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      COVID-19 in posttransplant patients—report of 2 cases

      case-report

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          Abstract

          Coronavirus Disease 2019 (COVID-19) has become a pandemic since March 2020. We describe here 2 cases of COVID-19 infection in a posttransplant setting. First one is a 59-year-old renal transplant recipient; the second is a 51-year-old allogeneic bone marrow transplant recipient. Both patients were on immunosuppressant therapy and had stable graft function before COVID-19 infection. After the diagnosis of COVID-19, immunosuppressive agents were discontinued and methylprednisolone with prophylactic antibiotics were initiated, however, the lung injury progressed. The T cells were extremely low in both patients after infection. Both patients died despite the maximal mechanical ventilatory support. Therefore, the prognosis of COVID-19 pneumonia following transplantation is not optimistic and remains guarded. Lower T cell count may be a surrogate for poor outcome.

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          Mechanisms of action of cyclosporine.

          Satoshi Matsuda, Shigeo Koyasu (2000)
          Cyclosporine (cyclosporin A, CsA) has potent immunosuppressive properties, reflecting its ability to block the transcription of cytokine genes in activated T cells. It is well established that CsA through formation of a complex with cyclophilin inhibits the phosphatase activity of calcineurin, which regulates nuclear translocation and subsequent activation of NFAT transcription factors. In addition to the calcineurin/NFAT pathway, recent studies indicate that CsA also blocks the activation of JNK and p38 signaling pathways triggered by antigen recognition, making CsA a highly specific inhibitor of T cell activation. Here we discuss the action of CsA on JNK and p38 activation pathways. We also argue the potential of CsA and its natural counterparts as pharmacological probes.
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            Does the evidence support the use of mycophenolate mofetil therapeutic drug monitoring in clinical practice? A systematic review.

            J. D. Morris, Daniel Knight (2008)
            The use of mycophenolate mofetil (MMF) as a primary immunosuppressant after transplantation is increasing. A number of factors interact to result in variability in blood levels of mycophenolic acid (MPA) increasing the risk of toxicity. This has led to interest in the application of therapeutic drug monitoring to optimize its use. A systematic literature search was performed using Medline, Embase, the Cochrane Central Registry of Clinical Trials, the Transplant Library, and clinical trial registries for studies investigating the clinical role of MMF pharmacokinetic drug monitoring. Studies relating monitoring regimens to clinical outcomes were included. The majority of studies are retrospective in nature, demonstrating good correlation between the full total MPA area-under-the-curve and the risk of acute rejection, but not toxicity. Free MPA levels may better predict toxicity. Single-point parameters, in particular trough levels, show poor correlation with the risk of acute rejection and toxicity, and in prospective studies do not improve clinical outcomes. Limited sampling strategies using samples from the first few hours postdose allow good prediction of the full area-under-the-curve, and monitoring using these strategies may improve clinical outcomes. The current data regarding therapeutic monitoring of MMF is of limited quality. The most promising results to date come from limited sampling strategies, with benefit seen in one prospective randomized trial. Further prospective trials and longer follow-up are required to investigate the optimum sampling strategy and subsets of patients who may benefit from monitoring, but the current evidence in favor of monitoring is weak.
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              Mycophenolate mofetil: selective T cell inhibition.

              R G McMurray, V Harisdangkul (2002)
              Mycphenolate mofetil is a suppressor of T cell proliferation and adhesion. Its primary mode of action is inhibition of inosine monophosphate dehydrogenase, a purine salvage pathway required by T lymphocytes. Although the role of T cells in rheumatoid arthritis (RA) has been controversial, a preliminary report of mycophenolate mofetil's successful use in RA patients clearly suggests that its efficacious properties need further investigation. Its favorable risk/benefit ratio, a broad clinical experience in kidney transplantation, and its recent extension to other rheumatic diseases suggests that this new antirheumatic agent has significant therapeutic potential for suppression of synovial inflammation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Am J Transplant
                Journal ID (iso-abbrev): Am J Transplant
                Title: American Journal of Transplantation
                Publisher: American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc.
                ISSN (Print): 1600-6135
                ISSN (Electronic): 1600-6143
                Publication date PMC-release: 30 December 2022
                Publication date (Print): July 2020
                Publication date (Electronic): 30 December 2022
                Volume: 20
                Issue: 7
                Pages: 1879-1881
                Affiliations
                [ 1 ]Department of Liver Research Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
                [ 2 ]Department of Oncology, Fuzhou Pulmonary Hospital, Fuzhou, China
                [ 3 ]Department of Tuberculosis, the Third People’s Hospital of Yichang City, Yichang, China
                [ 4 ]Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
                [ 5 ]Department of Respiratory, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
                Author notes
                [* ] Correspondence Su Lin Email: sumer5129@fjmu.edu.cn
                Article
                Publisher Item ID: S1600-6135(22)22426-5
                DOI: 10.1111/ajt.15896
                PMC ID: 9800441
                PubMed ID: 32243697
                SO-VID: ceb39754-91db-4218-b47e-1a4903a94423
                Copyright © Copyright © 2020 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved. Published by Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 19 March 2020
                Date revision received : 19 March 2020
                Date accepted : 24 March 2020
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Transplantation
                Keywords: coronavirus,covid-19,transplantation
                Data availability:
                ScienceOpen disciplines: Transplantation
                Keywords: coronavirus, covid-19, transplantation

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