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      Nafamostat Mesylate Improved Survival Outcomes of Sepsis Patients Who Underwent Blood Purification: A Nationwide Registry Study in Japan

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          Abstract

          Nafamostat mesylate (NM) is a synthetic serine protease inhibitor that can be used as an anticoagulant during blood purification in critically ill patients, as well as a treatment for disseminated intravascular coagulation. Although NM has been reported to reduce the risk of bleeding during blood purification, its effect on survival outcomes of patients who received blood purification treatments is unclear. We hypothesized that administration of NM during blood purification can reduce mortality in patients with sepsis. A post hoc analysis was conducted on a nationwide retrospective registry that included data from 3195 sepsis patients registered at 42 intensive care units throughout Japan. We evaluated the effect of NM on hospital mortality and bleeding complications using propensity score matching in 1216 sepsis patients who underwent blood purification in the intensive care unit (ICU). Two-hundred-and-sixty-eight pairs of propensity score-matched patients who received NM and conventional therapy were compared. Hospital and ICU mortality rates in the NM group were significantly lower than those in the conventional therapy group. However, rates of bleeding complications did not differ significantly between the two groups. These data suggest that administration of NM improved the survival outcomes of sepsis patients who underwent blood purification in the ICU.

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          Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators.

          Little information is available regarding current practice in continuous renal replacement therapy (CRRT) for the treatment of acute renal failure (ARF) and the possible clinical effect of practice variation. Prospective observational study. A total of 54 intensive care units (ICUs) in 23 countries. A cohort of 1006 ICU patients treated with CRRT for ARF. Collection of demographic, clinical and outcome data. All patients except one were treated with venovenous circuits, most commonly as venovenous hemofiltration (52.8%). Approximately one-third received CRRT without anticoagulation (33.1%). Among patients who received anticoagulation, unfractionated heparin (UFH) was the most common choice (42.9%), followed by sodium citrate (9.9%), nafamostat mesilate (6.1%), and low-molecular-weight heparin (LMWH; 4.4%). Hypotension related to CRRT occurred in 19% of patients and arrhythmias in 4.3%. Bleeding complications occurred in 3.3% of patients. Treatment with LMWH was associated with a higher incidence of bleeding complications (11.4%) compared to UFH (2.3%, p = 0.0083) and citrate (2.0%, p = 0.029). The median dose of CRRT was 20.4 ml/kg/h. Only 11.7% of patients received a dose of > 35 ml/kg/h. Most (85.5%) survivors recovered to dialysis independence at hospital discharge. Hospital mortality was 63.8%. Multivariable analysis showed that no CRRT-related variables (mode, filter material, drug for anticoagulation, and prescribed dose) predicted hospital mortality. This study supports the notion that, worldwide, CRRT practice is quite variable and not aligned with best evidence.
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            Improving propensity score weighting using machine learning.

            Machine learning techniques such as classification and regression trees (CART) have been suggested as promising alternatives to logistic regression for the estimation of propensity scores. The authors examined the performance of various CART-based propensity score models using simulated data. Hypothetical studies of varying sample sizes (n=500, 1000, 2000) with a binary exposure, continuous outcome, and 10 covariates were simulated under seven scenarios differing by degree of non-linear and non-additive associations between covariates and the exposure. Propensity score weights were estimated using logistic regression (all main effects), CART, pruned CART, and the ensemble methods of bagged CART, random forests, and boosted CART. Performance metrics included covariate balance, standard error, per cent absolute bias, and 95 per cent confidence interval (CI) coverage. All methods displayed generally acceptable performance under conditions of either non-linearity or non-additivity alone. However, under conditions of both moderate non-additivity and moderate non-linearity, logistic regression had subpar performance, whereas ensemble methods provided substantially better bias reduction and more consistent 95 per cent CI coverage. The results suggest that ensemble methods, especially boosted CART, may be useful for propensity score weighting. (c) 2009 John Wiley & Sons, Ltd.
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              Classifying types of disseminated intravascular coagulation: clinical and animal models

              Disseminated intravascular coagulation (DIC) has a common pathogenesis in terms of persistent widespread activation of coagulation in the presence of underlying disease, but the degree of fibrinolytic activation often differs by DIC type. DIC with suppressed fibrinolysis is a DIC type usually seen in sepsis. Coagulation activation is severe, but fibrinolytic activation is mild. DIC with enhanced fibrinolysis is a DIC type usually seen in acute promyelocytic leukemia (APL). Both coagulation activation and fibrinolytic activation are severe. DIC with balanced fibrinolysis is a DIC type usually seen in solid tumors, with an intermediate pathogenesis between the above two types. In animal DIC models, lipopolysaccharide (LPS)-induced models are similar to suppressed-fibrinolytic-type DIC, whereas tissue factor (TF)-induced models are similar to enhanced fibrinolytic/balanced fibrinolytic DIC. Appropriate diagnosis and treatment may also differ depending on the DIC type.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                13 August 2020
                August 2020
                : 9
                : 8
                : 2629
                Affiliations
                [1 ]Department of Emergency and Critical Care Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan; hkamijo@ 123456shinshu-u.ac.jp (H.K.); kmori@ 123456shinshu-u.ac.jp (K.M.); qqichikawa@ 123456shinshu-u.ac.jp (M.I.); nittaken@ 123456shinshu-u.ac.jp (K.N.); imamura@ 123456shinshu-u.ac.jp (H.I.)
                [2 ]Department of Emergency Medicine, Saiseikai Kumamoto Hospital, 5-3-1 Chikami Minami-ku, Kumamoto 861-4193, Japan; ghhhj309@ 123456yahoo.co.jp
                Author notes
                [* ]Correspondence: kmochizuki@ 123456shinshu-u.ac.jp ; Tel.: +81-263-37-3018
                Author information
                https://orcid.org/0000-0002-8609-6634
                https://orcid.org/0000-0002-1914-486X
                Article
                jcm-09-02629
                10.3390/jcm9082629
                7464767
                32823637
                75f562ff-51f0-491b-94d3-df0625a37d24
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 July 2020
                : 11 August 2020
                Categories
                Article

                sepsis,blood purification,nafamostat mesylate,anticoagulant

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