide evidence of in-utero stressors and immediate postnatal changes, which can impact both short and long-term outcomes in children. The mechanisms of these epigenetic changes can be leveraged for prevention, early …

A Multicenter Training And Interrater Reliability Study Of The Based Score For Infantile Epileptic Spasms Syndrome, John R Mytinger, Dara V F Albert, Shawn C Aylward, Christopher W Beatty, Sonam Bhalla, Sonal Bhatia, Guy N Brock, Micheal A Ciliberto, Purva R Choudhari, Daniel J Clark, Jennifer Madan Cohen, Theresa M Czech, Megan M Fredwall, Ernesto Gonzalez-Giraldo, Chellamani Harini, Senyene E Hunter, Amanda G Sandoval Karamian, Akshat Katyayan, Isaac Kistler, Neil Kulkarni, Virginia B Liu, Corinne Mccabe, Thomas Murray, Kerri Neville, Shital H Patel, Spriha Pavuluri, Donald J Phillips, Debopam Samanta, Deepa Sirsi, Emily M Spelbrink, Carl E Stafstrom, Maija Steenari, Danielle S Takacs, Tyler Terrill, Linh Tran, Jorge Vidaurre, Daniel W Shrey

Faculty, Staff and Students Publications

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE).

METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 …

Epidemiology Of Diagnostic Errors In Pediatric Emergency Departments Using Electronic Triggers, Prashant Mahajan, Emily White, Kathy Shaw, Sarah J Parker, James Chamberlain, Richard M Ruddy, Elizabeth R Alpern, Jacqueline Corboy, Andrew Krack, Brandon Ku, Daphne Morrison Ponce, Asha S Payne, Elizabeth Freiheit, Gregor Horvath, Giselle Kolenic, Michele Carney, Nicole Klekowski, Karen J O'Connell, Hardeep Singh

Faculty, Staff and Students Publications

Objectives: We applied three electronic triggers to study frequency and contributory factors of missed opportunities for improving diagnosis (MOIDs) in pediatric emergency departments (EDs): return visits within 10 days resulting in admission (Trigger 1), care escalation within 24 h of ED presentation (Trigger 2), and death within 24 h of ED visit (Trigger 3).

Methods: We created an electronic query and reporting template for the triggers and applied them to electronic health record systems of five pediatric EDs for visits from 2019. Clinician reviewers manually screened identified charts and initially categorized them as "unlikely for MOIDs" or "unable to rule …

Cagi6 Id Panel Challenge: Assessment Of Phenotype And Variant Predictions In 415 Children With Neurodevelopmental Disorders (Ndds), Maria Cristina Aspromonte, Alessio Del Conte, Shaowen Zhu, Wuwei Tan, Yang Shen, Yexian Zhang, Qi Li, Maggie Haitian Wang, Giulia Babbi, Samuele Bovo, Pier Luigi Martelli, Rita Casadio, Azza Althagafi, Sumyyah Toonsi, Maxat Kulmanov, Robert Hoehndorf, Panagiotis Katsonis, Amanda Williams, Olivier Lichtarge, Su Xian, Wesley Surento, Vikas Pejaver, Sean D Mooney, Uma Sunderam, Rajgopal Srinivasan, Alessandra Murgia, Damiano Piovesan, Silvio C E Tosatto, Emanuela Leonardi

Faculty, Staff and Students Publications

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age. Here, we assess the ability and accuracy of computational methods to predict comorbid phenotypes based on clinical …

Causes Of Mortality In The Congenital Disorders Of Glycosylation, Hana Alharbi, Seishu Horikoshi, Sabrina Malone Jenkins, Fernando Scaglia, Christina Lam, Eva Morava, Austin Larson, Andrew C Edmondson

Faculty, Staff and Students Publications

Congenital Disorders of Glycosylation (CDG) are a group of some 200 genetic disorders with PMM2-CDG being the most common disease. These disorders individually remain rare with poorly understood natural history (NH) and causes of mortality. We established a NH study for CDG and collected both prospective and retrospective data on CDG outcomes. In the current data set analysis on deceased patients, we describe the clinical phenotype and causes of death for thirty-seven individuals with various genetic causes of CDG. About a third of this cohort were affected with PMM2-CDG. All of the patients presented with multisystem features with involvement of …

Family Genetic Risk Communication And Reverse Cascade Testing In The Babyseq Project, Melissa K Uveges, Hadley Stevens Smith, Stacey Pereira, Casie Genetti, Amy L Mcguire, Alan H Beggs, Robert C Green, Ingrid A Holm

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Genomic sequencing of newborns can initiate disease surveillance and therapy for children and may identify at-risk relatives through reverse cascade testing. We explored genetic risk communication and reverse cascade testing among families of newborns who underwent exome sequencing and were identified as having a risk for an autosomal dominant disease.

Methods: We conducted semistructured interviews with parents of newborns enrolled in the BabySeq Project who had a pathogenic or likely pathogenic variant associated with an autosomal dominant childhood- and/or adult-onset disease returned. We used directed content analysis to derive themes.

Results: From 11 families, all first-degree relatives (n = …

Rhabdoid Tumor Of The Kidney And Soft Tissues: Results From National Wilms Tumor Study-5 And Children's Oncology Group Study Aren0321, James I Geller, Lindsay A Renfro, Paul E Grundy, Elizabeth J Perlman, John A Kalapurakal, Peter F Ehrlich, Jackie Biegel, Vicki Huff, Anne B Warwick, Arnold Paulino, Elizabeth A Mullen, Najat C Daw, Fredric A Hoffer, Zelig Tochner, Kenneth Gow, Eric Gratias, Deborah A Ward, James R Anderson, Conrad V Fernandez, Jeffrey S Dome

Faculty, Staff and Student Publications

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT).

Patients and methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1). We report event-free survival (EFS) and overall survival (OS) from each study.

Results: Thirty patients received Regimen RTK on NWTS-5; …

Parameterizing Toxic Stress In Early Childhood: Maternal Depression, Maltreatment, And Hpa-Axis Variation In A Pilot Intervention Study, Rachael E Wagner, Melissa Jonson-Reid, Brett Drake, Patricia L Kohl, Laura Pons, Yi Zhang, Robert T Fitzgerald, Mark L Laudenslager, John N Constantino

2020-Current year OA Pubs

Adverse experiences superseding a child's capacity to sustain regulation of emotion and adaptive function are theorized to constitute "toxic stressors" when they induce a deleterious biological response within an individual. We ascertained presumptive parameters of toxic stress among 164 low-income infants and toddlers (ages 4-48 months) from 132 families enrolled in Early Head Start (EHS). We randomized a subset of these families into a pilot intervention arm of parenting education (the Incredible Years, TIY), which supplemented the EHS curriculum. Official report child abuse and neglect (CAN) and child behavior were serially ascertained over the course of the study. We observed …

Invasive Haemophilus Influenzae Disease At A Us Children's Hospital In The Sars-Cov-2 Era, J Chase Mcneil, David R Mcdonald, James J Dunn, Sheldon L Kaplan, Kristina G Hulten, Jesus G Vallejo

Faculty, Staff and Students Publications

Background: National data previously demonstrated an increase in invasive disease due to non-type b Haemophilus influenzae from the 2000s to the 2010s. Significant shifts in the epidemiology of respiratory pathogens in children have occurred in the post-SARS-CoV-2 era. We examined pediatric invasive H. influenzae disease in the pre- and post-SARS-CoV-2 years.

Methods: Invasive H. influenzae infections were identified from culture records of the Texas Children's Hospital microbiology laboratory from January 2011 to December 2023. Invasive cases were considered those with isolation of H. influenzae from a sterile site. The annual number of cases/1000 admissions was used as a surrogate for …

Interim Estimates Of 2024-2025 Seasonal Influenza Vaccine Effectiveness - Four Vaccine Effectiveness Networks, United States, October 2024-February 2025., Aaron M. Frutos, Seana Cleary, Emily L. Reeves, Haris M. Ahmad, Ashley M. Price, Wesley H. Self, Yuwei Zhu, Basmah Safdar, Ithan D. Peltan, Kevin W. Gibbs, Matthew C. Exline, Adam S. Lauring, Sarah W. Ball, Malini Desilva, Sara Y. Tartof, Kristin Dascomb, Stephanie A. Irving, Nicola P. Klein, Brian E. Dixon, Toan C. Ong, Ivana A. Vaughn, Stacey L. House, Kiran A. Faryar, Mary Patricia Nowalk, Manjusha Gaglani, Karen J. Wernli, Vel Murugan, Olivia L. Williams, Rangaraj Selvarangan, Geoffrey A. Weinberg, Mary A. Staat, Natasha B. Halasa, Leila C. Sahni, Marian G. Michaels, Janet A. Englund, Marie K. Kirby, Diya Surie, Fatimah S. Dawood, Benjamin R. Clopper, Heidi L Moline, Ruth Link-Gelles, Amanda B. Payne, Elizabeth Harker, Kristina Wielgosz, Zachary A. Weber, Duck-Hye Yang, Nathaniel M. Lewis, Jennifer Decuir, Samantha M. Olson, Jessie R. Chung, Brendan Flannery, Lisa A. Grohskopf, Carrie Reed, Shikha Garg, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness-associated outpatient visits and hospitalizations from four VE networks during the 2024-25 influenza season (October 2024-February 2025). Among children and adolescents agedyears, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization …

Interim Estimates Of 2024-2025 Seasonal Influenza Vaccine Effectiveness - Four Vaccine Effectiveness Networks, United States, October 2024-February 2025, Aaron M Frutos, Seana Cleary, Emily L Reeves, Haris M Ahmad, Ashley M Price, Wesley H Self, Yuwei Zhu, Basmah Safdar, Ithan D Peltan, Kevin W Gibbs, Matthew C Exline, Adam S Lauring, Sarah W Ball, Malini Desilva, Sara Y Tartof, Kristin Dascomb, Stephanie A Irving, Nicola P Klein, Brian E Dixon, Toan C Ong, Ivana A Vaughn, Stacey L House, Kiran A Faryar, Mary Patricia Nowalk, Manjusha Gaglani, Karen J Wernli, Vel Murugan, Olivia L Williams, Rangaraj Selvarangan, Geoffrey A Weinberg, Mary A Staat, Natasha B Halasa, Leila C Sahni, Marian G Michaels, Janet A Englund, Marie K Kirby, Diya Surie, Fatimah S Dawood, Benjamin R Clopper, Heidi L Moline, Ruth Link-Gelles, Amanda B Payne, Elizabeth Harker, Kristina Wielgosz, Zachary A Weber, Duck-Hye Yang, Nathaniel M Lewis, Jennifer Decuir, Samantha M Olson, Jessie R Chung, Brendan Flannery, Lisa A Grohskopf, Carrie Reed, Shikha Garg, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Faculty, Staff and Students Publications

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness–associated outpatient visits and hospitalizations from four VE networks during the 2024–25 influenza season (October 2024–February 2025). Among children and adolescents aged <18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization in two networks. Preliminary estimates indicate that receipt of the 2024–2025 influenza vaccine reduced the likelihood of medically attended influenza and influenza-associated hospitalization. CDC recommends annual receipt of an age-appropriate influenza vaccine by all eligible persons aged ≥6 months as long as influenza viruses continue to circulate locally.

Characterization Of Factors Associated With Death In Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey, Alina Ivaniuk, Irina A Anselm, Aaron Bowen, Bruce H Cohen, Fatma Tuba Eminoglu, Jane Estrella, Renata C Gallagher, Rebecca D Ganetzky, Jennifer Gannon, Grainne S Gorman, Carol Greene, Andrea L Gropman, Richard H Haas, Michio Hirano, Seema Kapoor, Amel Karaa, Mary Kay Koenig, Cornelia Kornblum, Engin Kose, Austin Larson, Uta Lichter-Konecki, Piervito Lopriore, Michelangelo Mancuso, Robert Mcfarland, Aye Myat Moe, Eva Morava, Yi Shiau Ng, Russell P Saneto, Fernando Scaglia, Carolyn M Sue, Mark Tarnopolsky, Melissa A Walker, Sumit Parikh, Fung Cheuk-Wing, Tsz-Sum Wong, Kiran Belaramani, Chun-Kong Chan, Wing-Ki Chan, Wai-Lun Larry Chan, Hon-Wing Cheung, Ka-Yin Cheung, Shek-Kwan Chang, Sing-Ngai Cheung, Tsz-Fung Cheung, Yuk-Fai Cheung, Shuk-Ching Josephine Chong, Chi-Kwan Jasmine Chow, Hon-Yin B Chung, Sin-Ying Florence Fan, Wai-Ming Joshua Fok, Ka-Wing Fong, Tsui-Hang Sharon Fung, Kwok-Fai Hui, Ting-Hin Hui, Joannie Hui, Chun Hung Ko, Min-Chung Kwan, Mei-Kwan Anne Kwok, Sung-Shing Jeffrey Kwok, Moon-Sing Lai, Yau-On Lam, Ching-Wan Lam, Ming-Chung Lau, Chun-Yiu Eric Law, Hiu-Fung Law, Wing-Cheong Lee, Han-Chih Hencher Lee, Kin-Hang Leung, Kit-Yan Leung, Siu-Hung Li, Tsz-Ki Jacky Ling, Kam-Tim Timothy Liu, Fai-Man Lo, Colin Lui, Ching-On Luk, Ho-Ming Luk, Che-Kwan Ma, Karen Ma, Kam-Hung Ma, Yuen-Ni Mew, Alex Mo, Sui-Fun Hg, Wing-Kit Grace Poon, Bun Sheng, Cheuk-Ling Charing Szeto, Shuk-Mui Tai, Jing-Liang Tang, Choi-Ting Alan Tse, Li-Yan Lilian Tsung, Ho-Ming June Wong, Wing-Yin Winnie Wong, Kwok-Kui Wong, Suet-Na Sheila Wong, Chun-Nei Virginia Wong, Wai-Shan Sammy Wong, Chi-Kin Felix Wong, Shun-Ping Wu, Hiu-Fung Jerome Wu, Man-Mut Yau, Kin-Cheong Eric Yau, Wai-Lan Yeung, Hon-Ming Jonas Yeung, Kin-Keung Edwin Yip, Hui-Jun Wu, Pui-Hong Terence Young, Gao Yuan, Yuet-Ping Liz Yuen, Chi-Lap Yuen

Faculty, Staff and Student Publications

Background and objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023. Individuals with genetically confirmed mitochondrial disorders were included, along with patients with clinically or genetically diagnosed Leigh syndrome. Collected data included demographic and genetic diagnosis variables, clinical phenotype, involvement of organs and systems, conditions leading to death, and supportive care. We defined pediatric and adult groups based …

Aif3 Splicing Variant Elicits Mitochondrial Malfunction Via The Concurrent Dysregulation Of Electron Transport Chain And Glutathione-Redox Homeostasis, Mi Zhou, Shuiqiao Liu, Yanan Wang, Bo Zhang, Ming Zhu, Jennifer E Wang, Veena Rajaram, Yisheng Fang, Weibo Luo, Yingfei Wang

Faculty, Staff and Student Publications

Genetic mutations in apoptosis-inducing factor (AIF) have a strong association with mitochondrial disorders; however, little is known about the aberrant splicing variants in affected patients and how these variants contribute to mitochondrial dysfunction and brain development defects. We identified pathologic AIF3/AIF3-like splicing variants in postmortem brain tissues of pediatric individuals with mitochondrial disorders. Mutations in AIFM1 exon-2/3 increase splicing risks. AIF3-splicing disrupts mitochondrial complexes, membrane potential, and respiration, causing brain development defects. Mechanistically, AIF is a mammalian NAD(P)H dehydrogenase and possesses glutathione reductase activity controlling respiratory chain functions and glutathione regeneration. Conversely, AIF3, lacking these activities, disassembles mitochondrial complexes, increases …

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …

Dna-Binding Affinity And Specificity Determine The Phenotypic Diversity In Bcl11b-Related Disorders, Ivana Lessel, Anja Baresic, Ivan K Chinn, Jonathan May, Anu Goenka, Kate E Chandler, Jennifer E Posey, Alexandra Afenjar, Luisa Averdunk, Maria Francesca Bedeschi, Thomas Besnard, Rae Brager, Lauren Brick, Melanie Brugger, Theresa Brunet, Susan Byrne, Oscar De La Calle-Martín, Valeria Capra, Paul Cardenas, Céline Chappé, Hey J Chong, Benjamin Cogne, Erin Conboy, Heidi Cope, Thomas Courtin, Wallid Deb, Robertino Dilena, Christèle Dubourg, Magdeldin Elgizouli, Erica Fernandes, Kristi K Fitzgerald, Silvana Gangi, Jaya K George-Abraham, Muge Gucsavas-Calikoglu, Tobias B Haack, Medard Hadonou, Britta Hanker, Irina Hüning, Maria Iascone, Bertrand Isidor, Irma Järvelä, Jay J Jin, Alexander A L Jorge, Dragana Josifova, Ruta Kalinauskiene, Erik-Jan Kamsteeg, Boris Keren, Elena Kessler, Heike Kölbel, Mariya Kozenko, Christian Kubisch, Alma Kuechler, Suzanne M Leal, Juha Leppälä, Sharon M Luu, Gholson J Lyon, Suneeta Madan-Khetarpal, Margherita Mancardi, Elaine Marchi, Lakshmi Mehta, Beatriz Menendez, Chantal F Morel, Sue Moyer Harasink, Dayna-Lynn Nevay, Vincenzo Nigro, Sylvie Odent, Renske Oegema, John Pappas, Matthew T Pastore, Yezmin Perilla-Young, Konrad Platzer, Nina Powell-Hamilton, Rachel Rabin, Aisha Rekab, Raissa C Rezende, Leema Robert, Ferruccio Romano, Marcello Scala, Karin Poths, Isabelle Schrauwen, Jessica Sebastian, John Short, Richard Sidlow, Jennifer Sullivan, Katalin Szakszon, Queenie K G Tan, Undiagnosed Diseases Network, Matias Wagner, Dagmar Wieczorek, Bo Yuan, Nicole Maeding, Dirk Strunk, Amber Begtrup, Siddharth Banka, James R Lupski, Eva Tolosa, Davor Lessel

Faculty, Staff and Students Publications

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. …

Immunogenicity And Reactogenicity Of High- Or Standard-Dose Influenza Vaccine In A Second Consecutive Influenza Season., Hannah Bahakel, Andrew J. Spieker, Haya Hayek, Jennifer E. Schuster, Lubna Hamdan, Daniel E. Dulek, Carrie L. Kitko, Tess Stopczynski, Einas Batarseh, Zaid Haddadin, Laura S. Stewart, Anna Stahl, Molly Potter, Herdi Rahman, Justin Amarin, Spyros A. Kalams, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Christopher J. Harrison, Jason Freedman, Paul A. Carpenter, Janet A. Englund, Flor M. Munoz, Lara Danziger-Isakov, Natasha Halasa, Pediatric Hct Flu Study

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatric hematopoietic cell transplant (HCT) recipients are at high risk for morbidity from influenza virus infection. We demonstrated in a primary phase 2 randomized controlled trial that 2 post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given 4 weeks apart were more immunogenic than 2 doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present the immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen.

METHODS: A subcohort of study participants reenrolled and had hemagglutinin inhibition titers measured at baseline and 4 weeks after each vaccine dose in year 2. We estimated …

Short Duration Of Antenatal Corticosteroid Exposure And Outcomes In Extremely Preterm Infants, Sanjay Chawla, Myra H Wyckoff, Satyan Lakshminrusimha, Matthew A Rysavy, Ravi Mangal Patel, Dhuly Chowdhury, Abhik Das, Rachel G Greenberg, Girija Natarajan, Seetha Shankaran, Edward F Bell, Namasivayam Ambalavanan, Noelle E Younge, Abbot R Laptook, Leeann R Pavlek, Carl H Backes, Krisa P Van Meurs, Erika F Werner, Waldemar A Carlo, National Institute Of Child Health And Human Development (Nichd) Neonatal Research Network (Nrn)

Faculty, Staff and Student Publications

Importance: When preterm delivery is imminent, it remains unclear whether the timing from administration of antenatal betamethasone to birth may reduce mortality and morbidity among extremely preterm infants.

Objective: To evaluate the association of duration from exposure to first dose of antenatal betamethasone with outcomes among extremely preterm infants.

Design, setting, and participants: This cohort study enrolled infants born at 22 0/7 to 27 6/7 weeks' gestation from January 2016 to February 2021 at National Institute of Child Health and Human Development Neonatal Research Network centers. Infants exposed to multiple doses of antenatal betamethasone, infants who did not receive intensive …

Applications Of Metabolomics And Lipidomics In The Neonatal Intensive Care Unit, Jonathan D Reiss, Samson J Mataraso, Lindsay F Holzapfel, Ivana Marić, Maya M Kasowski, Camilia R Martin, Jonathan Z Long, David K Stevenson, Gary M Shaw

Faculty, Staff and Student Publications

The metabolome and lipidome comprise the thousands of molecular compounds in an organism. Molecular compounds consist of the upstream metabolic components of intracellular reactions or the byproducts of cellular pathways. Molecular and biochemical perturbations are associated with disorders in newborns and infants. The diagnosis of inborn errors of metabolism has relied on targeted metabolomics for several decades. Newer approaches offer the potential to identify novel biomarkers for common diseases of the newborn and infant. They may also elucidate novel predictive or diagnostic measures for a variety of health trajectories. Here, we review the relevance of the metabolome and lipidome for …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Association Between Early Immunosuppression Center Variability And One-Year Outcomes After Pediatric Liver Transplant., Vikram K. Raghu, Scott D. Rothenberger, James E. Squires, Elizabeth Eisenberg, Anna L. Peters, Jennifer Halma, Swati Antala, Irini D. Batsis, Ke-You Zhang, Amy G. Feldman, Daniel H. Leung, Steven J. Lobritto, John Bucuvalas, Simon P. Horslen, George V. Mazariegos, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

METHODS: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center. We categorized induction regimen as corticosteroids only vs. T-cell depleting antibody vs. non-T-cell depleting antibody. Primary exposures were coefficient of immunosuppression variability (CIV) in (1) induction and (2) mycophenolate mofetil (MMF) use. Primary outcomes were one-year graft survival, patient survival, …