Pediatrics Commons^™

Neuroanatomical Features Of Naa10 And Naa15-Related Neurodevelopmental Syndromes, Rahi Patel, Rikhil Makwana, Carolina Christ, Elaine Marchi, Christina Y Miyake, Fabricio Guimaraes Goncalves, Gholson J Lyon, Matthew T Whitehead

Faculty, Staff and Students Publications

Background: NAA10-related and NAA15-related neurodevelopmental (ND) syndromes present with intellectual disability, hypotonia, cardiac abnormalities, and delayed development. While data exists on the clinical manifestations of these conditions, there are few reports describing the neuroanatomical abnormalities present on imaging.

Objective: We aim to provide neuroimaging analyses for a subset of probands with NAA10- and NAA15-related neurodevelopmental symptoms and assess the severity and number of neuroanatomical anomalies and their associated functional impairments to better understand the pathophysiology of these disease processes.

Materials and methods: Neuroimaging studies were obtained from 26 probands (18 with pathogenic variants in NAA10, 8 with pathogenic variants in …

Plasma Microbial Cell-Free Dna Sequencing For The Detection Of Kingella Kingae Pediatric Spinal Infections, Asim A Ahmed, Sarah Y Park, Matthew J Smollin, Martin S Lindner, Adriana Sarmiento Clemente, Ana Del Valle Penella, P Marcelo Laufer, Carolina Sanchez-Vegas, Manuel R Cotilla, Marian E Melish, Connie Trieu, Nazia A Kabani, Joshua Cooper, Audrey R Lloyd, David W Kimberlin, John C Arnold, Alejandro Jordan-Villegas, Lori E Patterson, Catherine E Foster, Pablo Yagupsky

Faculty, Staff and Students Publications

Background: Diagnosis of Kingella kingae skeletal system infections is made challenging by the microbe's fastidious nature. Detection and quantification of circulating microbial cell-free DNA (mcfDNA) in plasma by the Karius Test, a commercial metagenomic sequencing test, may offer promise in diagnosing pediatric spinal infections caused by difficult-to-culture organisms such as K. kingae .

Methods: Plasma mcfDNA sequencing detections of K. kingae from April 2018 to December 2020 were reviewed to identify pediatric (age < 18 years) patients. Medical charts of those with spinal infections were reviewed, and mcfDNA sequencing diagnostic performance was compared with usual care tests (ie, cultures, polymerase chain reaction).

Results: Ten children with K. kingae spinal infections were identified across 7 institutions. The median age was 16.5 months (range 11-23 months). All case-patients had vertebral osteomyelitis …

Identification Of Surrogate Biomarkers For Mucopolysaccharidosis Type Iva, Yasuhiko Ago, Shaukat Khan, Kimberly Klipner, Allison Bradford, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 …

Trajectories Of Attention Problems In Preschoolers Born Very Preterm., Marie Camerota, Francisco Xavier Castellanos, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Thomas Michael O'Shea, Carmen J. Marsit, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children born preterm are at heightened risk for neurodevelopmental impairment, including specific deficits in attention. Few studies have investigated change over time in attention problems prior to school entry. The current study aims to describe trajectories of attention problems from age 2 through 5 years in a cohort of children born(GA), identify sociodemographic, medical, and neurobehavioral characteristics associated with attention trajectories, and test whether attention problem trajectories predict the risk of a reported attention-deficit/hyperactivity disorder (ADHD) diagnosis.

METHODS: We studied 608 infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a prospective, multisite study of …

Long-Term Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Children: An Open-Label Active Treatment (Realise Study), Jacqueline A Pongracic, Rémi Gagnon, Gordon Sussman, Dareen Siri, Roxanne C Oriel, Terri F Brown-Whitehorn, Sara Anvari, William E Berger, J Andrew Bird, Edmond S Chan, R Sharon Chinthrajah, Hey J Chong, Stanley M Fineman, David M Fleischer, Erika Gonzalez-Reyes, Edwin H Kim, Bruce J Lanser, Andrew Macginnitie, Hemalini Mehta, Daniel Petroni, Ned Rupp, Lynda C Schneider, Amy M Scurlock, Lawrence D Sher, Wayne G Shreffler, Sayantani B Sindher, Robert Wood, William H Yang, Hugh A Sampson, Timothée Bois, Todd D Green, Dianne E Campbell, Katharine J Bee, Philippe Bégin

Faculty, Staff and Students Publications

Background: Owing to limited treatment options for peanut allergy, patients remain at risk for allergic reactions due to accidental exposure. Epicutaneous immunotherapy (EPIT) is a novel treatment being investigated for peanut allergy.

Objective: This study assessed long-term safety of EPIT with VIASKIN peanut patch 250 μg (VP250) via an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial.

Methods: REALISE was a phase 3 trial in peanut-allergic children aged 4 through 11 years that included a 6-month, randomized, double-blind, placebo-controlled treatment phase, followed by an open-label, single-arm, active treatment period for up to 36 months.

Results: …

Feasibility And Acceptability Of The Team Pilot Trial With African American And Latino Families, Ashley M Butler, Marisa E Hilliard, Krystal Christopher, Marissa Baudino, Charles Minard, Lefkothea Karaviti

Faculty, Staff and Students Publications

Objective: We adapted the empirically supported Family Teamwork intervention protocol to support collaborative parent involvement in type 1 diabetes (T1D) management among African American and Latino parents of children with T1D. This randomized pilot study aimed to evaluate feasibility and acceptability of the Type 1 Diabetes Empowerment and Management (TEAM) intervention.

Methods: African American and Latino parents (n = 59; 65% recruitment rate) of youth (ages 5-10 years, M = 8.9 ± 1.6 years; 59% female, M hemoglobin A1c 9.0% ± 1.9%) with diabetes duration of ≥1 year and who were fluent in English and not planning to leave the …

Efficacy And Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Toddlers: Open-Label Extension To Epitope, Matthew Greenhawt, Deborah Albright, Sara Anvari, Nicolette Arends, Peter D Arkwright, Philippe Bégin, Katharina Blümchen, Terri Brown-Whitehorn, Heather Cassell, Edmond S Chan, Christina E Ciaccio, Antoine Deschildre, Amandine Divaret-Chauveau, Stacy Dorris, Morna Dorsey, George Du Toit, Thomas Eiwegger, Michel Erlewyn-Lajeunesse, David M Fleischer, Lara S Ford, Maria Garcia-Lloret, Jonathan O'B Hourihane, Nicola Jay, Stacie M Jones, Edwin H Kim, Kirsten Kloepfer, Stephanie Leonard, Guillaume Lezmi, Jay Lieberman, Jeanne Lomas, Melanie Makhija, Michael O'Sullivan, Christopher Parrish, Jane Peake, Kirsten P Perrett, Daniel Petroni, Jacqueline A Pongracic, Patrick Quinn, Rachel G Robison, Georgiana Sanders, Lynda Schneider, Hemant Sharma, Sayantani B Sindher, Juan Trujillo, Paul J Turner, Katherine Tuttle, Julia Upton, Pooja Varshney, Brian P Vickery, Christian Vogelberg, Brynn Wainstein, Julie Wang, Robert Wood, Katharine J Bee, Dianne E Campbell, Todd D Green, Rihab Rouissi, Henry T Bahnson, Timothée Bois, Hugh A Sampson, A Wesley Burks

Faculty, Staff and Students Publications

Background: The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN patch containing 250 μg of peanut protein (VP250), previously reported significant treatment response versus placebo in peanut-allergic toddlers aged 1 through 3 years.

Objective: To assess the interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study.

Methods: Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFCs) and safety assessments; here we report the first-year OLE (year 2) results.

Results: A total …

Testing For Bleeding Disorders In Child Abuse: Aap Recommendation Adherence And Testing Results, Lyndsey Hultman, Angela Doswell, Henry T Puls, Shannon L Carpenter, Angela Bachim, Caitlin R Mcnamara, Farah W Brink, Lori D Frasier, Nancy S Harper, Natalie Laub, Kristine A Campbell, Daniel M Lindberg, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Objectives: Using a multicenter child abuse pediatrics research network (CAPNET), the study objectives were to characterize the adherence to American Academy of Pediatrics (AAP) recommendations for bleeding disorder testing and the frequency of bleeding disorder identification.

Methods: We performed a descriptive study of bleeding disorder evaluations among children younger than 10 years of age who presented with bruising and/or intracranial hemorrhage (ICH) concerning for abuse from February 2021-May 2022 utilizing CAPNET. Cases were classified as bruising without ICH or ICH with or without bruising. Based on AAP guidance, testing was not recommended in cases with concomitant suspicious injuries, inflicted injury …

Nutrition Provision In Pediatric Extracorporeal Membrane Oxygenation: Evidence, Challenges, And Clinical Considerations, Marwa Mansour, Nicole Knebusch, Andrea Ontaneda, Stephanie Vazquez, Jennifer Daughtry, Katri Typpo, Jorge A Coss-Bu

Faculty, Staff and Students Publications

Background/objectives: Nutritional support is a critical yet challenging aspect of care for pediatric patients requiring extracorporeal membrane oxygenation (ECMO). Malnutrition is prevalent in this population and is associated with worse clinical outcomes. This review synthesizes current evidence on nutritional strategies for pediatric ECMO patients, emphasizing assessment methods, feeding routes, challenges, and clinical outcomes.

Methods: A literature review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published between January 2010 and 2025. Keywords included "pediatric ECMO", "nutrition", "enteral feeding", and "parenteral nutrition". Studies addressing nutritional assessment, enteral and parenteral feeding practices, and their impact on clinical …

Parapneumonic Empyema Complicating Community-Acquired Pneumonia: Etiology In The Era Of Pneumococcal Vaccination And Role Of Molecular Diagnosis, Antonio C Arrieta, Stephanie Osborne, Lindsay R Grant, Bradford D Gessner, Anne J Blaschke, Kristina G Hulten, Delma J Nieves, Ashley Miller, Cody Bender, Raul Isturiz, Ronika Alexander, Shannon M Nielsen, Linda B Lamberth, Alejandro Cane, Adriano Arguedas

Faculty, Staff and Students Publications

Background: Impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease is well described; pneumococcus is infrequently identified by culture in pneumonia. Yield is higher when pleural fluid is cultured. Polymerase chain reaction (PCR) in pleural fluid samples improves pathogen identification, particularly in the case of S. pneumoniae.

Methods: Healthy children with empyema who underwent pleural fluid drainage were eligible. Demographics and PCV immunization status were collected. Blood/pleural fluid cultures were obtained. Pleural fluid samples were sent for PCR for pathogen. Serotyping was done by Neufeld-Quellung reaction on pneumococcus isolates, and PCR in culture negative cases.

Results: From December 2018 to …

Combined Systemic Immunotherapy And Intrathecal Dexamethasone In Febrile Infection Related Epilepsy Syndrome, Kristen S Fisher, Alexander Ankar, Jon Cokley, Eyal Muscal, James J Riviello, Yi-Chen Lai

Faculty, Staff and Students Publications

Febrile infection related epilepsy syndrome (FIRES) is a rare presentation of refractory status epilepticus with immune dysregulation as a potential pathologic mechanism. Despite promising results from second-line immunomodulators, approximately 30% remain refractory to treatment. We describe two children with FIRES who were unable to wean from anesthetic infusions with immunomodulatory treatment and subsequently received concurrent intrathecal dexamethasone and anakinra/tocilizumab as escalation of therapy. Following the initiation of this combined regimen, anesthetic infusions were decreased while maintaining seizure freedom. These cases demonstrate proof of principle that a multi-modal approach may be beneficial and should be considered in the treatment of FIRES.

Comparing Rituximab And Cyclophosphamide In Induction Therapy For Childhood-Onset Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An Archive Registry Cohort Study, Samuel J Gagne, Vidya Sivaraman, Else S Bosman, Brett Klamer, Kimberly A Morishita, Adam Huber, Alvaro Orjuela, Barbara Eberhard, Charlotte Myrup, Dana Gerstbacher, Dirk Foell, Eslam Al-Abadi, Flora Mcerlane, Kathryn Cook, Linda Wagner-Weiner, Melissa Elder, L Nandini Moorthy, Paul Dancey, Rae Yeung, Raju Khubchandani, Samundeeswari Deepak, Sirirat Charuvanij, Stacey Tarvin, Susan Shenoi, Tamara Tanner, Kelly Brown, David A Cabral, Archive Investigators Network Within The Pedvas Initiative

Faculty, Staff and Students Publications

Objective: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction of GPA and MPA. Disease rarity has limited feasibility of similar trials with pediatric patients. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for patients with childhood GPA and MPA through registry-based comparative evaluation.

Methods: From A Registry of Childhood Vasculitis, we identified patients with GPA and MPA who received induction with RTX or CYC. Pediatric Vasculitis Activity Score (PVAS) and Pediatric Vasculitis Damage Index …

Variability In Treatment Of Utis In Children With Genitourinary Anomalies In Children's Hospitals, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Sanyukta Desai, Pearl W Chang, Michael J Tchou, John M Morrison, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Cynthia Abou Zeid, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

Objective: In children with urinary tract anomalies, febrile urinary tract infections (UTIs) are associated with increased risks of sepsis, hospitalization, and kidney injury. However, the best treatment strategies are unknown. We aimed to describe antibiotic treatment practices and outcomes for UTIs in children with urinary tract anomalies and evaluate whether variability in UTI treatment exists between hospitals.

Methods: We conducted a multicenter retrospective cohort study of children seen in emergency departments (EDs) in 6 free-standing US children's hospitals from January 1, 2017, through December 31, 2018. We included children aged 0-17 years with an anatomic or functional urinary tract anomaly …

Comparison Of Syndromic Surveillance And Hospital Discharge Data For Unintentional Drowning In Metropolitan Houston, Texas, Usa, Nicholas Peoples, Jennifer L Jones, Elizabeth A Camp, Ned Norman Levine, Rohit P Shenoi

Faculty, Staff and Students Publications

Background: Syndromic surveillance, which provides real-time data, may provide timely drowning surveillance compared with hospital discharge data where the release of data may be delayed. We compared data on hospital visits for unintentional drowning identified in hospital discharge and syndromic surveillance data sets for accuracy and completeness.

Methods: We compared data for hospital visits for unintentional drowning identified in the Texas Health Care Information Collection hospital discharge and syndromic surveillance data sets for metropolitan Houston, Texas, USA from 2019 to 2021. Hospital visits included emergency department-only visits and hospital admissions. We compared time-series visualisation of hospital visits between data sets. …

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.

Comprehensive Assessment Reveals Numerous Clinical And Neurophysiological Differences Between Mecp2-Allelic Disorders, Davut Pehlivan, Chengjun Huang, Holly K Harris, Christine Coquery, Aditya Mahat, Mirjana Maletic-Savatic, Laurence Mignon, Sukru Aras, Daniel G Glaze, Charles S Layne, Leonardo Sahelijo, Huda Y Zoghbi, Matthew J Mcginley, Bernhard Suter

Faculty, Staff and Students Publications

OBJECTIVE: Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS.

MATERIALS AND METHODS: We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8-10 months apart.

RESULTS: We identified numerous clinical and physiological …

Effectiveness Of The Primary Bacillus Calmette-Guérin Vaccine Against The Risk Of Mycobacterium Tuberculosis Infection And Tuberculosis Disease: A Meta-Analysis Of Individual Participant Data, Puck T Pelzer, Logan Stuck, Leonardo Martinez, Alexandra S Richards, Carlos Acuña-Villaorduña, Naomi E Aronson, Maryline Bonnet, Anna C Carvalho, Pei-Chun Chan, Li-Min Huang, Chi-Tai Fang, Gavin Churchyard, Helena Del Corral-Londoño, Manjula Datta, Marcos A Espinal, Katherine Fielding, Andrew J Fiore-Gartland, Alberto Garcia-Basteiro, Willem Hanekom, Mark Hatherill, Phillip C Hill, Helena Huerga, Edward C Jones-López, Afranio Kritski, Anna M Mandalakas, Punam Mangtani, Eduardo Martins Netto, Harriet Mayanja, Rufaida Mazahir, Megan Murray, Molebogeng Rangaka, Thomas Scriba, Jitendra Singh, Sarman Singh, Catherine M Stein, Johan Vekemans, Lilly M Verhagen, Julian A Villalba, Anne Wajja, Basilea Watson, Richard G White, Frank G J Cobelens

Faculty, Staff and Students Publications

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

Methods: We conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, M tuberculosis infection test (QuantiFERON …

Resurgence Of Pediatric Mycoplasma Pneumoniae Infections In Southeast Texas, November 2023-June 2024, Margaret Taylor Danner, Heather Colvin Binns, Khanh Nguyen, Coreen Johnson, Jim Dunn, Denver Niles, Diana K Nguyen

Faculty, Staff and Students Publications

We conducted a retrospective review of children tested for Mycoplasma pneumoniae from January 1, 2020 to June 30, 2024. M. pneumoniae polymerase chain reaction positivity increased starting in November 2023, peaking at 18.3% in June 2024. During the resurgence, children with laboratory-confirmed infection often had severe respiratory disease or extrapulmonary manifestations.

An Observational Study Of Discourse Tasks And Running Speech Sampling In The Assessment Of Paediatric Voice Quality, Victoria Reynolds, Kristin Scavo-Smith, Kate Oteng-Bediako, Sophie Scanlon

Speech-Language Pathology Faculty Publications

Introduction

Running speech sampling is an essential component of a paediatric voice evaluation, in that it should provide the examiner with a representative vocal sample of the child's everyday voice use outside of the clinic setting. Current speech sampling practices, consisting of reading tasks, informal conversation sampling and the voice question ('Tell me about your voice problem'), may not elicit consistent samples or samples of sufficient length to allow the examiner to make a reliable and valid judgement about vocal quality. The aim of this study is to compare the voice quality of children produced in response to existing running …

Efficacy And Safety Of Once-Daily Roflumilast Cream 005% In Pediatric Patients Aged 2-5 Years With Mild-To-Moderate Atopic Dermatitis (Integument-Ped): A Phase 3 Randomized Controlled Trial, Lawrence F Eichenfield, Rocco Serrao, Vimal H Prajapati, John C Browning, Lisa Swanson, Tracy Funk, Mercedes E Gonzalez, Adelaide A Hebert, Mark Lee, Mark Boguniewicz, Eric L Simpson, Melissa S Seal, David Krupa, Diane Hanna, Scott Snyder, Patrick Burnett, David H Chu, Erin Almaraz, Robert C Higham, David R Berk

Faculty, Staff and Student Publications

Background/objectives: Efficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel-group, double-blind trial (INTEGUMENT-PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2-5 years with AD.

Methods: Patients aged 2-5 years with mild-to-moderate AD were treated with once-daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2-grade improvement from baseline) at Week …

Detection Of Viral Rna And Dna And Immune Response Following Administration Of Live Attenuated Measles And Varicella Vaccines In Children With Chronic Liver Disease, Sarah Kemme, Jennifer D Canniff, Krystle M Garth, Shaobing Li, Krupa Mysore, Adriana Weinberg, Amy G Feldman

Faculty, Staff and Students Publications

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all …

Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, Isabel Haviland, Ralph D Hector, Lindsay C Swanson, Aubrie Soucy Verran, Emma Sherrill, Zoë Frazier, Annemarie M Denny, Jenna Lucash, Bo Zhang, Holly A Dubbs, Eric D Marsh, Judith L Weisenberg, Helen Leonard, Milena Crippa, Francesca Cogliati, Silvia Russo, Bernhard Suter, Rajsekar Rajaraman, Alan K Percy, John M Schreiber, Scott Demarest, Timothy A Benke, Maya Chopra, Timothy W Yu, Heather E Olson

Faculty, Staff and Students Publications

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 …

Impact Of Elevated Serum Triglycerides On Children With Acute Recurrent Or Chronic Pancreatitis From Insppire-2, Zachary M Sellers, Matthew J Giefer, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Z Cohen, Elissa M Downs, Douglas S Fishman, A Jay Freeman, Cheryl E Gariepy, Tanja Y Gonska, Amit S Grover, Doug 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, Madhura Y Phadke, Wenly Ruan, Sarah Jane Schwarzenberg, David M Troendle, Michael Wilschanski, 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

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (< 150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed.

Results: In children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic …

Hypertriglyceridemia In New-Onset Type 1 Pediatric Diabetes, Colleen A Macke, Iman Al-Gadi, Nidhi Bansal, Sarah K Lyons, Aikaterini A Nella

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new-onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single-center experience on severe HTG in pediatric patients with new-onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with …

Transition To Enteral Triazole Antifungal Therapy For Pediatric Invasive Candidiasis: Secondary Analysis Of A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Robert F T Bucayu, Craig L K Boge, Inci Yildirim, Martha Avilés-Robles, Surabhi B Vora, David M Berman, Tanvi S Sharma, Lillian Sung, Elio Castagnola, Debra L Palazzi, Lara Danziger-Isakov, Dwight E Yin, Emmanuel Roilides, Gabriela Maron, Alison C Tribble, Pere Soler-Palacin, Eduardo López-Medina, José Romero, Kiran Belani, Antonio C Arrieta, Fabianne Carlesse, Dawn Nolt, Natasha Halasa, Daniel Dulek, Sujatha Rajan, William J Muller, Monica I Ardura, Alice Pong, Blanca E Gonzalez, Christine M Salvatore, Anna R Huppler, Catherine Aftandilian, Mark J Abzug, Arunaloke Chakrabarti, Michael Green, Irja Lutsar, Elizabeth D Knackstedt, Sarah K Johnson, William J Steinbach, Brian T Fisher, Rachel L Wattier

Faculty, Staff and Students Publications

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.

Whispers In The Wind: Face Mask Sampling For Mycobacterium Tuberculosis Detection In Children With Pulmonary Tuberculosis, Lennard Meiwes, Irina Kontsevaya, Dumitru Chesov, Stela Kulciţkaia, Viola Dreyer, Doris Hillemann, Qiniso Dlamini, Caroline Williams, Michael Barer, Folke Brinkmann, Renate Krüger, Stephanie Thee, Alexander Kay, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods: Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results: Experiments with H37Ra M. …

The Study Of The Epidemiology Of Pediatric Hypertension Registry (Superhero): Rationale And Methods, Andrew M South, Victoria C Giammattei, Kiri W Bagley, Christine Y Bakhoum, William H Beasley, Morgan B Bily, Shupti Biswas, Aaron M Bridges, Rushelle L Byfield, Jessica Fallon Campbell, Rahul Chanchlani, Ashton Chen, Lucy D'Agostino Mcgowan, Stephen M Downs, Gina M Fergeson, Jason H Greenberg, Taylor A Hill-Horowitz, Elizabeth T Jensen, Mahmoud Kallash, Margret Kamel, Stefan G Kiessling, David M Kline, John R Laisure, Gang Liu, Jackson Londeree, Caroline B Lucas, Sai Sudha Mannemuddhu, Kuo-Rei Mao, Jason M Misurac, Margaret O Murphy, James T Nugent, Elizabeth A Onugha, Ashna Pudupakkam, Kathy M Redmond, Sandeep Riar, Christine B Sethna, Sahar Siddiqui, Ashley L Thumann, Stephen R Uss, Carol L Vincent, Irina V Viviano, Michael J Walsh, Blanche D White, Robert P Woroniecki, Michael Wu, Ikuyo Yamaguchi, Emily Yun, Donald J Weaver

Faculty, Staff and Students Publications

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research, such as small sample sizes, reliance on manual record review, and limited analytic methods, that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite, retrospective registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases, 10th …

Brain Gray Matter Changes In Children At Risk For Sudden Unexpected Death In Epilepsy, Bhaswati Roy, Jennifer A Ogren, Luke A Allen, Beate Diehl, Raman Sankar, Samden D Lhatoo, Rajesh Kumar, Ronald M Harper

Faculty, Staff and Student Publications

Background: Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children.

Methods: We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP. …

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …

Machine Learning-Based Prediction Model For Icu Mortality After Continuous Renal Replacement Therapy Initiation In Children, Sameer Thadani, Tzu-Chun Wu, Danny T Y Wu, Aadil Kakajiwala, Danielle E Soranno, Gerard Cortina, Rachana Srivastava, Katja M Gist, Shina Menon, Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Diseases (We-Rock) Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.

OBJECTIVE: We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.

DERIVATION COHORT: Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%).

VALIDATION COHORT: Internal validation occurred in a testing group of patients from the dataset (20%).

PREDICTION MODEL: Retrospective international …