Isao Matsushita

Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells

OBJECTIVE The therapeutic effects of histone deacetylase (HDAC) inhibitor combined with ultrasound (US) (1 MHz, 10% duty factor, 0.1 or 0.2 W/cm(2)) in RA synovial fibroblasts (RASFs) were examined. METHODS RASFs were isolated from rheumatoid synovial tissues obtained from patients with RA during total knee arthroplasty. RASFs were treated with an HDAC inhibitor, trichostatin A (TSA), with or without US. Cell viability was estimated using the Trypan blue dye exclusion test and cell cycle was examined by flow cytometry using propidium iodide (PI) staining. Gene expression of cell cycle-related genes cyclin D, cyclin A, cyclin B and p21(WAF1/Cip1) was analysed by semi-quantitative RT-PCR. Detection of apoptosis was examined by flow cytometry using annexin V-FITC and PI staining. Microarray analysis was carried out to profile gene expression of inflammation-related genes. RESULTS Dose-dependent decreases in cell viability, cell cycle arrest and apoptosis in RASFs due to TSA were observed. US treatment in the presence of microbubbles increased cellular uptake, but did not induce cell cycle arrest or apoptosis. The combination of TSA and US modulated cell cycle-related gene expression and significantly decreased S phase cells and increased G(2)-M phase cells. US also further enhanced TSA-induced RASF apoptosis and regulated expression of inflammation-related genes. CONCLUSIONS HDAC inhibitor in combination with US effectively reduces cell viability and induces apoptosis in RASFs. The combination therapy could be useful to control synovial proliferation and inflammation, since US can be easily applied to targeted joints as local physiotherapy.

Ultrasound Assessment of Synovial Pathologic Features in Rheumatoid Arthritis Using Comprehensive Multiplane Images of the Second Metacarpophalangeal Joint: Identification of the Components That Are Reliable and Influential on the Global Assessment of the Whole Joint

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).

Postoperative complications in patients with rheumatoid arthritis using a biological agent - A systematic review and meta-analysis

Abstract Objectives. To evaluate, through a systematic review of the literature, the association between the use of biological disease-modifying antirheumatic drugs (bDMARDs) and surgical site infection (SSI) or wound healing delay after orthopedic surgery in patients with rheumatoid arthritis (RA). Methods. A systematic review of articles indexed in the Cochrane Library, PubMed, and Web of Science from 1992 to 2012 was performed. The search aimed to identify studies describing SSI or wound healing delay in patients with RA treated with or without bDMARDs. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised. Results. There was no Cochrane review on this subject. We found 75 articles through specific searches of PubMed and Web of Science, and hand searching. After inclusion and exclusion by full-text review, 10 articles were found for SSI, and 5 articles for delayed wound healing. The use of bDMARDs appeared to increase the rate of SSI slightly, especially in large joint-replacement surgery. Delayed wound healing was not increased by the use of bDMARDs. However, the definitions of SSI and delayed wound healing varied between the reviewed articles. Most of the articles focused on tumor necrosis factor-α inhibitors. Conclusion. bDMARDs slightly increase the relative risk of SSI but not that of delayed wound healing after orthopedic surgery and should be used with appropriate caution.

Intraoperative patellar tendon strain: predicting the range of knee flexion after total knee arthroplasty

BackgroundThe preoperative range of motion is an important factor that influences the range of motion after total knee arthroplasty. Because the length and tightness of the extensor mechanism are extracapsular elements with an influence on knee flexion, it is reasonable to assume that the tension of the knee extensor mechanism during surgery has a considerable impact on the postoperative range of motion. The purpose of this study was to determine the influence of the tightness of knee extensor mechanism on postoperative knee flexion.MethodsIn 18 knees undergoing posterior-stabilized type total knee arthroplasty, we measured the longitudinal strain on the patellar tendon with all the components in position during passive knee flexion up to 135°. The patellar tendon strains measured during surgery were compared with the preoperative maximum knee flexion angle and postoperative maximum knee flexion angle at 1 year.ResultsThere was a significant inverse correlation between the patellar tendon strain during surgery at 60° (r = -0.54, P < 0.05), 90° (r = -0.55, P < 0.05), or 135° of flexion (r = -0.65, P < 0.05) and postoperative knee flexion.ConclusionsThe results indicated that subjects with high intraoperative patellar tendon strain during passive flexion of the knee had more restricted postoperative knee flexion. Therefore, the tightness of the knee extensor mechanism measured at total knee arthroplasty is a good predictor of maximum postoperative range of flexion.

Inhibitory effect of tacrolimus on progression of joint damage in patients with rheumatoid arthritis

To examine the inhibitory effect of tacrolimus on radiographic joint damage in patients with rheumatoid arthritis (RA).

Radiographic changes and factors associated with subsequent progression of damage in weight-bearing joints of patients with rheumatoid arthritis under TNF-blocking therapies—three-year observational study

Abstract Objectives: The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage. Methods: Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage. Results: Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p < 0.001, OR:24.85, 95%CI: 5.07–121.79) and disease activity at one year after treatment (p = 0.003, OR:3.34, 95%CI:1.50–7.46) as independent factors associated with the progression of joint damage. On the other hand, multivariate analysis for distal weight-bearing joints identified disease activity at one year after treatment (p < 0.001, OR:2.13, 95%CI:1.43–3.18) as an independent factor related to the progression of damage. Conclusions: Baseline Larsen grade was strongly associated with the progression of damage in the proximal weight-bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.

Long-term clinical and radiographic results of cementless total hip arthroplasty for patients with rheumatoid arthritis: minimal 10-year follow-up

Abstract Objectives. The aim of this study was to clarify the long-term clinical and radiographic results of cementless total hip arthroplasty (THA) for patients with rheumatoid arthritis (RA). Methods. Twenty-eight total hip arthroplasties in 24 patients with a diagnosis of RA were performed from October 1992 to October 1996. All components were titanium alloy with a circumferential porous coating. Six patients (six hips) died before the 10-year follow-up, and one patient (one hip) was lost to follow-up, leaving 21 joints of 17 patients for review at a minimum 10-year follow-up after surgery. There were 3 men and 14 women with an average age of 55.0 years. The average duration of RA at the time of the operation was 12.6 years, and the average follow-up period was 12.2 years. We evaluated the Japanese Orthopaedic Association (JOA) hip scores, radiographic changes and survivor rates of components. Results. Compared with the preoperative JOA hip scores, there was significant improvement in the postoperative scores. Spot welds consistent with bone ingrowth were identified in 95.0% of the femoral components. No femoral components showed radiographic loosening or required revision for aseptic loosening, but two acetabular revisions were performed because of aseptic loosening. The 14-year survivor rates of the stem and cup with the end point of loosening were 100% and 88.2%, respectively. Conclusions. Cementless THA with this component design in patients with RA appears to be a promising treatment.

Lumbar spine surgery in patients with rheumatoid arthritis (RA): what affects the outcomes?

BACKGROUND CONTEXT Although the cervical spine is only occasionally involved in rheumatoid arthritis (RA), involvement of the lumbar spine is even less common. A few reports on lumbar spinal stenosis in patients with RA have appeared. Although disc space narrowing occurs in aging, postoperative adjacent segment disease (ASD) in patients with RA has not been subject to much analysis. PURPOSE The objective of this study was to investigate differences in ASD and clinical outcomes between lumbar spinal decompression with and without fusion in patients with RA. STUDY DESIGN/SETTING This is a retrospective comparative study. PATIENT SAMPLE A total of 52 patients with RA who underwent surgery for lumbar spinal disorders were included. Twenty-seven patients underwent decompression surgery with fusion and 25 underwent decompression surgery alone. OUTCOME MEASURES Intervertebral disc space narrowing and spondylolisthesis of the segment immediately cranial to the surgical site were measured using a three-dimensional volume rendering software. Pre- and postoperative evaluation of RA activity and Japanese Orthopaedic Association (JOA) scores were conducted. MATERIALS AND METHODS All patients had preoperative and annual postoperative lumbar radiographs and were followed up for a mean of 5.1 years (range 3.5-10.9 years). Pre- and postoperative (2 years after surgery) JOA scores were recorded and any postoperative complications were investigated. Degrees of intervertebral disc narrowing and spondylolisthesis at the adjacent levels were evaluated on radiographs and were compared between the two groups. Analysis was performed to look for any correlation between ASD and RA disease activities. RESULTS Postoperative JOA scores were significantly improved in both groups. The rate of revision surgery was significantly higher in the fusion group than that in the non-fusion group. The rate of ASD was significantly greater in the fusion group than that in the non-fusion group at the final follow-up examination. Both matrix metalloproteinase 3 (MMP-3) and the 28-joint disease activity score incorporating C-reactive protein levels (DAS28-CRP) were significantly associated with the incidence and severity of ASD. CONCLUSIONS Adjacent segment disease and the need for revision surgery were significantly higher in the fusion group than those in the non-fusion group. A preoperative high MMP-3 and DAS28-CRP are likely to be associated with postoperative ASD.

The process of collecting and evaluating evidences for the development of Guidelines for the management of rheumatoid arthritis, Japan College of Rheumatology 2014: Utilization of GRADE approach

Objectives. To describe the process of collecting and evaluating evidence for treating rheumatoid arthritis (RA) for developing clinical practice guidelines (CPGs) for rheumatologists in Japan. Methods. The task force comprised rheumatologists, epidemiologists, health economists, and patients. First, the critical outcomes were determined according to a three-round Delphi method, and eight topics with 88 clinical questions (CQs) were formulated. A systematic review of CQs was conducted using the Cochran Database of Systematic Reviews, MEDLINE, and Japana Centra Revvo Medicina (2003–2012). A questionnaire survey and focus group interview were performed to capture the patients’ values and preferences. Data from the National Health Insurance drug price list and product information provided by pharmaceutical companies were collected to evaluate drug cost and safety. The GRADE approach was used to describe the evidence quality and determine the strength of recommendations. Recommendations were developed using a modified Delphi method by a multidisciplinary panel including patients. Results. Eight meetings and frequent e-mail communications were conducted to draft a quality assessment of evidence and recommendations. For 88 CQs, recommendation statements were determined. Conclusions. Using the GRADE approach, new CPGs successfully addressed important clinical issues for treating RA patients. Timely updating of recommendations should be routinely considered.

Extracapsular wide resection of a femoral neck osteosarcoma and its reconstruction using a pasteurized autograft‑prosthesis composite: A case report

The requirement for an extracapsular resection is indicated for malignant bone tumors that have disseminated intracapsularly. Extracapsular resections are often performed for malignant tumors arising from the knee joint, but there are relatively few studies that have described an extracapsular resection of a tumor arising from the hip joint. The present study describes a case of extracapsular wide resection of the hip joint using rotational acetabular osteotomy. The patient was a 17-year-old female and the diagnosis was an osteoblastic osteosarcoma with a pathological fracture of the femoral neck. The joint was reconstructed using an allograft-implant composite graft and total hip arthroplasty. Although the patient presented a slight Trendelenburg gait, no recurrence or metastases were identified during a follow-up period of 3 years. The clinical features and surgical procedure of the case are described.