28-day sepsis mortality prediction model from combined serial interleukin-6, lactate, and procalcitonin measurements: a retrospective cohort study.

Sepsis is a global medical issue owing to its unacceptably high mortality rate. Therefore, an effective approach to predicting patient outcomes is critically needed. We aimed to search for a novel 28-day sepsis mortality prediction model based on serial interleukin-6 (IL-6), lactate (LAC), and procalcitonin (PCT) measurements. We enrolled 367 septic patients based on Sepsis-3 (Third International Consensus Definitions for Sepsis and Septic Shock). Serum IL-6, LAC, and PCT levels were measured serially. Results collected within 24 and 48-72 h of admission were marked as D1 and D3 (e.g., IL-6D1/D3), respectively; the IL-6, LAC, and PCT clearance (IL-6c, LACc, PCTc) at D3 were calculated. Data were split into training and validation cohorts (7:3). Logistic regression analyses were used to select variables to develop models and choose the best one according to the Akaike information criterion (AIC). Receiver operating characteristic curves (ROC), calibration plots, and decision curve analysis (DCA) were used to test model performance. A nomogram was used to validate the model. There were 314 (85.56%) survivors and 53 (14.44%) non-survivors. Logistic regression analyses showed that IL-6D1, IL-6D3, PCTD1, PCTD3, and LACcD3 could be used to develop the best prediction model. The areas under the curves (AUC) of the training (0.849, 95% CI: 0.787-0.911) and validation cohorts (0.828, 95% CI: 0.727-0.929), calibration plot, and the DCA showed that the model performed well. Thus, the predictive value of the risk nomogram was verified. Combining IL-6D1, IL-6D3, PCTD1, PCTD3, and LACcD3 may create an accurate prediction model for 28-day sepsis mortality. Multiple-center research with a larger quantity of data is necessary to determine its clinical utility.

Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury.

BACKGROUND: Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. METHODS: First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. RESULTS: Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1ß (IL-1ß) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. CONCLUSION: Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

Combining Blood-Based Biomarkers to Predict Mortality of Sepsis at Arrival at the Emergency Department.

BACKGROUND Our aim was to determine a useful combination of blood biomarkers that can predict 28-day mortality of sepsis upon arrival at the Emergency Department (ED). MATERIAL AND METHODS Based on Sepsis-3.0, 90 sepsis patients were enrolled and divided into survivor and nonsurvivor groups with day 28 as the study end point. After comparing the demographic data and clinical characteristics of patients, we evaluated the predictive validity of a combination of markers including interleukin-6 (IL-6), procalcitonin (PCT), and lactate at arrival at the ED. Independent risk factors were found by using univariate and multivariate logistic regression analyses, and the prognostic value of markers was determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS There were 67 (74.4%) survivors and 23 (25.6%) nonsurvivors. The levels of IL-6 (survivors vs nonsurvivors: median 205.30 vs 3499.00 pg/mL, P=0.012) and lactate (survivors vs. nonsurvivors: median 2.37 vs 5.77 mmol/L, P=0.003) were significantly lower in survivor group compared with the nonsurvivor group. Markers including IL-6, PCT, lactate, and neutrophil-to-white blood cell ratio (NWR) were independent risk factors in predicting 28-day mortality due to sepsis. The combination of these 4 markers provided the best predictive performance for 28-day mortality of patients with sepsis, on arrival at the ED (AUC of 0.823, 95% confidence interval [CI] 0.723-0.924), and its accuracy, specificity, and sensitivity were 74.4% (95% CI 64.0-82.8%), 91% (95% CI 80.9-96.3%), and 65% (95% CI 42.8-82.8%), respectively. CONCLUSIONS The combination of IL-6, PCT, lactate, and NWR measurements is a potential predictor of 28-day mortality for patients with sepsis, at arrival at the ED. Further research is needed to confirm our findings.

Mortality prediction using a novel combination of biomarkers in the first day of sepsis in intensive care units.

Early identification of infection severity and organ dysfunction is crucial in improving outcomes of patients with sepsis. We aimed to develop a new combination of blood-based biomarkers that can early predict 28-day mortality in patients with sepsis or septic shock. We enrolled 66 patients with sepsis or septic shock and compared 14 blood-based biomarkers in the first 24 h after ICU admission. The serum levels of interleukin-6 (IL-6) (median 217.6 vs. 4809.0 pg/ml, P = 0.001), lactate (median 2.4 vs. 6.3 mmol/L, P = 0.014), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (median 1596.5 vs. 32,905.3 ng/ml, P < 0.001), prothrombin time (PT) (median 15.6 vs. 20.1 s, P = 0.030), activated partial thrombin time (APTT) (median 45.1 vs. 59.0 s, P = 0.026), and international normalized ratio (INR) (median 1.3 vs. 1.8, P < 0.001) were significantly lower in the survivor group. IL-6, NT-proBNP, and INR provided the best individual performance in predicting 28-day mortality of patients with sepsis or septic shock. Furthermore, the combination of these three biomarkers achieved better predictive performance (AUC 0.890, P < 0.001) than conventional scoring systems. In summary, the combination of IL-6, NT-proBNP, and INR may serve as a potential predictor of 28-day mortality in critically ill patients with sepsis or septic shock.