Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.

Purpose: Ewing Sarcoma (ES), a rare cancer with a pathognomonic translocation resulting in the Ewing sarcoma gene (EWS)::FLI1 oncoprotein, has a poor prognosis in the relapsed/refractory (R/R) setting. Tokalas (TK)216 was designed to bind EWS::FLI1 proteins directly, disrupt protein-protein interactions, and inhibit transcription factor function. TK216 plus vincristine showed synergistic activity in preclinical tumor models.

Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: Basing Care on Physiology.

Bronchopulmonary dysplasia (BPD) is the heterogeneous chronic lung developmental disease of prematurity, which is often accompanied by multisystem comorbidities. Pulmonary vascular disease and pulmonary hypertension (PH) contribute significantly to the pathogenesis and pathophysiology of BPD and dramatically influence the outcomes of preterm infants with BPD. When caring for those patients, clinicians should consider the multitude of phenotypic presentations that fall under the "BPD-PH umbrella," reflecting the need for matching therapies to specific physiologies to improve short- and long-term outcomes.

Management of Pediatric Solid Organ Injuries.

Solid organ injury (SOI) is common in children who experience abdominal trauma, and the management of such injuries has evolved significantly over the past several decades. In 2000, the American Pediatric Surgical Association (APSA) published the first societal guidelines for the management of blunt spleen and/or liver injury (BLSI), advocating for optimized resource utilization while maintaining patient safety. Nonoperative management (NOM) has become the mainstay of treatment for SOI, and since the publication of the APSA guidelines, numerous groups have evaluated how invasive procedures, hospitalization, and activity restrictions may be safely minimized in children with SOI.

Diagnosis of Post-Hematopoietic Stem Cell Transplantation Bronchiolitis Obliterans Syndrome in Children: Time for a Rethink?

Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

Objectives: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes.

Post-Acute Cardiovascular Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Project.

Background: The risk of cardiovascular outcomes in the post-acute phase of SARS-CoV-2 infection has been quantified among adults and children. This paper aimed to assess a multitude of cardiac signs, symptoms, and conditions, as well as focused on patients with and without congenital heart defects (CHDs), to provide a more comprehensive assessment of the post-acute cardiovascular outcomes among children and adolescents after COVID-19.

Methods: This retrospective cohort study used data from the RECOVER consortium comprising 19 US children's hospitals and health institutions between March 2020 and September 2023.

Implementation and outcomes of a quality improvement project to systematically assess the gross motor skills in school-aged children with cystic fibrosis.

Introduction: Limited data exist on the gross motor abilities of children with cystic fibrosis (CF). The objective of this research project was to implement a systematic gross motor assessment in children with CF ages 4-12 years. Secondarily, we aimed to assess demographic characteristics associated with gross motor delays.

A multicenter matched-cohort analysis of gastroschisis outcomes in infants born before 32 weeks gestation.

Objective: To examine neonatal outcomes of infants with gastroschisis born <32 weeks' gestation compared to matched infants without gastroschisis.

Study Design: Retrospective matched-cohort analysis of infants with gastroschisis born <32 weeks' gestation at Children's Hospitals Neonatal Consortium (CHNC) NICUs from 2010 to 2022 compared to gestational age-matched controls.

Results: The study included 119 infants with gastroschisis and 357 matched infants; 60% of infants born 29-32 weeks, 23% born 26-28 weeks, and 16% born < 25 weeks.

Risk factors for the development of severe or very severe respiratory syncytial virus-related lower respiratory tract infection in Indian infants: A cohort study in Melghat, India.

Objectives: Respiratory syncytial virus (RSV) is undoubtedly the single most important cause of severe lower respiratory tract infection (LRTI) globally. While new prevention measures in young infants have become available, their use in developing countries is likely many years away. While risk factors for severe or very severe RSV LRTI in impoverished rural areas likely differ to urban areas, there are very few studies, especially those conducted in India, the major country contributing to the global burden of disease.

A Mixed-Methods Comparison of Interventions to Increase Advance Care Planning.

Purpose: Although interventions can increase advance care planning (ACP) engagement, it remains unclear which interventions to choose in primary care settings. This study compares a passive intervention (mailed materials) to an interactive intervention (group visits) on participant ACP engagement and experiences.

Methods: We used mixed methods to examine ACP engagement at baseline and six months following two ACP interventions.

Changing patterns of routine laboratory testing over time at children's hospitals.

Background: Research into low-value routine testing at children's hospitals has not consistently evaluated changing patterns of testing over time.

Objectives: To identify changes in routine laboratory testing rates at children's hospitals over ten years and the association with patient outcomes.

Design, Settings, And Participants: We performed a multi-center, retrospective cohort study of children aged 0-18 hospitalized with common, lower-severity diagnoses at 28 children's hospitals in the Pediatric Health Information Systems database.

Respiratory Syncytial Virus Hospital-Based Burden of Disease in Children Younger Than 5 Years, 2015-2022.

Importance: Respiratory syncytial virus (RSV) resurgences have been noted following the COVID-19 pandemic in many countries. Recent findings suggest that the 2021 and 2022 RSV seasons were more severe than in past seasons, and age distribution may have shifted toward older children in the younger than 5 years age group.

Objectives: To estimate age-specific changes in RSV hospital-based burden of disease before and after the COVID-19 pandemic and to compare incidence by Medicaid use.

Mindfulness-based intervention for depression and insulin resistance in adolescents: Protocol for BREATHE, a multisite, pilot and feasibility randomized controlled trial.

Background: Elevated depression symptoms have been associated with higher insulin resistance in adolescents, and consequently, greater risk for type 2 diabetes (T2D). Mindfulness-based intervention (MBI) may be suited for adolescents at risk for T2D given its potential to decrease depression and improve stress-related behavior/physiology underpinning insulin resistance. To prepare for a future multisite efficacy randomized controlled trial, a rigorous, multisite, pilot and feasibility study is needed to test this approach.

Retrospective Multicenter Cohort Study on Safety and Electroencephalographic Response to Lacosamide for Neonatal Seizures.

Background: There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates.

Association of Pediatric Postcardiac Arrest Ventilation and Oxygenation with Survival Outcomes.

Adult and pediatric studies provide conflicting data regarding whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia, and/or hypocapnia are associated with worse outcomes. We sought to determine whether postarrest hypoxemia or postarrest hyperoxemia is associated with lower rates of survival to hospital discharge, compared with postarrest normoxemia, and whether postarrest hypocapnia or hypercapnia is associated with lower rates of survival, compared with postarrest normocapnia. An embedded prospective observational study during a multicenter interventional cardiopulmonary resuscitation trial was conducted from 2016 to 2021.

Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries.

Background: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation.

Methods And Findings: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018.

Vaccine communication training using the Brief Motivational Interviewing for Maternal Immunization intervention: A PRISM implementation evaluation.

Improving clinician-patient communication can increase uptake of recommended vaccinations during pregnancy. To evaluate adaptations to and pragmatism of the brief Motivational Interviewing for Maternal Immunizations (MI4MI) intervention and to use the Practical Robust Implementation and Sustainability Model (PRISM) to describe context and implementation outcomes among clinician and staff participants. We incorporated data from study team members, clinicians and staff participants, pregnant patients at participating clinics, and patient medical records.

Recurrent Intensive Care Episodes and Mortality Among Children With Severe Neurologic Impairment.

Importance: Children requiring care in a pediatric intensive care unit (PICU) are known to have increased risk of subsequent mortality. Children with severe neurologic impairment (SNI)-who carry neurologic or genetic diagnoses with functional impairments and medical complexity-are frequently admitted to PICUs. Although recurrent PICU critical illness episodes (PICU-CIEs) are assumed to indicate a poor prognosis, the association between recurrent PICU-CIEs and mortality in this patient population is poorly understood.