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Objective To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA). Materials and methods We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon’s test, Schirmer’s test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. Results 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. Conclusion Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

MicroRNAs (miRNAs, miRs) are small non-coding RNAs that mainly function in the post-transcriptional regulation of genes. miRNA that is secreted outside of cells, and which circulates in the peripheral blood, is called circulating microRNA. Systemic lupus erythematosus (SLE) is a typical autoimmune connective tissue disease and is mainly treated with immunosuppressive drugs. Therapeutic apheresis is often used to eliminate autoantibodies and cytokines. We have previously shown that circulating miRNAs in the blood of patients with SLE can be separated and removed from the blood using a plasma separation membrane. In the present study, we further separated circulating miRNA from three SLE patient's blood plasma by passing it through a plasma adsorption membrane, and then measured changes in miRNA levels using miRNAs microarray chip. Although the levels of many miRNAs were unaffected after passage through the plasma adsorption membrane, expression of some miRNAs, including miR-1246, miR-4732-5p, and miR-6088 are declined.

Rheumatoid arthritis (RA) is a systemic inflammatory disease in which the predominant symptom is polyarthritis that follows a chronic and progressive clinical course characterized by destructive synovitis and various immune disorders. Striking progress in RA treatment was achieved with the emergence of monoclonal antibodies to target cytokines. However, drug choices are limited for many patients due to resistance to multidrug antirheumatic therapy, concomitant disease, and infection. We evaluated the efficacy of treatment in 85 patients with RA for whom leukocytapheresis (LCAP) was initiated at our hospital between 2006 and 2015. All patients continued drug therapy and were treated with LCAP once a week for up to 5 weeks. The clinical response was evaluated at the completion of LCAP series and 4 weeks later using the American College of Rheumatology (ACR) criteria and the 28-joint disease activity score (DAS28) of European League Against Rheumatism (EULAR). The tender joint counts, swollen joint counts, and C-reactive protein (CRP) levels decreased remarkably. DAS28-CRP was significantly improved by LCAP. And furthermore, the efficacy lasted at least 4 weeks after the completion of LCAP. These results suggest that LCAP is a beneficial and are consistent with several trials' reported effect of LCAP. This treatment can contribute to improvements in activities of daily living (ADLs) and long-term outcome by improving swollen and tender joint counts and CRP levels even in refractory patients for whom the use of conventional disease-modifying antirheumatic drugs (DMARDs) and biopharmaceuticals is problematic. LCAP might be a promise therapy to refractory RA.

Introduction Temporal artery biopsy is essential for the diagnosis of giant cell arteritis. It has been shown that 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance angiography, and ultrasonography are useful for the diagnosis of giant cell arteritis. However, there are only a few reports on the usefulness of three-dimensional computed tomography angiography in the diagnosis of giant cell arteritis. We describe two cases in which giant cell arteritis was difficult to diagnose using positron emission tomography-computed tomography and magnetic resonance angiography but was diagnosed using three-dimensional computed tomography angiography, thus showing the importance of three-dimensional computed tomography angiography in the diagnosis of giant cell arteritis. Case presentation Case 1: An 81-year-old Japanese man. Laboratory investigations revealed normocytic anemia and raised inflammatory marker levels. Slight bleeding in the right posterior pole of his eyeball and leukoma of his left cornea were observed on fundus examination. Stenosis and stoppage of the temporal artery were detected on three-dimensional computed tomography angiography. A diagnosis of giant cell arteritis was made, and he was started on orally administered prednisolone. His headache and C-reactive protein levels improved. Four weeks after glucocorticoid steroid treatment, three-dimensional computed tomography angiography revealed improvement in stenosis and stoppage of temporal artery. Case 2: A 74-year-old Japanese woman. A dose of 20 mg of prednisolone was administered and her polymyalgia and polyarthritis improved; however, her headache and ear occlusion persisted. Although vasculitis was not detected on positron emission tomography-computed tomography, stenosis and stoppage of the temporal artery were detected on computed tomography angiography. She was diagnosed as having giant cell arteritis and started on orally administered prednisolone treatment (60 mg daily). Her headache and C-reactive protein levels improved. Four weeks after glucocorticoid treatment, three-dimensional computed tomography angiography showed improvement in stenosis and stoppage of temporal artery. Conclusions In both patients with giant cell arteritis, three-dimensional computed tomography angiography revealed improvement in stenosis and stoppage of temporal artery after glucocorticoid treatment. We conclude that computed tomography angiography along with magnetic resonance angiography, positron emission tomography-computed tomography, and ultrasonography are important for the diagnosis of giant cell arteritis.

Objective: We conducted a questionnaire survey within a standard clinical setting to clarify that picture superiority effect (PSE) could be obtained by musculoskeletal ultrasound (MSKUS) examinatio...

Background Japan is the world’s most aged country. The number of patients with polymyalgia rheumatica (PMR) is expected to increase more. Classification criteria including ultrasound findings were published in 2012, but the ability to differentiate PMR from rheumatoid arthritis (RA) was not significant. We will clarify whether recently reported ultrasound findings (1, 2) which could be characteristic in PMR are helpful for distinguishing from other diseases and treatment outcome in suspected PMR patients. Objectives Patients who were clinically suspected of PMR and underwent ultrasound examination from March 2015 to July 2018. Methods Recorded ultrasound images were retrospectively interpreted by the ultrasound expert, who was blind for clinical information. They were classified into three groups of PMR, RA, others/no inflammation. Initial dose of glucocorticoid (GC), therapeutic response, presence or absence of relapse, and concomitant medications were collected and compared among the 3 groups. Cases in which steroids had already been used before ultrasound examination were excluded from the analysis. Results The number of subjects was 81, and the number of ultrasound examination was 88. The ultrasound expert classified 29 PMR, 20 RA, 3 other/no inflammation. 18.5% (15/81) of the subjects were improved with no GC and relapse. The average prednisolone (PSL) dose was 15.3 mg in the PMR group, and 9.7 mg in the RA group. Concomitant medications were introduced in 31% (9/29) of PMR group, in 65% (13/20) of RA group. Conclusion Ultrasound is useful for distinguishing PMR from seronegative RA and other arthralgia. These findings showed that ultrasound is useful for the proper use of GC and concomitant medications. References [1] Suzuki T, Yoshida R, Hidaka Y, Seri Y. Proliferative Synovitis of the Shoulder Bursae is a Key Feature for Discriminating Elderly Onset Rheumatoid Arthritis Mimicking Polymyalgia Rheumatica From Polymyalgia Rheumatica. Clin Med Insights Arthritis Musculoskelet Disord 2017;10: 1179544117745851. [2] Suzuki T, Yoshida R, Okamoto A, Seri Y. Semiquantitative Evaluation of Extrasynovial Soft Tissue Inflammation in the Shoulders of Patients with Polymyalgia Rheumatica and Elderly-Onset Rheumatoid Arthritis by Power Doppler Ultrasound. Biomed Res Int 2017;2017: 4272560. Disclosure of Interests Tomohiro Kawaguchi: None declared, Michihiro Ogasawara: None declared, Ken Yamaji: None declared, Naoto Tamura Grant/research support from: Astellas Pharma Inc., Asahi Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. LTD, Eisai Inc., :Takeda Pharmaceutical Company Ltd., Speakers bureau: Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., :Mitsubishi Tanabe Pharma Co.

Background In the EULAR recommendation on rheumatoid arthritis (RA) treatment, short-term steroid combination should be considered at the start of DMARDs treatment. In this study, we analyzed the present condition of steroid combined use in Japan and the actual situation of side effects in recent years. Objectives RA patients who started treatment with DMARDs at our hospital during July 2008 to April 2018, Methods A new incidence of hypertension (HTN), diabetes (DIB), dyslipidemia (HLP), infection (INF) were compared between the two groups of steroid combined use group (D_PSL) and noncombined group (D_nonPSL) and analyzed by Cox regression analysis. The cases had there complications before the start of RA treatment were excluded from the analysis. Results The number of cases of analysis was 573 (D_PSL = 216, D_nonPSL = 357, average observation period: 5.22±2.70 year), and the new incidence of each complication was INF 50/561 (D_PSL 16.2%vs. D_nonPSL 4.56%[16/351], p=0.000094), HTN 48/527 cases (13.3%[25/188] vs.6.78%[23/339], P = 0.0148), DIB 24/558 (6.16%[13/211] vs. 3.17%[11/347], p = 0.136), HLP 72/542 (15.8%[32/202] vs. 11.8%[40/340], p = 0.198). The incidence of INF was high in D_PSL group in both groups over 65 and under 65 years old (p = 0.00658, p = 0.00267), HTN was high in D_PSL group only in group over 65 years old (p=0.0276, p=0.0554). Average starting amount of steroids was 6.07±10.2 mg, cases of non-withdrawal of steroid at 1, 2, 3 years later is 79.7%, 72.2% and 66.3% respectively. Conclusion Combined use of steroid at the start of DMARDs increased the rate of mortality of infection requiring hospitalization and hypertension. More than half of them were difficult cases of withdrawal of steroids. From the viewpoint of side effect, it is necessary to study the optimization of steroid therapy in the future. Disclosure of Interests Michihiro Ogasawara: None declared, Yosuke Shimada: None declared, Yoshiyuki Abe: None declared, Ken Yamaji: None declared, Satoshi Hori: None declared, Naoto Tamura Grant/research support from: Astellas Pharma Inc., Asahi Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. LTD, Eisai Inc., :Takeda Pharmaceutical Company Ltd., Speakers bureau: Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., :Mitsubishi Tanabe Pharma Co.

MicroRNAs (miRNAs), which are important inhibitors of mRNA translation, participate in differentiation, migration, cell proliferation, and cell death. The pathology of miRNAs results in alterations in protein expression. Recently, miRNAs circulating in peripheral blood have been shown to control the synthesis and translation of proteins at distal sites after intake into local cells. A number of studies are currently being conducted to investigate how to use miRNAs in disease treatment, but no studies have attempted to alleviate disease by directly eliminating miRNAs from blood. Therefore, we examined whether the removal or reduction of circulating miRNAs with apheresis improved pathologies caused by miRNAs. After approval of the study by our medical school's ethics committee, we collected blood and separated plasma samples from three patients with systemic lupus erythematosus who were undergoing plasmapheresis at our hospital. Peripheral blood was collected before and after it was passed through a primary membrane, centrifuged, and used to extract circulating miRNAs. A comprehensive expression analysis was then performed with a miRNA array chip. The levels of expression of a large number of circulating miRNAs were measured in the plasma samples separated by the primary membranes from all 3 patients with systemic lupus erythematosus. We present the first report that circulating miRNAs in peripheral blood can be separated and possibly directly removed using membrane separation apheresis.

Objectives: To determine which grade of ultrasound (US) synovitis corresponds to clinically involved joints in rheumatoid arthritis (RA) and develops a new US-adjusted composite measure. Methods: Clinical and US examinations were performed on 137 patients with RA (28 joints). Synovial effusion, hypertrophy, and blood flow were semiquantitatively graded from 0 to 3 using gray scale (GS) and power Doppler (PD) modes. We calculated US-adjusted simple disease activity index (SDAI) and assessed feasibility, and external validity by comparing with erythrocyte sedimentation rate (ESR), and modified health assessment questionnaires (MHAQ). Results: GS ≥2 and PD ≥0 corresponds to clinically swollen joints, and GS ≥2 and PD ≥1 corresponds to tender joints. The US-adjusted SDAI showed the highest correlation when US-determined swollen joints were defined as PD ≥2 with ESR, and GS ≥3 and PD ≥2 with MHAQ. A feasible US-adjusted SDAI examining only clinically involved joints still showed a higher correlation with ESR and MHAQ than SDAI. Conclusion: Our composite measure complemented by US only for clinically involved joints is feasible and reliable for monitoring disease activity.

IntroductionWe aimed to identify causes of false-positives in ultrasound scanning of synovial/tenosynovial/bursal inflammation and provide corresponding imaging examples.MethodsWe first performed systematic literature review to identify previously reported causes of false-positives. We next determined causes of false-positives and corresponding example images for educational material through Delphi exercises and discussion by 15 experts who were an instructor and/or a lecturer in the 2013 advanced course for musculoskeletal ultrasound organized by Japan College of Rheumatology Committee for the Standardization of Musculoskeletal Ultrasonography (JCR-CoSMUS).ResultsSystematic literature review identified 11 articles relevant to sonographic false-positives of synovial/tenosynovial inflammation. Based on these studies, 21 candidate causes of false-positives were identified in the consensus meeting. Of these items, 11 achieved a pre-defined consensus (≥ 80 %) in Delphi exercise and were classified as follows: I. Gray-scale assessment (A. Non-specific synovial findings, B. Normal anatomical structures which can mimic synovial lesions due to either their low echogenicity or anisotropy); II. Doppler assessment (A. Intra-articular normal vessels, B. Reverberation). Twenty-four corresponding examples with 49 still and 23 video images also achieved consensus.ConclusionsOur study provides a set of representative images that can help sonographers to understand false-positives in ultrasound scanning of synovitis and tenosynovitis.

Background:Japan is the world’s most aged country. The number of patients with polymyalgia rheumatic (PMR) is expected to increase more.Classification criteria including ultrasound findings were published in 2012(1), but the ability to differentiate PMR from other mimicking diseases was unknown.It is difficult to diagnose PMR accurately. We will clarify whether recently reported ultrasound findings (2, 3) which could be characteristic in PMR are helpful for distinguishing from other mimicking diseases and treatment outcome in suspected PMR patients. Neither diagnostic laboratory test nor specific antibody exist, and inflammatory markers such as C reactive protein and erythrocyte sedimentation rate are not specific.Objectives:Patients who were clinically suspected of PMR and underwent ultrasound examination from 2008 to 2018. And Patients who visited the hospital with PMR and were diagnosed with PMR from 2008 to 2018.Methods:Patients who visited the hospital and were diagnosed with PMR were extracted from the medical record database of the hospital. Patients who had been administrated GC at the first visit and whose records were not confirmed were excluded. Patients who were clinically diagnosed with PMR without ultrasound(Cli-PMR), patients who were diagnosed with PMR with ultrasound reports(US-Cli-PMR), patients who were diagnosed by the ultrasound expert only based on ultrasound images(US-PMR).Patient were followed up for one year. Clinical diagnoses were confirmed at the 6 months and 12 months since the first GC administration.Three groups were compared with each other in the rate of diagnosis change and the time intervals between the initiation of GC treatment and the occurrence of events: recurrence, methotrexate introduction and the normalization of C reactive protein.the Kaplan–Meier method was used to evaluate the outcomes. Statistical analyses were conducted with R software, version 3.5.2 (R Foundation for Statistical Computing) and EZR(4).Results:545 PMR patients were extracted. 403 of 545 was excluded because of preexisting GC therapy and record availability.At the 6 months follow-up, 92.8% of the non-US PMR group and 97% of US-PMR group remain PMR and at the 12 months follow-up 88.8% and 95% respectively. There was no significant difference in the three time-to-event outcomes.Conclusion:Ultrasound did not contribute the improvement of the PMR outcomes. However, this finding was affected by confounding factors for example assignment to ultrasound and atypical cases and rheumatologists’ uncertainness. Despite confounding factors, US-PMR group was not inferior. These findings showed that ultrasound may be useful for the complicated cases.References:[1]ARTHRITIS & RHEUMATISMVol. 64, No. 4, April 2012, pp 943–954[2]Clin Med Insights Arthritis Musculoskelet Disord 2017;10: 1179544117745851.[3]Biomed Res Int 2017;2017: 4272560.[4]Bone Marrow Transplantation 2013: 48, 452–458Disclosure of Interests:None declared

Background:The development of rapid and accurate methods of diagnosing giant cell arteritis (GCA) is critical to prevent blindness and stroke, which may develop rapidly in patients with GCA. In 2018, EULAR published recommendations that the first imaging modality for GCA should be vascular ultrasonography without biopsy. However, many institutions still consider biopsy to make an important contribution to the diagnosis of GCA.Objectives:Our purpose is to eliminate blindness and stroke among GCA patients by optimizing diagnostic imaging and method to diagnose GCA employed by vascular ultrasonography (V-US), CT Angiography (CTA), MRI/A, and PET/CT without biopsy.Methods:We evaluated the clinical and serological characteristics of 20 patients who were diagnosed with GCA at our hospital from 2012 to 2018, and compared the image and biopsy findings of these patients. We then evaluated the effect of optimizing diagnostic imaging and methods for patients with suspected GCA who visited our hospital during 2019. Vascular mapping was carried out using V-US for 3DCTA and other imaging methods as references.Results:Table 1 shows the clinical characteristics of the study population. The sensitivity of CTA for GCA was 85.7% (12 of 14 patients), which was the highest of the studied imaging methods. All biopsy-positive cases were diagnosed as GCA, and we compared these cases with cases with positive imaging findings. This revealed that CTA findings were correct (i.e., positive) in 66.7% (four of six patients), MRI/A findings were correct in in 33.3% (three of nine), V-US findings were correct in 50.0% (three of six). Therefore, CTA exhibited the highest sensitivity for positive findings. Comparison of biopsy-positive cases with cases in which imaging findings were negative revealed that CTA findings were correct (negative) in 33.3% (two of six patients), MRI/A findings were correct in 55.6% (five of nine), V-US was correct in 50.0% (three of six). Thus, CTA had the lowest sensitivity for negative findings. Comparison of CTA findings of positive cases with other imaging modalities which reported positive findings revealed MRI/A findings to be correct in 44.4% (four of nine patients), PET/CT findings to be correct in 50.0% (one of two), V-US to be correct in 63.3% (five of eight). Thus, V-US had the highest agreement with CTA. We carried out vascular mapping by V-US using 3DCTA and other imaging methods and produced references to improve the accuracy of diagnosis. Using these references, we diagnosed five cases of GCA among the 20 patients; the positive predictive value of V-US was 80% (four of five patients) and negative predictive value was 86.7% (13 of 15 patients).Table 1.Baseline characteristics of the study sample The number of biopsies performed decreased from 50% (10 of 20 patients) from 2012 to 2018 to 15% (3 of 20 patients) in 2019. Two cases in the present study had positive findings in both biopsy and V-US; in one case, biopsy, CTA, and MRI/A were negative while V-US revealed positive findings. No patients with GCA developed blindness or stroke during 2019.Conclusion:We propose that V-US should be performed as the first examination for the diagnosis of GCA by the creation of vascular mappings when GCA is suspected in order to prevent blindness and stroke.References:[1]Christian Dejaco et al.EULAR recommendations for the use of imaging in large vasculitis in clinical practice.Annals of the Rheumatic Diseases,2018 May;77(5):636-643[2]Kawamoto T et al.Diagnosis of giant cell arthritis by head-contrast three-dimensional computed tomography angiography.Journal of Medical Case Reports2019 Sep 11;13(1):285.Figure 1.Left side is before, right side is after thrapy. (A) 3DCTA finding, (B) determination of V-US arrangement with vascular location to evaluate wall thickening of V-US, compression sign, stenosis and stoppage of vessels.Disclosure of Interests:None declared

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that affects mostly young women. Multiorgan complications and prolonged treatment significantly cause physical and mental stress in patients. Improving patients’ quality of life (QOL) in SLE treatment is essential. We examined the treatment effects on disease activity and QOL of SLE patients.Objectives:In recent years, lupus low disease activity state (LLDAS) has been proposed as a treatment target for SLE. Patients who achieve LLDAS have a low recurrence rate for lupus and a low risk of serious complications (1). The aim of this study is to investigate whether achieving LLDAS reduces not only recurrence rate and complications of SLE but also improves patients’ QOL.Methods:A total of 104 SLE patients were enrolled in our prospective SLE registry study (Juntendo, Multi-center, Prospective cohort for investigation of clinical course and outcome in SLE: JUMP) conducted at our institution. SLE was diagnosed using the American College of Rheumatology (ACR) 1982 criteria (revised in 1997). QOL was evaluated using the standard version of the 36-item short form health survey version 2 (SF36v2). Participants were divided into the LLDAS achievement and non-achievement groups, and the characteristics of each group including results of SF36v2 were examined.Results:This study included 104 SLE patients, 94 female and 10 male, and the average age and disease duration were 46.4±13.8 and 14.5±11.3 years, respectively. The average corticosteroid dose was 8.0±17.4 mg/day in terms of prednisolone, and anti-dsDNA antibody titer was 16.8±38.5 IU/ml. Of the 104 patients, 57 achieved LLDAS. The subscale’s standard scoring using SF36v2 for role physical (RP) was 78.9±24.0 and 64.6±27.6 (P50. However, in the LLDAS non-achievement group, all categories were Conclusion:Results of examining the association between LLDAS and QOL using SF36v2 in SLE patients showed that patients who achieved LLDAS had significantly better standard statistical scores in many subscale categories. Thus, LLDAS achievement as a treatment target for SLE patients greatly contributes to improving patients’ QOL.References:[1]Franklyn K, et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS).Ann Rheum Dis. 2016 Sep;75(9):1615-21.Disclosure of Interests:None declared

Background Ankylosing spondylitis (AS) is the prototype of spondyloarthritis, which affects sacroiliac joints, spine, peripheral joints and enthuses. HLA-B27 is known to be related with AS and there is a considerable number of patients suffering from AS among other rheumatic diseases. In Japan, however, the prevalence of AS was reported to be less than 0.1% much lower than western countries and also other East Asian countries 1) 2) 3). This is due to the low frequency of HLA-B27 in Japanese (0.3%) compared to 5%–10% in the countries mentioned above. Because of small number of AS patients, clinical features and HLA-B27 positivity has not been well investigated in Japanese patients with AS. Since our hospital has an outpatient specialising in AS and there are many patients, we conducted a survey on AS Objectives In this study, we examined the characteristics of patients with AS in our hospital and compared the data of patients with AS in Japan and overseas. Methods We conducted a questionnaire survey on patients fulfilling the modified New York criteria for AS. A questionnaire included demographic data and histories. We also retrospectively investigated the data of blood test, radiographs and the presence of inflammatory back pain (IBP), HLA-B27, enthesitis, dactylitis, radiographic sacroiliitis and extra-articular manifestation. Results A total of 82 patients (82.9% male) including Japanese (68), Chinese,9 Korean5 with AS who fulfilled the modified New York criteria were enrolled from May in 2013 to April in 2016. Of 68 patients with HLA-B27 test result, 61 patients (89.7%) were HLA-B27 positive. Of 54 Japanese patients, 48 patients (88.9%) were HLA-B27 positive. IBP, enthesitis, dactylitis, bamboo spine and uveitis were found in 67 patients (81.7%), 31 patients (37.8%), 5 patients (6.1%), 44 patients (53.7%) and 30 patients (36.6%), respectively. Conclusions In Japanese AS patients, the prevalence of HLA-B27 was high (almost 90%) and other characteristics were similar with those of Western countries. In Japan where the frequency of HLA-B27 is very low, B27 positivity is considered to have high diagnostic value. References [1] Hukuda S, Minami M, Saito T, Spondyloarthropathies in Japan; Nationwide questionnaire survey performed by the japan ankylosing spondylitis society. J Rheumatol2001;28: 554–559. [2] Calin A, Fries JF. Striking prevalence of ankylosing spondylitis in “healthy” W27 positive males and gemales. N Engl J Med. 1975;293:835–839. [3] Akkoc N, Khan MA. Overestimation of the prevalence of ankylosing spondylitis in the Berlin study: comment on the article by Braun, et al. Arthritis Rheum2005;52–4048–4049. Disclosure of Interest None declared

MicroRNAs (miRNAs, miRs) are small non-coding RNAs that mainly function in the post-transcriptional regulation of genes. miRNA that is secreted outside of cells, and which circulates in the peripheral blood, is called circulating microRNA. Systemic lupus erythematosus (SLE) is a typical autoimmune connective tissue disease and is mainly treated with immunosuppressive drugs. Therapeutic apheresis is often used to eliminate autoantibodies and cytokines. We have previously shown that circulating miRNAs in the blood of patients with SLE can be separated and removed from the blood using a plasma separation membrane. In the present study, we further separated circulating miRNA from three SLE patient's blood plasma by passing it through a plasma adsorption membrane, and then measured changes in miRNA levels using miRNAs microarray chip. Although the levels of many miRNAs were unaffected after passage through the plasma adsorption membrane, expression of some miRNAs, including miR-1246, miR-4732-5p, and miR-6088 are declined.

Objectives This study aims to analyze the distribution and clinicopathological characteristics of anti-aminoacyl-transfer ribonucleic acid (tRNA) synthetase (ARS) antibodies in rheumatoid arthritis patients. Patients and methods We retrospectively studied the anti-ARS antibody levels in 228 RA patients' (44 males, 184 females; mean age 62.9±14.0 years; range 23 to 88 years) sera from their medical charts. We determined the association with anti-cyclic citrullinated peptide antibody levels, interstitial lung disease (ILD), rheumatoid factor, and methotrexate or biological disease modifying antirheumatic drug treatments. Results Anti-ARS antibodies were detected in 14 RA patients (6.1%). ILD complications were significantly higher among anti-ARS antibody-positive patients (57.1% vs 22.4%, p

Background Statins are the first-line agents used to treat patients with high serum low-density lipoprotein cholesterol levels, thus reducing the risk of death from arterial sclerotic cardiovascular disease; however, little is known about the effects of non-statin pharmacological interventions on mortality as well as about the potential protective effects of statin use against cancer death. This work aimed to compare all-cause and cancer mortality among patients with hyperlipidaemia who did and did not receive statin treatment. Methods Between 2003 and 2007 fiscal years, we recruited Japanese patients diagnosed with hyperlipidaemia from 66 hospitals. Patients in our cohort were followed up for a maximum of 12 years to observe the causes of death. Kaplan–Meier estimates from the baseline were used to compare the mortality of patients based on the administered medicine. All-cause mortality were compared among patients with/without administration of statins and other agents; any-organ and colorectal cancer mortality were compared between patients with/without administration of statins. Results Our cohort included 41,930 patients with mean ages of 64–66 years and mean body mass indices of 24–25 kg/m2. Patients who received statin monotherapy and were treated with lifestyle modification exhibited nearly identical survival curves, whereas statin use represented a non-significant but potentially protective effect against colorectal cancer-related mortality. The lowest mortality in this cohort was associated with resin monotherapy. Conclusions Mortality rate has been similar for patients treated with statin monotherapy and lifestyle modification. Statin monotherapy could potentially reduce any-organ- and colorectal cancer-related mortality., Highlights • Statin-mediated reduction of low-density lipoprotein levels reduces mortality. • Little is known on the effect of non-statin hyperlipidaemia medicines on mortality. • Statin monotherapy is safe in terms of cancer mortality. • Statin use may reduce colorectal cancer-related mortality. • Resin monotherapy was associated with the lowest mortality.

Autoantibodies to proliferating cell nuclear antigen (PCNA) are specifically, if rarely, present in systemic lupus erythematosus (SLE) patient sera. Even SLE patients lacking PCNA reactivity often show reaction to PCNA-binding protein. Here, immunoreactivity to chromatin assembly factor-1 (CAF-1), an essential molecule for DNA replication and a PCNA-binding protein, was compared for the sera of SLE patients, normal healthy controls (NHCs) and other disease controls, and in autoimmune sera reactive to standard autoantigens, by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence, and immunoblotting. CAF1 and IRF1 expression in SLE and NHC peripheral mononuclear cells were compared by quantitative real-time polymerase chain reaction. Serum interferon-γ-inducing protein-10 and anti-double-stranded (ds)DNA antibody levels were measured by ELISA. Increased CAF-1 autoimmune reactivity was recognized in SLE or serum anti-dsDNA antibody-positive patients. Significantly greater central nervous system (CNS) involvement (aseptic meningitis) and serum anti-dsDNA antibody titers were present more often in anti-CAF-1 antibody-positive than antibody-negative SLE patients. IFN-γ positively regulated CAF-1 expression in vitro and was associated with anti-CAF-1 antibody production in SLE. Thus, a novel anti-CAF-1 autoantibody is frequently found in patients with SLE and is a useful biomarker for diagnosis, especially in cases with CNS involvement. Aberrant IFN-γ regulation appears to play an important role in anti-CAF-1 antibody production in SLE.

To clarify the clinical features of systemic lupus erythematosus (SLE) patients, factors associated with flares, and changes over time.Patients having SLE with a visiting history were entered into the Juntendo University Database of Erythematosus. We included 423 cases in the long-term follow-up analysis, and 383 cases were followed for 10 years after the initiation of any therapeutic intervention (comparative analysis: 1973-1982, 82 cases; 1983-1992, 141, and 1993-2002, 160). We assessed changes in the patients' background characteristics, disease symptoms, flare rates, etc.Among the 423 cases, the mean follow-up period was 25.9 years, and mean number of flares was 0.51. Of those, 31.9% had ≥1 flares. Thrombocytopenia at onset contributed to the flares. For disease symptoms at onset, a recent trend in increasing thrombocytopenia was observed. The combination rate of immunosuppressive agents for diseases other than lupus nephritis was slightly increased, and there was no improvement until the first flare or in the flare rate.Thrombocytopenia at onset is predictive factor for flares. Since SLE is a diverse disease with varying symptoms at recurrence, the treatment guidelines should be improved for thrombocytopenia from a long-term perspective.

We evaluated the bradykinin generation level during leukocytapheresis (LCAP) using novel CellsorbaTM CS-180S, which has sodium pyrosulfite and sodium carbonate as a filling solution. Subjects of this study were 14 rheumatoid arthritis patients. Regardless of the type of anticoagulant used, bradykinin levels were lower with the novel CS-180S than with the conventional CS-180S (28.7 ± 53.3 vs. 8.0 ± 2.7 as the mean ± standard deviation). When anticoagulants other than nafamostat mesilate were used with the conventional CS-180S, bradykinin levels increased at the column outlet compared with the column inlet, and adverse effects of bradykinin were seen in several cases. In contrast, bradykinin levels remained low and no bradykinin-associated adverse events were observed with the novel CS-180S. We recommend using the novel column instead of the conventional column in the treatment of LCAP. J. Clin. Apheresis 29:90–96, 2014. © 2013 Wiley Periodicals, Inc.

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non-woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high-resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t-test. Calculations were performed with a statistical software R.basic package: if the P-value was less than 0.05, this was seen as a significant change. In a comparison of 25,370 gene expressions, the number of genes showing a P-value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.

MicroRNAs (miRNAs), which are important inhibitors of mRNA translation, participate in differentiation, migration, cell proliferation, and cell death. The pathology of miRNAs results in alterations in protein expression. Recently, miRNAs circulating in peripheral blood have been shown to control the synthesis and translation of proteins at distal sites after intake into local cells. A number of studies are currently being conducted to investigate how to use miRNAs in disease treatment, but no studies have attempted to alleviate disease by directly eliminating miRNAs from blood. Therefore, we examined whether the removal or reduction of circulating miRNAs with apheresis improved pathologies caused by miRNAs. After approval of the study by our medical school's ethics committee, we collected blood and separated plasma samples from three patients with systemic lupus erythematosus who were undergoing plasmapheresis at our hospital. Peripheral blood was collected before and after it was passed through a primary membrane, centrifuged, and used to extract circulating miRNAs. A comprehensive expression analysis was then performed with a miRNA array chip. The levels of expression of a large number of circulating miRNAs were measured in the plasma samples separated by the primary membranes from all 3 patients with systemic lupus erythematosus. We present the first report that circulating miRNAs in peripheral blood can be separated and possibly directly removed using membrane separation apheresis.

A 71-year-old woman was diagnosed with rheumatoid arthritis in 2002. Treatment was started with methotrexate and she was switched to adalimumab in 2006. In May 2008, she started complaining of swelling of the left axilla and the left elbow lymph nodes, and adalimumab was discontinued in December. Her lymphadenopathy did not resolve and she was admitted to hospital with fever in May 2009. Subsequent laboratory examinations showed that serum alkaline phosphatase, gamma-glutamyl transpeptidase, C-reactive protein, and soluble interleukin-2 receptor levels were 3,078 IU/l, 510 IU/l, 20 mg/dl, and 7,290 U/ml, respectively. Gallium scintigraphy showed high-intensity areas in the above-mentioned lymph nodes. She suddenly progressed to jaundice and died of pulmonary edema on the 25th day of hospitalization. Autopsy indicated large atypical cells with a distorted nucleus that had multiplied in the above-mentioned lymph nodes. On immunohistochemical staining these cells showed positive staining for CD15, CD30, PAX-5, Epstein-Barr virus (EBV) early small RNA (EBER), and LMP-1. Reactivation of EBV was diagnosed via EBV antibodies and an EBV DNA determination. We considered that she had developed EBV-associated lymphoproliferative disorders due to immunodeficiency caused by adalimumab administration. Reactivation of EBV associated with adalimumab and the relationship of this reactivation to malignant lymphoma have been rarely reported.

We conducted a study to evaluate the effect of various anticoagulant agents on large-volume leukocytapheresis using the new Cellsorba CS-180S Filter filled with a changed solution of sodium pyrosulfite and sodium carbonate. We conducted the study on a total of 12 cases of rheumatoid arthritis. As the anticoagulant agents we used sodium citrate, nafamostat mesilate and low molecular weight heparin. The new Cellsorba CS-180S was safely used with the various blood anticoagulant agents. Also, through adjustment of the sodium citrate percentage to the blood flow volume, it is hypothesized that it is possible to increase the neutrophil removal rate.

To retrospectively evaluate the efficacy and safety of combination therapy with tacrolimus (TAC) and other disease-modifying antirheumatic drugs (DMARDs). One hundred fifteen rheumatoid arthritis (RA) patients treated with tacrolimus were enrolled in this retrospective analysis. We collected clinical information, including patient background, treatment efficacy (evaluated using the DAS score), and adverse events observed. Multiple logistic regression analysis was conducted to analyze factors contributing to clinical response and adverse effects. The disease activity score of 28 joints (DAS28) improved significantly at 24 weeks, and continuation rate at 1 year was 57.9%. There was no difference in continuation rate between different DMARD combinations, and not only methotrexate (MTX) but also bucillamine (BUC) and salazosulfapyridine (SSZ) were effective combination partners with TAC. No serious adverse events were observed, and no different inefficacy or safety was observed between non-elderly (

Behavior has been proven to be extremely variable among human individuals. One of the most important factors for such variations of behavior is genetic diversity. A variety of mouse strains are reportedly suitable animal models for investigating the genetic basis of large individual differences in behavior. Laboratory strains have been shown to exhibit different behavioral traits due to variations in their genetic background. However, they show low-level genetic polymorphism because the original colony used for establishing the strains comprises a relatively small number of mice. Furthermore, because the laboratory strains were derived from fancy mice, they have lost the original behavioral phenotype of wild mice. Therefore, incorporation of inbred strains derived from wild mice of different mouse subspecies for behavioral studies is a marked advantage. In the long-term process of establishing a variety of wild-derived inbred strains from wild mice captured all over the world, a number of strains have been established. We previously identified a marked variety in behavioral traits using a Mishima battery. This review reports on the usefulness of wild-derived strains for genetic analyses of behavioral phenotypes in mice.

The aims of this study were to analyze the clinical and pathological features of lupus nephritis (LN) and examine the association between these features and pathological condition, treatment, and prognosis. Of the 177 systemic lupus erythematosus patients who died while receiving inpatient care at Juntendo University Hospital between 1960 and 2001, we investigated the clinical features, treatment, and pathological features of 73 of these who underwent pathological autopsy and had a clear medical history. We divided these cases into two groups, i.e., those up to 1979 (Group A) and those during and after 1980 (Group B) in order to investigate changes in tendencies by age. We also divided the cases into three groups by time interval between diagnosis and death to investigate long-term prognosis. Uremia was the direct cause of death in 38.9% of cases in Group A and only 10.8% of cases in Group B. Pathological features showed a tendency to change to a sclerotic lesion as the duration of the disorder became longer. Uremia attributable to LN was the direct cause of death in relatively fewer cases, although it is still found in the majority of LN cases and remains a problem requiring stringent management. The treatment of sclerotic lesions may be an issue that needs further attention.

Objective. To determine the degree of contribution and the contributing factors of ultrasound in the diagnosis of rheumatoid arthritis (RA) in daily clinical practice and the predictive differences depending on seropositivity. Methods. We included 122 patients who presented with the main complaint of finger and/or wrist joint pain but for whom no definite diagnosis was reached or treatment strategy was provided. Ultrasound was performed on at least 22 joints (both wrist joints, proximal interphalangeal joint, and metacarpophalangeal joints), and patients were followed for ≥6 months. Factors contributing to RA diagnosis were determined and compared between seropositive and seronegative RA patients. Results. RA was diagnosed in 52 of 122 patients, in whom the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria (odds ratio [OR] = 4.74, P = 0.01) and gray scale (GS) grade of 3 (OR = 3.64, P = 0.04) for ≥ 1 joint were the contributing factors. In seropositive RA, the ACR/EULAR criteria (OR = 15.53, P < 0.001) and power Doppler (PD) ≥ 2 for ≥ 1 joint (OR = 10.48, P = 0.0048) were the contributing factors. In seronegative RA, PD ≥ 1 for ≥ 1 joint contributed the most (OR = 20.00, P = 0.0044), but the ACR/EULAR criteria did not contribute to RA diagnosis (P = 0.57). Conclusion. Ultrasound findings contributed to RA diagnosis in clinical practice. The contributing factors are different in the presence or absence of seropositivity, and ultrasound complementation was particularly useful in seronegative RA patients.

Treatment for rheumatoid arthritis (RA) should aim to achieve full remission. The aim of this study was to investigate predictors of persistent subclinical synovitis and whether longer clinical remission is effective in reducing subclinical synovitis.Forty-four RA patients who achieved DAS28ESR clinical remission for at least 3 months were enrolled in this study and underwent ultrasound examination of 22 joints (bilateral proximal interphalangeal joints, metacarpophalangeal joints, and wrists); bilateral hand X-ray; and blood examination. The severity of synovial effusion, synovial hypertrophy, and blood flow were semi-quantitatively graded from 0 to 3 using gray-scale (GS) and power Doppler (PD) modes.Among patients with DAS28ESR-defined clinical remission, 59.1% (26/44) demonstrated residual synovitis (≥ PD1) in at least one joint. Genant-modified total Sharp score (TSS) demonstrated the highest statistical difference between patients with and without residual subclinical synovitis (p = 0.0057), and full remission was only observed in patients with low TSS. A nonsignificant trend for decreased residual synovitis with longer sustained clinical remission was also observed (p = 0.724).Residual synovitis can persist during clinical remission, particularly in patients with progressive bone destruction. Early treatment and longer sustained clinical remission prior to bone destruction are critical for full remission.

To determine whether weighting improves the correlation of ultrasound (US) score with serum matrix metalloproteinase-3 (MMP-3) level in rheumatoid arthritis (RA).As ultrasound examination was performed on 100 RA patients, and the severity of synovial effusion and synovial hypertrophy and the blood flow were semi-quantitatively graded from 0 to 3 by using the gray-scale (GS) and power Doppler (PD) modes. We then calculated the sums of the scores of the 28 joints of each patient in the 2 modes, that is, the GS28 and PD28 scores, as well as the respective scores weighted using the Lansbury articular index (LAI, shoulder and elbow, × 12; wrist, × 8; and knee, × 24)-Lans GS28 and Lans PD28 scores.The Lans PD28 score showed a higher correlation with MMP-3 (r = 0.591; 95% confidence interval, 0.446-0.705, p0.0001) than the existing measures. The scores of the large joints-the knee, shoulder, and elbow-correlated well with the serum MMP-3 level.Weighting with the LAI can improve the correlation of US findings with serum MMP-3 level. Bidirectional approach based on both serum MMP-3 level and US scores can further improve the assessment of disease activity in RA patients.

Objective The aim of this pilot study was to provide groundwork that could be utilized to optimize the global ultrasound (US) assessment of the whole joint for synovial pathologic features in patients with rheumatoid arthritis (RA). Methods US images of the second metacarpophalangeal joint in 8 predefined imaging planes, comprising regions that comprehensively capture the synovial pathologic features of the whole joint, were obtained from 30 patients with RA. Twelve experienced sonographers evaluated these images at the level of both the individual image and the whole joint, using a visual analog scale (VAS) to assess pathologic severity. Interrater reproducibility of the VAS scores was evaluated with intraclass correlation coefficients (ICCs), and factors that independently influenced the global assessment of the whole joint were identified using multiple linear regression analysis. Results A total of 14,276 VAS scores were analyzed. Interrater reproducibility of any eligible VAS assessment of synovial pathologic features was good (ICC 0.65). US assessment of synovial pathologic features in joints with mild inflammation was less reproducible than that in joints with severe inflammation. Although the most severely affected region in a joint did not always represent the average pathologic severity among the 8 regions, global assessment of the whole joint strongly correlated with assessment of the most severely affected region (P < 0.001). Importantly, the standard, midline imaging plane was not the most influential plane on the global assessment of the whole joint. Assessment of synovial fluid accumulation was not reproducible (ICCs 0.20–0.42) and did not substantially influence the global assessment of synovial inflammation (β = 0.06). Conclusion The results of this study provide a unique data set that could be utilized to optimize the global US assessment of synovial pathologic features of the whole joint in patients with RA.

The purpose of this study was to determine if routine clinical measures can predict the presence and severity of ultrasound synovitis in rheumatoid arthritis (RA) patients.Bilateral 1-5 MCP (metacarpopharangeal) and wrist joints were examined using power Doppler (PD) ultrasound (US). Correlations between PD scores and routine clinical measures of RA - swollen joint count (SJC), tender joint count, patient's global assessment (GA), physician's GA, CRP, ESR, MMP-3, RF and anti-CCP antibody - were determined and used to identify significant predictors of PD score. Clinical measures were then compared between two groups (patients with and without PD) and analysed using multiple logistic regression, to derive a model that predicted the absence of PD signals.SJC was the most significant predictor of PD score (R2 = 0.4566, p value0.0001), but was an inadequate predictor of PD signal remission. However, the combination of Steinbrocker's stage I or II (odds ratio [OR] 9.23, p=0.0049), SJC=0 in 1-5 MCP and wrist joints on both sides (OR 6.60, p=0.0039), and SDAI (or CDAI) remission (OR 5.06, p=0.0450) had a positive predictive value of 100%, predicting the absence of PD signals in all study patients meeting the 3 criteria.PD score and absence of PD signals can be predicted using routine clinical measures. When used in combination, Steinbrocker's stage, SJC and SDAI (or CDAI) can estimate disease activity and identify patients likely to have synovitis and requiring US.

Ultrasound (US) examination can visualise and clarify involved joints anatomically in patients with rheumatoid arthritis (RA), and it enables physicians to verify the accuracy of clinical assessments of involved joints. Here, we studied the practical 'miscount'- calculated by subtracting US-determined involved joint count from clinically determined involved joint count - and analysed possible contributing factors for increased miscount.The study population consisted of 137 patients with RA. Physical joint examination was performed by 3 assessors with different levels of experience in rheumatology, followed by US joint examination. Clinical and US examinations were performed on 28 joints (proximal interphalangeal, metacarpophalangeal, wrist, elbow, shoulder, and knee on both sides). Miscount was calculated for all patients, and multivariate analysis was conducted on possible contributing factors for miscount, including age, sex, body mass index, disease duration, Steinbrocker stage, erythrocyte sedimentation rate (ESR), C-reactive protein level, patient global assessment (GA), evaluator GA, matrix metalloproteinase-3 level, and power Doppler (PD) score.A high variability in concordance rate among the joint sites was observed among the 3 assessors. The average miscount was 1.07 (SD, 5.19; range, 18 to -11). ESR and patient GA were determined as significant contributing factors for false-positive miscount, whereas PD score and age were significant factors for false-negative miscount.In addition to the condition of the involved joint distribution and the assessor's clinical examination skills, the patients' background can also lead to increased miscount. Assessors should be blinded to patients' background information, and US complementation should be included in usual clinical joint examinations.

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non-woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high-resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t-test. Calculations were performed with a statistical software R.basic package: if the P-value was less than 0.05, this was seen as a significant change. In a comparison of 25,370 gene expressions, the number of genes showing a P-value0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.

Objective.Joint swelling, an important factor in the classification criteria and disease activity assessment in rheumatoid arthritis (RA), renders joint palpation a necessary skill for physicians. Ultrasound (US) examination that visualizes soft tissue abnormalities is now used to assess musculoskeletal disease. We assessed the usefulness of US assessments in enhancing physical joint examination skills.Methods.We examined 1944 joints (bilateral shoulder, elbow, wrist, metacarpophalangeal joints 1–5, and knee joints) in 108 patients with RA during April–July 2011. We first physically examined and confirmed joint swelling; subsequently, the same rheumatologist conducted US examinations and multiple assessors graded the joint swelling. When the 2 results differed, we received autofeedback from the US results to improve the physical examination skills.Results.The sensitivities and specificities of physical examination for US-detected swollen joint, the correlation coefficient (CC) of the swollen joint counts, and the concordance rate in each patient for joint swelling sites and power Doppler (PD)-positive sites with the κ coefficients between the physical and US examinations were compared over time. We found that the sensitivity of physical examination increased by 42 percentage points (pp), while the specificity decreased by 18 pp. The average CC in June–July was greater than that in April–May. The percentage of κ coefficients > 0.8 increased from 8.8% to 17% for joint swelling and from 8.3% to 14% for PD-positive sites.Conclusion.Our results suggest that autofeedback from US assessment provides quick improvement in palpation skills for identifying joint swelling in patients with RA.

We evaluated the bradykinin generation level during leukocytapheresis (LCAP) using novel Cellsorba(TM) CS-180S, which has sodium pyrosulfite and sodium carbonate as a filling solution. Subjects of this study were 14 rheumatoid arthritis patients. Regardless of the type of anticoagulant used, bradykinin levels were lower with the novel CS-180S than with the conventional CS-180S (28.7 ± 53.3 vs. 8.0 ± 2.7 as the mean ± standard deviation). When anticoagulants other than nafamostat mesilate were used with the conventional CS-180S, bradykinin levels increased at the column outlet compared with the column inlet, and adverse effects of bradykinin were seen in several cases. In contrast, bradykinin levels remained low and no bradykinin-associated adverse events were observed with the novel CS-180S. We recommend using the novel column instead of the conventional column in the treatment of LCAP.

Objective.To study the significance of anti-Ro/SSA antibodies (anti-Ro) in the clinical response to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA).Methods.The clinical responses of a cohort of 190 patients with RA who were treated with infliximab, etanercept, or adalimumab (n = 112, 64, and 14, respectively) as the first biologics were examined using the Disease Activity Score in 28 joints (DAS28) at 24 weeks and the discontinuation rate at 56 weeks. The baseline characteristics of responders and the nonresponders were compared. The clinical response was compared between anti-Ro-negative and -positive patients. The factors associated with the inefficiency of TNF inhibitors were estimated with a multivariable logistic regression analysis.Results.The positive rate of anti-Ro was significantly higher in patients with no European League Against Rheumatism (EULAR) response at 24 weeks (OR 3.64, 95% CI 1.45–9.01, p = 0.003). In anti-Ro-positive patients, a moderate or good EULAR response rate was significantly lower with a sustaining higher median DAS28 (p = 0.006), and this difference was greater among infliximab-treated patients. The discontinuation rate for TNF inhibitors due to inefficacy at 56 weeks was also higher in anti-Ro-positive patients (OR 4.68, 95% CI 1.82–11.99, p = 0.0005), and 75% of these patients received infliximab. The presence of anti-Ro was strongly associated with no EULAR response at 24 weeks and a higher discontinuation rate of TNF inhibitors by 56 weeks (OR 5.22, 95% CI 1.75–15.57, p = 0.003 and OR 10.18, 95% CI 2.18–49.56, p = 0.003).Conclusion.The presence of anti-Ro might be related to the lesser clinical response to infliximab compared to other TNF inhibitors, suggesting that the presence of anti-Ro should be considered when choosing the appropriate biologics for patients with RA.