M. Ozawa

Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes.

OBJECTIVE To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related transcription factor (RUNX)-2 and adisintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 in human chondrocytes. METHODS Human chondrocytes were seeded in stretch chambers at a concentration of 5 × 10(4)cells/chamber. Cells were pre-incubated with or without HDAC inhibitors (MS-275 or trichostatin A; TSA) for 12h, followed by uniaxial cyclic tensile strain (CTS) (0.5Hz, 10% elongation), which was applied for 30 min using the ST-140-10 system (STREX, Osaka, Japan). Total RNA was extracted and the expression of RUNX-2, ADAMTS-5, matrix metalloproteinase (MMP)-3, and MMP-13 at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The activation of diverse mitogen-activated protein kinase (MAPK) pathways with or without HDAC inhibitors during CTS was examined by western blotting. RESULTS HDAC inhibitors (TSA: 10 nM, MS-275: 100 nM) suppressed CTS-induced expression of RUNX-2, ADAMTS-5, and MMP-3 at both the mRNA and protein levels within 1h. CTS-induced activation of p38 MAPK (p38), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) MAPKs was downregulated by both HDAC inhibitors. CONCLUSION The CTS-induced expression of RUNX-2 and ADAMTS-5 was suppressed by HDAC inhibitors via the inhibition of the MAPK pathway activation in human chondrocytes. The results of the current study suggested a novel therapeutic role for HDAC inhibitors against degenerative joint disease such as osteoarthritis.

Abatacept management during the perioperative period in patients with rheumatoid arthritis: report on eight orthopaedic procedures

1 Department of Human Morphology, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, 2 Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, and 3 Department of Orthopaedic Surgery, Kurashiki Sweet Hospital, Kurashiki City, Okayama, Japan

Anterior transposition of the ulnar nerve with endoscopic assistance

We treated 20 patients with cubital tunnel syndrome by anterior transposition of the ulnar nerve with endoscopic assistance. Five elbows were classified preoperatively as McGowan’s stage 1, 11 as stage 2 and four as stage 3. Excellent outcomes were obtained in nine and good in eight patients. Three patients had fair results. Improvement of symptoms occurred in all patients. There were no serious complications. All ulnar nerves remained anteriorly transposed.

Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients

Abstract Objective: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery. Methods: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables. Results: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256–7.986; p = 0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436–11.389; p = 0.008) and disease duration (OR, 1.004; 95% CI, 1.000–1.007; p = 0.029) were associated with an increased risk of DWH. Conclusions: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH.

Short-term results of the PROSNAP linked elbow prosthesis with a snap-in structure and modular flange for the reconstruction of severely damaged rheumatoid elbows

BACKGROUND We aimed to evaluate the early clinical results of the reconstruction of problematic elbow joints due to rheumatoid arthritis (RA) using a PROSNAP linked elbow prosthesis (Kyocera Medical, Osaka, Japan) for total elbow arthroplasty. METHODS Seventeen elbows in 14 RA patients were replaced with a PROSNAP elbow with cement fixation. The patients comprised 1 man and 13 women, with a mean age of 63.9 years (range, 52-83 years) at the time of surgery. The preoperative conditions of the elbows were arthritis mutilans (n = 10), an ankylosed or stiff elbow with a preoperative range of motion of 45° or less (n = 4), and loosening of a primary total elbow arthroplasty (n = 3). The mean follow-up period was 47.7 months (range, 32-69 months), with a 100% follow-up rate. The clinical outcome of the elbows was evaluated by the Mayo Elbow Performance Index (maximum, 100 points). RESULTS The mean postoperative Mayo Elbow Performance Index score improved from 57.6 points to 97.1 points. Preoperatively, 3 of the 17 elbows were judged as good, 7 as fair, and 7 as poor; at final follow-up, 16 elbows were judged as excellent and 1 as good. Complications were noted in 1 elbow (6%), which had undergone a postoperative fracture. CONCLUSIONS The PROSNAP elbow prosthesis can be safely implanted through a relatively easy procedure and provides satisfactory short-term clinical outcomes for the reconstruction of severely damaged RA elbows. LEVEL OF EVIDENCE Level IV, case series, treatment study.

SAT0572 The Effect of Interleukin-4 on Mechanical Stress-Induced Protease Expressions by Human Chondrocytes

Background We previously reported that runt-related transcription factor 2 (RUNX-2) has an important role in regulation of mechanical stress-induced expression of ADAMTS aggrecanases in chondrocytes. Interleukin-4 (IL-4) is an anti-inflammatory cytokine, like IL-10 and IL-13, which is known to suppress pro-inflammatory cytokine production and activities. In osteoarthritis (OA) synovial tissue, IL-4 inhibits the production of tumor necrosis factor-α and IL-1β. Local overexpression of IL-4 protects cartilage from metalloproteinase (MMP)-induced destruction by preventing the activation of pro-MMPs during immune complex-mediated arthritis. More recently, we reported that intra-articular injection of IL-4 ameliorates subsequent destruction of cartilage in instability-induced OA in rat knee joints. Objectives To examine the effect of IL-4 on mechanical stress-induced expression of catabolic proteases by human chondrocytes. Methods Normal Human Articular Chondrocytes from knee joint were purchased from Lonza (Walkersville, MD, USA). IL-4 was purchased from CHEMICON International, Inc. (Temecula, USA). Cells were cultured at 37°, and were seeded onto type II collagen coated stretch chambers. They were transferred to serum-free medium with or without IL-4 (10ng/ml) for 12h before cyclic tensile strain (CTS), and a uni-axial CTS (0.5 Hz, 10% elongation) was applied for 30 min using the ST-140 mechanical stretch system (STREX, Osaka, Japan). RNA was isolated at 1, 6, 12, 24h after CTS, reverse transcribed, and the expression of ADAMTS-4, -5, -9, MMP-13, and RUNX-2 examined by real-time PCR. Results CTS induced the expression of ADAMTS-4, -9, MMP-13 at 24h, and MMP-3 at 6h after CTS in control samples. In IL-4 treated samples, the expression of ADAMTS-4, -5, -9, MMP-13 and RUNX-2 were significantly downregulated. ADAMTS-5 gene expression was biphasic (1h and 12h after CTS) in control samples, and both peaks (RUNX-2 dependent peak and cytokine dependent peak) were reduced in IL-4 treated samples. The concentration of IL-1β in the supernatant increased in control samples at 6h after CTS, but decreased in IL-4 treated samples. Conclusions IL-4 treatment effectively suppressed the mechanical stress-induced expression of ADAMTS-4, -5, -9 and MMP-13, presumably by inhibition through RUNX-2 pathways. These data suggest the clinical chondro-protective effects of IL-4 against mechanical stress-induced cartilage degeneration. References Tetsunaga T, Nishida K, Furumatsu T, Naruse K, Hirohata S, et al.Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2 transcriptional factor in SW1353 chondrocyte-like cells. Osteoarthritis Cartilage 2011; 19: 222-232. Goldring MB: The role of the chondrocyte in osteoarthritis. Arthritis Rheum 2000; 43: 1916-1926. Bendrups A, Hilton A, Meager A and Hamilton JA: Reduction of tumor necrosis factor alpha and interleukin-1 beta levels in human synovial tissue by interleukin-4 and glucocorticoid. Rheumatol Int 1993; 12: 217-220. Yorimitsu M, Nishida K, Shimizu A, et al: Intra-articular injection of interleukin-4 decreases nitric oxide production by chondrocytes and ameliorates subsequent destruction of cartilage in instability-induced osteoarthritis in rat knee joints. Osteoarthritis Cartilage 16(7): 764-71, 2008 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4837

FRI0284 Preoperative Use of Biologic Agents is not an Independent Risk Factor for SSI and Delayed Wound Healing in Patients with Rheumatoid Arthritis

Background The perioperative use of biologic DMARDs in patients with rheumatoid arthritis (RA) has potential risks for delayed wound healing and infectious complications. Surgeons are recommended to discontinue biologic DMARDs to reduce the risk of surgical site infection and delayed wound healing. The guidelines for periopetrative cessation periods of biologic DMARDs differ among countries, and a firm conclusion on this issue has not been reached. Objectives The aim of the study was to review the incidence of delayed wound healing and surgical site infection (SSI) in patients with RA undergoing orthopedic surgery and to evaluate risk for postoperative complications using biologic DMARDs. Methods We retrospectively investigated a total of 1029 elective orthopedic procedures for RA patients performed between January 2004 and December 2012 at two centers (Okayama University Hospital and Kurashiki Kosai Hospital). Identification of SSI was done based on the 1999 guidelines for prevention of surgical site infection1).Cases which removed suture longer than 2 weeks after surgery or required resuture were regarded as delayed wound healing. Risk factors for SSI and delayed wound healing were analyzed by logistic regression analysis between age, BMI, disease duration, operative procedure, corticosteroid use, diabetes mellitus, hypertension, cardiovascular disease, and use of non biologic and biologic DMARDs. Results In total 1039 procedures, SSIs and delayed wound healing were identified in 19 cases (1.83%) and 17 cases (1.64%), respectively. Superficial infection and deep infection were identified in 9 cases and 10 cases, respectively. One case of superficial infection and 4 cases of delayed wound healing were recorded in 198 procedures in patients using biologic agents including infliximab, etanercept, adalimumab, and tocilizumab. Foot surgery (OR 3.104, 95% CI 1.226-7.857), and age at the surgery (OR 1.064, 95% CI 1.010-1.117) were associated with increased risk of SSI. Total knee arthroplasty (OR 3.051, 95% CI 1.139-8.178) and disease duration (OR 1.003, 95% CI 1.000-1.006) were associated with increased risk of delayed wound healing. The preoperative use of biologic agents did not constitute an independent risk factor for SSI and delayed wound healing. Table 1. Patients characteristics and summary of the results Total Biologics (−) Biologics(+) Number (M/F) 1039 (86/953) 841 (75/766) 198 (11/187) Age, years 61.8 63.0 56.6 BMI, kg/m2 21.8 21.8 21.7 Disease duration, years 20.0 20.6 17.4 SSIs  Superficial infection 9 (0.87%) 8 (0.95%) 1 (0.50%)  Deep infection 10 (0.96%) 10 (1.19%) 0 (0%) Delayed wound healing 17 (1.64%) 13 (1.55%) 4 (2.0%) Conclusions In the current case-control study, the results suggest that biological agents are not risk factors for a significant increase of postoperative complications. However, more data are clearly needed and further prospective studies must be performed to confirm this finding. References Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital infection control practices advisory committee. Infect Control Hosp Epidermal. 1999;20:250–78. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5243

AB1097 Development of Statistical Analysis and Computer Tablet Based Clinical Score Input System on the Electronic Medical Record for Rheumatoid Arthritis

Background In clinical research, statistical analysis of clinical data is a costly process. Its cost is composed of data input, data store and statistical analysis. As usually clinical score is recorded on paper, manual data input is needed. For the protection of personal information, anonymization of data and isolation of database is needed. For statistical analysis, statistical software and statistical operation are needed. Objectives In order to solve these problems, we developed a computer tablet based clinical data input and statistical analysis system which can work on the electronic medical record system. Methods Our system consists of three modules. First module is a score input system, which can create and custom the clinical input screen for each clinical score (such as HAQ, DASH, and DAS28) and perform the calculation such as total score. Second module is a data store system, which can store the anonymized clinical data and connect to electronic medical record system (development of connecting module for each electronic medical manufacturer is needed). Third module is an analysis system, which can perform various kind of statistical procedure and record the statistical methods. For statistical analysis, we selected R, which is open source software for statistical computing. R can perform many kinds of statistics and describe statistical procedure. With combination of these modules, we can visualize the statistical results and graphics immediately after the data input. In order to verify the utility of this system, HAQ score input using tablet computer system was performed in 26 RA patients and 23 healthy controls. We recorded the score and time of entering data (input time), and examined the correlation between the score, time used for data input, input experience and age. These statistics were performed immediately after the data input. Results Input time was 170±83 seconds in RA patients and 88±38 seconds in healthy individuals. Age and input time has good correlation in healthy controls (r=0.63, p=0.05), but poor correlation in RA patients (r=0.11, p=0.57). HAQ and input time has good correlation in RA patients (r=0.50, p=0.01). Input time is shortened with an increase of the number of input experience. Real-time display of statistical results and graph drawing, and the connection to the electronic medical record was possible. Conclusions The cost of this system is low, because this system was all created by open source software and work on a UNIX system. So we can easily share this system with many hospitals, and decrease the cost of multicenter trial. We developed computer tablet based clinical score input and statistical analysis system, which can work on the electronic medical record system. Acknowledgements The authors thank Mr. Yasushi Takahashi (NEC corporation medical solutions division) for programming and helpful suggestions. Disclosure of Interest R. Nakahara Grant/research support: NEC, K. Nishida: None declared, K. Hashizume: None declared, Y. Nasu: None declared, M. Ozawa: None declared, R. Harada: None declared, T. Machida: None declared, T. Ozaki: None declared DOI 10.1136/annrheumdis-2014-eular.3429

AB0786 Clinical results of swanson and avanta silastic implant arthroplasty of the metacarpophalangeal for the rheumatoid hand

Background The arthroplasty of the metacarpophalangeal (MCP) for the rheumatoid hand was first described in 1940 by using vitallium prosthesis. After that, metallic hinge type, ball & socket type, surface replacement type and different type of prostheses are being developed, but none of these has been shown so far to be superior to the silastic implant, especially Swanson implant. Objectives In the silastic implants, Swanson arthroplasty is referred to as the gold standard. The AVANTA silastic implant was also based on the concept of “piston effect” and “encapsulation” as the Swanson implant1). The purpose of this investigation was to compare the clinical outcome of Swanson and AVANTA silastic implant arthroplasty of the MCP joints for patients with rheumatoid arthritis. Methods A total of 48 Swanson and 70 AVANTA implants were inserted in 38 hands of 34 patients (1 man, 33 women). The mean age of patients at the surgery was 61.9 ± 4.8 years in Swanson group and 61.0 ± 6.2 years in AVANTA group. The average follow-up period was 60.7 ± 20.5 and 21.3 ± 9.1 months in Swanson and AVANTA group, respectively. Pre- and post-operative clinical evaluations included active MCP extension and flexion, grip strength, pinch, ulnar deviation, osteolytic or sclerotic change in the radiograph, Health Assessment Questionnaire(HAQ), and Disabilities of the Arm, Shoulder and Hand(DASH) score. Statistical analysis were done using Mann-Whitney U test. Results The mean postoperative active extension was -13.3° ± 16.2° in Swanson group, -10.7° ± 10.2° in AVANTA group (p=0.72), and flexion was 58.6° ± 19.8° in Swanson group, 59.3° ± 21.5° in AVANTA group (p=0.78). According to the Parkkila’s criteria2), the GradeII and more radiographic osteolysis was seen in 29% of Swanson group and 25% of AVANTA group. The GradeI and more radiographic sclerosis was seen in 73% of Swanson group and 69% of AVANTA group. The functional scores at the final follow-up were 1.4 ± 0.7 and 1.2 ± 0.8 (p=0.48) for HAQ-disability index and 54.9 ± 21.6 and 41.8 ± 21.6 (p=0.12) for DASH disability score in Swanson group and AVANTA group, respectively. There were three implant fractures in Swanson group. No patients had revision surgery during follow-up period. Conclusions The AVANTA groups tend to obtain greater range of motion and better functional outcome, but there was not statistically significant difference between two groups. Implant fractures in the Swanson group might be associated with the silastic mechanical property and the longer follow-up period. References Swanson, A.B. Flexible implant arthroplasty for arthritic finger joints: rationale, technique and results of treatment. J Bone Joint Surg 1972; 54A: 435-455 Parkkila TJ, Belt EA, Hakala M, et al. Grading of radiographic osteolytic changes after silastic metacarpophalangeal arthroplasty and a prospective trial of osteolysis following use of Swanson and Sutter prostheses. J Hand Surg Br 2005; 30(4): 382-387 Disclosure of Interest None Declared

SAT0518 MRI of Rheumatoid Arthritis: Comparing the Omeract Scoring and Volume of Synovitis for the Assessment of Therapy

Background The Outcome Measures in Rheumatology Clinical Trials (OMERACT) scores are the most mature quantitation system for RA on digital images of the wrist and finger joints. However, the reliability of the OMERACT scoring system has low intra-reader validation. Several direct measuring techniques of synovial volume have been reported with good reproducibility, although a few reports demonstrated the responsibilities of changes of these measures to the treatments. Objectives To compare responsibilities of the changes of OMERACT scores and MRI-derived synovial volume to the changes of disease activity score (DAS28-CRP). Methods MRI data of the dominant affected wrist and finger joints were obtained from 40 joints of 8 RA patients who were treated with biologic agents at the baseline and one year after the treatment. DAS28-CRP was also assessed at baseline and 1 year. Wrist and 2nd to 5th metacarpophalangeal joints were scored using OMERACT scoring system and synovial volumes were measured at the same areas. Correlation of the changes of OMERACT score and synovial volume with the changes of DAS28-CRP were analyzed by Pearson correlation test. Results At baseline, all patients had clinically active RA with mean DAS28-CRP score 3.75 ± 0.75. At 1 year DAS28-CRP was significantly reduced to 1.92 ± 0.54. OMERACT score and synovial volume were reduced from 48.0 to 41.3, and from 15.4 to 8.8 (milliliter), respectively. In each joint, synovial volume had good correlation (r=0.88) with OMERACT synovitis score. The changes of OMERACT synovitis score(r=0.28), OMERACT total (sum of synovitis, erosion and bone oedema) score(r=0.43) and synovial volume (r=0.30) showed positive correlations with the changes of DAS28-CRP. Conclusions MRI synovial volume showed better correlation with clinical response to the treatment by biologic agents than OMERACT synovitis score. On the other hand, OMERACT total score showed better correlation with DAS28-CRP than synovial volume, probably due to the involvement of scores for bone erosion and bone oedema. References Hodgson, R.J., P. O’Connor, and R. Moots, MRI of rheumatoid arthritis image quantitation for the assessment of disease activity, progression and response to therapy. Rheumatology (Oxford), 2008. 47(1): p. 13-21. Haavardsholm, E.A., et al., Reliability and sensitivity to change of the OMERACT rheumatoid arthritis magnetic resonance imaging score in a multireader, longitudinal setting. Arthritis Rheum, 2005. 52(12): p. 3860-7. Ostergaard, M., et al., Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients. Arthritis Rheum, 2011. 63(12): p. 3712-22. Kita, J., et al., Significant improvement in MRI-proven bone edema is associated with protection from structural damage in very early RA patients managed using the tight control approach. Mod Rheumatol, 2012. Disclosure of Interest None Declared