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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Meta Analysis
ANGIOTENSIN II IN THE TREATMENT OF DISTRIBUTIVE SHOCK: A SYSTEMATIC-REVIEW AND META-ANALYSIS.
Objective: While nonnorepinephrine vasopressors are increasingly used as a rescue therapy in cases of norepinephrine-refractory shock, data on their efficacy are limited. This systematic review and meta-analysis aims to synthesize existing literature on the efficacy of angiotensin II (ATII) in distributive shock. Methods: We preregistered our meta-analysis with PROSPERO (CRD42023456136). ⋯ We used a random effects model to calculate pooled risk ratio (RR) and 95% confidence intervals (CIs). Results: By incorporating data from 1,555 patients included in 10 studies, we found that however, all-cause mortality was similar among patients receiving ATII and controls (RR = 1.02; 95% CI: 0.89 to 1.16, P = 0.81), the reduction in norepinephrine or norepinephrine-equivalent dose at 3 h after treatment initiation was greater among patients receiving ATII (MD = -0.06; 95% CI: -0.11 to -0.02, P = 0.008), while there were no higher rates of adverse events reported among ATII patients. Conclusions: While ATII did not reduce mortality among distributive shock patients, it allowed for significant adjunctive vasopressor reduction at 3 h without an increase in reported adverse events, deeming it a viable alternative for the increasingly adopted multimodal vasopressor for minimizing catecholamine exposure and its adverse events.
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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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Sepsis-induced acute kidney injury (SAKI) poses a significant clinical challenge with high morbidity and mortality. Excessive mitochondrial fission has been identified as the central pathogenesis of sepsis-associated organ damage, which is also implicated in the early stages of SAKI. Sirtuin 5 (SIRT5) has emerged as a central regulator of cellular mitochondrial function; however, its role in the regulation of sepsis-induced excessive mitochondrial fission in kidney and the underlying mechanism remains unclear. ⋯ Conversely, downregulation of SIRT5 decreased HK-2 cells viability and exacerbated LPS-induced mitochondrial fission. Mechanistically, the protective function of SIRT5 may be in part, ascribed to its desuccinylating action on ATPase inhibitory factor 1. In conclusion, this study provides novel insights into the underlying mechanisms of SAKI, suggesting the possibility of identifying future drug targets in terms of improved mitochondrial dynamics by SIRT5.
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Background: Diabetic nephropathy (DN) is a complication of diabetes that is the leading cause of death in diabetic patients. Circular RNA (circRNA) is a hot topic in the research of human diseases. However, the role of circ_Supt3 in DN remains unclear. ⋯ Circ_Supt3 regulated G3bp2 expression by miR-185-5p. Moreover, the circ_Supt3/miR-185-5p/G3bp2 axis regulated the cell behavior of HG-induced MPC5 cells. Conclusion: Our findings suggest that the knockdown of circ_Supt3 protects mouse MPC5 cells against HG-induced cell injury via the miR-185-5p/G3bp2 axis.
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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.