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The purpose of this study is to investigate the effect of TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] in K/BxN serum transfer arthritis model and fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLS). In in vivo experiments, TSAHC attenuated the incidence and severity of arthritis in comparison with the vehicle group. Histological findings showed that TSAHC decreased the inflammation, bone erosion, cartilage damage, and osteoclasts activity in the ankle. Furthermore, we confirmed by biochemical analysis that the observations were associated with the decreased expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and RANKL in serum and ankle. In in vitro experiments, TSAHC induced apoptosis, while it significantly suppressed tumor necrosis factor-α (TNF-α)-induced cell proliferation in RA-FLS. Moreover, TSAHC inhibited mRNA expression of TNF-α-induced interleukin (IL)-6, MMP-1, MMP-3, and MMP-13. Evaluation of signaling events showed that TSAHC inhibited the translocation and transcriptional activity of nuclear factor-kappa B (NF-κB) by regulating phosphorylated-IκB-α (p-IκB-α) and IκB-α in TNF-α-induced RA-FLS. Our results suggest that TSAHC inhibits experimental arthritis in mice and suppresses TNF-α-induced RA-FLS activities via NF-κB pathway. Therefore, TSAHC may have therapeutic potential for the treatment of RA.

Background:Rheumatoid arthritis (RA) predominantly affects women and has a significant impact on childbearing. Several population-based studies identifying incidence, prevalence, and medication use of RA have been reported, yet epidemiological studies focusing on women with RA in childbearing years are missing.Objectives:We aimed to identify the incidence, prevalence and medication use of RA among Korean women in childbearing years.Methods:From National Health Insurance Service (NHIS) data (2009-2016), containing inpatient and outpatient claim information for approximately 97% of the Korean population, we identified 9,217,139 women aged between 20-44 years. Incidence and prevalence of RA in the specific sociodemographic group of women in childbearing age were analyzed, and the prevalence of medication prescription were compared between women with RA and controls without rheumatic diseases such as RA, systemic lupus erythematosus, and ankylosing spondylitis. Individuals with RA were defined by the presence of International Classification of Disease, 10th revision code, M05. The medication use was defined as receiving > 90days prescriptions of NSAIDs, corticosteroids (CSs), and conventional synthetic (cs) disease modifying antirheumatic drugs (DMARDs) or > 1day prescription of biologic (b) DMARDs.Results:Total 24,590 women with RA were identified. The average incidence of RA during 2011-2016 among women in childbearing years was 24.1/100,000 person-years (PYs) (95% CI 20.91-27.31) with a yearly increase from 20.99/100,000 PYs in 2011 to 28.38/100,000 PYs in 2016. The average prevalence of RA during 2009-2016 among women in childbearing years was 105.2/100,000 PYs (95% CI 99.0-111.5) with a minimum of 95.7/100,000 PYs in 2009 and a maximum of 110.5/100,000 PYs in 2016. There were increasing trends in both incidence and prevalence of RA according to age among women in childbearing years peaking in the age group of 40-44 years. The prescriptions of NSAIDs, CSs, csDMARDs and bDMARDs were more frequent in women with RA than controls (NSAIDs; 94.21% vs 21.79%, CSs; 83.65% vs 4.28%, csDMARDs; 91.23% vs 0.41%, bDMARDs; 0.11% vs 0%, pConclusion:The incidence and prevalence of RA are high among Korean women in childbearing years, and medication use was significantly more frequent in this specific population than controls. High disease burden is imposed upon women in childbearing years.References:[1] Won S, Cho SK, Kim D, Han M, Lee J, Jang EJ, Sung YK, Bae SC: Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization. Rheumatol Int 2018, 38(4):649-656.[2] Smeele HTW, Dolhain R: Current perspectives on fertility, pregnancy and childbirth in patients with Rheumatoid Arthritis. Seminars in arthritis and rheumatism 2019, 49(3s):S32-s35.Table 1.Medication use among women with RA and controls in childbearing age between 20-44 years during 2009-2016Control(n=155,486)RA(n=23,756)n(%)n(%)PNSAIDs33,887(21.79)22,380(94.21)Steroids6,653(4.28)19,871(83.65)csDMARDs634(0.41)21,673(91.23)bDMARDs0(0.00)27(0.11)RA, rheumatoid arthritis; NSAID, non-steroidal anti-inflammatory drug; cs, conventional synthetic; b, biologic; DMARDs, disease modifying antirheumatic drugsDisclosure of Interests:None declared

Background:Rheumatoid arthritis is a chronic systemic inflammatory disease known to be associated with many comorbidities. Many women with rheumatoid arthritis (RA) are diagnosed with the disease before completing childbearing, but the risk of comorbidities associated with RA among women in childbearing years is not known.Objectives:We aimed to investigate the risk of comorbidities among Korean women with RA in childbearing years.Methods:From National Health Insurance Service data of 2009-2016, containing inpatient and outpatient claim information for approximately 97% of the Korean population, we identified 20-44 year aged-women with RA and controls without rheumatic diseases such as RA, systemic lupus erythematosus, and ankylosing spondylitis. Prevalence of comorbidities including cancer (Ca), hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM) were analyzed. The rheumatic diseases and comorbidities were defined by International Classification of Disease (ICD)-10 codes for disease classifications. The comorbidities associated with RA were defined by the ICD-10 codes presented after the RA diagnosis.Results:Total 23,756 women with RA and 208,941 controls were identified. Women with RA had significantly higher prevalence of all comorbidities analyzed compared with the controls (49.92% vs 25.58%, pConclusion:During childbearing years, women with RA are more susceptible to comorbidities leading to a significant burden in this specific population of Korean women in childbearing years.References:[1]Dougados M: Comorbidities in rheumatoid arthritis. Current opinion in rheumatology 2016, 28(3):282-288.[2]Choi IA, Park SH, Cha HS, Park W, Kim HA, Yoo DH, Baek HJ, Lee SG, Lee YJ, Park YB et al: Prevalence of co-morbidities and evaluation of their monitoring in Korean patients with rheumatoid arthritis: comparison with the results of an international, cross-sectional study (COMORA). International journal of rheumatic diseases 2018, 21(7):1414-1422.Table 1.Risk of comorbidities associated with RA among Korean women in childbearing years during 2009-2016RA(n=23,756)Controls(n=208,941)p-valueOR95% CIn(%)n(%)Any comorbidities10,859(45.71)53,423(25.57)2.302.234-2.367 Ca1,235(5.20)8,845(4.23)1.141.072-1.217 DM1,885(7.93)12,606(6.03)1.221.155-1.285 HTN3,274(13.78)17,052(8.16)1.561.495-1.628 HLD8,046(33.87)34,672(16.60)2.442.367-2.516RA, rheumatoid arthritis; Ca, cancer; DM, diabetes mellitus; HTN, hypertension; HLD, hyperlipidemia; OR, odds ratio; CI, confidence intervalDisclosure of Interests:None declared

Background: Coronary artery anomalies (CAAs) are rare. Some anomalies are associated with myocardial ischaemia, heart failure and sudden cardiac death. Objectives: The aims of this study were to determine the incidence of CAAs detected on multidetector computed tomography (MDCT) and their clinical relevance. Methods: We reviewed our center’s MDCT database from January 2005 to December 2015. Results: 76 out of 5677 (incidence 0.01%) patients were reported to have CAAs. They consisted of 44 patients (57.9%) with anomalous origin of right coronary artery (RCA), 7 (9.2%) with anomalous origin of left coronary artery (LCA), 3 (3.9%) with anomalous origin of the left circumflex artery (LCX), 1 (1.3%) with abnormal course of LCX, 15 (19.7%) with coronary artery fistulas, 3 (3.9%) with single coronary artery, 3 (3.9%) with anomalous left coronary artery from pulmonary artery (ALCAPA).We were able to retrieved 26 patients’ (mean age 49 ± 13 years, 17 male) case folder. They consisted of 11 patients with anomalous origin of the RCA (10 from left coronary sinus), 4 with anomalous origin of LCA from right coronary sinus (3 interarterial course), 7 with coronary fistulas (2 large fistulas), 1 with single coronary artery (Lipton LII, anterior course) , 3 with ALCAPA. Out of the 26 patients, 24 (92.3%) were alive and 2 were lost to follow-up. The commonest presenting symptom was chest pain (65.4%), followed by dyspnea (34.6%) and heart failure (11.5%). 3 patients underwent surgery and 1 underwent transcatheter coiling of fistula. 4 patients had positive functional test (2 anomalous origin of RCA, 1 anomalous origin of LCA from right coronary sinus and 1 ALCAPA). Only 1 patient who had positive functional test underwent surgery. The remaining 3 who did not undergo surgery were still alive. The patient with single coronary artery presented with heart failure and remained alive with pharmacotherapy. All 3 ALCAPA patients were alive, with the oldest patient survived to age 71 years. None of them had surgery performed. Conclusions: CAAs are rare. Majority of cases may be benign. Largescale studies are needed to better define the prognosis and optimal treatment of individual forms of CAAs.

Background: High sensitivity troponin (hsTn) has better sensitivity for myocardial tissue injury detection compared to standard troponin assays, despite lower diagnostic specificity and lack of hsTn assay standardization. Objectives: To examine implications of introducing hsTnI in clinical practice. Methods: We retrospectively collected information of patients presented to a single tertiary cardiac referral centre with suspected acute coronary syndrome (ACS), who had ≥1 hsTnI sample (Abbott ARCHITECT STAT), from 1st June 2016-17th August 2016. Upper range limit (URL), i.e. 99th percentile, was defined as 34.2 ng/L, 15.6 ng/L and 26.2 ng/L for male, female and both gender (“overall”) respectively. Patients were divided into 4 groups - Group 1: hsTnURL but b3 times URL, Group 3: hsTn between 3-5 times URL and Group 4: hsTnN5 times URL. Results: Data from 366 patients was analysed: 227(62.0%), 34(9.3%), 13(3.6%), 92(25.1%) in Group 1, 2, 3 and 4 respectively. In Group 1 to 4, the proportion of ACS was 8.8%, 38.0%, 53.8%, 82.6% and proportion of MI were 0.8%, 29.4%, 53.8%. 82.6%. By using N5 times URL as cut-off, hsTnI has higher specificity and PPV, but lower sensitivity and NPV in diagnosis of ACS {(sensitivity:0.66, specificity:0.0.94, PPV0.83, NPV0.85), with ROC curve AUC:0.896, pb0.001, 95% CI:0.861-0.931}. Our analysis showed serial paired hsTn samples increase the PPV of hsTn to detect ACS. There was no significant difference between using hsTn URL “overall” or “gender-specific” for ACS diagnosis. Kaplan-Meier analysis showed 30-day all-cause mortality in the group with maximal hsTn value NURL is significant higher (pb0.001). Multiple-logistic regression showed that URL of hsTn was an independent variable for 30-day all-cause mortality (p

The average age of onset for obsessive-compulsive disorder (OCD) is between 20 and 25 years old [1], with only 8.6% of OCD occurring after age of 40, which is termed as late onset OCD [2]. Significant association has been found between OCD and obsessive-compulsive personality disorder (OCPD) [3] in which the age of onset of OCD is earlier [4] and OCD symptoms are more prominent and more severe [5,6].

It has been reported that hypertension carries a greater risk of myocardial infarction (MI) in South Asians living in the UK than in the indigenous British population. This has been attributed to some specifically Asian susceptibility factor.Using a longitudinal approach, we investigated the relationship between coronary heart disease (CHD) risk factors amongst hypertension patients attending Sandwell and City Hospitals, and the onset of cardiovascular events over a 5-year follow-up period.A total of 350 Caucasian (83.7% male) and 104 South Asian (66.3% male) patients with hypertension [age 63.7 (7.6) years and 57.1 (11.1) years respectively, P0.001] were followed-up for a mean (SD) period of 64.7(12.1) months. There were 11 (6.4/1000 patient years) cases of MI in Caucasian patients vs. 11 (17.8/1000 patient years) in South Asians, with event-free survival times being significantly lower amongst South Asians (log-rank test P = 0.04). The prevalence of diabetes mellitus was 22.9% higher amongst South Asians (P0.001), whilst mean serum cholesterol and fasting triglyceride levels were higher amongst Caucasians (P = 0.001). There were no ethnic differences in HDL cholesterol concentrations, the use of tobacco, statin therapy or anti-platelet therapies (all P = NS), or in composite endpoint (MI, angina, peripheral vascular disease, stroke, revascularization or death; P = 0.74). On Cox regression analysis of all independent cardiovascular risk variables, associated treatments and ethnicity, MI risk was associated with diabetes mellitus (odds ratio 3.77, 95%CI 1.55-9.15, P = 0.003) but not ethnicity per se (P = 0.26).Increased risk of MI in hypertensive South Asians in the United Kingdom appears to be the result of a higher prevalence of diabetes mellitus. Further work is required to understand the pathophysiological basis with which diabetes increases CHD risk in this ethnic group.

Background Orchardists are expected to show high prevalence of upper limb musculoskeletal disorders (MSDs) due to their heavy works and working postures. However, there are no systematic studies relating upper limb MSDs in Korean orchardists. Objectives To evaluate the prevalence and characteristics of upper limb MSDs among orchardists in rural areas of Korea. Methods The study was carried out from June 2013 to May 2014 in a tertiary medical center. The physical examinations of upper extremities were performed by rheumatologists, orthopedists, and rehabilitation medicine specialists. The plain radiographs of shoulder, elbow, and hand, nerve conduction examination of upper extremities, and MRI of both shoulder were taken. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was used to assess symptoms and function of upper extremities. Results Five hundred and fifty orchardists were included. Participants comprised of 49.5% female and 50.5% male with mean age of 59.5±8.1 years. The mean farming duration was 31.3±13.2 years. A total of 34 different types of upper limb MSDs were detected. The most frequent disorder was myofascial pain syndrome (80.5%) followed by rotator cuff syndrome (58.9%), hand osteoarthritis (58.0%), carpal tunnel syndrome (42.9%), and lateral epicondylitis (39.5%). Prevalence of any form of MSD was 98.5% and of three and more of MSDs was 77.3%. Participants with longer duration of farming had higher numbers of MSDs. Almost part of pruning and harvesting postures in orchard farming were loaded works for musculoskeletal systems. Total DASH score was relatively high (14.9±14.4). Conclusions Almost orchardists have upper limb MSDs. Our results suggest the need to implement interventions in orchardists to prevent MSDs. References Gomez MI, Hwang S, Stark AD, May JJ, Hallman EM, Pantea CI. An analysis of self-reported joint pain among New York farmers. J Agric Saf Health. 2003;9:143–157. Holmberg S, Stiernstrom EL, Thelin A, Svardsudd K. Musculoskeletal symptoms among farmers and non-farmers: A population based study. Int J Occup Environ Health. 2002;8:339–345. Osborne A, Blake C, Fullen BM, Meredith D, Phelan J, McNamara J, Cunningham C. Prevalence of musculoskeletal disorders among farmers: A systematic review. Am J Ind Med. 2012;55(2):143-58. Acknowledgements This study was supported by a grant of the Center for Farmer9s Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

showed decreased bone destruction on radiograph (3.4±0.3 vs. 2.0±0.2, p

Objectives The type III histone deacetylase SIRT1 is a critical molecule in the modulation of immune and inflammatory response through the deacetylation of various histones and non-histone proteins. However, there are limited and controversial data regarding the roles of SIRT1 in rheumatoid arthritis (RA) and its role in dendritic cells (DCs) remains unknown. Thus, this study sought to assess the role of SIRT1 in collagen-induced arthritis (CIA) using a myeloid cell-specific SIRT1 knockout (mSIRT1 KO) mouse. Methods mSIRT1 KO mice were generated using the loxP/Cre recombinase system. CIA was induced in mSIRT1 KO mice and age-matched littermate loxP control mice. Arthritis severity was assessed by clinical, radiological, and pathological scoring. The levels of various cytokines in the joints, serum, lymph nodes were determined by quantitative polymerase chain reaction and ELISA. T cells and DCs were quantified using flow-cytometry and in vitro T cell cytokines and DCs markers were also measured. Results The mSIRT1 KO mice showed significantly lower arthritis severity and joint destruction compared with control mice. The expression of inflammatory cytokines, MMPs, and ROR-γT was also reduced in mSIRT1 KO mice. These effects were paralleled by reduction of Th1, Th17, CD69-positive T cells, CD80, and CD86 positive DCs in mSIRT1 KO mice. In addition, in vitro studies showed that interferon-γ and IL-17 production by T cells and the maturation of DCs were significantly decreased in mSIRT1 KO mice. Conclusions Unlike passive K/BxN serum transfer arthritis, myeloid cell-specific deletion of SIRT1 was associated with lower arthritis severity in CIA by modulating DCs maturation and Th1 and Th17 responses. The data suggest that SIRT1 plays a complex role in RA and careful investigation of cell-specific effects is necessary to delineate possible therapeutic uses of agents targeting SIRT1. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4188

Background Periostin is a matricellular protein that expressed in bone, periodontal ligament, heart valve, tendon and skin. Previous study indicated that periostinis linked with several inflammatory diseases such as airway hypersensitivity, periodontal inflammation, and pulmonary fibrosis. However, there is no study to investigate the role of periostin in rheumatoid arthritis (RA). Objectives This study was performed to assess the function of periostin in K/BxN serum transfer arthritic mice. Methods Synovial tissues, serum, joint fluid, and fibroblast-like synoviocyte (FLS) were obtained from patients with RA and osteoarthritis (OA). The expression of periostin in synovial tissues was assessed by immunohistochemistry. The levels of periostin were checked by Western blot and enzyme-linked immunosorbent assay (ELISA). K/BxN serum transfer arthritis was induced in periostin knockout (KO) and age-matched wild type (WT) mice. Arthritis severity was assessed by clinical and histopathologic scoring. The levels of inflammatory cytokines in ankles and serum were measured by quantitative PCR and ELISA. The osteoclastogenesis was assessed by using bone marrow monocytes (BMM) from periostin KO or WT mice. Results Periostin was highly expressed in the synovium of RA patient than OA. The periostin levels were increased in the presence of IL-1β and TNF-α in RA-FLS. The periostin KO mice showed more severe arthritis from day 4 to day 10. The peak clinical scores were: 5.0±0.6 in WT, 7.36±0.5 in periostin KO mice; p Conclusions This study suggests that regulation of periostin contributes to pathogenesis of RA and periostin has a potential protective role in RA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4201

Objectives: To compare cardiovascular risk factors and LDL particle size in well-controlled Type 2 diabetes mellitus and normal subjects. Methods: Ninety-three Type 2 diabetic males and 186 age-matched, male controls were studied. Glycaemic control was stable for at least 3 months prior to recruitment. None were on insulin or lipid lowering therapy. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A1 and B, LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h. Results: Diabetic subjects (mean HbA1c 6.6%±0.10) did not differ from controls in total cholesterol levels (5.04±0.08 vs. 5.16±0.05 mmol/l, respectively) but had lower serum HDL cholesterol (0.98±0.03 vs. 1.12±0.02 mmol/l, P