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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Background: Understanding of immune cell phenotypes associated with inflammatory and immunosuppressive host responses in sepsis is imprecise, particularly in low- and middle-income countries, where the global sepsis burden is concentrated. In these settings, elucidation of clinically relevant immunophenotypes is necessary to determine the relevance of emerging therapeutics and refine mechanistic investigations of sepsis immunopathology. Methods: In a prospective cohort of adults hospitalized with suspected sepsis in Uganda (N = 43; median age 46 years [IQR 36-59], 24 [55.8%] living with HIV, 16 [37.2%] deceased at 60 days), we combined high-dimensional flow cytometry with unsupervised machine learning and manual gating to define peripheral immunophenotypes associated with increased risk of 60-day mortality. ⋯ Abundance of T cells expressing inhibitory checkpoint proteins (PD-1, CTLA-4, LAG-3) was similar between patients who died versus those who survived. Conclusions: This is the first study to define high-risk immunophenotypes among adults with sepsis in sub-Saharan Africa, an immunologically distinct region where biologically informed treatment strategies are needed. More broadly, our findings highlight the clinical importance and complexity of myeloid derived suppressor cell expansion during sepsis and support emerging data that suggest a host-protective role for PD-L1 myeloid checkpoints in acute critical illness.
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Objective: The goal of this study is to investigate the clinical value of vasopressor inflection points in the evaluation of short-term prognosis among individuals afflicted with septic shock. Methods: A retrospective analysis was conducted on a cohort comprising 56 patients diagnosed with septic shock and receiving treatment at the department of critical care medicine of the hospital between January 2021 and March 2023. These patients were divided into two groups based on the prognostic outcome: a survival group consisting of 34 patients and a death group consisting of 22 patients. ⋯ Correspondingly, the Youden indices were calculated as 0.673, 0.791, and 0.864 on these respective days. Notably, all metrics at comparable intervals surpassed those of the PCT inflection point. Conclusion : The vasopressor inflection point presents as a robust prognostic tool for the short-term outcomes in patients with septic shock and exhibits superiority over PCT in prognostic assessment.
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Sepsis is a life-threatening disease due to a dysregulated host response to infection, with an unknown regulatory mechanism for prognostic necroptosis-related genes (NRGs). Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers ( ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 ) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses. Afterward, the ingenuity pathway analysis (IPA) highlighted enrichment in hepatic fibrosis pathways and BEX2 protein. ⋯ Additionally, DrugBank analysis identified paclitaxel, docetaxel, and rasagiline as potential BCL2-targeting sepsis treatments. Finally, real-time quantitative PCR confirmed ATRX, TSC1, and LEF1 downregulation in sepsis samples, contrasting CD40's increased expression in CTL samples. In conclusion, ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 may be critical regulatory targets of necroptosis in sepsis, providing a basis for further necroptosis-related studies in sepsis.
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Sepsis, a complex and multifaceted condition, is a common occurrence with serious implications for critically ill patients in the intensive care unit (ICU). The YWHAH gene encodes the 14-3-3n protein, a member of the 14-3-3 protein family. While existing research primarily focuses on the role of 14-3-3n in conditions such as schizophrenia and various cancers, our study revealed that the expression of the YWHAH gene remained relatively stable in both infected individuals and healthy controls. ⋯ In a comprehensive analysis of public single-cell transcriptome databases, the expression of YWHAH was found to be distinctive in cases of sepsis and infection. These findings were corroborated through an in vitro analysis utilizing real-time polymerase chain reaction. This study represents the initial identification of variations in YWHAH gene expression between patients with infection and sepsis, potentially offering insights for the development of early detection and treatment strategies for sepsis.
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Sepsis causes dysfunction in different organs, but the pathophysiological mechanisms behind it are similar and mainly involve complex hemodynamic and cellular dysfunction. The importance of microcirculatory dysfunction in sepsis is becoming increasingly evident, in which endothelial dysfunction and glycocalyx degradation play a major role. This study aimed to investigate the effects of hydrogen-rich saline (HRS) on renal microcirculation in septic renal failure, and whether Sirt1 was involved in the renoprotective effects of HRS. ⋯ Compared with the CLP group, HRS reduced renal apoptosis and upregulated Sirt1 expression, and inhibited the NF-κB/MMP9 signaling pathway. In addition, HRS did not damage immune function in septic rats as well. Generally speaking, our results suggest that HRS can alleviate the inflammatory response, inhibit glycocalyx shedding, improve septic kidney injury, and enhance survival rate.