Articles: sepsis.
-
When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety sepsis initiative (HMS-Sepsis). ⋯ The HMS-Sepsis mortality model showed strong discrimination and adequate calibration and reclassified one-third of hospitals to a different performance category from unadjusted mortality. Based on its strong performance, the HMS-Sepsis mortality model may aid in fair hospital benchmarking, assessment of temporal changes, and observational causal inference analysis.
-
Background: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo. ⋯ This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multiorgan damage and lethality resulting from cecal ligation and puncture. Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.
-
Objective : Vascular endothelial cells (ECs) sense and respond to both trauma factors (histone proteins) and sepsis signals (bacterial lipopolysaccharide, LPS) with elevations in calcium (Ca 2+ ), but it is not clear if the patterns of activation are similar or different. We hypothesized that within seconds of exposure, histones but not LPS would produce a large EC Ca 2+ response. We also hypothesized that histones would produce different spatio-temporal patterns of Ca 2+ events in veins than in arteries. ⋯ Exposure of ECs to histones or LPS both increased gene expression, but different mRNAs were induced. Conclusions : LPS and histones activate ECs through mechanisms that are distinct and additive; only histones produce large aberrant Ca 2+ events. ECs in arteries and veins display different patterns of Ca 2+ responses to histones.
-
Observational Study
Diagnostic utility of plasma translocator protein 18 kDa (TSPO) in sepsis: A case-control study.
Translocator protein 18 kDa (TSPO) is a mitochondrial membrane protein that is involved in inflammation, oxidative stress, and steroidogenesis. TSPO may be a marker of inflammatory responses in the brain and other organs, but there have been few studies of the potential clinical significance of measuring the circulating TSPO concentration, especially in patients with sepsis. In this study, we compared the circulating TSPO concentrations of patients with sepsis and healthy controls to investigate the utility of plasma TSPO for the diagnosis of sepsis. ⋯ The plasma TSPO concentrations of the patients with sepsis were significantly lower than those of the healthy controls (0.094 vs 0.25 ng/mL, P < .001), and receiver operating characteristic analysis generated an area under the curve of 0.81 (95% confidence interval: 0.72-0.91). In patients with sepsis, the TSPO concentration was not associated with the severity of sepsis, complications, or prognosis. Plasma TSPO may be a useful biomarker for the diagnosis of sepsis.