Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Observational Study
Predictive value of neutrophil extracellular traps components for 28-day all-cause mortality in patients with cardiac arrest: A pilot observational study.
Background: Ischemia-reperfusion after cardiac arrest (CA) activates peptidyl arginine deiminase and citrullinated histone H3 (CitH3), which leads to the formation of neutrophil extracellular traps (NETs). This study attempted to determine the alterations in NET components in post-CA patients as well as analyze the association of NETs with 28-day all-cause mortality. Methods : In this study, 95 patients with restoration of spontaneous circulation (ROSC) after CA were included. ⋯ Furthermore, these parameters on day 1 after ROSC had the biggest areas under the receiver operating characteristic curves (0.876, 0.862, and 0.861, respectively). Conclusions: Elevated serum levels of cfDNA, CitH3, myeloperoxidase, neutrophil elastase, and nucleosomes were positively correlated with disease severity after ROSC. However, only serum CitH3, cfDNA, and nucleosomes on day 1 after ROSC showed a good predictive value for 28-day all-cause mortality.
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Sepsis is associated with significant mortality and morbidity among critically ill patients admitted to intensive care units and represents a major health challenge globally. Given the significant clinical and biological heterogeneity among patients and the dynamic nature of the host immune response, identifying those at high risk of poor outcomes remains a critical challenge. Here, we performed secondary analysis of publicly available time-series gene-expression datasets from peripheral blood of patients admitted to the intensive care unit to elucidate temporally stable gene-expression markers between sepsis survivors and nonsurvivors. ⋯ Our model had robust performance in a test dataset, where patients' transcriptome was sampled at alternate time points, with an area under the curve of 0.89 (95% CI, 0.82-0.96) upon 5-fold cross-validation. We also identified 7 potential biomarkers of sepsis mortality (STAT5A, CX3CR1, LCP1, SNRPG, RPS27L, LSM5, SHCBP1) that require future validation. Pending prospective testing, our model may be used to identify sepsis patients with high risk of mortality accounting for the dynamic nature of the disease and with potential therapeutic implications.
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Sepsis-induced acute liver injury is a life-threatening condition involving inflammation, oxidative stress, and endothelial dysfunction. In the present study, the preventive effects of resveratrol (RV) alone and RV-loaded silver nanoparticles (AgNPs + RV) against sepsis-induced damage were investigated and compared in a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Rats were divided into four groups: Sham, CLP, RV, and AgNPs + RV. ⋯ Both RV and AgNPs + RV treatments increased SIRT1 levels, suggesting a potential role of SIRT1 activation in mediating the protective effects. In conclusion, AgNPs + RV treatment demonstrated extremely enhanced efficacy in alleviating sepsis-induced liver injury by modulating inflammation, oxidative stress, and endothelial dysfunction, potentially mediated through SIRT1 activation. In this study, the effect of AgNPs + RV on sepsis was evaluated for the first time, and these findings highlight AgNPs + RV as a promising therapeutic strategy for managing sepsis-induced liver injury, warranting further investigation.
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Background: Tissue trauma and hemorrhage result in pronounced activation of the innate immune system. Given known crosstalk between inflammation and coagulation, soluble inflammatory mediators could be associated with venous thromboembolisms (VTEs) after major trauma. Objectives : This study aimed to identify plasma inflammatory mediators that are independent predictors of VTE risk in trauma patients. ⋯ We identified significant correlations between inflammation and markers of coagulation and endothelial activation. Conclusion: Sustained systemic inflammation is a key driver of VTE risk after major trauma. Therapeutics targeting innate immune activation should be considered for development of future multimodal strategies to augment current VTE prophylaxis.
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Objective: Neurological complications after myocardial ischemia/reperfusion (IR) injury remain high and seriously burden patients and their families. Dexmedetomidine (Dex), an α 2 agonist, is endowed with analgesic-sedative and anti-inflammatory effects. Therefore, our study aims to explore the mechanism and effect of Dex on brain damage after myocardial IR injury. ⋯ Results: Dex was capable of reducing myocardial IR-induced brain damage including inflammatory factor secretion, blood-brain barrier disruption, neuronal edema, microglial activation, and acute cognitive dysfunction. However, the protective role of Dex was attenuated in HIF-1α knockout mice. Conclusion: Dex protects against myocardial IR-induced brain injury, and the neuroprotection of Dex is at least partially dependent on the activation of the HIF-1 pathway.