Medicine and Health Sciences Commons^™

Kawasaki Disease Shock Syndrome Vs Classical Kawasaki Disease: A Meta-Analysis And Comparison With Sars-Cov-2 Multisystem Inflammatory Syndrome., Loubna Lamrani, Cedric Manlhiot, Matthew D Elias, Nadine F Choueiter, Audrey Dionne, Ashraf S. Harahsheh, Michael A Portman, Brian W Mccrindle, Nagib Dahdah

Pediatrics Faculty Publications

No abstract provided.

Triglyceride-Glucose Index: A Potential New Biomarker For Lung Disease Associated With Metabolic Dysregulation., Xilei Xu Chen, Deepa Rastogi

Pediatrics Faculty Publications

No abstract provided.

Integrated Omics Endotyping Of Infants With Respiratory Syncytial Virus Bronchiolitis And Risk Of Childhood Asthma., Yoshihiko Raita, Marcos Pérez-Losada, Robert J. Freishtat, Brennan Harmon, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa

Pediatrics Faculty Publications

Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinical

Plasticizer Interaction With The Heart: Chemicals Used In Plastic Medical Devices Can Interfere With Cardiac Electrophysiology., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, Daniel Mcinerney, James Hiebert, Erick A Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa G Tereshchenko, Nikki Gillum Posnack

Pediatrics Faculty Publications

BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.

METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure.

RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 …

Usage Of 3d Models Of Tetralogy Of Fallot For Medical Education: Impact On Learning Congenital Heart Disease., Yue-Hin Loke, Ashraf S Harahsheh, Axel Krieger, Laura J Olivieri

Pediatrics Faculty Publications

BACKGROUND: Congenital heart disease (CHD) is the most common human birth defect, and clinicians need to understand the anatomy to effectively care for patients with CHD. However, standard two-dimensional (2D) display methods do not adequately carry the critical spatial information to reflect CHD anatomy. Three-dimensional (3D) models may be useful in improving the understanding of CHD, without requiring a mastery of cardiac imaging. The study aimed to evaluate the impact of 3D models on how pediatric residents understand and learn about tetralogy of Fallot following a teaching session.

METHODS: Pediatric residents rotating through an inpatient Cardiology rotation were recruited. The …

Training Us Health Care Professionals On Human Trafficking: Where Do We Go From Here?, Clydette Powell, Kirsten Dickins, Hanni Stoklosa

Pediatrics Faculty Publications

Some 21 million adults and children are labor-trafficked or sex-trafficked through force, fraud, or coercion. In recognition of the interface between trafficking victims and the healthcare setting, over the last 10 years there has been a notable increase in training of health care professionals (HCPs) on human trafficking (HT) and its health implications. Many organizations have developed curricula and offered training in various clinical settings. However, methods and content of this education on trafficking vary widely, and there is little evaluation of the impact of the training. The goal of this study was to assess the gaps and strengths in …

The Current Consensus On The Clinical Management Of Intracranial Ependymoma And Its Distinct Molecular Variants., Kristian W Pajtler, Stephen C Mack, Vijay Ramaswamy, Christian A Smith, Hendrik Witt, Amy Smith, Eugene Hwang, +Several Additional Authors

Pediatrics Faculty Publications

Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients …

Population Pharmacokinetics Of Liposomal Amphotericin B In Immunocompromised Children., Jodi M Lestner, Andreas H Groll, Ghaith Aljayyoussi, Nita L Seibel, Aziza Shad, Corina Gonzalez, Lauren V Wood, Paul F Jarosinski, Thomas J Walsh, William W Hope

Pediatrics Faculty Publications

Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg(-1) daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = …

Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency., Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas Ahmew, +Several Additional Authors

Pediatrics Faculty Publications

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ …

How Complicated Can It Be? The Link Between Apol1 Risk Variants And Lipoprotein Heterogeneity In Kidney And Cardiovascular Diseases., Chien-An A Hu, Patricio E Ray

Pediatrics Faculty Publications

The beginning of human apolipoprotein L1 study (gene: APOL1; protein: ApoL1) originated from the identification of circulating ApoL1 as an interacting protein of ApoA1 and a minor component of high-density lipoprotein subfraction 3 (HDL3) in 1997 [1]. In the past 18 years, ApoL1 has been investigated in the context of complex human diseases such as African sleeping sickness, schizophrenia, host innate immunity, cancer, hyperlipidemia, cardiovascular diseases, stroke and type 2 diabetes [2–10]. A major breakthrough, however, was the documentation of two haplotypes of APOL1, harboring three coding-sequence mutations as risk variants associated with non-diabetic …

Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial., Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Lori Luchtman-Jones, +Several Additional Authors

Pediatrics Faculty Publications

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible …

Effect Of Kidney Function On Drug Kinetics And Dosing In Neonates, Infants, And Children., Frederique Rodieux, Melanie Wilbaux, Johannes N. Van Den Anker, Marc Pfister

Pediatrics Faculty Publications

Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood …

Intracellular Cd24 Disrupts The Arf-Npm Interaction And Enables Mutational And Viral Oncogene-Mediated P53 Inactivation., Lizhong Wang, Runhua Liu, Peiying Ye, Chunshu Wong, Guo-Yun Chen, Penghui Zhou, +11 Additional Authors

Pediatrics Faculty Publications

CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the …

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …

Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced …

Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis.

METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded …

Proposed Guidelines For The Diagnosis And Management Of Methylmalonic And Propionic Acidemia., Matthias R Baumgartner, Friederike Hörster, Carlo Dionisi-Vici, Goknur Haliloglu, Daniela Karall, Kimberly A. Chapman, +19 Additional Authors

Pediatrics Faculty Publications

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100'000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA …

Aspirin Use And Knowledge In The Community: A Population- And Health Facility Based Survey For Measuring Local Health System Performance., Gregory A Roth, Catherine W. Gillespie, Ali A Mokdad, Danny D Shen, David W Fleming, Andy Stergachis, Christopher J L Murray, Ali H Mokdad

Pediatrics Faculty Publications

BACKGROUND: Little is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.

METHODS: The Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for …

Is Adrenalectomy Necessary During Unilateral Nephrectomy For Wilms Tumor? A Report From The Children's Oncology Group., Kathleen Kieran, James R Anderson, Jeffrey S Dome, Peter F Ehrlich, Michael L Ritchey, Robert C Shamberger, Elizabeth J Perlman, Daniel M Green, Andrew M Davidoff

Pediatrics Faculty Publications

PURPOSE: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome.

METHODS: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy.

RESULTS: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially …