Purpose: Early lactate clearance is an important parameter for prognosis assessment and therapy control in sepsis. Patients with a lactate clearance >0% might differ from patients with an inferior clearance in terms of intensive care management and outcomes. This study analyzes a large collective with regards to baseline risk distribution and outcomes. Methods: In total, 3299 patients were included in this analysis, consisting of 1528 (46%) ≤0% and 1771 (54%) >0% patients. The primary endpoint was intensive care unit (ICU) mortality. Multilevel logistic regression analyses were used to compare both groups: A baseline model (model 1) with lactate clearance as a fixed effect and ICU as a random effect was installed. For model 2, patient characteristics (model 2) were included. For model 3, intensive care treatment (mechanical ventilation and vasopressors) was added to the model. Models 1 and 2 were used to evaluate the primary and secondary outcomes, respectively. Model 3 was only used to evaluate the primary outcomes. Adjusted odds ratios (aORs) with respective 95% confidence intervals (CI) were calculated. Results: The cohorts had no relevant differences regarding the gender, BMI, age, heart rate, body temperature, and baseline lactate. Neither the primary infection focuses nor the ethnic background differed between both groups. In both groups, the most common infection sites were of pulmonary origin, the urinary tract, and the gastrointestinal tract. Patients with lactate clearance >0% evidenced lower sepsis-related organ failure assessment (SOFA) scores (7 ± 6 versus 9 ± 6; p < 0.001) and creatinine (1.53 ± 1.49 versus 1.80 ± 1.67; p < 0.001). The ICU mortality differed significantly (14% versus 32%), and remained this way after multivariable adjustment for patient characteristics and intensive care treatment (aOR 0.43 95% CI 0.36–0.53; p < 0.001). In the additional sensitivity analysis, the lack of lactate clearance was associated with a worse prognosis in each subgroup. Conclusion: In this large collective of septic patients, the 6 h lactate clearance is an independent method for outcome prediction.

Altered plasma sphingosine-1-phosphate (S1P) concentrations are associated with clinical manifestations of atherosclerosis. However, whether long-term elevation of endogenous S1P is pro- or anti-atherogenic remains unclear. Here, we addressed the impact of permanently high S1P levels on atherosclerosis in cholesterol-fed apolipoprotein E-deficient (ApoE^−/−) mice over 12 weeks. This was achieved by pharmacological inhibition of the S1P-degrading enzyme S1P lyase with 4-deoxypyridoxine (DOP). DOP treatment dramatically accelerated atherosclerosis development, propagated predominantly unstable plaque phenotypes, and resulted in frequent plaque rupture with atherothrombosis. Macrophages from S1P lyase-inhibited or genetically deficient mice had a defect in cholesterol efflux to apolipoprotein A-I that was accompanied by profoundly downregulated cholesterol transporters ATP-binding cassette transporters ABCA1 and ABCG1. This was dependent on S1P signaling through S1PR3 and resulted in dramatically enhanced atherosclerosis in ApoE^−/−/S1PR3^−/− mice, where DOP treatment had no additional effect. Thus, high endogenous S1P levels promote atherosclerosis, compromise cholesterol efflux, and cause genuine plaque rupture.

Purpose: Although a moderate proportion of cardiac arrest (CA) patients achieve a return of spontaneous circulation (ROSC), few survive to discharge, mostly with poor neurological development. As serum phosphate levels were described as elevated after cardiopulmonary resuscitation (CPR), we asked whether these elevations would predict a higher risk of mortality and impaired neurological outcome in CA patients following ROSC. Methods: Initial serum phosphate levels, survival, and neurologic status at discharge of 488 non-traumatic CA patients treated at a single German hospital after achieving ROSC were analyzed. The cut-off value of phosphate for mortality prediction was determined using the receiver operator characteristic (ROC) curve, and patients were divided accordingly for comparison. Results were validated by analyzing phosphate levels in a multi-centric cohort containing 3299 CA patients from the eICU database of the United States. Results: In the German cohort, ROC analysis showed a 90% specificity for phosphate levels >2.7 mmol/L to predict mortality (AUC: 0.76, p < 0.0001), and phosphate level elevations were associated with higher in-hospital mortality (crude odds ratio 3.04, 95% CI 2.32 to 4.08). Patients with initial phosphate levels >2.7 mmol/L had significantly higher mortality in both analyzed collectives (p < 0.0001). Similarly, patients from the German cohort who initially had higher phosphate levels also showed a higher proportion of impaired neurological status at discharge and morphological signs of brain injury. Conclusions: In CA patients following ROSC, initial serum phosphate levels >2.7 mmol/L predict higher mortality and impaired neurological outcome. Our data suggests that phosphate determination might improve the preciseness of the overall and neurologic prognostication in patients after CPR following ROSC.

Background: The search for the best therapeutic approach in cardiopulmonary resuscitations (CPR) remains open to question. In this study, we evaluated if Amiodarone administration during CPR was associated with short-term mortality or neurological development. Methods: A total of 232 patients with sudden cardiac arrest (CA) with shockable rhythms were included in our analysis. Propensity score matching based on age, gender, type of CA, and CPR duration was used to stratify between patients with and without Amiodarone during CPR. Primary endpoints were short-term mortality (30-day) and neurological outcomes assessed by the cerebral performance category. Secondary endpoints were plasma lactate, phosphate levels at hospital admission, and the peak Neuron-specific enolase. Results: Propensity score matching was successful with a caliper size used for matching of 0.089 and a sample size of n = 82 per group. The 30-day mortality rates were similar between both groups (p = 0.24). There were no significant differences in lactate levels at hospital admission and during the following five days between the groups. Patients receiving Amiodarone showed slightly higher phosphate levels at hospital admission, while the levels decreased to a similar value during the following days. Among CA survivors to hospital discharge, no differences between the proportion of good neurological outcomes were detected between the two groups (p = 0.58), despite slightly higher peak neuron-specific enolase levels in CA patients receiving Amiodarone (p = 0.03). Conclusions: Amiodarone administration is not associated with short-term mortality or neurological outcomes in CA patients with shockable rhythms receiving CPR.