Daily Sepsis Research Analysis

BACKGROUND: Sepsis is a global health burden characterized by high heterogeneity and uncontrolled immune response, with a notable lack of reliable methods for early prognosis and risk stratification. Epigenetic modifications, particularly lactylation, have recently emerged as key regulators in the early pathophysiology of sepsis. However, their potential for immune-related mortality risk stratification remains largely unexplored. This study aimed to investigate dynamic changes in lactylation during sepsis progression and to develop a rapid, lactylation-based prognostic signature. METHODS: Blood transcriptional profiles and single-cell RNA sequencing data from septic patients were analyzed to assess glycolytic activity and lactylation in relation to patient mortality. Patients were stratified into subgroups using k-means clustering based on lactylation levels. Machine learning algorithms, integrated with pseudotime trajectory reconstruction, were employed to map the temporal dynamics of lactylation. A prognostic model was then constructed using lactylation-associated hub genes and validated in external transcriptomic datasets, a prospective single-center clinical cohort. The underlying mechanism was further explored RESULTS: The study systematically characterized the dynamic alterations in lactylation patterns and immune microenvironment across distinct patient clusters. A lactylation-based prognostic model was developed, comprising eight key genes (CD160, HELB, ING4, PIP5K1C, SRPRA, CDCA7, FAM3A, PPP1R15A), and demonstrated strong predictive performance for sepsis outcomes (AUC = 0.78 in the training cohort; AUC = 0.73 in the validation cohort). Temporal expression patterns of lactylation-related hub genes revealed dynamic immune responses throughout disease progression. In the prospective cohort of septic patients (N = 51), the model showed high predictive accuracy for survival, with AUCs of 0.82 (7-day), 0.80 (14-day), and 0.86 (28-day). Additionally, global lactylation levels were significantly elevated in THP-1 cells following treatment with Sephin1, a selective PPP1R15A inhibitor, suggesting a mechanistic link. CONCLUSIONS: Lactylation is significantly associated with increased mortality risk in sepsis. The proposed individualized prognostic model, based on dysregulated immune cell metabolism, accurately predicts early mortality and may inform optimized clinical management of septic patients.

BACKGROUND: Sepsis poses a significant threat to human health, and extensive research has examined the relationship between proton pump inhibitors (PPI) and adverse outcomes in patients with sepsis. However, a consensus on this issue remains elusive. Therefore, this study aims to develop a prognostic model to assess the effectiveness of prophylactic PPI administration in patients with sepsis. METHODS: A retrospective cohort study was conducted using the open-access Medical Information Mart for Intensive Care (MIMIC-IV) database. Patients diagnosed with sepsis according to the Sepsis-3.0 criteria were selected for inclusion. The primary outcome of interest was all-cause mortality occurring between 28 and 90 days following prophylactic PPI use. Secondary outcomes included in-hospital and intensive care unit (ICU) mortality, duration of hospital and ICU stays, and the incidence of adverse events. Stepwise Cox proportional hazards regression analysis was performed, and multivariate Cox regression models were developed and evaluated using receiver operating characteristic (ROC) curves. Additionally, Kaplan-Meier curves were utilized to compare patient survival at 28 and 90 days. RESULTS: This study included 18,198 sepsis patients. The results demonstrated that prophylactic PPI use was significantly associated with increased 90-day all-cause mortality following ICU admission ( CONCLUSION: Prophylactic PPI use failed to improve 28-day or 90-day survival rates in adult sepsis patients. Although PPI use was associated with reduced ICU length of stay, it did not shorten total hospital stay duration. Additionally, PPI administration was linked to clinically significant adverse reactions.

OBJECTIVE: Given the lack of data on long-term outcomes among patients with sepsis, this study aimed to examine all-cause 2-year mortality and factors associated with mortality in adults admitted to an emergency department with sepsis. STUDY DESIGN: Prospective cohort study. METHODS: This study included all emergency department patients admitted with sepsis to Slagelse Hospital, Denmark, between October 1, 2017, and March 31, 2018. Data on patients with infectious diseases was prospectively extracted from electronic health records during the study period. Sepsis was defined as a Sequential Organ Failure Assessment (SOFA) score ≥ 2 from baseline. The outcome was 2-year all-cause mortality. The Kaplan-Meier method was used to estimate the mortality. Cox regression analyses were used to compute adjusted hazard ratios (aHR) with 95% confidence intervals for prognostic factors associated with mortality. RESULTS: A total of 714 patients (58.4% men) with a median age of 75 years were diagnosed with sepsis. After two years, 354 (49.6%; 45.9-53.3) patients had died. Factors associated with elevated mortality risk included age (< 65 years as reference) 65-85 years (aHR 1.89; 1.35-2.64) or age > 85 years (aHR 2.99; 2.07-4.31); SOFA score > 4 (aHR 2.45; 1.82-3.30) (score of 2 as reference); and history of malignancy (aHR 1.91; 1.44-2.53), ischemic heart disease (aHR 1.38; 1.03-1.84), dementia (aHR 1.84; 1.34-2.53), previous sepsis admission (aHR 1.45; 1.15-1.82), new-onset atrial fibrillation (aHR 1.56; 1.05-2.34), and mildly decreased (6.9-7.9 mmmol/L) hemoglobin values (aHR 1.68; 1.29-2.19) and significantly decreased (<6.9 mmol/L) hemoglobin values (aHR 2.30; 1.74-3.02) with normal range (≥ 8mmol/L) as reference. Skin infection was associated with diminished mortality risk (aHR 0.50; 0.29-0.85) compared to patients with other sources of infection. CONCLUSION: Sepsis is associated with a poor prognosis. Our findings underscore the prognostic effects of age, SOFA score, and specific comorbidities on 2-year mortality among patients with sepsis.