Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment.

Aged hematopoietic stem cells (HSCs) show reduced reconstitution potential, limiting their use in transplantation settings in the clinic. We demonstrate here that exposure of aged HSCs ex vivo to a pH of 6.9 instead of the commonly used pH of 7.

One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial.

Background: A 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively affect quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy.

Objective: We performed a multisite, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE.

Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on data in the USA for those carrying at least one of 177 rare (cystic fibrosis transmembrane conductance regulator) variants.

Methods: PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively.

Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.

Background: Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.

Methods: We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics.

Results: We identified 2 potentially protective gene network modules associated with vascular cells, and we validated , coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH.

Biomarker Changes in Response to Tofacitinib Treatment in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis.

Objective: We examine levels of candidate blood-based biomarkers (CBBs) in patients with juvenile idiopathic arthritis (JIA) treated with tofacitinib.

Methods: Patients with JIA who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBBs (S100A8/9, S100A12, interleukin-18 [IL-18], serum amyloid A, resistin, vascular endothelial growth factor, angiopoietin-1, angiopoietin-2, matrix metalloproteinase 8 [MMP8], MMP2, tissue inhibitor of metalloproteinases 1, leptin, chemokine [C-X-C motif] ligand 9, soluble IL-2 receptor, intercellular adhesion molecule 1, soluble tumor necrosis factor receptor, IL-6, IL-23, monocyte chemotactic protein 1, chemokine [C-C motif] ligand 18 [CCL18], and CCL20).

Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During the COVID-19 Pandemic.

Objectives: This study seeks to identify demographic and clinical factors prompting clinician prescribing of nirmatrelvir/ritonavir to pediatric patients for management of coronavirus disease 2019 (COVID-19) infection.

Methods: Patients aged 12 to 17 years with a COVID-19 infection and nirmatrelvir/ritonavir prescription during an outpatient clinical encounter within a PEDSnet-affiliated institution between January 2022 and August 2023 were identified using electronic health record data. A multivariate logistic regression analysis was used to estimate odds of nirmatrelvir/ritonavir prescription after adjusting for various factors.

Comparing Self-Fitting Strategies for Over-the-Counter Hearing Aids: A Crossover Clinical Trial.

Importance: Fewer than 20% of US adults with hearing loss use hearing aids due to barriers like high cost. Over-the-counter (OTC) hearing aids offer a potential solution, incorporating self-fitting strategies via smartphone apps. Self-fitting strategies have been validated for Food and Drug Administration (FDA)-approved OTC hearing aids compared with prescription-based approaches.

Classification Criteria for Axial Disease in Youth With Juvenile Spondyloarthritis.

Objective: The goal was to develop and validate classification criteria for axial juvenile spondyloarthritis (SpA; AxJSpA).

Methods: This international initiative consisted of four phases: (1) item generation, (2) item reduction, (3) criteria development, and (4) validation of the AxJSpA criteria by an independent team of experts in an internationally representative validation cohort.

Results: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected.

Development of machine learning models predicting mortality using routinely collected observational health data from 0-59 months old children admitted to an intensive care unit in Bangladesh: critical role of biochemistry and haematology data.

Introduction: Treatment in the intensive care unit (ICU) generates complex data where machine learning (ML) modelling could be beneficial. Using routine hospital data, we evaluated the ability of multiple ML models to predict inpatient mortality in a paediatric population in a low/middle-income country.

Method: We retrospectively analysed hospital record data from 0-59 months old children admitted to the ICU of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh.

Long-Term Outcomes of Self-Fit vs Audiologist-Fit Hearing Aids.

Importance: With rising interest in over-the-counter (OTC) hearing aids as an alternative to traditional audiologist-fit devices, understanding their long-term efficacy is crucial. However, given the novelty of the US Food and Drug Administration category of OTC hearing aids, minimal evidence currently supports their long-term efficacy.

Objective: To compare the long-term self-reported outcomes at 8 months of self-fit OTC hearing aids to the same hearing aids fit by audiologists.

Post-acute and Chronic Kidney Function Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Initiative.

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI.

Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age.

Background: Dupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents.

Methods: In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B).

Reimagining Initial Certification as a Process That Begins During Residency to Support Continuous Development Across Training and Practice.

In the United States, initial board certification remains focused on a high-stakes knowledge examination after completion of training. A more contemporary view supports a program of assessment that includes multiple types and sources of data with an emphasis on direct workplace observation to get the best picture of an individual's performance. In this article, the authors reimagine initial certification as a continuous assessment for learning that begins in residency, focuses on both knowledge acquisition and its application, and interdigitates intentionally with the first cycle of maintenance of certification to advance learning and smooth the transition from training to practice.

An International Survey Investigating the Incidence and Management of Brown Fat Uptake on F-FDG PET/CT at Children's Hospitals and Interventions for Mitigation.

Brown fat can present challenges in patients with cancer who undergo F-FDG PET scans. Uptake of F-FDG by brown fat can obscure or appear similar to active oncologic lesions, causing clinical challenges in PET interpretation. Small, retrospective studies have reported environmental and pharmacologic interventions for suppressing brown fat uptake on PET; however, there is no clear consensus on best practices.

Neural Signature of Rhyming Ability During Story Listening in Preschool-Age Children.

Rhyming is a phonological skill that typically emerges in the preschool-age range. Prosody/rhythm processing involves right-lateralized temporal cortex, yet the neural basis of rhyming ability in young children is unclear. The study objective was to use functional magnetic resonance imaging (fMRI) to quantify neural correlates of rhyming abilities in preschool-age children.

Post-acute sequelae of SARS-CoV-2 infection in health care workers from South Africa.

Health care workers (HCWs) are primary health providers therefore ensuring their protection and recovery from Covid-19 is of high interest. We investigated post-acute sequelae of SARS-CoV-2 infection (PASC) in HCWs who had previously been infected with SARS-CoV-2. Overall, 68 HCWs were classified as PASC according to duration of persisting symptoms.