Daily Sepsis Research Analysis

Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Interleukin 40 (IL-40), a novel cytokine with immune regulatory functions in human diseases, was elevated at admission in two independent cohorts of patients with sepsis. High levels of secreted IL-40 in septic patients were positively correlated with PCT, CRP, lactate (LDH), and Sequential Organ Failure Assessment (SOFA) scores, in which IL-40 levels were used to stratify the early death of critically ill patients with sepsis. Moreover, genetic knockout of IL-40 (IL-40

Pulmonary endothelial cell (EC) activation is a key factor in acute respiratory distress syndrome (ARDS). In sepsis, increased glycolysis leads to lactate buildup, which induces lysine lactylation (Kla) on histones and other proteins. However, the role of protein lactylation in EC dysfunction during sepsis-induced ARDS remains unclear. Integrative lactylome and proteome analyses were performed to identify the global lactylome profile in the lung tissues of septic mice. Cut&Tag analysis was used to identify the transcriptional targets of histone H3 lysine 14 lactylation (H3K14la) in ECs. Septic mice presented elevated levels of lactate and H3K14la in lung tissues, particularly in pulmonary ECs. Suppressing glycolysis reduced both H3K14la and EC activation, suggesting a link between glycolysis and lactylation. Moreover, H3K14la was enriched at promoter regions of ferroptosis-related genes such as transferrin receptor (TFRC) and solute carrier family 40 member 1 (SLC40A1), which contributed to EC activation and lung injury under septic conditions. For the first time, we reported the role of lactate-dependent H3K14 lactylation in regulating EC ferroptosis to promote vascular dysfunction during sepsis-induced lung injury. Our findings suggest that manipulation of the glycolysis/H3K14la/ferroptosis axis may provide novel therapeutic approaches for sepsis-associated ARDS.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a common complication in sepsis patients which exacerbates patient outcomes. The prevalence and outcomes of DIC in sepsis is wide-ranging and highly depends on the severity of the disease and diagnostic approaches utilized. Varied diagnostic criteria of DIC have been developed and their performance in diagnosis and prognosis is not consistent. Therefore, this study aimed to determine the score positivity rate and performance of different DIC scoring systems in predicting mortality in sepsis patients. METHODS: Four databases, including Medline (through PubMed), Scopus, Embase, and Web of Science were searched for studies that determined DIC in sepsis patients using the three scoring systems namely: the International Society on Thrombosis and Hemostasis DIC (ISTH-DIC) criteria, the Japanese association for acute medicine DIC (JAAM-DIC) criteria, and the sepsis-induced coagulopathy (SIC) criteria. A random-effect meta-analysis was performed with a 95% confidence interval (CI). Subgroup analysis was conducted in view of geographic region and sepsis stages. the protocol was submitted to the Prospective Register for Systematic Reviews (PROSPERO) with an identifier (CRD42023409614). RESULTS: Twenty-one studies, published between 2009 and 2024, comprising 9319 sepsis patients were included. The pooled proportion of cases diagnosed as positive using ISTH-DIC criteria, JAAM-DIC criteria, and SIC were 28% (95% CI: 24-34%), 55% (95% CI:42-70%), and 57% (95% CI: 52-78%), respectively. The pooled mortality rates were 44% (95% CI:33-53%), 37% (95% CI: 29-46%), and 35% (95% CI: 29-41%), respectively. The pooled sensitivity and specificity of ISTH-DIC to predict mortality were 0.43 (95% CI: 0.34-0.52), and 0.81 (95% CI: 0.74-0.87), respectively, while for JAAM-DIC it was 0.73 (95% CI: 0.57-0.85) and 0.46 (95% CI: 0.28-0.65), respectively. Pooled sensitivity and specificity for SIC were 0.71 (95% CI: 0.57-0.82) and 0.49 (95% CI: 0.31-0.66), respectively. CONCLUSION: The SIC and JAAM-DIC scores exhibited higher sensitivity to identify patients with coagulopathy and predict patient outcomes, and thus are valuable to identify patients for possible treatment at an early stage. The ISTH-DIC score perhaps identified patients at later stages and demonstrated better specificity to predict disease outcomes. Thus, early identification of patients using the SIC and JAAM-DIC scores and later confirmation using the ISTH-DIC score would be beneficial approach for improved management of patients with sepsis.