Atherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality

AbstractOBJECTIVESThis study was undertaken to determine whether atherosclerosis of the ascending aorta is a predictor of long-term neurologic events and mortality.BACKGROUNDAtherosclerosis of the thoracic aorta has been recently considered a significant predictor of neurologic events and peripheral embolism, but not of long-term mortality.METHODSLong-term follow-up (a total of 5,859 person-years) was conducted of 1,957 consecutive patients ≥50 years old who underwent cardiac surgery. Atherosclerosis of the ascending aorta was assessed intraoperatively (epiaortic ultrasound) and patients were divided into four groups according to severity (normal, mild, moderate or severe). Carotid artery disease was evaluated (carotid ultrasound) in 1,467 (75%) patients. Cox proportional-hazards regression analysis was performed to assess the independent effect of predictors on neurologic events and mortality.RESULTSA total of 491 events occurred in 472 patients (neurologic events 92, all-cause mortality 399). Independent predictors of long-term neurologic events were: hypertension (p = 0.009), ascending aorta atherosclerosis (p = 0.011) and diabetes mellitus (p = 0.015). The independent predictors of mortality were advanced age (p < 0.0001), left ventricular dysfunction (p < 0.0001), ascending aorta atherosclerosis (p < 0.0001), hypertension (p = 0.0001) and diabetes mellitus (p = 0.0002). There was >1.5-fold increase in the incidence of both neurologic events and mortality as the severity of atherosclerosis increased from normal-mild to moderate, and a greater than threefold increase in the incidence of both as the severity of atherosclerosis increased from normal-mild to severe.CONCLUSIONSAtherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality. These results provide additional evidence that in addition to being a direct cause of cerebral atheroembolism, an atherosclerotic ascending aorta may be a marker of generalized atherosclerosis and thus of increased morbidity and mortality

Introductory programming: a systematic literature review

As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival