X-Linked Agammaglobulinemia: Infection Frequency and Infection-Related Mortality in the USIDNET Registry.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. A potential benefit of earlier diagnosis and treatment initiation on morbidity and mortality in XLA is incompletely understood. In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation.

Pathogen-Specific Humoral Immunity and Infections in B Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy Recipients with Multiple Myeloma.

Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA-CARTx) is an emerging treatment for relapsed or refractory multiple myeloma (R/R MM). Here we characterize the epidemiology of infections, risk factors for infection, and pathogen-specific humoral immunity in patients receiving BCMA-CARTx for R/R MM. We performed a retrospective cohort study in 32 adults with R/R MM enrolled in 2 single-institution phase 1 clinical trials of BCMA-CARTx administered after lymphodepleting chemotherapy alone (n = 22) or with a gamma secretase inhibitor (GSI).

Chronic Granulomatous Disease With Inflammatory Bowel Disease: Clinical Presentation, Treatment, and Outcomes From the USIDNET Registry.

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity caused by defects in the phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex, leading to increased susceptibility to infection and inflammatory autoimmune diseases. Up to 50% of patients have gastrointestinal (GI) involvement and meet diagnostic criteria for inflammatory bowel disease (CGD-IBD).

Objective: We analyzed patients with CGD from the US Immunodeficiency Network (USIDNET) registry to determine whether IBD changes the presentation, treatment, and outcomes of patients with CGD.

Lymphoma in Partial DiGeorge Syndrome: Report of 2 Cases.

Primary immunodeficiency diseases are associated with an increased tendency for noninfectious complications of autoimmunity and malignancy, particularly leukemia and lymphoma. The mechanisms of immune dysregulation have been linked to the combination of dysregulated immune cells and environmental factors such as infections. In particular, dysfunction in T-cell subsets and Epstein-Barr virus contributes to the development of autoimmunity and lymphoproliferative disease in primary immunodeficiency diseases.

Neonatal Herpes Simplex Virus Infection: Epidemiology and Outcomes in the Modern Era.

Background: Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV.

Methods: Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016.

Development of ADHD: Etiology, Heterogeneity, and Early Life Course.

ADHD represents a powerful entry point for developmental approaches to psychopathology due to its major role in early emergence of major life problems. One key issue concerns the role of early environmental risks in etiology and maintenance in the context of genetic liability. Here, psychosocial aspects of development need more attention.

Urinary glyphosate concentration in pregnant women in relation to length of gestation.

Human exposure to glyphosate-based herbicides (GBH) is increasing rapidly worldwide. Most existing studies on health effects of glyphosate have focused on occupational settings and cancer outcomes and few have examined this common exposure in relation to the health of pregnant women and newborns in the general population. We investigated associations between prenatal glyphosate exposure and length of gestation in The Infant Development and the Environment Study (TIDES), a multi-center US pregnancy cohort.

Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects.

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies.

Enrolling Children in Clinical Trials for Genetic Neurodevelopmental Conditions: Ethics, Parental Decisions, and Children's Identities.

Knowledge of genetic mechanisms contributing to neurodevelopmental conditions is advancing. This is informing development of new drugs to treat or ameliorate these conditions, through targeting underlying genetic pathways. Drugs are tested in clinical trials, necessitating parents to engage with decisions about whether to enroll their child.

Institutionally chartered Data and Safety Monitoring Boards: structured approaches to assuring participant safety in clinical research.

Data and Safety Monitoring Boards (DSMBs) derived from the need to monitor large federally funded multi-center clinical trials and evolved to include commercial and other large and complex trials. Eventually, academic health centers also created institutionally focused trial monitoring mechanisms. The basic general principles that define traditional DSMBs extend to the institutional level.

Racial Disparities in Developmental Delay Diagnosis and Services Received in Early Childhood.

Background And Objective: Racial disparities in diagnosis and receipt of services for early childhood developmental delay (DD) are well known but studies have had difficulties distinguishing contributing patient, healthcare system, and physician factors from underlying prevalence. We examine rates of physician diagnoses of DD by preschool and kindergarten entry controlling for a child's objective development via scoring on validated developmental assessment along with other child characteristics.

Methods: We used data from the preschool and kindergarten entry waves of the Early Childhood Longitudinal Study, Birth Cohort.

Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4 T cell perturbations.

FOXP3 deficiency in mice and in patients with immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome results in fatal autoimmunity by altering regulatory T (T) cells. CD4 T cells in patients with IPEX syndrome and Foxp3-deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous T-like cells, some very similar to normal T cells, others more distant. Conventional T cells showed no widespread activation or helper T cell bias, but a monomorphic disease signature affected all CD4 T cells.

Maternal urinary levels of glyphosate during pregnancy and anogenital distance in newborns in a US multicenter pregnancy cohort.

Human exposure to glyphosate has become ubiquitous because of its increasing agricultural use. Recent studies suggest endocrine disrupting effects of glyphosate. Specifically, in our work in rodents, low-dose early-life exposure to Roundup® (glyphosate-based herbicide) lengthened anogenital distance (AGD) in male and female offspring.

Examining the consumer restaurant environment and dietary intake in children.

Within the away-from-home food environment there is a need to account for individual exposure (e.g., frequency of visitation) to that environment.

Kawasaki Disease and Clinical Outcome Disparities Among Black Children.

Objective: To determine whether Black children with Kawasaki disease exhibit disparities in prevalence, sequelae, and response to intravenous gamma globulin (IVIG) treatment.

Study Design: International Classification of Diseases codes were used to identify children with Kawasaki disease admitted to a tertiary center in the southeastern US. Subjects diagnosed and treated according to American Heart Association criteria were included.

Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research.

Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item "short" to 65-item "full" SRS scores. Results demonstrated highly overlapping distributions of short and full scores.

General and Eating Disorder Psychopathology in Relation to Short- and Long-Term Weight Change in Treatment-Seeking Children: A Latent Profile Analysis.

Background: Concurrent general psychopathology (GP) and eating disorder psychopathology (EDP) are commonly reported among youth with overweight/obesity and may impact weight change.

Purpose: We identified patterns of GP and EDP in children with overweight/obesity and examined the impact on weight change following family-based behavioral obesity treatment (FBT) and maintenance interventions.

Methods: Children (N = 172) participated in 4 month FBT and subsequent 8 month weight maintenance interventions.

Increasing Early Childhood Screening in Primary Care Through a Quality Improvement Collaborative.

Objectives: Multiple early childhood screenings are recommended, but gaps persist in implementation. Our aim for this project was to improve screening, discussion, referral, and follow-up of development, autism spectrum disorder (ASD), maternal depression, and social determinants of health (SDoH) to 90% by July 2018.

Methods: This 1-year national quality improvement collaborative involved 19 pediatric primary care practices.

The urgent need for integrated science to fight COVID-19 pandemic and beyond.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic.

ED Visits and Readmissions After Follow-up for Mental Health Hospitalization.

Objectives: A national quality measure in the Child Core Set is used to assess whether pediatric patients hospitalized for a mental illness receive timely follow-up care. In this study, we examine the relationship between adherence to the quality measure and repeat use of the emergency department (ED) or repeat hospitalization for a primary mental health condition.

Methods: We used the Truven MarketScan Medicaid Database 2015-2016, identifying hospitalizations with a primary diagnosis of depression, bipolar disorder, psychosis, or anxiety for patients aged 6 to 17 years.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review.

Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder characterized by early onset fatal multi-system autoimmunity due to loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor which is crucial for the development, maturation, and maintenance of CD4 regulatory T (T-reg) cells. Various autoimmune phenomena such as enteropathy, endocrinopathies, cytopenias, renal disease, and skin manifestations are characteristic findings in patients affected by IPEX syndrome.

Objectives: In this systematic review, we focus on both clinical and demographic characteristics of IPEX patients, highlighting possible genotype-phenotype correlations and address prognostic factors for disease outcome.

Correction to: Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee.

The original version of this article unfortunately contained mistakes in reference numbers. The in-text citations and the references were mismatched. The original article has been corrected.

Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification.

Since 2013, the International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) has published an updated phenotypic classification of IEI, which accompanies and complements their genotypic classification into ten tables. This phenotypic classification is user-friendly and serves as a resource for clinicians at the bedside. There are now 430 single-gene IEI underlying phenotypes as diverse as infection, malignancy, allergy, autoimmunity, and autoinflammation.