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BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available BMJ Open: first published as 10.1136/bmjopen-2019-031512 on 12 February 2020. Downloaded from BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] http://bmjopen.bmj.com/ on September 28, 2021 by guest. Protected copyright. BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-031512 on 12 February 2020. Downloaded from Relatively frequent rheumatic manifestations and autoantibodies in infective endocarditis: differentiating infective endocarditis from autoimmune disease is needed ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-031512 Article Type: Research Date Submitted by the 18-May-2019 Author: Complete List of Authors: Zhou, Zhuochao; Shanghai Jiao Tong University School of Medicine, ; Ye, Junna Teng, Jialin Liu, Honglei Cheng, Xiaobing Sun, Yue Su, Yutong Chi, Huihui Wang, Fan Yang, Chengde; Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital Jin, Wei http://bmjopen.bmj.com/ Infective endocarditis, Rheumatic manifestation, ANCA, Antiphospholipid Keywords: antibody on September 28, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 23 BMJ Open 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-031512 on 12 February 2020. Downloaded from 4 5 6 7 8 9 I, the Submitting Author has the right to grant and does grant on behalf of all authors of the Work (as defined 10 in the below author licence), an exclusive licence and/or a non-exclusive licence for contributions from authors 11 who are: i) UK Crown employees; ii) where BMJ has agreed a CC-BY licence shall apply, and/or iii) in accordance 12 with the terms applicable for US Federal Government officers or employees acting as part of their official 13 duties; on a worldwide, perpetual, irrevocable, royalty-free basis to BMJ Publishing Group Ltd (“BMJ”) its 14 licensees and where the relevant Journal is co-owned by BMJ to the co-owners of the Journal, to publish the 15 Work in this journal and any other BMJ products and to exploit all rights, as set out in our licence. 16 17 The Submitting Author accepts and understands that any supply made under these terms is made by BMJ to 18 the Submitting Author Forunless you peer are acting as review an employee on behalf only of your employer or a postgraduate 19 student of an affiliated institution which is paying any applicable article publishing charge (“APC”) for Open 20 Access articles. Where the Submitting Author wishes to make the Work available on an Open Access basis (and 21 intends to pay the relevant APC), the terms of reuse of such Open Access shall be governed by a Creative 22 Commons licence – details of these licences and which Creative Commons licence will apply to this Work are set 23 out in our licence referred to above. 24 25 Other than as permitted in any relevant BMJ Author’s Self Archiving Policies, I confirm this Work has not been 26 accepted for publication elsewhere, is not being considered for publication elsewhere and does not duplicate 27 material already published. I confirm all authors consent to publication of this Work and authorise the granting 28 of this licence. 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on September 28, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 23 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-031512 on 12 February 2020. Downloaded from 4 Relatively frequent rheumatic manifestations and 5 6 7 autoantibodies in infective endocarditis: 8 9 10 differentiating infective endocarditis from 11 12 autoimmune disease is needed 13 14 15 16 17 Zhuochao Zhou1,*, Junna Ye1,*, Jialin Teng1, Honglei Liu1, Xiaobing Cheng1, Yue 18 For peer review only 19 1 1 1 1 1,# 2,# 20 Sun , Yutong Su , Huihui Chi , Fan Wang , Chengde Yang , Wei Jin 21 22 23 24 25 1Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong 26 27 University School of Medicine; 28 29 30 2Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School 31 32 33 of Medicine 34 35 36 37 http://bmjopen.bmj.com/ 38 *These authors contributed equally to this work. 39 40 41 42 43 #Correspondence: 44 45 on September 28, 2021 by guest. Protected copyright. 46 Wei Jin, MD, PhD 47 48 Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of 49 50 51 Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai 200025, China. 52 53 Tel.: +86 21 64370045; 54 55 56 Fax: +86 21 34186000; 57 58 59 E-mail: [email protected] 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 23 BMJ Open 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-031512 on 12 February 2020. Downloaded from 4 5 6 7 Chengde Yang, MD, PhD 8 9 Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong 10 11 12 University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, 13 14 Shanghai 200025, China. 15 16 17 Tel.: +86 21 64370045; 18 For peer review only 19 20 Fax: +86 21 34186000; 21 22 E-mail: [email protected] 23 24 25 26 27 28 29 30 31 32 33 Abstract 34 35 Objective: This study aimed to characterize rheumatic manifestations and 36 37 http://bmjopen.bmj.com/ 38 auto-antibodies of 432 patients diagnosed with infective endocarditis (IE). 39 40 Design, setting and participants: A retrospective study was conducted in Ruijin 41 42 43 Hospital from 1997 to 2017. The clinical and laboratory characteristics of a total of 44 45 on September 28, 2021 by guest. Protected copyright. 46 432 patients were analyzed. Besides, the differences between patients with positive 47 48 and negative antineutrophil cytoplasmic antibody (ANCA) and anti-phospholipid 49 50 51 antibody (aPL), as well as survival rate of these patients, were compared. 52 53 Results: 432 patients with 278 male patients and 154 female patients were included. 54 55 56 The mean age of patients was 45.61±16.12 years. At last, 346 patients (80.09%) had 57 58 59 cardiac surgery and 55 patients (12.73%) died in the hospital. Among IE patients, 104 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 23 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-031512 on 12 February 2020. Downloaded from 4 of them were either tested ANCA or aPL, and were analyzed in different groups. 5 6 7 Interestingly, positive ANCA patients were all of proteinase 3(PR3)-ANCA. 8 9 Compared with ANCA-negative group, patients with positive ANCA had higher IgM 10 11 12 (P=0.048), lower hemoglobin (P=0.001), more presentation of arthritis (P=0.003), and 13 14 more serositis (P=0.06). However, IE patients with positive aPL had higher level of 15 16 17 erythrocyte sedimentation rate (ESR) compared to aPL-negative group (P=0.003). In 18 For peer review only 19 20 addition, survival rate of ANCA-positive IE patients was lower (P=0.032) than 21 22 ANCA-negative group, while there was no difference in patients with or without aPL 23 24 25 antibody (P=0.728). 26 27 Conclusion: The present study supports the claim that atypical rheumatic 28 29 30 manifestations and presentation of antibodies are frequent in patients with IE and lead 31 32 33 to early misdiagnosis. Physicians should pay more attention to the measurement of 34 35 autoantibodies in these patients. 36 37 http://bmjopen.bmj.com/ 38 39 40 Keywords: infective endocarditis, rheumatic manifestation, ANCA, aPL 41 42 43 44 45 on September 28, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 Strengths and limitations of this study 53 54 55 1. The study analyzed the differences and survival rate between patients with and 56 57 without ANCA or aPL antibodies in IE patients, which were not analyzed together 58 59 60 before. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 23 BMJ Open 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-031512 on 12 February 2020. Downloaded from 4 2. In patients who tested both ANCA and aPL, positive LAC and proteinase 5 6 7 3(PR3)-ANCA were the most common types. 8 9 3.
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