Molecular analysis of duodenal eosinophilia.

Background: Eosinophilic duodenitis (EoD), characterized by nonspecific gastrointestinal symptoms and increased numbers of duodenal eosinophils, may be in the eosinophilic gastrointestinal disease spectrum. However, diagnostic thresholds and pathogenic processes of duodenal tissue eosinophilia are inadequately characterized.

Objective: We aimed to define an EoD transcriptome and pathologic pathways.

The Mediatory Role of Executive Functioning on the Association Between Sleep and Both Everyday Memory and ADHD Symptoms in Children and Youth With Down Syndrome.

People with Down syndrome (DS) commonly experience challenges with sleep, executive functioning, everyday memory, and symptoms of attention deficit hyperactivity disorder (ADHD). A path analysis was conducted to determine if executive function mediated the relationship between sleep problems and both everyday memory and ADHD symptoms. Parents of 96 children and youth with DS completed questionnaires related to sleep, executive functioning, everyday memory, and ADHD symptoms.

Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis.

Background: Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis.

Methods: We conducted a three-part, phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (Part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo (Part B) up to week 24. Eligible patients who completed Part A or Part B continued the trial in Part C, in which those who completed Part A received dupilumab at a weekly dose of 300 mg up to week 52 (the Part A-C group); Part C that included the eligible patients from Part B is ongoing.

Using change in predicted adult height during GnRH agonist treatment for individualized treatment decisions in girls with central precocious puberty.

Objectives: It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care.

Methods: Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years.

Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in children with SCD: a V114-023 (PNEU-SICKLE) study.

Sickle cell disease (SCD) is an inherited red blood cell disease that results in a multitude of medical complications, including an increased risk of invasive disease caused by encapsulated bacteria, such as Streptococcus pneumoniae. Pneumococcal vaccines have contributed to a significant reduction in pneumococcal disease (PD) in children and adults, including those with SCD. This phase 3 study evaluated the safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), in children with SCD.

Impact of the COVID-19 Pandemic on Early Career Investigators in Rheumatology: Recommendations to Address Challenges to Early Research Careers.

Objective: The COVID-19 pandemic has impacted the careers of trainees and early career investigators (ECIs). We sought to assess how the American College of Rheumatology (ACR) and the Rheumatology Research Foundation (RRF) can address the needs of those pursuing research careers.

Methods: The Committee on Research created a survey to assess the impact of COVID-19 and identify topics for the ACR and the RRF to address.

The prognostic role of liver volumetry in Fontan patients.

Background And Hypotheses: High venous pressures and associated hepatic congestion are important drivers for Fontan-associated liver disease. The prognostic significance of hepatomegaly as a marker of congestion however is not well defined and is further explored in this research study.

Methods: Fontan patients who have had liver ultrasound scans were identified from the Prince Sultan Cardiac Centre Fontan Database and had their anatomic, surgical, clinical histories abstracted from the electronic medical records following institutional ethics approval.

Complement receptor C5aR1 on osteoblasts regulates osteoclastogenesis in experimental postmenopausal osteoporosis.

In recent years, evidence has accumulated that the complement system, an integral part of innate immunity, may be involved in the regulation of bone homeostasis as well as inflammatory bone loss, for example, in rheumatoid arthritis and periodontitis. Complement may also contribute to osteoporosis development, but investigation of the mechanism is limited. Using mice with a conditional deletion of the complement anaphylatoxin receptor C5aR1, we here demonstrated that C5aR1 in osteoblasts ( mice) or osteoclasts ( mice) did not affect physiological bone turnover or age-related bone loss in either sex, as confirmed by micro-computed tomography, histomorphometry, and biomechanical analyses of the bone and by the measurement of bone turnover markers in the blood serum.

Characterizing the Adolescent Premature Ovarian Insufficiency Phenotype: A Case Control Study.

Study Objectives: To characterize the skeletal, cardiometabolic, cognitive, and mental health phenotype of adolescents with idiopathic premature ovarian insufficiency (POI) DESIGN: Case control SETTING: Pediatric tertiary referral center in Cincinnati, Ohio PARTICIPANTS: Nine adolescents (ages 11-18.99 years) with newly diagnosed POI and 9 normally menstruating controls, matched by age and body mass index MAIN OUTCOME MEASURES: Between-group comparisons of bone characteristics assessed by dual energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), psychosocial health (anxiety, depression, and quality of life), and cognition and memory by questionnaire RESULTS: Adolescents with POI had lower bone density Z-scores by DXA (lumbar spine -1.93 vs 0.

The relevance of complement in pemphigoid diseases: A critical appraisal.

Pemphigoid diseases are autoimmune chronic inflammatory skin diseases, which are characterized by blistering of the skin and/or mucous membranes, and circulating and tissue-bound autoantibodies. The well-established pathomechanisms comprise autoantibodies targeting various structural proteins located at the dermal-epidermal junction, leading to complement factor binding and activation. Several effector cells are thus attracted and activated, which in turn inflict characteristic tissue damage and subepidermal blistering.

Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents.

Importance: The postacute sequelae of SARS-CoV-2 infection (PASC) has emerged as a long-term complication in adults, but current understanding of the clinical presentation of PASC in children is limited.

Objective: To identify diagnosed symptoms, diagnosed health conditions, and medications associated with PASC in children.

Design, Setting And Participants: This retrospective cohort study used electronic health records from 9 US children's hospitals for individuals younger than 21 years who underwent antigen or reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 between March 1, 2020, and October 31, 2021, and had at least 1 encounter in the 3 years before testing.

High Levels of the Carcinogenic Tobacco-Specific Nitrosamine NNAL and Associated Findings in Children of Smokers: A Case Series.

High levels of NNAL, the tobacco smoke exposure (TSE) biomarker of the carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicate future cancer risk. A prior study of smokers' children revealed NNAL levels as high as active smokers. Therefore, we conducted a case series to examine the sociodemographics, TSE and clinical patterns, and other TSE biomarker levels in 9 children with extreme NNAL levels of >200 pg/ml to generate hypotheses and explore potential causes and implications.

Comprehensiveness of Testing Among Herpes Simplex Virus Infected Infants: A Multicenter Cohort Study.

Despite clear testing recommendations for herpes simplex virus (HSV) infection in infants, few data exist on the comprehensiveness of HSV testing in practice. In a 23-center study of 112 infants with confirmed HSV disease, less than one-fifth had all recommended testing performed, highlighting the need for increased awareness of and adherence to testing recommendations for this vulnerable population.

Radiologists' Diagnostic Performance in Differentiation of Rickets and Classic Metaphyseal Lesions on Radiographs: A Multicenter Study.

Despite evidence supporting the specificity of classic metaphyseal lesions (CML) for the diagnosis of child abuse, some medicolegal practitioners claim that CML result from rickets rather than trauma. The purpose of this study was to evaluate radiologists' diagnostic performance in differentiating rickets and CML on radiographs. This retrospective seven-center study included children younger than 2 years who underwent knee radiography from January 2007 to December 2018 and who had either rickets (25-hydroxyvitamin D level < 20 ng/mL and abnormal knee radiographs) or knee CML and a diagnosis of child abuse from a child abuse pediatrician.

genotypic associations with endostatin levels and clinical features in pulmonary arterial hypertension: a quantitative trait association study.

https://bit.ly/3shXrNR.

Monoallelic and biallelic mutations in RELN underlie a graded series of neurodevelopmental disorders.

Reelin, a large extracellular protein, plays several critical roles in brain development and function. It is encoded by RELN, first identified as the gene disrupted in the reeler mouse, a classic neurological mutant exhibiting ataxia, tremors and a 'reeling' gait. In humans, biallelic variants in RELN have been associated with a recessive lissencephaly variant with cerebellar hypoplasia, which matches well with the homozygous mouse mutant that has abnormal cortical structure, small hippocampi and severe cerebellar hypoplasia.

Validation of Prediction Models for Pneumonia Among Children in the Emergency Department.

Background: Several prediction models have been reported to identify patients with radiographic pneumonia, but none have been validated or broadly implemented into practice. We evaluated 5 prediction models for radiographic pneumonia in children.

Methods: We evaluated 5 previously published prediction models for radiographic pneumonia (Neuman, Oostenbrink, Lynch, Mahabee-Gittens, and Lipsett) using data from a single-center prospective study of patients 3 months to 18 years with signs of lower respiratory tract infection.

An Ethical Analysis of Newborn Congenital Cytomegalovirus Screening.

Congenital cytomegalovirus (cCMV) affects approximately 1 in every 200 US infants and can be associated with long-term neurodevelopmental sequelae, including sensorineural hearing loss, cerebral palsy, and intellectual disability. As cCMV is infrequently diagnosed based on clinical suspicion alone, newborn cCMV screening programs have been gaining traction, especially hearing-targeted programs which only test infants who fail their newborn hearing screen. cCMV screening programs raise unique ethical dilemmas of both under- and over-diagnosis of cCMV.

Reducing Pediatric Unplanned Extubation Across Multiple ICUs Using Quality Improvement.

Objectives: Unplanned extubation (UE) in pediatric patients can result in significant harm or mortality. In our institution, efforts to reduce UE in the ICU were siloed and learnings were not shared. Our goal was to implement shared initiatives across ICUs in a pediatric institution using quality improvement methodology, with the global aim of reducing serious harm caused by UEs.

Severity of Acute COVID-19 in Children <18 Years Old March 2020 to December 2021.

This national study evaluated trends in illness severity among 82 798 children with coronavirus disease 2019 from March 1, 2020, to December 30, 2021.

The spectrum of indomethacin-responsive headaches in children and adolescents.

Background: Headaches with marked, specific response to indomethacin occur in children, but the phenotypic spectrum of this phenomenon has not been well-studied.

Methods: We reviewed pediatric patients with headache showing ≥80% improvement with indomethacin, from seven academic medical centers.

Results: We included 32 pediatric patients (16 females).

Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Cardiosphere-derived cells (CDCs) ameliorate skeletal and cardiac muscle deterioration in experimental models of Duchenne muscular dystrophy. The HOPE-2 trial examined the safety and efficacy of sequential intravenous infusions of human allogeneic CDCs in late-stage Duchenne muscular dystrophy.

Methods: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients with Duchenne muscular dystrophy, aged 10 years or older with moderate upper limb impairment, were enrolled at seven centres in the USA.