Background/Objectives: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy with axicabtagene ciloleucel (axi-cel) improves outcomes in relapsed/refractory large B-cell lymphoma (LBCL), but many patients relapse despite retained CD19 expression. We explored baseline tumor transcriptional features associated with event-free survival (EFS) after axi-cel. Methods: We reanalyzed baseline NanoString IO 360 profiles from the randomized ZUMA-7 trial (axi-cel, n = 134; standard of care [SOC], n = 122) using differential expression, gene set enrichment, MCP-counter deconvolution, Kaplan–Meier and Cox models adjusted for tumor burden and cell of origin, and gene-by-treatment interaction models. Results: T-cell exhaustion and HLA transcripts were not associated with response in either arm, and no transcript passed FDR correction in differential expression. In the axi-cel arm, 13 of 14 modeled transcripts remained associated with EFS after adjustment; eight (MS4A1, CD19, TNFRSF17, HLA-DOB, CD45RA, DUSP5, KLRD1 and WNT11) were FDR-supported at every survival-analysis stage within the 25 prioritized candidates, but not panel-wide. Consistent with the primary ZUMA-7 report, higher B-cell transcript expression was associated with longer EFS. Interaction testing gave borderline support for a differential association between arms only for KLRD1 and DUSP5 (FDR = 0.049), robust to arm-stratified models; other candidates showed no or only nominal specificity. Apart from the B-lineage score (FDR = 0.029), no estimated immune or stromal population was associated with response. Conclusions: Baseline B-cell transcriptional programs and a small set of gene-level candidates are associated with EFS after axi-cel in ZUMA-7. These exploratory findings do not establish predictive value and require independent validation.

Background/Objectives: To map mental illness-related stigma and identity-based stigma and discrimination in relation to depression, anxiety, and mental health care processes among Brazilian youth. Methods: This scoping review followed PRISMA-ScR guidelines and the Arksey and O’Malley framework. PubMed/MEDLINE, Scopus, SciELO, LILACS, and CAPES were searched for studies examining stigma in relation to depression, anxiety, mental health outcomes, or care-related processes among Brazilian children and adolescents. Mixed adolescent and young-adult samples were included when they contained adolescents within the target age range. Results: Seven studies met the inclusion criteria. Stigma was identified across four domains: public, structural, self-, and courtesy stigma. Perceived discrimination was associated with major depression (aPR = 2.00, 95% CI 1.37–2.97) and severe depressive symptoms (aOR = 1.71, 95% CI 1.23–2.38) in studies examining racial discrimination and discrimination affecting sexual and gender minority youth. These estimates were derived from samples that included young adults. Qualitative evidence linked stigma to symptom concealment, barriers to help-seeking and diagnostic processes, and difficulties engaging with care. Evidence was limited by predominantly cross-sectional and qualitative designs, uneven geographic representation across Brazil, and a lack of culturally validated stigma measures. Conclusions: Stigma appears to be a multi-level factor associated with adverse mental health outcomes and with reported barriers across the mental health care pathway among Brazilian youth. Stigma-informed approaches may support earlier engagement with care among marginalized youth, but their effectiveness remains to be evaluated.

Background/Objectives: Timely identification of autism spectrum disorder (ASD) is essential for access to early intervention; however, diagnostic delay remains a persistent challenge. Methods: This scoping review synthesized evidence from eight studies (>24,000 participants), most conducted in the Southeast region, on diagnostic pathways, screening practices, and barriers to ASD identification in Brazil, following PRISMA-ScR guidelines. Results: Across studies, mean age at diagnosis frequently exceeded 48–60 months, while the interval between first caregiver concern and diagnosis ranged from 24 to 36 months, with tertiary-care samples reporting diagnostic ages approaching 79 months. Diagnosis was predominantly specialist-driven, with limited involvement of primary care providers (PCPs). Later identification was associated with reliance on the public health system in a multinational analysis that included Brazil, while geographic concentration of specialized services and socioeconomic inequalities were identified as reported barriers across the included studies. Race/ethnicity was rarely reported. Delays emerged from interacting multilevel barriers, including limited caregiver awareness, dismissal of parental concerns, inconsistent developmental surveillance, fragmented referral pathways, and shortages of specialists. Structural inequities, particularly geographic disparities and urban concentration of services, compounded these challenges. Conclusions: The evidence suggests delayed ASD diagnosis in Brazil reflects systemic gaps in care organization rather than isolated clinical factors. Strengthening PCP-based developmental surveillance and improving referral coordination are key strategies to reduce preventable delays and promote earlier access to intervention.

Background/Objectives: CD19-directed chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed/refractory large B-cell lymphoma (r/r LBCL), yet primary resistance and relapse remain common. We evaluated how recent clinical and translational evidence refines established resistance frameworks and which knowledge gaps prevent the relative contribution of individual mechanisms from being determined. Methods: We conducted a structured narrative review of 14 selected clinical and translational studies addressing tumor-, product-, host-, and microenvironment-related dimensions of treatment failure, synthesized across four interpretive domains and compared with nine previous reviews. Results: Durable benefit was associated with favorable tumor and immune transcriptional programs and greater CAR T-cell fitness, expansion, or persistence. Treatment failure was associated with tumor-intrinsic resistance programs, exhausted T-cell states, systemic inflammatory signals, and suppressive tumor-microenvironment features, including PD-L1-expressing macrophages. Antigen escape remained relevant, but incomplete serial CD19 assessment precluded conclusions about its relative contribution. Comparison with earlier reviews showed continuity rather than replacement, with LBCL-focused evidence adding biological resolution. Conclusions: Resistance and relapse after CD19 CAR T-cell therapy in LBCL are multifactorial. Prospective longitudinal studies integrating tumor tissue, apheresis and manufactured products, peripheral blood, and matched relapse samples are needed to validate predictive biomarkers and guide rational treatment strategies.

Background: Fragile X syndrome (FXS) requires molecular confirmation, yet diagnostic workflows vary in their capacity to characterize expansions and connect diagnosis with subsequent care. This review evaluated alignment between current recommendations and published diagnostic practice. Methods: We combined a structured review of recommendations for FMR1 molecular diagnosis, complementary testing, genetic counseling, and family testing with a scoping review of peer-reviewed primary studies reporting FMR1 diagnostic or screening workflows relevant to pediatric FXS. PubMed/MEDLINE, Embase, and Scopus were searched without date restrictions. Thirty-four studies were included, with design-specific risk-of-bias assessment and exploratory exact analyses of factors associated with post-initial FMR1 testing. Results: Molecular or genomic testing was reported in all 34 studies, but workflows ranged from conventional PCR and Southern blot to TP-PCR, methylation-sensitive assays, and sequencing-based approaches. Post-initial FMR1 testing was reported in 22/34 studies (64.7%), with positive-result follow-up documented in 19/34 (55.9%) and follow-up of inconclusive or initially negative results in 14/34 (41.2%). FMR1 sequencing was uncommon (3/34, 8.8%). Genetic counseling was addressed in 32/34 studies (94.1%), but documented as delivered in only 9/34 (26.5%); family evaluation and multidisciplinary management were also inconsistently reported. Conclusions: Published evidence broadly supports molecular FMR1 testing but shows variability in molecular characterization and downstream care. Standardization should prioritize analytically appropriate workflows, additional testing when required by the initial result or assay limitations, and stronger integration of molecular diagnosis with genetic counseling, family evaluation, and multidisciplinary management.