4 years) with STEMI who underwent acute catheter-based reperfusion therapy within the first 12 h after onset of symptoms. Blood samples were taken at admission and after 4, 8, 12 and 24 h. Thrombin
activity and generation was measured by changes in the thrombin/antithrombin-III complex (TAT) and prothrombin fragment (F1.2); plasmin was measured by changes in the plasmin-alpha(2)/antiplasmin complex (PAP). A follow-up with respect to the combined primary endpoint consisting of death, acute myocardial infarction or urgent need for revascularization up to 6 weeks post-discharge was carried out.\n\nResults: TAT values showed no significant change over time in patients with and without the primary endpoint but there was a borderline difference between these groups at 4 h after admission (event group 9.0 vs no event group 4.7 mu g l(-1), p=0.057). F1.2 values were different between groups only after 24 h (event group 1.5 vs no event LDN-193189 concentration group 0.9 nmol l(-1), p=0.028) and did not differ in serial sampling of 24 h. PAP values were
higher in patients with events after 4 and 8 h and declined over time in the group without events (p<0.001). Odds ratios (OR) with respect to the primary endpoint were highest for TAT>4.8 mu g l(-1) at 0 h and TAT>8.4 mu g l(-1) at 4h (OR 7.1, 95% confidence interval (CI) 1.5-34, p=0.015 and OR 5.5, 95% CI 1.5-20.0, p=0.01, respectively). The predictive value of plasmin concentrations were equally high after 4h (PAP>962 mu g l(-1); OR 6.8, 95% CI 1.8-26.2, p=0.005) PCI-34051 in vivo PD-1/PD-L1 Inhibitor 3 concentration and 8 h (PAP>495 mu g l(-1), OR 6.7, 95% CI 1.4-32.9, p=0.024). Values for F1.2 were only predictive after 24 h (F1.2>0.85 nmol l(-1), OR 13, 95% CI 1.4-117.8, p=0.023).\n\nConclusions: Markers of thrombin and plasmin activity in acute STEMI are related to outcome. The marker for thrombin generation F1.2 becomes a significant predictor of outcome at 24 h after admission, reflecting the potentially adverse effects of ongoing thrombin generation. This underlines the potential for direct thrombin inhibition and individualization
of treatment by thrombin markers in STEMI.”
“IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02(+) subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)(+) regulatory T (T-reg) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of T-reg cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival.