Inflammation enhanced by accumulation of reactive oxygen species plays an essential role in the progression of cardiovascular diseases. Using the 2D-oxyblot analysis and 2D-difference image gel electrophoresis (2D-DIGE), we compared the levels of ROS-induced carbonyl modification of myocardial proteins in the whole left ventricles between 6-week-old hamsters with dilated (TO-2) and hypertrophic cardiomyopathy (Bio14.6) and control hamsters (F1B). Then, 2D electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry detected 18 proteins with increased carbonyl level in cardiomyopathy hamsters compared with control hamster. Carbonyl modification of proteins related to ATP synthesis, including citric acid cycle and electron transport system, was observed in the hearts of hamsters with both types of cardiomyopathy. Further analysis indicated that left ventricular carbonyl production correlated negatively with succinyl-CoA:3-ketoacid-coenzyme A transferase 1 activity (r 2 = 0.60, P = 0.0007) and ATP concentration (r 2 = 0.29, P = 0.037), suggesting that protein carbonylation has negative effects on the levels of these biomolecules. Furthermore, carbonyl production significantly correlated with plasma Troponin T level (r 2 = 0.33, P = 0.026). Reduction of energy metabolism by oxidative damage may contribute to the development of left ventricular impairment in cardiomyopathy.

ObjectivesA few studies on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treatments have shown the therapeutic efficacy of mycophenolate mofetil (MMF). However, the therapeutic efficacy of MMF compared with that of cyclophosphamide (CYC) in patients with AAV has not been established. We conducted a systematic review and meta-analysis to assess the efficacy of MMF as a remission induction therapy in patients with AAV comparing it with the efficacy of CYC.MethodsWe searched randomised controlled trials (RCTs) comparing the efficacy of MMF with that of CYC in patients with AAV on three different websites: PubMed, Cochrane Library and Google Scholar. We compared the difference in the relative risk (RR) of each outcome based on a Mantel-Haenszel random-effects model.ResultsWe analysed data from four RCTs with 300 patients for the study. The 6-month remission rate (RR 1.09, 95% CI 0.86 to 1.38, p=0.48), the 6-month ANCA negativity (RR 1.31, 95% CI 0.91 to 1.90, p=0.15) and the long-term relapse rate (RR 1.36, 95% CI 0.80 to 2.31, p=0.26) were all similar between the two treatments. The rates of death, infection and leucopenia were also similar between the two groups (RR 1.05, 95% CI 0.40 to 2.74, p=0.93; RR 1.26, 95% CI 0.79 to 2.01, p=0.33; RR 0.45, 95% CI 0.16 to 1.32, p=0.15, respectively).ConclusionsWe found no difference between the therapeutic efficacy of MMF and that of CYC in patients with AAV. MMF may be an alternative remission induction therapy in patients with non-life-threatening AAV.

A 26-year-old woman with Takayasu's arteritis (TAK) experienced back and neck pain during tocilizumab (TCZ) treatment. The levels of C-reactive protein were normal, and ultrasonography revealed no significant changes. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) showed signal enhancement in the walls of several arteries. Contrast computed tomography showed arterial inflammation in the same lesion. After increasing the dose of prednisolone and TCZ, all signal enhancements decreased and continued to decrease, as observed on days 76 and 132. Thus, DWIBS may be a novel imaging modality for assessing the disease activity of TAK, particularly during follow-up.

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Given the hypothesis that inflammation plays a critical role in the progression of cardiovascular diseases, the aim of the present study was to identify new diagnostic and prognostic biomarkers of myocardial proteins involved in early-phase cardiac impairment, using proteomics analysis. Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression of proteins in the whole left ventricles between control hamsters, dilated cardiomyopathic hamsters (TO-2), and hypertrophy cardiomyopathic hamsters (Bio14.6) at 6 weeks of age (n = 6, each group). Proteomic analysis identified 10 protein spots with significant alterations, with 7 up-regulated and 3 down-regulated proteins in the left ventricles of both TO-2 and Bio 14.6 hamsters, compared with control hamsters. Of the total alterations, peroxiredoxin 2 (PRDX2) showed significant upregulation in the left ventricles of TO-2 and Bio 14.6 hamsters. Our data suggest that PRDX2, a redox regulating molecule, is involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.

We report the case of a 40-year-old patient with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) overlap syndrome with pulmonary arterial hypertension (overlap-PAH) that was successfully treated with a combination of immunosuppressive therapy and the soluble guanylate cyclase stimulator riociguat. She was diagnosed with mixed connective tissue disease (MCTD) two years prior to admission. She was admitted to our hospital with dyspnea on exertion and progressive skin sclerosis. She fulfilled both SLE and SSc classification criteria and was re-diagnosed with overlap syndrome. The tricuspid valve pressure gradient (TRPG) on echocardiography was 64 mmHg at admission. On right heart catheterization, mean pulmonary arterial pressure (mPAP) was 43 mmHg and pulmonary capillary wedge pressure was 15 mmHg. We diagnosed her with SSc-SLE overlap-PAH and started treatment with corticosteroids and intravenous cyclophosphamide. We also started treatment with riociguat because we speculated she had a component of SSc-PAH and that immunosuppressive therapy alone may be insufficient. We chose riociguat because of its favorable treatment effect on SSc-PAH. Two months after treatment, her TRPG improved to 33 mmHg and the skin sclerosis improved dramatically, suggesting the efficacy of multi-drug treatment and the importance of early intervention.

BackgroundSevere infections that complicate rheumatoid arthritis may cause significant morbidity and mortality. The Modified Health Assessment Questionnaire (MHAQ) is one of the scores most used for measuring the functional status of rheumatoid arthritis (RA) patients. However, the relationship between the MHAQ score and severe infection risk has not been well studied [1].ObjectivesTo examine the relationship between disease-associated functional status (MHAQ) and severe infection events (SIE) in rheumatoid arthritis patients.MethodsWe used data from the “MiRAi” cohort in Japan. In total, 2174 RA outpatients were examined at the Osaka Minami Medical Center between January 2012 and October 2017. The risk factors were identified and evaluated by multivariate logistic regression, linearity analysis. Interactions of SIE risk between MHAQ and treatment were also observed.ResultsThe cohort contributed to 8206 patient-years of follow-up. Overall, 251 SIEs were observed and the incidence of SIE was 3.0 infections per 100 patient-years. The mean age at first observation was 61.7 years and the mean disease duration was 10.3 years. The use of glucocorticoids (GCs), methotrexate (MTX), and biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs/tsDMARDs) was 59.2%, 63.8%, and 40.3%, respectively. The mean Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Scores of 28 joints (DAS28), and MHAQ at first observation were 9.76±6.39, 10.1±6.87, 2.67±0.96, and 0.43±0.58, respectively. Disease duration, the MHAQ score, and prednisolone dose (p=0.015, 0.007, and <0.001, respectively) were significantly associated with SIE risk (Figure). Age, sex, stage, bDMARDs/tsDMARDs use, DAS28-CRP, and MTX dose (mg/week) did not predict a significant increase in SIE. The risk of SIE increased linearly with the MHAQ. The SIE risk increased rapidly from 0 to 5 mg of prednisolone, and then increased gradually over 5 mg. The SIE risk peaked at around 20 years disease duration. No significant interaction between MHAQ and bDMARDs/tsDMARDs or glucocorticoid use were observed (p=0.307, 0.282, respectively).ConclusionAn increased MHAQ score was lineally associated with SIE, and did not show significant interactions with bDMARD/tsDMARD use or the oral glucocorticoid dose. Therefore, the MHAQ score is considered to be a strong, independent risk factor for infection in RA patients.Abstract THU0109 – Figure 1Reference[1] Yamanaka H, Askling J, Berglind N, Franzen S, Frisell T, Garwood C, Greenberg JD, Ho M, Holmqvist M, Novelli Horne L, et al: Infection rates in patients from five rheumatoid arthritis (R017, 3(2):e000498A) registries: contextualising an RA clinical trial programme. RMD Open 2017, 3(2):e000498.Disclosure of InterestsYuji Yoshida: None declared, Shiro Ohshima Grant/research support from: AbbVie, Eisai, Asahikasei, Speakers bureau: AbbVie, Eisai, Bristol-Meyers, Novartis, Astellas, Nippon-Kayaku, Pfizer, UCB, Ayumi, Daiichi-Sankyo, Takeda, Tanabe-Matsubishi, Chugai, Eri Oguro...

A 66-year-old woman with symptoms of fatigue and headache was diagnosed with giant cell arteritis (GCA). Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) revealed the strong accumulation of FDG in the descending aorta, abdominal aorta, bilateral subclavian artery, and total iliac artery. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) showed signal enhancement at the descending aorta and abdominal aorta. We repeated FDG-PET and DWIBS 2 months after the initiation of therapy with prednisolone. In line with the FDG-PET findings, the signal enhancement of the aortic wall completely vanished on DWIBS. DWIBS may be a novel useful tool for the diagnosis and follow-up of GCA treatment.