Medical Specialties Commons^™

Epidemiology Of Intestinal Parasite Infections And Multiparasitism And Their Impact On Growth And Hemoglobin Levels During Childhood In Tropical Ecuador: A Longitudinal Study Using Molecular Detection Methods, Rojelio Mejia, Irina Chis Ster, Martha E Chico, Irene Guadalupe, Andrea Arévalo-Cortés, Andrea Lopez, Aida Y Oviedo-Vera, Philip J Cooper

Faculty, Staff and Students Publications

Background: There are few longitudinal epidemiological studies of intestinal parasitic infections (IPI) and their health effects. We studied the epidemiology and determinants of IPI and multiparasitism during childhood using molecular methods for parasite detection and analysed their effects on growth and hemoglobin levels.

Methods: Random sample of 401 children from an Ecuadorian birth cohort followed up to 8 years of age. Data on environmental and sociodemographic characteristics were collected by questionnaires. Stool samples were collected, and weight, height, and hemoglobin levels were measured at 7 and 13 months, and 2, 3, 5, and 8 years. Stool samples were analysed using …

Reliability Of Physician Estimation Of Pelvic Free Fluid Volume On The Pediatric Focused Assessment With Sonography For Trauma., Ashkon Shaahinfar, Jennifer Rosin Wiebelhaus, Newton Addo, Ronald A. Cohen, Pinar Karakas-Rothey, Aaron E. Kornblith

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To evaluate the reliability of physician gestalt estimation of pelvic free fluid volume on pediatric Focused Assessment with Sonography for Trauma (FAST). To determine a reliable cut-off volume and characteristics associated with small pelvic free fluid.

METHODS: Our study assessed the ability of 2 ultrasound-trained pediatric emergency medicine (PEM) physicians and 2 pediatric radiologists to characterize pelvic free fluid in a retrospective convenience sample of archived FAST from a Level 1 pediatric trauma center, April 2018-June 2020. Inter- and intra-rater reliability were measured to determine the most reliable volume cut-off. Chi-squared and Fisher's exact tests determined characteristics associated with …

Time To Treatment In Pediatric Patients With Repeated Episodes Of Status Epilepticus, Jennifer V Gettings, Iván Sánchez Fernández, Anne Anderson, J Nicholas Brenton, Afra Can, Justice Clark, Raquel Farias Moeller, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Edward Novotny, Adam P Ostendorf, Juan Piantino, James J Riviello, Kumar Sannagowdara, Robert C Tasker, Dmitry Tchapyjnikov, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Bo Zhang, Tobias Loddenkemper, Marina Gaínza-Lein, Pediatric Status Epilepticus Research Group (Pserg)

Duncan NRI Faculty and Staff Publications

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to …

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

Department of Pediatrics Faculty Papers

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

Characterising Acute And Chronic Care Needs: Insights From The Global Burden Of Disease Study 2019, A. A. Asadi-Pooya

Department of Neurology Faculty Papers

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic …

Spectrum Of Coronary Artery Involvement With Multisystem Inflammatory Syndrome In Children Versus Kawasaki Disease., Simon Lee, Ashraf S. Harahsheh, Geetha Raghuveer, Michael A. Portman, Arash A. Sabati, Michael Khoury, Nagib Dahdah, Marianna Fabi, Supriya S. Jain, Audrey Dionne, Kyle Runeckles, Frederic Dallaire, Nadine F. Choueiter, Tyler H. Harris, Matthew D. Elias, Anji T. Yetman, Balasubramanian Sundaram, Luis M. Garrido-Garcia, Nilanjana Misra, Cedric Manlhiot, Pedrom Farid, Brian W. Mccrindle

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: There is significant overlap in clinical features between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD). We sought to compare the prevalence, severity, and associated factors for coronary artery (CA) involvement.

METHODS AND RESULTS: From January 1, 2020 through January 31, 2023, 1191 patients with MIS-C and 554 patients contemporaneously diagnosed with KD were enrolled into the International Kawasaki Disease Registry. Demographic and clinical features, laboratory values, maximum Z score in any CA branch +2.5 or greater) were determined separately for each diagnosis using multivariable logistic regression analyses. The prevalence of CA aneurysms was lower for MIS-C …

Changes In Adequacy Of Splanchnic Oxygen Delivery And Splanchnic Artery Doppler After Bolus Feedings In Infants: A Systematic Review And Meta-Analysis, Rohit S Loomba, Saloni P Sheth, Joshua Wong, Megan Davis, Juan S Farias, Enrique G Villarreal, Saul Flores

Faculty, Staff and Students Publications

Background: Current practice regarding timing of feed initiation and feed tolerance largely relies on anecdotal practice and protocols. This study aims to provide an objective measure to guide clinical practice by analyzing changes in splanchnic regional oxygen saturation and Doppler patterns with feeds.

Methods: A systematic review was performed. Inclusion criteria were: 1) patients under 1 year of age; 2) splanchnic regional oxygen saturation with near infrared spectroscopy before and after feeds or mesenteric Doppler findings before and after feeds; and 3) clinical parameters must have been presented as either mean and standard deviation or median and range. Endpoints of …

Early Prediction Of Mortality And Morbidities In Vlbw Preterm Neonates Using Machine Learning, Chi-Hung Shu, Rema Zebda, Camilo Espinosa, Jonathan Reiss, Anne Debuyserie, Kristina Reber, Nima Aghaeepour, Mohan Pammi

Faculty, Staff and Students Publications

Background: Predicting mortality and specific morbidities before they occur may allow for interventions that may improve health trajectories.

Hypothesis: Integrating key maternal and postnatal infant variables in the first 2 weeks of age into machine learning (ML) algorithms will reliably predict survival and specific morbidities in VLBW preterm infants.

Methods: ML algorithms were developed to integrate 47 features for predicting mortality, bronchopulmonary dysplasia (BPD), neonatal sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP). A retrospective cohort (n = 3341) was used to train and validate the models with a repeated 10-fold cross-validation …

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

Faculty, Staff and Students Publications

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

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

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

Results: A total …

The Central Role Of Cytochrome P450 Reductase (Cpr) In Hyperoxic Lung Injury, Deven Narke, Bhagavatula Moorthy

Faculty, Staff and Students Publications

Introduction: Hyperoxic lung injury results from excessive supplemental oxygen therapy in conditions such as bronchopulmonary dysplasia (BPD) in preterm infants and acute respiratory distress syndrome (ARDS) in adults. This review explores the role of cytochrome P450 reductase (CPR) in hyperoxic lung injury.

Areas covered: Hyperoxia induces the production of reactive oxygen species in excessive amounts, overwhelming the body's antioxidant defenses and exacerbating lung injury in ARDS/BPD. This review examines the differential roles of CPR-dependent enzymes in the context of hyperoxic lung injury. Additionally, we highlight the potential of targeting CPR to study mechanisms of lung injury and leverage gene-editing technologies …

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

Faculty, Staff and Students Publications

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

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

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

Bi-Allelic Uggt1 Variants Cause A Congenital Disorder Of Glycosylation, Zain Dardas, Laura Harrold, Daniel G Calame, Claire G Salter, Takashi Kikuma, Kevin P Guay, Bobby G Ng, Kanae Sano, Ahmad K Saad, Haowei Du, Riccardo Sangermano, Sohil G Patankar, Shalini N Jhangiani, Semra Gürsoy, Mohamed S Abdel-Hamid, Mahmoud K H Ahmed, Reza Maroofian, Rauan Kaiyrzhanov, Kamran Salayev, Wendy D Jones, Ana Pérez Caballero, Lucy Mcgavin, Michael Spiller, Miranda Durkie, Nick Wood, Lauren O'Grady, Paula Goldenberg, Ann M Neumeyer, Amber Begtrup, Sherif F Abdel-Ghafar, Maha S Zaki, Hilde Van Esch, Jennifer E Posey, Olivia K Wenger, Ethan M Scott, Kinga M Bujakowska, Richard A Gibbs, Davut Pehlivan, Dana Marafi, Joseph S Leslie, Nishanka Ubeyratna, Jacob Day, Martina Owens, Jessica Settle, Soher Balkhy, Abdullah Tamim, Lama Alabdi, Fowzan S Alkuraya, Yoichi Takeda, Hudson H Freeze, Daniel N Hebert, James R Lupski, Andrew H Crosby, Emma L Baple

Faculty, Staff and Students Publications

Congenital disorders of glycosylation (CDGs) comprise a large heterogeneous group of metabolic conditions caused by defects in glycoprotein and glycolipid glycan assembly and remodeling, a fundamental molecular process with wide-ranging biological roles. Herein, we describe bi-allelic UGGT1 variants in fifteen individuals from ten unrelated families of various ethnic backgrounds as a cause of a distinctive CDG of variable severity. The cardinal clinical features of UGGT1-CDG involve developmental delay, intellectual disability, seizures, characteristic facial features, and microcephaly in the majority (9/11 affected individuals for whom measurements were available). The more severely affected individuals display congenital heart malformations, variable skeletal abnormalities including …

Enterovirus D68-Associated Respiratory Illness In Children., Benjamin R. Clopper, Adriana S. Lopez, Leah A. Goldstein, Terry Fei Fan Ng, Ariana P. Toepfer, Mary A. Staat, Elizabeth P. Schlaudecker, Leila C. Sahni, Julie A. Boom, Jennifer E. Schuster, Rangaraj Selvarangan, Natasha B. Halasa, Laura S. Stewart, John V. Williams, Marian G. Michaels, Geoffrey A. Weinberg, Peter G. Szilagyi, Eileen J. Klein, Janet A. Englund, Meredith L. Mcmorrow, Heidi L. Moline, Claire M. Midgley

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Enterovirus D68 (EV-D68) typically causes mild to severe acute respiratory illness (ARI). Testing and surveillance for EV-D68 in the US are limited, and important epidemiologic gaps remain.

OBJECTIVE: To characterize the epidemiology and clinical severity of EV-D68 among US children seeking care for ARI from 2017 to 2022, using a multisite, active, systematic surveillance network.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study collected data from the New Vaccine Surveillance Network, an active, prospective, population-based surveillance system of emergency departments (EDs) and hospitals at 7 US academic medical centers. Children with ARI and EV-D68-positive results were enrolled during platform-wide EV-D68 …

Further Delineation Of The Scaf4-Associated Neurodevelopmental Disorder, Cosima M Schmid, Anne Gregor, Anna Ruiz, Carmen Manso Bazús, Isabella Herman, Farah Ammouri, Urania Kotzaeridou, Vanda Mcniven, Lucie Dupuis, Katharina Steindl, Anaïs Begemann, Anita Rauch, Aude-Annick Suter, Bertrand Isidor, Sandra Mercier, Mathilde Nizon, Benjamin Cogné, Wallid Deb, Thomas Besnard, Tobias B Haack, Ruth J Falb, Amelie J Müller, Tobias Linden, Chad R Haldeman-Englert, Charlotte W Ockeloen, Francesca Mattioli, Alexandre Reymond, Nazia Ibrahim, Shagufta Naz, Elodie Lacaze, Jennifer A Bassetti, Julia Hoefele, Theresa Brunet, Korbinian M Riedhammer, Houda Z Elloumi, Richard Person, Fanggeng Zou, Juliette J Kahle, Kirsten Cremer, Axel Schmidt, Marie-Ange Delrue, Pedro M Almeida, Fabiana Ramos, Siddharth Srivastava, Aisling Quinlan, Stephen Robertson, Eva Manka, Alma Kuechler, Stephanie Spranger, Malgorzata J M Nowaczyk, Reem M Elshafie, Hind Alsharhan, Paul R Hillman, Leslie A Dunnington, Hilde M H Braakman, Shane Mckee, Angelica Moresco, Andrea-Diana Ignat, Ruth Newbury-Ecob, Guillaume Banneau, Olivier Patat, Jeffrey Kuerbitz, Susan Rzucidlo, Susan S Sell, Patricia Gordon, Sarah Schuhmann, André Reis, Yosra Halleb, Radka Stoeva, Boris Keren, Zainab Al Masseri, Zeynep Tümer, Sophia Hammer-Hansen, Sofus Krüger Sølyst, Connolly G Steigerwald, Nicolas J Abreu, Helene Faust, Amica Müller-Nedebock, Frédéric Tran Mau-Them, Heinrich Sticht, Christiane Zweier

Faculty, Staff and Student Publications

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one …

Changes In Adequacy Of Splanchnic Oxygen Delivery And Splanchnic Artery Doppler After Bolus Feedings In Infants: A Systematic Review And Meta-Analysis., Rohit S. Loomba, Saloni P. Sheth, Joshua Wong, Megan Davis, Juan S. Farias, Enrique G. Villarreal, Saul Flores

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Current practice regarding timing of feed initiation and feed tolerance largely relies on anecdotal practice and protocols. This study aims to provide an objective measure to guide clinical practice by analyzing changes in splanchnic regional oxygen saturation and Doppler patterns with feeds.

METHODS: A systematic review was performed. Inclusion criteria were: 1) patients under 1 year of age; 2) splanchnic regional oxygen saturation with near infrared spectroscopy before and after feeds or mesenteric Doppler findings before and after feeds; and 3) clinical parameters must have been presented as either mean and standard deviation or median and range. Endpoints of …

Temporal Trends Of Subsequent Central Nervous System Malignancies Among Survivors Of Childhood Cancer, Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Susan Smith, Michael A Arnold, Miriam Conces, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.

Results: A total of 157 CNS …

Development Of A Reference Standard To Assign Bacterial Versus Viral Infection Etiology Using An All-Inclusive Methodology For Comparison Of Novel Diagnostic Tool Performance, Coburn Allen, J Kate Deanehan, Yaniv Dotan, Matthew A Eisenberg, Andrew M Fine, Jonathan Isenberg, Ann Kane, Dani Kirshner, Todd W Lyons, Yasmin Maor, Ami Neuberger, Daniel G Ostermayer, Sharona Paz, Oded Scheuerman, Shachaf Shiber, Victoria A Statler, Michal Stein, Renata Yakubov, Shirly Yanai, Roy Navon, Lior Kellerman, Tanya M Gottlieb, Eran Eden

Faculty, Staff and Student Publications

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included. Adjudicators, blinded to C-reactive protein, procalcitonin, and MeMed BV (MMBV), labeled each case (bacterial/viral/non-infectious/indeterminate). Initial adjudication involved 3 adjudicators. Reference standard cohorts were defined: Microbiologically confirmed (3/3 adjudicators concur with high confidence and a concordant microbiological finding), unanimous (3/3 adjudicators concur with high confidence), suspected (3/3 adjudicators concur with …

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

Faculty, Staff and Students Publications

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

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

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

Faculty, Staff and Students Publications

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

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

Results: From December 2018 to …

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

Germline Pathogenic Drosha Variants Are Linked To Pineoblastoma And Wilms Tumor Predisposition, Peter N Fiorica, Lisa Golmard, Jung Kim, Riyue Bao, Frank Y Lin, Angshumoy Roy, Allison Pribnow, Melissa R Perrino, Julien Masliah-Planchon, Sophie Michalak-Provost, Jennifer Wong, Mathilde Filser, Dominique Stoppa-Lyonnet, Franck Bourdeaut, Afane Brahimi, Olivier Ingster, Giselle Saulnier Sholler, Sarah A Jackson, Mark M Sasaki, Trent Fowler, Anita Ng, Ryan J Corbett, Rebecca S Kaufman, Jeremy S Haley, David J Carey, Kuan-Lin Huang, Sharon J Diskin, Jo Lynne Rokita, Hussam Al-Kateb, Rose B Mcgee, Joshua D Schiffman, Kenneth S Chen, Douglas R Stewart, D Williams Parsons, Sharon E Plon, Kris Ann P Schultz, Kenan Onel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported.

Experimental design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts.

Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a …

A Cluster Randomized Trial Of Xylitol Chewing Gum For Prevention Of Preterm Birth: The Ppax Trial, Gregory C Valentine, Kathleen M Antony, Haleh Sangi-Haghpeykar, Alexis C Wood, Rose Chirwa, Saukani Petro, Mary Dumba, Deborah Nanthuru, Cynthia Shope, Jesse Mlotha-Namarika, Jeffrey Wilkinson, Joshua Aagaard, Ellen J Aagaard, Maxim D Seferovic, Judy Levison, Peter Kazembe, Kjersti M Aagaard

Children’s Nutrition Research Center Staff Publications

Background: Maternal periodontal disease is associated with preterm and low-birthweight deliveries, but randomized trials of likely efficacious treatments (e.g., dental scaling and root planing) during pregnancy have not reduced these adverse outcomes. As an alternative, we hypothesized that periconception initiation of xylitol chewing gum would reduce the occurrence of preterm or low-birthweight deliveries among a historical high-prevalence population in Malawi.

Methods: We conducted an open-label, parallel-enrollment, matched-pair, cluster-randomized, controlled clinical trial across eight health centers (sites) in and around Lilongwe, Malawi. Sites were paired by anticipated delivery volume and randomized to prenatal and oral health education alone (active control) or …

Protocol For A Multisite, Observational Clinical Study Of The Association Between Skin Colour And Pulse Oximeter Accuracy In Children Undergoing Cardiac Catheterisation (Pach Study), Halley Ruppel, Liming Huang, Christopher J Petit, Athar M Qureshi, Christopher P Bonafide, Elizabeth E Foglia, Jeffery Feldman, Meghan B Lane-Fall, Jennifer M Lynch, Anna Chien, Michelle Dunn, Michael L O'Byrne

Faculty, Staff and Students Publications

Introduction: Prospective, real-world clinical studies of the association between skin color and pulse oximeter (SpO2) accuracy in children are needed to address the limitations of previous research. Such studies are essential for generating evidence for clinicians, regulators and industry. This is the protocol for a multisite study funded by the National Heart, Lung, and Blood Institute (R01HL171313; 1 January 2024-31 December 2028).

Methods and analysis: In this pragmatic, observational study conducted in three large paediatric cardiac catheterisation centres in the USA, children undergoing cardiac catheterisation with directly measured arterial oxygen saturation will be prospectively enrolled. The outcome variable (SpO2 bias) …

De Novo Variants In Cdkl1 And Cdkl2 Are Associated With Neurodevelopmental Symptoms, Ali H Bereshneh, Jonathan C Andrews, Daniel F Eberl, Guney Bademci, Nicholas A Borja, Stephanie Bivona, Wendy K Chung, Shinya Yamamoto, Michael F Wangler, Shane Mckee, Mustafa Tekin, Hugo J Bellen, Oguz Kanca

Duncan NRI Faculty and Staff Publications

The CDKL (cyclin-dependent kinase-like) family consists of five members in humans, CDKL1-5, that encode serine-threonine kinases. The only member that has been associated with a Mendelian disorder is CDKL5, and variants in CDKL5 cause developmental and epileptic encephalopathy type 2 (DEE2). Here, we study four de novo variants in CDKL2 identified in five individuals, including three unrelated probands and monozygotic twins. These individuals present with overlapping symptoms, including global developmental delay, intellectual disability, childhood-onset epilepsy, dyspraxia, and speech deficits. We also identified two individuals with de novo missense variants in CDKL1 in the published Deciphering Developmental Disorders (DDD) and GeneDx …

Clinical And Genetic Delineation Of Autosomal Recessive And Dominant Actl6b-Related Developmental Brain Disorders, Elisa Cali, Tania Quirin, Clarissa Rocca, Stephanie Efthymiou, Antonella Riva, Dana Marafi, Maha S Zaki, Mohnish Suri, Roberto Dominguez, Hasnaa M Elbendary, Shahryar Alavi, Mohamed S Abdel-Hamid, Heba Morsy, Frederic Tran Mau-Them, Mathilde Nizon, Pavel Tesner, Lukáš Ryba, Faisal Zafar, Nuzhat Rana, Nebal W Saadi, Zahra Firoozfar, Pinar Gencpinar, Bulent Unay, Canan Ustun, Ange-Line Bruel, Christine Coubes, Jennifer Stefanich, Ozlem Sezer, Emanuele Agolini, Antonio Novelli, Gessica Vasco, Donatella Lettori, Mathieu Milh, Laurent Villard, Shimriet Zeidler, Henry Opperman, Vincent Strehlow, Mahmoud Y Issa, Hebatallah El Khassab, Prem Chand, Shahnaz Ibrahim, Ali Rashidi-Nezhad, Mohammad Miryounesi, Pegah Larki, Jennifer Morrison, Ingrid Cristian, Isabelle Thiffault, Nicole L Bertsch, Grace J Noh, John Pappas, Ellen Moran, Nikolaos M Marinakis, Joanne Traeger-Synodinos, Susan Hosseini, Mohammad Reza Abbaszadegan, Roseline Caumes, Lisenka E L M Vissers, Maedeh Neshatdoust, Mostafa Montazer Zohour, Elmostafa El Fahime, Christina Canavati, Lara Kamal, Moien Kanaan, Omar Askander, Victoria Voinova, Olga Levchenko, Shahzhad Haider, Sara S Halbach, Rayana Elias Maia, Salehi Mansoor, Vivek Jain, Sanjukta Tawde, Viveka Santhosh R Challa, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Lucas Alves Victor, Benito Pinero-Banos, Jennifer Hague, Heba Ahmed Elawady, Adelia Maria De Miranda Henriques-Souza, Huma Arshad Cheema, Muhammad Nadeem Anjum, Sara Idkaidak, Firas Alqarajeh, Osama Atawneh, Hagar Mor-Shaked, Tamar Harel, Giovanni Zifarelli, Peter Bauer, Fernando Kok, Joao Paulo Kitajima, Fabiola Monteiro, Juliana Josahkian, Gaetan Lesca, Nicolas Chatron, Dorothe Ville, David Murphy, Jeffrey L Neul, Sureni V Mullegama, Amber Begtrup, Isabella Herman, Tadahiro Mitani, Jennifer E Posey, Chee Geap Tay, Iram Javed, Lucinda Carr, Farah Kanani, Fiona Beecroft, Lee Hane, Elsayed Abdelkreem, Milan Macek, Luciana Bispo, Marwa Abd Elmaksoud, Farzad Hashemi-Gorji, Davut Pehlivan, David J Amor, Rami Abou Jamra, Wendy K Chung, Eshan Ghayoor Karimiani, Philippe M Campeau, Fowzan S Alkuraya, Alistair T Pagnamenta, Joseph G Gleeson, James R Lupski, Pasquale Striano, Andres Moreno-De-Luca, Denis L J Lafontaine, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.

Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, …

Genetic Testing Utilization In The U.S. Registry For Childhood Interstitial And Diffuse Lung Diseases., Laura A. Voss, Rebekah J. Nevel, Jennifer A. Wambach, Lawrence M. Nogee, Robin R. Deterding, Alicia M. Casey, Michael G. O'Connor, Daniel I. Craven, Jane B. Taylor, Gail H. Deutsch, Jade B. Tam-Williams, Lea C. Steffes, Steven K. Brennan, Maria T. Santiago, Sara C. Sadreameli, Andrea F. Heras, Michael R. Powers, Antonia P. Popova, Manvi Bansal, Aaron Hamvas, William A. Gower, Fernando Urrego, Lisa R. Young, Child Registry Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Childhood interstitial and diffuse lung diseases (chILD) comprise a diverse group of rare disorders. Identifying the underlying cause is crucial for treatment, prognosis, and estimating recurrence risk. The objective of this study was to assess the utilization of genetic testing for subjects enrolled in the United States National Registry for ChILD, a multicenter observational study.

METHODS: Genetic data from participating sites were reviewed and analyzed in relationship to clinical characteristics.

RESULTS: Of 609 children enrolled from 22 centers, genetic testing was performed for 55.5% (n = 338). Genetic testing results were positive (diagnostic) for 22.8% (n = 77), negative …

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

Faculty, Staff and Students Publications

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

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

Factors Associated With Shock At Presentation In Kawasaki Disease Versus Multisystem Inflammatory Syndrome In Children Associated With Covid-19., Supriya S. Jain, Ashraf S. Harahsheh, Simon Lee, Geetha Raghuveer, Nagib Dahdah, Michael Khoury, Michael A. Portman, Melissa Wehrmann, Arash A. Sabati, Marianna Fabi, Deepika Thacker, Nilanjana Misra, Mark D. Hicar, Nadine F. Choueiter, Matthew D. Elias, Audrey Dionne, William B. Orr, Jacqueline R. Szmuszkovicz, Seda Selamet Tierney, Luis Martin Garrido-Garcia, Frederic Dallaire, Balasubramanian Sundaram, Deepa Prasad, Tyler H. Harris, Elizabeth Braunlin, Elisa Fernandez Cooke, Cedric Manlhiot, Pedrom Farid, Brian W. Mccrindle, International Kawasaki Disease Registry

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: While clinical overlap between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) has been evident, information regarding those presenting with shock has been limited. We sought to determine associations with shock within and between diagnosis groups.

METHODS: The International KD Registry enrolled contemporaneous patients with either KD or MIS-C from 39 sites in 7 countries from January 1, 2020, to January 1, 2023. Demographics, clinical features and presentation, management, laboratory values, and outcomes were compared between the diagnosis and shock groups.

RESULTS: Shock at presentation was noted for 19 of 672 KD patients (2.8%) and 653 of …

Pediatric Myeloid Neoplasms With Ubtf Tandem Duplications: Morphologic, Immunophenotypic, And Clinical Characterization, Mahsa Khanlari, Wei Wang, Yonghui Ni, Paul E Mead, Masayuki Umeda, Tami Westover, Jing Ma, Jeffrey E Rubnitz, Juan M Barajas, Stanley Pounds, Jeffery M Klco

Faculty, Staff and Student Publications

Tandem duplications (TDs) in exons of upstream binding transcription factor (UBTF-TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF-TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF-TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts …