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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Postsepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at the transcriptomic level. ⋯ Using single-cell RNA sequencing and pathway analyses, we identified gene expression patterns between these two groups that are consistent with differences in TNF-α production based on clinical outcome. This may provide therapeutic targets for those at risk for chronic critical illness in order to improve their phenotype/endotype, morbidity, and long-term mortality.
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Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. ⋯ Similar findings were demonstrated on fibronectin, collagen I, collagen IV, and laminin, suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. Conclusion: This report identifies VLA-3 and CD151 on the activated human neutrophil, which are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.
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Background: Pulmonary artery catheterization (PAC) has been widely used in critically ill patients, yielding mixed results. Prior studies on cardiogenic shock (CS) predominantly included patients with acute myocardial infarction. This study aims to examine the effect of PAC use in patients with nonischemic CS. ⋯ After inverse probability of treatment weighting, patients in the PAC group had significantly lower in-hospital mortality (24.8% vs. 35.3%, P < 0.001), renal replacement therapy (10.7% vs. 12.4%, P = 0.002), in-hospital cardiac arrest (7.1% vs. 9.6%, P < 0.001), and mechanical ventilation (44.6% vs. 50.4%, P < 0.001) compared to non-PAC group. In contrast, the PAC group had higher use of intra-aortic balloon pump (15.4% vs. 3.4%, P < 0.001), percutaneous ventricular assist devices (12.6% vs. 2.6%, P < 0.001), extracorporeal membrane oxygenation (3.9% vs. 2.5%, P < 0.001), and heart transplantation (2.1% vs. 0.4%, P < 0.001). Conclusion: In the real-world setting, invasive hemodynamic monitoring with PAC in patients with nonischemic CS is associated with survival benefits and a reduction in adverse events, including reduced need for renal replacement therapy, mechanical ventilation and risk of in-hospital cardiac arrest.
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Background: Myocardial infarction (MI) is a severe condition that typically results from the ischemia and necrosis of heart muscle. Kruppel-like factor 6 (KLF6) can aggravate myocardial ischemia/reperfusion injury. This work aims to reveal its role and mechanism in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. ⋯ Additionally, WTAP stabilized KLF6 mRNA by regulating its m6A modification. Furthermore, WTAP knockdown rescued H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis by decreasing KLF6 expression. Conclusion: WTAP-mediated m6A modification of KLF6 aggravated hypoxia/reoxygenation-induced apoptosis, inflammatory response, oxidative stress, and ferroptosis of human cardiomyocytes, providing a therapeutic strategy for MI.