Staphylococcus aureus is a leading human pathogen capable of producing severe invasive infections such as bacteremia, sepsis and endocarditis with high morbidity and mortality, exacerbated by expanding antibiotic-resistance exemplified by methicillin-resistant strains (MRSA). S. aureus pathogenesis is fueled by secretion of secreted toxins including the membrane damaging pore-forming α-toxin that have diverse cellular targets including epithelium, endothelium, leukocytes and platelets. Here we examine human platelet membrane-coated nanoparticles (PNPs) as a biomimetic decoy strategy to neutralize S. aureus toxins and preserve host cell defense functions. PNPs blocked platelet damage induced by S. aureus secreted toxins, supporting platelet activation and bactericidal activity. Likewise, PNPs blocked macrophage damage induced by S. aureus secreted toxins, supporting macrophage oxidative burst and nitric oxide production and bactericidal activity, and diminishing MRSA-induced neutrophil extracellular trap release. In a mouse model of MRSA systemic infection, PNP administration reduced bacterial counts in the blood and protected against mortality. Taken together, the present work provides proof-of-principle of therapeutic benefit of PNPs in toxin neutralization, cytoprotection and increased host resistance to invasive S. aureus infection.

In patients with end-stage renal disease (ESRD) undergoing dialysis, hypertension is common but often inadequately controlled. The prevalence of hypertension varies widely among studies because of differences in the definition of hypertension and the methods of used to measure blood pressure (BP), i.e., peri-dialysis or ambulatory BP monitoring (ABPM). Recently, ABPM has become the gold standard for diagnosing hypertension in dialysis patients. Home BP monitoring can also be a good alternative to ABPM, emphasizing BP measurement outside the hemodialysis (HD) unit. One thing for sure is pre- and post-dialysis BP measurements should not be used alone to diagnose and manage hypertension in dialysis patients. The exact target of BP and the relationship between BP and all-cause mortality or cause-specific mortality are unclear in this population. Many observational studies with HD cohorts have almost universally reported a U-shaped or even an L-shaped association between BP and all-cause mortality, but most of these data are based on the BP measured in HD units. Some data with ABPM have shown a linear association between BP and mortality even in HD patients, similar to the general population. Supporting this, the results of meta-analysis have shown a clear benefit of BP reduction in HD patients. Therefore, further research is needed to determine the optimal target BP in the dialysis population, and for now, an individualized approach is appropriate, with particular emphasis on avoiding excessively low BP. Maintaining euvolemia is of paramount importance for BP control in dialysis patients. Patient heterogeneity and the lack of comparative evidence preclude the recommendation of one class of medication over another for all patients. Recently, however, β-blockers could be considered as a first-line therapy in dialysis patients, as they can reduce sympathetic overactivity and left ventricular hypertrophy, which contribute to the high incidence of arrhythmias and sudden cardiac death. Several studies with mineralocorticoid receptor antagonists have also reported promising results in reducing mortality in dialysis patients. However, safety issues such as hyperkalemia or hypotension should be further evaluated before their use.

Background: Sarcopenia is a prevalent complication in patients with chronic kidney disease and is associated with poor quality of life, morbidity, and mortality. Several candidate biomarkers have been evaluated for this condition. This study assessed the serum cystatin C to creatinine (serum cystatin C/Cr) ratio as a potential biomarker for sarcopenia in patients with non-dialysis-dependent chronic kidney disease. Methods: This study enrolled 517 outpatients. Muscle mass (lean tissue index) was measured using a bioimpedance spectroscopic device, and muscle strength (handgrip strength) was also measured. Sarcopenia was defined as a combination of low muscle strength and low muscle mass. Results: Sarcopenia was observed in 25.5% of patients, and the mean serum cystatin C/Cr ratio was significantly higher in patients with sarcopenia than in those without it (1.14 ± 0.26 vs. 1.01 ± 0.27, p < 0.001). The prevalence of sarcopenia and low lean tissue index increased as the cystatin C/Cr ratio increased. The negative predictive value of the cystatin C/Cr ratio for sarcopenia or low lean tissue index was ≥80%. Multivariate analyses revealed that when the serum cystatin C/Cr ratio increased by 1, the risk of sarcopenia, low lean tissue index, and low handgrip strength increased by 4.6-, 7.2-, and 2.6-fold, respectively (p = 0.003, p < 0.001, and p = 0.048). The association was maximized in patients with an estimated glomerular filtration rate of <30 mL/min/1.73 m2. Conclusion: Calculating the serum cystatin C/Cr ratio could be helpful for detecting and managing sarcopenia in patients with chronic kidney disease.

Background.Neutrophils are involved in the pathogenesis of atherosclerosis by neutrophil extracellular trap (NET) formation. We hypothesized that the NET formation of neutrophils might be changed in end-stage renal disease (ESRD) patients, explaining their higher incidence of coronary artery diseases (CAD).Method.A cross-sectional study was performed in 60 maintenance hemodialysis (MHD) patients, 30 age- and sex-matched healthy individuals (HV, negative control), and 30 patients with acute infection (positive control). Neutrophil activation and function were measured with reactive oxygen species (ROS) activity, degranulation, NET formation, and phenotypical changes.Result.Compared with HV, neutrophils extracted from MHD patients displayed significantly increased levels of basal NET formation, ROS production, and degranulation, suggesting spontaneous activation in uremia. Also, an increase in citrullinated histone H3 was detected in this group compared to the HV. And neutrophils from HV were normal CD16^bright/CD62L^brightcells; however, neutrophils from MHD were CD16^bright/CD62L^dim, similar to those from patients with acute infections. Interestingly, multivariate analyses identified the prevalent CAD and neutrophil counts as independent determinants of baseline NET formation (β=0.323,p=0.016andβ=0.369,p=0.006, resp.).Conclusions.Uremia-associated-increased NET formation may be a sign of increased burden of atherosclerosis.

Background: Although higher body mass index (BMI) is associated with better survival in patients undergoing dialysis, BMI is not an adequate obesity indicator. We hypothesized that the fat-to-lean (F/L) mass ratio could be a suitable marker of nutritional status and evaluated its prognostic impact on long-term outcomes in patients undergoing hemodialysis (HD). Methods: In total, 131 patients undergoing HD were recruited and monitored prospectively for up to 5 years. Body composition was analyzed, and other nutritional and inflammatory parameters were measured. Results: The mean age of the cohort was 60.7 ± 13.6 years, and 65 patients were diabetic. Age, sex, diabetes, comorbidity, and inflammation were associated significantly with the F/L mass ratio. During the follow-up period, 21 patients experienced cardiac events and 22 patients died. Patients with higher F/L mass ratios had significantly higher risks of all-cause death (hazard ratio [HR] 3.61, 95% CI 1.07–12.13; p = 0.038) and cardiac events (HR 3.54, 95% CI 1.05-11.94; p = 0.041) than those with lower F/L mass ratios. Conclusions: The F/L mass ratio was a useful surrogate marker of nutritional and inflammatory status, and an independent predictor of cardiac events and all-cause mortality, in patients undergoing HD.