Pediatric relapsed/refractory ALK+ anaplastic large cell lymphoma treatment and outcomes in the targeted drug era.

Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK) inhibitors. However, there is no standard treatment and limited published data evaluating their use. The goal of this retrospective study is to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL.

Impact of social determinants of health on the outcomes of Latin American children with Multisystem Inflammatory Syndrome (MIS-C).

Importance: There is growing understanding that Social Determinants of Health (SDH) impact on the outcomes of different pediatric conditions. We aimed to determine whether SDH affect the severity of MIS-C.

Design: Retrospective cohort study, 2021-2023.

AAPM&R consensus guidance on spasticity assessment and management.

Background: The American Academy of Physical Medicine and Rehabilitation (AAPM&R) conducted a comprehensive review in 2021 to identify opportunities for enhancing the care of adult and pediatric patients with spasticity. A technical expert panel (TEP) was convened to develop consensus-based practice recommendations aimed at addressing gaps in spasticity care.

Objective: To develop consensus-based practice recommendations to identify and address gaps in spasticity care.

Characteristics and Perspectives of Human Trafficking Education: A Survey of U.S. Medical School Administrators and Students.

To assess the timing, duration, methodology, and content of human trafficking (HT) curricula in U.S. medical schools.

Advances in Transcatheter Electrosurgery for Treating Valvular Heart Disease.

Delivery of electrosurgery energy through catheters and guidewires enables interventionists to 'cut' through obstructive intravascular lesions or across cardiac chambers. A novel application of transcatheter electrosurgery is to make controlled lacerations in heart valve leaflets. This review describes three applications of transcatheter electrosurgery of aortic and mitral valve leaflets to enable transcatheter heart valve implantation.

Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

Transcatheter Electrosurgery: JACC State-of-the-Art Review.

Transcatheter electrosurgery refers to a family of procedures using radiofrequency energy to vaporize and traverse or lacerate tissue despite flowing blood. The authors review theory, simulations, and benchtop demonstrations of how guidewires, insulation, adjunctive catheters, and dielectric medium interact. For tissue traversal, all but the tip of traversing guidewires is insulated to concentrate current.

De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy.

Purpose: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures. Because DEEs are clinically and genetically heterogeneous, next-generation sequencing, especially exome sequencing (ES), is becoming a first-tier strategy to identify the molecular etiologies of these disorders.

Methods: We combined ES analysis and international data sharing.

Effect of inhaled corticosteroid use on weight (BMI) in pediatric patients with moderate-severe asthma.

Objectives: Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI).

Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis.

Effects of MetAP2 inhibition on hyperphagia and body weight in Prader-Willi syndrome: A randomized, double-blind, placebo-controlled trial.

Aims: There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib.

Materials And Methods: Participants with PWS (12-65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.

Single Agent and Synergistic Activity of the "First-in-Class" Dual PI3K/BRD4 Inhibitor SF1126 with Sorafenib in Hepatocellular Carcinoma.

Deregulated PI3K/AKT/mTOR, Ras/Raf/MAPK, and c-Myc signaling pathways are of prognostic significance in hepatocellular carcinoma (HCC). Sorafenib, the only drug clinically approved for patients with advanced HCC, blocks the Ras/Raf/MAPK pathway but it does not inhibit the PI3K/AKT/mTOR pathway or c-Myc activation. Hence, there is an unmet medical need to identify potent PI3K/BRD4 inhibitors, which can be used either alone or in combination with sorafenib to treat patients with advanced HCC.

PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma.

Sonic hedgehog (SHH) medulloblastoma (MB) subtype is driven by a proliferative CD15+ tumor propagating cell (TPC), also considered in the literature as a putative cancer stem cell (CSC). Despite considerable research, much of the biology of this TPC remains unknown. We report evidence that phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI-3K) play a crucial role in the propagation, survival and potential response to therapy in this CD15+ CSC/TPC-driven malignant disease.

Anti-tumor effect of a novel PI3-kinase inhibitor, SF1126, in (12) V-Ha-Ras transgenic mouse glioma model.

Background: Growth factor mediated activation of RAS-MAP-kinase and PI3-kinase-AKT pathways are critical for the pathogenesis of glioblastoma. The attenuation of PI3-kinase/AKT signaling will be effective in regulating the tumorigenic phenotypes of the glioma cells.

Methods: Glioma cells derived from the brain of the (12) V-Ha-Ras transgenic mice were used to study the effect of PI-3 kinase inhibitor SF1126 on activation of AKT and ERK signaling, proliferation, vitronectin mediated migration and changes in the distribution of cortical actin on vitronectin in the glioma cells in vitro.

A macrophage-dominant PI3K isoform controls hypoxia-induced HIF1α and HIF2α stability and tumor growth, angiogenesis, and metastasis.

Unlabelled: Tumor growth, progression, and response to the hypoxic tumor microenvironment involve the action of hypoxia-inducible transcription factors, HIF1 and HIF2. HIF is a heterodimeric transcription factor containing an inducible HIFα subunit and a constitutively expressed HIFβ subunit. The signaling pathways operational in macrophages regulating hypoxia-induced HIFα stabilization remain the subject of intense investigation.

Sudden cardiac death and malignant arrhythmias: the scope of the problem in adult congenital heart patients.

A key component of recognizing sudden cardiac death (SCD) risk in the adult congenital heart disease (ACHD) patient is the recognition of heart failure risk for each physiology. The risk of SCD is an accrued phenomenon, representing the influences of anatomy, genetics, surgical and catheter interventions, and long-term sequelae of residual hemodynamic issues. These all lead to a substrate for tachyarrhythmia.