The additional value of lung cancer screening program in identifying unrecognized diseases.

BACKGROUND: A systematic examination of low-dose CT (LDCT) scan, beside lung nodules, may disclose the presence of undiagnosed diseases, improving the efficacy and the cost/efficacy of these programs. The study was aimed at evaluating the association between LDCT scan findings and non-oncologic and oncologic diseases. METHODS: The LDCT scan of participants to the "Un Respiro per la vita"® lung cancer screening program were checked and abnormal findings, beside lung nodules, recorded. First admission to the acute care because of cardiovascular (CD), respiratory (RD) and oncological diseases (OD) in the following three years were retrieved. The association of LDCT scan abnormal findings with CD, RD and OD was assessed through univariable and multivariable logistic regression models. RESULTS: Mean age of 746 participants was 62 years (SD:5), 62% were male. 11 (1.5%) received a diagnosis of lung cancer. 16.1% participants were admitted to the acute care in the following three years: 8.6% for CD, 4.3% for RD and 5.2% for OD. Valve calcification (OR 2.02, p:0.02) and mucus plugs (OR 3.37, p:0.04) were positively associated with CD, while sub-pleural fibrosis had a protective role (OR 0.47, p:0.01). Lung nodules > 8 mm (OR 5.54, p: < 0.01), tracheal deviation (OR 6.04, p:0.01) and mucus plugs (OR 4.00, p:0.04) were positively associated with OD admissions. Centrilobular emphysema OR for RD admissions was 1.97 (p:0.06). CONCLUSIONS: The observed association between selected LDCT findings and ensuing CD, RD and OD suggests that the information potential of LCDT goes beyond the screening of lung cancer.

Platelet mean volume, distribution width, and count in type 2 diabetes, impaired fasting glucose, and metabolic syndrome: a meta-analysis.

BACKGROUND: Platelet activation contributes to cardiovascular disease (CVD), the main complication of type 2 diabetes mellitus (T2DM) and pre-diabetic conditions. Mean platelet volume is an easy-to-measure platelet parameter that has been associated with CVD. We sought to assess mean platelet volume, platelet distribution width, and platelet count in T2DM, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and metabolic syndrome. METHODS: Web-based literature search (PubMed, EMBASE, and Web of Science) of studies published in English through June 2014 was performed to select case-control and cross-sectional studies that reported data on mean platelet volume, platelet distribution width, or platelet count in cases (subjects with T2DM, IFG, IGT, or metabolic syndrome) and noncases. Descriptive and quantitative information was extracted, and within-study standardized mean difference was estimated from means and standard deviations. Standardized mean differences across studies were synthesized using a random random-effects model, and subgroup analyses were performed on pre-specified study-level characteristics. RESULTS: Thirty-nine studies were included. Compared with controls, mean platelet volume was significantly higher in T2DM (standardized mean difference, 95% confidence interval: 0.70, 0.50-0.91; N = 24,245), IFG (0.14, 0.02-0.26; N = 17,389) but not in metabolic syndrome (0.15, -0.24 to 0.55; N = 14,990). Platelet distribution width was wider in T2DM (0.93, 0.09-1.76; N = 471). Platelet count resulted higher in IFG (0.18, 0.12-0.24; N = 3960) and metabolic syndrome (0.39, 0.01-0.78; N = 4070). Only two studies included IGT. CONCLUSIONS: Available data suggest that T2DM subjects tend to have higher mean platelet volume and platelet distribution width values, but nondifferent platelet count as compared with subjects without T2DM. Whether and how these morphometric changes contribute to CVD of T2DM or can be used as CVD biomarker awaits further investigation.

Impact of Glycemic Variability on Chromatin Remodeling, Oxidative Stress, and Endothelial Dysfunction in Patients With Type 2 Diabetes and With Target HbA1c Levels.

Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D); however, the underlying mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigated whether epigenetic regulation of the adaptor protein p66Shc, a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in patients with T2D despite IGC. Thirty-nine patients with uncontrolled T2D (HbA1c >7.5%) and 24 age- and sex-matched healthy control subjects were consecutively enrolled. IGC was implemented for 6 months in patients with T2D to achieve a target HbA1c of ≤7.0%. Brachial artery flow-mediated dilation (FMD), urinary 8-isoprostaglandin F2α (8-isoPGF2α), and epigenetic regulation of p66Shc were assessed at baseline and follow-up. Continuous glucose monitoring was performed to determine the mean amplitude of glycemic excursion (MAGE) and postprandial incremental area under the curve (AUCpp). At baseline, patients with T2D showed impaired FMD, increased urinary 8-isoPGF2α, and p66Shc upregulation in circulating monocytes compared with control subjects. FMD, 8-isoPGF2α, and p66Shc expression were not affected by IGC. DNA hypomethylation and histone 3 acetylation were found on the p66Shc promoter of patients with T2D, and IGC did not change such adverse epigenetic remodeling. Persistent downregulation of methyltransferase DNMT3b and deacetylase SIRT1 may explain the observed p66Shc-related epigenetic changes. MAGE and AUCpp but not HbA1c were independently associated with the altered epigenetic profile on the p66Shc promoter. Hence, glucose fluctuations contribute to chromatin remodeling and may explain persistent vascular dysfunction in patients with T2D with target HbA1c levels.

In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes.

Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.