BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

Calcyclin (S100A6) is a cell-specific, calcium binding protein of the S100 family whose expression is augmented in many types of cancer. By means of luciferase activity assays, RT-PCR and Northern blot hybridization, we established that transcription of S100A6 gene is increased by agents known to evoke oxidative stress. Mutation of the antioxidant response element (ARE) located at position -290/-281 of the calcyclin gene promoter, and overlapping the E-box sequence recognized by the upstream stimulatory factor (USF), led to inhibition of calcyclin gene promoter activity stimulated by cadmium ions. Electrophoretic mobility shift assays (EMSA) with the -302/-260 calcyclin gene promoter fragment revealed, apart from USF binding, the presence of another protein complex (N) shown by competitive EMSA to be bound to ARE. DNA affinity chromatography followed by Western blot showed the binding of Nrf2 transcription factor to the immobilized calcyclin gene promoter fragment and concomitant appearance of complex N in EMSA of the eluted fractions. The results indicate that agents evoking oxidative stress activate calcyclin gene via the ARE sequence in its promoter.

Background There are several scores used for in-hospital mortality prediction in critical illness. Their application in a local scenario requires validation to ensure appropriate diagnostic accuracy. Moreover, their use in assessing post-discharge mortality in intensive care unit (ICU) survivors has not been extensively studied. We aimed to validate APACHE II, APACHE III and SAPS II scores in short- and long-term mortality prediction in a mixed adult ICU in Poland. APACHE II, APACHE III and SAPS II scores, with corresponding predicted mortality ratios, were calculated for 303 consecutive patients admitted to a 10-bed ICU in 2016. Short-term (in-hospital) and long-term (12-month post-discharge) mortality was assessed. Results Median APACHE II, APACHE III and SAPS II scores were 19 (IQR 12–24), 67 (36.5–88) and 44 (27–56) points, with corresponding in-hospital mortality ratios of 25.8% (IQR 12.1–46.0), 18.5% (IQR 3.8–41.8) and 34.8% (IQR 7.9–59.8). Observed in-hospital mortality was 35.6%. Moreover, 12-month post-discharge mortality reached 17.4%. All the scores predicted in-hospital mortality (p < 0.05): APACHE II (AUC = 0.78; 95%CI 0.73–0.83), APACHE III (AUC = 0.79; 95%CI 0.74–0.84) and SAPS II (AUC = 0.79; 95%CI 0.74–0.84); as well as mortality after hospital discharge (p < 0.05): APACHE II (AUC = 0.71; 95%CI 0.64–0.78), APACHE III (AUC = 0.72; 95%CI 0.65–0.78) and SAPS II (AUC = 0.69; 95%CI 0.62–0.76), with no statistically significant difference between the scores (p > 0.05). The calibration of the scores was good. Conclusions All the scores are acceptable predictors of in-hospital mortality. In the case of post-discharge mortality, their diagnostic accuracy is lower and of borderline clinical relevance. Further studies are needed to create scores estimating the long-term prognosis of subjects successfully discharged from the ICU.

Delirium is one of the most frequently reported neuropsychiatric complications in the perioperative period, especially in the population of elderly patients who often suffer from numerous comorbidities undergoing extensive or urgent surgery. It can affect up to 80% of patients who require hospitalization in an intensive care setting postoperatively. Delirium increases mortality, morbidity, length of hospital stay, and cost of treatment. An episode of delirium in the acute phase may lower the general quality of life and increases the risk of cognitive decline long-term. Since pharmacological treatment of delirium is not highly effective, focus of research has shifted towards developing preventive strategies. We aimed to perform a review of the topic based on the most recent literature. We conclude that, based on the available data, it seems impossible to make strong recommendations for using antipsychotic drugs in prophylaxis. Further research should answer the question what, if any, benefit patients receive from the pharmacological prevention of delirium, and which agents should be used.

Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.