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      Perioperative Dexmedetomidine Improves Outcomes of Kidney Transplant

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          Abstract

          Graft function is crucial for successful kidney transplantation. Many factors may affect graft function or cause delayed graft function (DGF), which decreases the prognosis for graft survival. This study was designed to evaluate whether the perioperative use of dexmedetomidine (Dex) could improve the incidence of function of graft kidney and complications after kidney transplantation. A total of 780 patients underwent kidney transplantations, 315 received intravenous Dex infusion during surgery, and 465 did not. Data were adjusted with propensity scores and multivariate logistic regression was used. The primary outcomes are major adverse complications, including DGF and acute rejection in the early post‐transplantation phase. The secondary outcomes included length of hospital stay (LOS), infection, overall complication, graft functional status, post‐transplantation serum creatinine values, and estimated glomerular filtration rate (eGFR). Dex use significantly decreased DGF (19.37% vs. 23.66%; adjusted odds ratio, 0.744; 95% confidence interval, 0.564–0.981; P = 0.036), risk of infection, risk of acute rejection in the early post‐transplantation phase, the risk of overall complications, and LOS. However, there were no statistical differences in 90‐day graft functional status or 7‐day, 30‐day, and 90‐day eGFR. Perioperative Dex use reduced incidence of DGF, risk of infection, risk of acute rejection, overall complications, and LOS in patients who underwent kidney transplantation.

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          Most cited references48

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          CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting.

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            KDIGO clinical practice guideline for the care of kidney transplant recipients.

            (2009)
            The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression, graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially on the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.
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              Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.

              Physiological anti-inflammatory mechanisms can potentially be exploited for the treatment of inflammatory disorders. Here we report that the neurotransmitter acetylcholine inhibits HMGB1 release from human macrophages by signaling through a nicotinic acetylcholine receptor. Nicotine, a selective cholinergic agonist, is more efficient than acetylcholine and inhibits HMGB1 release induced by either endotoxin or tumor necrosis factor-alpha (TNF-alpha). Nicotinic stimulation prevents activation of the NF-kappaB pathway and inhibits HMGB1 secretion through a specific 'nicotinic anti-inflammatory pathway' that requires the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). In vivo, treatment with nicotine attenuates serum HMGB1 levels and improves survival in experimental models of sepsis, even when treatment is started after the onset of the disease. These results reveal acetylcholine as the first known physiological inhibitor of HMGB1 release from human macrophages and suggest that selective nicotinic agonists for the alpha7nAChR might have therapeutic potential for the treatment of sepsis.
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                Author and article information

                Contributors
                hualiu@ucdavis.edu
                Journal
                Clin Transl Sci
                Clin Transl Sci
                10.1111/(ISSN)1752-8062
                CTS
                Clinical and Translational Science
                John Wiley and Sons Inc. (Hoboken )
                1752-8054
                1752-8062
                16 June 2020
                November 2020
                : 13
                : 6 ( doiID: 10.1111/cts.v13.6 )
                : 1279-1287
                Affiliations
                [ 1 ] Department of Anesthesiology The First Affiliated Hospital of Soochow University Suzhou Jiangsu China
                [ 2 ] Department of Anesthesiology and Pain Medicine University of California Davis Health Sacramento California USA
                [ 3 ] Department of Surgery University of California Davis Health Sacramento California USA
                [ 4 ] Department of Internal Medicine University of California Davis Health Sacramento California USA
                Author notes
                [*] [* ] Correspondence: Hong Liu ( hualiu@ 123456ucdavis.edu )

                Author information
                https://orcid.org/0000-0002-1454-4549
                https://orcid.org/0000-0003-3611-7131
                Article
                CTS12826
                10.1111/cts.12826
                7719359
                32506659
                1560d7a6-9861-4cf3-873e-7f121cbdc5bb
                © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 21 February 2020
                : 13 May 2020
                Page count
                Figures: 3, Tables: 2, Pages: 9, Words: 6731
                Funding
                Funded by: Department of Anesthesiology and Pain Medicine
                Funded by: Department of Surgery , open-funder-registry 10.13039/100008237;
                Funded by: Department of Internal Medicine of University of California Davis Health
                Funded by: University of California , open-funder-registry 10.13039/100005595;
                Funded by: Davis Health
                Categories
                Article
                Research
                Articles
                Custom metadata
                2.0
                November 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.5 mode:remove_FC converted:06.12.2020

                Medicine
                Medicine

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