28-day Mortality Of Sepsis Patients Research Articles

Development and validation of an interpretable machine learning for mortality prediction in patients with sepsis.

Sepsis is a leading cause of death. However, there is a lack of useful model to predict outcome in sepsis. Herein, the aim of this study was to develop an explainable machine learning (ML) model for predicting 28-day mortality in patients with sepsis based on Sepsis 3.0 criteria. We obtained the data from the Medical Information Mart for Intensive Care (MIMIC)-III database (version 1.4). The overall data was randomly assigned to the training and testing sets at a ratio of 3:1. Following the application of LASSO regression analysis to identify the modeling variables, we proceeded to develop models using Extreme Gradient Boost (XGBoost), Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) techniques with 5-fold cross-validation. The optimal model was selected based on its area under the curve (AUC). Finally, the Shapley additive explanations (SHAP) method was used to interpret the optimal model. A total of 5,834 septic adults were enrolled, the median age was 66 years (IQR, 54-78 years) and 2,342 (40.1%) were women. After feature selection, 14 variables were included for developing model in the training set. The XGBoost model (AUC: 0.806) showed superior performance with AUC, compared with RF (AUC: 0.794), LR (AUC: 0.782) and SVM model (AUC: 0.687). SHAP summary analysis for XGBoost model showed that urine output on day 1, age, blood urea nitrogen and body mass index were the top four contributors. SHAP dependence analysis demonstrated insightful nonlinear interactive associations between factors and outcome. SHAP force analysis provided three samples for model prediction. In conclusion, our study successfully demonstrated the efficacy of ML models in predicting 28-day mortality in sepsis patients, while highlighting the potential of the SHAP method to enhance model transparency and aid in clinical decision-making.

Peripheral PD-1+NK cells could predict the 28-day mortality in sepsis patients.

Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model. Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38+CD8+T cells, PD-1+NK cells, HLA-DR+CD8+T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1+ NK cells, while cluster 2 featured higher proportions of naïve CD4+T cells. Furthermore, the level of PD-1+NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, P<0.01). Moreover, the levels of PD1+ NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1+ NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1+ NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; P<0.001). The study provides novel insights into the association between PD1+NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.

The relationship between potassium levels and 28-day mortality in sepsis patients: Secondary data analysis using the MIMIC-IV database

ObjectiveThe goal of the research is to investigate the link between serum potassium levels and death after 28 days in sepsis patients, utilizing an extensive sample of patients from the multi-center Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Current research on serum potassium levels and 28-day mortality in sepsis patients is questionable. This study adds to the growing body of evidence linking serum potassium levels to the 28-day possibility of death in patients with sepsis. MethodsWe collected 349,08 patients with sepsis from the retrospective cohort MIMIC-IV database, using serum potassium level on the first day of admission to the intensive care unit as the exposure variable and mortality at 28 days as the outcome variable. And controlled for confounding characteristics including gender, age, ethnicity, and vital signs during admission. ResultsSerum potassium has a U-shaped connection with 28-day mortality in patients suffering from sepsis. The turning point was 4.10 mmol/L (95 % confidence interval: 4.03 to 4.22). Serum potassium and 28-day mortality were negatively linked on the inflection point’s left side (OR: 0.72; 95 % CI: 0.63 to 0.83, P < 0.0001); on the opposing side of the point of inflexion, serum potassium was enthusiastically attached to 28-day mortality. (OR: 1.13; 95 % CI: 1.06 to 1.21, P < 0.0001). ConclusionThe research conducted found that too high or too low potassium levels were linked to a 28-day risk of mortality in humans with sepsis.

Red blood cell distribution width-to-albumin ratio: a prognostic biomarker of sepsis patients

IntroductionTo explore the association of red blood cell distribution width-to-albumin ratio (RAR) with 28-day mortality among septic patients, as well as to develop predictive models for evaluating the prognostic significance of RAR.Material and methodsRelevant information was obtained from the Medical Information Mart for Intensive Care (MIMIC-III). A total of 1475 individuals diagnosed with sepsis were enrolled. Data on patients’ age, creatinine levels, and mechanical ventilation status in the initial 24 h after intensive care unit (ICU) admission were gathered. We employed multivariate COX analyses to investigate the correlation between RAR and 28-day mortality, and we conducted subgroup analyses stratified by gender, age, intervention modality, and disease progression. We established 4 prediction models relevant to RAR to forecast the 28-day mortality of septic patients. Additionally, we evaluated the predictive value using receiver operator characteristic curves.ResultsThe significance of the association between RAR and 28-day mortality was maintained among sepsis patients regardless of their use or non-use of mechanical ventilation or vasopressor, presence or absence of septic shock, and gender (male or female). Additionally, these developed models associated with RAR demonstrated a good predictive value in forecasting the 28-day mortality rate among septic patients.ConclusionsThis study provides evidence, suggesting a significant correlation between RAR and the 28-day mortality among sepsis patients of ICU admission. It might show promise of RAR as a potential dependable prognostic marker for the prediction of 28-day mortality in sepsis patients.

Immune Dysfunction-Associated Elevated RDW, APACHE-II, and SOFA Scores Were a Possible Cause of 28-Day Mortality in Sepsis Patients.

To explore the early predictors and their predicting value of 28-day mortality in sepsis patients and to investigate the possible causes of death. 127 sepsis patients were included, including 79 cases in the survival group and 48 cases in the death group. The results of all patients on admission were recorded. After screening the risk factors of 28-day mortality, the receiver operating characteristic curve (ROC) was used to determine their predictive value for the 28-day mortality rate on admission, and the Kaplan-Meier curve was drawn to compare the 28-day mortality rate between groups. Finally, patients with cytokine and lymphocyte subsets results were included for investigating the possible causes of death through correlation analysis. APACHE II (acute physiology and chronic health evaluation II), SOFA (Sequential Organ Failure Assessment) and red blood cell distribution width (RDW) were the risk factors for 28-day mortality in sepsis patients (OR: 1.130 vs.1.160 vs.1.530, P < 0.05). The area under the curve (AUC), sensitivity and specificity of APACHE II, SOFA and RDW in predicting the mortality rate at 28 days after admission in sepsis patients were 0.763 vs 0.806 vs 0.723, 79.2% vs 68.8% vs 75.0%, 65.8% vs 89.9% vs 68.4%. The combined predicted AUC was 0.873, the sensitivity was 89.6%, and the specificity was 82.3%. The Kaplan-Meier survival curve showed that the 28-day mortality rates of sepsis patients with APACHE II≥18.5, SOFA≥11.5 and RDW≥13.8 were 58.5%, 80.5% and 59.0%, respectively. In the death group, APACHE II was positively correlated with SOFA, IL-2, and IL-10, and RDW was positively correlated with PLT, TNF-α, CD3+ lymphocyte count, and CD8+ lymphocyte count. Sepsis patients with high APACHE II, SOFA and RDW levels at admission have an increased 28-day mortality rate. The elevation of these indicators in dead patients are related to immune dysfunction.

Effect of early serum phosphate disorder on in-hospital and 28-day mortality in sepsis patients: a retrospective study based on MIMIC-IV database

BackgroundThis study aims to assess the influence of early serum phosphate fluctuation on the short-term prognosis of sepsis patients.MethodsThis retrospective study used the Medical Information Mart for Intensive Care IV database to analyze serum phosphate levels in sepsis patients within 3 days of ICU admission. According to the absolute value of delta serum phosphate (the maximum value minus the minimum value of serum phosphorus measured within three days), the patients were divided into four groups, 0–1.3, 1.4–2.0, 2.1–3.1, and ≥ 3.2 mg/dl. Meanwhile, the direction of delta serum phosphate was compared. With the serum phosphate change group of 0–1.3 mg/dl as the reference group, the relationship between delta serum phosphate and in-hospital mortality and 28-day mortality was analyzed by multivariate Logistics regression analysis.ResultsThe study involved 1375 sepsis patients. Serum phosphate changes (0–1.3, 1.4–2.0, 2.1–3.1, and ≥ 3.2 mg/dl) correlated with in-hospital and 28-day mortality variations (p = 0.005, p = 0.008). Much higher serum phosphate fluctuation elevated in-hospital and 28-day mortality. Compared to the 0–1.3 mg/dl change group, adjusted odds ratios (OR) in other groups for in-hospital mortality were 1.25 (0.86–1.81), 1.28 (0.88–1.86), and 1.63 (1.10–2.43), and for 28-day mortality were 1.21 (0.86–1.72), 1.10 (0.77–1.57), and 1.49 (1.03–2.19). Under the trend of increasing serum phosphate, the ORs of in-hospital mortality and 28-day mortality in ≥ 3.2 mg/dl group were 2.52 and 2.01, respectively.ConclusionIn conclude, the delta serum phosphate ≥ 3.2 mg/dl was associated with in-hospital mortality and 28-day mortality in patients with sepsis.

Bisphosphoglycerate mutase predicts myocardial dysfunction and adverse outcome in sepsis: an observational cohort study

BackgroundSepsis not only causes inflammation, but also damages the heart and increases the risk of death. The glycolytic pathway plays a crucial role in the pathogenesis of sepsis-induced cardiac injury. This study aims to investigate the value of bisphosphoglycerate mutase (BPGM), an intermediate in the glycolytic pathway, in evaluating cardiac injury in septic patients and predicting poor prognosis in sepsis.MethodsThis prospective study included 85 patients with sepsis. Serum BPGM was measured at the time of enrollment, and the patients were divided into a BPGM-positive group (n = 35) and a BPGM-negative group (n = 50) according to their serum BPGM levels. Baseline clinical and echocardiographic parameters, and clinical outcomes were analyzed and compared between the two groups. Kaplan–Meier analysis was used to compare the 28-day survival rate between BPGM-negative and BPGM-positive patients. Multivariate logistic regression analysis was conducted to explore the independent risk factors for 28-day mortality in septic patients. The predictive value of serum BPGM for sepsis-induced myocardial injury and poor prognosis in sepsis was evaluated using receiver operating characteristic (ROC)curve analysis.ResultThe serum level of BPGM was significantly higher in patients who died within 28 days compared to survivors (p < 0.001). Kaplan–Meier analysis showed that serum BPGM-positive sepsis patients had a significantly shorter 28-day survival time (p < 0.001). Multivariate logistic regression analysis showed that serum BPGM (OR = 9.853, 95%CI 1.844–52.655, p = 0.007) and left ventricular ejection fraction-simpson(LVEF-S) (OR = 0.032, 95% CI 0.002–0.43, p = 0.009) were independent risk factors for 28-day mortality in sepsis patients. Furthermore, BPGM levels was negatively correlated with LVEF-S (p = 0.005) and positively correlated with the myocardial performance (Tei) index (p < 0.001) in sepsis patients. ROC curve analysis showed that serum BPGM was a good predictor of septic myocardial injury and 28-day mortality in sepsis patients.ConclusionThe level of BPGM in the serum of sepsis patients can serve as a monitoring indicator for myocardial injury, with its high level indicating the occurrence of secondary myocardial injury events and adverse outcomes in sepsis patients.

DEVELOPMENT AND VALIDATION OF A NOMOGRAM FOR PREDICTING 28-DAY IN-HOSPITAL MORTALITY IN SEPSIS PATIENTS BASED ON AN OPTIMIZED ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION II SCORE.

Purpose : The objective of this study is to establish a nomogram that correlates optimized Acute Physiology and Chronic Health Evaluation II (APACHE II) score with sepsis-related indicators, aiming to provide a robust model for early prediction of sepsis prognosis in clinical practice and serve as a valuable reference for improved diagnosis and treatment strategies. Methods : This retrospective study extracted sepsis patients meeting the inclusion criteria from the MIMIC-IV database to form the training group. An optimized APACHE II score integrated with relevant indicators was developed using a nomogram for predicting the prognosis of sepsis patients. External validation was conducted using data from the intensive care unit at Lanzhou University Second Hospital. Results : The study enrolled 1805 patients in the training cohort and 203 patients in the validation cohort. A multifactor analysis was conducted to identify factors affecting patient mortality within 28 days, resulting in the development of an optimized score by simplifying evaluation indicators from APACHE II score. The results showed that the optimized score (area under the ROC curve [AUC] = 0.715) had a higher area under receiver operating characteristic curve than Sequential Organ Failure Assessment score (AUC = 0.637) but slightly lower than APACHE II score (AUC = 0.720). Significant indicators identified through multifactor analysis included platelet count, total bilirubin level, albumin level, prothrombin time, activated partial thromboplastin time, mechanical ventilation use and renal replacement therapy use. These seven indicators were combined with optimized score to construct a nomogram based on these seven indicators. The nomogram demonstrated good clinical predictive value in both training cohort (AUC = 0.803) and validation cohort (AUC = 0.750). Calibration curves and decision curve analyses also confirmed its good predictive ability, surpassing the APACHE II score and Sequential Organ Failure Assessment score in identifying high-risk patients. Conclusions : The nomogram was established in this study using the MIMIC-IV database and validated with external data, demonstrating its robust discriminability, calibration, and clinical practicability for predicting 28-day mortality in sepsis patients. These findings aim to provide substantial support for clinicians' decision making.

Prognostic value of neutrophil-to-monocyte/lymphocyte ratio for 28-day mortality in ICU sepsis patients: a retrospective cohort study.

Sepsis is a life-threatening condition that requires rapid assessment to reduce mortality. This study investigates the relationship between the Neutrophil-to-Monocyte/Lymphocyte Ratio (NMLR) upon ICU admission and 28-day mortality in sepsis patients. A retrospective analysis was performed using clinical data from sepsis patients in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Multivariate logistic regression, sensitivity analyses, and Restricted Cubic Spline (RCS) models were employed to explore the relationship between ICU admission NMLR and 28-day mortality. Kaplan-Meier method and inverse probability weighting (IPW) were used to adjust for confounders and estimate survival outcomes. Receiver operating characteristic (ROC) curve evaluating the predictive value of NLMR for 28-day mortality in ICU sepsis patients. Subgroup analyses considered factors like age, sex, race, comorbidities, and disease severity. In total, 8,710 patients were included. Increased NMLR was associated with higher 28-day all-cause mortality, confirmed by multiple logistic regression models. In Model 3, after adjusting for confounders, each standard deviation increase in NMLR was associated with a 1.5% increase in 28-day mortality risk. Kaplan-Meier and IPW survival analyses showed higher 28-day all-cause mortality in patients with elevated NMLR levels at ICU admission compared to those with lower levels (p < 0.0001, p = 0.031). RCS models suggested a potential non-linear relationship between NMLR and 28-day mortality. ROC curve for the NMLR model, with an AUC of 0.658 (95% CI: 0.642-0.673). Sensitivity analyses confirmed the association even after excluding patients with myocardial infarction and severe liver disease. Elevated NMLR at ICU admission is significantly associated with increased 28-day all-cause mortality in sepsis patients, suggesting its potential as an early prognostic indicator for risk assessment and intervention.

Association between Lactate Dehydrogenase to Albumin Ratio and 28-Day Mortality in Patients with Sepsis: a Retrospective Cohort Study.

This study aims to evaluate the lactate dehydrogenase to albumin ratio and mortality at 28 days in patients with sepsis. Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were used for this retrospective cohort analysis. The level of the lactate dehydrogenase to albumin ratio was recovered at admission and the outcome index was mortality at 28 days. Multivariate Cox regression, survival curve analysis, and subgroup analysis were used to study the relationship between lactate dehydrogenase to albumin ratio and 28-day mortality in sepsis patients. This study included a total of 4,265 patients with sepsis, with a 28-day mortality rate of 51.9%. After conducting multivariable COX regression analysis and adjusting for all potential confounding factors, we observed that compared to the LDH/ALB (Q1) group, the Q2 group had a 1.34-fold higher risk of 28-day mortality (HR = 1.34, 95% CI: 1.20 - 1.49, p < 0.001), while the Q3 group had a 1.90-fold higher risk (HR = 1.90, 95% CI: 1.69 - 2.14, p < 0.001). Furthermore, the survival analysis curve indicated a gradual increase in the 28-day mortality rate of septic patients as LDH/ALB levels increased. In addition, the ROC curve demonstrated that the area under the curve for LDH/ALB was 0.6507 (95% CI: 63.4991% - 66.6368%), which was higher than that of LDH (AUC = 0.6434), ALB (AUC = 0.55), and SOFA SCORE (AUC = 0.5564). Finally, subgroup analysis revealed no significant interaction between LDH/ALB and the various subgroups. The LDH/ALB ratio is significantly correlated with mortality at 28 days in patients with sepsis, which is of significant clinical importance and deserves further study.

Prognosis analysis of multi-indicator combined with sequential organ failure assessment in patients with sepsis

To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients. A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis. A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05). The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.

Dynamic expression analysis of peripheral blood derived small extracellular vesicle miRNAs in sepsis progression.

Immune disorders caused by sepsis have recently drawn much attention. We sought to dynamically monitor the expression of small extracellular vesicle (sEV) miRNAs in peripheral blood during sepsis to explore these miRNAs as potential biomarkers for monitoring immune function in sepsis patients. This study included patients with sepsis. Blood samples were obtained from 10 patients on the first through 10th days, the 12th day and the 14th day since sepsis onset, resulting in 120 collected samples. Serum sEVs were extracted from peripheral venous blood, and levels of MIR497HG, miR-195, miR-497, and PD-L1 in serum sEVs were detected by qPCR, and clinical information was recorded. Our study revealed that the levels of MIR497HG, miR-195, miR-497 and PD-L1 in serum sEVs showed periodic changes; the time from peak to trough was approximately 4-5 days. The levels of sEV MIR497HG and miR-195 had a positive linear relationship with SOFA score (r values were -0.181 and -0.189; p values were 0.048 and 0.039, respectively). The recorded quantities of sEV MIR497HG, miR-195 and PD-L1 showed a substantial correlation with ARDS. ROC curve analysis revealed that sEV MIR497HG, miR-195 and miR-497 could predict the 28-day mortality of sepsis patients with an AUC of 0.66, 0.68 and 0.72, respectively. Levels of sEVs MIR497HG, miR-195, miR-497 and PD-L1 showed periodic changes with the immune status of sepsis, which provides a new exploration direction for immune function biomarkers and immunotherapy timing in sepsis patients.

Association between serum sodium and 28-day mortality in sepsis patients: A secondary data analysis from three large critical illness cohorts.

The present study was designed to explore the association between serum sodium and mortality in patients with sepsis by using a large sample, multicenter MIMIC-IV database. We extracted the data of 34 925 sepsis patients from the retrospective cohort mimicIV database. After adjusting the confounders, we explored the independent effects of serum sodium on 28-day mortality. A nonlinear relationship existed between serum sodium and 28-day mortality, of which a negative association was found between serum sodium and 28-day mortality (odds ratio: 0.95, 95% CI: 0.94, 0.96, p = 0.0001) when serum sodium was in 102 mmol/L to 138 mmol/L, but a positive correlation appeared when sodium climbed to the range of 140-179 mmol/L (odds ratio: 1.04, 95% CI: 1.03-1.06, p = 0.0001). Both lower and higher serum sodium levels are associated with an increased risk of death in sepsis patients.

Clinical application of serum NLRP3 on the diagnosis and prognosis of sepsis patients complicated with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a common complication of sepsis, which significantly increases the mortality rate. This work explored the diagnostic value of serum NOD-like receptor family pyrin domain containing 3 (NLRP3) concentration in patients with sepsis for ARDS, and the predictive value of serum NLRP3 concentration at the time of diagnosis for death 28 days after treatment. A total of 150 sepsis patients were included in this study, including age-matched two groups of patients, 75 patients with ARDS and 75 patients without ARDS. In addition, 60 age-matched healthy patients with physical examination were recruited in this study. Serum NLRP3 concentration was determined by enzyme-linked immunosorbent assay (ELISA). The diagnostic values of serum NLRP3 concentration for ARDS in sepsis patients were evaluated by receiver operating characteristics (ROC) analysis. Correlation of serum NLRP3 with APACHE II score and SOFA were performed by Spearman correlation analysis. Pulmonary infection, APACHE II score and serum NLRP3 concentration were risk factors for patients with sepsis complicated with ARDS. ROC curve results showed that the specificity of serum NLRP3 concentration was 74.67%, the sensitivity was 76.00%, and the area under the curve (AUC) was 0.82 (p<0.001). APACHE II score and SOFA were significantly positively correlated with serum NLRP3 concentration. Baseline serum NLRP3 levels had significant predictive value for 28-day mortality in sepsis patients complicated with ARDS. Serum NLRP3 concentration has clinical value in the diagnosis of sepsis complicated with ARDS.

Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis.

The impact of lipid-lowering medications on sepsis is still not well defined. A Mendelian randomization (MR) study was carried out to probe the causal connections between genetically determined lipids, lipid-reducing drugs, and the risk of sepsis. Data on total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and triglycerides (TG) were retrieved from the MR-Base platform and the Global Lipids Genetics Consortium in 2021 (GLGC2021). Our study categorized sepsis into two groups: total sepsis and 28-day mortality of sepsis patients (sepsis28). The inverse-variance weighted (IVW) method was the primary method used in MR analysis. Cochran's Q test and the MR-Egger intercept method were used to assess the heterogeneity and pleiotropy. In the MR analysis, we found that ApoA-I played a suggestively positive role in protecting against both total sepsis (OR, 0.863 per SD increase in ApoA-I; 95% CI, 0.780-0.955; P = 0.004) and sepsis28 (OR, 0.759; 95% CI, 0.598-0.963; P = 0.023). HDL-C levels were also found to suggestively reduce the incidence of total sepsis (OR, 0.891 per SD increase in HDL-C; 95% CI, 0.802-0.990; P = 0.031). Reverse-MR showed that sepsis28 led to a decrease in HDL-C level and an increase in TG level. In drug-target MR, we found that HMGCR inhibitors positively protected against total sepsis (, 0.719 per SD reduction in LDL-C; 95% CI, 0.540-0.958; P = 0.024). LDL-C and HDL-C proxied CETP inhibitors were found to have a protective effect on total sepsis, with only LDL-C proxied CETP inhibitors showing a suggestively protective effect on sepsis28. In Mediated-MR, BMI exhibited a negative indirect effect in HMGCR inhibitors curing sepsis. The indirect impact of ApoA-I explained over 50% of the curative effects of CETP inhibitors in sepsis. Our MR study suggested that ApoA-I and HDL-C protected against sepsis, while HMGCR and CETP inhibitors showed therapeutic potential beyond lipid-lowering effects. ApoA-I explained the effects of CETP inhibitors. Our study illuminates how lipids affect sepsis patients and the effectiveness of new drugs, opening new avenues for sepsis treatment.

Early Lactate/Albumin and Procalcitonin/Albumin Ratios as Predictors of 28-Day Mortality in ICU-Admitted Sepsis Patients: A Retrospective Cohort Study.

BACKGROUND Lactate/albumin (LA/ALB) and procalcitonin/albumin (PCT/ALB) ratios have been implicated in predicting mortality in sepsis patients. However, their prognostic value and relationship to sepsis severity require further investigation. This retrospective study aimed to assess the prognostic value of lactate/albumin (LA/ALB) and procalcitonin/albumin (PCT/ALB) ratios in septic patients admitted to the Intensive Care Unit (ICU). MATERIAL AND METHODS A total of 340 adult sepsis patients admitted to the ICU were included in the derivation cohort. LA/ALB and PCT/ALB ratios were calculated and analyzed in relation to sepsis severity and survival status. Additionally, a validation cohort of 75 sepsis patients from another medical center was selected. RESULTS In the derivation cohort, higher LA/ALB and PCT/ALB ratios and SOFA scores were significantly associated with increased mortality (P<0.001). The LA/ALB and PCT/ALB ratios positively correlated with SOFA score. Survival analysis revealed significantly higher 28-day mortality in sepsis patients with elevated PCT/ALB (≥0.256) and LA/ALB (≥0.079) ratios upon ICU admission. The constructed prediction model incorporating LA/ALB ratio, PCT/ALB ratio, and SOFA score yielded an AUC of 0.826, demonstrating good predictive ability. The associations between LA/ALB and PCT/ALB ratios and 28-day mortality in sepsis patients were validated in the validation cohort. CONCLUSIONS The LA/ALB and PCT/ALB ratios at ICU admission provide valuable prognostic information for predicting 28-day mortality in sepsis patients. Combining these ratios with SOFA score improves the assessment of prognosis in sepsis patients.

The correlation of hemoglobin and 28-day mortality in septic patients: secondary data mining using the MIMIC-IV database

BackgroundPrevious studies found minimal evidence and raised controversy about the link between hemoglobin and 28-day mortality in sepsis patients. As a result, the purpose of this study was to examine the association between hemoglobin and 28-day death in sepsis patients by analyzing the Medical Intensive Care IV (MIMIC-IV) database from 2008 to 2019 at an advanced medical center in Boston, Massachusetts.MethodsWe extracted 34,916 sepsis patients from the MIMIC-IV retrospective cohort database, using hemoglobin as the exposure variable and 28-day death as the outcome variable, and after adjusting for confounders (demographic indicators, Charlson co-morbidity index, SOFA score, vital signs, medication use status (glucocorticoids, vasoactive drugs, antibiotics, and immunoglobulins, etc.)), we investigated the independent effects of hemoglobin and 28-day risk of death by binary logistic regression as well as two-piecewise linear model, respectively.ResultsHemoglobin levels and 28-day mortality were shown to be non-linearly related.The inflection points were 104 g/L and 128 g/L, respectively. When HGB levels were between 41 and 104 g/L, there was a 10% decrease in the risk of 28-day mortality (OR: 0.90; 95% CI: 0.87 to 0.94, p-value = 0.0001). However, in the range of 104–128 g/L, we did not observe a significant association between hemoglobin and 28-day mortality (OR: 1.17; 95% CI: 1.00 to 1.35, P value = 0.0586). When HGB was in the range of 128–207 g/L, there was a 7% increase in the risk of 28-day mortality for every 1 unit increase in HGB (OR: 1.07; 95% CI: 1.01 to 1.15, P value = 0.0424).ConclusionIn patients with sepsis, baseline hemoglobin was related to a U-shaped risk of 28-day death. When HGB was in the range of 12.8–20.7 g/dL, there was a 7% increase in the risk of 28-day mortality for every 1 unit increase in HGB.

Association between base excess and 28-day mortality in sepsis patients: A secondary analysis based on the MIMIC- IV database

ObjectiveThe relationship between base excess (BE) and 28-day death in sepsis patients remains to be elucidated. The aim of our clinical study is to explore the association of BE with 28-day mortality in patients with sepsis by using a large sample, multicenter Medical Information Mart for Intensive Care IV (MIMIC-IV) database. MethodsWe extracted the data of 35,010 patients with sepsis from the MIMIC-IV database, in which we used BE as an exposure variable and the 28-day mortality as an outcome variable, respectively, so as to explore the impact of BE on the 28-day mortality of patients with sepsis after adjusting for covariates. ResultsBE and the 28-day mortality of patients with sepsis appeared to have a U-shaped relationship. The calculated inflection points were −2.5 mEq/L and 1.9 mEq/L, respectively. Our data demonstrated that BE was negatively associated with 28-day mortality in the range of −41.0 mEq/L to −2.5 mEq/L (odds ratio: 0.95; 95% confidence intervals (95%CI): 0.93 to 0.96), p < 0.0001. When BE was in the range of 1.9 mEq/L to 55.5 mEq/L, however, a positive association existed between BE and 28-day mortality of patients with sepsis (odds ratio: 1.03; 95% CI: 1.00 to 1.05; p < 0.05). ConclusionThe BE levels have a U-shaped relationship with the 28-day mortality in patients with sepsis, in which the mortality of patients will gradually decrease with a BE value from −41.0 mEq/L to −2.5 mEq/L, while the mortality will increase with a BE value from 1.9 mEq/L to 55.5 mEq/L.

Value of IL-1β and IL-23 in Predicting 28-Day Mortality Due to Sepsis: A Retrospective Study.

BACKGROUND This research aimed to explore the utility of Interleukin-1ß (IL-1ß) and IL-23 as potential biomarkers for the diagnosis and prognosis of sepsis. MATERIAL AND METHODS This study included 74 adult individuals with sepsis, 45 ICU controls, and 50 healthy individuals attending routine physical examinations. IL-1ß and IL-23 levels were assessed and analyzed on the admission day. Univariate Cox regression analyses were utilized to explore the association of IL-1ß and IL-23 with sepsis survival. Furthermore, receiver operating characteristic (ROC) analysis was employed to evaluate the value of IL-1ß and IL-23 to predict 28-day mortality due to sepsis. RESULTS Serum concentrations of IL-1ß and IL-23 were significantly higher in septic patients relative to healthy and ICU controls (P<0.001). IL-1ß and IL-23 levels in non-survivors were significantly higher than in survivors (P<0.001). IL-1ß (hazard ratio; HR=1.06, P<0.001) and IL-23 (HR=1.02, P=0.031) were independent risk variables for 28-day mortality in sepsis patients, which were strongly associated with the severity of sepsis. The area under the ROC curve for predicting 28-day fatality in sepsis was 0.66 for IL-1ß (P=0.024, 95% confidence interval; CI: 0.54-0.76) and 0.77 for IL-23 (P<0.001, 95% CI: 0.65-0.86). Furthermore, compared with low serum IL-1ß (<9.41 pg/mL) and IL-23 (<6.77 pg/mL) levels, septic patients with high serum IL-1ß (≥9.41 pg/mL) and IL-23 (≥6.77 pg/mL) levels had poorer survival. CONCLUSIONS Serum IL-1ß and IL-23 values were higher in patients with sepsis and are potential diagnostic and prognostic markers for sepsis, but this needs to be confirmed by prospective studies.

Predictive value of early lactate/albumin ratio in the prognosis of sepsis

To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis. A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed. A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95%CI) of lactate, albumin, and L/A were 0.794 (95%CI was 0.741-0.840), 0.589 (95%CI was 0.528-0.647), 0.807 (95%CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve. The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.