Low-Concentration Brachial Plexus Block.

PURPOSE: We devised a low-concentration brachial plexus block (LCBB) that allows for intraoperative, active motion by blocking only sensory nerves. This study evaluated the efficacy of the LCBB. METHODS: Thirty-eight patients (14 men and 24 women; mean age, 60.0 years) underwent surgery with the LCBB. An ultrasound-guided supraclavicular brachial plexus block with 30-40 mL of 0.6 mg/ml ropivacaine hydrochloride hydrate was performed approximately 2 hours before starting the surgery. A local anesthetic (LA) was administered as a local infiltration if the intraoperative pain relief was locally insufficient. The surgery was performed using a tourniquet as usual, which was released for approximately 1 minute when there was a requirement to check for intraoperative, active motion. We recorded the waiting time required between LCBB administration and surgery, the total surgery time, the total tourniquet time, the number of patients administered an LA, the total LA volume (1% lidocaine equivalent), and the muscle strength at intraoperative, active motion (evaluated by manual muscle testing and categorized as ≥grade 4 or ≤grade 3). RESULTS: The mean waiting time was 137.0 minutes, the mean surgery time was 124.6 minutes, and the mean tourniquet time was 70.6 minutes. In 2 patients, the anesthetic effect was not achieved, and we switched to other methods of anesthesia (1 patient was switched to an intravenous, regional anesthesia; 1 patient was switched to a standard brachial plexus block). Excluding those 2 cases, the mean LA volume was 8.7 mL among 22 cases (61.1%), and 33 cases (91%) had manual muscle testing of ≥grade 4. In 36 of 38 cases (94.7%), surgery could be performed by LCBB. CONCLUSIONS: Although an LCBB may require additional LA, it is a useful anesthesia method that allows intraoperative active motion and tourniquet use. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Illustrations of rheumatoid arthritis symptoms to promote communications between patients and physicians.

OBJECTIVES: To develop an illustrative tool presenting visualized rheumatoid arthritis (RA) symptoms using pictures to promote a better understanding between patients and physicians. METHODS: The tool named 'Okomarigoto Sheet' was developed through an Internet survey of patients with RA and certified rheumatologists by repeated in-person interviews. RESULTS: An Internet survey on the reality of communication between patients with RA and physicians in 200 patients and 200 certified rheumatologists revealed various local and systemic symptoms of RA and difficulties in sharing those symptoms between patients and physicians during a short consultation. Interviews from patients and certified rheumatologists suggested that illustrations of symptoms would be helpful for better communication between them; therefore, an illustrative tool presenting visualized RA symptoms was drafted. The draft illustrations were refined through multiple rounds of interviews with the patients. The final version of the tool was discussed and evaluated at a joint meeting of patients and rheumatologists. CONCLUSIONS: A picture sheet presenting RA symptoms was developed. Future prospective studies should evaluate the usefulness of the sheet in clinical practice to promote better communication between patients and physicians.

A nationwide questionnaire survey on the prevalence of ankylosing spondylitis and non-radiographic axial spondyloarthritis in Japan.

OBJECTIVE: This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan. METHODS: The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017. We estimated the total number of these patients using response and extraction rates. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B27 positivity rate and clinical features. RESULTS: The estimated total numbers of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400-3900) and 800 (530-1100), suggesting that the prevalence values of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5% (76/137) of patients with AS were HLA-B27-positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing. CONCLUSION: This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features.

Parsing multiomics landscape of activated synovial fibroblasts highlights drug targets linked to genetic risk of rheumatoid arthritis.

OBJECTIVES: Synovial fibroblasts (SFs) are one of the major components of the inflamed synovium in rheumatoid arthritis (RA). We aimed to gain insight into the pathogenic mechanisms of SFs through elucidating the genetic contribution to molecular regulatory networks under inflammatory condition. METHODS: SFs from RA and osteoarthritis (OA) patients (n=30 each) were stimulated with eight different cytokines (interferon (IFN)-α, IFN-γ, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6/sIL-6R, IL-17, transforming growth factor-ß1, IL-18) or a combination of all 8 (8-mix). Peripheral blood mononuclear cells were fractioned into five immune cell subsets (CD4+ T cells, CD8+ T cells, B cells, natural killer (NK) cells, monocytes). Integrative analyses including mRNA expression, histone modifications (H3K27ac, H3K4me1, H3K4me3), three-dimensional (3D) genome architecture and genetic variations of single nucleotide polymorphisms (SNPs) were performed. RESULTS: Unstimulated RASFs differed markedly from OASFs in the transcriptome and epigenome. Meanwhile, most of the responses to stimulations were shared between the diseases. Activated SFs expressed pathogenic genes, including CD40 whose induction by IFN-γ was significantly affected by an RA risk SNP (rs6074022). On chromatin remodelling in activated SFs, RA risk loci were enriched in clusters of enhancers (super-enhancers; SEs) induced by synergistic proinflammatory cytokines. An RA risk SNP (rs28411362), located in an SE under synergistically acting cytokines, formed 3D contact with the promoter of metal-regulatory transcription factor-1 (MTF1) gene, whose binding motif showed significant enrichment in stimulation specific-SEs. Consistently, inhibition of MTF1 suppressed cytokine and chemokine production from SFs and ameliorated mice model of arthritis. CONCLUSIONS: Our findings established the dynamic landscape of activated SFs and yielded potential therapeutic targets associated with genetic risk of RA.

Evaluations of daily teriparatide using finite-element analysis over 12 months in rheumatoid arthritis patients.

INTRODUCTION: The objective of this study was to quantitatively evaluate the effects of daily teriparatide on rheumatoid arthritis patients using predicted bone strength (PBS) assessed by quantitative computed tomography-based finite-element analysis (QCT/FEA) and using bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), and to prospectively investigate clinical determinants associated with PBS and BMD increases. MATERIALS AND METHODS: Participants comprised 39 patients (mean age, 69 years; disease activity score assessing 28 joints with CRP, 3.0; previous vertebral fractures, 82%) enrolled in this study. BMD by DXA and PBS by QCT/FEA of lumbar spine (LS) and proximal femur were measured at baseline, and after 6 and 12 months. In the groups showing increases in these values, variables that may have affected these increases were evaluated using univariate logistic regression analysis. RESULTS: Daily teriparatide treatment significantly increased not only LS BMD, but also LS PBS in RA patients with osteoporosis after both 6 and 12 months of treatment. Increases in N-terminal type I procollagen propeptide (PINP) at 1 and 3 months were significantly associated with increased LS PBS at 12 months according to univariate logistic regression analysis. The threshold value for increased PINP at 1 month for increased PBS at 12 months was 75 µg/L. CONCLUSIONS: Increased LS PBS at 12 months was predicted by increased PINP at 1 month from baseline.

Non-radiographic axial spondyloarthritis.

Non-radiographic axial spondyloarthritis (nr-axSpA) is a subgroup of axial spondyloarthritis (axSpA) without fulfilling the modified New York criteria of sacroiliac joint radiographs for ankylosing spondylitis (AS). AS and nr-axSpA share various demographic and clinical features and disease burden, although sex and objective inflammatory findings such as elevated serum C-reactive protein level are slightly different between AS and nr-axSpA. Recently, diagnostic guidance for nr-axSpA in Japan was proposed for epidemiological studies of a population with a low prevalence of HLA-B27 positivity and the use of molecular targeted agents suitable for the unique medical care system in Japan. A biological agent targeting interleukin-17 was approved for nr-axSpA by the Pharmaceutical and Medical Devices Agency (PMDA) in August 2020. Some other biological agents will be also available for Japanese patients with nr-axSpA in the near future.

Temporal hemiarthroplasty for distal femoral osteosarcoma in early childhood: a case report.

BACKGROUND: Prosthetic reconstruction for distal femoral osteosarcoma is challenging for younger children. We herein report a successful case of limb-sparing surgery for a younger patient with distal femoral osteosarcoma requiring osteo-articular resection. CASE PRESENTATION: A 5-year-old girl with high-grade conventional osteosarcoma in the left distal femur underwent a series of surgeries. After three cycles of neoadjuvant chemotherapy, limb-salvage surgery was planned because femoral rotationplasty had been refused. At 6 years and 2 months old, distal femoral resection and temporary spacer insertion using a 7-mm-diameter intramedullary nail and molded polymethylmethacrylate was performed. At 7 years and 8 months old, secondary surgery was performed because the first spacer had been dislocated and the residual femur became atrophic. The distal end of the residual femur was removed by 1 cm, but the periosteum and induced membrane around polymethylmethacrylate was preserved. In order to stabilize the spacer against the tibia, a custom-made ceramic spacer with a smooth straight 8-mm-diameter stem was utilized. The bone-spacer junction was fixed with polymethylmethacrylate and then covered with the preserved periosteum and induced membrane. After surgery, the bone atrophy improved. At 9 years and 7 months old, the second spacer was removed because it had loosened, and the knee joint was reconstructed using a custom-made growing femoral prosthesis with a curved porous 8.5-mm-diameter stem. Cancellous bone tips from the proximal tibia were grafted around the bone-prosthesis junction underneath the induced membrane. At 10 years and 5 months old, the patient was able to walk unsupported and a radiograph showed further thickening of the cortex of the residual femur without any stress shielding. Although having 5 cm of limb length discrepancy, the patient and her mother were satisfied with the function. The MSTS score was 24 out of 30 points. Repeated limb length extensions are planned. CONCLUSIONS: This case report provides an example of limb-salvage surgery after distal femoral resection in a small child. The use of a temporary spacer utilizing partial cementation and preservation of the periosteum and induced membrane appears to afford a viable limb-salvage option after distal femoral resection for younger children.

Assessing joint destruction in the knees of patients with rheumatoid arthritis by using a semi-automated software for magnetic resonance imaging: therapeutic effect of methotrexate plus etanercept compared with methotrexate monotherapy.

OBJECTIVES: To evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX monotherapy in patients with rheumatoid arthritis (RA) by using semi-automated software for magnetic resonance imaging (MRI) scan analysis. MATERIALS AND METHODS: This study enrolled patients with active moderate-to-severe RA who displayed an inadequate response to oral MTX at screening. Patients were assigned to receive either MTX plus ETN or MTX monotherapy (≥10 mg/week). The primary endpoint was the quantitative knee cartilage volume using our software developed for MRI scan analysis. RESULTS: A total of 18 female patients were enrolled in this study and allocated to the MTX + ETN group (n = 9) or the MTX monotherapy group (n = 9). At 52 weeks, the quantitative knee cartilage volume was significantly reduced compared with baseline in both groups (MTX plus ETN group: 2.3 ± 2.3 cm3; MTX monotherapy group: 2.4 ± 1.6 cm3); however, the difference was not significant. CONCLUSION: The semi-automated software for MRI scan analysis can reveal useful and potentially clinically important information about the characteristics of knee joint destruction in patients with RA.

Complete Circumferential Osseous Extension in the Acetabular Rim Occurs Regardless of Acetabular Coverage.

BACKGROUND: Complete circumferential osseous extension in the acetabular rim has been reported to occur in the deep hip with pincer impingement. However, this phenomenon occasionally is observed in dysplastic hips without pincer impingement, and the degree to which this finding might or might not be associated with hip pain, and how often it occurs bilaterally among patients, are not well characterized. QUESTIONS/PURPOSES: (1) To determine the proportion of patients with complete circumferential osseous extension in the acetabular rim using three-dimensional (3-D) CT in patients with and without hip pain who had CT scans obtained for various reasons. (2) To elucidate how often this complete circumferential osseous extension occurred bilaterally among those patients. (3) To investigate the relationship between the proportions of patients with complete circumferential osseous extension observed on CT scans among three different acetabular coverage groups: dysplasia, normal, and overcoverage. (4) To determine how often the finding of hip pain was associated with complete circumferential osseous extension. PATIENTS AND METHODS: Between September 2011 to July 2016, we evaluated 3788 patients with pelvic complaints such as hip, groin, thigh, buttock, or sacroiliac joint pain. We obtained consent from 26% (992 of 3788) of them, and obtained 3-D CT scans as part of that evaluation. For the current retrospective study, we excluded patients younger than 20 years or 80 years or older (181 patients), patients who had previous hip surgery (185 patients), patients with severe osteoarthritis with Tönnis Grades 2 or 3 (301 patients), and patients who could not have an accurate lateral center-edge (LCE) angle measured owing to poor-quality radiographs (24 patients), leaving 301 patients (602 hips) for this analysis. In this study population, patients reported pain in 131 hips (22%), defined as all types of hip pain except for trauma, including activity pain, pain with sports, pain on motion, and impingement pain; the others did not report hip pain. The mean age of the patients was 56 ± 16 years, and the mean LCE angle was 26° ± 8° (range, -9° to 47°). We first determined the proportion of patients with complete circumferential osseous extension in the acetabular rim using 3-D CT for those with and without hip pain who had CT obtained for various reasons. We next elucidated how often this complete circumferential osseous extension occurred bilaterally among the patients, and finally we investigated the relationship between the proportion of patients with complete circumferential osseous extension observed on CT scans among the three groups: dysplasia (defined as LCE angles of 22° or smaller), normal, and overcoverage (defined as LCE angles of 34° or larger) groups. We finally determined how often the finding was associated with hip pain attributable to complete circumferential osseous extension. RESULTS: The proportion of patients with complete circumferential osseous extension was 6% (18 of 301 patients). Eighty-nine percent (16 of 18) of the patients had bilateral complete circumferential osseous extension. There were no differences in the proportions of patients with complete circumferential osseous extension among the three groups: 5.3% (odds ratio [OR], 1.02; 95% CI, 0.45-2.31; p = 0.97), 5.3%, and 7.4% (OR, 0.70; 95% CI, 0.28-1.73; p = 0.44) in the dysplasia, normal, and overcoverage groups, respectively, with the numbers available. Eighteen percent (six of 34) of the hips with complete circumferential osseous extension had pain. CONCLUSIONS: Complete circumferential osseous extension in the acetabular rim is relatively uncommon. When it occurs, it usually is bilateral, it occurs regardless of acetabular coverage, and it is associated with pain in a minority of patients. LEVEL OF EVIDENCE: Level III, prognostic study.

Relationship between roentgenographic joint destruction in the hands and functional disorders among patients with rheumatoid arthritis.

OBJECTIVES: Although a relationship between joint destruction and functional disorders seems apparent in patients with rheumatoid arthritis (RA), it has not been well proven in the literature. The aims of this study were to clarify the relationship between roentgenographic joint destruction in the hands and functional disorders in patients with RA, and to explore the appropriate assessment measures for functional disorders. METHODS: Cross-sectional data of the Genant-modified Total Sharp Score (Genant-mTSS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Disabilities of the Arm, Shoulder, and Hand (DASH), and Michigan Hand Outcomes Questionnaire (MHQ) were collected from 50 consecutive RA patients and analyzed. RESULTS: HAQ-DI, DASH, and MHQ had close correlations with Genant-mTSS, with correlation coefficients of 0.69, 0.71, and -0.70, respectively, among patients with low disease activity (DAS28 < 3.2). A floor effect was observed in HAQ-DI, but neither floor nor ceiling effects were observed in DASH and MHQ. Both DASH and MHQ were strongly correlated with HAQ-DI, with correlation coefficients of 0.87 and 0.73, respectively. CONCLUSIONS: Functional disorders had significant relationships with roentgenographic joint destruction in the hands among RA patients with low disease activity. As assessment measures of functional disorders, DASH and MHQ had no floor or ceiling effects, being different from HAQ-DI.

Time trends and risk factors for perioperative complications in total ankle arthroplasty: retrospective analysis using a national database in Japan.

BACKGROUND: Total ankle arthroplasty (TAA) has become increasingly popular worldwide as an alternative to ankle arthrodesis for surgical treatment of end-stage ankle arthritis. The aim of this epidemiological study, using a national inpatient database in Japan, was to describe the volume, utilization, patient characteristics, and temporal trends regarding these procedures in Japan, and to identify the risk factors associated with perioperative adverse events in TAA. METHODS: This was a population-based, retrospective cohort study. We retrospectively identified 2775 patients in the Diagnosis Procedure Combination database who underwent ankle arthrodesis or TAA for ankle arthritis at 559 hospitals in Japan from 2007 to 2013. Information on sex, age, main diagnosis, use of blood transfusion, duration of anesthesia, length of hospital stay, in-hospital mortality, hospitalization costs, additional procedures after primary surgery, and use of negative pressure wound therapy was extracted. Multivariable logistic regression analysis was performed to analyze the effect of various factors on the incidence of perioperative adverse events in TAA, including additional procedure during hospitalization, negative pressure wound therapy, blood transfusion, and in-hospital death. RESULTS: We identified 465 patients who underwent TAA and 2310 patients who underwent ankle arthrodesis. There was no apparent increase in the proportion of TAAs performed during the survey period. Patients undergoing TAA tended to be older, female, and have rheumatoid arthritis compared with those undergoing ankle arthrodesis. Patients undergoing TAA had shorter length of stay, higher hospitalization costs, and more blood transfusions compared with those undergoing ankle arthrodesis. Lower hospital volume and shorter anesthesia time were associated with higher rates of adverse events after TAA. CONCLUSIONS: Despite an increase in the popularity of TAA internationally, the number of TAAs performed remains low in Japan. Lower hospital volume and anesthesia time were associated with higher rates of perioperative adverse events after TAA. LEVEL OF EVIDENCE: IV, Cross-sectional study.

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.

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.

Prevalence of total knee arthroplasty and its predictive factors in Japanese patients with rheumatoid arthritis: Analysis using the NinJa cohort.

OBJECTIVES: The aim of this study was to clarify the prevalence and the predictive factors for undergoing total knee arthroplasty (TKA) among patients with rheumatoid arthritis (RA). METHODS: The data of 1,134 patients with RA who were enrolled in the Japanese nationwide cohort database NinJa in 2003 and consecutively followed up until 2009 were analyzed. RESULTS: Seventy-six patients underwent TKA during the observation period. The yearly progression of the modified Health Assessment Questionnaire or mHAQ score from 2003 to 2004, but not the yearly progression of the Disease Activity Score in 28 Joints or DAS28 or patient visual analog scale (VAS) score, was significantly higher in the patients who underwent TKA than those who did not. Multivariate analysis showed that knee involvement in the disease, high Steinbrocker stage (III or IV), and high patient VAS score at the time of enrollment were powerful predictive factors, with hazard ratios of 4.01, 3.71, and 1.20, respectively. According to survival analysis with TKA as an endpoint, patients with knee involvement in the disease at the time of enrollment had a significantly worse 5-year survival rate than did those without knee involvement (83.5% vs. 97.0%, respectively). CONCLUSION: Several factors were elucidated as predictive factors for undergoing TKA among patients with RA.

Prophylactic effect of fondaparinux and enoxaparin for preventing pulmonary embolism after total hip or knee arthroplasty: A retrospective observational study using the Japanese Diagnosis Procedure Combination database.

OBJECTIVES: The aim of this study was to estimate the effect of fondaparinux and enoxaparin combined with mechanical prophylaxis (MP) after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We also investigated the occurrence of pulmonary embolism (PE) and its associated risk factors. METHODS: Data were retrospectively collected on patients who underwent THA or TKA between 2008 and 2010 from the Japanese Diagnosis Procedure Combination database (n = 49,678). We extracted information on sex, age, main diagnosis, types of anesthesia, duration of anesthesia, comorbidities, hospital volume, the use of MP, and the use of anticoagulant drugs. RESULTS: The overall occurrence of PE was 0.41%. Multivariate logistic regression analysis showed that the occurrence of PE was significantly higher in females (odds ratio, 2.17; p < 0.001, compared with males), TKA (1.47; p = 0.039, compared with THA), and longer-duration anesthesia (2.63; p = 0.008 in the ≥ 240-min. group compared with the ≤ 119-min. group). Compared with the MP-alone group, the occurrence of PE was significantly reduced in the fondaparinux group (0.58; p = 0.025) and the enoxaparin group (0.59; p = 0.046). CONCLUSIONS: Fondaparinux or enoxaparin combined with MP decreased the occurrence of PE. The risk factors for PE were female patients, TKA, and longer-duration anesthesia (≥ 240 min.).

Vertebral fractures affect functional status in postmenopausal rheumatoid arthritis patients.

Functional disability is a major concern in patients with rheumatoid arthritis (RA). This retrospective study investigated the risk factors for vertebral fractures (VFs) in postmenopausal RA patients and determined the impact of VFs on functional status. Data from a cohort of 200 postmenopausal RA patients in a single hospital registry were analyzed. Demographic and clinical data, imaging data from spine radiographs, and bone mineral density (BMD) data were collected from the patients at baseline and at the final visit (a mean of 2.9 years after the first visit). Risk factors for incident VFs and their impact on the modified health assessment questionnaire (mHAQ) were analyzed. Twenty-eight patients (14%) developed new VFs (NVFs). Logistic regression analysis adjusted for age, BMI, and disease duration revealed that daily dose of prednisolone, femoral neck BMD, use of active vitamin D3, and use of a bisphosphonate at baseline were factors associated with NVF, with odds ratios (95% confidence interval) of 1.27 (1.05-1.54), 0.94 (0.91-0.97), 0.34 (0.13-0.89), and 0.31 (0.12-0.82), respectively. Patients with NVF exhibited worse mHAQ scores and a greater increase in mHAQ scores from baseline compared with those without NVF. In conclusion, incident VFs were associated with reduced functional status in postmenopausal patients with RA. It is important to prevent VFs to maintain the functional status of RA patients.

Clinical characteristics of rheumatoid arthritis patients undergoing cervical spine surgery: an analysis of National Database of Rheumatic Diseases in Japan.

BACKGROUND: The aim of this study was to examine the clinical characteristics of rheumatoid arthritis (RA) patients who underwent cervical spine surgery using a multicenter observational database. METHODS: We obtained data from a nationwide observational cohort database of patients with rheumatic diseases (National Database of Rheumatic Diseases by iR-net in Japan (NinJa)) for the fiscal years 2003 to 2011. A total of 39 out of 60 patients who underwent cervical spine surgery for a RA-related cause and whose data were available for two consecutive years (to assess the preoperative patient status) were chosen as cases. Patients with a non-RA-related cause of surgery (e.g., trauma) were excluded. First, we compared the patient characteristics between the cases and total patients in the same fiscal year. Next, 106 eligible controls, who were defined as RA patients enrolled in the same fiscal year as the case subjects, who were matched for age, gender and disease duration (within ±1 year), were selected. We compared the demographic data between the two groups. We also calculated the percentage of patients who underwent cervical spine surgery (surgeries/total number of patients) in fiscal years 2003 to 2011. RESULTS: Although the proportion of patients using biologics linearly increased during study period, the percentage of patients undergoing cervical spine surgeries remained unchanged, at approximately 0.15%. These cases had more tender joints (3 vs. 1, p < 0.01) and exhibited a significantly higher Modified Health Assessment Questionnaire (MHAQ) score (1.13 vs. 0.5, p < 0.01), C-reactive protein (CRP) (1.5 vs. 0.36, p < 0.01), and disease activity score (DAS) 28-CRP (3.63 vs. 2.81, p < 0.01) compared to the controls. CONCLUSIONS: Our study revealed that RA patients requiring cervical spine surgery have a higher disease activity (as represented by the DAS28-CRP) and are more functionally disabled (as represented by the MHAQ) than control patients.

Midterm results of resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis and the risk factors associated with patient dissatisfaction.

We investigated the midterm results of resection arthroplasty of all 5 metatarsal heads in patients with rheumatoid arthritis and forefoot deformity and analyzed the factors that affect patient satisfaction levels. Of 64 patients (1 male, 63 females), 107 feet were treated with resection arthroplasty for forefoot deformity at our hospital from January 1992 to December 2005. The mean follow-up period was 5.8 ± 3.1 years, with all patients having at least 1 year of follow-up. Of the 64 patients, 75% were satisfied with the surgery. The mean score for the postoperative Japanese Society for Surgery of the Foot lesser metatarsophalangeal-interphalangeal scale was 75.0 ± 15.8 points. Multivariate logistic regression analysis showed that patient-reported dissatisfaction was significantly associated with the recurrence of hammer toe deformity (odds ratio 2.66, 95% confidence interval 1.07 to 6.97), shortening of the resection arthroplasty space (odds ratio 0.85 for a 1-unit increase, 95% confidence interval 0.74 to 0.96), and the recurrence of hallux valgus (odds ratio 1.04 for a 1-unit increase, 95% confidence interval 1.00 to 1.09) during the postoperative period. From our results, interventions to prevent recurrence of hammer toe deformity, especially in toes with preoperative metatarsophalangeal joint dislocations, have been shown to be important in preventing complications and patient dissatisfaction after resection arthroplasty.

Regulation of cytokine and chemokine expression by histone lysine methyltransferase MLL1 in rheumatoid arthritis synovial fibroblasts.

Histone lysine methylation is thought to play a role in the pathogenesis of rheumatoid arthritis (RA). We previously reported aberrant expression of the gene encoding mixed-lineage leukemia 1 (MLL1), which catalyzes methylation of histone H3 lysine 4 (H3K4), in RA synovial fibroblasts (SFs). The aim of this study was to elucidate the involvement of MLL1 in the activated phenotype of RASFs. SFs were isolated from synovial tissues obtained from patients with RA or osteoarthritis (OA) during total knee joint replacement. MLL1 mRNA and protein levels were determined after stimulation with tumor necrosis factor α (TNFα). We also examined changes in trimethylation of H3K4 (H3K4me3) levels in the promoters of RA-associated genes (matrix-degrading enzymes, cytokines, and chemokines) and the mRNA levels upon small interfering RNA-mediated depletion of MLL1 in RASFs. We then determined the levels of H3K4me3 and mRNAs following treatment with the WD repeat domain 5 (WDR5)/MLL1 inhibitor MM-102. H3K4me3 levels in the gene promoters were also compared between RASFs and OASFs. After TNFα stimulation, MLL1 mRNA and protein levels were higher in RASFs than OASFs. Silencing of MLL1 significantly reduced H3K4me3 levels in the promoters of several cytokine (interleukin-6 [IL-6], IL-15) and chemokine (C-C motif chemokine ligand 2 [CCL2], CCL5, C-X-C motif chemokine ligand 9 [CXCL9], CXCL10, CXCL11, and C-X3-C motif chemokine ligand 1 [CX3CL1]) genes in RASFs. Correspondingly, the mRNA levels of these genes were significantly decreased. MM-102 significantly reduced the promoter H3K4me3 and mRNA levels of the CCL5, CXCL9, CXCL10, and CXCL11 genes in RASFs. In addition, H3K4me3 levels in the promoters of the IL-6, IL-15, CCL2, CCL5, CXCL9, CXCL10, CXCL11, and CX3CL1 genes were significantly higher in RASFs than OASFs. Our findings suggest that MLL1 regulates the expression of particular cytokines and chemokines in RASFs and is associated with the pathogenesis of RA. These results could lead to new therapies for RA.

A case of osteogenesis imperfecta diagnosed after subchondral insufficiency fracture of bilateral femoral heads.

Osteogenesis imperfecta (OI) is a heterogeneous disorder characterised by bone fragility. Herein, we report a case of OI diagnosed after subchondral insufficiency fracture (SIF) of bilateral femoral heads. A 37-year-old woman was referred to Saitama Medical University Hospital due to left hip pain without any trauma that lasted for 2 months. She was subsequently diagnosed with SIF of the left femoral head. After 3 months, she further developed SIF of the right hip without any trauma. Magnetic resonance imaging of the bilateral hips showed linear low-signal changes of the subchondral bone and bone marrow oedema of the femoral head on T2-weighted coronal and sagittal images, diagnosing of both SIFs. The bone mineral density was 0.851 g/cm2 (T-score, -1.3) at the lumbar spine, 0.578 g/cm2 (T-score, -1.9) at the right femoral neck, and 0.582 g/cm2 (T-score, -1.9) at the left femoral neck. Considering that the patient had multiple histories of fracture, blue sclera, and mild bilateral sensorineural hearing loss, she satisfied the diagnostic criteria for OI. Genetic testing revealed a mutation in COL1A1 (NM_000088.3, c.3806G>A: p. Trp1269*). After 7 months of conservative therapy, her symptoms improved. After 4 years, both hips were pain-free with no evidence of osteoarthritis progression. OI can result in insufficiency fractures due to bone fragility in adolescence and adulthood or later, and none of the cases of OI, except for the current case, were diagnosed as a result of bilateral SIF.

Patellar fracture after total knee arthroplasty for rheumatoid arthritis.

Patellar fracture is one of the most challenging complications of total knee arthroplasty, but relatively, little is known about it in patients with rheumatoid arthritis. We retrospectively analyzed 329 total knee arthroplasties performed in 230 female patients with rheumatoid arthritis to identify the incidence and risk factors for postoperative patellar fractures. The mean age was 61.8 years, and the mean follow-up period was 6.2 years. Patellar resurfacing was performed in all cases. Five postoperative patellar fractures (1.51%) were identified, and a thin residual patellar thickness and the use of posterior-stabilizing components were identified as significant risk factors, although the number of fractures was small in both groups. There was also tendency of higher age and greater joint line change observed in patients with fracture compared with those without fracture.