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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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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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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Background: Although central venous oxygen saturation (ScvO 2 ) has been used as an endpoint for the treatment of circulatory shock, its role in guiding the evaluation and treatment of patients with severe hypoxemia remains to be assessed. The aim of this study was to assess the incidence of low ScvO 2 in a cohort of hypoxemic patients and the association of this finding with differences in clinical management and patient outcomes. Methods: Retrospective review of data from adult intensive care unit patients with hypoxemia who required invasive mechanical ventilation for over 24 h and had at least one ScvO 2 measured within 6 h of a PaO 2 /FiO 2 ratio <200. ⋯ Conclusion: Low ScvO 2 is frequently observed in mechanically ventilated patients with severe hypoxemia, and these patients receive different interventions. Clinicians often use therapies targeting systemic oxygen delivery to correct low ScvO 2. Prospective research is needed to identify patients with severe hypoxemia that might benefit from interventions targeting systemic oxygen delivery.
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Background: Trauma-induced hypocalcemia is common and associated with adverse outcomes, but the mechanisms remain unclear. Thus, we aimed to characterize the metabolomic and proteomic differences between normocalcemic and hypocalcemic trauma patients to illuminate biochemical pathways that may underlie a distinct pathology linked with this clinical phenomenon. Methods: Plasma was obtained on arrival from injured patients at a Level 1 Trauma Center. ⋯ Hypocalcemic patients had evidence of mitochondrial dysfunction (tricarboxylic acid cycle disruption, dysfunctional fatty acid oxidation), inflammatory dysregulation (elevated damage-associated molecular patterns, activated endothelial cells), aberrant coagulation pathways, and proteolytic imbalance with increased tissue destruction. Conclusions: Independent of injury severity, hemorrhagic shock, and transfusion, trauma-induced hypocalcemia is associated with early metabolomic and proteomic changes that may reflect unique pathology in hypocalcemic trauma patients. This study paves the way for future experiments to investigate mechanisms, identify intervenable pathways, and refine our management of hypocalcemia in severely injured patients.