Pediatrics Commons^™

Adrenomedullin Overexpression Protects Mice From Experimental Bronchopulmonary Dysplasia And Associated Pulmonary Hypertension, Shyam Thapa, Poonam Sarkar, M Waleed Gaber, Roberto Barrios, Madhulata Chauhan, Chandrasekhar Yallampalli, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) or BPD-PH is a lung disease of infants with significant morbidity. Adrenomedullin (Adm) is an angiogenic peptide that signals through calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2 (RAMP2). Adm deficiency potentiates hyperoxia-induced experimental BPD-PH in mice; however, whether Adm overexpression can mitigate this lung disease is unclear. Thus, we tested the hypothesis that Adm overexpression attenuates hyperoxia (HO)-induced murine experimental BPD-PH by using a novel transgenic mouse that overexpresses Adm globally (Admhi/hi mice). One-day-old Admhi/hi mice or their wild-type littermates (Adm+/+ mice) were exposed to …

Common Severity-Based Definitions Of Bronchopulmonary Dysplasia Are Not Associated With Outpatient Morbidities, Robin L Mckinney, Antonia P Popova, Milenka Cuevas Guaman, Matthew J Kielt, Paul E Moore, Sharon A Mcgrath-Morrow, Joseph M Collaco

Faculty, Staff and Students Publications

Objectives: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, which can have life-long effects. Commonly used definitions of BPD severity are based on respiratory support at 36 weeks post-menstrual age. The utility of these definitions for tertiary referral centers outside the initial birth hospitalization is unclear.

Study design: Retrospective cohort study of infants born < 34 weeks gestation in the BPD Collaborative registry using three common definitions of BPD severity at 36 weeks post menstrual age and associated their severity with outpatient respiratory outcomes during the first 3 years of life.

Results: BPD severity by all three definitions was applied to 608 patients. Although the definitions had different distributions of BPD severity for the cohort, a majority of participants (75.7%) had moderate/Grade 2 or severe/Grade 3 BPD irrespective of the definition. Using clustered logistic …

Racial And Ethnic Disparities In Pediatric Autoimmune Encephalitis: A Systematic Review, Jennifer H Yang, Kristen S Fisher, Julia Dumcum, Sophie Zacharek, Alexandra B Kornbluh, Kelsey Poisson, Mary C Karalius, Leigh Sepeta

Faculty, Staff and Students Publications

Objectives: Health disparities and social determinants of health are increasingly recognized as important predictors for clinical outcomes in autoimmune disease. However, this is poorly studied in pediatric autoimmune encephalitis (AE).

Methods: We conducted a systematic literature review in accordance with PRISMA guidelines. Searches included Medline (Pubmed), EMBASE, and Web of Science databases from inception years to October 4, 2024. Inclusion criteria were: 1) Patients diagnosed with AE ≤ 18 years old; 2) any report of race and/or ethnicity, 3) report of specific diagnostics and disease outcomes, 4) observational cohort studies, epidemiological studies or case series/ cohort studies of n ≥ …

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 …

Plasma Metabolomic And Proteomic Signatures Of Blood Pressure Management After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Juan Pablo Lewinger, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Todd M Jenkins, Stephanie Sisley, Stephen R Daniels, Douglas I Walker, Max T Aung, Erika Garcia, Rob Mcconnell, Sandrah P Eckel, Michele A La Merrill, Tanya L Alderete, Zhuanghua Chen, Frank D Gilliland, Thomas H Inge, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Background: Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery.

Methods: We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and …

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 …

Insights From A Survey Of School Nurses: Assessing The Challenges Of Constipation In Schools, Andrew S Chu, Eric H Chiou

Faculty, Staff and Students Publications

Objectives: School nurses are key responders to students with constipation, yet their experiences are underreported. This study surveyed their observations regarding constipation, identified barriers to student restroom access, and assessed educational needs.

Methods: In this descriptive, cross-sectional survey study, an anonymous online survey was distributed to school nurses participating in a virtual education series. The survey assessed nurse demographics, frequency of encounters with constipation and encopresis, school restroom policies, barriers to restroom use, accommodation requests, and training in constipation management.

Findings: Of 125 respondents, 95% encountered students with constipation at least monthly and 55% reported ≥ 6 encounters monthly. Commonly …

Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025., Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Emily R. Levy, Tamara T. Bradford, Stephanie P. Schwartz, Tracie C. Walker, Melissa S. Stockwell, Austin Biggs, Alexander H. Hogan, Katherine Lindsey, Angela P. Campbell, Adrienne G. Randolph, Overcoming Rsv Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < 1 year) in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

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 …

Cordmilk: Umbilical Cord Milking Versus Early Cord Clamping On Short-And Long-Term Outcomes In Neonates Who Are Non-Vigorous At Birth-Study Protocol Of A Multi-Center, Cluster-Randomized, Crossover-Controlled Trial, S. Yogeshkumar, Sunil S. Vernekar, Sangappa M. Dhaded, Kiran Talekar, Benjamin E Leiby, Rebecca Hartman, Yvonne Vaucher, Nitin Chouthai, Meenakshi Girish, Manish Jain, Shuchi Jain, Seema Parvekar, Vinita Jain, Alka Patankar, Milind Suryawanshi, Manish Tiwari, Manjushri Waikar, Nidhi Nashine, Deepali Ambike, Mahesh Asalkar, Rajesh Kulkarni, Sandhya Haribhaktha, Hemraj Narkhede, Sudha Chaudhari, Milind Kamble, Deepti Shrirame, Balchandra Falke, Seema Mehta, Asha Verma, Sunil Gothwal, Shivaprasad S. Goudar, Richard Derman, Anup Katheria, Zubair H. Aghai

Department of Radiology Faculty Papers

BACKGROUND: Facilitating placental transfusion-the transfer of blood from the placenta to the newborn-via delayed cord clamping (DCC) or umbilical cord milking (UCM) at birth has been shown to improve iron stores in healthy term infants and may positively impact long-term neurodevelopmental outcomes. Infants who are non-vigorous at birth and at risk of developing hypoxic-ischemic encephalopathy (HIE) are particularly likely to benefit from placental transfusion. This process may offer neuroprotection by enhancing cardiopulmonary transition, supporting cardiac preload, improving systemic and cerebral perfusion, delivering stem cells and neurotrophic factors, and preventing iron deficiency. While DCC is not currently recommended for non-vigorous term …

Genome-Wide Discovery Of Multiple Sclerosis Genetic Risk Variant Allelic Regulatory Activity, Marissa Granitto, Lois Parks, Molly S Shook, Carmy Forney, Xiaoting Chen, Lee E Edsall, Omer A Donmez, Sreeja Parameswaran, Kristen S Fisher, Aram Zabeti, Lucinda P Lawson, Matthew T Weirauch, Leah C Kottyan

Faculty, Staff and Students Publications

Multiple sclerosis is an immune-mediated demyelinating disease of the central nervous system with a complex etiology involving environmental and genetic factors. Numerous genetic risk loci for multiple sclerosis have been nominated through genome-wide association studies, with most associated variants residing in noncoding regions. However, further work is needed to understand how genetic variation contributes to disease-related alterations to gene expression. Here, we use Massively Parallel Reporter Assays to identify genetic risk variants with genotype-dependent enhancing or silencing activity within a set of 14,275 variants distributed among multiple sclerosis risk loci that have reached genome-wide or suggestive significance. We applied our …

Genetic Architecture And Analysis Practices Of Circulating Metabolites In The Nhlbi Trans-Omics For Precision Medicine Program, Nannan Wang, Franklin P Ockerman, Laura Y Zhou, Megan L Grove, Taryn Alkis, John Barnard, Russell P Bowler, Clary B Clish, Shinhye Chung, Emily Drzymalla, Anne M Evans, Nora Franceschini, Robert E Gerszten, Madeline G Gillman, Scott R Hutton, Rachel S Kelly, Charles Kooperberg, Martin G Larson, Jessica Lasky-Su, Deborah A Meyers, Prescott G Woodruff, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Ramachandran S Vasan, Scott T Weiss, Kari E Wong, Alexis C Wood, Lang Wu, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Ronit Yarden, Thomas W Blackwell, Albert V Smith, Han Chen, Laura M Raffield, Bing Yu

Faculty, Staff and Students Publications

Circulating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. From our comparison of multiple methods, we provided a set of reasonable strategies for outlier and imputation handling to process metabolite data and show that inverse …

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 …

Use And Outcomes Of The Medical Hybrid Procedure For Stage 1 Palliation In Infants With Hypoplastic Left Heart Syndrome And Variants., Daniel N. Beauchamp, Christopher J. Statile, Huaiyu Zang, David A. Parra, Justin Godown, Natalie Jayaram, Matthew L. Moehlmann, Garick D. Hill

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Staged palliation of hypoplastic left heart syndrome and variants begins with the Norwood or hybrid procedure. Hybrid palliation is used in a minority of cases and often reserved for high-risk patients. Stented hybrid (SH) comprises bilateral pulmonary artery bands and ductal stenting, and medical hybrid (MH) comprises bilateral pulmonary artery bands and prostaglandins. MH use and outcomes have not been well described. We sought to compare MH, SH, and surgical stage 1 (SS1) using a national database.

METHODS: Patients from the National Pediatric Cardiology Quality Improvement Collaborative database born between 2016 and 2021 were categorized by initial intervention: MH, …

Global Trends And Forecast Of Cardiovascular Diseases, Cancer, And Shared Risk Factors: Insights From The Gbd 2021, Chieh Y Koo, Bryan Chong, Jayanth Jayabaskaran, Srinithy Nagarajan, Silingga M Jauhari, Yiming Chen, Li L Tan, Anurag Mehta, Muhammad S Khan, Mark Muthiah, Derek Hausenloy, A M Richards, Dennis T Ko, Christian D Mallen, Eric A Secemsky, Mark Y Chan, Paaladinesh Thavendiranathan, Nicholas W S Chew, Mamas A Mamas

Faculty, Staff and Students Publications

Background: Cardiovascular disease (CVD) and cancer share multiple risk factors and are the leading causes of morbidity and death worldwide. This study aims to examine historical and projected trends of the combined CVD-cancer global estimates and their shared risk factors.

Methods: Death and disability-adjusted life years (DALYs) associated with CVDs, cancers, and their risk factors were obtained from the GBD (Global Burden of Disease) 2021 study. Historical estimates from 1990 to 2021 and forecast data from 2025 to 2050 were examined across age groups, regions, sociodemographic index, and sex.

Results: In 2021, CVD-cancer resulted in age-standardized DALY rates of 8009 …

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 …

Factors Influencing 25-Year Survival In Pediatric Liver Transplant Recipients, Garrett Wortham, Megan Crawford, John Miggins, Chun-Sing Huang, John A Goss, Abbas Rana, Nhu Thao Galván

Faculty, Staff and Students Publications

Background: This study assesses the impact of cholestatic liver disease, including biliary atresia, on 25-year survival post-transplantation and additional factors influencing long-term outcomes after pediatric liver transplantation.

Methods: We conducted a retrospective analysis of pediatric liver transplant recipients (1987-1998) using de-identified data from the OPTN 2023 Liver Database. After exclusions for multi-organ transplants (n = 222), prior transplants (n = 2256), and deaths within 1 year (n = 526), 2429 patients remained, including 645 with cholestatic disease. Univariate and multivariate analyses identified factors associated with 25-year survival.

Results: A primary diagnosis of cholestatic disease was associated with improved 25-year survival …

From Pachymeningitis Hemorrhagica To Abusive Head Trauma: A Journey Through The Centuries, Oliver Berthold, Flora Blangis, Christopher Spencer Greeley

Faculty, Staff and Students Publications

The development of medical knowledge follows specific principles. These also apply to abusive head trauma. The seminal literature from the early 20th century is based on earlier research from Europe, which is fundamental to understand the evolution of understanding and nomenclature of abusive head trauma. A review of original medical literature on intracranial injuries in children, published in German, English, and French, was conducted using PubMed and Google Scholar for articles before 1950. The primary search focused on subdural hemorrhages and pachymeningitis in children, followed by a snowball search of references. Full texts of available manuscripts were reviewed. Primary literature …

Differences In Patient And Parent Preferences For Prognostic Communication Across Disease Milestones In Advanced Childhood Cancer, Rachel A Kentor, Shoshana Mehler, Caroline Christianson, Harmony Farner, Tara M Brinkman, Justin N Baker, Pamela S Hinds, Jennifer W Mack, Erica C Kaye

Faculty, Staff and Students Publications

Background: Navigating prognostic communication is challenging for clinicians caring for adolescents and young adults (AYAs) with poor-prognosis cancer. Presently, little is known about how AYA and parent preferences for prognostic disclosure evolve over time. This study explored communication preferences at key illness milestones of disease progression to inform individualized, person-centered approaches to optimize prognostic disclosure.

Procedure: Sixty-five participants, including 25 AYAs aged 12-25 years and 40 parents, were recruited at distinct illness timepoints-diagnosis, relapse/progression, Phase I/II trial enrollment, and bereavement-to participate in semi-structured interviews about their preferences for timing, style, and content of prognostic communication. Rapid analysis was conducted to …

Call To Action-Pediatric Masld Requires Immediate Attention To Curb Health Crisis, Phillipp Hartmann, Marialena Mouzaki, Sara Hassan, Mohit Kehar, Krupa R Mysore, Erin Mauney, Dieudonne Nonga, Sara Karjoo, Shilpa Sood, Andrea Tou, Christine Brichta, Rachel E Herdes, Nikhil Pai, Donna K Garner, Mary E Rinella, Mazen Noureddin, Zobair Younossi, Alina M Allen, Arun Sanyal, Taisa Kohut, Rohit Kohli, Charina M Ramirez, Stavra Xanthakos, Miriam B Vos, Jeffrey B Schwimmer, Samar H Ibrahim, Jennifer Panganiban

Faculty, Staff and Students Publications

Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a …

Parental Psychosocial Outcomes After A Positive Newborn Screen For A Lysosomal Storage Disorder., Courtney D. Berrios, Randi N. Gadea, Meghan Strenk, Twisha Nadella, Jennifer L. Gannon, Janelle R. Noel-Macdonnell Phd

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study explores the psychosocial impact of a positive newborn screen (NBS) result for four lysosomal storage disorders (LSDs) (Fabry disease, Krabbe disease, Mucopolysaccharidosis Type I, Pompe disease) across confirmatory results.

METHODS: Parents whose child who had a positive NBS for one of the included LSDs were recruited for a retrospective cohort (n = 80) or prospective, longitudinal cohorts (n = 50). Surveys assessed uncertainty, anxiety, intrusive or avoidant thoughts, and perceived vulnerability of their child's health. In-depth interviews explored the NBS experience and psychosocial response.

RESULTS: Participants experienced uncertainty and anxiety during confirmatory testing that improved as parents …

Beyond Seizures As An Outcome Measure: A Global Severity Scoring System For Cdkl5 Deficiency Disorder, Peter Jacoby, Eric D Marsh, Scott Demarest, Jacinta M Saldaris, Helen Leonard, Heather E Olson, Joni N Saby, Elia Pestana-Knight, Rajsekar Rajaraman, Dana Price, Judith Weisenberg, Bernhard Suter, Jenny Downs, Tim A Benke

Faculty, Staff and Students Publications

Background: CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease-modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated.

Methods: The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment-Clinician and -Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance …

A Rare Molecular Diagnosis In A Patient With Hepatocerebral Syndrome Contributes To The Expansion Of The Phenotypic Spectrum Of Polg2 -Related Mitochondrial Disorder, Vittoria Rossi, Dan Brooks, Hongzheng Dai, Elizabeth Mizerik, Karla Salazar, Daniel Davila-Williams, Yishay Ben-Moshe, Seema R Lalani, Sarah H Elsea, Charul Gijavanekar, Daryl A Scott, Keren Machol, Mir Reza Bekheirnia, Fernando Scaglia

Faculty, Staff and Students Publications

POLG2 encodes an accessory subunit in DNA polymerase gamma that is required for mitochondrial DNA synthesis. Monoallelic pathogenic variants in POLG2 are associated primarily with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant type 4 (PEOA4, MIM #610131). We report a rare case of severe infantile hepatocerebral syndrome associated with biallelic variants in POLG2. The proband, a 5-week-old female infant, presented with seizures and acute liver failure. Extensive metabolic workup, including untargeted metabolomics analysis and elevated plasma growth differentiation factor 15, was suggestive of mitochondrial dysfunction. Rapid trio genome sequencing identified compound heterozygous variants, a likely pathogenic variant and …

A Novel Approach To Calculating Expected Total Fetal Lung Volume In Fetuses With Isolated Congenital Diaphragmatic Hernia And Fetal Growth Restriction: A Theoretical Computational Simulation, Morcos Hanna, Jonathan Davies, Amaryllis Fernandes, Pamela M Ketwaroo, Amy R Mehollin-Ray, Roopali Donepudi, Alice King, Joseph Hagan, Sundeep G Keswani, Sharada H Gowda, Caraciolo J Fernandes

Faculty, Staff and Students Publications

Objectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.

Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to …

Using The Electronic Health Record To Facilitate Drug Allergy Delabeling., Matthew J Molloy, Adam P Yan, Averi E Wilson, Jonathan Beus, Lauren M Hess

Faculty, Staff and Students Publications

Purpose of review: There is a growing number of allergy delabeling programs across diverse clinical specialties and care settings. The electronic health record (EHR) can be leveraged to facilitate allergy delabeling. The purpose of this review is to describe EHR tools that have been used in allergy delabeling programs. We also provide recommendations for organizations considering EHR-based allergy delabeling workflows that incorporate clinical informatics best practices.

Recent findings: Recent literature describes several EHR tools used in delabeling. These tools can be organized around the steps of the allergy delabeling workflow: 1. Identify eligible patients, 2. Risk stratify, 3. Evaluation and …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Maia Madison, Katie Scandrett, Tara Ness, Pauline Amuge, Leeberk Raja Inbaraj, Mukesh Kumar Sathya Narayanan, Lucia González Fernández, Michael Eisenhut, Nazir Ismail, Alexei Korobitsyn, Sabine E Verkuijl, Annemieke Brands, Kerri Viney, Tiziana Masini, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

Background: In 2023, an estimated 1.3 million children (aged 0-14 years) became ill with tuberculosis, and 166,000 children (aged 0-15 years) died from the disease. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that detects Mycobacterium tuberculosis complex and rifampicin resistance. This is an update of a Cochrane review first published in 2020 and last updated in 2022. Parts of the current update informed the 2024 WHO updated guidance for the diagnosis of tuberculosis.

Objectives: To assess the diagnostic accuracy of Xpert Ultra for detecting pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and …

Defining Endotypes Of Bronchopulmonary Dysplasia In Preterm Infants To Improve Precision-Based Therapies., Megha Sharma, Gangaram Akangire, Noah H. Hillman, Winston M. Manimtim, Mark Ivan Attard, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Bronchopulmonary dysplasia (BPD) remains a debilitating disease in premature infants. The chronic pathogenesis of BPD with complex prenatal and postnatal programming challenges attempts at precisely defining or treating disease. While existing BPD definitions categorize disease severity, a lack of consideration of disease heterogeneity and endotypes has contributed to the failure of clinical trials to improve BPD outcomes. Recent studies have used advanced lung imaging techniques, echocardiography, and lung function tests to identify airway, parenchymal, and vascular BPD endotypes. These endotypes carry different prognoses and require endotype-specific treatment strategies to optimize infant outcomes. In this Review, we focus on the pathogenic …

A Hybrid Model For Youth Engagement In Adolescent Health Studies: Insights From The Teen Research Advisors Program At A Midwestern Pediatric Academic Medical Center In The United States., John Tumberger, Alaina N. Burns, Michael Bartkoski, Mariah E. Brewe, Amelia Whittier, Kendyll Gethers, Ailisi Bogdon, Emerie Peterson, Stephani L. Stancil

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Engaging adolescents in research ensures studies are relevant, ethical, and beneficial while fostering authentic and applicable findings. Traditional in-person advisory boards face barriers to equitable participation, highlighting the need for innovative, flexible models tailored to specific research programs and individuals with lived experience. The primary aim of this article is to describe a novel hybrid youth advisory board suitable for informing ongoing operations of a research program while supporting youths' education and career exploration. Our secondary aim was to evaluate initial impact over the first 2 years of the program (2023-2024).

METHODS: Adolescents aged 12-21 with prior involvement in …

Everolimus And Low-Dose Tacrolimus After Heart Transplant In Children: A Randomized Clinical Trial, Christopher S Almond, Kevin P Daly, Erin L Albers, Juan C Alejos, Rebecca Ameduri, Scott R Auerbach, Lynsey Barkoff, Aliessa P Barnes, Matthew J Bock, Arene Butto, Waldemar F Carlo, Chesney D Castleberry, Maryanne R Chrisant, Shriprasad R Deshpande, William J Dreyer, Melanie D Everitt, Brian Feingold, Selena Gonzales, Seth A Hollander, Steven J Kindel, Gloria L Klein, Ashwin K Lal, Jacqueline M Lamour, Joanne Lee, Minmin Lu, Irene D Lytrivi, Shelley D Miyamoto, Elfriede Pahl, David M Peng, Thomas D Ryan, Tajinder P Singh, Jennifer A Su, David L Sutcliffe, A Marian Ybarra, Steven Zangwill, Joseph W Rossano, Lynn A Sleeper

Faculty, Staff and Students Publications

Importance: Studies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.

Objective: To evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in …