Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.

Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial.

Background: Progressive familial intrahepatic cholestasis (PFIC) is a group of inherited paediatric liver diseases resulting from mutations in genes that impact bile secretion. We aimed to evaluate the effects of odevixibat, an ileal bile acid transporter inhibitor, versus placebo in children with PFIC.

Methods: Patients eligible for this 24-week, randomised, double-blind, completed, phase 3 study were paediatric outpatients diagnosed with PFIC1 or PFIC2 who had pruritus and elevated serum bile acids at screening.

Neonatal pain, thalamic development and sensory processing behaviour in children born very preterm.

Background: Altered sensory processing is commonly reported in children born very preterm (≤32 weeks' gestational age [GA]). The immature nervous system, particularly the development of connections from the thalamus to the cortex, may show enhanced vulnerability to excessive sensory stimulation, and may contribute to altered sensory processing. Our objective was to determine whether sensory processing assessed at preschool-aged in children born very preterm was predicted by neonatal procedural pain and thalamic development.

Temsirolimus combined with cyclophosphamide and etoposide for pediatric patients with relapsed/refractory acute lymphoblastic leukemia: a Therapeutic Advances in Childhood Leukemia Consortium trial (TACL 2014-001).

Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in acute lymphoblastic leukemia (ALL). The TACL2014-001 phase I trial of the mTOR inhibitor temsirolimus in combination with cyclophosphamide and etoposide was performed in children and adolescents with relapsed/refractory ALL. Temsirolimus was administered intravenously (IV) on days 1 and 8 with cyclophosphamide 440 mg/m2 and etoposide 100 mg/m2 IV daily on days 1-5.

Hyperglycemia associated with acute brain injury in neonatal encephalopathy.

Objective: To identify how alterations in glucose levels are associated with regional brain injury in neonatal encephalopathy.

Methods: This was a prospective cohort study of 102 newborns with neonatal encephalopathy, with continuous glucose monitoring for 72 h. 97 (95%) completed 72 h of therapeutic hypothermia.

Care processes and structures associated with higher medication adherence in adolescent and young adult transplant recipients.

Background: We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients.

Methods: We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25 years old. Patients were ≥3 months post-transplant, ≥2 months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada.

Nutrition and management of glycemia in neonates with neonatal encephalopathy treated with hypothermia.

Adequate nutrition and glycemic homeostasis are increasingly recognized as potentially neuroprotective for the developing brain. In the context of hypoxia-ischemia, evidence is scarce regarding optimal nutritional support and administration route, as well as the short- and long-term consequences of such interventions. In this review, we summarize current knowledge on disturbances of brain metabolism of glucose and substrates by hypoxia-ischemia, and compound effects of these mechanisms on brain injury characterized by specific patterns on EEG and MRI.

International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis.

Objective: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology.

Methods: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2).

Management of comfort and sedation in neonates with neonatal encephalopathy treated with therapeutic hypothermia.

Ensuring comfort for neonates undergoing therapeutic hypothermia (TH) after neonatal encephalopathy (NE) exemplifies a vital facet of neonatal neurocritical care. Physiologic markers of stress are frequently present in these neonates. Non-pharmacologic comfort measures form the foundation of care, benefitting both the neonate and parents.

STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.

Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) is an autosomal dominant immune disorder marked by wide infectious predisposition, autoimmunity, vascular disease, and malignancy. Its molecular hallmark, elevated phospho-STAT1 (pSTAT1) following interferon (IFN) stimulation, is seen consistently in all patients and may not fully account for the broad phenotypic spectrum associated with this disorder. While over 100 mutations have been implicated in STAT1 GOF, genotype-phenotype correlation remains limited, and current overexpression models may be of limited use in gene expression studies.

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure.

Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may influence white matter (WM) development, as previous studies report widespread microstructural alterations and reduced interhemispheric connectivity in SSRI-exposed infants. In rodents, perinatal SSRIs had sex-specific disruptions in corpus callosum (CC) axon architecture and connectivity; yet it is unknown whether SSRI-related brain outcomes in humans are sex specific. In this study, the neonate CC was selected as a region-of-interest to investigate whether prenatal SSRI exposure has sex-specific effects on early WM microstructure.

Image interpretation: Learning analytics-informed education opportunities.

Objectives: Using a sample of pediatric chest radiographs (pCXR) taken to rule out pneumonia, we obtained diagnostic interpretations from physicians and used learning analytics to determine the radiographic variables and participant review processes that predicted for an incorrect diagnostic interpretation.

Methods: This was a prospective cross-sectional study. A convenience sample of frontline physicians with a range of experience levels interpreted 200 pCXR presented using a customized online radiograph presentation platform.

Surgical Reconstruction of Isolated Upper Trunk Brachial Plexus Birth Injuries in the Presence of an Avulsed C5 or C6 Nerve Root.

Background: Avulsion of either the C5 or C6 root with intact middle and lower trunks in brachial plexus birth injury is rare. In these cases, only 1 proximal root is available for intraplexal reconstruction. The purpose of the present study was to determine the outcomes of these patients when single-root reconstruction was balanced across the anterior and posterior elements of the upper trunk.

Surgical Reconstruction of Isolated Upper Trunk Brachial Plexus Birth Injuries in the Presence of an Avulsed C5 or C6 Nerve Root.

Background: Avulsion of either the C5 or C6 root with intact middle and lower trunks in brachial plexus birth injury is rare. In these cases, only 1 proximal root is available for intraplexal reconstruction. The purpose of the present study was to determine the outcomes of these patients when single-root reconstruction was balanced across the anterior and posterior elements of the upper trunk.

Use of a Comprehensive 66-Gene Cholestasis Sequencing Panel in 2171 Cholestatic Infants, Children, and Young Adults.

Objectives: Cholestasis is caused by a wide variety of etiologies, often genetic in origin. Broad overlap in clinical presentations, particularly in newborns, renders prioritizing diagnostic investigations challenging. In this setting, a timely, comprehensive assessment using a multigene panel by a clinical diagnostic laboratory would likely prove useful.

P value and Bayesian analysis in randomized-controlled trials in child health research published over 10 years, 2007 to 2017: a methodological review protocol.

Background: There is an unresolved debate about the reliability of the interpretation of P value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years.

Disruption of exon-bridging interactions between the minor and major spliceosomes results in alternative splicing around minor introns.

Vertebrate genomes contain major (>99.5%) and minor (<0.5%) introns that are spliced by the major and minor spliceosomes, respectively.