Medical Sciences Commons^™

Residence In A Latinx Enclave And End-Induction Minimal Residual Disease Positivity Among Children With Acute Lymphoblastic Leukemia, Joshua P Muñiz, John P Woodhouse, Amy E Hughes, Sandi L Pruitt, Karen R Rabin, Michael E Scheurer, Philip J Lupo, Jeremy M Schraw

Center for Medical Ethics and Health Policy Staff Publications

Racial and ethnic inequities in survival persist for children with acute lymphoblastic leukemia (ALL). In the US, there are strong associations between SES, race/ethnicity, and place of residence. This is evidenced by ethnic enclaves: neighborhoods with high concentrations of ethnic residents, immigrants, and language isolation. The Latinx enclave index (LEI) can be used to investigate how residence in a Latinx enclave is associated with health outcomes. We studied the association between LEI score and minimal residual disease (MRD) in 142 pediatric ALL patients treated at Texas Children's Hospital. LEI score was associated with end-induction MRD positivity (OR per unit increase …

Incidence And 5-Year Survival Of Children And Adolescents With Hepatoblastoma In The United States, Justin A Kahla, David A Siegel, Shifan Dai, Philip J Lupo, Jennifer H Foster, Michael E Scheurer, Andras A Heczey

Center for Medical Ethics and Health Policy Staff Publications

Objective: Hepatoblastoma (HB) is the most common pediatric primary malignant liver tumor, its incidence has been increasing worldwide, but recent changes in incidence and outcomes with high population coverage are not well characterized.

Methods: We defined the incidence of HB diagnosed during 2003-2017 from United States Cancer Statistics (USCS) database, and survival during 2001-2016 from the National Program of Cancer Registries (NPCR). Data were stratified by sex, race/ethnicity, age, tumor stage, county population, and diagnosis year. Incidence trends were assessed by calculating average annual percent change (AAPC) using Joinpoint regression. Differences in overall 5-year survival were estimated using Cox regression …

Longitudinal Investigation Of Suicidal Ideation And Associated Factors During Pediatric Acute Lymphoblastic Leukemia Chemotherapy, Kimberly P Raghubar, Tiffany Chambers, Ryan M Hill, Olga Taylor, Marilyn Hockenberry, M Casey Hooke, Pauline Mitby, Ida Ki Moore, Austin L Brown, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Objective: This study describes the prevalence of suicidal ideation (SI) during acute lymphoblastic leukemia (ALL) therapy and investigates the influence of clinical factors and physical symptoms on SI.

Methods: The Children's Depressive Inventory (CDI-2) was administered to ALL patients (diagnosed 2012-2017) at start of consolidation, delayed intensification (DI), maintenance cycle 1 (MC1), and maintenance cycle 2 (MC2) in a multi-site study. SI was present if patients endorsed the item "I want to kill myself." Logistic regression models evaluated associations between SI and sociodemographic factors; depressive symptoms; and below average, average, and above average symptom clusters identified using latent class analysis …

Psychiatric Polygenic Risk Scores: Child And Adolescent Psychiatrists’ Knowledge, Attitudes, And Experiences, Stacey Pereira, Katrina A Muñoz, Brent J Small, Takahiro Soda, Laura N Torgerson, Clarissa E Sanchez, Jehannine Austin, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently …

Psychiatric Polygenic Risk Scores: Child And Adolescent Psychiatrists’ Knowledge, Attitudes, And Experiences, Stacey Pereira, Katrina A Muñoz, Brent J Small, Takahiro Soda, Laura N Torgerson, Clarissa E Sanchez, Jehannine Austin, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently …

Children With Functional Abdominal Pain Disorders Successfully Decrease Fodmap Food Intake On A Low Fodmap Diet With Modest Improvements In Nutritional Intake And Diet Quality, Vishnu Narayana, Ann R Mcmeans, Rona L Levy, Robert J Shulman, Bruno P Chumpitazi

Faculty, Staff and Students Publications

BACKGROUND: We sought to determine how a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) affected high FODMAP food intake, nutrient intake, and diet quality in children with functional abdominal pain disorders (FAPD).

METHODS: Children (ages 7-13 years) with Rome IV FAPD began a dietitian-guided LFD. Three-day food records were captured at baseline and 2-3 weeks into the LFD. Intake of high FODMAP foods, energy, macronutrients, micronutrients, food groups, and ultra-processed foods were determined.

KEY RESULTS: Median age of participants was 11 years, and 19/31 (61%) were female. Twenty-eight (90%) decreased high FODMAP food intake on the LFD: …

Clinical Relevance Of Proteomic Profiling In De Novo Pediatric Acute Myeloid Leukemia: A Children’S Oncology Group Study, Fieke W Hoff, Anneke D Van Dijk, Yihua Qiu, Chenyue W Hu, Rhonda E Ries, Andrew Ligeralde, Gaye N Jenkins, Robert B Gerbing, Alan S Gamis, Richard Aplenc, E Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Amina A Qutub, Eveline S J M De Bont, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

Pediatric acute myeloid leukemia (AML) remains a fatal disease for at least 30% of patients, stressing the need for improved therapies and better risk stratification. As proteins are the unifying feature of (epi)genetic and environmental alterations, and are often targeted by novel chemotherapeutic agents, we studied the proteomic landscape of pediatric AML. Protein expression and activation levels were measured in 500 bulk leukemic patients' samples and 30 control CD34+ cell samples, using reverse phase protein arrays with 296 strictly validated antibodies. The multistep MetaGalaxy analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein …

Analysis Of The Efficacy Of Autologous Peripheral Blood Stem Cell Transplantation In High-Risk Neuroblastoma, Jin Yan, Li Jie, Yang Jiaxing, Cao Yanna, Li Zhanglin, Li Zhongyuan, Wang Daowei, Zhao Guangzong, Zhong Benfu, Yan Jie, Zhao Qiang

Faculty, Staff and Student Publications

Objective: This study aimed to analyze the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China.

Methods: The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen were reviewed. The baseline clinicopathological characteristics and prognosis were analyzed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared.

Results: The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and …

External Validation Of A Prediction Model For Estimating Fat Mass In Children And Adolescents In 19 Countries: Individual Participant Data Meta-Analysis, Mohammed T Hudda, Jonathan C K Wells, Linda S Adair, Jose R A Alvero-Cruz, Maxine N Ashby-Thompson, Martha N Ballesteros-Vásquez, Jesus Barrera-Exposito, Benjamin Caballero, Elvis A Carnero, Geoff J Cleghorn, Peter S W Davies, Malgorzata Desmond, Delan Devakumar, Dympna Gallagher, Elvia V Guerrero-Alcocer, Ferdinand Haschke, Mary Horlick, Houda Ben Jemaa, Ashraful I Khan, Amani Mankai, Makama A Monyeki, Hilde L Nashandi, Luis Ortiz-Hernandez, Guy Plasqui, Felipe F Reichert, Alma E Robles-Sardin, Elaine Rush, Roman J Shypailo, Jakub G Sobiecki, Gill A Ten Hoor, Jesús Valdés, V Pujitha Wickramasinghe, William W Wong, Richard D Riley, Christopher G Owen, Peter H Whincup, Claire M Nightingale

Children’s Nutrition Research Center Staff Publications

Objective: To evaluate the performance of a UK based prediction model for estimating fat-free mass (and indirectly fat mass) in children and adolescents in non-UK settings.

Design: Individual participant data meta-analysis.

Setting: 19 countries.

Participants: 5693 children and adolescents (49.7% boys) aged 4 to 15 years with complete data on the predictors included in the UK based model (weight, height, age, sex, and ethnicity) and on the independently assessed outcome measure (fat-free mass determined by deuterium dilution assessment).

Main outcome measures: The outcome of the UK based prediction model was natural log transformed fat-free mass (lnFFM). Predictive performance statistics of …

Covid-19 And Children, Carl A Pierce, Kevan C Herold, Betsy C Herold, Janet Chou, Adrienne Randolph, Binita Kane, Sammie Mcfarland, Deepti Gurdasani, Christina Pagel, Peter Hotez, Sarah Cobey, Scott E Hensley

Center for Medical Ethics and Health Policy Staff Publications

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Tara Ness, Sabine E Verkuijl, Kerri Viney, Annemieke Brands, Tiziana Masini, Lucia González Fernández, Michael Eisenhut, Anne K Detjen, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of …

Leveraging Clinical Trial Populations And Data From The Children's Oncology Group For Cancer Survivorship Research, Eric J Chow, Lena E Winestone, Philip J Lupo, Lisa R Diller, Tara O Henderson, Nina S Kadan-Lottick, Jennifer M Levine, Kirsten K Ness, Smita Bhatia, Saro H Armenian

Center for Medical Ethics and Health Policy Staff Publications

Children and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship …

Risk Of Variceal Hemorrhage And Pretransplant Mortality In Children With Biliary Atresia, Lee M Bass, Wen Ye, Kieran Hawthorne, Daniel H Leung, Karen F Murray, Jean P Molleston, Rene Romero, Saul Karpen, Philip Rosenthal, Kathleen M Loomes, Kasper S Wang, Robert H Squires, Alexander Miethke, Vicky L Ng, Simon Horslen, M Kyle Jensen, Ronald J Sokol, John C Magee, Benjamin L Shneider, Children

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of VH in a longitudinal multicenter study.

APPROACH AND RESULTS: Participants enrolled in either an incident (Prospective Database of Infants with Cholestasis [PROBE]) or prevalent (Biliary Atresia Study of Infants and Children [BASIC]) cohort of BA were included. Variceal hemorrhage (VH) was defined based on gastrointestinal bleeding in the presence of varices accompanied by endoscopic or nontransplant surgical intervention. Cumulative incidence of VH and transplant-free survival was compared based on features of portal hypertension …

Precision Diabetes: Lessons Learned From Maturity-Onset Diabetes Of The Young (Mody), Mustafa Tosur, Louis H Philipson

Faculty, Staff and Students Publications

Maturity-onset of diabetes of the young (MODY) are monogenic forms of diabetes characterized by early onset diabetes with autosomal dominant inheritance. Since its first description about six decades ago, there have been significant advancements in our understanding of MODY from clinical presentations to molecular diagnostics and therapeutic responses. The prevalence of MODY is estimated as at least 1.1-6.5% of the pediatric diabetes population with a high degree of geographic variability that might arise from several factors in the criteria used to ascertain cases. GCK-MODY, HNF1A-MODY, and HNF4A-MODY account for >90% of MODY cases. While some MODY forms do not require …

Factors Associated With Severe Illness In Patients Aged <21 Years Hospitalized For Covid-19, Rewa Choudhary, Bryant J Webber, Lindsay S Womack, Hannah K Dupont, Sophia K Chiu, Valentine Wanga, Megan E Gerdes, Sophia Hsu, Dallas S Shi, Theresa M Dulski, Osatohamwen I Idubor, Arthur M Wendel, Nickolas T Agathis, Kristi Anderson, Tricia Boyles, Eleanor S Click, Juliana Da Silva, Mary E Evans, Jeremy A W Gold, Julia C Haston, Pamela Logan, Susan A Maloney, Marisol Martinez, Pavithra Natarajan, Kevin B Spicer, Mark Swancutt, Valerie A Stevens, Jessica Rogers-Brown, Gyan Chandra, Megan Light, Frederick E Barr, Jessica Snowden, Larry K Kociolek, Matthew Mchugh, David L Wessel, Joelle N Simpson, Kathleen C Gorman, Kristen A Breslin, Roberta L Debiasi, Aaron Thompson, Mark W Kline, Julie A Boom, Ila R Singh, Michael Dowlin, Mark Wietecha, Beth Schweitzer, Sapna Bamrah Morris, Emilia H Koumans, Jean Y Ko, David A Siegel, Anne A Kimball

Faculty, Staff and Students Publications

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness.

METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients agedchildren's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation.

RESULTS: Of 947 hospitalized patients, 759 …

Rates Of Laboratory Adverse Events By Course In Paediatric Leukaemia Ascertained With Automated Electronic Health Record Extraction: A Retrospective Cohort Study From The Children’S Oncology Group, Tamara P Miller, Kelly D Getz, Yimei Li, Biniyam G Demissei, Peter C Adamson, Todd A Alonzo, Evanette Burrows, Lusha Cao, Sharon M Castellino, Marla H Daves, Brian T Fisher, Robert Gerbing, Robert W Grundmeier, Edward M Krause, Judy Lee, Philip J Lupo, Karen R Rabin, Mark Ramos, Michael E Scheurer, Jennifer J Wilkes, Lena E Winestone, Douglas S Hawkins, M Monica Gramatges, Richard Aplenc

Center for Medical Ethics and Health Policy Staff Publications

Background: Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia.

Methods: For this retrospective cohort study from the Children's Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Children's Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Children's Hospital of Philadelphia …

An Ultra-Brief Screening Scale For Pediatric Obsessive-Compulsive Disorder: The Oci-Cv-5, Amitai Abramovitch, Jonathan S Abramowitz, Dean Mckay, Heining Cham, Kennedy S Anderson, Lara J Farrell, Daniel A Geller, Gregory L Hanna, Sharna Mathieu, Joseph F Mcguire, David R Rosenberg, S Evelyn Stewart, Eric A Storch, Sabine Wilhelm

Center for Medical Ethics and Health Policy Staff Publications

Background: Obsessive-compulsive disorder (OCD) is an often disabling and chronic condition that is normally assessed using diagnostic interviews or lengthy self-report questionnaires. This makes routine screening in general health settings impractical, and as a result OCD is often under-(or mis-)recognized. The present study reports on the development of an ultra-brief version of the Obsessive-Compulsive Inventory-Child Version (OCI-CV) which may be administered routinely as a screener for pediatric OCD.

Method: A total of 489 youth diagnosed with OCD, 259 non-clinical controls, and 299 youth with other disorders completed the OCI-CV and other indices of psychopathology. Using item analyses, we extracted five …

Limited Utility Of Structural Mri To Identify The Epileptogenic Zone In Young Children With Tuberous Sclerosis, Maaike Nijman, Edward Yang, Camilo Jaimes, Anna K Prohl, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Hope Northrup, Scellig S D Stone, Joseph R Madsen, Aria Fallah, Jeffrey P Blount, Howard L Weiner, Leslie Grayson, E Martina Bebin, Brenda E Porter, Simon K Warfield, Sanjay P Prabhu, Jurriaan M Peters, Tacern Study Group

Faculty, Staff and Students Publications

BACKGROUND AND PURPOSE: The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC.

METHODS: We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12 months or more follow-up. Two neuroradiologists, blinded to surgical outcome data, reviewed 10 candidate lesions on preoperative MRI for characteristics of the tuber (large affected area, calcification, cyst-like properties) and of focal cortical dysplasia (FCD) features (cortical malformation, gray-white matter junction blurring, …

Quantifying The Risk And Dosimetric Variables Of Symptomatic Brainstem Injury After Proton Beam Radiation In Pediatric Brain Tumors, Rituraj Upadhyay, Kaiping Liao, David R Grosshans, Susan L Mcgovern, Mary Frances Mcaleer, Wafik Zaky, Murali M Chintagumpala, Anita Mahajan, Debra Nana Yeboa, Arnold C Paulino

Faculty, Staff and Student Publications

Background: Brainstem toxicity after radiation therapy (RT) is a devastating complication and a particular concern with proton radiation (PBT). We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with PBT.

Methods: All patients < 21 years with brain tumors treated with PBT at our institution from 2007-2019, with a brainstem Dmean >30 Gy and/or Dmax >50.4 Gy were included. Symptomatic brainstem injury (SBI) was defined as any new or progressive cranial neuropathy, ataxia, and/or motor weakness with corresponding radiographic abnormality within brainstem.

Results: A total of 595 patients were reviewed and 468 (medulloblastoma = 200, gliomas = 114, ependymoma = 87, ATRT = 43) met our inclusion criteria. Median age at RT …

A Decade's Experience In Pediatric Chromosomal Microarray Reveals Distinct Characteristics Across Ordering Specialties, Mariam T Mathew, Austin Antoniou, Naveen Ramesh, Min Hu, Jeffrey Gaither, Danielle Mouhlas, Sayaka Hashimoto, Maggie Humphrey, Theodora Matthews, Jesse M Hunter, Shalini Reshmi, Matthew Schultz, Kristy Lee, Ruthann Pfau, Catherine Cottrell, Kim L Mcbride, Nicholas E Navin, Bimal P Chaudhari, Marco L Leung

Faculty, Staff and Student Publications

Chromosomal microarray (CMA) is a testing modality frequently used in pediatric patients; however, published data on its utilization are limited to the genetic setting. We performed a database search for all CMA testing performed from 2010 to 2020, and delineated the diagnostic yield based on patient characteristics, including sex, age, clinical specialty of providers, indication of testing, and pathogenic finding. The indications for testing were further categorized into Human Phenotype Ontology categories for analysis. This study included a cohort of 14,541 patients from 29 different medical specialties, of whom 30% were from the genetics clinic. The clinical indications for testing …

Kctd7 Deficiency Induces Myoclonic Seizures Associated With Purkinje Cell Death And Microvascular Defects, Justine H Liang, Jonathan Alevy, Viktor Akhanov, Ryan Seo, Cory A Massey, Danye Jiang, Joy Zhou, Roy V Sillitoe, Jeffrey L Noebels, Melanie A Samuel

Duncan NRI Faculty and Staff Publications

Mutations in the potassium channel tetramerization domain-containing 7 (KCTD7) gene are associated with a severe neurodegenerative phenotype characterized by childhood onset of progressive and intractable myoclonic seizures accompanied by developmental regression. KCTD7-driven disease is part of a large family of progressive myoclonic epilepsy syndromes displaying a broad spectrum of clinical severity. Animal models of KCTD7-related disease are lacking, and little is known regarding how KCTD7 protein defects lead to epilepsy and cognitive dysfunction. We characterized Kctd7 expression patterns in the mouse brain during development and show that it is selectively enriched in specific regions as the brain matures. We further …

Phenotypic And Genetic Spectrum Of Atp6v1a Encephalopathy: A Disorder Of Lysosomal Homeostasis, Renzo Guerrini, Davide Mei, Katalin Kerti-Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, Kimberly Mcdonald, Janice Baker, Vikas Bhambhani, Zöe Powis, Lance Rodan, Rima Nabbout, Giulia Barcia, Jill A Rosenfeld, Carlos A Bacino, Cyril Mignot, Lillian H Power, Catharine J Harris, Dragan Marjanovic, Rikke S Møller, Trine B Hammer, Riikka Keski Filppula, Päivi Vieira, Clara Hildebrandt, Stephanie Sacharow, Luca Maragliano, Fabio Benfenati, Katherine Lachlan, Andreas Benneche, Florence Petit, Jean Madeleine De Sainte Agathe, Barbara Hallinan, Yue Si, Ingrid M Wentzensen, Fanggeng Zou, Vinodh Narayanan, Naomichi Matsumoto, Alessandra Boncristiano, Giancarlo La Marca, Mitsuhiro Kato, Kristin Anderson, Carmen Barba, Luisa Sturiale, Domenico Garozzo, Roberto Bei, Laura Masuelli, Valerio Conti, Gaia Novarino, Anna Fassio

Faculty, Staff and Student Publications

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased …

Notes From An Epicenter: Navigating Behavioral Clinical Trials On Autism Spectrum Disorder Amid The Covid-19 Pandemic In The Bronx, Alaina S Berruti, Roseann C Schaaf, Emily A Jones, Elizabeth Ridgway, Rachel L. Dumont, Benjamin E Leiby, Catherine Sancimino, Misung Yi, Sophie Molholm

Department of Occupational Therapy Faculty Papers

Background: The COVID-19 pandemic impacted nearly all facets of our daily lives, and clinical research was no exception. Here, we discuss the impact of the pandemic on our ongoing, three-arm randomized controlled trial (RCT) Sensory Integration Therapy (SIT) in Autism: Mechanisms and Effectiveness (NCT02536365), which investigates the immediate and sustained utility of SIT to strengthen functional daily-living skills and minimize the presence of maladaptive sensory behaviors in autistic children.

Main text: In this text, we detail how we navigated the unique challenges that the pandemic brought forth between the years 2020 and 2021, including the need to rapidly …

Dietary Intake Among Children Attending Childcare Centers: Impact Of The New Cacfp Meal Guidelines, Jayna M Dave, Tzuan A Chen, Maha Almohamad, Sonia Cotto-Moreno

Children’s Nutrition Research Center Staff Publications

Through the Healthy, Hunger-Free Kids Act of 2010, USDA (US Department of Agriculture) made the first major changes in the CACFP (Child and Adult Care Food Program) meal and snack menu patterns. Childcare centers that serve low-income families qualify to participate and receive reimbursement for meals and snacks served. The purpose of this study was to assess what changes in children's dietary behaviors occurred as a result of the new CACFP meal pattern requirements. This study evaluated these changes at childcare centers operating in Houston and San Antonio, Texas, USA, areas enrolled in the CACFP, pre- (Spring 2016) and post-implementation …

Adiposity, Insulin Resistance, Cardiorespiratory Fitness, And Bone Health In Hispanic Children, Reem S Shawar, Maurice Puyau, Roman Shypailo, Salma Musaad, Nancy F Butte, Fida Bacha

Faculty, Staff and Students Publications

CONTEXT: Childhood obesity disproportionately affects Hispanic youth. The skeletal system appears to be a target organ of the adverse effects of obesity. Yet, the relationship between adiposity and bone health in youth and the modulating factors are not well understood.

OBJECTIVE: This work aims to examine the relationship between adiposity, insulin resistance (IR), cardiorespiratory fitness (CRF), and bone mass in Hispanic youth.

METHODS: A total of 951 Hispanic youth (50% male), aged 4 to 19 years, participated in this cross-sectional design study from the Viva La Familia Study at Children's Nutrition Research Center. Bone mineral content (BMC) and density (BMD), …

A Case Series Of Children With Acute Hepatitis And Human Adenovirus Infection, L Helena Gutierrez Sanchez, Henry Shiau, Julia M Baker, Stephanie Saaybi, Markus Buchfellner, William Britt, Veronica Sanchez, Jennifer L Potter, L Amanda Ingram, David Kelly, Xiaoyan Lu, Stephanie Ayers-Millsap, Wesley G Willeford, Negar Rassaei, Julu Bhatnagar, Hannah Bullock, Sarah Reagan-Steiner, Ali Martin, Michael E Rogers, Anna M Banc-Husu, Sanjiv Harpavat, Daniel H Leung, Elizabeth A Moulton, Daryl M Lamson, Kirsten St George, Aron J Hall, Umesh Parashar, Adam Macneil, Jacqueline E Tate, Hannah L Kirking

Faculty, Staff and Students Publications

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia.

METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children’s of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing.

RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 …

Genetic Variants In Aldh1l1 And Gldc Influence The Serine-To-Glycine Ratio In Hispanic Children, Sergey A Krupenko, Shelley A Cole, Ruixue Hou, Karin Haack, Sandra Laston, Nitesh R Mehta, Anthony G Comuzzie, Nancy F Butte, V Saroja Voruganti

Children’s Nutrition Research Center Staff Publications

Background: Glycine is a proteogenic amino acid that is required for numerous metabolic pathways, including purine, creatine, heme, and glutathione biosynthesis. Glycine formation from serine, catalyzed by serine hydroxy methyltransferase, is the major source of this amino acid in humans. Our previous studies in a mouse model have shown a crucial role for the 10-formyltetrahydrofolate dehydrogenase enzyme in serine-to-glycine conversion.

Objectives: We sought to determine the genomic influence on the serine-glycine ratio in 803 Hispanic children from 319 families of the Viva La Familia cohort.

Methods: We performed a genome-wide association analysis for plasma serine, glycine, and the serine-glycine ratio …

Acylcarnitines And Genetic Variation In Fat Oxidation Genes In Hiv-Infected, Antiretroviral-Treated Children With And Without Myopathy, Brian Kirmse, Charlotte Hobbs, Lisa Aaron, Grace Montepiedra, Marshall Summar, Paige L Williams, Caitlin J Smith, Russell Van Dyke, Chunli Yu, Kelli K Ryckman, William Borkowsky

Faculty, Staff and Student Publications

BACKGROUND: Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).

METHODS: Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)-containing ARV. Thirty-seven participants with ≥2 creatine kinase measurements >500 IU (n = 18) or evidence of echocardiographic cardiomyopathy (n = 19) were matched with 37 participants without myopathy. Single nucleotide polymorphisms (SNPs) in FAO genes were also evaluated.

RESULTS: Abnormal ACP …

Chronic Granulomatous Disease-Like Presentation Of A Child With Autosomal Recessive Pkcδ Deficiency, Anna-Lena Neehus, Karen Tuano, Tom Le Voyer, Sarada L Nandiwada, Kruthi Murthy, Anne Puel, Jean-Laurent Casanova, Javier Chinen, Jacinta Bustamante

Faculty, Staff and Students Publications

BACKGROUND: Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and viral infections. PKCδ is involved in the intracellular production of reactive oxidative species (ROS).

MATERIAL AND METHODS: We studied a 5-year old girl presenting with a history of Burkholderia cepacia infection. She had no history of autoimmunity, lymphocyte counts were normal, and no auto-antibodies were detected in her plasma. We performed a targeted panel analysis of 407 immunity-related genes and immunological investigations of the underlying genetic condition in this patient.

RESULTS: Consistent with a history suggestive of …

Factors Associated With Parental Acceptance Of Covid-19 Vaccination: A Multicenter Pediatric Emergency Department Cross-Sectional Analysis, Brigitte M Baumann, Robert M Rodriguez, Amy M Delaroche, David Rayburn, Stephanie A Eucker, Nicole L Nadeau, Lisa A Drago, Danielle Cullen, Sarah Dennis Meskill, Suzanne Bialeck, Michael Gillman

Faculty, Staff and Students Publications

STUDY OBJECTIVE: During the delta surge of the COVID-19 pandemic in 2021, we sought to identify characteristics and beliefs associated with COVID-19 vaccination acceptance in parents of pediatric emergency department (ED) patients.

METHODS: We conducted a cross-sectional survey-based study of the parents of children aged 3 to 16 years presenting to 1 of 9 pediatric EDs from June to August 2021 to assess the parental acceptance of COVID-19 vaccines. Using multiple variable regression, we ascertained which factors were associated with parental and pediatric COVID-19 vaccination acceptance.

RESULTS: Of 1,491 parents approached, 1,298 (87%) participated, of whom 50% of the parents …