Disease burden of adverse childhood experiences across 14 states.

OBJECTIVE: To examine whether the relationship between Adverse Childhood Experiences (ACEs) and health outcomes is similar across states and persists net of ACEs associations with smoking, heavy drinking, and obesity. METHODS: We use data from the Behavioral Risk Factor Surveillance System for 14 states. Logistic regressions yield estimates of the direct associations of ACEs exposure with health outcomes net of health risk factors, and indirect ACEs-health associations via health risk factors. Models were estimated for California (N = 22,475) and pooled data from 13 states (N = 110,076), and also separately by state. RESULTS: Exposure to ACEs is associated with significantly higher odds of smoking, heavy drinking, and obesity. Net of these health risk factors, there was a significant and graded relationship in California and the pooled 13-state data between greater ACEs exposure and odds of depression, asthma, COPD, arthritis, and cardiovascular disease. Four or more ACEs were less consistently associated across states with cancer and diabetes and a dose-response relationship was also not present. There was a wide range across individual states in the percentage change in health outcomes predicted for exposure to 4+ ACEs. ACEs-related smoking, heavy drinking, and obesity explain a large and significant proportion of 4+ ACEs associations with COPD and cardiovascular disease, however some effect, absent of risk behavior, remained. CONCLUSIONS: ACE's associations with most of the health conditions persist independent of behavioral pathways but only asthma, arthritis, COPD, cardiovascular disease, and depression consistently exhibit a dose-response relationship. Our results suggest that attention to child maltreatment and household dysfunction, mental health treatment, substance abuse prevention and promotion of physical activity and healthy weight outcomes might mitigate some adverse health consequences of ACEs. Differences across states in the pattern of ACEs-health associations may also indicate fruitful areas for prevention.

Diffuse large B-cell lymphoma classification system that associates normal B-cell subset phenotypes with prognosis.

PURPOSE: Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification system based on subset-specific B-cell-associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. PATIENTS AND METHODS: We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n = 270; treated with rituximab plus CHOP [R-CHOP], n = 869) gathered across geographic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. RESULTS: Similar BAGS subtype frequencies were assigned across 1,139 samples from five different cohorts. Among R-CHOP-treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell-like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1-signature and major histocompatibility complex class II-signature genes, which are known to have a positive impact on prognosis. CONCLUSION: Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.