Cosmetic Tattooing and Early Onset Basal Cell Carcinoma: A Population-based Case-Control Study from New Hampshire.

BACKGROUND: Cosmetic tattoos use dyes with carcinogenic potential. Skin cancers arising in tattoos have been reported. METHODS: We investigated whether risk of early onset basal cell carcinoma was related to the site and colors of cosmetic tattoos as part of a population-based case-control study of cases (ages 25-50 years), identified from a state-wide surveillance system, and age- and gender-matched controls, selected from driver's license records, randomly assigned an anatomic site of the cases. RESULTS: One hundred fifty-six cases (17%) with early onset basal cell carcinoma and 213 controls (26%) reported cosmetic tattoos. Among those with tattoos, the adjusted odds ratio of basal cell carcinoma at the tattoo site compared to another site was 1.8 (95% confidence interval = 1.0, 3.2). We observed the strongest associations for yellow and green tattoo colors. CONCLUSION: Our preliminary findings support the possibility of an enhanced risk of early onset basal cell carcinomas at the site of cosmetic tattoos.

Experimentally-derived fibroblast gene signatures identify molecular pathways associated with distinct subsets of systemic sclerosis patients in three independent cohorts.

Genome-wide expression profiling in systemic sclerosis (SSc) has identified four 'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and normal-like), each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks. Pathway-specific gene signatures were analyzed across a compendium of microarray datasets consisting of skin biopsies from three independent cohorts representing 80 SSc patients, 4 morphea, and 26 controls. IFNα signaling showed a strong association with early disease, while TGFß signaling spanned the fibroproliferative and inflammatory subsets, was associated with worse MRSS, and was higher in lesional than non-lesional skin. The fibroproliferative subset was most strongly associated with PDGF signaling, while the inflammatory subset demonstrated strong activation of innate immune pathways including TLR signaling upstream of NF-κB. The limited and normal-like subsets did not show associations with fibrotic and inflammatory mediators such as TGFß and TNFα. The normal-like subset showed high expression of genes associated with lipid signaling, which was absent in the inflammatory and limited subsets. Together, these data suggest a model by which IFNα is involved in early disease pathology, and disease severity is associated with active TGFß signaling.

Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients.

BACKGROUND: Mechanisms predisposing HIV-infected patients to increased cardiovascular disease (CVD) risk remain unclear. OBJECTIVE: To determine the interrelationship between arterial inflammation and high-risk coronary plaque morphology in HIV-infected patients with subclinical coronary atherosclerosis. METHODS: Forty-one HIV-infected patients on stable antiretroviral therapy without known CVD but with atherosclerotic plaque on coronary CT angiography were evaluated with F-FDG-PET. Patients were stratified into 2 groups based on relative degree of arterial inflammation [aortic target-to-background ratio (TBR)]. High-risk coronary atherosclerotic plaque morphology features were compared between groups. RESULTS: HIV-infected patients with higher and lower TBRs were similar with respect to traditional CVD risk parameters. Among HIV-infected patients with higher TBR, an increased percentage of patients demonstrated at least 1 low-attenuation coronary atherosclerotic plaque (40% vs. 10%, P = 0.02) and at least 1 coronary atherosclerotic plaque with both low attenuation and positive remodeling (35% vs. 10%, P = 0.04). Moreover, in the higher TBR group, both the number of low-attenuation plaques per patient (P = 0.02) and the number of vulnerability features in the most vulnerable plaque (P = 0.02) were increased. TBR grouping remained significantly related to the number of low-attenuation plaques/subject (ß = 0.35, P = 0.004), controlling for age, gender, low-density lipoprotein, duration of HIV, and CD4. CONCLUSIONS: These data demonstrate a relationship between arterial inflammation on F-FDG-PET and high-risk coronary atherosclerotic plaque features among HIV-infected patients with subclinical coronary atherosclerosis. Further studies are needed to determine whether arterial inflammation and related high-risk coronary morphology increase the risk of clinical CVD events in the HIV population.

HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque.

BACKGROUND: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. METHODS: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. RESULTS: HRA was higher in HIV-infected versus non-HIV subjects (1.4 ±0.01 versus 1.3 ±0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects (P=0.03). CONCLUSIONS: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to non-calcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk. CLINICAL TRIAL REGISTRATION NUMBER: NCT 00455793.

Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men.

OBJECTIVE: Among HIV-infected patients, high rates of myocardial infarction (MI) and sudden cardiac death have been observed. Exploring potential underlying mechanisms, we used multidetector spiral coronary computed tomography angiography (coronary CTA) to compare atherosclerotic plaque morphology in HIV-infected patients and non-HIV-infected controls. METHODS: Coronary atherosclerotic plaques visualized by CTA in HIV-infected (101) and non-HIV-infected (41) men without clinically apparent heart disease matched on cardiovascular risk factors were analyzed for three vulnerability features: low attenuation, positive remodeling, and spotty calcification. RESULTS: Ninety-five percent of HIV-infected patients were receiving ART (median duration 7.9 years) and had well controlled disease (median CD4 cell count, 473 cells/µl; median HIV RNA <50 copies/ml). Age and traditional cardiovascular risk factors were similar in HIV-infected patients and controls. Among the HIV-infected (versus control) group, there was a higher prevalence of patients with at least one: low attenuation plaque (22.8 versus 7.3%, P = 0.02), positively remodeled plaque (49.5 versus 31.7%, P = 0.05) and high-risk 3-feature plaque (7.9 versus 0%, P = 0.02). Moreover, patients in the HIV-infected (versus control) group demonstrated a higher number of low attenuation plaques (P = 0.01) and positively remodeled plaques (P = 0.03) per patient. CONCLUSION: Our data demonstrate an increased prevalence of vulnerable plaque features among relatively young HIV-infected patients. Differences in coronary atherosclerotic plaque morphology - namely, increased vulnerable plaque among HIV-infected patients - are here for the first time reported and may contribute to increased rates of MI and sudden cardiac death in this population.