Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease.

Background: Danon disease is a rare, X-linked, monogenic cardiomyopathy caused by mutations in the lysosomal-associated membrane 2 gene (), which encodes the LAMP2 protein. In male patients, the predominant phenotype is progressive cardiac hypertrophy, cardiac dysfunction, and early death. There are no directed therapies for the disease.

Clinical ethics consultation services: public-facing information on NCI-designated cancer center websites.

Clinical ethics consultation services (CECS) can be particularly complex in oncology, and widespread misconceptions exist about their nature. As a result, visibility and accessibility of information regarding CECS is critical. We investigated the availability and content of information regarding CECS on websites of NCI-designated comprehensive cancer centers and cancer centers (CCs).

Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of upper and lower limb nerve blocks.

Background: Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks.

Methods: We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques.

The RITA-T (Rapid Interactive Screening Test for Autism in Toddlers) Community Model to Improve Access and Early Identification of Autism in Young Children.

To evaluate improved identification and the generalization of the RITA-T (Rapid interactive Screening Test for Autism in Toddlers) model through partnerships with Primary Care (PC), Early Intervention (EI), and Autism Diagnosticians. Over 3 years (2018-2021), 15 EI and 9 PC (MD and NP) centers participated in this project. We trained providers on the RITA-T and established screening models.

Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK).

We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys.

A study protocol for the randomized controlled trial SAFIR FAMILY TALK: a selective primary preventive intervention vs. service as usual for children of parents with mental illness.

Background: Children of parents with mental illness have an increased risk of developing mental illness themselves throughout their lifespan. This is due to genetic factors but also environmental disadvantages during childhood associated with parental mental illness. Selective primary preventive interventions for the children are recommended to mitigate risk factors and strengthen protective factors, but large-scale, longitudinal studies are needed.

Reported rates of all-cause serious adverse events following immunization with BNT-162b in 5-17-year-old children in the United States.

Vaccine development against COVID-19 has mitigated severe disease. However, reports of rare but serious adverse events following immunization (sAEFI) in the young populations are fuelling parental anxiety and vaccine hesitancy. With a very early season of viral illnesses including COVID-19, respiratory syncytial virus (RSV), influenza, metapneumovirus and several others, children are facing a winter with significant respiratory illness burdens.

Criteria for placental examination for obstetrical and neonatal providers.

Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach.

Standards of Care for the Health of Transgender and Gender Diverse People, Version 8.

Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health.

External signals regulate continuous transcriptional states in hematopoietic stem cells.

Hematopoietic stem cells (HSCs) must ensure adequate blood cell production following distinct external stressors. A comprehensive understanding of in vivo heterogeneity and specificity of HSC responses to external stimuli is currently lacking. We performed single-cell RNA sequencing (scRNA-Seq) on functionally validated mouse HSCs and LSK (Lin-, c-Kit+, Sca1+) progenitors after in vivo pharmacological perturbation of niche signals interferon, granulocyte colony-stimulating factor (G-CSF), and prostaglandin.

Recombinant growth hormone therapy for cystic fibrosis in children and young adults.

Background: Cystic fibrosis (CF) is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with CF often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant human growth hormone (rhGH), has been proposed as a potential intervention.

Correction of pathology in mice displaying Gaucher disease type 1 by a clinically-applicable lentiviral vector.

Gaucher disease type 1 (GD1) is an inherited lysosomal disorder with multisystemic effects in patients. Hallmark symptoms include hepatosplenomegaly, cytopenias, and bone disease with varying degrees of severity. Mutations in a single gene, glucosidase beta acid 1 (), are the underlying cause for the disorder, resulting in insufficient activity of the enzyme glucocerebrosidase, which in turn leads to a progressive accumulation of the lipid component glucocerebroside.

Development of Entrustable Professional Activities and Standards in Training in Pediatric Neurogastroenterology and Motility: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and American Neurogastroenterology and Motility Society Position Paper.

Neurogastroenterology and motility (NGM) disorders are common in childhood and are often very debilitating. Although pediatric gastroenterology fellows are expected to obtain training in the diagnosis and management of patients with these disorders, there is an ongoing concern for unmet needs and lack of exposure and standardized curriculum. In the context of tailoring training components, outcome and expressed needs of pediatric gastroenterology fellows and programs, members of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and American Neurogastroenterology and Motility Society (ANMS) developed guidelines for NGM training in North America in line with specific expectations and goals of training as delineated through already established entrustable professional activities (EPAs).

Pepsin Triggers Neutrophil Migration Across Acid Damaged Lung Epithelium.

Pepsin represents a potential biomarker for extraesophageal reflux disease when detected in airways, however a direct role for pepsin in lung dysfunction has not been clearly established. Children experiencing gastroesophageal and extraesophageal reflux are often prescribed proton pump inhibitors (PPIs) to reduce gastric acid associated damage to esophageal and airway mucosa. The potential of pepsin and gastric fluid, from children that were either on or off PPI therapy, to cause inflammation and damage using a human in vitro co-culture model of the airway mucosa was evaluated herein.

Optically-guided instrument for transapical beating-heart delivery of artificial mitral chordae tendineae.

Objective: We sought to develop an instrument that would enable the delivery of artificial chordae tendineae (ACT) using optical visualization of the leaflet inside the beating heart.

Methods: A delivery instrument was developed together with an ACT anchor system. The instrument incorporates an optically clear silicone grasping surface in which are embedded a camera and LED for direct leaflet visualization during localization, grasping, and chordal delivery.

A Pilot Study of the Association of Amino-Terminal Pro-B-Type Natriuretic Peptide and Severity of Illness in Pediatric Septic Shock.

Objectives: Biomarkers that can measure illness severity and predict the risk of delayed recovery may be useful in guiding pediatric septic shock. Amino-terminal pro-B-type natriuretic peptide has not been assessed in pediatric septic patients at the time of presentation to the emergency department prior to any interventions. The primary aim was to assess if emergency department amino-terminal pro-B-type natriuretic peptide is associated with worse outcomes and severity of illness.

Evaluation of the EpiCore outbreak verification system.

Objective: To describe a crowdsourced disease surveillance project (EpiCore) and evaluate its usefulness in obtaining information regarding potential disease outbreaks.

Methods: Volunteer human, animal and environmental health professionals from around the world were recruited to EpiCore and trained to provide early verification of health threat alerts in their geographical region via a secure, easy-to-use, online platform. Experts in the area of emerging infectious diseases sent requests for information on unverified health threats to these volunteers, who used local knowledge and expertise to respond to requests.

Moving On: Transition Readiness in Adolescents and Young Adults With IBD.

Background: Inflammatory bowel diseases (IBD) often begins early in life. Adolescents and young adults (AYA) with IBD have to acquire behaviors that support self-care, effective healthcare decision-making, and self-advocacy to successfully transition from pediatric to adult health care. Despite the importance of this critical time period, limited empirical study of factors associated with transition readiness in AYA exists.