Effects of airway clearance in hospitalized children with neurologic impairment.

Airway clearance therapies (ACT) are often used to optimize respiratory function for children with neurologic impairment (CNI) hospitalized with acute respiratory infections (ARI). In a five-center retrospective cohort study of CNI aged 1-18 years hospitalized between 2013 and 2015 with ARI, we assessed the association of admission ACT with hospital outcomes (days to return to baseline respiratory support and length of stay [LOS]). Generalized estimated equation (GEE) models examined the association between ACT and outcomes, while accounting for clustering.

Clinical features and genotype-phenotype correlations in epilepsy patients with de novo DYNC1H1 variants.

Objective: DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1-related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patients harboring de novo DYNC1H1 pathogenic variants, identify subphenotypes on the DYNC1H1-related epilepsy spectrum, and compare the genotype-phenotype correlations observed in our cohort with the literature.

Role of maternal hyperoxygenation in predicting need for postnatal balloon atrial septostomy in fetal d-transposition of the great arteries.

Objective: Predicting whether postnatal balloon atrial septostomy (BAS) will be necessary for fetuses with dextro-transposition of the great arteries (d-TGA) remains challenging. We sought to determine whether fetal echocardiographic measurements obtained during maternal hyperoxygenation (MH) can improve our ability to predict the need for postnatal BAS.

Methods: This was a retrospective, single-institution review of d-TGA fetuses whose mothers had undergone MH at 33-38 weeks' gestation at the Children's Hospital of Philadelphia, between 1 January 2017 and 30 March 2020.

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.

Immune dysfunction signatures predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia.

BackgroundImmune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8+ T cells and whether they have prognostic relevance.METHODSWe analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).

Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

The seventh multi-stakeholder Paediatric Strategy Forum focused on chimeric antigen receptor (CAR) T-cells for children and adolescents with cancer. The development of CAR T-cells for patients with haematological malignancies, especially B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), has been spectacular. However, currently, there are scientific, clinical and logistical challenges for use of CAR T-cells in BCP-ALL and other paediatric malignancies, particularly in acute myeloid leukaemia (AML), lymphomas and solid tumours.

Factors Associated With COVID-19 Disease Severity in US Children and Adolescents.

Background: Little is known about the clinical factors associated with COVID-19 disease severity in children and adolescents.

Methods: We conducted a retrospective cohort study across 45 US children's hospitals between April 2020 to September 2020 of pediatric patients discharged with a primary diagnosis of COVID-19. We assessed factors associated with hospitalization and factors associated with clinical severity (eg, admission to inpatient floor, admission to intensive care unit [ICU], admission to ICU with mechanical ventilation, shock, death) among those hospitalized.

Analgesia, Sedation, and Neuromuscular Blockade in Infants with Congenital Diaphragmatic Hernia.

Objective: The aim of this study was to describe the use, duration, and intercenter variation of analgesia and sedation in infants with congenital diaphragmatic hernia (CDH).

Study Design: This is a retrospective analysis of analgesia, sedation, and neuromuscular blockade use in neonates with CDH. Patient data from 2010 to 2016 were abstracted from the Children's Hospitals Neonatal Database and linked to the Pediatric Health Information System.

The COVID-19 Pandemic and Changes in Healthcare Utilization for Pediatric Respiratory and Nonrespiratory Illnesses in the United States.

The impact of COVID-19 public health interventions on pediatric illnesses nationwide is unknown. We performed a multicenter, cross-sectional study of encounters at 44 children's hospitals in the United States to assess changes in healthcare utilization during the pandemic. The COVID-19 pandemic was associated with substantial reductions in encounters for respiratory diseases; these large reductions were consistent across illness subgroups.

Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032.

Purpose: Previously our randomized phase III trial demonstrated that immunotherapy including dinutuximab, a chimeric anti-GD2 mAb, GM-CSF, and IL2 improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers.

Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma.

The ability to utilize preclinical models to predict the clinical toxicity of chimeric antigen receptor (CAR) T cells in solid tumors is tenuous, thereby necessitating the development and evaluation of gated systems. Here we found that murine GD2 CAR-T cells, specific for the tumor-associated antigen GD2, induce fatal neurotoxicity in a costimulatory domain-dependent manner. Meanwhile, human B7H3 CAR-T cells exhibit efficacy in preclinical models of neuroblastoma.

Autosomal recessive hypotrichosis with loose anagen hairs associated with TKFC mutations.

Background: Loose anagen hair is a rare form of impaired hair anchorage in which anagen hairs that lack inner and outer root sheaths can be gently and painlessly plucked from the scalp. This condition usually occurs in children and is often self-limiting. A genetic basis for the disorder has been suggested but not proven.

Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations.

African Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome-wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA.

Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response.

An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis.

Thousands of epigenomic data sets have been generated in the past decade, but it is difficult for researchers to effectively use all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for aldated ystematic ntegrati of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic features and transcriptomes from many sources, including individual laboratories and consortia, to produce a comprehensive view of the regulatory landscape of differentiating hematopoietic cell types in mouse.

Extracorporeal membrane oxygenation and bloodstream infection in congenital diaphragmatic hernia.

Objective: To characterize the risk of bloodstream (BSI) and urinary tract infection (UTI) and describe antibiotic use in infants with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO).

Study Design: The Children's Hospitals Neonatal Database was queried for infants with CDH and ECMO treatment from 2010 to 2016. The outcomes included BSI, UTI, and antimicrobial medication.

A parsimonious 3-gene signature predicts clinical outcomes in an acute myeloid leukemia multicohort study.

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy with variable responses to chemotherapy. Although recurring cytogenetic abnormalities and gene mutations are important predictors of outcome, 50% to 70% of AMLs harbor normal or risk-indeterminate karyotypes. Therefore, identifying more effective biomarkers predictive of treatment success and failure is essential for informing tailored therapeutic decisions.

The challenge of defining "ultra-high-risk" neuroblastoma.

Given the biological and clinical heterogeneity of neuroblastoma, risk stratification is vital to determining appropriate treatment. Historically, most patients with high-risk neuroblastoma (HR-NBL) have been treated uniformly without further stratification. Attempts have been made to identify factors that can be used to risk stratify these patients and to characterize an "ultra-high-risk" (UHR) subpopulation with particularly poor outcome.

Impact of Discharge Components on Readmission Rates for Children Hospitalized with Asthma.

Objectives: To describe hospital-based asthma-specific discharge components at children's hospitals and determine the association of these discharge components with pediatric asthma readmission rates.

Study Design: This is a multicenter retrospective cohort study of pediatric asthma hospitalizations in 2015 at children's hospitals participating in the Pediatric Health Information System. Children ages 5 to 17 years were included.