Rethinking the rise of early onset gastrointestinal cancers: a call to action.

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend.

Patent Ductus Arteriosus Morphology Changes in Preterm Neonates Undergoing Transcatheter Device Closure.

Evaluate patent ductus arteriosus (PDA) morphology changes in the preterm neonate undergoing transcatheter PDA closure (TCPC). We propose the type F ductus is associated with lower corrected gestational age (CGA) and improved TCPC outcomes. Retrospective review of premature neonates undergoing TCPC at a large volume institution from November 2020 to November 2023.

The association of perceived health status and presence of chronic conditions with physical activity in childhood cancer survivors.

Purpose: Childhood cancer survivors (CCS) are at risk for therapy-related late effects. Physical activity (PA) can minimize some late effects risk, but rates of PA are low in CCS. We aimed to determine how perception of survivor health status and presence of chronic conditions are associated with patient- or proxy-reported PA.

Spaceflight alters protein levels and gene expression associated with stress response and metabolic characteristics in human cardiac spheroids.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous advantage for cardiac regeneration. However, cell survival is challenging upon cell transplantation. Since microgravity can profoundly affect cellular properties, we investigated the effect of spaceflight on hiPSC-CMs.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

Treatment of focal anaplastic Wilms tumor: A report from the Children's Oncology Group AREN0321 and AREN03B2 studies.

Background: In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II-IV FAWT. Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.

Blood Transfusion and Survival of Children, Adolescent, and Young Adult Patients with Osteosarcoma: A Multicenter Retrospective Cohort Study.

: Prior studies suggest that blood transfusion may adversely affect the survival of patients with cancer via transfusion-related immunomodulation. The objective of our study is to investigate the association between transfusion during neoadjuvant chemotherapy and survival in children, adolescent, and young adult (CAYA, 39 years old or younger) patients with osteosarcoma. : This is a multicenter retrospective cohort study of patients between 2007 and 2022.

Preferences for Inguinal Hernia Repair in Infants: A Survey of the Eastern Pediatric Surgery Network.

Introduction: Laparoscopic inguinal hernia repair (IHR) is being performed more frequently in children, but few studies have evaluated surgical practice patterns in infants. In this study, we surveyed pediatric surgeons within a regional consortium to assess current preferences for IHR strategy in infants. We hypothesized that early-career pediatric surgeons would prefer laparoscopic IHR over open IHR in this patient population.

SIV Env RhmAbs + N-803 at ART initiation prolongs viral decay without disrupting reservoir establishment in SIV-infected infant macaques.

The latent viral reservoir remains the major barrier to HIV cure, placing the burden of strict adherence to antiretroviral therapy (ART) on people living with HIV to prevent recrudescence of viremia. For infants with perinatally acquired HIV, adherence is anticipated to be a lifelong need. In this study, we tested the hypothesis that administration of ART and viral Envelope-specific rhesus-derived IgG1 monoclonal antibodies (RhmAbs) with or without the IL-15 superagonist N-803 early in infection would limit viral reservoir establishment in SIV-infected infant rhesus macaques.

Towards a Provider Builder Maturity Model to Empower Clinicians to Actively Participate in Electronic Health Record Design.

Background: Engagement of clinicians who understand clinical workflows and technology constraints can accelerate the development and implementation of better electronic health record (EHR) designs that improve quality and reduce burnout. Provider builder programs can accelerate clinical informatics education for a broader coalition of clinical specialties.

Objective: In this State of the Art / Best Practice paper, we aim to (1) propose a provider builder maturity model informed by the experience of three institutions using a single EHR vendor (Epic Systems©) and (2) describe the program elements and relationships necessary to advance along this model to yield organizational benefits.

Prevention and Management of Infectious Complications in Pediatric Patients With Cancer: A Survey Assessment of Current Practices Across Children's Oncology Group Institutions.

Introduction: While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers.

Methods: An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution.

Results: The response rate was 57% (129/227 institutions).

Establishing Minimal Clinically Important Differences for the Cognitive and Linguistic Scale (CALS) in Pediatric Neurorehabilitation.

The Cognitive and Linguistic Scale (CALS) was developed to serially monitor cognitive recovery of children and young people after severe acquired brain injury (ABI), during inpatient rehabilitation. The CALS can be used to derive Cognitive Ability Estimates (CAE) which are Rasch-propertied (unidimensional, interval-scale) and therefore may be ideally applied for use in research including within the context of clinical trials. Here, we used established statistical distribution-based and expert consensus-based methods to estimate the Minimal Clinically Important Difference (MCID) for CAE derived from the CALS.

Neuromodulation Strategies in Lennox-Gastaut Syndrome: Practical Clinical Guidance from the Pediatric Epilepsy Research Consortium.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS), have emerged as important treatment options for patients with LGS who do not respond adequately to antiseizure medications. This review, developed with input from the Pediatric Epilepsy Research Consortium (PERC) LGS Special Interest Group, provides practical guidance for clinicians on the use of these neuromodulation approaches in patients with LGS.

Apnea After 2-Month Vaccinations in Hospitalized Preterm Infants: A Randomized Clinical Trial.

Importance: Preterm infants are recommended to receive most vaccinations at the same postnatal age as term infants. Studies have inconsistently observed an increased risk for postvaccination apnea in preterm infants.

Objective: To compare the proportions of hospitalized preterm infants with apnea and other adverse events in the 48 hours after 2-month vaccinations vs after no vaccinations.

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.

Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells.

The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia.

Interview Results from a Telehealth Hospice Intervention for Children and Young Adults with Cancer.

Background And Aims: Surveyed families of children and young adults with cancer who participated in a pilot study of three coordinated telehealth visits (triad of patient/family, hospital clinician, and hospice nurse) during the first month of hospice enrollment found telehealth feasible and were highly satisfied with hospice care. The aim of this study is to further explore adult patient and caregiver perspectives on telehealth, specifically the benefits of telehealth, trade-offs with in-person appointments, and the impact on patient care and family end-of-life preparations.

Methods: This is a single-arm prospective pilot study of patients aged 0-29-with cancer initiating hospice care between 2021-2022 and their caregivers.

Engraft: A Collaborative Learning Health Network for Enhanced Transplant and Cellular Therapy Outcomes.

The Engraft Learning Health Network (LHN) aims to improve outcomes for patients undergoing transplant and cellular therapy (TCT) through a collaborative, data-driven approach. Engraft brings together diverse stakeholders, including clinicians, patients, caregivers, and institutions, to standardize best practices and accelerate the dissemination of innovations in TCT care. By establishing a multicenter, real-world clinical registry focused on rapid-cycle quality improvement (QI) and implementation research, Engraft seeks to reduce variability in clinical practice to improve TCT outcomes across centers.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part IV. Patient Important Outcomes.

Chronic graft versus host disease (cGVHD), occurs in approximately one in five pediatric allogeneic HCT patients and is a leading cause of late morbidity and mortality. Late effects of HCT may lead to long-term chronic health conditions and shortened life expectancy. In addition to direct physiological challenges from cGVHD and other late-effects, numerous patient-important outcomes impact the quality of life (QOL) of patients and their families.

Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement.

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations.

Allogeneic haematopoietic stem-cell transplantation for children with refractory systemic juvenile idiopathic arthritis and associated lung disease: outcomes from an international, retrospective cohort study.

Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.

Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT.

Enhanced engraftment of human haematopoietic stem cells via mechanical remodelling mediated by the corticotropin-releasing hormone.

The engraftment of haematopoietic stem and progenitor cells (HSPCs), particularly in cord-blood transplants, remains challenging. Here we report the role of the corticotropin-releasing hormone (CRH) in enhancing the homing and engraftment of human-cord-blood HSPCs in bone marrow through mechanical remodelling. By using microfluidics, intravital two-photon imaging and long-term-engraftment assays, we show that treatment with CRH substantially enhances HSPC adhesion, motility and mechanical remodelling, ultimately leading to improved bone-marrow homing and engraftment in immunodeficient mice.

A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose.

Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.