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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Introduction: The dysregulated immune response in sepsis is highly variable, ranging from hyperinflammation to immunoparalysis. Obesity is associated with the release of inflammatory mediators from adipose tissue, known as adipocytokines, causing a chronic inflammatory state. Perhaps counterintuitively, obesity is also associated with lower mortality in sepsis patients. ⋯ Although resistin is related to the immune response and an increased risk of adverse clinical outcomes, these associations are similar in patients with normal weight, overweight, and obesity. This implies that the relationship between resistin and clinical outcome is likely driven by the inflammatory response and not by obesity itself. Taken together, although there exists a strong association between inflammation and sepsis mortality, our results do not point toward a role for obesity and BMI-related adipocytokines in immune dysregulation in sepsis patients.
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Observational Study
Identification of Subphenotypes of Sepsis-Associated Liver Dysfunction Using Cluster Analysis.
Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. ⋯ In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.
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Purpose: This study aimed to identify the association between hyperchloremia at intensive care unit (ICU) admission and/or the increase of blood chloride levels and the incidence of major adverse kidney events within 30 days (MAKE30) in critically ill adults. Methods: We conducted a retrospective study to analyze the data of all adult patients admitted to the ICU of a tertiary academic hospital in China between April 2020 and April 2022. Patients were categorized based on their admission chloride levels (hyperchloremia ≥110 mmol/L and nonhyperchloremia <110 mmol/L) and stratified on the increased chloride levels 48 h after ICU admission (∆Cl ≥5 mmol/L and ∆Cl <5 mmol/L). ⋯ After adjusted for confounders, it was found that ΔCl ≥5 mmol/L (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.096-1.93; P = 0.010), but not hyperchloremia (OR, 0.99; 95% CI, 0.77-1.28; P = 0.947), was associated with increased incidence of MAKE30. Conclusion: An increased chloride level in the first 48 h of ICU admission was an independent risk factor for MAKE30, whereas hyperchloremia at ICU admission was not associated with an increased incidence of MAKE30. Large-scale prospective studies are needed to verify our findings.
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Background: Monocytes and monocyte-derived tissue factor (TF) promote the development of sepsis-induced acute lung injury (ALI). Classical monocytes (C-Mcs) can be induced to express TF. Valproic acid (VPA) alleviates hemorrhagic shock (HS)-induced ALI (HS/ALI) and inhibits TF expression in monocytes. ⋯ VPA inhibited hypoxia-induced TF expression in THP-1 cells by regulating the p-ERK1/2-Egr-1 axis. Conclusion: C-Mcs and C-Mc-derived TF accelerate the development of HS/ALI by increasing thrombin production. VPA inhibits HS-induced C-Mc production of TF by regulating the p-ERK1/2-Egr-1 axis and alleviates HS/ALI.
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Objective: The aim of the study is to screen transcription factor genes related to the prognosis of adult patients with sepsis. Methods: Twenty-three patients with sepsis and 10 healthy individuals admitted for RNA-seq. Differential factors were enriched by four transcription factor databases, and survival analysis was adopted for core factors. ⋯ Compared with those in the control group, FOXO3, SP1, SPI1, STAT3, and USF1 were highly expressed in the sepsis group, while PPARA had low expression. Conclusions: Transcription factors, such as FOXO3, PPARA, SP1, SPI1, STAT3, and USF1, are correlated with the prognosis of sepsis patients and thus may have a potential research value. Clinical Trial Registration: The clinical trial registration number is ChiCTR1900021261.