No abstract

Recently, augmented renal clearance (ARC), which accelerates glomerular filtration of renally eliminated drugs thereby reducing the systemic exposure to these drugs, has started to receive attention. However, the clinical features associated with ARC are still not well understood, especially in the Japanese population. This study aimed to evaluate the clinical characteristics and outcomes of ARC patients with infections in Japanese intensive care unit (ICU) settings. We conducted a retrospective observational study from April 2013 to May 2017 at two tertiary level ICUs in Japan, which included 280 patients with infections (median age 74 years; interquartile range, 64–83 years). We evaluated the estimated glomerular filtration rate (eGFR) at ICU admission using the Japanese equation, and ARC was defined as eGFR >130 mL/min/1.73 m2. Multivariable logistic regression analysis was performed to identify the independent risk factors for ARC and to determine if it was a predictor of ICU mortality. In addition, a receiver operating curve (ROC) analysis was performed, and the area under the ROC (AUROC) was determined to examine the significant variables that predict ARC. In total, 19 patients (6.8%) manifested ARC. Multivariable logistic regression analysis identified younger age as an independent risk factor for ARC (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.91–0.96). However, ARC was not found to be a predictor of ICU mortality (OR, 0.57; 95% CI, 0.11–2.92). In addition, the AUROC of age was 0.79 (95% CI, 0.68–0.91), and the optimal cut off age for ARC was ≤63 years (sensitivity, 68.4%; specificity, 78.9%). The incidence of ARC was, therefore, low among patients with infections in the Japanese ICUs. Although younger age was associated with the incidence of ARC, it was not an independent predictor of ICU mortality.

Our previous study suggested that plasminogen activator inhibitor‐1 (PAI‐1) levels of ≥83 ng/mL were associated with poor outcomes in patients with sepsis. The results indicate that high PAI‐1 levels (≥83 ng/mL) were associated with increased risks of coagulopathy, organ failure, and mortality. Patients with sepsis and PAI‐1 levels of ≥83 ng/mL tended to develop disseminated intravascular coagulation within 1 week after the sepsis diagnosis.

The purpose of this study was to classify patients with severe COVID-19 into more detailed risk groups using coagulation/fibrinolysis, inflammation/immune response, and alveolar/myocardial damage biomarkers, as well as to identify prognostic markers for these patients. These biomarkers were measured every day for eight intensive care unit days in 54 adult patients with severe COVID-19. The patients were classified into survivor (n = 40) and non-survivor (n = 14) groups. Univariate and multivariate analyses showed that the combined measurement of platelet count and presepsin concentrations may be the most valuable for predicting in-hospital death, and receiver operating characteristic curve analysis further confirmed this result (area under the curve = 0.832). Patients were consequently classified into three groups (high-, medium-, and low-risk) on the basis of their cutoff values (platelet count 53 × 103/µL, presepsin 714 pg/mL). The Kaplan–Meier curve for 90-day survival by each group showed that the 90-day mortality rate significantly increased as risk level increased (P < 0.01 by the log-rank test). Daily combined measurement of platelet count and presepsin concentration may be useful for predicting in-hospital death and classifying patients with severe COVID-19 into more detailed risk groups.

Background: C-type lectin-like receptor 2 (CLEC-2) is a platelet-activated receptor expressed on the surface of platelet membranes. Soluble CLEC-2 (sCLEC-2) has been receiving attention as a predictive marker for thrombotic predisposition, such as cerebral or myocardial infarction. In the present study, we examined the relationship between sCLEC-2 level and degree of coagulation disorder, especially platelet activation, in sepsis patients. Methods: Seventy sepsis patients were enrolled and divided into two groups, sepsis-induced disseminated intravascular coagulation (DIC) (SID) group (n=44) and non-SID group (n=26), at the time of intensive care unit admission. In addition, 37 healthy adult volunteers were enrolled as a control group. The sCLEC-2 levels were measured and compared among the groups. Because we suspected that the sCLEC-2 level was likely to be affected by the platelet count, we also calculated the sCLEC-2/platelet count ratio (termed C2PAC index) in the groups. We further divided the sepsis patients into four groups using the Japanese Acute Medical Association (JAAM) DIC scoring system (DIC scores: 0–1, 2–3, 4–5, 6–8) and investigated the C2PAC indexes in the healthy volunteers and the four JAAM DIC score groups. Finally, we examined whether the C2PAC index could be a predictor of DIC by receiver-operating curve (ROC) analysis.Results: The C2PAC indexes in the healthy volunteers, non-SID group, and SID group were 0.34±0.14, 1.2±0.5, and 2.6±1.7, respectively. The index was significantly higher in the non-SID and SID groups compared with the healthy volunteers and also significantly higher in the SID group compared with the non-SID group (all P<0.001). The C2PAC indexes in the healthy volunteers and the four JAAM DIC score groups were 0.3±0.1, 0.9±0.3, 1.1±0.3, 1.7±0.7, and 3.6±1.0, respectively. Furthermore, the C2PAC index increased significantly as the DIC score increased (P<0.001). According to the ROC analysis, the area under the curve and optimal cut-off value for the diagnosis of DIC were 0.80507 and 1.40 (sensitivity, 75.0%; specificity, 76.9%), respectively.Conclusions: The present findings suggest that evaluation of the C2PAC index may be a useful early predictor of sepsis-induced coagulopathy progression and DIC diagnosis in sepsis patients.Trial registration: This study was approved by the institutional ethics committees at Fukuoka University Hospital (U19-01-001), Yamanashi University Hospital (2289), and LSI Medience Corporation (Shindan/Narita 19-04).