BackgroundEndothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomarkers of coagulation and inflammation and to determine a significant predictor of AKI in patients with sepsis.MethodsWe conducted a single-center, retrospective, observational study on patients with sepsis fulfilling the Third International Consensus Definitions for Sepsis and Septic Shock criteria admitted to an adult intensive care unit (ICU) at a university hospital from June 2011 to December 2016. Levels of 13 biomarkers were measured on ICU admission, including markers of endothelial injury (soluble thrombomodulin [sTM], E-selectin, protein C, and plasminogen activator inhibitor-1 [PAI-1]) and markers of coagulation derangement (platelet count, fibrin degradation product [FDP], prothrombin time [PT], fibrinogen, α2-plasminogen inhibitor [α2-PI], antithrombin III [AT III], plasminogen, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex). All patients with sepsis were reviewed, and the development of AKI was evaluated. Multivariate logistic regression analysis was performed to identify significant independent predictive factors for AKI.ResultsOf the 514 patients admitted with sepsis, 351 (68.3%) developed AKI. Compared with the non-AKI group, all the endothelial biomarkers were significantly different in the AKI group (sTM [23.6 vs. 15.6 U/ml, P < 0.0001], E-selectin [65.5 vs. 46.2 ng/ml, P = 0.0497], PAI-1 [180.4 vs. 75.3 ng/ml, P = 0.018], and protein C [45.9 vs. 58.7 ng/ml, P < 0.0001]). Biomarkers of coagulopathy and inflammation, platelet counts, FDP, PT, α2-PI, AT III, plasminogen, and C-reactive protein were significantly different between the two groups. Multivariable logistic regression analysis showed that sTM was an independent predictive factor of AKI, with an AUROC of 0.758 (P < 0.0001).ConclusionsEndothelial biomarkers were significantly changed in the sepsis patients with AKI. Particularly, sTM was an independent predictive biomarker for the development of AKI that outperformed other coagulation and inflammation biomarkers as well as organ function in patients with sepsis.
IntroductionThe pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis.MethodsThis retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital. Two hundred five consecutive sepsis patients were stratified into four groups according to nadir platelet count: severe (nadir ≤40×103/μL), moderate (41–80×103/μL), or mild thrombocytopenia (81–120×103/μL), or normal-increased platelet count (>120×103/μL). The development of thrombocytopenia was assessed during the first week; mortality was assessed at day 28.ResultOf the 205 patients included, 61 (29.8%) developed severe thrombocytopenia. On admission, AIPC did not differ among the four groups. In patients with severe thrombocytopenia, AIPC decreased significantly from days 2 to 7, but remained within or above the normal range in the other three groups (overall group comparison, P<0.0001). Multivariate analysis including coagulation biomarkers revealed that AIPC was independently associated with the development of severe thrombocytopenia (day 3 AIPC, odds ratio 0.49 [95% confidence interval (CI) 0.35–0.66], P<0.0001; day 5 AIPC, 0.59 [95% CI 0.45–0.75], P<0.0001). AIPC was a significant predictor of 28-day mortality in Cox hazard models adjusted for Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores (day 3 AIPC, hazard ratio 0.70 [95% CI 0.52–0.89], P = 0.0029; day 5 AIPC, 0.68 [95% CI 0.49–0.87], P = 0.0012).ConclusionsThrombopoietic activity was generally maintained in the acute phase of sepsis. However, a decrease in AIPC after admission was independently associated with the development of severe thrombocytopenia and mortality, suggesting the importance of suppressed thrombopoiesis in the pathophysiology of sepsis-induced thrombocytopenia.
BackgroundCD86-CD28 interaction has been suggested as the principal costimulatory pathway for the activation and differentiation of naïve T cells in allergic inflammation. However, it remains uncertain whether this pathway also has an essential role in the effector phase. We sought to determine the contribution of CD86 on dendritic cells in the reactivation of allergen-specific Th2 cells.MethodsWe investigated the effects of the downregulation of CD86 by short interfering RNAs (siRNAs) on Th2 cytokine production in the effector phase in vitro and on asthma phenotypes in ovalbumin (OVA)-sensitized and -challenged mice.ResultsTreatment of bone marrow-derived dendritic cells (BMDCs) with CD86 siRNA attenuated LPS-induced upregulation of CD86. CD86 siRNA treatment impaired BMDCs’ ability to activate OVA-specific Th2 cells. Intratracheal administration of CD86 siRNA during OVA challenge downregulated CD86 expression in the airway mucosa. CD86 siRNA treatment ameliorated OVA-induced airway eosinophilia, airway hyperresponsiveness, and the elevations of OVA-specific IgE in the sera and IL-5, IL-13, and CCL17 in the bronchoalveolar lavage fluid, but not the goblet cell hyperplasia.ConclusionThese results suggest that local administration of CD86 siRNA during the effector phase ameliorates lines of asthma phenotypes. Targeting airway dendritic cells with siRNA suppresses airway inflammation and hyperresponsiveness in an experimental model of allergic asthma.
BackgroundWe hypothesized that the use of actual body weight might lead to more frequent misdiagnosis of acute kidney injury (AKI) than when ideal body weight is used in underweight and/or obese patients. We examined which definition of body weight is most effective in establishing a urinary diagnosis of AKI in septic patients.MethodsConsecutive patients aged ≥ 20 years admitted to the intensive care unit of a university hospital between June 2011 and December 2016 were analyzed. Sepsis was defined in accordance with the Sepsis-3 criteria. AKI was defined as a urinary output of < 0.5 mL/kg/6h during intensive care unit stay. Patients were divided into one of four body mass index-based classes. The severity of illness and 90-day mortality were compared across the body mass index subgroups in patients diagnosed using the actual body weight or ideal body weight.ResultsOf 5764 patients, 569 septic patients were analyzed. One hundred and fifty-three (26.9%) and 140 (24.6%) patients were diagnosed as having AKI using actual body weight and ideal body weight, respectively. There were no significant differences in the severity of illness among these groups. Also, 90-day mortality did not differ significantly among these groups. According to body mass index, 90-day mortality significantly differed in patients diagnosed using their actual body weights (underweight vs. normal vs. overweight vs. obese: 76.7% vs. 39.5% vs. 26.0% vs. 35.7%, P = 0.033).ConclusionGenerally, using actual body weight to calculate the weight-adjusted hourly urine output for diagnosing AKI increased the sensitivity compared to ideal body weight, irrespective of the severity of illness in septic patients. Delayed diagnosis, however, was more common among underweight patients in this situation, and clinicians should be cautious when diagnosing urinary AKI using actual body weight.
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