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.

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.

Imaging Findings and Management Strategies for Liver Masses in Children with Predisposition Disorders: A Review by the Pediatric LI-RADS Group.

Liver masses in children with underlying systemic disease or a predisposing syndrome can be benign or malignant, ranging from focal fat to hepatocellular carcinoma (HCC). Knowledge of the underlying condition, the pathophysiologic effect on the liver, and the development of liver disease and specific liver lesions allows radiologists to guide imaging with regard to modality and frequency and give recommendations for biopsy when appropriate. In some predisposition disorders, such as Beckwith Wiedemann spectrum, familial adenomatous polyposis syndrome, and tuberous sclerosis complex, established guidelines for imaging screening exist.

Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation.

Background: When human leukocyte antigen (HLA)-matched donors are not available for hematopoietic stem cell transplants (HSCT), there are no well-accepted guidelines for ranking 7/8 HLA-matched unrelated donors to achieve optimal transplant outcomes. A novel scoring system for ranking HLA mismatches for these donors was investigated.

Methods: High-resolution HLA types were used to determine amino acid mismatches located in the HLA antigen-recognition domain.

Oral Health Care for Children and Youth With Developmental Disabilities: Clinical Report.

Oral health is an essential component of overall health for all individuals. The oral health of children and youth with developmental disabilities (CYDD) involves unique characteristics and needs of which pediatricians and pediatric clinicians can be aware. Risk for oral disease in CYDD is multifactorial and includes underlying medical conditions, medications, and ability to participate in preventive oral health care and treatment, and lack of access to providers is common for this population despite being eligible for Medicaid.

Artificial Intelligence Outcome Prediction in Neonates with Encephalopathy (AI-OPiNE).

Purpose To develop a deep learning algorithm to predict 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy using MRI and basic clinical data. Materials and Methods In this study, MRI data of term neonates with encephalopathy in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial (ClinicalTrials.gov: NCT02811263), who were enrolled from 17 institutions between January 25, 2017, and October 9, 2019, were retrospectively analyzed.

Health Justice and Systems of Care: A Required Longitudinal Course for MD Students.

Problem & Background: Medical education has acknowledged the impact of structural societal factors on health, prompting the need for curricula seeking to eliminate health inequities upstream while simultaneously caring for downstream effects of existing inequities. The Keck School of Medicine of USC (KSOM) implemented one such comprehensive curriculum, Health Justice and Systems of Care (HJSC), integrating health systems science, structural competency, and service-learning in a required course spanning the pre-clerkship and clerkship phases with an optional post clerkship elective.

Approach: The HJSC course addresses topics including racism in medicine, health inequities, and health systems science.

Nonacog beta pegol prophylaxis in children with hemophilia B: safety, efficacy, and neurodevelopmental outcomes for up to 8 years.

Background: Nonacog beta pegol (N9-GP) is an extended half-life PEGylated factor (F)IX product with established efficacy and short-term safety in persons with hemophilia B (HB). Long-term safety has been evaluated for polyethylene glycol exposure but not N9-GP.

Objectives: To assess safety, neurodevelopmental, and efficacy outcomes of children with HB receiving N9-GP prophylaxis across 2 open-label, single-arm, phase 3 studies: paradigm5 (previously treated patients [PTPs]) and paradigm6 (previously untreated patients [PUPs]) in this interim analysis.

Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells.

Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in nonphysiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis.

High Symptom Burden Predicts Poorer Quality of Life Among Children and Adolescents Receiving Hematopoietic Stem Cell Transplantation or Chimeric Antigen Receptor T-Cell Therapy.

Background: Children with cancer and other serious illnesses experience symptom burden during hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy, yet limited research has characterized how these symptoms interact with overall quality of life over time.

Objective: The aim of this study was to examine the longitudinal relationship between symptoms and quality of life in children receiving hematopoietic stem cell transplantation or chimeric antigen receptor T-cell therapy.

Methods: A multisite study design was used to collect symptom and quality of life information at pre-cell infusion and days +30, +60, and +90 from children (N = 140) receiving hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy.

Prescription Drug Prices: An AAN Position Statement.

This position statement serves to establish the AAN's stance on the methods to address the cost of prescription drugs being considered by state and federal policymakers so that the AAN can continue to advocate effectively for its members. Neurologists seek to provide high-value care for patients with neurologic diseases at the lowest cost possible. However, many therapies for neurologic diseases are among the most expensive in the United States.

Solving the health disparity of eczema assessment: A role for skin tape soluble protein?

Background: The assessment of erythema in patients with atopic dermatitis (AD) is based on clinical examination. The difficulty of perceiving erythema in Black patients with AD has led to underestimation of AD severity in these patients.

Objective: In this study, we analyzed the concentration of skin tape soluble protein of AD lesions against common AD clinical signs.

Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

Purpose: Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered.

AAPM Task Group Report 307: Use of EPIDs for Patient-Specific IMRT and VMAT QA.

Purpose: Electronic portal imaging devices (EPIDs) have been widely utilized for patient-specific quality assurance (PSQA) and their use for transit dosimetry applications is emerging. Yet there are no specific guidelines on the potential uses, limitations, and correct utilization of EPIDs for these purposes. The American Association of Physicists in Medicine (AAPM) Task Group 307 (TG-307) provides a comprehensive review of the physics, modeling, algorithms and clinical experience with EPID-based pre-treatment and transit dosimetry techniques.

CAR NK-92 cell-mediated depletion of residual TCR+ cells for ultrapure allogeneic TCR-deleted CAR T-cell products.

Graft-versus-host disease (GVHD) is a major risk of the administration of allogeneic chimeric antigen receptor (CAR)-redirected T cells to patients who are HLA unmatched. Gene editing can be used to disrupt potentially alloreactive T-cell receptors (TCRs) in CAR T cells and reduce the risk of GVHD. Despite the high knockout rates achieved with the optimized methods, a subsequent purification step is necessary to obtain a safe allogeneic product.

Non-viral chimeric antigen receptor (CAR) T cells going viral.

Chimeric antigen receptor (CAR) T cell therapy has made significant strides in the treatment of B-cell malignancies, but its application in treating solid tumors still poses significant challenges. Particularly, the widespread use of viral vectors to deliver CAR transgenes into T cells comes with limitations, including high costs and regulatory restrictions, which hinder the translation of novel genetic engineering concepts into clinical applications. Non-viral methods, such as transposon/transposase and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems, offer promising alternatives for stable transgene insertion in CAR-T cells.

Toward Systematic Assessment and Improvement of Radiation Therapy Plan Quality of Cooperative Group Trial Submissions: A Report From the Children's Oncology Group.

Purpose: This study evaluates the quality of plans used for the treatment of patients in the Children's Oncology Group study ACNS1123. Plan quality is quantified based on a scoring system specific to the protocol. In this way, the distribution of plan quality scores is determined that can be used to identify plan quality issues for this study and for future plan quality improvement.

Physics Considerations for Evaluation of Dose for Dose-Response Models of Pediatric Late Effects From Radiation Therapy: A PENTEC Introductory Review.

Purpose: We describe the methods used to estimate the accuracy of dosimetric data found in literature sources used to construct the Pediatric Normal Tissue Effects in the Clinic (PENTEC) dose-response models, summarize these findings of each organ-specific task force, describe some of the dosimetric challenges and the extent to which these efforts affected the final modeling results, and provide guidance on the interpretation of the dose-response results given the various dosimetric uncertainties.

Methods And Materials: Each of the PENTEC task force medical physicists reviewed all the journal articles used for dose-response modeling to identify, categorize, and quantify dosimetric uncertainties. These uncertainties fell into 6 broad categories.