Early engraftment and immune kinetics following allogeneic transplant using a novel reduced-toxicity transplant strategy in children/adolescents with high-risk transfusion-dependent thalassemia: Early results of the ThalFAbS trial.

Background: Allogeneic transplant for patients with transfusion-dependent thalassemia is challenging once there has been iron overload and chronic transfusion support.

Objective(s): A transplant strategy that reduced intensity of the preparative regimen and tailored immunosuppression to both support donor engraftment and prevent GVHD was developed for this population. The combination of a pretransplant immunosuppression phase with reduced dosing of fludarabine/prednisone, treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/ATG was tested.

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.

Circulating High Mobility Group Box-1 Does Not Predict Pulmonary Arterial Hypertension in Children with Congenital Heart Disease: A Prospective Cohort Study.

Objectives: Pulmonary arterial hypertension (PAH) is a devastating complication of pediatric congenital heart disease (CHD). A recent study has identified the protein high mobility group box-1 (HMGB1) as a diagnostic tool in adults with CHD-associated PAH. HMGB1 levels in adults with CHD-associated PAH correlated with mean pulmonary artery pressure and pulmonary vascular resistance, and HGMB1 levels fell in response to sildenafil therapy.

IBAT inhibitors in pediatric cholestatic liver diseases: Transformation on the horizon?

Historically, the therapeutic options available to hepatologists managing cholestasis have been limited. Apart from bile acid--binding resins and the choleretic ursodeoxycholic acid, the medical management of cholestasis in children has been predominately focused on managing the complications of cholestasis, namely pruritus, malnutrition, fat-soluble vitamin deficiencies, and portal hypertension. As such, invasive surgical procedures such as biliary diversion and liver transplantation may become the only options for progressive and unremitting cases of cholestasis.

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.

Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.

Background And Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study.

Neuroimaging to guide neuroprognostication in the neonatal intensive care unit.

Purpose Of Review: Neurological problems are common in infants admitted to the neonatal intensive care unit (NICU). Various neuroimaging modalities are available for neonatal brain imaging and are selected based on presenting problem, timing and patient stability.

Recent Findings: Neuroimaging findings, taken together with clinical factors and serial neurological examination can be used to predict future neurodevelopmental outcomes.

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.

Pediatric Rheumatology Care and Outcomes Improvement Network's Quality Measure Set to Improve Care of Children With Juvenile Idiopathic Arthritis.

Objective: To describe the selection, development, and implementation of quality measures (QMs) for juvenile idiopathic arthritis (JIA) by the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN), a multihospital learning health network using quality improvement methods and leveraging QMs to drive improved outcomes across a JIA population since 2011.

Methods: An American College of Rheumatology-endorsed multistakeholder process previously selected initial process QMs. Clinicians in PR-COIN and parents of children with JIA collaboratively selected outcome QMs.

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.

Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum.

Purpose: Bone morphogenic proteins (BMPs) regulate gene expression that is related to many critical developmental processes, including osteogenesis for which they are named. In addition, BMP2 is widely expressed in cells of mesenchymal origin, including bone, cartilage, skeletal and cardiac muscle, and adipose tissue. It also participates in neurodevelopment by inducing differentiation of neural stem cells.

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.