Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers.

Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients.

Comparative analysis of ambient, in-home, and personal exposures reveals associations between breathing zone pollutant levels and asthma exacerbations in high-risk children.

Background: Air pollution is associated with poor asthma outcomes in children. However, most studies focus on ambient or indoor monitor pollution levels. Few studies evaluate breathing zone exposures, which may be more consequential for asthma outcomes.

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Learning from the roundtable on obesity solutions experiences: A 10-year anniversary point of view.

The Roundtable on Obesity Solutions (ROOS), established in 2014, is a unique organization of multisectoral voices addressing the public health challenge of obesity. The ROOS brings together practitioners, researchers, funders, companies, health systems, government agencies, and the lived experience to dialogue and guide the national conversation about the multilevel challenges and opportunities related to obesity. This paper presents insights and key learnings from a symposium developed to celebrating the 10th Anniversary of the ROOS.

GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia.

Stemness-associated cell states are linked to chemotherapy resistance in AML. We uncovered a direct mechanistic link between expression of the stem cell transcription factor GATA2 and drug resistance. The GATA-binding protein 2 (GATA2) plays a central role in blood stem cell generation and maintenance.

Valve Frame Geometry and Arrhythmia Risk Following Self-Expanding Transcatheter Pulmonary Valve Replacement.

Though major complications during transcutaneous pulmonary valve replacement (TPVR) are rare, clinically-significant ventricular arrythmia (CSVA) has been reported following self-expanding valve placement. We assess whether alterations in valve frame dimensions and geometry within the right ventricular outflow tract (RVOT) post-implantation in patients who underwent TPVR with Harmony TPV25 or Alterra contribute to CSVA risk. A single center review was performed of patients who underwent TPVR with either Harmony TPV25 or Alterra Pre-stent between August 2019 and April 2023.

Integrated Phase I Pharmacokinetics and Pharmacodynamics of Epinephrine Administered via Sublingual Film, Autoinjector, or Manual Injection.

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered via intramuscular (IM) or subcutaneous (SC) injection. AQST-109, a sublingual film containing a prodrug of epinephrine, is in development as an alternative delivery method for the treatment of severe allergic reactions including anaphylaxis.

Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine following administration of AQST-109 to epinephrine delivered by manual IM injection and epinephrine autoinjectors (EAIs).

Management of Vascular Complications from Button Battery Ingestions.

Purpose: To propose a gastrointestinal bleeding management algorithm that incorporates an endoscopic and imaging scoring system and specifies management of vascular complication from button battery ingestion.

Recent Findings: Button batteries (BB) are found in many electronic devices and ingestions are associated with serious complications especially in cases of unwitnessed ingestions, prolonged impaction, and in children less than 5 years of age. Gastrointestinal bleeding from BB related vascular injury is rare but often rapidly fatal, with a mortality rate as high as 81%.

Biomarker Panels for Discriminating Risk of CKD Progression in Children.

Background: We have previously studied biomarkers of tubular health (EGF), injury (KIM-1), dysfunction (alpha-1 microglobulin), and inflammation (TNFR-1, TNFR-2, MCP-1, YKL-40, suPAR), and demonstrated that plasma KIM-1, TNFR-1, TNFR-2 and urine KIM-1, EGF, MCP-1, urine alpha-1 microglobulin are each independently associated with CKD progression in children. In this study, we used bootstrapped survival trees to identify a combination of biomarkers to predict CKD progression in children.

Methods: The CKiD Cohort Study prospectively enrolled children 6 months to 16 years old with an eGFR of 30-90 ml/min/1.

Epidemiology and population-based incidence of influenza in two communities, Bandung district, West Java, Indonesia, 2008-2011.

Influenza surveillance is important for monitoring influenza virus circulation and disease burden to inform influenza prevention and control measures. The aim of this study was to describe the epidemiology and to estimate the incidence of influenza in two communities in West Java, Indonesia, before and after the 2009 H1N1 pandemic. A population-based surveillance study in the community health care setting was conducted to estimate the annual incidence of influenza.

Impact of antiparasitic therapy on cardiovascular outcomes in chronic Chagas disease. A systematic review and meta-analysis.

Background: Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

Comparison of clinical and radiological outcomes of three-column lumbar osteotomies with and without interbody cages for adult spinal deformity.

Background Context: Correcting sagittal malalignment in adult spinal deformity (ASD) is a challenging task, often requiring complex surgical interventions like pedicle subtraction osteotomies (PSOs). Different types of three-column osteotomies (3COs), including Schwab 3, Schwab 4, Schwab 4 with interbody cages, and the "sandwich" technique, aim to optimize alignment and fusion outcomes. The role of interbody cages in enhancing fusion and segmental correction remains unclear.

Sexual Health Advocacy for Guys (SHAG): a randomized trial of the impact of a text-messaging program on HIV incidence and STI testing among a national sample of sexual minority cisgender adolescent and young adult men.

Background: Disparities in sexually transmitted infections (STI) including human immunodeficiency virus (HIV) among sexual minority boys and young men are substantial. Effective HIV and STI prevention programs that include access to pre-exposure prophylaxis (PrEP) medication do not consistently include younger sexual minority men. Text-messaging programs for HIV prevention have been associated with increases in HIV testing among sexual minority adolescent boys, but these programs have not incorporated a focus on PrEP or STIs beyond HIV.

Propensity Score Analysis of Possible Medication Effects on Outcomes in Patients With Systemic Right Ventricles.

Background: Patients with systemic right ventricle (SRV), either d-transposition of the great arteries following an atrial switch procedure or congenitally corrected transposition of the great arteries, develop severe right ventricular dysfunction, prompting appropriate medical therapy. However, the efficacy of beta-blockers and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (ACEI) in SRV patients is unproven.

Objectives: The objective of this study was to determine the effects of ACEI/ARB and beta-blockers on outcomes in SRV patients after accounting for likely cofounders affecting their use.

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment.

Background: Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.

Transplacental signals involved in the programming effects of prenatal psychosocial stress on neurodevelopment.

Exposure to psychosocial stress during pregnancy has been associated with the emergence of neurodevelopmental and neuropsychiatric disorders in offspring. The placenta is known to orchestrate various functions that are essential for normal fetal development, including the brain. It has therefore been postulated that alterations in such functions, and downstream signaling, have the potential to dramatically affect brain developmental trajectories and contribute to adverse neurodevelopmental outcomes.

The gap between surgeon goal and achieved sagittal alignment in adult cervical spine deformity surgery.

Objective: Malalignment following cervical spine deformity (CSD) surgery can negatively impact outcomes and increase complications. Despite the growing ability to plan alignment, it remains unclear whether preoperative goals are achieved with surgery. The objective of this study was to assess how good surgeons are at achieving their preoperative goal alignment following CSD surgery.

Comparison of Two Interferon-Gamma Release Assays for Pediatric Tuberculosis Infection.

Introduction: Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values.