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      Effect of plasma exchange on in-hospital mortality in patients with pulmonary hemorrhage secondary to antineutrophil cytoplasmic antibody-associated vasculitis: A propensity-matched analysis using a nationwide administrative database

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      PLoS ONE
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          Abstract

          Background

          Secondary pulmonary hemorrhage increases the risk of mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV); plasma exchange therapy may improve outcomes in these patients. We conducted a retrospective cohort study to investigate the effect of plasma exchange therapy on short-term prognoses in patients with pulmonary hemorrhage secondary to AAV.

          Methods

          This study utilized the Diagnosis Procedure Combination database, which is a nationwide inpatient database in Japan. We checked the abstract data and medical actions and identified the patients with pulmonary hemorrhage secondary to AAV who required proactive treatment between 2009 and 2014. To compare the in-hospital mortality, we performed propensity score matching between the plasma exchange and non-plasma exchange groups at a ratio of 1:1.

          Results

          Of the 52,932 patients with AAV, 940 developed pulmonary hemorrhage as a complication. A total of 249 patients from 194 hospitals were eligible for the study. Propensity score matching at a ratio of 1:1 was performed, and 59 pairs were formed (plasma exchange group, n = 59; non-plasma exchange group, n = 59). A statistically significant difference was found in the all-cause in-hospital mortality between the plasma exchange and non-plasma exchange groups (35.6% vs. 54.2%; p = 0041; risk difference, −18.6; 95% confidence interval (CI), −35.4% to −0.67%).

          Conclusion

          Thus, plasma exchange therapy was associated with improved in-hospital mortality in patients with pulmonary hemorrhage secondary to AAV.

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          Most cited references23

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          Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology.

          In rheumatology and other medical specialties there is a discrepancy between the widespread use and the imprecise designation of glucocorticoid treatment regimens. Verbal descriptions of glucocorticoid treatment regimens used in various phases of diseases vary between countries and institutions. Given this background, a workshop under the auspices of the EULAR Standing Committee on International Clinical Studies including Therapeutic Trials was held to discuss this issue and to seek a consensus on nomenclature for glucocorticoid treatment. This report summarises the panel's discussion and recognises that answers derived from consensus conferences are not definitive. Nevertheless, recommendations on glucocorticoid treatment are presented that (1) reflect current and best knowledge available and (2) take into account current clinical practice. A question-answer rationale presentation style has been chosen to convey the messages, to summarise the meeting in a readable format, and to avoid dogmatism.
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            Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice.

            Antineutrophil cytoplasmic autoantibodies (ANCAs) are identified in the circulation of approximately 80% of patients with pauci-immune necrotizing and crescentic glomerulonephritis and systemic small vessel vasculitis, such as microscopic polyangiitis and Wegener granulomatosis. The most common antigen target for ANCAs is myeloperoxidase (MPO), which is found in neutrophils and monocytes. We report definitive experimental animal evidence that ANCAs are pathogenic. MPO knockout (Mpo(-/-)) mice were immunized with mouse MPO. Splenocytes from these mice or from control mice were injected intravenously into recombinase-activating gene-2-deficient (Rag2(-/-)) mice, which lack functioning B lymphocytes and T lymphocytes. All mice that received splenocytes developed mild to moderate glomerular immune deposits, but only mice that received 1 x 10(8) or 5 x 10(7) anti-MPO splenocytes developed severe necrotizing and crescentic glomerulonephritis, granulomatous inflammation, and systemic necrotizing vasculitis, including necrotizing arteritis and hemorrhagic pulmonary capillaritis. To test the pathogenic potential of antibodies alone, purified anti-MPO IgG or control IgG was injected intravenously into Rag2(-/-) mice and wild-type mice. Mice that received anti-MPO IgG but not mice that received control IgG developed focal necrotizing and crescentic glomerulonephritis with a paucity of glomerular Ig deposition. Thus, anti-MPO IgG alone was able to cause pauci-immune glomerular necrosis and crescent formation in the absence of functional T or B lymphocytes in Rag2(-/-) mice and in the presence of an intact immune system in wild-type C57BL/6J mice. This animal model offers strong support for a direct pathogenic role for ANCA IgG in human glomerulonephritis and vasculitis.
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              BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis.

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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                23 April 2018
                2018
                : 13
                : 4
                : e0196009
                Affiliations
                [1 ] Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School, Yushima, Bunkyo-ku, Tokyo, Japan
                [2 ] Division of Rheumatology, Tomishiro Central Hospital, Ueta, Tomigusuku-shi, Okinawa, Japan
                [3 ] Immuno-Rheumatology Center, St. Luke’s International Hospital, St. Luke’s International University, Akashi-cho Chuo-Ku, Tokyo, Japan
                Postgraduate Medical Institute, INDIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-1894-0290
                Article
                PONE-D-17-40447
                10.1371/journal.pone.0196009
                5912736
                29684034
                5efab029-126e-43e6-9818-8c74b9670d3b
                © 2018 Uechi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 November 2017
                : 4 April 2018
                Page count
                Figures: 1, Tables: 5, Pages: 12
                Funding
                Funded by: a Grant-in-Aid for Research on Policy Planning and Evaluation from the Ministry of Health, Labour, and Welfare, Japan
                Award ID: H28-Seisaku-Shitei-009
                Award Recipient :
                KF had a Grant-in-Aid for Research on Policy Planning and Evaluation from the Ministry of Health, Labour, and Welfare, Japan (H28-Seisaku-Shitei-009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Custom metadata
                DPC data contains anonymized patient data, but there is a possibility of identifying individuals by combining multiple pieces of information. Therefore there are some regulations to handle DPC data. This study was approved by the Ethics Committee, Tokyo Medical and Dental University Medical School which permits the use of data only for researchers participating in the DPC group. Consequently our data are not available for public release. However, processed data which we used in this study will be available for researchers who meet the criteria for data access. Requests to access the data should be submitted to DPC Research Institute, Address: 2-5-1-4113 Toyosu, Koto-ku, Tokyo 135-0061 Japan, E-mail: info@ 123456dpcri.or.jp .

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