Articles: sepsis.
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Background: Sepsis commonly leads to skeletal muscle atrophy, characterized by substantial muscle weakness and degeneration, ultimately contributing to an adverse prognosis. Studies have shown that programmed cell death is an important factor in the progression of muscle loss in sepsis. However, the precise role and mechanism of pyroptosis in skeletal muscle atrophy are not yet fully comprehended. ⋯ Studies conducted in living organisms ( in vivo ) and in laboratory conditions ( in vitro ) have shown that the absence of the Gsdmd gene decreases indicators of muscle loss associated with sepsis by blocking the IL18/AMPK signaling pathway. Conclusion: The results of this study demonstrate that the lack of Gsdmd has a beneficial effect on septic skeletal muscle atrophy by reducing the activation of IL18/AMPK and inhibiting the ubiquitin-proteasome system and autophagy pathways. Therefore, our research provides vital insights into the role of pyroptosis in sepsis-related skeletal muscle wasting, which could potentially lead to the development of therapeutic and interventional approaches for preventing septic skeletal muscle atrophy.
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Sepsis is a life-threatening condition widely studied by animal models. Cecal ligation and puncture (CLP) is still regarded as the gold standard model for sepsis. However, CLP has limitations due to its invasiveness and variability. ⋯ CS model also induced increased production of nitric oxide metabolites and bacterial spread to tissues. CS model causes less animal suffering, it is a nonsurgical model, and, more importantly, it replicates the cardiovascular dysfunction induced by sepsis with better homogeneity than CLP. Therefore, CS model serves as an alternative and possibly as a better model for sepsis research.
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Curr Opin Crit Care · Oct 2024
ReviewSepsis phenotypes, subphenotypes, and endotypes: are they ready for bedside care?
Sepsis remains a leading global cause of morbidity and mortality, and despite decades of research, no effective therapies have emerged. The lack of progress in sepsis outcomes is related in part to the significant heterogeneity of sepsis populations. This review seeks to highlight recent literature regarding sepsis phenotypes and the potential for further research and therapeutic intervention. ⋯ Sepsis therapies including care bundles, fluid resuscitation, and source control procedures may be better guided by validated phenotypes than universal application. Novel biomarkers may improve upon the sensitivity and specificity of existing markers and identify complications and sequelae of sepsis. Multiomics have demonstrated significant differences in sepsis populations, most notably expanding our understanding of immunosuppressed sepsis phenotypes. Despite progress, these findings may be limited by modest reproducibility and logistical barriers to clinical implementation. Further studies may translate recent findings into bedside care.
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Multicenter Study
Derivation and validation of generalized sepsis-induced acute respiratory failure phenotypes among critically ill patients: a retrospective study.
Septic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis, considering multi-organ dynamics. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate the generalizability of the derived phenotypes. ⋯ The phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies.