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.

Persistent inflammation and neuronal loss in the mouse brain induced by a modified form of attenuated herpes simplex virus type I.

Herpes simplex virus-1 (HSV-1) is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis (HSE) with a high mortality rate. Most patients present with changes in neurological and behavioral status, and survivors suffer long-term neurological sequelae. To date, the pathogenesis leading to brain damage is still not well understood. HSV-1 induced encephalitis in the central nervous system (CNS) in animals are usually very diffuse and progressing rapidly, and mostly fatal, making the analysis difficult. Here, we established a mouse model of HSE via intracerebral inoculation of modified version of neural-attenuated strains of HSV-1 (deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region), in which the LMR-αΔpA strain initiated moderate productive infection, leading to strong host immune and inflammatory response characterized by persistent microglia activation. This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage, amyloidosis, Alzheimer's disease, and neurodegeneration, eventually leading to neuronal loss and behavioral changes characterized by hypokinesia. Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled, mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.

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.

Intercellular adhension molecule-1 in the pathogenesis of heroin-induced acute lung injury in rats.

The expression of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of heroin-induced acute lung injury (ALI) in rats was investigated. The model of ALI was established by intravenous injection of heroin into tail vein in rats. Thirty-six rats were randomly divided into heroin-treated groups (1 h, 2 h, 4 h, 6 h and 24 h) and normal control group. Changes in histopathologic morphology and biological markers of ALI were measured. The expression of ICAM-1 in lung tissue was detected by using immunohistochemistry and RT-PCR. The results showed that the W/D ratio and protein contents in BALF of the heroin-treated groups were significantly higher than that of the, control group (P<0.01). The histopathological changes in the lung tissue were more obvious in heroin-treated groups. The ICAM-1 protein and mRNA expression in the lung tissue of heroin-treated groups were significantly increased as compared with that of the control group (P<0.01), and correlated with the ALI parameters in a time-dependent manner. Increasing of ICAM-1 expression was involved in the formation of heroin-induced lung injury. Furthermore, the level of expression was positively correlated with the severity of lung injury.