Targeted Therapy in Pediatric Langerhans Cell Histiocytosis: Describing a Novel Strategy to Minimize Long-Term Exposure While Maintaining Efficacy.

Background: Langerhans cell histiocytosis (LCH) is a rare malignancy driven by MAPK pathway activation and often involves BRAF V600E mutations. Targeted therapy with trametinib, a MEK inhibitor, is a promising alternative to conventional chemotherapy.

Procedure: We retrospectively analyzed the records of patients treated with trametinib either at relapse or as front-line therapy between 2020 and 2024.

A survey of adult caregivers of people with developmental and epileptic encephalopathies: A long-term care planning needs assessment.

Objective: Provide the perspective of caregivers planning for adulthood in people with developmental and epileptic encephalopathies (DEEs).

Results: Family members (N = 134) of people with DEE (1-44 years old) responded to an anonymous, internet-based survey to assess the needs of DEE families. Respondents included parents/guardians (n = 121, 90.

An Analysis of Diagnostic Metabolomic Profiles Associated with Hepatotoxicity During Childhood ALL Induction Therapy.

Hepatotoxicity is a well-documented complication of induction chemotherapy for acute lymphoblastic leukemia (ALL), but our understanding of the biological mechanisms is limited. We identified 314 patients with ALL (age 1-19 years) treated at Texas Children's Hospital (2007-2018) with diagnostic bone marrow plasma available for metabolomic profiling: 234 for discovery and 80 for replication. Hepatotoxicity during induction therapy was defined as: 1) transaminitis: grade ≥3 AST or ALT, or 2) conjugated hyperbilirubinemia: conjugated bilirubin (c.

Sebelipase Alfa Improves Aminotransferase Levels in Lysosomal Acid Lipase Deficiency: Data From an International Registry.

Background And Aims: In patients with lysosomal acid lipase deficiency (LAL-D), elevations in alanine and aspartate aminotransferases (ALT, AST) are associated with liver damage. The objective of this analysis was to evaluate aminotransferase levels in patients treated with sebelipase alfa enzyme replacement therapy and untreated patients.

Methods: Patients in this observational study were from the International LAL-D Registry and included untreated and treated patients who started sebelipase alfa at age ≥ 6 months.

Immediate-use rescue medication and the epilepsy monitoring unit: experiences from an expert panel.

Background: People with epilepsy (PWE) may experience seizure clusters, broadly defined as ≥2 seizures that occur in close proximity. In epilepsy monitoring units (EMUs), seizure clusters can spontaneously occur during long-term videoelectroencephalogram monitoring (LTVEM) or as a result of antiseizure medication dose adjustments. In this survey, we examined the experiences and practices of expert clinicians with seizure clusters in EMUs.

Implementation of a Pediatric Oncology Precision Medicine Clinic to Personalize Approaches for Diagnosing and Treating Solid Tumors.

Background: Precision medicine is an emerging approach for treating pediatric cancer due to its ability to target tumor-specific genetic drivers rather than provide broad and aggressive treatments. The study aimed to outline the establishment and impact of a Precision Medicine Clinic (PMC) in the setting of pediatric oncology, with the objective of offering targeted treatment options within the institution and creating a scalable model for adoption by other healthcare systems to achieve a wider impact.

Methods: Recognizing this need for an individualized approach to treating patients, Cook Children's Medical Center (CCMC) established a multidisciplinary molecular tumor board in 2019, followed by the launch of an official PMC in 2021.

Depressive symptoms in youth with refractory epilepsy: Exploration of seizure, sociodemographic and cognitive factors.

Introduction: Rates of depressive symptoms in children and youth with epilepsy (CYE) vary among studies, ranging from 12 to 41%. The current study examined depressive symptoms in a large, multi-site sample of CYE who completed measures of emotional and behavioral functioning as part of a pre-surgical neuropsychological evaluation.

Methods: CYE ranged in age from 5 to 18 years old, had refractory epilepsy (n = 416), and underwent neuropsychological assessment, including standardized assessment of intellectual (IQ), emotional, and behavioral functioning using caregiver-proxy.

Improving Modulator Management and Side Effect Screening: A CF Learning Network Innovation Lab.

Background: Despite eligibility of over 90% of people with cystic fibrosis (PwCF) for CFTR modulators, 12% of eligible PwCF are not prescribed these therapies. The CF Foundation CF Learning Network (CFLN) convened a quality improvement (QI) innovation lab (iLab) to investigate gaps in modulator use and identify best practices for modulator initiation, management, and side effect screening.

Methods: Thirty-one CF centers used the Model for Improvement to adapt interventions to local context by Plan-Do-Study-Act cycles and approach aims in two phases: (1) increase documented elexacaftor-tezacaftor-ivacaftor or ivacaftor (ETI/I) use or co-produced deferral by 4% by 5/2023 and (2) increase side effect screening rates for PwCF taking ETI to 80% by 8/2024.

Characterization and prediction of hematotoxicity in pediatric patients receiving tisagenlecuecel.

Hematotoxicity is the most frequent severe toxicity following chimeric antigen receptor (CAR) T therapy. However, limited data exist on risk factors and outcomes for hematotoxicity for children and young adults (CAYA) with B-acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel. We conducted a multi-institutional study involving 326 CAYA, with 144 evaluable in an initial training cohort and 141 evaluable in a validation cohort, through the Pediatric Real World CAR Consortium to characterize the incidence and outcomes of prolonged severe neutropenia (PSN) and to develop a predictive risk score for PSN, tailored for use in this population.

Medicaid expansion and overall mortality among women with cervical cancer.

Objective: To assess the association between Medicaid expansion under the Affordable Care Act (ACA) and overall mortality among women with cervical cancer, specifically evaluating changes in stage at diagnosis and treatment utilization and emphasizing differences in survival between early expansion states (implemented by 2014) and non-expansion states.

Methods: Researchers conducted a retrospective cohort study using data from the National Cancer Database for the period 2006-2021, involving individuals aged 18-64 years. Medicaid expansion served as the primary explanatory variable, classifying states that implemented Medicaid expansion before January 2014 as early expansion states and states that did not expand as non-expansion states.

Current and Future Treatment Strategies in Developmental and/or Epileptic Encephalopathy With Spike-Wave Activation in Sleep (DEE-SWAS): A Time for Precision Medicine?

Developmental and/or epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS) is a childhood-onset epilepsy syndrome characterized by cognitive regression or stagnation and marked activation of epileptiform activity during sleep. DEE-SWAS refers to cases with pre-existing neurodevelopmental disorders, whereas EE-SWAS is applied when development was initially normal before the onset of epileptic encephalopathy. This syndrome comprises approximately 0.

The impact of loneliness on depression, mental health, and physical well-being.

Background: Loneliness is a growing public health concern, with substantial implications for mental and physical health. Despite increasing attention, it remains an underrecognized determinant of health outcomes in population-based research.

Objective: This study evaluates the association between loneliness and key health outcomes, including depression diagnosis, poor mental health days, and poor physical health days, using a nationally representative sample.

Altered Expression of NK Receptors in Racially/Ethnically Diverse and Risk-of-Relapse Pediatric Acute Lymphoblastic Leukemia Patients.

Acute Lymphoblastic Leukemia (ALL) is a cancer that predominantly affects white blood cells within the blood and bone marrow of adults and children. Currently, ALL is one of the most prevalent malignancies in pediatric patients and is most seen among Caucasian and Hispanic descent, with lower incidence in African American children. The goal of the study was to investigate the expression of immune cell receptors in racial/ethnic populations and risk factors for relapse that could potentially influence the pediatric ALL outcomes.