28-day Mortality In Septic Patients Research Articles

Establishment and assessment of mortality risk prediction model in patients with sepsis based on early-stage peripheral lymphocyte subsets.

This study is aimed to explore the value of lymphocyte subsets in evaluating the severity and prognosis of sepsis. The counts of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and NK cells significantly decreased between day 1 and day 3 in both the survivor and the non-survivor groups. The peripheral lymphocyte subsets (PLS) at day 1 were not significantly different between the survivor and the non-survivor groups. However, at day 3, the counts of lymphocytes, CD3+ T cells, CD4+ T cells, and NK cells were remarkably lower in the non-survivor group. No significant differences in CD8+ T cells, or CD19+ B cells were observed. The PLS index was independently and significantly associated with the 28-day mortality risk in septic patients (OR: 3.08, 95% CI: 1.18-9.67). Based on these clinical parameters and the PLS index, we developed a nomograph for evaluating the individual mortality risk in sepsis. The area under the curve of prediction with the PLS index was significantly higher than that from the model with only clinical parameters (0.912 vs. 0.817). Our study suggests that the decline of PLS occurred in the early stage of sepsis. The new novel PLS index can be an independent predictor of 28-day mortality in septic patients. The prediction model based on clinical parameters and the PLS index has relatively high predicting ability.

Obesity and septic patient outcomes: Shaping the puzzle through age and sex perspectives

While obesity has been reported as a protective factor in septic patients, little is known about the potential modifying effects of age and sex. The objective of this study is to investigate age and sex-specific associations between obesity and the prognosis of septic patients. A retrospective analysis was conducted on a cohort of 15,464 septic patients, categorized by body mass index (BMI) into four groups: underweight (<18.5kg/m2, n=483), normal (18.5-24.9kg/m2, n=4344), overweight (25-29.9kg/m2, n=4949) and obese (≥30kg/m2, n=5688). Multivariable logistic regression and inverse probability weighting were employed to robustly confirm the protective effect of a higher BMI on 28-day mortality, with normal weight serving as the reference category. Subgroup analyses based on age (young: 18-39, middle-aged: 40-64 and elderly: ≥65) and sex were performed. The findings demonstrate that high BMI independently confers a protective effect against 28-day mortality in septic patients. However, the relationship between BMI and 28-day mortality exhibits a non-linear trend, with a BMI of 34.5kg/m2 displaying the lowest odds ratio. Notably, the survival benefits associated with a high BMI were not observed in the young group. Moreover, being underweight emerges as an independent risk factor for middle-aged and elderly female patients, while in males it is only a risk factor in the elderly group. Interestingly, being overweight and obese were identified as independent protective factors in middle-aged and elderly male patients, but not in females. The effect of BMI on mortality in septic patients varies according to age and sex. Elderly individuals with sepsis may derive more prognostic benefits from obesity.

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.

Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis

BackgroundSepsis is defined as a life-threatening syndrome caused by an unbalanced host response to infection. The role of interleukin (IL)-36 cytokines binding to the IL-36 receptor (IL-36R) in host response during sepsis remains unknown.MethodsSerum IL-36 level was measured in 47 septic patients sampled on the day of intensive care unit (ICU) and emergency department admission, 21 non-septic ICU patient controls, and 21 healthy volunteers. In addition, the effects of IL-36R deletion on host inflammatory response in cecal ligation and puncture (CLP)-induced polymicrobial sepsis was determined.ResultsOn the day of ICU and emergency department admission, the patients with sepsis showed a significant increase in serum IL-36 levels compared with ICU patient controls and healthy volunteers, and the serum IL-36 levels were related to the severity of sepsis. Non-survivors of septic patients displayed significantly lower serum IL-36 levels compared with survivors. A high serum IL-36 level in ICU and emergency department admission was associated with 28-day mortality, and IL-36 was found to be an independent predictor of 28-day mortality in septic patients by logistic regression analysis. Furthermore, IL-36R deletion increased lethality in CLP-induced polymicrobial sepsis. Septic mice with IL-36R deletion had higher bacterial load and demonstrated more severe multiple organ injury (including lung, liver, and kidney) as indicated by clinical chemistry and histopathology. Mechanistically, IL-36R ligands released upon lung damage activated IL-36R+lung fibroblasts thereby inducing expression of the antimicrobial protein lipocalin 2. Moreover, they induced the apoptosis of lung epithelial cells.ConclusionsSeptic patients had elevated serum IL-36 levels, which may correlate with disease severity and mortality. In experimental sepsis, we demonstrated a previously unrecognized role of IL-36R deletion in increasing lethality.

Altered Ex Vivo NLRP3 Inflammasome Activation Is Associated with 28-Day Mortality in Septic Patients.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to infection. In this context, the aberrant activation of the NLRP3 inflammasome has been documented mostly through the measurement of increased plasmatic concentrations of IL-1β and IL-18. At the cellular level, contradictory results have been published. However, no study has comprehensively monitored NLRP3 inflammasome activation at the basal level and after ex vivo reactivation of whole blood monocytes and neutrophils focusing on ICU patients with bacterial and viral sepsis, including a longitudinal analysis. Thus, we conducted a prospective longitudinal study, examining NLRP3 inflammasome functionality in COVID-19 ICU patients (n = 15) and bacterial septic shock patients (n = 17) during the first week of ICU hospitalization, compared with healthy donors. Using two whole-blood flow cytometry assays, we detected ASC speck-positive monocytes (i.e., monocytes presenting the polymerization of ASC proteins) and activated caspase-1 in polymorphonuclear cells as read-outs, both at baseline and following nigericin stimulation, a drug that forms pores and activates the NLRP3 inflammasome. Our findings showed that, at baseline and regardless of the type of infection, patients exhibited reduced ASC speck-positive monocytes and decreased activated caspase-1 in PMN compared to healthy volunteers. This decrease was prominent at day 0. Following nigericin stimulation, this reduction was also observed and persisted throughout the first week of hospitalization, irrespective of the cellular population or parameter being considered. Notably, at day 0, this diminished activation and response to stimulation of NLRP3 was associated with a higher 28-day mortality rate. Consequently, our observations highlighted a concurrent decline in both basal expression and ex vivo activation of the NLRP3 inflammasome in circulating myeloid cells from patients with bacterial and viral sepsis in association with increased mortality.

Clinical implications of endotoxin activity and Polymyxin-B hemoperfusion in critically ill patients with septic cardiomyopathy: A single-center, retrospective, observational study.

To explore the association between endotoxin activity (EA) and septic cardiomyopathy (SCM), the relationship between endotoxin removal by Polymyxin-B hemoperfusion (PMX-HP) and recovery from SCM (R-SCM), and the correlation between R-SCM and the 28-day mortality in septic patients admitted to the intensive care unit (ICU). Observational study that included patients admitted to two ICUs of a tertiary university hospital between April 2011 and December 2019, who received PMX-HP for sepsis/septic shock. The SCM and R-SCM were assessed by transthoracic echocardiography. Among 148 patients, SCM was diagnosed in 60 (46%) of them and had no relationship with median EA (SCM group: 0.73; no-SCM group: 0.66, p = 0.48). Recovery from SCM was observed in 24 patients (49%) and was independently associated with the PMX-HP (OR 4.19, 95%CI [1.22, 14.3]; p = 0.02) and the SAPS2 II score (OR 0.94, 95%CI [0.9, 0.98]; p = 0.006). In the SCM group, the 28-day mortality was 60% and was independently predicted by R-SCM (OR 0.02, 95%CI [0.001, 0.3] p = 0.005) and SAPS II score (OR 1.11, 95%CI [1.01, 1.23] p = 0.037). In septic patients, EA was not associated with SCM. However, endotoxin removal by Polymyxin-B hemoperfusion was associated with recovery from cardiomyopathy, which was a predictor of lower 28-day mortality.

U-SHAPED ASSOCIATION BETWEEN SERUM CALCIUM LEVELS AND 28-DAY MORTALITY IN PATIENTS WITH SEPSIS: A RETROSPECTIVE ANALYSIS OF THE MIMIC-III DATABASE.

Background: Serum calcium levels disorder have been reported to be associated with poor prognosis in different diseases. Studies on the association between serum calcium and outcomes of septic patients remained limited. The aim of this study is to investigate the association between serum calcium and 28-day mortality in septic patients. Method: Patients diagnosed with sepsis in the Medical Information Mart for Intensive Care III database were included. Patients were divided into five groups according to the quintiles of serum calcium levels, and their baseline characteristics were compared. Multivariate Cox regression models were used to assess the association between serum calcium and 28-day mortality. Smooth curve fitting and segmented regression models were used to visualize the association between serum calcium levels and 28-day mortality risk. The 28-day survival probability between five groups was analyzed using Kaplan-Meier curves. Results: A total of 3,016 patients with sepsis were enrolled, and the 28-day mortality rate was 35.64%. After adjusting for confounders, compared with the reference quintile (Q4: 9.00-9.50), the lowest serum calcium level quintile (Q1: 5.70-8.20) was independently associated with an increased risk of 28-day mortality (hazard ratio [HR], 2.12; 95% CI, 1.76-2.56). Smooth spline fitting revealed a U-shaped association between serum calcium and 28-day mortality. When serum calcium was <9.0 mg/dL, 28-day mortality risk increased by 58% per unit decrease in serum calcium (HR, 0.42; 95% CI, 0.37-0.48). When serum calcium was >9.0 mg/dL, the 28-day mortality risk increased by 12% per unit increase in serum calcium (HR, 1.12; 95% CI, 1.04-1.20). Conclusion: A U-shaped association was observed between serum calcium levels and 28-day mortality in septic patients. Lower or higher serum calcium levels were associated with increased risk of 28-day mortality in septic 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.

DEVELOPMENT OF A MACHINE LEARNING MODEL FOR PREDICTING 28-DAY MORTALITY OF SEPTIC PATIENTS WITH ATRIAL FIBRILLATION.

Introduction: Septic patients with atrial fibrillation (AF) are common in the intensive care unit accompanied by high mortality. The early prediction of prognosis of these patients is critical for clinical intervention. This study aimed to develop a model by using machine learning (ML) algorithms to predict the risk of 28-day mortality in septic patients with AF. Methods: In this retrospective cohort study, we extracted septic patients with AF from the Medical Information Mart for Intensive Care III (MIMIC-III) and IV database. Afterward, only MIMIC-IV cohort was randomly divided into training or internal validation set. External validation set was mainly extracted from MIMIC-III database. Propensity score matching was used to reduce the imbalance between the external validation and internal validation data sets. The predictive factors for 28-day mortality were determined by using multivariate logistic regression. Then, we constructed models by using ML algorithms. Multiple metrics were used for evaluation of performance of the models, including the area under the receiver operating characteristic curve, sensitivity, specificity, recall, and accuracy. Results: A total of 5,317 septic patients with AF were enrolled, with 3,845 in the training set, 960 in the internal testing set, and 512 in the external testing set, respectively. Then, we established four prediction models by using ML algorithms. AdaBoost showed moderate performance and had a higher accuracy than the other three models. Compared with other severity scores, the AdaBoost obtained more net benefit. Conclusion: We established the first ML model for predicting the 28-day mortality of septic patients with AF. Compared with conventional scoring systems, the AdaBoost model performed moderately. The model established will have the potential to improve the level of clinical practice.

Assessment of 28-day survival of patients with sepsis based on vitamin D status: a hospital-based prospective cohort study in Indonesia.

sepsis is a potentially life-threatening condition caused by the body´s response to an infection. Recent studies have demonstrated a correlation between low vitamin D status and high mortality in septic patients. This study aims to evaluate the vitamin D status of septic patients at Dr. Sardjito Hospital and describe 28-day survival with very low vitamin D levels (< 8.1 ng/mL). this prospective cohort study was conducted in the intensive care unit and internal medicine ward at Dr. Sardjito Hospital in septic patients admitted between December 2018 and October 2019. Vitamin D [25(OH)D] was prospectively measured within 24 hours of admission. Data collection used SPSS software for statistical analysis. In addition, the sample size was calculated using the sample size formula used in a comparative survival study intended to find the incidence rate in septic patients. The minimum sample for each group is 23 samples. sepsis-related mortality was higher in patients with low vitamin D. The analysis included 88 septic patients during the study period. The mean age was 56.09 ± 16.82 years and the proportion of males was 46.6%. 26 of 28 patients with vitamin D levels < 8.1 ng/mL died (92.6%), whereas 39 of 60 patients with vitamin D levels ≥ 8.1 ng/mL (65%) died. Multivariate Cox regression analysis showed that vitamin D concentrations < 8.1 ng/mL at admission (p=0.01) and sepsis shock (p=0.02) were associated with increased sepsis mortality. The hazard ratio of 28-day mortality was 1.95 (95% CI 1.15-3.29, p=0.01) for vitamin D levels < 8.1 ng/mL. The average survival was 9 days for patients with vitamin D levels < 8.1 ng/mL (median: 6 days) compared with 14 days for those with vitamin D levels ≥ 8.1 ng/mL (median: 10 days). low serum vitamin D levels (< 8.1ng/mL) at admission were associated with increased 28-day mortality in septic patients.

Combined Serum NGAL and Fetuin A to Predict 28-Day Mortality in Patients with Sepsis and Risk Prediction Model Construction.

It was to investigate the predictive value of NGAL and Fetuin-A for 28-day mortality in patients with sepsis, and to construct a mortality risk prediction model. 120 patients admitted to The Affiliated Hospital of Xuzhou Medical University Hospital were grouped. Serum biochemical parameters were measured and scale scores were performed. The patient data were divided into a training set and test set in a ratio of 7:3, and the logistic regression model and random forest model were included to evaluate the 28-day mortality prediction efficacy of each index and model. The results showed that WBC, PLT, RBCV, and PLR decreased, SCr, Lac, PCT, D-dimer, NPR, NGAL, and Fetuin-A increased, APACHE II scale, SOFA scale, and OASIS scale scores increased in the death group (P < 0.05). SCr ≥ 408 μmol/L, Lac ≥ 2.3 mmol/L, PCT ≥ 30 ng/mL, D-dimer ≥ 2.33 mg/L, PLR ≥ 190, APACHE II ≥ 18 points, SOFA ≥ 2, OASIS ≥ 30, NGAL ≥ 352 mg/L, and Fetuin-A ≥ 0.32 g/L were found to be risk factors for 28-day death, while WBC ≥ 12 × 109/L, PLT ≥ 172 × 103/μL, and RBCV ≥ 30% were found to be protective factors for 28-day mortality. The predicted AUCs of APACHE II, SOFA, OASIS, NGAL, Fetuin-A, NGAL & Fetuin-A, logistic regression model, and random forest model were 0.80, 0.71, 0.77, 0.69, 0.86, 0.92, 0.83, and 0.81. NGAL combined with Fetuin-A has good prediction efficacy in 28-day mortality in septic patients.

Predictive Value of Combination of Procalcitonin and Predisposition, Infection, Response, and Organ Dysfunction (PIRO) System in Septic Patients with Positive Blood Cultures in the Emergency Department.

PurposeProcalcitonin and predisposition, infection, response, and organ dysfunction (PIRO) system have high predictive value for the prognosis of critically ill patients. There are few studies on the predictive value of patients with positive blood cultures. The aim of the study was to evaluate risk stratification and sepsis-related mortality in patients with positive blood cultures via procalcitonin (PCT) combined with the PIRO system in emergency departments (ED).MethodsA total of 1074 patients with positive blood cultures were admitted to Beijing Chao-Yang Hospital ED from December 2017 to October 2020. Their serum PCT was recorded, along with a Sequential Organ Failure Assessment (SOFA) score, Mortality in Emergency Department Sepsis (MEDS) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and PIRO score to predict the prognosis of septic patients with positive blood culture in terms of ICU (intensive care unit) admission, multiple organ dysfunction syndrome (MODS) development, and 28-day mortality. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to assess the prognostic value of the scoring systems.ResultsA total of 978 patients met the inclusion criteria. PCT, MEDS, APACHE II, and PIRO scores were found to independently predict ICU-admission, MODS development, and 28-day mortality (P<0.05), whereas SOFA did not. The AUC values of the PCT, MEDS, APACHE II, and PIRO scores for ICU-admission were 0.620, 0.740, 0.780, and 0.751, respectively. In the prediction of 28-day mortality, the AUC values of PCT, MEDS, APACHE II, and PIRO were 0.782, 0.745, 0.805, and 0.831, respectively. The AUC values combined PCT and PIRO system in predicting MODS and 28-day mortality were better than when predicting ICU-admission.ConclusionThis study indicates that PCT combined with the PIRO scoring system has a higher predictive value and is superior in predicting MODS and 28-day mortality in septic patients with positive blood cultures.

Independent risk factors of mortality in patients with sepsis receiving single-dose etomidate as an induction agent during rapid sequence intubation in a large tertiary emergency department in Thailand

BackgroundThere is limited evidence regarding factors associated with mortality in septic patients receiving etomidate. This study aimed to determine independent pre-intubation factors predicting 28-day mortality in septic patients receiving single-dose etomidate as an induction agent during rapid sequence intubation (RSI).MethodsThis single-center retrospective cohort study included intubated septic patients receiving etomidate as an induction agent during RSI in the emergency department of Siriraj hospital, Bangkok, Thailand, between January 1st, 2016 and June 30th, 2020. Pre-intubation characteristics were compared between survivors and non-survivors. Independent risk factors associated with 28-day mortality were identified using the Cox proportional hazards regression model. Association between etomidate dosage and mortality was also determined.ResultsA total of 344 patients, 238 (69%) survivors and 106 (31%) non-survivors, were included in the analyses. The initial Cox hazards model identified a pre-intubation lactate level ≥ 4 mmol/L as an independent factor associated with mortality (adjusted Hazards ratio [aHR] 2.66, 95% confidence interval [CI] 1.55–4.56). After removing lactate level from the model due to limited lactate values in the data, cancer was also predictive of 28-day mortality (aHR 1.83, 95%CI 1.10–3.04), while patients with respiratory infections and underlying chronic lung disease were associated with lower mortality (aHR 0.54, 95%CI 0.37–0.80 and aHR 0.57, 0.33–0.96, respectively). Etomidate dosage was not associated with mortality in our study.ConclusionIn septic patients who received a single dose of etomidate, a pre-intubation lactate level ≥ 4 mmol/L and cancer were associated with increased 28-day mortality, while respiratory infection and underlying chronic lung disease were associated with lower mortality. Physicians may take these factors into consideration when selecting induction agents for septic patients.

Risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) in sepsis patients.

Sepsis is a host response with life-threatening organ dysfunction caused by an infection. Although the overall mortality rate has increased from 30% to 37% by the surviving sepsis campaign, it is still not acceptable. Early identification, accurate stratification and appropriate intervention can improve the prognosis. In this study we assessed the risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) as a biomarker in sepsis patients. A total of 112 sepsis patients (38 patients with sepsis, 41 patients with severe sepsis, 33 patients with septic shock) and 25 healthy controls were enrolled in this study. Serum samples of all patients were collected and frozen before testing. Basic patient information was collected, including age, gender, primary infection, complications, and so on. Results of serum calcitonin, lactic acid, and SOFA score were followed up for 28 days. Levels of serum procalcitonin (PCT), serum lactate, Sequential Organ Failure Assessment (SOFA) score and sNGAL of sepsis patients were significantly higher (p<0.05) than those of controls. The sNGAL level in sepsis patients who were alive on the 28th day of follow-up was significantly lower (p<0.05) than that of sepsis patients who had died before the 28th day of follow-up. Multiple logistic regression analysis showed that sNGAL-0h and lactates were independent risk factors of death due to sepsis within 28 days. At cut-off value of 250 ng/mL, the sensitivity and specificity sNGAL-0h predicting the 28-day mortality in septic patients were 0.838 and 0.827, respectively. The sNGAL level in sepsis patients with acute kidney injury (AKI) was significantly higher (p<0.05) than in sepsis patients without AKI. Serum NGAL may contribute to the assessment of the severity of sepsis. Serum NGAL and lactate can be independent risk factors for 28-day mortality in sepsis patients. Serum NGAL has potential of predicting septic-AKI.

Lipocalin 10 as a New Prognostic Biomarker in Sepsis-Induced Myocardial Dysfunction and Mortality: A Pilot Study.

Introduction Sepsis-induced myocardial dysfunction (SIMD) is the most common complications of sepsis and septic shock with extremely high incidence and mortality. Lipocalin 10 (Lcn10) has recently been identified as a potential biomarker for heart failure, yet its relation to sepsis has not been investigated. The purpose of this study was to explore whether circulating Lcn10 could be used as a prognostic tool in patients with SIMD. Methods In this single-center observational pilot study, seventy-five sepsis patients were enrolled after sepsis diagnosis or ICU admission (45.3% female, median age 60 years), and 35 patients (46.7%) developed myocardial dysfunction. Serum Lcn10 levels of septic patients were measured using the enzyme-linked immunosorbent assay (ELISA) at the time of admission. Other biomarkers of cardiac function and Lcn10 concentration were compared between SIMD and non-SIMD groups. Results We observed that the median Lcn10 levels were 2.780 ng/mL in patients with SIMD and 2.075 ng/mL in patients without SIMD (P < 0.05). The area under the receiver operating characteristic (ROC) curve for the diagnosis of SIMD was 0.797 (P < 0.05). In addition, elevated serum Lcn10 levels at the time of admission were positively associated with 28-day mortality in septic patients. Conclusions Our study indicates that circulating Lcn10 levels may serve as a novel biomarker for the diagnosis and prognosis of myocardial dysfunction induced by sepsis. An additional large multicenter study may be warranted to confirm the findings of this study.

Interleukin-9 promotes intestinal barrier injury of sepsis: a translational research

BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Intestinal mucosal barrier injury is one of the important manifestations of sepsis. Interleukin-9 (IL-9) and IL-9-producing CD4(+) T cells were emerging pro-inflammatory mediators with development of intestinal injury. However, it is unclear whether IL-9 is related to the intestinal barrier injury of sepsis.MethodsTo investigate the roles of IL-9-producing CD4(+) T cells and IL-9 in the process of barrier injury in sepsis, serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were measured in septic patients and controls. The markers of barrier function in serum and intestinal tissue were also collected in septic rats. Moreover, the barrier injury degree and survival rate of septic rats were also investigated after increasing or interfering with IL-9 expression.ResultsThe serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were significantly higher in septic patients or rats than those in controls. IL-9-producing CD4(+) T cells and IL-9 levels were positively correlated with D-lactate levels and had a high predictive value of 28-day mortality in septic patients. The non-survivors had significantly higher serum T cell percentages, IL-9, and D-lactate levels compared with survivors. In septic rats, IL-9 increased the expression levels of D-lactate, whereas that decreased the expression levels of zonula occludens 1. Moreover, the barrier injury was aggravated or alleviated by increasing or interfering with IL-9 expression, respectively. Survival rate analysis also showed that IL-9 decreased the 14-day survival rate of septic rats.ConclusionIL-9 is closely related to intestinal mucosal barrier injury and mortality in sepsis. IL-9 blockade has the potential to improve the barrier injury in sepsis.Trial registrationThe study was registered at ClinicalTrials.gov (ID: NCT03791866, Date: December 2018).

The prognostic value of myoglobin difference in sepsis related chronic critical illness

Objective: To investigate the predictive value of myoglobin (Mb) for the prognosis of sepsis related chronic critical illness (CCI). Methods: Retrospective study was conducted on septic patients with the length of ICU stay equal or greater than 14 days, and sepsis-related organ failure assessment (SOFA) score equal or greater than 2 on the 14th day in ICU in the First Department of Critical Care Medicine at the First Affiliated Hospital of Sun Yat-sen University from January 2017 to March 2020. Patients' clinical and laboratory data were collected on the 1st and 14th day in ICU. The survival on day 28 in ICU was recorded. According to the myoglobin levels on day 1 and day 14, all subjects were divided into myoglobin elevation group and decline group. Kaplan-Meier survival curve was used to compare the cumulative survival rate at day 28. Cox regression analysis was used to analyze the independent risk factors of mortality. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of myoglobin. Results: A total of 131 patients with sepsis related CCI were recruited, including 58 patients in the elevation group and 73 in the decline group. The Mb level in elevation group on day 1 was significantly lower than that in decline group [172.40(59.99, 430.53) μg/L vs. 413.60(184.40, 1 328.50) μg/L, Z=3.749, P=0.000], and the Mb level on day 14 was the opposite change in two groups [483.65(230.38, 1 471.75)μg/L in elevation group vs. 132.20(76.86, 274.35)μg/L in decline group, Z=5.595, P=0.000]. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate of the elevation group was significantly lower than that of decline group (χ²=7.051, P=0.008). Cox ratio regression analysis suggested that elevated myoglobin was an independent risk factor for 28-day mortality in septic patients with CCI (OR=2.534, 95%CI 1.212-5.295, P=0.013). ROC curve analysis suggested that the sensitivity of myoglobin elevation in predicting mortality related to CCI within 28 days was 64.5%, and the specificity was 32.0% with area under the curve(AUC) 0.661(95%CI 0.550-0.773,P=0.007) and Jorden Index was 0.325. Conclusion: Elevated myoglobin, an independent risk factor for mortality within 28 days in ICU, can predict the prognosis of sepsis related chronic critical illness.

Effects of Neutrophil-to-Lymphocyte Ratio Combined With Interleukin-6 in Predicting 28-Day Mortality in Patients With Sepsis.

BackgroundThe current study aimed to evaluate the relationship between the neutrophil-to-lymphocyte ratio (NLR) combined with interleukin (IL)-6 on admission day and the 28-day mortality of septic patients.Material and MethodsWe conducted an observational retrospective study. Patients with presumed sepsis were included. We observed the correlation of studied biomarkers (NLR, IL-6, PCT, and CRP) and the severity scores (APACHE II and SOFA scores) by plotting scatter plots. The relationships of the studied biomarkers and 28-day mortality were evaluated by using Cox regression model, receiver-operating characteristic (ROC) curve, and reclassification analysis.ResultsA total of 264 patients diagnosed with sepsis were enrolled. It was revealed that IL-6 had the strongest correlation with both APACHE II and SOFA scores, followed by the NLR and PCT, and there was no obvious correlation between CRP and the illness severity. NLR and IL-6 were independent predictors of the 28-day mortality in septic patients in the Cox regression model [NLR, odds ratio 1.281 (95% CI 1.159–1.414), P < 0.001; IL-6, odds ratio 1.017 (95% CI 1.005–1.028), P=0.004]. The area under the ROC curve (AUC) of NLR, IL-6 and NLR plus IL-6 (NLR_IL-6) was 0.776, 0.849, and 0.904, respectively.ConclusionOur study showed that the levels of NLR and IL-6 were significantly higher in the deceased patients with sepsis. NLR and IL-6 appeared to be independent predictors of 28-day mortality in septic patients. Moreover, NLR combined with IL-6 could dramatically enhance the prediction value of 28-day mortality.

Predictive value of immune cell counts and neutrophil-to-lymphocyte ratio for 28-day mortality in patients with sepsis caused by intra-abdominal infection.

BackgroundThe current study aimed to evaluate the value of immune cell counts and neutrophil-to-lymphocyte ratio (NLR) when attempting to predict 28-day mortality.MethodsWe conducted an observational retrospective study that included consecutive septic patients. Severity scores on the first day and peripheral circulating immune cell counts (at day 1, day 3, day 5 and day 7 of admission) were collected during each patient’s emergency intensive care unit stay. We assessed the associations of peripheral circulating immune cell counts and NLR with the severity of illness. The relationships between 28-day mortality and peripheral circulating immune cell counts and NLR with were evaluated using Cox proportional cause-specific hazards models.ResultsA total of 216 patients diagnosed with sepsis caused by IAI were enrolled. The lymphocyte counts (days 1, 3, 5 and 7) and monocyte counts (days 3, 5 and 7) were significantly lower in non-survivors (n = 72) than survivors (n = 144). The NLR values at each time point were significantly higher in non-survivors. The day 1 lymphocyte counts, as well as the monocyte counts, were significantly lower in the highest-scoring group, when stratified by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, than in the other groups (p < 0.05). The day 1 NLR was significantly higher in the highest-scoring group than in the other groups (p < 0.05). The day 5 and day 7 lymphocyte counts, day 3 and day 7 monocyte counts and day 7 NLR were significant predictors of 28-day mortality in the Cox proportional hazards models (day 5 lymphocyte count: hazard ratio, 0.123 (95% CI, 0.055–0.279), p < 0.001; day 7 lymphocyte count: hazard ratio, 0.115 (95% CI, 0.052–0.254), p < 0.001; day 3 monocyte count: hazard ratio, 0.067 (95% CI, 0.005–0.861), p = 0.038; day 7 monocyte count: hazard ratio, 0.015 (95% CI, 0.001–0.158), p < 0.001; day 7 NLR: hazard ratio, 0.773 (95% CI, 0.659–0.905), p = 0.001).ConclusionsThe results showed that circulating lymphocytes and monocytes were dramatically decreased within 7 days in non-survivors following sepsis from an IAI. Lymphocyte counts, monocyte counts and NLR appeared to be associated with the severity of illness, and they may serve as independent predictors of 28-day mortality in septic patients with IAIs.

The prognostic role of the programmed death-1 expression on T lymphocytes in septic patients

Objective: To investigate the value of programmed death-1（PD-1） expression on the T lymphocytes for the prognosis of septic patients. Methods: From September 2017 to May 2019, septic patients were included in Department of Intensive Care Unit at 6 hospitals. The PD-1 expression on T cells were measured by flow cytometry. Logistic regression was conducted to analyze independent risk factors related to death within 28 days，and receiver operating characteristic curve(ROC) was conducted to evaluate the prognostic value of PD-1 expression on T cells in septic patients. Results: A total of 64 septic patients were enrolled to this study，including 32 survivors and 32 deaths. The PD-1 expression on T cells in the death group was significantly higher than that in the surviving group (P<0.05). Correlation analysis showed that the percentages of PD-1+/CD3+T cells and PD-1+/CD8+T cells were positively correlated with procalciton in (r=0.313, P =0.015；r=0.375, P=0.003), logistic regression analysis showed that the percentages of PD-1+/CD3+，PD-1+/CD4+，PD-1+/CD8+T cells were independent risk factors for the death of sepsis patients. The percentage of PD-1+/CD3+T cell was 3.63%, with AUC 0.842, sensitivity to predict the mortality 96.43% and specificity 59.38%, (P<0.000 1). The percentage of PD-1+/CD4+T cell was 4.65%, with AUC 0.847, sensitivity 96.43%, specificity 62.50%，(P<0.000 1). The percentage of PD-1+/CD8+T cell was 3.91%, with AUC 0.771, sensitivity 64.29%, specificity 81.25%，(P=0.000 3). Conclusions: The T cell PD-1 expression is an independent risk factor to predict the 28-day mortality in septic patients. Combining the proportions of PD-1+/CD3+, PD-1+/CD4+and PD-1+/CD8+T cells may further enhance the predictive value for death.