Medical Specialties Commons^™

Timing And Mode Of Death Following Treatment Of Neonatal Symptomatic Tetralogy Of Fallot, Sara M Trucco, Yun Zhang, Andrew C Glatz, Michael L O'Byrne, Christopher J Petit, Athar M Qureshi, Jeffrey D Zampi, Shabana Shahanavaz, George T Nicholson, Allen Ligon, Jennifer C Romano, Shiraz A Maskatia, Jeffery J Meadows, Christopher Mascio, Jay Patel, Kathryn Stack, Asaad G Beshish, Mark Law, Sarosh P Batlivala, Jeannette Wong-Siegel, Kristal Hock, Sarah Speed, Hala Khan, Disha Goel, Courtney Mccracken, Bryan H Goldstein

Faculty, Staff and Students Publications

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, using a staged or primary repair strategy. Postprocedural mortality risk within this group is considerable. The mode of death and associated factors have been inadequately defined in early childhood mortality following treatment of sTOF. This study aims to describe the timing, cause, and associated risk factors of postprocedural death in infants with sTOF.

Methods: Neonates with sTOF who had an initial intervention from 2005 to 2017 at 9 centers of the Congenital Cardiac Research Collaborative were reviewed. Among nonsurvivors, details regarding timing, cause of death, and last …

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, …

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 …

National Alliance Of Sickle Cell Centers Consensus Recommendations On Sickle Cell Disease Health Maintenance: A Consensus Statement, Seethal A. Jacob, Melissa Frei-Jones, Sana Saif-Ur-Rehman, Monica L. Hulbert, Andrew R. W. O'Brien, Crawford Strunk, Anthony Villella, Ravi Talati, Amma Owusu-Ansah, Francis Coyne, Patrick T. Mcgann, Parul Rai, Robin Miller, Angeli Rampersad, Vishwas Sakhalkar, Neha Bhasin, Deepa Manwani, Sophie Lanzkron, Julie Kanter

Cardeza Foundation for Hematologic Research

IMPORTANCE: The most common inherited blood disorder in the world, sickle cell disease (SCD) is a known global health concern. While survival of children into adulthood has improved significantly over the last few decades in high-resource countries, substantial gaps in care standards and limited practice harmonization persist.

OBJECTIVE: To provide up-to-date recommendations for preventive care and treatment of all people living with SCD and its related comorbidities.

EVIDENCE REVIEW: As part of the National Alliance of Sickle Cell Centers (NASCC), 41 pediatric and adult sickle cell disease experts developed consensus standards and recommendations based on available evidence and expert consensus …

Acute Kidney Injury Is Associated With Elevated Urinary Endotrophin, Amanda J Clark, Brenda Mendoza Flores, Marie Christelle Saade, Kyle Q Vu, Isaac J Pence, Ningyan Zhang, Zhiqiang An, Dawei Bu, Philipp E Scherer, Samir M Parikh

Faculty, Staff and Student Publications

Acute kidney injury (AKI) is prevalent among hospitalized patients. Novel biomarkers are needed to diagnose AKI and target therapies. Endotrophin (ETP) is a molecule released during collagen type VI formation that may promote injury and fibrosis. Although serum ETP elevation has been associated with adverse outcomes in AKI, urinary ETP has not been assessed in AKI, nor has ETP been evaluated in a pediatric population. Urine samples were collected from a tertiary children's hospital. Medical records were reviewed, and patients who met criteria were sorted into three categories:

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 …

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 …

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 …

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 …

Predictors Of Response To Emergent Therapies In Paediatric Immune Thrombocytopenia, Candelaria O'Farrell, Taylor M Luckie, Matthew J Willis, Susan E Kirk, Brandon R Lucari, Michael E Scheurer, Xiaotian Gao, Amanda B Grimes

Faculty, Staff and Students Publications

Emergent therapies (ET), which include intravenous immunoglobulin (IVIG), corticosteroids and intravenous anti‐Rho(D) immunoglobulin, are used to treat acute episodes of bleeding in children with immune thrombocytopenia (ITP). There are currently no known biomarkers or clinical features predictive of treatment response to any specific ET. Thus, the treatment of ITP remains largely trial and error, exposing patients to potentially ineffective medications, which are often expensive and associated with adverse effects. We therefore sought to identify the predictors of treatment response through comparison of clinical characteristics in paediatric patients with ITP responsive to ET versus those non‐responsive to ET. We identified high …

Colorectal-Specific Radiation Dose And Chemotherapy Risk For Subsequent Colorectal Malignancies In Childhood Cancer Survivors: A Childhood Cancer Survivor Study (Ccss) Report, Constance A Owens, Ethan B Ludmir, Qi Liu, Weiyu Qiu, Aashish C Gupta, Susan A Smith, Bastien Rigaud, Kristy K Brock, James E Bates, Taylor G Meyers, Arnold C Paulino, Christine B Peterson, Stephen F Kry, Jop C Teepen, Cécile M Ronckers, Joseph P Neglia, Wendy M Leisenring, Kevin C Oeffinger, Paul C Nathan, Lucie M Turcotte, David C Hodgson, Melissa M Hudson, Leslie L Robison, Chaya S Moskowitz, Gregory T Armstrong, Tara O Henderson, Yutaka Yasui, Rebecca M Howell

Faculty, Staff and Student Publications

Purpose: Among childhood cancer survivors, we evaluated not previously explored relationships between colorectal subsequent malignant neoplasm (SMN) incidence and colorectum-specific radiation dose metrics currently used in radiation therapy (RT) planning and expanded upon previously reported chemotherapy associations.

Methods: The Childhood Cancer Survivor Study (CCSS) includes 5-year survivors of childhood cancer diagnosed between 1970 and 1999. RT was assessed as mean colorectal dose (MCD) and the percent volume (VX Gy) receiving ≥5, 10, 20, 30, and 40 Gy. Chemotherapy was assessed as cumulative doses for procarbazine and platinum agents, cyclophosphamide-equivalent doses for alkylating agents, and doxorubicin-equivalent doses for anthracyclines. Piecewise-exponential models …

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 …

Genome-Wide Association Study Of Childhood B-Cell Acute Lymphoblastic Leukemia Reveals Novel African Ancestry-Specific Susceptibility Loci, Cindy Im, Andrew R Raduski, Lauren J Mills, Kashi Raj Bhattarai, Robert J Mobley, Kelly R Barnett, Zhanni Lu, Kenneth Liao, Nathan Anderson, Rebecca A Johnson, Erica Langer, Anthony J Hooten, Alix E Seif, Kathrin M Bernt, Matthew Tsang, Brandon A Mamou, Luis Gil-De-Gómez, Julie A Wolfson, Danielle N Friedman, Neerav Shukla, Laura J Klesse, Erin L Marcotte, Lingyun Ji, Alice Dang, Minjie Luo, Yiming Zhong, Jalen Langie, Charleston W K Chiang, Adam De Smith, Joseph L Wiemels, Andrew Dewan, Xiaomei Ma, Catherine Metayer, Zhaoming Wang, Heather H Nelson, Nathan Pankratz, Tianzhong Yang, Saonli Basu, Lucie M Turcotte, Jun J Yang, Daniel Savic, Michael E Scheurer, Logan G Spector

Faculty, Staff and Students Publications

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Given racial/ethnic differences in incidence and outcomes, B-ALL genome-wide association studies among children of African ancestry are needed. Leveraging multi-institutional datasets with 840 African American children with B-ALL and 3360 controls, nine loci achieved genome-wide significance (P <  5 × 10−8) after meta-analysis. Two loci were established trans-ancestral susceptibility regions (IKZF1, ARID5B), while the remaining novel loci were specific to African populations. Five-year overall survival among children carrying novel risk alleles was significantly worse (83% versus 96% in non-carriers, P = 4.8 × 10−3). Novel risk variants were also associated with subtype-specific disease (P <  0.05), including higher susceptibility for a subtype overrepresented in African American children (TCF3-PBX1) and lower …

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 …

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Ambient Fine Particulate Matter, Residential Greenness, And Childhood Cancer Risk By Trimester Of Exposure In Minnesota 2000 To 2014: A Case-Control Study, Cassandra J Clark, David Haynes, Zhanni Lu, Jeannette M Sample, Laura A Mcguinn, Thanh T Hoang, Philip J Lupo, Michael E Scheurer, Erin L Marcotte, Lindsay A Williams

Faculty, Staff and Students Publications

Background: Outdoor air pollution is a suspected risk factor for childhood cancer, and there is some evidence that greenness may reduce cancer risk. We examined relationships between prenatal exposure to ambient fine particle air pollution [particulate matter < 2.5 µg/m3 (PM2.5)], greenness, and childhood cancer risk in Minnesota.

Methods: Cases included individuals born in the state of Minnesota and reported to the Minnesota Cancer Reporting System between 2000 and 2014 (n = 1272, ages 0-14 years at diagnosis) and birth year-matched cancer-free controls (n = 5245). We used Network Common Data Form to estimate monthly PM2.5 exposure and the normalized difference vegetation index for census tract-level greenness. We estimated ORs and …

High Prevalence Of Abnormal Baseline Lung Function In Pediatric And Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report From The Transpire Study, Jane Koo, Richard Cooper, Stephanie L Edwards, Adam Lane, Sara Katherine Loveless, Lauren Strecker, Kelly E Lake, Kasiani C Myers, Christopher Towe, Jessica Patti, Laura L Walkup, Kathryn A Wikenheiser-Brokamp, Margaret L Macmillan, Philip Lacher, Tamara Griffin, Merve Tekman, Gabriel Salinas Cisneros, Kevin Wu, Matthew S Zinter, Fernando A Urrego, K Scott Baker, Matthew F Abts, Sheri Ballard, Jason L Freedman, Alexander Caraballo, Lisa R Young, Maureen B Josephson, Julian L Allen, Devaney M Camburn, Erin E Doherty, Mashid Sababi Azamian, Martha Arredondo, Manuel Silva-Carmona, Leslie E Lehmann, Wai Wong, Jonathan M Gaffin, William Mcalpine, Mona Li, Samuel B Goldfarb, Jason C Woods, Stella M Davies

Faculty, Staff and Students Publications

Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.

Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.

Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), …

Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).

Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.

Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …

Single Cell Sequencing Analysis Of Respiratory Syncytial Virus-Infected Pediatric And Adult Human Nose Organoids Reveals Age Differences, Proliferative Diversity And Identifies Novel Cellular Tropism, Anubama Rajan, Divya Nagaraj, Carolyn Bomidi, Gina M Aloisio, Ashley M Murray, Emily M Schultz, Amal Kambal, Mary K Estes, Erin Nicholson, Vasanthi Avadhanula, Sarah E Blutt, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a leading cause of infant death across the globe. Age is a significant factor that contributes to the severity of infection in young children. RSV primarily infects the ciliated cells of the airway epithelium, induces mucus hypersecretion, and impaired mucociliary clearance. Better understanding of RSV infection at the cellular level is needed for the development of effective therapeutic interventions. To investigate the age difference and comprehensively understand gene signatures associated with RSV infection, we performed single-cell transcriptomic analysis of adult and pediatric human nose organoids (HNOs) infected with RSV. Our analysis revealed a significant difference …

Germline Cancer Predisposition Results From The National Cancer Institute-Children's Oncology Group Pediatric Match Trial, Sarah Scollon, Sharon E Plon, Steven Joffe, Jaclyn A Biegel, Shashikant Kulkarni, George Miles, David R Patton, Brent Coffey, Cynthia L Winter, Gregory J Tsongalis, Mark J Routbort, Nilsa C Ramirez, Lauren Saguilig, Jin Piao, Todd A Alonzo, Stacey L Berg, Elizabeth Fox, Brenda Weigel, Douglas S Hawkins, Jeffrey S Abrams, Margaret Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, D Williams Parsons

Faculty, Staff and Students Publications

Purpose: Precision oncology trials have generally focused on tumor testing to identify actionable alterations. The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial incorporated return of germline results to assess feasibility of reporting in a cooperative group setting and characterize germline cancer predisposition in patients with refractory cancers.

Patients and methods: Tumor and blood DNA from patients 1-21 years of age with treatment-refractory solid tumors, non-Hodgkin lymphomas, or histiocytic disorders underwent cancer gene panel sequencing. Clinical germline reports returned to 151 study sites included pathogenic/likely pathogenic (P/LP) germline variants found in 38 cancer predisposition genes (CPGs). European Society of Medical …

Associations Among Human Milk Polyunsaturated Fatty Acids And Infant Sleep Patterns: A Cross-Sectional Study, Ana M Palacios, Dominick J Lemas, Bridget E Young, Erik Parker, Stephanie Dickinson, Nandi Marshall, Kelly L Sullivan, Haley Wilt, Michelle I Cardel, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Infant sleep is critical for cognitive, emotional, and long-term health outcomes. Although diet-sleep relationships are established, limited research has explored how polyunsaturated fatty acids (PUFAs) in human milk (HM) relate to infant sleep.

Objectives: This study aims to examine associations between PUFAs in HM and sleep patterns in 2-mo-old infants exclusively fed with HM.

Methods: This cross-sectional secondary analysis used data from a lactation cookie trial involving 131 parents of healthy, term infants. Participants provided a fasting HM sample and completed sociodemographic and Brief Infant Sleep Questionnaire surveys. Multivariate linear models were adjusted for infant sex assigned at birth, …

Changes In Antiviral Prescribing For Children With Influenza In Us Emergency Departments., Tess Stopczynski, Olla Hamdan, Justin Z. Amarin, James W. Antoon, Laura S. Stewart, Haya Hayek, James Chappell, Andrew J. Spieker, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, John V. Williams, Marian G. Michaels, Julie A. Boom, Leila C. Sahni, Mary Allen Staat, Elizabeth P. Schlaudecker, Jennifer E. Schuster, Rangaraj Selvarangan, Ayzsa Tannis, Heidi L. Moline, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite national recommendations, antiviral prescribing in emergency departments (EDs) for children at higher risk of severe influenza, such as those younger than 5 years and those with specific underlying conditions, remains low.

OBJECTIVE: To assess whether there were changes in antiviral prescribing for children at higher risk of severe influenza in academic pediatric EDs before the COVID-19 pandemic (2016-2020) vs the late pandemic period (2021-2023).

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, cross-sectional study included influenza-positive children younger than 18 years presenting to the ED at 1 of 7 US pediatric academic hospitals participating in the Centers for Disease Control …

Functional Outcomes In Pediatric Patients On Renal Replacement Therapy In A Worldwide Registry, Kristin J Dolan, Katja M Gist, Abby Basalely, Gabriella Bottari, Abhishek Chakraborty, Mihaela Damian, Dana Fuhrman, Denise C Hasson, Catherine Joseph, Dave Kwiatkowski, Susan Martin, Jenn Nhan, Nicolas Ollberding, David T Selewski, Danielle Soranno, Michelle C Starr, Amy Strong, Sameer Thadani, Huaiyu Zang, Ayse Akcan Arikan

Faculty, Staff and Students Publications

Background and hypothesis: Mortality rates of children supported with continuous renal replacement therapy (CRRT) have improved, yet morbidity remains high. We aimed to evaluate the functional outcomes of children receiving CRRT using Functional Status Scale (FSS). We hypothesized that children receiving CRRT will have worse FSS compared with their baseline and acquire new morbidity at hospital discharge and 6 and 12 months post-discharge, and that lack of renal recovery will contribute to worsening functional status.

Methods: This is a retrospective chart review from The Worldwide Exploration of Renal Replacement Outcomes Collaborate in Kidney Disease (WE-ROCK), an international multi-center registry. Twenty-eight …

Salvage Therapies For First Relapse Of Shh Medulloblastoma In Early Childhood., Craig Erker, Martin Mynarek, Marie Simbozel, Brandon T. Craig, Virginia L. Harrod, Andrea M. Cappellano, Kenneth J. Cohen, Vicente Santa-Maria Lopez, Andres Morales La Madrid, Chantel Cacciotti, Lorena Baroni, Ralph Salloum, Ashley S. Margol, George Michaiel, Dolly Aguilera, Claire M. Mazewski, Cassie N. Kline, Jonathan L. Finlay, Mohamed S. Abdelbaki, Jeffrey C. Murray, Kathleen Dorris, Bruce Crooks, Kevin Ginn, Nisreen Amayiri, Stephan Tippelt, Gudrun Fleischhack, Svenja Tonn, Nicolas U. Gerber, Alvaro Lassaletta, Jordan R. Hansford, Sara Khan, Stephen W. Gilheeney, Lindsey M. Hoffman, Michal Zapotocky, Valérie Larouche, Shafqat Shah, Vijay Ramaswamy, Amar Gajjar, Sébastien Perreault, Sabine Mueller, Juliette Hukin, Sylvia Cheng, Zhihong J. Wang, Kara Matheson, Simon Bailey, Eric Bouffet, Steven C. Clifford, Giles Robinson, Christelle Dufour, Stefan Rutkowski, Lucie Lafay-Cousin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sonic hedgehog (SHH) medulloblastoma is the most common molecular group of infant and early childhood medulloblastoma (iMB) and has no standard of care at relapse. This work aimed to evaluate the post-relapse survival (PRS) and explore prognostic factors of patients with nodular desmoplastic (ND) and/or SHH iMB.

METHODS: This international retrospective study included 147 subjects diagnosed with relapsed ND/SHH iMB between 1995 and 2017, < 6 years old at original diagnosis, and treated without initial craniospinal irradiation (CSI). Univariable and multivariable Cox models with propensity score analyses were used to assess PRS for those in the curative intent cohort.

RESULTS: The 3-year PRS was 61.6% (95% confidence interval [CI], 52.2-69.6). The median age at relapse was 3.4 years (interquartile range [IQR], 2.6-4.1). Those with local relapse (40.8%) more often received salvage treatment with surgery …

Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study., James W. Antoon, Justin Z. Amarin, Olla Hamdan, Tess Stopczynski, Laura S. Stewart, Marian G. Michaels, John V. Williams, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, Jennifer E. Schuster, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Flor M. Muñoz, Mary Allen Staat, Elizabeth P. Schlaudecker, James D. Chappell, Benjamin R. Clopper, Heidi L. Moline, Angela P. Campbell, Andrew J. Spieker, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

METHODS: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network. The cohort consisted of children hospitalized with influenza A or B confirmed by clinical or research testing. The primary outcome was frequency of antiviral receipt during hospitalization. We used logistic regression to obtain adjusted …

Clinical Testing For Covid-19, Influenza, And Rsv In Hospitalized Youths, 2016-2024., Ariana P. Toepfer, Rachel E. Rutkowski, Leila C. Sahni, Geoffrey A. Weinberg, Marian G. Michaels, Rangaraj Selvarangan, Mary Allen Staat, Natasha Halasa, Janet A. Englund, Julie A. Boom, Peter G. Szilagyi, Jennifer E. Schuster, Elizabeth P P. Schlaudecker, Laura S. Stewart, Eileen J. Klein, Samantha M. Olson, Sascha Ellington, Meredith L. Mcmorrow, Heidi L. Moline, Fatimah S. Dawood, New Vaccine Surveillance Network Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Studies of COVID-19, influenza, and respiratory syncytial virus (RSV) disease clinical epidemiology, disease burden, and vaccine effectiveness often rely on clinical testing to identify cases, particularly with increasing use of electronic health record data. However, few data are available describing clinical testing practices to inform interpretation of these studies.

OBJECTIVE: To characterize clinical testing frequency for SARS-CoV-2, influenza, and RSV among children and adolescents hospitalized with acute respiratory illness during the 2016 to 2024 respiratory illness seasons by age, intensive care unit admission, and time period (2016-2020 and each season in 2020-2024); estimate the case fraction missed by clinical …

Changes In Child Placement After Child Abuse Pediatrics Consultation For Suspected Physical Abuse, Kristine A Campbell, Antoinette L Laskey, Daniel M Lindberg, M Katherine Henry, Porcia Vaughn, James D Anderst, Megan M Letson, Angela N Bachim, Nancy S Harper, Carmen M Coombs, Lori D Frasier, Joanne N Wood

Faculty, Staff and Students Publications

Background: The association between child abuse pediatric (CAP) assessments and child welfare outcomes is unknown.

Objective: To determine the association between a CAP determination of the likelihood of physical abuse and change in child placement. We hypothesized that child race would be associated with CAP determination of abuse likelihood and child welfare outcomes.

Participants and setting: Children under age ten years with in-person CAP consultation and referral to child protective services for suspected physical abuse at a U.S. pediatric referral center participating in CAPNET, a CAP research network, from 02/2021 to 01/2023.

Methods: We created a series of generalized estimating …

Phenotypic Divergence Of Jag1- And Notch2-Associated Alagille Syndrome & Disease-Specific Notch2 Variant Classification Guidelines., Shannon M. Vandriel, Li-Ting Li, Huiyu She, Jian-She Wang, Kathleen M. Loomes, David A. Piccoli, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzińska, Lorenzo D'Antiga, Emanuele Nicastro, Florence Lacaille, Dominique Debray, Étienne M. Sokal, Tanguy Demaret, Rima L. Fawaz, Silvia Nastasio, Kyung Mo Kim, Seak Hee Oh, Björn Fischler, Henrik Arnell, Catherine Larson-Nath, Winita Hardikar, Sahana Shankar, Shikha S. Sundaram, Alexander Chaidez, Pinar Bulut, Pier Luigi Calvo, Mureo Kasahara, Niviann Blondet, Eberhard Lurz, Anna-Maria Kavallar, Emmanuel M. Gonzales, Emmanuel Jacquemin, Jérôme Bouligand, Noelle H. Ebel, Jeffrey A. Feinstein, Susan M. Siew, Michael O. Stormon, Saul J. Karpen, Rene Romero, M Kyle Jensen, Catalina Jaramillo, James E. Squires, Sarah M. Bedoyan, Deirdre A. Kelly, Jane Hartley, Henkjan J. Verkade, Way Seah Lee, Chatmanee Lertudomphonwanit, Ryan T. Fischer, Henry C. Lin, Nathalie Rock, Yael Mozer-Glassberg, Amin J. Roberts, Helen M. Evans, Wikrom Karnsakul, Gabriella Nebbia, Victorien M. Wolters, Pamela L. Valentino, Jesus Quintero Bernabeu, Amal A. Aqul, Cigdem Arikan, María Legarda Tamara, Cristina Molera Busoms, Thomas Damgaard Sandahl, Giuseppe Indolfi, Andréanne N. Zizzo, Aglaia Zellos, Ruben E. Quiros-Tejeira, Ermelinda Santos-Silva, Kathleen B. Schwarz, Jernej Brecelj, Maria Camila Sanchez, Maria Lorena Cavalieri, Christos Tzivinikos, Sabina Wiecek, John Eshun, Nanda Kerkar, Quais Mujawar, Zerrin Önal, Cristina Gonçalves, Jennifer Garcia, Seema Alam, Carolina Jimenez-Rivera, Luis Bujanda, Richard J. Thompson, Bettina E. Hansen, Nancy B. Spinner, Melissa A. Gilbert, Binita M. Kamath, Global Alagille Alliance (Gala) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: Alagille syndrome (ALGS) is a rare, autosomal dominant disorder with high phenotypic heterogeneity. Disease-causing variants are primarily identified in Jagged1 (JAG1), with fewer reported in NOTCH2. JAG1 variants cause disease through a mechanism of haploinsufficiency, but the mechanism for NOTCH2 variants is not completely understood, making classification of variants more challenging. Using a large, international patient cohort acquired through the Global ALagille Alliance (GALA) study, we sought to improve classification of NOTCH2 variants and study phenotypic differences between NOTCH2- and JAG1-related disease.

METHODS: Clinical and molecular data from 952 individuals with ALGS in GALA were analysed and …

Contemporary Characteristics And Outcomes Of Pediatric Oncology Patients Participating In Early Phase Clinical Trials., Avina Rami, Kira Bona, Suzanne Shusterman, Karen Wright, Andrew E. Place, Puja J. Umaretiya, Ketki Bhushan, Steven G. Dubois, Kevin Campbell

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development. Currently, there is a paucity of information regarding contemporary outcomes for pediatric patients enrolled in these trials. We describe characteristics and outcomes of patients enrolled in pediatric phase 1 clinical trials over a 9-year period at a single institution.

METHODS: We queried our clinical trials management system to generate a list of patients enrolled and treated on pediatric phase 1 or phase 1/2 trials from 2011 to 2019. We collected baseline demographics, clinical data, efficacy, and safety endpoints post-enrollment including: time to death, objective …