Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in and Vici syndrome patients.

Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms.

De novo FRMD5 Missense Variants in Patients with Childhood-Onset Ataxia, Prominent Nystagmus, and Seizures.

Background: FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities.

Objectives: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain.

Persistently high HBsAg levels during HBeAg-seropositive stage predict lower risk of hepatocellular carcinoma in chronic hepatitis B patients.

Background: High hepatitis B surface antigen (HBsAg) level predicts hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with low viral load. The role of longitudinal HBsAg levels in predicting HCC in HBeAg-positive CHB patients remains unknown.

Method: HBeAg-positive CHB participants from the REVEAL-HBV cohort with ≥2 HBsAg measurements before HBeAg seroclearance were enrolled.

Association Between Urinary Biomarkers and CKD in Extremely Low Gestational Age Neonates.

Rationale & Objective: Children born before 28 weeks' gestation are at increased risk of chronic kidney disease (CKD). Urine biomarkers may shed light on mechanistic pathways and improve the ability to forecast CKD. We evaluated whether urinary biomarkers in neonates of low gestational age (GA) are associated with a reduced estimated glomerular filtration rate (eGFR) over time.

Phase I trial of panobinostat in children with diffuse intrinsic pontine glioma: A report from the Pediatric Brain Tumor Consortium (PBTC-047).

Background: Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood cancer with median survival of less than 1 year. Panobinostat is an oral multihistone deacetylase inhibitor with preclinical activity in DIPG models. Study objectives were to determine safety, tolerability, maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics of panobinostat in children with DIPG.

Rapid Decline Rather Than Absolute Level of HBsAg Predicts Its Seroclearance in Untreated Chronic Hepatitis B Patients From Taiwanese Communities.

Introduction: Hepatitis B surface antigen (HBsAg) clearance leads to favorable outcomes in patients with chronic hepatitis B. HBsAg levels <200 IU/mL with HBsAg decline >0.5 log 10 IU/mL in 1 year have been reportedly predictive of HBsAg loss.

Survey of Pediatric ICU EEG Monitoring-Reassessment After a Decade.

Purpose: In 2011, the authors conducted a survey regarding continuous EEG (CEEG) utilization in critically ill children. In the interim decade, the literature has expanded, and guidelines and consensus statements have addressed CEEG utilization. Thus, the authors aimed to characterize current practice related to CEEG utilization in critically ill children.

Biallelic CACNA2D1 loss-of-function variants cause early-onset developmental epileptic encephalopathy.

Voltage-gated calcium (CaV) channels form three subfamilies (CaV1-3). The CaV1 and CaV2 channels are heteromeric, consisting of an α1 pore-forming subunit, associated with auxiliary CaVβ and α2δ subunits. The α2δ subunits are encoded in mammals by four genes, CACNA2D1-4.

Immune System Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

Context: Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions.

Objective: To evaluate evidence for criteria that define immune system dysfunction in critically ill children and associations with adverse outcomes and develop consensus criteria for the diagnosis of immune system dysfunction in critically ill children.

Data Sources: We conducted electronic searches of PubMed and Embase from January 1992 to January 2020, using medical subject heading terms and text words to define immune system dysfunction and outcomes of interest.

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis.

Importance: Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear.

Objective: To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score.

Data Sources: Systematic search in PubMed from inception to January 1, 2019.

COVID-19 Vaccination-Associated Myocarditis in Adolescents.

Objectives: In this study, we aimed to characterize the clinical presentation, short-term prognosis, and myocardial tissue changes as noted on cardiovascular magnetic resonance (CMR) or cardiac MRI in pediatric patients with coronavirus disease 2019 vaccination-associated myocarditis (C-VAM).

Methods: In this retrospective multicenter study across 16 US hospitals, patients <21 years of age with a diagnosis of C-VAM were included and compared with a cohort with multisystem inflammatory syndrome in children. Younger children with C-VAM were compared with older adolescents.

Delineating the genotypic and phenotypic spectrum of -related neurodevelopmental disorders.

Background: Variants in have recently been reported to cause a neurodevelopmental disorder with hypotonia, seizures and impaired language; however, only six variants have been reported and the clinical characteristics have only broadly been defined.

Methods: Molecular and clinical data were collected from clinical and research cohorts. Massive parallel sequencing was performed and identified individuals with a related neurodevelopmental disorder.

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

Objective: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE).

Methods: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement).

Quality of Care in US NICUs by Race and Ethnicity.

Background: Summary measures are used to quantify a hospital's quality of care by combining multiple metrics into a single score. We used Baby-MONITOR, a summary quality measure for NICUs, to evaluate quality by race and ethnicity across and within NICUs in the United States.

Methods: Vermont Oxford Network members contributed data from 2015 to 2019 on infants from 25 to 29 weeks' gestation or of 401 to 1500 g birth weight who were inborn or transferred to the reporting hospital within 28 days of birth.

Characteristics of patients ≥10 years of age with diffuse intrinsic pontine glioma: a report from the International DIPG/DMG Registry.

Background: Diffuse intrinsic pontine gliomas (DIPG) generally occur in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry (IDIPGR).

Methods: Patients ≥10 years of age at diagnosis enrolled in the IDIPGR with imaging confirmed DIPG diagnosis were included.

The Impact of Erythropoietin on Short- and Long-Term Kidney-Related Outcomes in Neonates of Extremely Low Gestational Age. Results of a Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial.

Objective: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.

Study Design: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.

Results: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.

Applying the Behavior Change Technique Taxonomy to Four Multicomponent Childhood Obesity Interventions.

Applying the Behavior Change Technique Taxonomy has the potential to facilitate identification of effective childhood obesity intervention components. This article evaluates the feasibility of coding Childhood Obesity Prevention and Treatment Consortium interventions and compares reliability between external taxonomy-familiar coders and internal intervention-familiar coders. After training, coder pairs independently coded prespecified portions of intervention materials.

The role of asparagine synthetase on nutrient metabolism in pancreatic disease.

The pancreas avidly takes up and synthesizes the amino acid asparagine (Asn), in part, to maintain an active translational machinery that requires incorporation of the amino acid. The de novo synthesis of Asn in the pancreas occurs through the enzyme asparagine synthetase (ASNS). The pancreas has the highest expression of ASNS of any organ, and it can further upregulate ASNS expression in the setting of amino acid depletion.

Clinical Response to Discordant Therapy in Third-Generation Cephalosporin-Resistant UTIs.

Objectives: To describe the initial clinical response and care escalation needs for children with urinary tract infections (UTIs) resistant to third-generation cephalosporins while on discordant antibiotics.

Methods: We performed a retrospective study of children <18 years old presenting to an acute care setting of 5 children's hospitals and a large managed care organization from 2012 to 2017 with third-generation cephalosporin-resistant UTIs (defined as the growth of ≥50 000 colony-forming units per mL of or spp. nonsusceptible to ceftriaxone with a positive urinalysis).