DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.

Background: Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children.

Methods: We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.

Leveraging genetic discoveries for sleep to determine causal relationships with common complex traits.

Sleep occurs universally and is a biological necessity for human functioning. The consequences of diminished sleep quality impact physical and physiological systems such as neurological, cardiovascular, and metabolic processes. In fact, people impacted by common complex diseases experience a wide range of sleep disturbances.

MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere.

Operative and Nonoperative Outcomes of Emergency General Surgery Conditions: An Observational Study Using a Novel Instrumental Variable.

Objective: To determine the effect of operative versus nonoperative management of emergency general surgery conditions on short-term and long-term outcomes.

Background: Many emergency general surgery conditions can be managed either operatively or nonoperatively, but high-quality evidence to guide management decisions is scarce.

Methods: We included 507,677 Medicare patients treated for an emergency general surgery condition between July 1, 2015, and June 30, 2018.

Clinical Pharmacokinetics and Pharmacodynamics of Cefepime.

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against Gram-positive and Gram-negative pathogens. It is generally administered as an infusion over 30-60 min or as a prolonged infusion with infusion times from 3 h to continuous administration. Cefepime is widely distributed in biological fluids and tissues with an average volume of distribution of ~ 0.

Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type and are Associated with Features of Immunometabolic Dysregulation.

Background: Sepsis is the leading cause of death in hospitalized children worldwide. Despite its hypothesized immune-mediated mechanism, targeted immunotherapy for sepsis is not available for clinical use.

Objective: To determine the association between longitudinal cytometric, proteomic, bioenergetic, and metabolomic markers of immunometabolic dysregulation and pathogen type in pediatric sepsis.

Durability of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Booster Vaccine Protection Against Omicron Among Healthcare Workers With a Vaccine Mandate.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread rapidly throughout the world since being identified in South Africa in November 2021. Few studies have assessed primary series and booster vaccine effectiveness against Omicron among US healthcare workers.

Methods: We conducted a test-negative case-control design to estimate BNT162b2 and mRNA1273 primary vaccination and booster effectiveness against SARS-CoV-2 infection and symptomatic coronavirus disease 2019 during an Omicron surge among employees of the University of Pennsylvania Health System.

Management of neurofibromatosis type 1-associated plexiform neurofibromas.

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management.

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C.

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5-11, 12-21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron.

Reference Ranges for Bone Mineral Content and Density by Dual Energy X-Ray Absorptiometry for Young Children.

Background: Assessment of bone health in young children has been hampered by limited reference values for bone mineral content (BMC) and areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA).

Objectives: To identify age, sex, and population ancestry effects on BMC and aBMD and develop smoothed reference ranges for BMC and aBMD in young children. To quantify precision of bone measurements and influence of height-for-age Z-scores on bone Z-scores.

Variant-to-gene-mapping analyses reveal a role for pancreatic islet cells in conferring genetic susceptibility to sleep-related traits.

We investigated the potential role of sleep-trait associated genetic loci in conferring a degree of their effect via pancreatic α- and β-cells, given that both sleep disturbances and metabolic disorders, including type 2 diabetes and obesity, involve polygenic contributions and complex interactions. We determined genetic commonalities between sleep and metabolic disorders, conducting linkage disequilibrium genetic correlation analyses with publicly available GWAS summary statistics. Then we investigated possible enrichment of sleep-trait associated SNPs in promoter-interacting open chromatin regions within α- and β-cells, intersecting public GWAS reports with our own ATAC-seq and high-resolution promoter-focused Capture C data generated from both sorted human α-cells and an established human beta-cell line (EndoC-βH1).

Primary Care Appointment Completion Rates and Telemedicine Utilization Among Black and Non-Black Patients from 2019 to 2020.

To understand how differences in primary care appointment completion rates between Black and non-Black patients changed in 2020 within the context of the COVID-19 pandemic and when telemedicine utilization peaked. We conducted a retrospective cohort study using the electronic health record from January 1 to December 31, 2020, among all adults scheduled for a primary care appointment within a large academic medical center. We used mixed-effects logistic regression to estimate adjusted appointment completion rates for Black patients compared with those for non-Black patients in 2020 as compared with those in 2019 within four time periods: (1) prepandemic (January 1, 2020, to March 12, 2020), (2) shutdown (March 13, 2020, to June 3, 2020), (3) reopening (June 4, 2020, to September 30, 2020), and (4) second wave (October 1, 2020, to December 31, 2020).

Left Ventricular Structure, Tissue Composition, and Aortic Distensibility in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications.

Alterations in myocardial structure, function, tissue composition (e.g., fibrosis) may be associated with metabolic syndrome (MetS).

Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome.

Dravet syndrome is a neurodevelopmental disorder characterized by epilepsy, intellectual disability, and sudden death due to pathogenic variants in SCN1A with loss of function of the sodium channel subunit Nav1.1. Nav1.

Near-infrared spectroscopy during cardiopulmonary resuscitation for pediatric cardiac arrest: A prospective, observational study.

Aim: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge.

Methods: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020.

The Use and Duration of Preintubation Respiratory Support Is Associated With Increased Mortality in Immunocompromised Children With Acute Respiratory Failure.

Objectives: To determine the association between preintubation respiratory support and outcomes in patients with acute respiratory failure and to determine the impact of immunocompromised (IC) diagnoses on outcomes after adjustment for illness severity.

Design: Retrospective multicenter cohort study.

Setting: Eighty-two centers in the Virtual Pediatric Systems database.

Preexposure Prophylaxis Acceptability Among Pregnant Individuals and Implications for Human Immunodeficiency Virus Prevention.

Objective: To understand perspectives on and preferences for preexposure prophylaxis (PrEP) for pregnant individuals who are at risk for human immunodeficiency virus (HIV) infection.

Methods: In this qualitative study, we purposively sampled and conducted in-depth interviews with pregnant participants at risk of HIV infection (indicated by a recent sexually transmitted infection [STI]) from a U.S.

Measurement of Severe Acute Respiratory Syndrome Coronavirus 2 Antigens in Plasma of Pediatric Patients With Acute Coronavirus Disease 2019 or Multisystem Inflammatory Syndrome in Children Using an Ultrasensitive and Quantitative Immunoassay.

Background: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood has high sensitivity in adults with acute coronavirus disease 2019 (COVID-19), but sensitivity in pediatric patients is unclear. Recent data suggest that persistent SARS-CoV-2 spike antigenemia may contribute to multisystem inflammatory syndrome in children (MIS-C). We quantified SARS-CoV-2 nucleocapsid (N) and spike (S) antigens in blood of pediatric patients with either acute COVID-19 or MIS-C using ultrasensitive immunoassays (Meso Scale Discovery).

Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome.

Dravet syndrome (DS) is a neurodevelopmental disorder due to pathogenic variants in encoding the Nav1.1 sodium channel subunit, characterized by treatment-resistant epilepsy, temperature-sensitive seizures, developmental delay/intellectual disability with features of autism spectrum disorder, and increased risk of sudden death. Convergent data suggest hippocampal dentate gyrus (DG) pathology in DS () mice.

Paediatric acute care cardiology collaborative data registry validation.

Background: The Pediatric Acute Care Cardiology Collaborative (PAC) was established to improve acute care cardiology outcomes through the development of an accurate and well-validated clinical registry. We report the validation results of the initial PAC registry audits and describe a novel regional audit format developed to accommodate a rapidly expanding membership facilitate collaborative learning and allow for necessary modification due to the COVID-19 pandemic.

Materials And Methods: Six hospitals were audited using a regional audit format and three hospitals were subsequently audited virtually.

Adeno-Associated Viral Vector Immobilization and Local Delivery from Bare Metal Surfaces.

Spatially and temporally controlled delivery of biologicals, including gene vectors, represents an unmet need for regenerative medicine and gene therapy applications. Here we describe a method of reversible attachment of serotype 2 adeno-associated viral vectors (AAV2) to metal surfaces. This technique enables localized delivery of the vector to the target cell population in vitro and in vivo with the subsequent effective transduction of cells adjacent to the metal substrate.

Health Literacy and Clinical Outcomes Following Hematopoietic Stem-Cell Transplantation.

Purpose: To test associations between health literacy and clinical outcomes in patients undergoing hematopoietic stem-cell transplantation (HSCT).

Methods: English- and Spanish-speaking patients age ≥ 18 years were recruited while admitted for first allogeneic HSCT. Associations between low health literacy (Newest Vital Sign ≤ 3 or Short Test of Functional Health Literacy in Adults ≤ 22) and HSCT outcomes were evaluated.