Pediatrics Commons^™

A Phase I/Ii Trial Of Nivolumab Plus Ipilimumab In Children And Young Adults With Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study Advl1412, Kara L Davis, Elizabeth Fox, Emasenyie Isikwei, Joel M Reid, Xiaowei Liu, Charles G Minard, Stephan Voss, Stacey L Berg, Brenda J Weigel, Crystal L Mackall

Faculty, Staff and Students Publications

PURPOSE: In many cancers, nivolumab in combination with ipilimumab improves response rates compared with either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors.

PATIENTS AND METHODS: ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1 mg/kg of each drug and DL2 3 mg/kg nivolumab plus 1 mg/kg ipilimumab. Part D evaluated response at the recommended phase II dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1 …

Prediction Value Of Krebs Von Den Lungen-6 (Kl-6) Biomarker In Covid-19 Patients: A Systematic Review And Meta-Analysis, Michal Matuszewski, Lukasz Szarpak, Zubaid Rafique, Frank W Peacock, Michal Pruc, Piotr Szwed, Francesco Chirico, Alla Navolokina, Jerzy R Ladny, Andrea Denegri

Faculty, Staff and Students Publications

The SARS-CoV-2 (COVID-19) pandemic is a major issue that necessitates the use of cutting-edge disease prediction models. The aim of the study was to assess the existing evidence regarding association between Krebs von den Lungen-6 levels and COVID-19 severity. A literature search was performed on Web of Science, PubMed, Scopus and Cochrane Central Register of Controlled Trials databases from 1 January 2020 up to 2 August 2022. The electronic database search was supplemented by searching Google Scholar. In addition, reference lists of relative articles were also reviewed. KL-6 levels among COVID-19 positive vs. negative patients varied and amounted to 443.37 …

Clinical Exome Sequencing Uncovers A High Frequency Of Mendelian Disorders In Infants With Stroke: A Retrospective Analysis, Runjun D Kumar, Linyan Meng, Pengfei Liu, Christina Y Miyake, Kim C Worley, Weimin Bi, Seema R Lalani

Faculty, Staff and Students Publications

Background:

Stroke causes significant disability and is a common cause of death worldwide. Previous studies have estimated that 1-5% of stroke is attributable to monogenic etiologies. We set out to assess the utility of clinical exome sequencing (ES) in the evaluation of stroke.

Methods:

We retrospectively analyzed 124 individuals who received ES at the Baylor Genetics reference lab between 2012 and 2021 who had stroke as a major part of their reported phenotype.

Results:

Ages ranged from 10 days to 69 years. 8.9% of the cohort received a diagnosis, including 25% of infants less than 1 year old; an additional …

Cardiac Size, Shape, And Ventricular Contractility In Fetuses At Sea Level With An Estimated Weight Less-Than 10th Centile, Wesley Lee, Lauren M Mack, Roxanna Miremadi, Betul Yilmaz Furtun, Haleh Sangi-Haghpeykar, Greggory R Devore

Faculty, Staff and Students Publications

OBJECTIVES: To investigate cardiac size, shape, and ventricular contractility in fetuses with estimated fetal weight (EFW)(Houston).

METHODS: A prospective ultrasound study examined 37 fetuses with EFWsize, shape, and contractility of both ventricles were analyzed with speckle tracking methods. Z scores were calculated using the mean ± standard deviation (SD) derived from normal controls. Measurements were abnormal if their Z score values were+1.65. The proportion of small fetuses with abnormal parameters was compared to normal reference ranges. Results were compared to a similar published study of small fetuses at higher altitude in Denver.

RESULTS: About one-third of Houston fetuses with EFW(RV) …

The Roles Of Sleep And Eating Patterns In Adiposity Gain Among Preschool-Aged Children, Amy R Goetz, Ishita Jindal, Jennette P Moreno, Maurice R Puyau, Anne L Adolph, Salma Musaad, Nancy F Butte, Fida Bacha

Faculty, Staff and Students Publications

BACKGROUND: Short sleep durations are related to risks for obesity in preschool children. However, the underlying mechanism or mechanisms are not clear.

OBJECTIVES: We evaluated the relationships between sleep characteristics and body composition, energetics, and weight-regulating behaviors in preschool-aged children, as well as the longitudinal associations between children's sleep and eating patterns and body composition at a 1-year follow-up.

METHODS: Data were drawn from a longitudinal study of 118 children aged 3-5 years. Sleep (duration, midpoint, regularity) and physical activity (PA) were measured by accelerometry over 6 consecutive days; total energy expenditure (TEE) was measured using the doubly labeled water …

Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon

Faculty, Staff and Students Publications

BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).

PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.

RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second …

Nurturing Children’S Development Through Healthy Eating And Active Living: Time For Policies To Support Effective Interventions In The Context Of Responsive Emotional Support And Early Learning, Helen Skouteris, Rachael Green, Alexandra Chung, Heidi Bergmeier, Lisa H Amir, Sukhpreet Kaur Baidwan, Angel Marie Chater, Catherine Chamberlain, Ruth Emond, Kay Gibbons, Michelle Gooey, Kostas Hatzikiriakidis, Emma Haycraft, Andrew P Hills, Daryl J Higgins, Oliver Hooper, Sue-Anne Hunter, Pam Kappelides, Sue Kleve, Jacynta Krakouer, Julie C Lumeng, Yannis Manios, Athar Mansoor, Michael Marmot, Louise C Mâsse, Karen Matvienko-Sikar, Zandile June-Rose Mchiza, Caroline Meyer, George Moschonis, Emily R Munro, Teresia Margareta O'Connor, Adrienne O'Neil, Thomas Quarmby, Rachel Sandford, Janet U Schneiderman, Simone Sherriff, Doug Simkiss, Alison Spence, Elizabeth Sturgiss, Dave Vicary, Rebecca Wickes, Luke Wolfenden, Mary Story, Maureen M Black

Faculty, Staff and Students Publications

Fostering the growth, development, health, and wellbeing of children is a global priority. The early childhood period presents a critical window to influence lifelong trajectories, however urgent multisectoral action is needed to ensure that families are adequately supported to nurture their children's growth and development. With a shared vision to give every child the best start in life, thus helping them reach their full developmental potential, we have formed the International Healthy Eating Active Living Matters (HEALing Matters) Alliance. Together, we form a global network of academics and practitioners working across child health and development, and who are dedicated to …

Disease Progression Of Whim Syndrome In An International Cohort Of 66 Pediatric And Adult Patients, Christoph B Geier, Maryssa Ellison, Rachel Cruz, Sumit Pawar, Alexander Leiss-Piller, Katarina Zmajkovicova, Shannon M Mcnulty, Melis Yilmaz, Martin Oman Evans, Sumai Gordon, Boglarka Ujhazi, Ivana Wiest, Hassan Abolhassani, Asghar Aghamohammadi, Sara Barmettler, Saleh Bhar, Anastasia Bondarenko, Audrey Anna Bolyard, David Buchbinder, Michaela Cada, Mirta Cavieres, James A Connelly, David C Dale, Ekaterina Deordieva, Morna J Dorsey, Simon B Drysdale, Stephan Ehl, Reem Elfeky, Francesca Fioredda, Frank Firkin, Elizabeth Förster-Waldl, Bob Geng, Vera Goda, Luis Gonzalez-Granado, Eyal Grunebaum, Elzbieta Grzesk, Sarah E Henrickson, Anna Hilfanova, Mitsuteru Hiwatari, Chihaya Imai, Winnie Ip, Soma Jyonouchi, Hirokazu Kanegane, Yuta Kawahara, Amer M Khojah, Vy Hong-Diep Kim, Marina Kojić, Sylwia Kołtan, Gergely Krivan, Daman Langguth, Yu-Lung Lau, Daniel Leung, Maurizio Miano, Irina Mersyanova, Talal Mousallem, Mica Muskat, Flavio A Naoum, Suzie A Noronha, Monia Ouederni, Shuichi Ozono, G Wendell Richmond, Inga Sakovich, Ulrich Salzer, Catharina Schuetz, Filiz Odabasi Seeborg, Svetlana O Sharapova, Katja Sockel, Alla Volokha, Malte Von Bonin, Klaus Warnatz, Oliver Wegehaupt, Geoffrey A Weinberg, Ke-Juin Wong, Austen Worth, Huang Yu, Yulia Zharankova, Xiaodong Zhao, Lisa Devlin, Adriana Badarau, Krisztian Csomos, Marton Keszei, Joao Pereira, Arthur G Taveras, Sarah L Beaussant-Cohen, Mei-Sing Ong, Anna Shcherbina, Jolan E Walter

Faculty, Staff and Students Publications

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not …

A Multinational Delphi Consensus To End The Covid-19 Public Health Threat, Jeffrey V Lazarus, Diana Romero, Christopher J Kopka, Salim Abdool Karim, Laith J Abu-Raddad, Gisele Almeida, Ricardo Baptista-Leite, Joshua A Barocas, Mauricio L Barreto, Yaneer Bar-Yam, Quique Bassat, Carolina Batista, Morgan Bazilian, Shu-Ti Chiou, Carlos Del Rio, Gregory J Dore, George F Gao, Lawrence O Gostin, Margaret Hellard, Jose L Jimenez, Gagandeep Kang, Nancy Lee, Mojca Matičič, Martin Mckee, Sabin Nsanzimana, Miquel Oliu-Barton, Bary Pradelski, Oksana Pyzik, Kenneth Rabin, Sunil Raina, Sabina Faiz Rashid, Magdalena Rathe, Rocio Saenz, Sudhvir Singh, Malene Trock-Hempler, Sonia Villapol, Peiling Yap, Agnes Binagwaho, Adeeba Kamarulzaman, Ayman El-Mohandes

Faculty, Staff and Students Publications

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and …

Impact Of Udenafil On Echocardiographic Indices Of Single Ventricle Size And Function In Fuel Study Participants, Michael V Di Maria, David J Goldberg, Victor Zak, Chenwei Hu, Adam M Lubert, Andreea Dragulescu, Andrew S Mackie, Andrew Mccrary, Angela Weingarten, Anitha Parthiban, Benjamin Goot, Bryan H Goldstein, Carolyn Taylor, Christopher Lindblade, Christopher J Petit, Christopher Spurney, David M Harrild, Elaine M Urbina, Eleanor Schuchardt, Gi Beom Kim, Ja Kyoung Yoon, Jamie N Colombo, Matthew D Files, Megan Schoessling, Peter Ermis, Pierre C Wong, Ruchira Garg, Sara K Swanson, Shaji C Menon, Shubhika Srivastava, Thor Thorsson, Tiffanie R Johnson, Usha S Krishnan, Stephen M Paridon, Peter C Frommelt

Faculty, Staff and Students Publications

BACKGROUND: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied.

METHODS: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular …

Analysis Of Insppire-2 Cohort: Risk Factors And Disease Burden In Children With Acute Recurrent Or Chronic Pancreatitis, Aliye Uc, Gretchen A Cress, Fuchenchu Wang, Maisam Abu-El-Haija, Kate M Ellery, Douglas S Fishman, Cheryl E Gariepy, Tanja Gonska, Tom K Lin, Quin Y Liu, Megha Mehta, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).

METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP.

RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR …

Infant Behavioral State And Stool Microbiome In Infants Receiving Lactocaseibacillus Rhamnosus Gg In Formula: Randomized Controlled Trial, Robert J Shulman, Maciej Chichlowski, Fabiola Gutierrez Orozco, Cheryl L Harris, Jennifer L Wampler, Nicholas A Bokulich, Carol Lynn Berseth

Faculty, Staff and Students Publications

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).

METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with …

Tryptophan Oxidation In Young Children With Environmental Enteric Dysfunction Classified By The Lactulose Rhamnose Ratio, Nirupama Shivakumar, Jean W Hsu, Sindhu Kashyap, Tinku Thomas, Anura V Kurpad, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: In young children, associations between linear growth faltering, environmental enteric dysfunction (EED), and the plasma kynurenine (Kyn)/tryptophan (Trp) ratio (KTR) have led to the proposal that higher Trp catabolism in response to intestinal/systemic inflammation limits Trp availability for protein synthesis, resulting in impaired growth.

OBJECTIVES: We sought to estimate the Trp oxidation rate and the Trp conversion rate to Kyn in young children with and without EED.

METHODS: Children aged 18-24 mo, from urban slums, were assigned to EED (n = 19) or no-EED (n = 26) groups on the basis of a urinary lactulose/rhamnose ratio (LRR) cutoff based …

Covid-19 Pandemic And Infant Neurodevelopmental Impairment: A Systematic Review And Meta-Analysis, Kamran Hessami, Amir Hossein Norooznezhad, Sonia Monteiro, Enrico R Barrozo, Abolfazl Shirdel Abdolmaleki, Sara E Arian, Nikan Zargarzadeh, Lara S Shekerdemian, Kjersti M Aagaard, Alireza A Shamshirsaz

Faculty, Staff and Students Publications

IMPORTANCE: Primary studies proposed that aberrant maternal antiviral immunity and/or giving birth in quarantine, such as during the ongoing COVID-19 pandemic, may be associated with the risk of neurodevelopmental impairment (NDI) in offspring.

OBJECTIVES: To evaluate the associations of birth and being raised during the COVID-19 pandemic with risk of NDI among infants and to assess the association of gestational exposure to SARS-CoV-2 with risk of NDI.

DATA SOURCES: PubMed, Web of Science, Scopus, Embase, and preprint servers were systematically searched from inception to March 25, 2022.

STUDY SELECTION: Studies evaluating the neurodevelopment of infants born during the SARS-CoV-2 pandemic …

Association Of Early Steroid Administration With Outcomes Of Children Hospitalized For Covid-19 Without Multisystem Inflammatory Syndrome In Children, Sandeep Tripathi, Meghana Nadiger, Jeremy S Mcgarvey, Aaron A Harthan, Monica Lombardo, Varsha P Gharpure, Nicholas Perkins, Kathleen Chiotos, Imran A Sayed, Erica C Bjornstad, Utpal S Bhalala, Umamaheswara Raju, Aaron S Miller, Heda Dapul, Vicki Montgomery, Karen Boman, Grace M Arteaga, Vikas Bansal, Neha Deo, Aysun Tekin, Ognjen Gajic, Vishakha K Kumar, Rahul Kashyap, Allan J Walkey

Faculty, Staff and Students Publications

IMPORTANCE: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).

OBJECTIVE: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data retrospectively for children (<18 >years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate …

Cardiac Crises: Cardiac Arrhythmias And Cardiomyopathy During Tango2 Deficiency Related Metabolic Crises, Christina Y Miyake, Erica J Lay, Cheyenne M Beach, Scott R Ceresnak, Caridad M Delauz, Taylor S Howard, Christopher M Janson, Kate Jardine, Prince J Kannankeril, Maina Kava, Jeffrey J Kim, Leonardo Liberman, Scott L Macicek, Tam Dam Pham, Terry Robertson, Santiago O Valdes, Gregory Webster, Sara B Stephens, Diana M Milewicz, Mahshid Azamian, Saad A Ehsan, Kimberly M Houck, Claudia Soler-Alfonso, Kevin E Glinton, Mustafa Tosur, Na Li, Weiyi Xu, Seema R Lalani, Lilei Zhang

Faculty, Staff and Students Publications

BACKGROUND: TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy. Data regarding treatment, management, and outcomes of cardiac manifestations of TDD are lacking.

OBJECTIVE: The purpose of this study was to describe TDD-related cardiac crises.

METHODS: Retrospective multicenter chart review was made of TDD patients admitted with cardiac crises, defined as development of ventricular tachycardia (VT), cardiomyopathy, or cardiac arrest during metabolic crises.

RESULTS: Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4-9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all …

First Steps: Primary Outcomes Of A Randomized, Stepped-Care Behavioral Clinical Trial For Parents Of Young Children With New-Onset Type 1 Diabetes, Marisa E Hilliard, Carrie Tully, Maureen Monaghan, Tom Hildebrandt, Christine H Wang, John R Barber, Lauren Clary, Katherine Gallagher, Wendy Levy, Fran Cogen, Celia Henderson, Lefkothea Karaviti, Randi Streisand

Faculty, Staff and Students Publications

OBJECTIVE: Despite the emotional challenges of parental adjustment to a child's type 1 diabetes diagnosis and the unique complexities of early childhood, there are few programs designed to meet the needs of parents of young children at new onset. This study evaluated First STEPS (Study of Type 1 in Early childhood and Parenting Support), a stepped-care behavioral intervention designed to support parents' psychosocial functioning and promote children's glycemic outcomes.

RESEARCH DESIGN AND METHODS: Using a two-site randomized clinical trial design, parents (n = 157) of children aged 1-6 years completed baseline data within 2 months of diabetes diagnosis and were …

From World War Ii To Covid-19: A Historical Perspective On The American Medical Supply Chain, Hunter D Bechtold, Andrea T Cruz, Brent D Kaziny

Faculty, Staff and Students Publications

COVID-19 is the latest episode of shortages of critical medical supplies. Historically and to the present day, medical supplies have been sourced from single regions in the world, thus rendering the supply chain vulnerable to a myriad of harmful circumstances. We argue that shortages in medications related and unrelated to COVID have illustrated the need for the United States to diversify its medical supply sources before future pandemics, political crises, or natural disasters occur.

Noninvasive Respiratory Support Does Not Prevent Extubation Failure In High-Risk Norwood Patients, Adel M Hassan, Sebastian Acosta, Feng Zheng, Craig Rusin, Fabio Savorgnan

Faculty, Staff and Students Publications

UNLABELLED: This study aims to determine whether bilevel positive airway pressure (BiPAP) and continuous positive airway pressure (CPAP) effectively mitigate the risk of extubation failure in children status post-Norwood procedure.

DESIGN: Single-center, retrospective analysis. Extubation events were collected from January 2015 to July 2021. Extubation failure was defined as the need for reintubation within 48 hours of extubation. Demographics, clinical characteristics, and ventilatory settings were compared between successful and failed extubations.

SETTING: Pediatric cardiovascular ICU.

PATIENTS: Neonates following Norwood procedure.

INTERVENTIONS: Extubation following the Norwood procedure.

MEASUREMENTS AND MAIN RESULTS: The analysis included 311 extubations. Extubation failure occurred in 31 …

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: …

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 …

Rolling Stones: An Instructive Case Of Neonatal Cholestasis, Paige Killelea, Shruti Sakhuja, Jose Hernandez, M John Hicks, Sanjiv Harpavat

Faculty, Staff and Students Publications

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin.

CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this …

Quality Of Life, Illness Perceptions, And Parental Lived Experiences In Tango2-Related Metabolic Encephalopathy And Arrhythmias, Chaya N Murali, Seema R Lalani, Mahshid S Azamian, Christina Y Miyake, Hadley Stevens Smith

Faculty, Staff and Students Publications

TANGO2 disorder is a rare genetic disease with multi-system effects that causes episodic crises. Quality of life and psychosocial effects of this rare disease have not previously been studied. To examine health-related quality of life (HRQoL), illness perceptions, and lived experience, we surveyed 16 children and 31 parents of children with TANGO2 disorder identified via a disease-specific social media group and research foundation email distribution list. We assessed HRQoL by parent proxy-report and child self-report using the Pediatric Quality of Life Inventory (PedsQL™). Parental perceptions of their child's condition were assessed using the revised illness perceptions questionnaire adapted for TANGO2 …

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 …

Extracellular Vesicles In Β Cell Biology: Role Of Lipids In Vesicle Biogenesis, Cargo, And Intercellular Signaling, Rebecca S Aguirre, Abhishek Kulkarni, Matthew W Becker, Xiaoyong Lei, Soumyadeep Sarkar, Sasanka Ramanadham, Edward A Phelps, Ernesto S Nakayasu, Emily K Sims, Raghavendra G Mirmira

Faculty, Staff and Students Publications

BACKGROUND: Type 1 diabetes (T1D) is a complex autoimmune disorder whose pathogenesis involves an intricate interplay between β cells of the pancreatic islet, other islet cells, and cells of the immune system. Direct intercellular communication within the islet occurs via cell surface proteins and indirect intercellular communication has traditionally been seen as occurring via secreted proteins (e.g., endocrine hormones and cytokines). However, recent literature suggests that extracellular vesicles (EVs) secreted by β cells constitute an additional and biologically important mechanism for transmitting signals to within the islet.

SCOPE OF REVIEW: This review summarizes the general mechanisms of EV formation, with …

Dietary Fat Composition Shapes Bile Acid Metabolism And Severity Of Liver Injury In A Pig Model Of Pediatric Nafld, Rodrigo Manjarín, Kayla Dillard, Morgan Coffin, Gabriella V Hernandez, Victoria A Smith, Trista Noland-Lidell, Tanvi R Gehani, Hayden J Smart, Kevin Wheeler, Kimberly A Sprayberry, Mark S Edwards, Rob K Fanter, Hunter Glanz, Chad Immoos, Tasha M Santiago-Rodriguez, Jason M Blank, Douglas G Burrin, Brian D Piccolo, Mohammed Abo-Ismail, Michael R La Frano, Magdalena Maj

Faculty, Staff and Students Publications

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were …

Delayed Large Local Reactions To Moderna Covid-19 Vaccine: A Follow-Up Report After Booster Vaccination, Kimberly G Blumenthal, Catherine Ahola, Sara Anvari, Upeka Samarakoon, Esther E Freeman

Faculty, Staff and Students Publications

No abstract provided.

Associations Between Maternal Reports Of Periconceptional Fever From Miscellaneous Causes And Structural Birth Defects, Nithya Lakshmi Mohan Dass, Lorenzo D Botto, Sarah C Tinker, Mark A Canfield, Richard H Finnell, Michael Shayne Gallaway, Syed Shahrukh Hashmi, Adrienne T Hoyt, Wendy N Nembhard, Dorothy K Waller, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

BACKGROUND: Associations between birth defects and fevers attributed to colds, influenza, and urinary tract infections (UTIs) have been observed in previous studies. Our aim was to study associations between birth defects and fevers attributed to other causes.

METHODS: We analyzed data from 34,862 participants in the National Birth Defects Prevention Study, a multistate case-control study of major structural birth defects. Using multivariable logistic regression, we assessed the association between maternal report of fever during early pregnancy due to causes other than colds, influenza, or UTI and 36 categories of birth defects.

RESULTS: Maternal reports of fever due to other causes …

Harmonization Of Multi-Center Diffusion Tensor Tractography In Neonates With Congenital Heart Disease: Optimizing Post-Processing And Application Of Combat, Benjamin Meyers, Vincent K Lee, Lauren Dennis, Julia Wallace, Vanessa Schmithorst, Jodie K Votava-Smith, Vidya Rajagopalan, Elizabeth Herrup, Tracy Baust, Nhu N Tran, Jill Hunter, Daniel J Licht, J William Gaynor, Dean B Andropoulos, Ashok Panigrahy, Rafael Ceschin

Faculty, Staff and Students Publications

Advanced brain imaging of neonatal macrostructure and microstructure, which has prognosticating importance, is more frequently being incorporated into multi-center trials of neonatal neuroprotection. Multicenter neuroimaging studies, designed to overcome small sample sized clinical cohorts, are essential but lead to increased technical variability. Few harmonization techniques have been developed for neonatal brain microstructural (diffusion tensor) analysis. The work presented here aims to remedy two common problems that exist with the current state of the art approaches: 1) variance in scanner and protocol in data collection can limit the researcher's ability to harmonize data acquired under different conditions or using different clinical …