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 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 (ATPIF1). 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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The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The ELISpot assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity. Herein, we tested the hypothesis that the ELISpot assay can detect dynamic changes in both innate and adaptive immunity as they often occur during sepsis. We also tested whether ELISpot could detect the effect of immune drug therapies to modulate innate and adaptive immunity. ⋯ ELISpot offers a unique capability to assess the functional status of both adaptive and innate immunity over time. The results presented herein demonstrate that ELISpot can also be used to detect and follow the in vivo effects of drugs to ameliorate sepsis-induced immune dysfunction. This capability would be a major advance in guiding new immune therapies in sepsis.
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Post-sepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness (CCI) 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 TNFα production based on clinical outcome. This may provide therapeutic targets for those at risk for CCI in order to improve their phenotype/endotype, morbidity, and long-term mortality.
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Ischemia can cause reversible or irreversible cell or tissue damage, and reperfusion after ischemia not only has no therapeutic effect but also aggravates cell damage. Notably, gut tissue is highly susceptible to ischemia-reperfusion (IR) injury under many adverse health conditions. Intestinal IR (IIR) is an important pathophysiological process in critical clinical diseases. ⋯ This article reviews the pathogenesis of IR and the current treatment measures, and further points out that hyperbaric oxygen has a better effect in IR. We found that not only improved hypoxia but also regulated IR induced injury in a certain way. From the perspective of clinical application, these changes and the application of hyperbaric oxygen therapy have important implications for treatment, especially IIR.
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Background: Both sepsis-induced cardiomyopathy and worsening of preexisting cardiac disease can contribute to circulatory shock in septic patients. The early use of pulmonary artery catheter (PAC) could play a pivotal role in the management of sepsis-associated cardiogenic shock. In this study, we aimed to evaluate the impact of early invasive hemodynamic monitoring with PAC in patients with sepsis-associated cardiogenic shock. ⋯ The use of PAC was also associated with increased use of mechanical circulatory support in those with sepsis-associated cardiogenic shock (aOR = 12.26, 95% CI = 9.37-16.03, P < 0.001). For patients with sepsis-associated cardiogenic shock, the use of PAC after 2 days of admission was associated with significantly higher in-hospital mortality and decreased use of mechanical circulatory support. Conclusion: The use of pulmonary artery catheters in sepsis-associated cardiogenic shock was associated with significantly lower in-hospital mortality and increased use of mechanical circulatory supports in patients with sepsis-associated cardiogenic shock.