Multiple Sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system. Approximately 10% of cases present before 18 years of age, constituting paediatric-onset MS (POMS). Compared with adults, children with MS exhibit higher relapse rates and shorter intervals between the first event and subsequent relapses, yet generally demonstrate better recovery. The latest revision of the diagnostic criteria (2024) incorporates: the optic nerve as an additional location; specific MRI radiologically isolated syndrome; and CSF kappa free light chain as an adjunctive biomarker. In paediatric populations, the typically high burden of inflammatory lesions and high relapse rate warrants special consideration. The principal differential diagnosis is MOG-antibody-associated disease, Evidence indicates that early initiation of high-efficacy disease-modifying therapies is associated with improved long-term outcomes.

Autism is a neurodevelopmental disorder with a neurobiological basis, affecting 1 in 31 people, with a male predominance (3.8 to 1). Characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors, along with sensory processing difficulties, this condition accompanies individuals throughout their lives, with variations in its progression. According to support needs, it is divided into levels 1 (mild), 2 (moderate), and 3 (severe). While the classification is clear, it does not include clinical subtypes related to the presence of neurodevelopmental and psychiatric disorders, genetic bases, neurogenetic entities, and/or variations in its progression. In this work, I will analyze some frequently observed autistic phenotypes not described in the DSM-5 and delve into four specific ones, recently defined in the literature, that show a genotype-phenotype correlation. These are: 1. Social and behavioral autismo, 2. Mixed autism with developmental delay, 3. Moderate autism, and 4. Widespread autism. Different genes and their expression timing were identified in these phenotypes, suggesting a pre- and postnatal temporality that impacts clinical presentation and age of diagnosis. Identifying different phenotypes facilitates research and allows for a phenotype/genotype correlation, defining clinical profiles and therapeutic guidance.

This study aimed to evaluate the survival outcomes of pediatric patients with head and neck (HN) rhabdomyosarcoma (RMS) treated at a reference center in Brazil, comparing them with those of patients with non-head and neck (NHN) RMS. Additionally, it sought to identify the clinical-pathological variables, histological subtypes, and antineoplastic therapy regimens that significantly influence patient prognosis. The study included RMS patients treated between 1990 and 2022. Statistical analyses comprised t-tests, chi-square tests, Kaplan-Meier survival analysis, and Cox regression for overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). A total of 64 patients (60.9% male) were included, with head and neck tumors being the most common presentation. Prognostic factors associated with OS included age ≥ 10 years, intermediate-risk classification, tumor relapse, and surgery. DFS was significantly influenced by age ≥10 years and high-risk classification, while EFS was associated with lesion size, histological subtype, and radiotherapy. In conclusion, anatomical site was not a significant prognostic factor. Age and risk classification significantly influenced OS and DFS, while histological subtype emerged as an independent factor for EFS. This study, conducted at a reference center in Latin America with a 30-year history of care, provides clinically relevant insights by identifying specific prognostic factors for RMS in Brazilian pediatric patients. These findings enable comparisons with international data and contribute to planning health interventions.

The aim of this study was to establish comprehensive normative values and generate robust predictive equations for isometric upper limb muscle strength using hand-held dynamometry (HHD) in healthy adults aged 18 to 80 years. A cross-sectional multicenter study was conducted with 210 healthy volunteers aged 18 to 80 years. Participants were rigorously screened to exclude cognitive impairment, acute musculoskeletal symptoms, or systemic conditions that could influence strength. Participants underwent standardized assessment of isometric strength using a handheld dynamometer for 10 key upper limb muscle groups (dominant and non-dominant limbs), and maximal isometric strength (kgf) of each muscle group was recorded. Primary analytical outcomes included age- and sex-specific reference values and derived predictive equations for strength. Novel predictive equations were successfully developed for all 10 upper limb muscle groups from this diverse sample. A very good correlation (r2 range: 0.62-0.77, P<0.001) was observed between direct HHD measurements and the proposed equations. Importantly, these new equations demonstrated superior predictability for this population compared to previously published North American reference equations. This study provides the first comprehensive set of age- and sex-specific normative values and predictive equations for isometric upper limb muscle strength via HHD in healthy adults. These invaluable normative data enable rehabilitation professionals to objectively assess strength, identify weakness early, and enhance treatment monitoring, thus strengthening evidence-based practice in physical medicine and rehabilitation.

Chimeric Antigen Receptor T-cell (CAR‑T) therapy, genetically engineered patient T cells targeting tumor antigens, has transformed care for hematologic malignancies but requires careful tracking of adverse events (AEs) often documented only in unstructured electronic health record (EHR) notes. We evaluated a Large Language Model (LLM)-based approach in UCSF's secure environment to extract AEs, dates, grades, and interventions within 30 days post‑infusion for six commercial CAR‑T products (2012-2023), benchmarking against two evaluators. Using GPT‑4‑0314 in a zero‑shot setting with four prompts (prespecified AEs, non‑prespecified AEs, CRS, ICANS), we compared outputs against dual annotations on a random sample of 50 notes using accuracy, precision, recall, F1, and Cohen's kappa. From 4,762 progress notes for 293 patients (median age 65.6), CRS occurred in 80.2% (median onset 4 days); neutropenia 70.0% (16 days); neutropenic fever 64.8% (4 days); ICANS in 34.8%. Interventions included tocilizumab and corticosteroids. Grades were frequently undocumented (CRS 62.3%, ICANS 56.1%); documented cases were mainly CRS grade 1 (59.4%) and ICANS grade 2 (28.0%). Performance was high on CRS and ICANS grading (accuracy of 0.97 and 0.91, respectively). Moderate performances were assessed for prespecified AE extraction (accuracies 0.62-0.76), and non‑prespecified AEs (accuracies 0.76-0.84). Inter‑rater reliability (IRR) was strong for CRS/ICANS presence and grade (kappa 0.86-0.96), moderate for dates and interventions, and weaker for broader AE attributes. LLM‑derived insights can augment AE monitoring and real‑world evidence generation by unlocking unstructured clinical detail and characteristic timelines after CAR T. However, performance varied for broader AE attributes, warranting cautious use. Performance was highest for detecting and grading CRS and ICANS, with strong to near-perfect IRR. While cautious use of LLMs is warranted due to the variable performance observed in this study, these results support further evaluation of supervised CRS/ICANS extraction in controlled EHR-based research or pilot settings, with monitoring and prospective validation.

Secreted proteins are essential to modulate homeostasis in the extracellular space and facilitate communication to distal cells or tissues. Yet, the identity and functional importance of extracellular proteins in aging have been understudied. Here we use proximity labeling followed by quantitative proteomics to systematically characterize proteins along the intestinal secretory pathway in C. elegans, focusing on secreted proteins. We identify intestine-secreted proteins that are modulated with age, and validate the secretion of these proteins in vivo. One of these secreted proteins, ACP7, is well conserved in humans, and its overexpression extends lifespan in a secretion-dependent manner. Interestingly, we find that ACP7 acts as a secreted phosphatase in the extracellular space. Finally, we identify additional proteins along the secretory pathway that regulate lifespan. Our systematic characterization of tissue-specific secreted proteins during aging uncovers conserved proteins that impact lifespan and highlights extracellular enzymes associated with lifespan regulation.