BACKGROUND Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported. METHODS In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function. RESULTS As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P = 0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events. CONCLUSIONS Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide.

Background: Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis. Methods: Adults with non-high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non-HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3. Results: Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58-69) years, 44% were female, the median non-HDL-C was 132.4 (interquartile range, 118.0-154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4-270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non-HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all P <0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all P <0.001). The effects on LDL-C and ApoB were more modest (7.9%-16.0% and 6.0%-15.1%, respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all P <0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3x elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%). Conclusions: Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non-HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic f at fraction.

Aim: The aim of the present study was to evaluate the influence of cycle exercise during hemodialysis (HD) on patients’ physical proficiency, muscle strength, quality of life and selected laboratory parameters. Patients and Methods: In a group of 29 (15 female, 14 male) HD patients (age 64.2 ± 13.1 years), 3 months of cycle training during dialysis sessions was performed. The following data were analyzed: strength of lower extremities (six-minute walk test, isokinetic knee extension, flexion peak torque), nutrition parameters (albumin, BMI), inflammation intensity (CRP, IL-6), and quality of life (SF-36v2). Results: In the six-minute walk test, the increase in walk velocity was 4% (3.56 km/h before and 3.73 km/h after cycle training; p < 0.01). At angular velocity (AV) of 60°/s, extension peak torque in the knee joint rose by 7% and at AV of 300°/s by 4% (p = 0.04). Flexion peak torque at AV of 180°/s increased by 13% (p = 0.0005). The program does not influence nutrition or inflammation parameters. No complications directly related to exercise were observed. Conclusion: Cycle exercise during dialysis is safe even in older HD patients with multiple comorbidities. It results in a significant increase in general patient walking ability and in a gain in lower extremity muscle strength.

IntroductionMore than 1/3 of patients with end-stage renal disease who are in a chronic dialysis program suffer from chronic pain and depression/anxiety. The aim of the study was to determine the impacts of symptoms of depression/anxiety, chronic pain and quality of life (QoL) on 6-year patient survival.Material and methodsObservational study of end-stage renal disease patients on maintenance hemodialysis (n = 205) who met the inclusion criteria. Patients from three dialysis centers in Lower Silesia were asked to complete a battery of validated questionnaires: the Hospital Anxiety and Depression Scale (HADS), the 36-item Short Form Health Survey Questionnaire, the Verbal Rating Scale (VRS) and the Visual Analog Scale (VAS). Clinical and biochemical data (dialysis adequacy) were recorded.ResultsOne hundred thirty from 205 enrolled hemodialysis patients (63.4%) suffered from chronic pain. Patients with pain were on maintenance dialysis for longer times and had higher levels of parathyroid hormone, more depressive symptoms and a lower QoL than those without pain. In the 6-year period, 96 (46.8%) patients died. The most common cause of death was cardiovascular disease in 44 (45.8%) patients. Highly depressed patients (HADS depression score > 8) exhibited higher mortality (< 8 vs. > 8 points; p = 0.016) independent of age, diabetes, cardiovascular disease, C-reactive protein or albumin level.ConclusionsChronic pain, although common among hemodialysis patients, did not lower survival. Depressive symptoms are an important predictor for all-cause mortality in hemodialysis patients, with the relationship independent of nutritional or inflammatory status.

Obesity does not prevent successful autogenous arteriovenous fistula formation, and may protect forearm venous vessels from the iatrogenic damage that occurs before the onset of haemodialysis therapy.