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Although the relationship between the material properties of the coracoacromial ligament and rotator cuff tears has been clarified, it is difficult to evaluate these properties in the clinical setting. The purpose of this study was to clarify the relationship between rotator cuff tears and the length and thickness of the coracoacromial ligament in living shoulders, in order to assess the potential use of these parameters as clinical indicators of the possible risk or progression of rotator cuff tears. Thirty-five volunteers (46 shoulders, mean age: 52 years) were enrolled. The presence or absence of rotator cuff tears and the length and thickness of the coracoacromial ligament were evaluated by ultrasonography. Longitudinal images of the coracoacromial ligaments with the acromion and coracoid process as landmarks were obtained, and the lengths of the ligaments were measured using acoustic shadows as the index. On the same screens, the thicknesses at the center of the ligaments were measured. Ligaments in shoulders with a rotator cuff tear were significantly shorter than ligaments in shoulders without a rotator cuff tear (25.9 ± 2.5 mm vs. 28.6 ± 1.7 mm, respectively; P < 0.0001). There was no significant difference in the thicknesses of the ligaments. The length and thickness of the coracoacromial ligament of living shoulders were easily evaluated with ultrasonography in the present study, and the coracoacromial ligament was found to be significantly shorter in shoulders with a rotator cuff tear. The risk and progression of rotator cuff tears can be evaluated clinically by measuring the length of the coracoacromial ligament.

The interplay among magnetism, electronic nematicity, and superconductivity is the key issue in strongly correlated materials including iron-based, cuprate, and heavy-fermion superconductors. Magnetic fluctuations have been widely discussed as a pairing mechanism of unconventional superconductivity, but recent theory predicts that quantum fluctuations of nematic order may also promote high-temperature superconductivity. This has been studied in FeSe1−xSx superconductors exhibiting nonmagnetic nematic and pressure-induced antiferromagnetic orders, but its abrupt suppression of superconductivity at the nematic end point leaves the nematic-fluctuation driven superconductivity unconfirmed. Here we report on systematic studies of high-pressure phase diagrams up to 8 GPa in high-quality single crystals of FeSe1−xTex. When Te composition x(Te) becomes larger than 0.1, the high-pressure magnetic order disappears, whereas the pressure-induced superconducting dome near the nematic end point is continuously found up to x(Te) ≈ 0.5. In contrast to FeSe1−xSx, enhanced superconductivity in FeSe1−xTex does not correlate with magnetism but with the suppression of nematicity, highlighting the paramount role of nonmagnetic nematic fluctuations for high-temperature superconductivity in this system., Despite studies in FeSe1−xSx, it is yet unconfirmed whether nematic fluctuation can induce superconductivity. Here, the authors study single crystals of FeSe1−xTex showing enhanced superconductivity upon suppression of nematicity.

A fundamental issue concerning iron-based superconductivity is the roles of electronic nematicity and magnetism in realising high transition temperature ($T_{\rm c}$). To address this issue, FeSe is a key material, as it exhibits a unique pressure phase diagram involving nonmagnetic nematic and pressure-induced antiferromagnetic ordered phases. However, as these two phases in FeSe overlap with each other, the effects of two orders on superconductivity remain perplexing. Here we construct the three-dimensional electronic phase diagram, temperature ($T$) against pressure ($P$) and isovalent S-substitution ($x$), for FeSe$_{1-x}$S$_{x}$, in which we achieve a complete separation of nematic and antiferromagnetic phases. In between, an extended nonmagnetic tetragonal phase emerges, where we find a striking enhancement of $T_{\rm c}$. The completed phase diagram uncovers two superconducting domes with similarly high $T_{\rm c}$ on both ends of the dome-shaped antiferromagnetic phase. The $T_{\rm c}(P,x)$ variation implies that nematic fluctuations unless accompanying magnetism are not relevant for high-$T_{\rm c}$ superconductivity in this system., 8 pages, 9 figures. A revised version will appear in Nature Communications

Background Rheumatoid arthritis (RA) is one of the causes of secondary osteoporosis, and steroids are often used in combination, therefore osteoporosis is highly associated with RA. Furthermore, joint disorders due to RA cause various degrees of dysfunction and ADL declines. The Steinbrocker classification is often used as the degree of dysfunction. Immobilization progresses with the progress of dysfunction, possibly causing severe osteoporosis. Objectives Of the 2238 cases in Akita Orthopedic Group omn Rheumatoid Arthrotis (AORA) registry 2017, 101 cases simultaneously measuring bone metabolism markers (TARCP-5b, NTX, urinary DPD, BAP, total P1NP) and pentosidine were involved. Methods Patients were divided by Steinbrocker classification into class 1,2 (group A 84 cases) and clss 3, 4 (group B 17 cases). we examined whether there is a difference in bone metabolism markers in each group according to Steinbrocker classification. Results The average age in group B (75.9) was significantly higher than group A (66.9) (p = 0.01). DAS 28 ESR was significantly higher in group B (p Conclusion Immobilization by long-term bed rest is known to enhance bone resorption. In 2002, Wakae reported DPD in urine showed a higher value in the group of not going out in femoral neck fracture cases. Based on the results of this study, urinary DPD showed a high value in RA group with high degree of dysfunction, which possibly reflected immobilization due to progress of functional disorder. Moreover, it is known that pentosidine will be higher in cases with high disease activity, severe osteoporosis will be occurred in the group with progressive functional disorder which is difficult to tight control. Disclosure of Interests None declared

Background Treatment outcomes for rheumatoid arthritis (RA) have been improved by advances in drugs. In daily clinical practice, treatment outcomes are assessed with both inflammatory findings and based on swollen joints (SJ), tender joints (TJ), a patient’s global assessment on visual analogue scale (GVAS) score, a physician’s GVAS score, etc. Although composite measures indicate suppressed inflammatory or articular symptoms, many patients show no improvement in GVAS scores. The reported residual symptoms include morning stiffness (MS), pain (P), and dullness (D). Objectives We investigated the residual symptoms of patients achieving low disease activity (LDA) or complete remission (CR). Methods His study included 111 RA patients who received outpatient treatment at our department (31 men and 80 women). The mean age was 65.1 (range, 27–89) years. The disease stages were distributed as follows: 36 patients with Stage 1, 23 patients with Stage 2, 20 patients with Stage 3, and 32 patients with Stage 4. The severity of dysfunction was distributed as follows: Class 1 in 73 patients, Class 2 in 25 patients, Class 3 in 11 patients, and Class 4 in 2 patients (Steinbrocker classification). Based on the disease activity score in 28 joints using the erythrocyte sedimentation rate, disease activity was graded as CR in 54 patients, LDA in 19, moderate disease activity in 37, and high disease activity in 1. Questionnaire forms were used to assess the presence or absence and duration of MS and the presence or absence and severity of P (Pain VAS) and of D (Dullness VAS). These variables were assessed to determine how they were associated with clinical outcome measures, drugs, and surgery. Results The following residual symptoms were observed in 73 patients who achieved the treatment target of LDA or CR: MS in 34 patients (46.6%), P in 48 (65.6%), and D in 38 (52.8%). In the LDA+CR group, the Pain VAS (P Conclusion Residual symptoms were frequently observed even in patients achieving LDA or CR, which is regarded as the treatment target. Because P and D were significantly correlated with the GVAS, relief of these residual symptoms is expected to improve treatment effects. Although D was relieved by bDMARDs, further studies on the treatment of residual P in patients achieving LDA or CR are necessary. Disclosure of Interests None declared

Background While the number of rheumatoid arthritis (RA) surgeries has been declining due to advances in pharmacotherapies for RA, forefoot surgeries are on the rise. In recent years, the common use of joint ultrasonography in RA consultations has led to the early detection of synovitis. However, little is known about how much forefoot deformities such as hallux valgus and metatarsophalangeal (MTP) joint dislocation are affected by synovitis in the forefoot of RA patients. Objectives The present study examined factors involved in forefoot deformity among patients with foot synovitis identified on joint ultrasound. Methods Subjects (71 patients, 91 feet) were RA patients who had undergone foot joint ultrasonography more than 2 years earlier and underwent standing X-rays of the feet before and after ultrasonography. Surgery cases were excluded. Mean age was 64.9 years (range, 15-90 years). Disease stage was Stage 1 in 14 patients, Stage 2 in 14 patients, Stage 3 in 16 patients, and Stage 4 in 27 patients. According to the Steinbrocker functional classification, RA was Class 1 in 45 patients, Class 2 in 19 patients, Class 3 in 6 patients and Class 4 in 1 patient. Twenty-five patients had been administered biological drugs. At the time of joint ultrasonography, patients were questioned regarding whether they had any complaints involving the forefoot, midfoot or hindfoot (noted separately). The following scans were performed: forefoot (MTP joints 1-5); midfoot (calcaneocuboid, calcaneocuboid and cuneonavicular joints) and hindfoot (peroneal muscle tendon, talocrural joint, talocalcaneal joint and posterior tibial muscle tendon). Foot deformity score (FDS) (hallux valgus angle + first-second intermetatarsal angle [M1M2 angle] + first-fifth intermetatarsal angle [M1M5 angle]) was used as the benchmark for forefoot deformity, and an increase >5° was considered to indicate worsening deformity. Results Forefoot deformity had progressed in 25 patients. Mid- and hindfoot synovitis and the presence of complaints were not associated with deformity. However, significant worsening of FDS was observed in patients with forefoot synovitis or forefoot complaints. While no difference in age, disease activity, biologic disease-modifying antirheumatic drug usage or health assessment questionnaire results were seen in the advanced deformity group, duration of disease was significantly shorter in this group. Conclusion Mid- and hindfoot synovitis was unrelated to forefoot deformity. MTP joint synovitis in the forefoot was related to forefoot deformity. Continuous synovitis in the forefoot must damage the articular capsule and ligament structure, leading to progression of deformity. As shown by the short duration of the disease in the advanced deformity group, deformity may progress in the early stages among patients with forefoot deformity. Disclosure of Interests None declared

This study aimed to investigate the efficacy of denosumab (compared with that of bisphosphonates) for preventing secondary osteoporosis and inflammation caused by excessive bone resorption in Japanese rheumatoid arthritis (RA) patients never previously treated for osteoporosis.Ninety-eight patients with coexisting RA and osteoporosis were enrolled. The patients were subdivided by whether they were treated with denosumab (n = 49) or traditional bisphosphonates (n = 49). RA disease activity, bone turnover markers, and bone mineral density (BMD) were compared between the two groups before treatment, and after 6 and 12 months of treatment.There was no significant difference between the groups in any of the disease activity indices and BMD at any of the measured time points. With regard to bone metabolism, denosumab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, suggesting an effect on the bone formation rate, but not on the bone resorption rate.Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis.

The goal of treatment for distal humeral fractures in patients with rheumatoid arthritis (RA) is to obtain sufficient bone union and good elbow function. However, treating comminuted distal humeral fractures in patients with RA and osteoporosis is challenging. We present the case of a 58-year-old woman with RA and osteoporosis who suffered a comminuted distal humeral fracture and was successfully treated with the Ilizarov technique. The Ilizarov technique is minimally invasive compared with conventional open surgery, can obtain good stabilization, and allows earlier rehabilitation, even if the fractured bone is severely osteoporotic. The patient exhibited good elbow function and alignment at the final follow-up examination (18 postoperative months). To the best of our knowledge, the present case is the first in which a comminuted distal humeral fracture in a patient with RA and severe osteoporosis was successfully treated with an Ilizarov external fixator. Keywords: Distal humeral fracture, Rheumatoid arthritis, Ilizarov technique

Background:Treatment outcomes in rheumatoid arthritis (RA) have been improved with advances in drug therapy. In daily clinical practice, the outcomes are assessed based on the presence of swollen or tender joints, global assessment using a visual analog scale by a patient (GVAS) and a physician (DrVAS), etc., in addition to inflammatory findings. Although inflammation and joint symptoms are suppressed, many patients show no improvement in GVAS scores. The reported residual RA symptoms include morning stiffness (MS), pain (P), and dullness (D), but their causes are not completely known. Latent cervical spine lesions sometimes exist in RA, but their association with residual RA symptoms is unknown.Objectives:We examined cervical spine lesions and residual symptoms in patients with RA who achieved the therapeutic goal.Methods:Of 124 patients with RA, 82 (25 men and 57 women) who achieved a low disease activity (LDA) state on the Disease Activity Score for 28 joints with erythrocyte sedimentation rate (DAS28-ESR) were included. The mean age was 65.7 (28- 83) years, and the disease stage was Stage I in 28 patients, Stage II in 14, Stage III in 13, and Stage IV in 27. Dysfunction was graded as Class 1 in 63 patients, Class 2 in 18, and Class 3 in one (Steinbrocker classification). Biopharmaceuticals had been administered in 27 patients. As for disease activity, the DAS28-ESR scores indicated complete remission in 54 patients and LDA in 28. The survey form was used to investigate the presence or absence/duration of MS, the presence or absence/severity of P (Pain VAS), and the presence or absence/severity of D (Dullness VAS). On lateral functional radiographs of the cervical spine, patients with spinal lesions were selected and divided into the asymptotic stability (ASS; atlantoaxial dislocation ≥3 mm) + vertical setting (VS; Ranawat value Results:According to cervical spine lesions, the patients who achieved the therapeutic goal were divided into the ASS+VS group comprising 15 patients (18.3%), the spondylolisthesis group comprising 11 (13.4%), and the stenosis group comprising 18 (22.0%). Among them, only the spondylolisthesis group showed significant differences in residual RA symptoms. In the spondylolisthesis group, the disease duration was longer, but there was no difference in age. MS, P, and D were significantly severer. The duration of MS was longer, and both Pain and Dullness VAS scores were higher. The score on each component of the DAS28 showed no difference in inflammatory findings. GVAS and DrVAS scores were higher. No common perceptions of spinal symptoms were shared between any patients with cervical spine lesions and physicians.Conclusion:Improved patient-reported outcomes (PROs) are considered to be important to achieve more complete remission. There are various reports on the causes of residual RA symptoms, but many aspects remain unknown. Based on the results of this study, because asymptomatic subaxial subluxation is one of concerns in patients with spondylolisthesis with dynamic instability of the cervical spine, cervical spine diseases should also be considered in patients with severe residual symptoms. Not only radiography but also magnetic resonance imaging needs to be performed.Acknowledgments:The authors wish to acknowledge Miss SasakiDisclosure of Interests:None declared

Background: Hip fracture is a frequent cause of hospital admission in older adults.1 The prevalence of hip fracture associated with osteoporosis in the elderly is 18% in women and 6% in men.2 Likewise, the attention of this event requires an approximate value of 2,943 dollars, which represents an average of 18,95% of the per capita income of most countries.3 It is also established that appropriate and timely treatment of osteoporosis can prevent the appearance of fractures.4 Objectives: The aim of this study was to determine the prevalence of hip fracture associated with osteoporosis, as well as the associated factors to its presentation in a geriatric population in Colombia. Methods: Cross-sectional study that included 130 patients over 65 years old, who consulted the University Hospital of Santander with hip fracture. The main variable of exposition was the medical history of osteoporosis. Descriptive analysis was performed with absolute and relative frequency measurements for the qualitative variables and central tendency measures and dispersion according to the distribution of the variables. Subsequently, the bivariate logistic regression analysis was performed to identify the associated risk variables. The analysis was performed with the Stata 12.0 Software. Results: From the 130 patients included in the study, 33.85% corresponded to the male gender. The average age was 82.49 years with a DS of 8.35 years. The median length of hospital stay was 17.5 days with an interquartile range of 11 to 26 days. The most common comorbidity was hypertension in 65.38%, followed by diabetes and COPD in 21.54%, heart failure in 19.23% and chronic kidney disease in 17.69%. The median Charlson score was 5 with an interquartile range between 4 and 6 points. 13.85% of the patients admitted had concomitant osteoporosis, 77.7% of them were women and 8,46% of them had severe osteoporosis, with history of prior fracture, without treatment. In the bivariate analysis, an association was found between having COPD (OR: 4.89, 95% CI 1.71-13.95, p = 0.003), dementia (OR: 3.20, 95% CI 1.05-19.56, p = 0.044), malnutrition (OR: 3.42, IC95 % 1.10 - 10.60, p = 0.032), and osteoporosis associated with hip fracture at hospital admission. Likewise, a greater probability was found for the development of in-hospital pneumonia (OR: 2.48, 95% CI 1.14 - 7.98, p = 0.04) in patients with osteoporosis compared to those who did not have bone disease. Conclusion: 13.85% of patients who entered due to hip fracture had osteoporosis as comorbidity, data comparable to that previously reported. Variables associated with the presence of osteoporosis at admission in patients with hip fracture were found like history of COPD, dementia, and malnutrition, which makes it likely that those patients with pathologies that decrease physical activity or food intake can impact in an important way the appearance of osteoporosis. One of the most important contributions of this study is the identification of in-hospital complication (pneumonia), which should be actively monitored in these patients. References: [1]Falaschi P (Paolo), Marsh DR. Orthogeriatrics. Springer; 2017. [2]Cooper C, Campion G, Melton LJ. Hip fractures in the elderly: A world-wide projection. Osteoporos Int. 1992 Nov;2(6):285–9. [3]Mohd-Tahir NA, Li SC. Economic burden of osteoporosis-related hip fracture in Asia: a systematic review. Vol. 28, Osteoporosis International. Springer London; 2017. p. 2035–44. [4]Solimeo SL, Mccoy K, Reisinger HS, Adler RA, Sarrazin MV. Factors Associated With Osteoporosis Care of Men Hospitalized for Hip Fracture: A Retrospective Cohort Study. 2019; Disclosure of Interests: None declared

Background:Locomotive syndrome is a condition in which activities of daily living are affected by impairment of the motor organs, most often due to rheumatoid arthritis (RA). Locomo25 is a new index developed for the early detection of locomotive syndrome. It consists of 25 items associated with pain, physical activity, and subjective state of health, with a score of 7 points or higher classed as Grade 1 locomotive syndrome and a score of 16 points or higher as Grade 2. In RA, joint impairment causes the appearance of problems affecting motor organs as a whole, as well as progressive functional impairment. As functional impairment progresses, it causes increasing immobility, which raises the risk of osteoporosis.Objectives:Locomo25 was used to investigate functional impairment and its association with RA disease activity and osteoporosis indicators.Methods:The subjects were 105 patients with RA (24 men and 81 women) with a mean age of 68.7 (28–91) years. In terms of staging, 25 were Stage I, 22 Stage II, 17 Stage III, and 41 Stage IV, and their motor disability was Steinbrocker Class 1 in 68 cases, Class 2 in 27, Class 3 in 9, and Class 4 in 1. Disease activity according to the Disease Activity Score 28 with erythrocyte sedimentation rate (DAS28 ESR) was assessed as remission in 44 cases, low disease activity in 24, moderate in 33, and high in 4. The associations between the Locomo25 score and disease activity indices, bone mineral density (BMD), and bone turnover markers (TRACP-5b, NTX, urinary DPD, BAP, total P1NP, and 25(OH)D) were investigated.Results:Locomo25 grade was 0 in 37 cases (35.2%), 1 in 24 (22.9%), and 2 in 44 (41.9%). Locomo25 grade was significantly associated with Steinbrocker class (r= 0.4299, Spearman’s rank correlation coefficient,p< 0.0001). DAS28 ESR and Health Assessment Questionnaire scores increased as locomotive syndrome progressed. There was no significant difference in eGFR between groups, but bone resorption markers (TRACP-5b, NTX, and urinary DPD) and a bone quality marker (pentosidine) decreased significantly as locomotive syndrome progressed. There were no significant differences in BMD or other bone turnover markers.Conclusion:The Locomo25 score was useful for evaluating functional impairment in RA. The prevalence of Grade 2 locomotive syndrome in the general population is reported to be around 25%, and many patients with RA had advanced locomotive syndrome. Although there was no significant difference in BMD, elevated bone resorption and deteriorating bone quality were associated with progressive functional impairment, suggesting that RA patients with advanced locomotive syndrome may be at risk of increasingly severe osteoporosis as a result of immobility.References:[1]Yoshimura Y, Ishijima M, Ishibashi M, Liu L, Arikawa-Hirasawa E, Machida S, Naito H, Hamada C, Kominami E. J Orthop Sci. 2019 Nov;24(6):1094-1104. doi: 10.1016/j.jos.2019.08.009. Epub 2019 Sep 3.[2]Siu PPY, Cheung PWH, Cheung JPY. J Orthop Sci. 2019 Nov;24(6):1110-1117. doi: 10.1016/j.jos.2019.07.012. Epub 2019 Aug 14.Disclosure of Interests:None declared

Background We sought to evaluate the hip abduction strength in patients before and after lumbar surgery. Materials and methods Eighty-four patients (51 males and 33 females) undergoing surgery for lumbar disc herniation or lumbar canal stenosis were selected. Mean age was 64.7 ± 13.8 years. Seven patients (8.3%) had surgery at multiple levels, including L2-L3 (group A), 27 (32.1%) patients had surgery at multiple levels including L3-L4 (group B), 32 (38.1%) patients had surgery at the L4-L5 level only (group C), and 18 (21.4%) patients had surgery at the L5-S1 level only (group D). Hip abduction strength was measured in the 84 patients preoperatively and in 49 patients postoperatively. Results In all patients, preoperative mean hip abduction strength on the symptomatic side and the asymptomatic side was 71.4 ± 34.5 N and 90.7 ± 36.5 N, respectively (p = 0.0008). In groups A and B, there were no significant differences between the mean hip abduction strength on the symptomatic and contralateral side. In group C, those on the symptomatic and contralateral side were 68.0 ± 33.5 N and 89.3 ± 34.8 N, respectively (p = 0.0181). In group D, those on the symptomatic and contralateral side were 74.3 ± 42.4 N and 101.7 ± 44.7 N, respectively (p = 0.0314). In the 49 patients of all groups that could be measured postoperatively, there were no significant differences between the mean hip abduction strength on both sides. Conclusions It was confirmed that the gluteus medius, which was main hip abductor, was mainly innervated by L5 and its mean strength significantly improved postoperatively. The possibility of improvement of hip abduction strength, especially with unchanged tibialis anterior strength, could be very useful for operative decisions.

Background Treatment of rheumatoid arthritis (RA) has improved dramatically with the widespread use of biological disease-modifying antirheumatic drugs. In this context, the number of RA patients who undergo orthopaedic surgery is reportedly decreasing. However, the number of RA patients who undergo foot surgery is increasing. Joint ultrasonography has been used for early diagnosis and disease activity assessment in RA, allowing visualisation of synovitis. However, few detailed studies or evaluations of clinical parameters related to synovitis in the foot have been performed. Objectives This study investigated the association between synovitis in the foot as observed on joint ultrasonography and the degree of disability on the health assessment questionnaire (HAQ) in RA patients. Methods The study included 79 outpatients (101 feet) with RA. Patients who had undergone surgery were excluded. The mean age was 66.0 years (24–92 years), and the mean disease duration was 13 years and 5 months (ranging from 1 month to 49 years). Joint ultrasonography was performed by the same examiner using the same diagnostic instrument in the same room. Synovitis was defined as a power Doppler score of ≥Grade 1. The scanning sites were forefoot (metatarsophalangeal joints of toes 1–5), metatarsus (calcaneocuboid and talonavicular joints), and hindfoot (talocrural and subtalar joints, peroneal tendon, posterior tibial tendon). The presence or absence of synovitis was evaluated at each site, and the association with the HAQ score was examined. Results Synovitis was detected in the forefoot of 40 feet (39.6%), in the metatarsus of 34 feet (33.7%), and in the hindfoot of 63 feet (62.4%). Patients with synovitis in the forefoot (PD+: 0.41±0.1, PD-: 0.80±0.1, p=0.018) and hindfoot (PD+: 0.52±0.1, PD-: 0.86±0.1, p=0.043) had significantly lower HAQ scores. Conclusions Given that assessment of foot impairment is not included in the disease activity index for RA, there may be a delay in diagnosis of foot lesions. Our results showed that patients with synovitis in the forefoot and rearfoot had lower HAQ scores (disability measure), suggesting that increased physical activity may be associated with increasing incidence of synovitis in the foot. The ability of RA patients to perform activities of daily living may have improved with advances in pharmacotherapy, leading to increased physical stimulation, resulting in an increased incidence of synovitis of the foot. References [1] Brown AK. Arthtitis Rheum58(10); 2958–67: 2008 [2] Wakefield RJ. Ann Rheum Dis63; 382–5: 2004 Disclosure of Interest None declared

Background Few studies have reported long term clinical outcome of patients with early phase rheumatoid arthritis (RA). Objectives The objectives of this study were to investigate outcome of 2 years treatment for RA which was started less than 12 months after RA symptoms first appeared and to evaluate prediction factors of poorly controlled patients at 2 years. Methods From a total of 1663 RA patients registered in the Akita Orthopedic Group on Rheumatoid Arthritis (AORA) in 2012, 66 patients were treated within the first year of RA appearance, and enrolled in this study. Sex, age, RA disease duration, Steinbroker9s stage, Steinbroker9s class, medications and DAS28-CRP at the baseline and 2 years post-treatment were evaluated. Furthermore, we compared the group of remission (REM) or low disease activity (LDA) with the group of medium disease activity (MDA) or high disease activity (HDA) at 2 years. Results At the baseline, the patients included 13 males and 53 females. Mean age and RA disease duration were 59 (21–85) years and 7 (1–11) months, respectively. Fifty-four, 8, 4 and 0 patients were classified into Steinbroker9s stage I, II, III, and IV, respectively. Thirty-nine, 25, 2 and 0 patients were classified into Steinbroker9s class I, II, III, and IV, respectively. Thirty-seven (56%), 24 (36%), and 16 (24%) patients were treated with MTX, DMARDs, and PSL, respectively. In DAS28-CRP, 19 (29%), 13 (20%), 32 (48%), and 2 (3%) patients showed REM, LDA, MDA, and HDA, respectively. Forty-four patients were followed-up for 2 years. At 2 years, 30, 7, 5, and 2 patients were classified into Steinbroker9s stage I, II, III, and IV, respectively. Thirty-one, 12, 1, and 0 patients are classified into Steinbroker9s class I, II, III, and IV, respectively. In DAS28-CRP, 33 (75%), 4 (9%), 7 (16%), and 0 (0%) patients showed REM, LDA, MDA, and HDA, respectively. Compared with the group of REM or LDA, the group of MDA or HDA had significantly older age (P=0.018), higher Steinbroker9s stage (P=0.012) and higher DAS28-CRP (P=0.049) at the baseline. Conclusions At 2 years, 75% of patients with early phase RA achieved REM. Older age, higher Steinbroker9s stage and higher DAS28-CRP at the baseline could be prediction factors of poorly controlled patients at 2 years. Acknowledgement We wish to thank the members of AORA. Disclosure of Interest None declared

Background Multi-slice computed tomography (CT) is frequently used to evaluate the morphology, arrangement, and other characteristics of bone. Three-dimensional volume rendering (3D-VR) has made it possible to three-dimensionally visualise tendons and other structures by arbitrarily changing CT values. In deformities of the forefoot region in rheumatoid arthritis (RA), dislocation of the metatarsophalangeal (MTP) joints results in the formation of painful calluses that require surgery; however, the toes can sometimes be displaced inwards or outwards by this dislocation. MTP joint dislocation also causes the flexor tendons to dislocate from their original positions, although the relationship with toe displacement is unclear. Objectives We therefore used 3D-VR to examine the relationship between the flexor tendons and toe displacement in the dislocated toes of RA patients. Methods Thirty-one feet (10 right and 21 left) of 24 patients (5 men and 19 women) were examined. The Tsuboi classification was used to classify MTP joint dislocation into subluxation (Grade 2) or dislocation (Grade 3). CT images taken with no load applied to the feet were used for preoperative evaluation. The mean age of the patients at the time of imaging was 59.0 (36–76) years. A Fujifilm volume analyzer (SYNAPSE VINCENT) was used for 3D-VR reconstruction and CT values were adjusted to visualise the flexor tendons and examine their relationship with the heads of the metatarsal bones. When the flexor tendons were displaced inward or outward from the base of the metatarsal bone head, this was classified as flexor tendon dislocation. Toe displacement was identified when the proximal phalanx was displaced inward or outward from the extended line of the metatarsal axis. Results MTP joint dislocation was seen in 80 toes (63 cases of dislocation and 17 cases of subluxation). The flexor tendons were dislocated in 27 s toes (15 inward and 12 outward), 27 third toes (21 inward and 6 outward) and 16 fourth toes (15 inwards and 1 outward). Of the cases of MTP joint dislocation, toe displacement was seen in 12 s toes (1 inward and 11 outward), 12 third toes (12 outward) and 2 fourth toes (1 inward and 1 outward). The flexor tendons were dislocated towards the displaced toes in all cases. No flexor tendon dislocation was seen in any of the cases of subluxation. Conclusions RA is often accompanied by hallux valgus and toe displacement is affected by retraction of the first toe. The results of this study demonstrate that the toes are displaced inwards in some cases and can become dislocated independent of the influence of the first toe. All the toes were displaced towards the dislocated flexor tendons and MTP arthritis had resulted in loosening of the joint capsule and ligaments and dislocation of the flexor tendons, which was likely to cause displacement. Disclosure of Interest None declared

Background In recent years, joint ultrasonography has been widely used for the diagnosis and treatment of rheumatoid arthritis (RA), allowing visualization of synovitis. Its clinical usefulness in early diagnosis and evaluation of disease activity has been reported. Continuous inflammation, osteochondral destruction, and soft tissue destruction due to synovitis in toe joints result in various clinical pictures of the foot. In the lateral toes in the forefoot, subluxation or luxation of the metatarsophalangeal (MTP) joints may occur, leading to painful callosities and resultant disturbance in activities of daily living. Few reports have addressed toe deformity and joint ultrasonographic findings of synovitis in the forefoot. Objectives In this study, lateral MTP joints were assessed using joint ultrasonography in RA patients to examine the correlation with deformity. Methods Seventy feet of 61 RA patients were examined in the outpatient clinic of our hospital. Patients who underwent surgery were excluded. The mean age of the patients was 66 years (24 to 92 years), and the mean duration of disease was 12 years and 9 months (1 month to 40 years). Biologic products were used for 23 feet. Joint ultrasonography was performed by the same examiner, using the same room and apparatus. Synovitis was defined as Grade 1 or more as determined by the power Doppler method. Based on foot radiographs in upright position obtained before and after ultrasonography, patients with luxation, subluxation, and joint fissure narrowing were classified into the deformity group, those with bone erosion and geode formation into the bone erosion group, and lack of abnormal findings into the normal group. Results Synovitis was found in MTP joints in 41 (14.6%) of 280 toes. The incidence rates of synovitis in the deformity group, the bone erosion group, and the normal group were 27.3%, 13.1%, and 6.7%, respectively. Synovitis was found in 21.7% of patients on therapy with biologic products and in 38.3% of those without such therapy. There were no significant differences in the mean duration of the disease, visual analogue scale score, erythrocyte sedimentation rate, matrix metallopeptidase 3 level, or health assessment questionnaire score among the 3 groups. Conclusions Synovitis was also found in patients who showed no changes on imaging of the toes. Synovitis persisted in some patients even after establishment of toe deformity. Drug therapy, intensification of conservative therapy, and synovectomy should be considered to prevent further deformation. References Wakefield RJ. Ann Rheum Dis 63; 382–5: 2004. Brown AK. Arthtitis Rheum 58(10); 2958–67: 2008. Acknowledgements The authors wish to acknowledge Miss Sasaki, for her help in interpreting the significance of the results of this study. Disclosure of Interest None declared

Background Few studies have compared rheumatoid arthritis (RA)-related disorders of the cervical and lumbar spine. Objectives The objectives of this study were to examine the prevalence of and risk factors for cervical and lumbar spinal instability in patients with RA. Methods From a total of 1,843 patients registered in the Akita Orthopedic Group on Rheumatoid Arthritis (AORA), 135 patients [118 women, 17 men; mean age, 66 (41–84) years; mean disease duration, 14 (1–63) years] who underwent a radiographic examination were enrolled in this study. In the cervical spine, we defined instability as one of the following characteristics: (1) atlantodental interval (ADI) >3 mm, (2) Ranawat value 3 mm at the subaxial cervical spine on an anteroposterior bending plain radiograph. In the lumbar spine, instability was defined as anteroposterior translation >3 mm on a neutral plain radiograph. At the time of radiographs evaluation, demographic characteristics, clinical variables, medical history and current medications were investigated. The patients were classified into two groups: with both cervical and lumbar spinal instabilities and without. The independent risk factors for both cervical and lumbar spinal instabilities were then determined using multivariate logistic regression analysis. Results Forty-six (34.1%) patients exhibited cervical spinal instability, and 50 (37.0%) patients exhibited lumbar spinal instability. Twenty-four patients (17.8%) exhibited both cervical and lumbar spinal instability. The presence of both cervical and lumbar spinal instability was significantly and independently associated with disease duration (OR: 1.06; 95% CI: 1.01–1.12). Conclusions The prevalence of both cervical and lumbar spinal instability in patients with RA was 17.8%. Disease duration was independent risk factor for presence of both cervical and lumbar spinal instability in this study. Disclosure of Interest None declared

Background The Akita Orthopedic Group on Rheumatoid Arthritis (AORA) encompasses 32 physicians and 28 clinics providing medical care to rheumatoid arthritis (RA) patients in Akita Prefecture, Japan. The patient registry for this group (the AORA registry) reflects actual clinical data on RA therapy in Akita, where the proportion of elderly (age ≥65 years) residents in the population is the highest in Japan. Etanercept (ETN) is a tumor necrosis factor inhibitor reportedly associated with fewer adverse event-related treatment discontinuations than other drugs of this class. However, few evaluations of the efficacy and safety of ETN have been reported for elderly populations. Objectives Based on data from the AORA registry, we aimed to investigate the continuation rate for ETN therapy, reasons for discontinuation, and therapeutic effects among elderly RA patients living in Akita. Methods Among 204 AORA-registered patients starting ETN therapy between January 2009 and August 2014, data for the 73 patients (35.8%) who were ≥65 years old at the initiation of therapy were evaluated. Mean age was 72.4±4.7 years (range 65–83 years), and 79.5% were women. Mean disease duration was 15.1±12.6 years (range 9 months-55 years), 13.7% of patients were switching from another biologic agent, 49.3% could perform activities of daily living (ADL) independently, and 65.8% had at least one of the following comorbidities: hypertension, diabetes, respiratory disorder, cardiovascular disease, and cerebrovascular disease. We evaluated the 1-year cumulative continuation rate for ETN therapy using the Kaplan–Meier method, and investigated the characteristics of patients who discontinued treatment because of adverse events (AE cohort) or lack of efficacy (LOE cohort). We evaluated efficacy in 55 patients for whom Disease Activity Score – C-reactive protein assessments were possible, based on European League Against Rheumatism (EULAR) criteria. Results The 1-year cumulative continuation rate for ETN therapy was 87.2%, and 24 patients discontinued treatment. The AE and LOE cohorts contained 12 and 7 patients, respectively. The AE cohort had a mean age of 75.5 years at the start of treatment, with a mean disease duration of 20.7 years, 8.3% of patients switching from another biologic agent, 16.7% performing ADL independently, and a comorbidity rate of 100%. Corresponding values for the LOE cohort were: mean age, 71.4 years; disease duration, 12.7 years; switching from another biologic agent, 42.9%; performing ADL independently, 57.1%; and comorbidity rate, 28.6%. Efficacy was noted for 81.8% of all patients with 52 weeks of ETN therapy, achieving good efficacy in 21 cases and moderate efficacy in 24 cases. Conclusions Retention rate and efficacy were considered satisfactory in elderly RA patients receiving ETN therapy. The risk of adverse events was suggested to increase with increasing age, declining ADL, and presence of comorbidities. These factors require attention when prescribing ETN therapy. References Cho SK, Sung YK, Kim D, et al. Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis. BMC Musculoskelet Disord. 2016; 17: 333. Disclosure of Interest None declared

A fundamental issue concerning iron-based superconductivity is the roles of electronic nematicity and magnetism in realising high transition temperature (T c). To address this issue, FeSe is a key material, as it exhibits a unique pressure phase diagram involving non-magnetic nematic and pressure-induced antiferromagnetic ordered phases. However, as these two phases in FeSe have considerable overlap, how each order affects superconductivity remains perplexing. Here we construct the three-dimensional electronic phase diagram, temperature (T) against pressure (P) and isovalent S-substitution (x), for FeSe1−xSx. By simultaneously tuning chemical and physical pressures, against which the chalcogen height shows a contrasting variation, we achieve a complete separation of nematic and antiferromagnetic phases. In between, an extended non-magnetic tetragonal phase emerges, where T c shows a striking enhancement. The completed phase diagram uncovers that high-T c superconductivity lies near both ends of the dome-shaped antiferromagnetic phase, whereas T c remains low near the nematic critical point., The overlap between different phases has hindered the understanding of how each phase affects superconductivity in FeSe. Here, Matsuura et al. achieve a complete separation of non-magnetic nematic and antiferromagnetic phases for FeSe1-xSx, observing a tetragonal phase in between with a strikingly enhanced T c.

The central amygdala (CeA) has key functions in modulating pain-related behaviors and exhibits experience-dependent plasticity in the context of chronic pain. Recent work from our lab has further revealed that distinct CeA cell types contribute differently to behavioral outcomes in pathological pain states in mice. Cells expressing Protein Kinase C delta (CeA-PKCδ), for example, promote hypersensitivity and display increased excitability following injury. By contrast, somatostatin-expressing CeA (CeA-Som) neurons contribute to an endogenous analgesic tone at baseline and display suppressed excitability during nerve-injury. The cellular mechanisms driving this opposing modulation of pain-related behaviors are still poorly understood. We hypothesized that the convergence of genetic identity, intrinsic membrane properties and morphological characteristics of distinct subpopulations of neurons contributes to the functional heterogeneity in the CeA. Here, we begin to test this hypothesis by characterizing the electrophysiological and morphological properties of CeA-PKCδ and CeA-Som neurons. Preliminary results from whole-cell patch-clamp electrophysiology experiments in acute amygdala slices show that the electrophysiological properties of CeA-PKCδ and CeA-Som neurons are distinct. Firing properties in CeA-PKCδ neurons, for example, are highly heterogeneous, with spontaneously active, accommodating, and non-accommodating cells found among this population. In contrast, the overwhelming majority of CeA-Som neurons are either spontaneously active or non-accommodating. Notably, non-accommodating CeA-Som neurons are more excitable than non-accommodating CeA-PKCδ neurons, displaying increased firing responses to depolarizing current injection, reduced latencies to first spike and after hyperpolarizations and changes in resting membrane potentials. Ongoing experiments are evaluating the morphological properties of these genetically distinct cells, with the end goal of correlating pain-related behaviors with morphological properties, genetic identity and firing properties. Altogether, our results demonstrate that the output gain of CeA-Som cells is significantly greater than that of CeA-PKCδ neurons, suggesting that cell-type-specific differences in neuronal excitability might contribute to functional heterogeneity in the CeA.

Background Here we report the first autopsied case involving pathological examination after two resections of symptomatic ossification of the anterior longitudinal ligament with anterior osteophytes and etidronate treatment with more than 8 years of follow-up. Case presentation A 51-year-old Japanese man complained of severe dysphagia due to esophageal compression by ossification of his anterior longitudinal ligament with anterior cervical osteophytes. Although surgical removal of the anterior cervical osteophytes was performed following etidronate treatment (800 mg/day for 6 months), dysphagia occurred secondary to recurrent ossification of his anterior longitudinal ligament with anterior osteophytes 7 years after the initial resection. A second resection of the anterior cervical osteophytes was performed, and cyclic administration of etidronate disodium (1000 mg/day, 3-month administration and 3-month cessation) did not result in re-outgrowth of ossification of his anterior longitudinal ligament with anterior osteophytes. At 1 year and 6 months after the second surgery, he suddenly died. The pathological findings associated with the ossification of his anterior longitudinal ligament during etidronate therapy showed no recurrence of ossification of the anterior longitudinal ligament with anterior osteophytes. Conclusion A recurrence of ossification of the anterior longitudinal ligament with anterior osteophytes formation, which caused dysphagia, was not observed with the cyclic administration of etidronate disodium at a dose of 1000 mg/day every 3 months for a period of 1 year and 5 months in the present case.

We present a patient who had adult-onset Still's disease (AOSD) complicated by thrombotic thrombocytopenic purpura (TTP) that resulted in retinal microangiopathy and rapidly fatal cerebral edema. The patient was a 37-year-old male who developed fever, eruption, arthritis and hepatic dysfunction, that, based on close examination, was diagnosed as AOSD. Despite treatment with corticosteroids, the patient developed acute visual field defect, neurological deterioration including convulsions and impaired consciousness, as well as acute renal failure that ultimately resulted in death. Pathological examination of autopsy specimens revealed multiple fibrin thrombi disseminated in small vessels of the brain and kidney, which was consistent with TTP, along with marked cerebral edema. Although TTP has rarely been reported in association with AOSD, awareness of the possible coexistence of these two diseases is important for diagnosis and treatment.

Tree species composition is influenced not only by edaphic and climatic factors but also by natural and human-caused disturbances. To understand interactions among these influences, we compared forest species composition data from the time of European settlement with modern data. We derived elevation data for 2529 trees mapped by early land surveys (1770–1850) across a 1000 m elevation gradient in central New Hampshire and compared these with modern data (2004–2009) from the Forest Inventory and Analysis program (123 plots containing 2126 trees) and from permanent plots representing case studies of different land-use histories. Spruce and beech are much less abundant today at all elevations than they were prior to settlement, while maples and birches have increased. Fir, hemlock, pines, and oaks have changed little in distribution, although pines and oaks increased in abundance somewhat. Land-use history (agriculture below 500 m and cutting of various intensities at all elevations) is likely the primary explanation for these shifts, although climate change is also an important factor for some. A clearer understanding of presettlement forest composition improves our ability to separate the relative importance of natural and human-driven influences on the species composition of today’s forests.

To investigate the prevalence of and elucidate risk factors for lumbar spondylolisthesis in patients with rheumatoid arthritis (RA).From 1843 patients registered to the Akita Orthopedic Group on Rheumatoid Arthritis registry, participants comprised 128 patients who had undergone comprehensive radiographic examinations. The presence of lumbar spondylolisthesis (≥5% slip percentage) was assessed from L1 to L5 on lateral plain radiographs. At the time of radiographic evaluation, we also determined the following: RA disease duration; stage and class of Steinbrocker's classification; serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity for RA; history of joint surgery; the presence of cervical spinal instability; and details and doses of medications for RA.Forty-seven (36.7%) patients showed lumbar spondylolisthesis (L4, 48%; L3, 29%; L2, 13%; L5, 10%). Among these, Meyerding Grade was I in 89% and II in 11%. Multivariate analysis showed lumbar spondylolisthesis as significantly and independently associated with higher serum CRP level (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.00-2.25; p = 0.048) and history of joint surgery (OR, 2.87; 95%CI, 1.22-6.72; p = 0.015).More than one-third of patients with RA in this cohort had lumbar spondylolisthesis, and significant associations with higher serum CRP levels and history of joint surgery were identified.

It has recently been reported that bisphosphonates are the most common treatment for osteoporotic patients. However, they are many problems, including poor bioavailability and adherence, as well as adverse drug reactions. Therefore, intravenous administration of bisphosphonates has been developed to resolve these problems. In Japan today, alendronate and ibandronate have been approved for intravenous administration, and they have advantages, such as good adherence and better gastrointestinal tolerability, compared to oral administration. We attempted to confirm the effects of administration of intravenous alendronate, which is not inferior to oral administration, for osteoporotic patients in earlier research. 200 consecutive Japanese over 70 years-old postmenopausal women who visited the first author’s orthopedic clinic and had femoral neck or lumbar spine bone mineral density (BMD) values more than 2.5 SD lower than the reference values were randomly enrolled in this study. 100 subjects were recruited for administration of intravenous alendronates because of their poor adherence, no respond of treatment status, and gastrointestinal adverse effects. Furthermore, 10 of these subjects were excluded due to discontinuation, and a total of 90 subjects were eligible for the intravenous group. The remaining 50 patients received oral alendronate. The present study also showed no significant difference between intravenous and oral administration with respect to BMD, biochemical bone turnover markers, and the incidence of fractures. These results show that intravenous administration of alendronate is not inferior to oral alendronate for the treatment of osteoporosis. Therefore, intravenous administration of alendronate can be recommended if patients do not tolerate or adhere to oral bisphosphonates.

This paper deals with the quenching problem of vortex-induced vibrations by using devices composed of Hula-Hoops and generators. These devices are also able to generate electricity. The experiment was made concerning the quenching problem of the vortex-induced vibrations of towering structures with the devices. Moreover, a numerical analysis was also carried out using the Runge–Kutta–Gill method. An optimum approach for quenching the vortex-induced vibrations of low and high flexural rigidity directions are discussed. As a result, the following was made clear: (1) The vortex-induced vibrations of both flexural rigidity directions were well quenched for a wide range of wind velocities and the different wind directions by using four devices simultaneously. (2) The optimally quenched vibration was a chaos of intermittency. (3) A condition of maximum power generation was not equal to that of the optimum vibration quenching of the main system. (4) The experimental and the analytical results were in good qualitative agreement with each other.

The cyclic compression of a cellular Al alloy has been evaluated. Plastic compression occurs beyond a critical number of cycles, NT. At N NT, strain accumulates rapidly and preferentially within deformation bands, until the densification strain has been reached. The bands form preferentially from large cells in the ensemble. Such cells develop plastically buckled membranes which experience large strains upon further cycling, which lead to cracks. The cracks, once formed, result in rapid cyclic straining. This feature controls the fatigue life.

In this paper the dynamic response of a system of two structures placed adjacent to each other is studied. The force on the system consists of earthquake loading applying for its spatial variability over short distances. The spatially variable ground motion is defined and explored by two different approaches. First, the deterministic approach accounting only for effects of wave passage of surface waves and inclined body waves, and second, the stochastic (random) approach considering also degree of coherency between motions at every two points of the ground surface as a factor. Effects of the ground motions identified as above on the response of the system are examined assuming a harmonic excitation and considering type of the wave and angle of incidence of the body waves. It is shown that resonance frequency increases with closeness of structures. Moreover, for some cases depending on the distance between the adjacent structures, the structural response increases. The random approach gives more satisfactory results in this comparison study.

The thermomechanical properties of thin DLC films on steel substrates have been measured and related to their structure. The modulus and thermal expansion coefficient have been determined from beam curvature measurements conducted on Si and steel substrates. The fracture toughness and the adhesion have been characterized by using probes that introduce controlled strains into the DLC, through the substrate. Multistrain and sphere impression methods have been used for this purpose. The strains cause multiple cracking and local spalling events that can be analyzed to obtain the toughnesses. The DLC toughness is found to be similar to that for typical carbides. The interfaces have a much greater toughness, attributed to the use of a thin Cr adhesion layer.

The mechanical properties of three different commercially available closed cell Al alloys all made by foam casting are examined. The objective is to assess the roles of cell morphology and of imperfections in governing the basic properties: stiffness, yield strength and fracture resistance. This assessment provides goals for manufacturing strategies that enable attainment of good mechanical performance with affordable process technologies. A prevalent role of curves and wiggles in the cell walls on stiffness and strength (anticipated by models) is affirmed by the present measurements. Systematically larger stiffnesses and yield strengths found in tension than in compression are consistent with a prominent role exerted by such imperfections. Moreover, foam casting is apparently capable of cell morphologies that impart properties approaching the best achievable values for an isotropic closed cell solid, devoid of imperfections. There are associated implications for performance and affordability. Fracture measurements indicate crack growth occurring along the cell walls by a mechanism analogous to the plastic tearing of thin sheets. The crack growth resistances are in the range of 1 kJm−2. This mechanism infers a toughness that scales with the cell wall thickness and its yield strength.

The fracture characteristics of monotonically loaded cracks located parallel to, in the vicinity of, and at arbitrary angles to the interface between two elastic solids have the subjects of considerable theoretical research in the literature. The present experimental work on steel-steel bimaterials clearly demonstrates that, for essentially the same elastic properties, the plastic mismatch between the constituent layers of bilayer composite can dictate whether a fatigue crack approaching the interface at various angles continues to advance through the interface or arrests prior to penetrating the interface. The former crack arrest phenomenon occurs when the fatigue crack approaches the interface from the plastically weaker material, whereas continued crack growth results when the crack approaches the interface from the plastically stronger material. The observed experimental trends are qualitatively consistent with the numerical predictions of crack-tip shielding or amplification from the interaction of the near-tip plastic zone with an interface oriented normal to the plane of the crack. When the fatigue crack is initiated parallel to the interface, it deviates from the strongly bonded interface to advance in one of the two steels. This trend appears to experimentally confirm predictions of the possible evolution of strong mode mixity ahead of interface cracks subjectedmore » to cyclic tensile loading.« less

Background The goal of rheumatoid arthritis (RA) treatment is to achieve clinical, functional, and structural remission. Tocilizumab (TCZ), an anti-interleukin-6 receptor monoclonal antibody agent, has a high compliance rate and can maintain clinical and functional remissions. Imaging examination for structural remission is advanced; however, the accuracy of evaluation results is inconsistent. Joint ultrasonography is an important measurement tool to comprehensively evaluate synovitis according to the presence or absence of blood flow signal. However, only a few reports have evaluated the efficacy of TCZ by using joint ultrasonography. Objectives The objective of this study was to evaluate the correlation between positive blood flow signal on joint ultrasonography and progression of joint destruction in patients with RA treated with TCZ for 4 years. Methods Among 111 patients who were treated with TCZ in the Akita Orthopedic Group on Rheumatoid Arthritis (AORA), 16 patients were receiving TCZ for 4 years or longer and enrolled this study. We examined age, sex, disease duration, C-reactive protein (CRP) level, MMP3 level, DAS28-ESR score, and clinical disease activity index (CDAI) at the start of TCZ administration and once a year. Moreover, we examined for blood flow signal (power Doppler signal) on joint ultrasonography at 4 years and modified total Sharp score (mTSS) on radiography at the baseline and once a year. Joint ultrasonography was performed in 34 joints, including bilateral proximal interphalangeal and metacarpophalangeal joints of the five fingers, wrists, knees, and metatarsophalangeal joints of the five toes in all of the patients, as well as other joints with symptoms. The subjects were divided into the P(+) and P(−) groups according to the presence or absence of blood flow signal on joint ultrasonography at 4 years. Eight patients were classified into the P(+) group and 8 were the P(−) group. Furthermore, progression of joint destruction by using mTSS were compared among both groups. Results The mean patient age was 52 (range, 38–63) years, and the mean disease duration was 92 (range, 30–159) months. Women accounted for 69% of the patients. At the start of TCZ administration, no significant differences in age, proportion of women, disease period, CRP, CMMP3, and CDAI were observed between both groups. However, the DAS28-ESR score was significantly higher in the P(+) group than in the P(−) group (p=0.0279). Before the start of TCZ therapy, the scores of mTSS/year were 3.9 in the P(+) group and 2.7 in the P(−) group, showing no significant difference. After the start of TCZ therapy, the scores of mTSS/4 years were 3.4 in the P(+) group and 0.2 in the P(−) group, showing a significant difference (p=0.0347). Conclusions The presence of positive blood flow signal on joint ultrasonography at 4 years was significantly correlated with progression of joint destruction in patients with RA treated with TCZ. Acknowledgement We wish to thank the members of AORA. Disclosure of Interest None declared

Background The proportion of the aging population is increasing worldwide. Currently, the population of aging individuals is the highest in Japan; the percentage of 65-year-old people is 26.7%, indicating an aged society. Furthermore, the proportion of elderly people over 65 years of age is the highest (33.6%) in Akita prefecture, Japan. Objectives We investigated the data of patients with rheumatoid arthritis (RA) in various medical centers where in the orthopedic surgeons belonged to Akita Orthopedic Group on RA (AORA) in Akita. We think that Akita registry is the future vision for RA treatment. Methods In this cohort study, we examined 324 of 2021 cases of patients aged ≥80 years (16.0%) from AORA registry in 2015 (average age, 66 years). Results The average age of our cohort was 84 years (range, 80–99 years); of the 324 patients, 59 were men and 265 were women, and the average disease period was 14 years (range, 2 months–66 years). Two-hundred sixty eight (83.0%) cases were of elderly-onset RA (EORA). According to the Steinbrocker classification criteria, 82 cases were stage I; 69, stage II; 80 stage III; and 87, stage IV. Further, 77cases were cass 1; 128 class 2; 89 class 3; and 22, class 4. The past medical history of the patients was as follows: 176 cases of hypertension, 59 cases of respiratory diseases, 56 cases of heart diseases, and 38 cases of diabetes. MTX (average, 5.5 mg per week; range, 1–14 mg per week) was administered to 101 patients. Prednisolone (average, 3.8 mg/d; range, 1–12.5 mg/d) was administered to 170 patients. A combination of conventional systemic disease-modifying antirheumatic drugs was administered as follows: bucillamine to 97, salazosulfapyridine to 84, tacrolimus to 21, mizoribine to 8, gold sodium isothiomalate to 7, actarit to 5, iguratimod to3, and auranofin to 1 patient. Biologics were administered to 33 patients (10.2%); etanercept was administered to 15, abatacept to 6, adalimumab to 4, tocilizumab to 4, infliximab to 3, golimumab to 1, and certolizumab pegol 1 patient. DAS28CRP remission was observed in 149 patients. The disease activity was low, moderate, and high in 53, 74, and 4 patients, respectively. In our study, a few patients showed high disease activity and an increase in the extent of functional disorder. These results may be attributed to the limited number of patients visiting the orthopedic department and the quality of the patients. Conclusions The study showed the low using ratio of MTX and high using ratio of PSL as much as previous reports. Sixty two percent of RA patients over 80 years of age showed rather low disease activity. Conventional therapy, without the use of bDMARDs, was used to treat 89.8% of the elderly patients with RA. References Miyamoto S, Sugimura Y, Kashiwagura T, Urayama M, Kobayashi M, et al; Evaluation for treatment of rheumatoid arthritis patients in AORA cohort. The Japanese Society for Clinical Rheumatology and Related Reserch 2015, 27: 135–45. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA), caused by upregulation of proinflammatory cytokines, is characterized by overexpression of receptor activator of nuclear factor kappa-B ligand (RANKL) in the synovial membrane, which promotes osteoclast differentiation and thus increases bone resorption. Denosumab, an antibody against RANKL, prevents RANKL/RANK interactions and inhibits osteoclast-mediated bone resorption. This study investigated whether denosumab can prevent the inflammation caused by excessive bone resorption in RA patients in comparison with bisphosphonates, which directly prevent osteoclast-mediated bone resorption. Objectives RA patients in the Akita Orthopedic Group on Rheumatoid Arthritis (AORA) registry included 58 and 49 newly denosumab-treated and bisphosphonate-treated patients, respectively. Methods For RA, the Steinbrocker classification was measured at pretreatment and use of glucocorticoid, methotrexate, and biological agents, DAS28-ESR, simplified disease activity index (SDAI), erythrocyte sedimentation rate, and matrix metalloproteinase 3 were measured at pre-treatment and 6 and 12 months post-treatment. For bone metabolism, bone-specific alkaline phosphatase (BAP), indicating bone formation, tartrate-resistant acid phosphatase 5b (TRACP-5b), indicating bone resorption, and bone mineral density (BMD) of the lumbar and femoral neck were measured at pre-treatment, and 6 and 12 months post-treatment. Results For RA, the Steinbrocker class and stage were significantly higher in the denosumab group compared with the bisphosphonate group (p Conclusions Denosumab and bisphosphonates did not suppress RA activity, but denosumab prevented excessive bone turnover more effectively than bisphosphonates. References Cohen SB, Dore RK, Lane NE, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 58 (5): 1299–1309, 2008. Acknowledgement We thank all the patients and AORA members who participated in this research. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) causes a variety of foot lesions, but the feet and ankles are not included in disease activity indices such as the Disease Activity Score (DAS). The spread and usefulness of joint ultrasonography in RA diagnosis and treatment have recently been reported. Many disease activity indices use tender (painful) joints and swollen joints, but few reports have examined the association between synovitis on joint ultrasonography and physical findings. This study evaluated joint ultrasonography of the metatarsophalangeal (MTP) joint in RA patients and examined the results in conjunction with physical findings. Objectives This study evaluated joint ultrasonography of the metatarsophalangeal (MTP) joint in RA patients and examined the results in conjunction with physical findings. Methods The subjects were 65 RA patients (82 feet) visiting our department on an outpatient basis. Surgical patients were excluded. Their mean age was 64.1 (27–84) years, and the disease stage was Stage I in 19 subjects, II in 11 subjects, III in 10 subjects, and IV in 25 subjects. The degree of functional disability according to the Steinbrocker classification was Class I in 45 subjects, Class II in 16 subjects, and Class III in four subjects. Disease activity according to the DAS28-ESR was complete response in 16 subjects, low disease activity (LDA) in 27 subjects, moderate disease activity in 14 subjects, and high disease activity in 7 subjects. Twenty-two subjects were taking a combination of biological agents. After interviewing subjects about any foot-related complaints, pain and swelling were evaluated, and joint ultrasonography was performed. The same examiner examined all subjects in the same room using the same diagnostic equipment. Grade 1 or higher on power Doppler ultrasonography was defined as synovitis. Results The detection rates of pain, swelling, and synovitis in all 410 toes were 33.9%, 14.1%, and 13.4%, respectively. Forefoot-related complaints were cited in 13 feet, and pain was observed in all subjects. However, synovitis was only detected in 38.5%, and many cases had asymptomatic synovitis. The detection rates of synovitis in subjects taking biological agents and subjects not taking biological agents were 11.0% and 24.4%, respectively, with no significant difference (Pearson9s chi-squared test). When examined according to disease activity, synovitis was observed in 27.9% of those with LDA or less, which was the treatment objective. During the evaluations, joint swelling had to be differentiated from edema in a large number of cases. Conclusions Out of pain, swelling, and synovitis, the detection rate was highest for pain. This was likely due to the inclusion of pain other than that from arthritis, such as from subluxation and dislocation of the MTP joint and plantar calluses. There was a high prevalence of asymptomatic synovitis, suggesting the utility of evaluating synovitis by joint ultrasonography. Acknowledgement The authors thank Miss Sasaki, for her assistance with this project. Disclosure of Interest None declared

The problem of a crack approaching a bimaterial interface is considered in this paper. Attention is focused on an interface between two elastoplastic solids whose elastic properties are identical and whose plastic properties are different. For the case of a crack approaching a bimaterial interface perpendicularly, it is shown by recourse to detailed finite element analyses that the near-tip “driving force” for fracture is strongly influenced by whether the crack approaches the interfaces from the lower strength or the higher strength materials. Specifically, it is demonstrated that the crack-tip is “shielded” from the remote loads when it approaches the interface from the weaker material, and that the effective J-integral at the crack tip is greater than the remote J when it approaches the interface from the stronger material. This plasticity effect determines whether a crack approaching the bimaterial interface continues to advance through the interface or is arrested before penetrating the interface. These theoretical findings are substantiated using controlled experiments of fatigue crack growth perpendicular to a ferrite—austenite bimaterial interface. The effect of the non-singular T-stress, acting parallel to the crack plane, on shielding and amplification of the stress fields is also discussed.

To provide information on the efficacy, safety, and quality of medicine promptly and accurately, we have developed two databases: a literature database with numerical data, and a Drug Information database. By an easy-to-use, company-wide information network system, over 1,000 medical representatives in more than 80 offices throughout Japan can retrieve information. Information derived from the system is displayed on the terminal and the original documents are automatically output through a facsimile.