Jinju Nishino

Disease Activity Score 28 (DAS28) using C-reactive protein underestimates disease activity and overestimates EULAR response criteria compared with DAS28 using erythrocyte sedimentation rate in a large observational cohort of rheumatoid arthritis patients in Japan

Objectives: To compare disease activity and the improvement of disease activity evaluated between by Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) and by DAS28 using C-reactive protein (DAS28-CRP) in Japanese patients with rheumatoid arthritis (RA). Methods: Data from 3073 RA patients registered in the large cohort database (NinJa: National Database of Rheumatic Diseases by iR-net in Japan) of 2003 was used to calculate DAS28-ESR and DAS28-CRP and disease activities were evaluated. Improvements in disease activities were also evaluated according to the European League Against Rheumatism (EULAR) response criteria in 1482 RA patients whose DAS28-ESR and DAS28-CRP could be calculated from data for both 2002 and 2003. Results: The mean value of DAS28-CRP (3.59, SD 1.25) was significantly smaller than that of mean DAS28-ESR (4.31, SD 1.32) (p < 0.0001). The number of patients who satisfied the criteria of remission was 297 (9.7%) in DAS28-ESR versus 705 (22.9%) in DAS28-CRP and the number of patients with high disease activity was 842 (27.4%) versus 357 (11.6%) for DAS28-ESR and DAS28-CRP, respectively; there was a significant difference between the two (p < 0.0001). Change of respective DAS28 was significantly correlated (ΔDAS28-ESR −0.05, SD 1.14 versus ΔDAS28-CRP −0.10, SD 1.10) (p < 0.0001); however, the number of “good response” patients was significantly different (p < 0.03) between DAS28-ESR (97 patients, 6.5%) and DAS28-CRP (136 patients, 9.2%). Conclusions: DAS28-CRP significantly underestimated disease activity and overestimated the improvement in disease activity compared with DAS28-ESR. DAS28-CRP should be evaluated using different criteria from that for DAS28-ESR.

Meniscal suture: An experimental study in the dog

A longitudinal tear was made and then sutured in the peripheral quarter of the medial meniscus of 43 dogs. The sutured menisci were examined using histologic and microangiographic techniques at regular intervals during a 12-week period. Biomechanical tests were also performed. The healing process was promoted not only by the synovial blood supply but also by the peripheral blood supply. Even at the end of 12 weeks, the healing tissue was mainly composed of fibrous tissue, but chondrocytelike cells were also found. The tensile forces were calculated and compared with the opposite leg. The maximum tensile strength reached 80% of that of the opposite side at the end of the 12-week period.

Recent trends in orthopedic surgery performed in Japan for rheumatoid arthritis

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

Incidence of Malignancy and the Risk of Lymphoma in Japanese Patients with Rheumatoid Arthritis Compared to the General Population

Objective. Recent advances in the management of patients with rheumatoid arthritis (RA) increased the rates of disease remission and patient life expectancy, while malignancy has become a more common cause of death. Here, we report the incidence of malignancy in a nationwide survey of Japanese patients with RA compared to the general population, focusing on the risk of lymphoma, which often arises in patients with RA. Methods. Data on the occurrence of malignancy were collected from patients registered in a nationwide Japanese cohort database, the National Database of Rheumatic Diseases by iR-net in Japan, from 2003 to 2012. To adjust for different population composition and to compare the incidence of malignancy with the general population, standardized incidence rates (SIR) were calculated. To identify risk factors for lymphoma, individual patient data were obtained for multivariate analysis for the year before lymphoma diagnosis. Results. In 10 years, the cohort composed of 66,953 patient-years yielded 559 malignancies, most frequently lung cancer, followed by gastric cancer, breast cancer, and lymphoma. The overall incidence of malignancies in patients with RA was slightly lower than in the general population (SIR 0.89, 95% CI 0.82–0.97). However, lymphoma risk was significantly higher (SIR 3.43, 95% CI 2.59–4.28), whereas risk of colon, rectal, or liver cancer was lower. Significant risk factors for lymphoma were the use of methotrexate or tacrolimus, and higher age. Conclusion. Patients with RA had no higher overall incidence of malignancies, but lymphoma was significantly more frequent than in the general population.

The usefulness of neutrophil CD64 expression in the diagnosis of local infection in patients with rheumatoid arthritis in daily practice

BackgroundThe diagnosis of local infection in patients with rheumatoid arthritis (RA) is frequently difficult because clinical signs and symptoms and laboratory test results of local infection are also observed in arthritis of active RA. The need for a specific marker of infection is high in RA patients. The usefulness of neutrophil CD64 expression (CD64) to diagnose local musculoskeletal infection (local infection) and discriminate local infection from RA-related inflammation in RA patients was examined.MethodsCD64 was measured by a quantitative method using flow cytometry in 61 RA patients in whom local infection was suspected, and the usefulness of CD64 was examined by comparing the findings with clinical results.ResultsThere were 25 patients with local infection and 36 patients without infection. The median CD64 value the patients with local infection was 3148 molecules/cell (interquartile range [IQR], 2140–6231) and that of the patients without infection was 1106 molecules/cell (IQR, 804–1464) with a statistically significant difference (P < 0.0001). In contrast, no significant difference between the groups was observed in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. The area under the curve of CD64 calculated by receiver operating characteristic curve analysis was larger than that of CRP, ESR, or WBC count, suggesting that CD64 has superior ability to discriminate of infection compared to these other markers. When the cutoff value of CD64 was set at 2000 molecules/cell, the sensitivity and specificity of CD64 for the detection of local infection in RA patients were 76.0% and 94.4%, respectively.ConclusionsCD64 is a useful marker in RA patients to discriminate local infection from RA-related inflammation.

Impact of biologics on the prevalence of orthopedic surgery in the National Database of Rheumatic Diseases in Japan

The aim of this study was to investigate changes in the treatment strategy of rheumatoid arthritis (RA) and the prevalence of RA-related surgeries after approval of biologics in Japan and to analyze the impact of biologics on the incidence of orthopedic surgeries using a nationwide observational cohort database of rheumatic diseases [National Database of Rheumatic Diseases by iR-net in Japan (NinJa)]. The proportion of patients using biologics linearly increased from 2004 (1.8%) to 2007 (10.0%), but neither the number nor type of RA-related surgery significantly changed during this period. Patients treated with biologics exhibited relatively more severe disease activity and lower physical function. Among patients using biologics, those who underwent RA-related surgeries exhibited background characteristics of longer disease duration and worse physical function, while disease activity was not different from patients without surgery. These results suggest that the potential value of biologics in avoiding surgical procedure is limited in patients with severe functional disorders caused by long disease duration. Further investigation with a longer observation period is required to obtain more definite conclusions as to the impact of biologics usage on orthopedic surgeries.

Analysis of the affected joints in rheumatoid arthritis patients in a large Japanese cohort

ObjectiveRheumatoid arthritis (RA) is a chronic inflammatory disorder involving multiple joints. We investigated the distribution of the affected joints and the relationships among this distribution, the disease activity, and the disease duration in Japanese RA patients by cross-sectional analysis using the National Database of Rheumatic Diseases by iR-net in Japan.Materials and methodsA total of 6408 RA patients registered in the database were analyzed. In each patient, the location of joint swelling and joint tenderness of 68 joints was examined, and the relationships among the distribution of the affected joints, the disease activity as determined using the DAS28-ESR, and the disease duration were analyzed statistically.ResultsFor the 6408 RA patients examined, the wrist was the most frequently affected site. There were some differences in the prevalence of tenderness and swelling; tenderness was frequently observed in large joints such as the knee, elbow and shoulder, while swelling was frequently observed in small joints such as the metacarpophalangeal joints. Although the frequency of involvement increased in all joints as disease activity increased, the pattern of distribution was not affected by disease activity. Furthermore, the distribution was not influenced by disease duration.ConclusionsBased on the results of this study, we can draw the following conclusions: (1) the wrist was the most affected joint; (2) there was a discrepancy between the distribution of swollen joints and that of tender joints; and (3) the distribution of affected joints was uniform regardless of disease activity.

The impact of joint disease on the Modified Health Assessment Questionnaire scores in rheumatoid arthritis patients: A cross-sectional study using the National Database of Rheumatic Diseases by iR-net in Japan

Abstract Objectives: To investigate the effect of bilateral and unilateral joint disease on the Modified Health Assessment Questionnaire (MHAQ) scores and the differences in joint weighting in rheumatoid arthritis patients. Methods: A total of 9212 subjects from the Japanese nationwide cohort database NinJa, 2011, were analyzed. The presence or absence of disease in each joint, including swelling and/or tenderness, was investigated. The correlations between bilateral and unilateral disease in each joint and MHAQ scores were investigated using multivariable logistic regression analysis. Results: The patients’ mean age and disease duration was 63.2 and 12.2 years, respectively. The Disease Activity Score-28 was 3.3. The odds ratios of physical impairment according to the MHAQ using multivariable logistic regression models for bilateral and unilateral joints, respectively, were: shoulder, 4.0 and 1.8; elbow, 2.6 and 1.8; wrist, 1.9 and 1.5; hip, 1.7 and 3.0; knee, 2.6 and 1.9; ankle, 2.3 and 2.0, finger, 1.4 and 1.2; and toe, 1.0 and 1.1. The shoulder, elbow, wrist, knee, and ankle had a significant effect on physical impairment. Conclusions: The MHAQ score was significantly affected by shoulder, elbow, wrist, knee, and ankle joint disease. Furthermore, bilateral disease tended to have a greater effect on physical impairment than unilateral disease.

Trends in Treatment, Outcomes, and Incidence of Orthopedic Surgery in Patients with Rheumatoid Arthritis: An Observational Cohort Study Using the Japanese National Database of Rheumatic Diseases

Objective. In this study, we investigated the changes in clinical outcome, treatment, and incidence of orthopedic surgery in patients with rheumatoid arthritis (RA) from 2004 to 2014. Methods. Data were studied from the Japanese nationwide cohort database, NinJa (National Database of Rheumatic Diseases by iR-net in Japan), from 2004 to 2014. The time trends in the incidence of orthopedic procedures were analyzed using linear regression analysis. The cross-sectional annual data were compared between 2004 and 2014 to analyze the changes in clinical outcome and treatment. Results. The incidence of orthopedic surgeries in patients with RA consistently decreased from 72.2 procedures per 1000 patients in 2004 to 51.5 procedures per 1000 patients in 2014 (regression coefficient = −0.0028, 95% CI −0.0038 to −0.0019, p < 0.001). The greatest reduction was found in total knee arthroplasty and total hip arthroplasty. Disease activity and functional disability improved significantly over this decade. The proportions of patients receiving methotrexate and biologic disease-modifying antirheumatic drugs significantly increased from 39.6% and 1.7% in 2004 to 63.8% and 27.4% in 2014, respectively. Conclusion. The overall incidence of orthopedic surgeries in patients with RA significantly decreased, accompanied by improved clinical outcomes because of the expanded use of effective drugs; however, the declining trend differed between procedures or locations. The results from the present study suggest that there might be a change in supply and demand for orthopedic surgeries.

The age at onset of rheumatoid arthritis is increasing in Japan: a nationwide database study

To determine whether the age at onset of rheumatoid arthritis (RA) has increased in Japan using a nationwide database (National Database of Rheumatic Diseases by iR‐net in Japan, NinJa).