Project description:Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype. Frozen tumor biopsies were obtained from 20 HIV-positive patients with an AIDS-defining lymphoma. Cases were ascertained at the University of Nebraska Medical Center and through the NCI AIDS and Cancer Specimen Resource tumor bank. Sufficient RNA for hybridization to Affymetrix U133 plus 2 arrays was obtained on 17 ARL cases. Details of all 20 HIV-positive patients can be found in the supplementary file linked below.
Project description:Background and aimsFrailty and cardiovascular disease share many risk factors. We evaluated whether frailty is independently associated with subclinical coronary atherosclerosis and whether any relationships differ by HIV-serostatus.MethodsWe studied 976 [62% HIV-infected] male participants of the Multicenter AIDS Cohort Study who underwent assessment of frailty and non-contrast cardiac CT scanning; of these, 747 men also underwent coronary CT angiography (CCTA). Frailty was defined as having ≥3 of 5 of the following: weakness, slowness, weight loss, exhaustion, and low physical activity. Coronary artery calcium (CAC) was assessed by non-contrast CT, and total plaque score (TPS), mixed plaque score (MPS), and non-calcified plaque score (NCPS) by CCTA. Multivariable-adjusted regression was used to assess the cross-sectional associations between frailty and subclinical coronary atherosclerosis.ResultsMean (SD) age of participants was 54 (7) years; 31% were black. Frailty existed in 7.5% and 14.3% of HIV-uninfected and HIV-infected men, respectively. After adjustment for demographics, frailty was significantly associated with prevalence of any CAC (CAC>0), any plaque (TPS>0), and mixed plaque (MPS>0) in HIV-uninfected but not in HIV-infected men (p-interactionHIV<0.05 for all). Among HIV-uninfected men, after adjustment for cardiovascular risk factors, frailty was significantly associated only with CAC>0 [Prevalence Ratio 1.27 (95%CI 1.02, 1.59)] and TPS>0 [1.19 (1.06, 1.35)]. No association was found for NCPS.ConclusionsFrailty was independently associated with subclinical coronary atherosclerosis among HIV-uninfected men, but not among HIV-infected men. Further work is needed to ascertain mechanisms underlying these differences and whether interventions that improve frailty (i.e. strength training) can improve cardiovascular outcomes.