Kenzo Hashizume

Recent trends in orthopedic surgery performed in Japan for rheumatoid arthritis

The aim of this report was to review the use of orthopedic surgeries performed to manage rheumatoid arthritis (RA). Our review of studies published in English indicates that there has been a decrease in RA-associated surgeries in Western countries. Improvements in medical treatment may partly explain the reduction in numbers of orthopedic joint surgeries, which also suggests a worldwide trend toward improved long-term outcomes. However, the results of our multicenter study in Japan indicate that the number of RA-associated operations has not decreased, and that the numbers of operations performed annually have been relatively stable from 1998 to 2008. Although there definitely has been a decline in the numbers of synovectomy surgeries, the numbers of operations on the upper limbs and foot arthroplasties have increased. With the trend toward milder disease because of improved medical treatment, we speculate that RA patients may want and need better function for the activities of daily living. The combination of medical treatment and surgical intervention is thought to improve outcomes in RA patients who will develop joint destruction. Additional studies, including analyses of RA databases containing long-term data on a variety of surgical interventions, are needed.

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

Time–concentration profile of serum etanercept in Japanese patients with rheumatoid arthritis after treatment discontinuation before orthopedic surgery

The treatment strategy for rheumatoid arthritis (RA) has changed dramatically over the past decade with the introduction of biologic agents [1]. In Japan, three inhibitors of tumor necrosis factor-alpha (TNFa), infliximab, etanercept, and adalimumab, and the anti-interleukin (IL)-6 receptor antibody tocilizumab are available as new treatment options for RA. Surgical-site infections (SSIs) are the major concern in orthopedic surgery for RA patients treated with biologic agents [2]. Most national guidelines suggest withholding biologic agents before surgery and restarting them postoperatively if there is no evidence of infection and delayed wound healing. In general, it was accepted that orthopedic surgery could be carried out relatively safely in the middle of the 8-week interval in which infliximab was administered at 3 mg/kg [3]. However, perioperative management in patients using etanercept has not reached a general consensus because of the lack of information about the pharmacokinetics of the serum concentration of etanercept after treatment discontinuation in patients with RA. In the present study, all subjects gave their written informed consent and the study was approved by the ethics committees of two institutes (Okayama University, number 410; and Kurashiki Kosai Hospital). Seven patients with RA undergoing orthopedic surgery were the study population. The patients’ characteristics are summarized in Table 1. Patients were treated with etanercept (25 mg, s.c.) twice a week for a mean duration of 12.7 months (range, 3–23 months). Blood samples were obtained 1, 4, 7, 11, 14, and 21 days after treatment discontinuation. The samples were centrifuged, and the serum compartments were stored at -80 C before analyses. Etanercept concentrations were measured by a validated enzyme-linked immunosorbent assay (ELISA) method at SRL (Tokyo, Japan). This ELISA method utilized a ‘‘sandwich’’ format to measure etanercept, as previously reported [4, 5]. Table 2 presents the mean and median ± SD values for the serum concentration of etanercept (ng/mL) at each time-point after discontinuation. The revised guidelines from the Japan College of Rheumatology in 2008 suggest that treatment with infliximab, etanercept, and adalimumab should be withheld 2–4 weeks before major surgical procedures. Treatment may be restarted postoperatively if there is no evidence of infection and once wound healing is deemed satisfactory [6]. Guidelines from the British Society for Rheumatology for prescribing TNFa blockers in adults with RA also suggest the same protocol for discontinuation [7]. However, long-term discontinuation of etanercept may induce flareup of the disease, and a shorter discontinuation period before surgery may be associated with the risk of SSI and delayed wound healing. The interruption of etanercept K. Nishida (&) Department of Human Morphology, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Okayama 700-8558, Japan e-mail: knishida@md.okayama-u.ac.jp

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.

Outcomes of Resection and Joint-Preserving Arthroplasty for Forefoot Deformities for Rheumatoid Arthritis

Background: We investigated the clinical outcomes of resection and joint-preserving arthroplasty for forefoot deformities in patients with rheumatoid arthritis. Methods: Sixteen feet of 14 women (average age, 67.1 years; range, 53-82) underwent resection arthroplasty of the metatarsal head (resection group), and 18 feet of 15 women (average age, 61.3 years; range, 40-73) underwent a metatarsophalangeal joint-preserving procedure with shortening oblique metatarsal osteotomies of the lesser toes (joint preservation group). The mean disease duration in the resection and joint preservation groups was 23.6 and 19.1 years, and the average follow-up period was 37.3 and 33.5 months, respectively. The classification of Larsen was used to assess the severity of destruction of the metatarsophalangeal (MTP) joint. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) score and postoperative complications. Results: The number of preoperative radiographic destruction of the MTP joints (Larsen grade II, III, IV, and V) was 0, 29, 39, and 12 joints in the resection group and 13, 67, 9, and 1 joints in the joint preservation group. The mean JSSF score improved significantly from 61.3 to 83.9 points in the resection group (P < .001) and from 62.2 to 90.8 points in the joint preservation group (P < .001). In the resection group, recurrence of callosities and claw toe deformity was observed in 6 and 3 feet, respectively. In the joint-preserving group, recurrence of callosities and hammer toe deformity was observed in 1 foot each. Conclusion: The resection arthroplasty and joint-preserving procedure showed satisfactory clinical outcomes. However, whether both procedures can maintain the good clinical results without the recurrence of forefoot deformity will require longer follow-up. Level of Evidence: Level III, retrospective comparative series.

Clinical and radiographic study of partial arthrodesis for rheumatoid wrists

Objectives. To retrospectively investigate the clinical and radiographic results of partial arthrodesis for the wrists with rheumatoid arthritis (RA). Methods. Forty-one wrists with RA were treated by radiolunate (RL) or radiolunotriquetral (RLT) arthrodesis with ulnar head resection. The average follow-up period after surgery was 7.1 years. Preoperative radiographs of all wrists were classified according to Schulthess classification. We performed RL arthrodesis for all Type II (n = 26) and Type III wrists (n = 7), and RLT arthrodesis for Type III wrists (n = 8). Pre- and postoperative pain score (visual analog scale), grip strength, range of motion, and radiographic parameters were statistically compared. Results. Pain scores in all groups were significantly improved at final follow-up (P < 0.05). Grip strength increased from 5.9 to 12.4 (kg) significantly in Type II wrists (P < 0.01), from 7.2 to 9.1 in Type III wrists after RLT arthrodesis, but decreased from 6.9 to 6.0 in Type III wrists after RL arthrodesis. In all groups, the arc of pronation and supination improved significantly (P < 0.05), and all radiographic parameters improved. Conclusions. RL arthrodesis for Type II wrists showed satisfactory clinical results. RLT arthrodesis would be a reliable method in case of unstable wrist joint.

AB0177 Patient-Reported Outcome of Upper Extremity Surgery for Rheumatoid Arthritis

Background The goal of treat to target (T2T) is the clinical remission in patients with early disease, but it is difficult to achieve the functional remission. Although patients subjective evaluation is important for the assessment of postoperative functions of rheumatoid arthritis (RA) patients, there are few reports examined the patients-reported functions after upper extremity surgery for RA. Objectives Between 2011 and 2014, 158 RA patients underwent the surgical treatment on upper extremities, and all patients were available for detailed clinical review over a 1-year follow-up period. There were 144 females and 14 males with a mean age at surgery of 59.7 (range, 18–85) years. The average disease duration at the surgery was 19.6 (range, 1–59) years. Methods The clinical outcome of the surgery was assessed by the disease activity (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), Disability of Arm Shoulder and Hand (DASH), Hand20 questionnaire (Hand20). The patients were divided by surgical site into 3 groups (elbow, wrist and finger groups) and by the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) into 2 groups (bDMARDs and non-bDMARDs groups) to compare and evaluate the outcomes. Results The mean of preoperative/postoperative DAS28-CRP, HAQ-DI, DASH and Hand20 were 2.9/2.3, 0.88/0.94, 46.4/39.1 and 59.1/47.6, respectively. All outcomes except for HAQ-DI significantly improved after the surgery. All outcomes improved significantly in the elbow group, but could not reach significant improvement in the finger group. We further examined the postoperative change in each items of DASH and Hand20, and found the significant improvements in items about pain and weakness in elbow group, pain and rotation of forearm in wrist group, and delicate movement and cosmetic factor in finger group. Postoperative DASH and Hand20 scores were tend to improve in the both bDMARDs and non-bDMARDs group. Conclusions Our results confirmed the surgery on upper extremity of RA improved the patients reported function, as well as the disease activity. There were surgical site-specific pattern of improvement of DASH and Hand20, such as that gross movement and pain significantly improved in larger joints, and dexterity movement and cosmetic factor in smaller joints. Postoperative upper extremity function was tend to improve, but more significantly in non-bDMARDs group, probably because the patients might had relatively better baseline function in the bDMARDs group. Understanding of site-specific patterns of improvement after surgery might be useful to achieve the functional remission, and may contribute to decision making of surgical indication, priority of surgical site on upper extremity, and prospection of surgical outcome. References Moromoto H, et al. Reliability of the Hand20 questionnaire: comparison with the 36-Item Short-Form Health Survey. Hand Surg. 2014;19(1):1–6 Hudak PL, et al. Development of an upper extremity outcome measure: the DASH (disabilities of the arm, shoulder and hand) [corrected]. The Upper Extremity Collaborative Group (UECG). Am J Ind Med. 1996 Jun;29(6):602–8. Disclosure of Interest None declared

AB0172 Usefulness of The Japanese Version of The Patient-Rated Elbow Evaluation in Patients with Rheumatoid Arthritis

Background Patient self-administered questionnaires remove the possibility of observer bias, and are important instruments for the assessment of clinical outcome. The patient-rated elbow evaluation (PREE) is a joint-specific, self-administered questionnaires. Objectives We aimed to investigate the correlation between the Japanese version of PREE (PREE-J) and other clinical parameters in rheumatoid arthritis (RA) patients before and after total elbow arthroplasty (TEA). Methods Thirty-five elbows in 32 RA patients (M/F: 3/29) were replaced by TEA. The mean age was 62.1 (range 41–79) years at the time of surgery, the mean follow-up period was 21.5 (range 12–36) months. All patients were assessed pre- and post-operatively by PREE-J, elbow and forearm range of motion (ROM), Disease Activity Score with 28 joint using CRP (DAS28-CRP), Mayo Elbow Performance Score (MEPS), Japanese version of the Disabilities of the Arm, Shoulder and HAND (DASH-JSSH) and Health Assessment Questionnaire Disability Index (HAQ-DI). The changes of parameters after surgery were examined by Wilcoxon signed-rank test, and the correlation between PREE-J and other parameters was examined using Spearmans correlation coefficients. Results Both pre- and post-operative PREE-J significantly correlated with DAS28-CRP, DASH-JSSH, and HAQ-DI. Significant improvement was observed after surgery in all parameters except for HAQ-DI. The mean postoperative MEPS improved from 50.3±16.4 points to 98.1±3.2 points, the average postoperative PREE-J improved from 54.7±19.3 points to 27.1±24.4 points. The correlation between PREE-J and MEPS was significant preoperatively (p<0.01), but the correlation disappeared postoperatively. The correlation between PREE-J and ROM was not significant pre- and post-operatively. Conclusions The current study indicated that elbow evaluation by patients who underwent TEA showed significant correlation with disease activity, upper limb function and disability in daily life. It was revealed preoperative PREE-J also well correlated with MEPS, which is widely accepted evaluation system by elbow surgeons. Interestingly, PREE-J did not correlate with MEPS and ROM postoperatively. As PREE-J contains many questions about complex motions required the multiple joint function of upper extremity, it is possible PREE-J might be influenced by other joints affected by RA. MEPS (up to 100 points) evaluates pain (45), ROM (20), function (25) and instability (10) of the elbow, and reached almost perfect score by TEA. PREE-J evaluates pain and function with more detailed questionnaires than MEPS, some of them cannot be solved by a single joint surgery. Our results suggested PREE-J might be useful and wide range evaluation instrument for functional improvement of upper extremity after TEA. Disclosure of Interest None declared

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