Investigation of a Novel Noninvasive Risk Analytics Algorithm With Laboratory Central Venous Oxygen Saturation Measurements in Critically Ill Pediatric Patients.

Background: Accurate assessment of oxygen delivery relative to oxygen demand is crucial in the care of a critically ill patient. The central venous oxygen saturation (Svo) enables an estimate of cardiac output yet obtaining these clinical data requires invasive procedures and repeated blood sampling. Interpretation remains subjective and vulnerable to error.

Maralixibat Reduces Serum Bile Acids and Improves Cholestatic Pruritus in Adolescents With Alagille Syndrome.

Background: Alagille syndrome (ALGS) is a multisystem cholestatic disorder. Maralixibat is approved for the treatment of cholestatic pruritus in ALGS with limited data in adults.

Methods: Participants were included if they received ≥ 2 doses of maralixibat at age ≥ 16 years in one of the three previously published maralixibat ALGS clinical trials.

Predictive model of neurodevelopmental outcome in neonatal hypoxic ischemic encephalopathy.

Objectives: To build an early, prognostic model for adverse outcome in infants with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) based on brain magnetic resonance images (MRI), electrophysiological tests and clinical assessments were performed during the first 5 days of life.

Methods: Retrospective study of 182 neonates with HIE and managed with TH. The predominant pattern of HIE brain injury on MRI performed following cooling was scored by neuroradiologists.

Radiation Reduction in Paediatric Cardiac Catheterization: We Can Go Even Lower.

Background: Radiation reduction is an integral component in the management of a paediatric cardiac catheterization laboratory. Simple and easily implementable protocol changes and technical upgrades have been shown to significantly reduce radiation exposure.

Methods: Radiation exposures (2020-2022) at Safra Children's Hospital, Sheba Medical Center, Israel (unit A: n = 672) were retrospectively reviewed, including dose area product (DAP) (μGy m), DAP/kg, Air Kerma (mGy), and fluoroscopy time (minutes) for 16 procedural types.

Preterm Sex Differences in Neurodevelopment and Brain Development from Early Life to 8 Years of Age.

Objective: To examine sex differences in neurodevelopmental outcomes and brain development from early life to 8 years in males and females born preterm.

Study Design: This was a prospective cohort study of infants born very preterm (24-32 weeks of gestation) and followed to 8 years with standardized measures of neurodevelopment. Brain magnetic resonance imaging scans were performed soon after birth, term-equivalent age, and 8 years.

Utilization of next-generation sequencing to define the role of heterozygous variants in immunodeficiency.

Background: Forkhead box protein N1 (FOXN1) transcription factor plays an essential role in the development of thymic epithelial cells, required for T-cell differentiation, maturation, and function. Biallelic pathogenic variants in cause severe combined immunodeficiency (SCID). More recently, heterozygous variants in identified by restricted gene panels, were also implicated with causing a less severe and variable immunodeficiency.

Outcomes and management in paediatric autoimmune hepatitis presenting as acute liver failure: Individual patient data meta-analysis.

Background And Aims: Autoimmune hepatitis (AIH) in children presenting in acute liver failure (ALF) can be fatal and often requires liver transplantation (LTx). This individual patient data meta-analysis (IPD) aims to examine management and outcomes of this population, given the lack of large cohort studies on paediatric AIH first presenting as ALF (AIH-ALF).

Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses of IPD statement using PubMed and Excerpta Medica dataBASE, and included English studies published between 2000 and 2020.

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

Background And Objectives: We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants.

Methods: A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.

A novel model to study mechanisms of cholestasis in human cholangiocytes reveals a role for the SIPR2 pathway.

Background: Ductular reactivity is central to the pathophysiology of cholangiopathies. Mechanisms underlying the reactive phenotype activation by exogenous inflammatory mediators and bile acids are poorly understood.

Methods: Using human extrahepatic cholangiocyte organoids (ECOs) we developed an injury model emulating the cholestatic microenvironment with exposure to inflammatory mediators and various pathogenic bile acids.

Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis.

Objective: Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR.

Methods: Consenting children or young adults with CNO were enrolled into CHOIR.

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor.

Background And Aims: Refractory pruritus and other complications of cholestasis are indications for liver transplantation (LT) in patients with Alagille syndrome (ALGS). We evaluated predictors of event-free survival and transplant-free survival in patients with ALGS treated with maralixibat (MRX), an ileal bile acid transporter inhibitor.

Approach And Results: We assessed patients with ALGS from 3 clinical trials of MRX with up to 6 years of follow-up.

Deep phenotypic characterization of the retinal dystrophy in patients with RNU4ATAC-associated Roifman syndrome.

Purpose: To characterize the retinal phenotype in RNU4ATAC-associated Roifman syndrome.

Methods: Ten patients (including 8 males) with molecularly confirmed Roifman syndrome underwent detailed ophthalmologic evaluation including fundus imaging, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), and electroretinography (ERG). Six patients had follow-up eye exams.

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy.

Background And Objectives: Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE.

Methods: This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU).

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.

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.

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.

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).

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.

Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia.

Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.