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Objectives: To investigate the safety, effectiveness, and risk-benefit balance of intravenous abatacept (ABA) in non-elderly (

Objective: To perform a postmarketing surveillance study evaluating the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis (RA). Methods: Safety and effectiveness data were collected for all RA patients (at 772 sites) treated with intravenous abatacept between September 2010 and June 2011. Patients were treated by the approved dosing regimen according to the package insert. Treatment effectiveness was evaluated at baseline and at weeks 4, 12, and 24 using Disease Activity Score 28 (DAS28) according to erythrocyte sedimentation rate or serum C-reactive protein concentrations. Results: Overall, 3882 and 3016 abatacept-naïve RA patients were included in safety and effectiveness analyses, respectively. Adverse drug reactions (ADRs) were reported for 15.66% of patients and serious ADRs were detected for 2.52% of patients. The incidence of serious infections was 1.03% and these were mainly attributed to different types of bacterial pneumonia. Disease activity improved significantly over 6 months. Separate multivariate analysis identified predictors of severe ADR, and severe infections and factors predictive of clinically meaningful DAS28 improvement after 6 months of treatment with abatacept. Conclusions: Abatacept was efficacious and well tolerated in a clinical setting. No new safety concerns were detected.

SummaryObjectivesThe purpose of this study was to reveal the accurate prevalence and related factors to the presence of calcium pyrophosphate dihydrate (CPPD) crystal deposition in cadaveric knee joints.DesignControlled laboratory study.MethodsSix hundred and eight knees from 304 cadavers (332 male knees and 276 female knees, formalin fixed, Japanese anatomical specimens) were included in this study. The average age of the cadavers was 78.3 ± 10.7 years. Knees were macroscopically evaluated for the existence of CPPD, and the depth of cartilage degeneration of the femoro-tibial joint following the Outerbridge's classification. CPPD crystal was confirmed under Fourier transform infrared spectroscopy (FTIR) analysis using light microscopy. Statistical analysis was performed to reveal the correlation between the occurrence of CPPD deposition in the knee joint and gender, age, and the depth of cartilage degeneration of the femoro-tibial joint.ResultsThe prevalence of grossly visible CPPD crystal was 13% (79 knees). In all of these knees, CPPD crystal was confirmed under FTIR analysis. Statistical analysis showed significant correlation between the occurrence of CPPD deposition and gender (P

Objective.An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan.Methods.Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness.Results.A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score–erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously.Conclusion.These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.

Objective.To assess real-world safety, tolerability, and effectiveness of etanercept monotherapy, etanercept plus methotrexate (MTX), or etanercept plus other disease-modifying antirheumatic drugs (DMARD) in Japanese patients with active rheumatoid arthritis (RA) despite previous treatment with DMARD.Methods.In this 24-week, all-cases postmarketing surveillance study, adverse events (AE) were coded using the Medical Dictionary for Regulatory Activities. Effectiveness was assessed every 4 weeks using the 28-joint Disease Activity Score and the European League Against Rheumatism response criteria.Results.Of 13,861 patients (81% women) in the analysis, 3616, 2506, and 7739, respectively, were classified into etanercept monotherapy (ETN-mono), etanercept plus DMARD other than MTX (ETN + DMARD), and etanercept plus MTX (ETN + MTX) groups. Rates of AE and serious AE (SAE) in the ETN + MTX group were lower than in other groups. Risk of SAE or serious infections was not significantly increased with higher versus lower MTX doses at baseline or with concomitant use of salazosulfapyridine or bucillamine in ETN + DMARD versus ETN-mono groups. A greater likelihood of achieving clinical remission was seen with ETN + MTX versus ETN-mono (OR 1.36; 95% CI, 1.16–1.60; p < 0.001). Higher MTX dose at baseline was associated with a higher remission rate (> 8 mg vs 0 to ≤ 4 mg, OR 1.47, 95% CI 1.07–2.00, p = 0.016; 6 to ≤ 8 mg vs 0 to ≤ 4 mg, OR 1.27, 95% CI 1.01–1.60, p = 0.038).Conclusion.Combination therapies with etanercept plus MTX or other DMARD were reasonably well tolerated, and ETN + MTX at higher doses was more effective than ETN-mono in Japanese patients with RA.

We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was observed when rabbit DFAT cells were loaded onto a β-tricalcium phosphate (TCP)/collagen sponge and cultured in an osteogenic differentiation medium for 3 weeks. Autologous implantation of DFAT cell-mediated TEB constructs promoted bone regeneration in a rabbit tibial defect model. Regenerated bone tissue induced by transplantation of DFAT cell-mediated TEB constructs was histologically well differentiated and exhibited higher bone strength in a three-point bending test compared to that induced by the β-TCP/collagen sponge alone. In OVX-induced osteoporosis model rabbits, DFAT cells were obtained with the osteogenic activity similar to cells from healthy rabbits. Intrabone marrow injection of autologous DFAT cells significantly increased the bone mineral density (BMD) at the injected site in the OVX rabbits. Transplanted DFAT cells remained mainly on the injection side of the bone marrow by at least 28 days after intrabone marrow injection and a part of them expressed osteocalcin. In conclusion, these results demonstrate that autologous implantation of DFAT cells contributed to bone regeneration in a rabbit bone defect model and an OVX-induced osteoporosis model. DFAT cells may be an attractive cell source for cell-based bone tissue engineering to treat nonunion fractures in all patients, including those with osteoporosis.

Histological and molecular changes were examined to investigate the effects of long-term administration of glucosamine (GlcN) and chondroitin sulfate (CS) in a model of spontaneous osteoarthritis (OA) in Hartley guinea pigs. Three groups of female 3-week-old Hartley guinea pigs received GlcN, CS, and neither agent, respectively. Five animals in each group were sacrificed at 8, 12, and 18 months of age. At 8 months of age, Hartley guinea pigs had severe degeneration of knee joint cartilage, chondrocyte apoptosis, marked reduction of tissue total RNA, decreases of aggrecan and collagen type 2 mRNAs, and increases in MMP-3 and MMP-8 mRNAs. Long-term administration of GlcN and CS reduced cartilage degeneration at 8 months of age. The marked loss of total RNA and the increase in MMP-3 mRNA were also inhibited by GlcN and CS. Thus, long-term oral administration of GlcN or CS inhibits OA progression, maintains total RNA and down-regulates MMP-3 mRNA in a spontaneous OA model in Hartley guinea pigs.

Objective An interim analysis of an all-patient postmarketing surveillance programme in Japan to investigate the safety of tocilizumab for the treatment of rheumatoid arthritis (RA) in the real world. Methods This analysis included 3881 patients. Patients received 8 mg/kg of tocilizumab every 4 weeks, and were observed for 28 weeks. Data on baseline characteristics and adverse events (AE) were collected. Results Total and serious AE were reported as 167 and 27 events/100 patient-years, respectively. The most frequent AE and serious AE were infections. Logistic regression analysis identified the following risk factors for the development of serious infection: concurrent or medical history of respiratory disorders; prednisolone dose at baseline ≥5 mg/day; and age ≥65 years. Twenty-five patients died, and the standardised mortality ratio, with the Japanese general population in 2008 as reference, was 1.66, similar to the results from the Japanese cohort study for RA patients. Conclusions Tocilizumab is acceptably safe in the real clinical setting. Tocilizumab needs to be used with consideration of the benefit–risk balance to avoid serious infections in elderly patients and those on high doses of corticosteroids or with a concurrent or medical history of respiratory disorders.

Total knee arthroplasty (TKA) has been proven to be the most effective treatment for patients with severe joint disease. Although infection is not a frequent complication, it is certainly one of the most dreaded. The purpose of this study was to identify factors associated with infection after TKA.Between 1995 and 2006, 2,022 primary TKAs in 1,146 patients were evaluated. Flexible Nichidai Knee (FNK) was used as a prothesis in all subjects. Twenty-four patient-specific data items were collected via chart review for each patient. Revision arthroplasty procedures and infected knees were excluded. The medical records were reviewed to extract the following information: age, gender, body mass index (BMI), preoperative C-reactive protein (CRP), preoperative erythrocyte sedimentation rate (ESR), preoperative total protein (TP), duration of surgery, operative blood loss, total blood loss, duration of surgical drain, duration of antibiotic prophylaxis, primary diagnoses, smoking, diabetes mellitus, steroid or disease modifying anti-rheumatic drugs (DMARDs) therapy, previous operation around the knee joint, previous arthroscopic surgery, previous non-arthroscopic surgery, previous high tibial osteotomy (HTO) or open reduction internal fixation (ORIF), remnants of previous internal fixation material, bone graft, patella replacement, and bone cement.The median age of the patients at the time of primary TKA was 72 (range, 26-91) years. The median follow-up period after primary TKA was 42 (range, 6-145) months. During the study period, 17 infected knee arthroplasties in 17 patients were identified. Previous history of ORIF, male gender, remnants of previous internal fixation material, and BMI showed significant correlation with postoperative infection.This study identified previous history of fracture and remnants of internal fixation as major risk factors of infection after TKA. For clinical relevance, surgeons should be aware of potential infection when performing TKA in patients with these risk factors and patients should be informed of the potential risks.

The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2-5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pre-treatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for

Our aim was to evaluate real-world safety and effectiveness in a 6-month postmarketing surveillance study covering all Japanese patients with rheumatoid arthritis (RA) who received etanercept during a 2-year period. Data for 13,894 patients (1334 sites) enrolled between March 2005 and April 2007 were collected. Adverse events (AEs) and serious adverse events (SAEs) were reported in 4336 (31.2%) and 857 (6.2%) patients, respectively. The most frequent AEs were injection site reactions (n = 610, 4.4%) and rash (n = 339, 2.4%), whereas pneumonia (n = 116, 0.8%) and interstitial lung disease (n = 77, 0.6%) were the most frequent SAEs. Significant improvement in the proportion of patients with a good European League Against Rheumatism (EULAR) response was observed from week 4 (17.6%) to week 24 (31.6%) (p < 0.001); 84.3% of patients had good or moderate EULAR responses at week 24. The percentage of patients achieving remission increased significantly from week 4 (9.3%) to week 24 (18.9%) (p < 0.001). Patients with early moderate RA were less likely to experience SAEs and were more likely to achieve remission compared with patients with more severe disease. The safety and effectiveness of etanercept was demonstrated in Japanese patients in one of the largest observational trials conducted thus far in RA patients treated with biologics.

Reconstruction of the knee extensor mechanism after the excision of a malignant bone tumor is often difficult, particularly if the tumor is located in the proximal tibia. We developed a novel method to reconstruct the knee extensor mechanism using autologous fasciae, and subsequently evaluated the efficacy of this method.We examined the studied reconstruction method, range of motion, extension lag, knee extensor strength, and functional evaluation of three patients with a malignant bone tumor in the proximal tibia. All three patients underwent reconstruction of the knee extensor mechanism by our method.All patients experienced satisfactory outcomes with regard to the above-mentioned parameters. The functional evaluation scores in the three patients were 90%, 95%, and 95% (mean, 90%).In this analysis of our recently devised reconstruction method, the follow-up duration was short and only three patients were investigated. However, if appropriate patients are carefully selected for this procedure, long-term outcomes associated with new technique may be better than those associated with other methods of the knee extensor reconstruction.

Objective. To examine the views of rheumatology physicians concerning clinical practice guidelines in Japan, and changes to them following the dissemination of new guidelines for rheumatoid arthritis (RA) in 2004. Design. Two cross-sectional questionnaire surveys, the first conducted before publication of new evidence-based RA clinical practice guidelines and the second conducted after implementation. Setting. Rheumatology-focused practices in Japan. Participants. A random sample of physicians registered with the Japan Rheumatism Foundation who satisfied the registration criteria with regard to experience with RA care. Results. The percentage of guideline users increased from 48 to 60% following publication of the new RA guidelines in 2004 ( P < 0.01). The majority agreed that clinical practice guidelines support decision-making in practice, although the proportion of supportive responses decreased slightly in the second survey, from 83 to 77% ( P < 0.01) for decision-making, while concern about restricting physician autonomy increased from 18 to 22% ( P = 0.01). While only 39% of physicians felt that clinical practice guidelines would contribute to malpractice litigation, the proportion of physicians who were concerned that clinical practice guidelines would be used to bring legal action against providers was larger than that who expected they would defend providers (58 vs 30%, P < 0.001). Conclusions. Clinical practice guidelines are well accepted among Japanese rheumatology physicians, albeit that the proportion decreased slightly after the introduction of new guidelines. One reason for this may be concern about the use of the guidelines in malpractice litigation. To facilitate implementation, trends in physician support for the guidelines should be closely monitored.

肺癌骨転移に対する予後予測と治療戦略の確立目的で 93 例の生存期間と予後関連因子，ゾレドロン酸水和物の効果について検討した．その結果，後ろ向き検討 30 例では，performance status (以下 PS)， 麻痺，術前予後判定点数総計点数が有意に予後に影響を与えていた．前向き検討 63 例では，PSと visual analogue scale (以下 VAS) が生存 6 ヵ月未満とそれ以上とで有意差があり，Cox 分析では PS だけが有意に予後に影響を与えていた．ゾレドロン酸水和物投与の 64.7%で VAS を 10/100 未満にできた．

To evaluate the efficacy of photodynamic therapy (PDT) against methicillin resistant-Staphylococcus aureus (MRSA) by selecting different light sources for irradiation and combining them with the photosensitizer Na-Pheophorbide a (Na-Phde a).The treatment of drug-resistant bacterial infection is a serious issue. Recently, as a new clinical approach against septic arthritis, an experimental in vivo and in vitro model for the inactivation of MRSA by PDT using the photosensitizer Na-Phde a has been developed.Na-Phde a solution (280 micromol/L) was mixed with MRSA strain bacterial inoculum. After 60 minutes, light was irradiated for 30 minutes using the following light sources: GaA1p semiconductor laser (300 mW, 670 nm), halogen lamp (75 W), xenon lamp (300 W) and fluorescent lamp (27 W). Bacterial growth was evaluated after 24 hours incubation in a blood agar culture.The semiconductor laser and halogen lamp groups showed perfect bactericidal effects after PDT. The xenon lamp and fluorescent lamp groups showed partial bactericidal effects.The results of this experiment showed that PDT using the combination of Na-Phde a with a semiconductor laser or halogen lamp showed a better bactericidal performance than with xenon or fluorescent lamps. These findings indicated that PDT using Na-Phde a could be a useful treatment for septic arthritis and soft tissue infection.

Objective.Postmarketing surveillance (PMS) was conducted evaluating safety and effectiveness of etanercept (ETN; Enbrel®) in Japan, following all patients with rheumatoid arthritis (RA) during the conditional approval period of ETN.Methods.Registration of patients from 1,334 medical sites was conducted between March 2005 and April 2007. Patients were followed for 24 weeks; data regarding patients’ background, safety, and effectiveness was recorded centrally. Adverse events (AE) and adverse drug reactions (ADR) were coded using the Medical Dictionary for Regulatory Activities. Effectiveness was measured using the Disease Activity Score 28 (DAS28).Results.Of 14,369 patients registered, data collection and evaluation for 7,091 patients by March 2006 is reported. At least 1 AE was observed for 2,173 patients (30.6%); 60% of AE occurred within 8 weeks of starting ETN. Most frequent AE were injection site reaction (n = 377, 5.3%) and rash (n = 228, 3.2%). Serious AE occurred in 403 patients (5.7%); most frequent were pneumonia (n = 59, 0.8%) and interstitial lung disease (n = 42, 0.6%). Pneumonia was the most common specifically important ADR (n = 102, 1.4%). Mean baseline DAS28 was 6.0, which reduced to 4.4 within 4 weeks, and to 3.9 within 24 weeks. The proportion of patients having good or moderate EULAR response measured by DAS28 was 84.1% at Week 24. Effectiveness rates were more favorable in patients concomitantly using methotrexate. Good or moderate EULAR response rate among patients switched from infliximab was 84.9%.Conclusion.This extensive observational trial, including all patients with RA in Japan taking ETN, found ETN to be both effective and well tolerated by Japanese patients with RA. Trial registration: clinicaltrials.gov identifier NCT00503503.

The Japan Orthopedic Association has led the way with endoscopic surgery for the spine and has developed its own training course and technical authorization system. Endoscopic surgery can be classified roughly as an anterior procedure from the pleural or peritoneal cavity or as a posterior procedure from the posterior interlaminar space in spine endoscopic surgeries. A representative technique of the endoscopic posterior spine surgery, which uses the posterior method, is microendoscopic discectomy (MED). While MED was initially utilized for lumbar herniotomy, it has recently been used for lumbar spinal canal stenosis and cervical spine disease. Therefore, all the posterior operative procedures are generally used with an MED system and they are referred to as MED. Thus, MED accounts for 98.7% of spine endoscopic operations performed in Japan (2006). There is little soft tissue damage with this approach and the lamina can be reached between the muscles for lumbar disc herniation. In the MED, radiographic control is indispensable for localization of the tube retractor, and it is necessary to resect the yellow ligament little by little to divide the superficial layer and the deep layer. MED is superior in visual safety for retraction of the nerve root to herniotomy. As for issues with MED, there is a substantial learning curve, the operation requires a long time, expensive instrumentation, there is the lack of haploscopic vision, the visual field to operate is limited, there is a tendency to become disoriented, and the lack of sensation of palpating an organ. Additional approaches include video-assisted thoracoscopic spine surgery (VATS) and endoscopic anterior lumbar spine surgery via the peritoneal or retroperitoneal cavity, but they do not lead to global operations.

Purpose: Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult ­tissues. However, survivin expression has been detected in various human cancers and ­correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the correlations between survivin mRNA expres­sion in osteosarcoma tissues and clinicopathological parameters. Methods: There were 22 osteosarcoma patients in our hospital with paraffin-embedded ­tissues which could be extracted from biopsy specimens. We used the RT-PCR method after extracting total RNA and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker. Results: Expression of survivin mRNA was detected in all osteosarcoma samples. Patients with metastasis had high survivin mRNA levels in initial biopsy specimens (p

We present a case of malignant fibrous histiocytoma accompanied by prolonged spiking fevers, which disappeared after tumor resection. Sarcoma with fever as a primary symptom is rare. Furthermore, in this case, fever was closely related to the clinical course of the tumor. In order to detect possible production of febriferous substance(s), we used blood and tumor tissue samples to investigate nine candidate cytokines possibly responsible for the fever. Expression of IL-8 mRNA was detected in preoperative peripheral blood mononuclear cells by RT-PCR. Expressions of IL-6, IL-8, IFN-gamma and TNF-alpha mRNAs were also detected in tumor tissue, while IL-1alpha, IL-1beta, IL-2, IL-4 and COX-2 mRNAs were not. We suspected IL-8 to be a causative factor, and examined its localization by immunohistochemical staining, paraffin sections of tumor tissue stained positive for IL-8. Since infiltrating mononuclear cells were positive for IL-8, this may explain the tumor-associated fever. This case involves intratumoral production of IL-8 as a causative factor, and IL-6, IL-8, IFN-gamma and TNF-alpha cytokine production might have resulted from stimulation with a substance(s) derived from tumor tissue, since the fever disappeared postoperatively. To date the patient is alive and in good health for 7 years and 2 months since the surgery.

Purpose: Surgical treatment of sacrococcygeal chordoma is very difficult and the recurrence rate is high. We investigated the outcomes of wide excision in 12 sacrococcygeal chordoma patients treated between 1983 and 2003. Methods: The 12 patients underwent primary wide excision. The conventional procedure was wide excision employing a chisel and airtome for sacral tumours, and in 1997 a new threadwire saw procedure was introduced. All 12 patients were included in a retrospective analysis of tumour- and treatment-related variables, and outcomes. Results: Six patients underwent surgery with a combined anterior–posterior approach at the cephalad sacral border. In 12 patients, 11 lesions were broadly excised, and in the 1 remaining patient the intralesional margin showed tumour contamination due to a fracture macroscopically. The latter patient received post-operative radiation therapy, but suffered a recurrence 8.0 years later. Three patients died before final follow-up: one from subsequent metastases, two elderly patients from complications. For the 10 chordoma patients, i.e. excluding the two who died due to complications, the 5, 10 and 20 years recurrence rates were 100, 66.7 and 66.7%, respectively. For the 12 patients, overall 5, 10 and 20 years survival rates were 83.3, 55.6 and 55.6%, respectively. Conclusions: Our results suggest that large chordoma should be widely excised, using a modified threadwire saw, with a combination of anterior–posterior procedures.

Study design A semi-prospective clinical study was conducted. Objectives To evaluate the accuracy of a revised scoring system predicting metastatic spinal tumor prognosis and the suitability of the subsequent treatment strategy. Summary of the background data We used a scoring system for the preoperative evaluation of the prognosis of metastatic spinal tumors and selected treatment methods for the predicted prognosis. In the previous version of our scoring system, the reliability of the predicting prognosis was 63.3% in 128 patients with metastatic spinal tumors. Methods The study participants were 164 patients who died after surgery and 82 who died after conservative treatment. Six parameters were used in the revised scoring system. Each parameter ranged from 0 to 5 points, and the total score was 15 points. In principle, conservative treatment or palliative procedures were indicated in patients with a total score of 8 or less (predicted survival period, less than 6 months) or those with multiple vertebral metastases, while excisional procedures were performed in patients with a total score of 12 or more (predicted survival period, 1 year or more) or those with a total score of 9 to 11 (predicted survival period, 6 months or more) and with metastasis in a single vertebra. The selection of treatment modality was followed faithfully according to the criteria of the revised scoring system after 1998. The prognosis predicted by the revised scoring system and the actual survival period after treatment were compared, and the reliability of the prognostic criteria was analyzed for the group subjected to it prospectively after 1998 (n = 118) and for all 246 patients it was applied to retrospectively. Results The total score for each patient could be correlated with the survival period. This correlation was also observed in each treatment group. The consistency rate between the predicted prognosis from the criteria of the total scores and the actual survival period was high in patients within each score range (0-8, 9-11, or 12-15), 86.4% in the 118 patients evaluated prospectively after 1998, and 82.5% in the 246 patients evaluated retrospectively. Furthermore, a similar result was also observed in both the surgical procedure group and conservative treatment group. The rate of consistency between the predicted prognosis and the actual survival period in each local extension of the lesion was 75% or more in all types, excluding Type 6 in the surgical classification of Tomita et al. Conclusion The prognostic criteria using the total scores from our revised scoring system were useful for the pretreatment evaluation of metastatic spinal tumor prognosis irrespective of treatment modality or local extension of the lesion.

We undertook a descriptive, observational study to determine the prevalence of the discoid lateral menisci. The relation between the lateral meniscal shapes and the incidence of meniscal tears were studied, and the gender differences in discoid lateral menisci and the similarities of the lateral meniscal shapes in bilateral knees were examined. A total of 602 knees from 306 cadavers were macroscopically analyzed. Altogether, 577 lateral menisci were classified into the following three types: normal type (NM); incomplete discoid type (ICDM); and complete discoid type (CDM). Each lateral meniscus was examined for meniscal tears. The prevalence of a discoid lateral meniscus and gender differences in its prevalence were examined, as were the presence of a meniscal tear for the three types of lateral meniscus. In all, there were 21 (3. 6%) CDM cases and 171 ICDM cases (29.6%). The prevalence of discoid lateral meniscus, including ICDM and CDM, in the female cadavers was significantly higher than that in the male cadavers, but there was no significant gender difference in the prevalence of CDM. It was found that the shape of the lateral meniscus was similar bilaterally. The incidence of meniscal tears for ICDM was significantly higher than that for NM.

The aim of this study was to describe the indication, planning, technique, rehabilitation, and clinical results after cryopreserved allograft meniscus transplantation. Forty consecutive patients, 33 men and 7 women (mean, 37.3 years of age), were evaluated at 1-year follow-up post surgery. Symptoms, patient satisfaction, ROM (range of motion), surgical time, blood loss, and surgical history were evaluated. Thirty-eight (95%) patients had previous total or partial meniscectomy (mean, 11.4 years ago). Preoperatively, chief complaints were knee joint line pain and swelling. Mean surgical time and blood loss were 123 min and 87 g, respectively. At 12 months postsurgery, 5% and 10%, respectively, complained of pain and swelling; ROM was 0 degrees -132 degrees. Thirty-eight (95%) patients were satisfied. According to the results, meniscus transplantation can lead to significant pain relief and satisfaction in young symptomatic meniscectomized patients. However, long-term results must be obtained to prove the effectiveness of this technique in prevention of degenerative joint changes.

Malignant degree of human chondrosarcoma can be difficult to determine using only histological findings. We therefore assessed expression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase (ADAM) with thrombospondin motifs (ADAMTSs) and tissue inhibitor of metalloproteinases (TIMPs) in chondrosarcoma and ascertained relationships to histological degree of malignancy. As methods, in 28 chondrosarcoma cases, immunostaining was performed using antibodies against MMP 2, 3, 7, 9, 13, ADAMTS 4, 5 and TIMP 1, 2, 3. Chondrosarcoma were classified into groups of 7, 15 and 6 cases based on histologically malignant grade I, II and III, respectively. All target proteins were expressed in chondrosarcoma. Positive correlations (p

Study design This study was designed to investigate the pathologic mechanisms of idiopathic scoliosis using experimentally induced scoliosis in chickens. Objective To understand the process of producing a scoliotic deformity in pinealectomized chickens. Summary of background data Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. Pinealectomized chickens are an important animal model for the study of idiopathic scoliosis. Methods In this study, 40 chickens were divided into two groups; 20 chickens treated with pinealectomy and 20 with a sham operation as control subjects on the second after hatching. The chickens in both groups then were killed at intervals ranging from 1 to 20 weeks after surgery. Their spines were examined visually and radiologically for the presence of a scoliotic curve and vertebral deformities. Results Rotational lordoscoliosis developed in pinealectomized chickens. The chickens with severe scoliosis were characterized by apically wedge-shaped vertebrae. In contrast, no scoliosis with any vertebral deformity developed in any of the chickens that received a sham operation. Conclusions Because there normally is evidence of lordosis in the thoracic spine of chickens, the rotational instability of the spine induced by pinealectomy may produce a scoliotic deformity as a secondary phenomenon. Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. The authors believe that disturbance of the equilibrium and the posture mechanism associated with a defect in melatonin synthesis after pinealectomy may promote the development of rotational lordoscoliosis.

The function of Epstein-Barr virus (EBV)-specific cytotoxic T cells is disturbed in rheumatoid arthritis (RA) patients but the mechanism for this disturbance has remained unknown. In a recent study searching for the causative gene of X-linked lymphoproliferative syndrome, the gene possibly linked to EBV-specific cytotoxic T cells or NK cell-mediated cytotoxic activity to EBV-infected cells was discovered, and its product is now referred to as signaling lymphocytic-activation molecule-associated protein (SAP) or Src homology 2 domain-containing protein (SH2D1A). In the present study, we attempted to investigate the involvement of the SAP gene in RA using a quantitative real-time PCR; the expression level of SAP transcripts in peripheral leukocytes or T cells was examined for patients with RA. The expression level of SAP transcripts in peripheral leukocytes of 21 RA patients was significantly lower than that of 13 normal individuals (P = 0.0007), four patients with palindromic RA, 11 with inactive systemic lupus erythematosus (SLE) or 17 with chronic renal diseases. The decreased expression of SAP transcripts in RA patients was also observed in peripheral CD2(+) T cells compared with normal individuals. There was no mutation in the coding region of SAP cDNAs derived from peripheral leukocytes of five RA patients. The decreased expression of SAP transcripts in peripheral leukocytes or T cells of RA patients might lead to the failure of the immune system to eliminate the EBV-infected synovial lining cells in joints of RA patients. Our findings have suggested that decreased expression of the SAP gene might be involved in the onset or progress of RA.

We examined the effects of various growth factors and cytokines on proteoglycan (PG) and collagen synthesis by chondrocytes isolated from osteoarthritic and normal articular cartilage of Hartley strain guinea pigs. The guinea pig represents a useful animal model of spontaneous osteoarthritis (OA). Cartilage tissue samples were obtained from the knee joints of under-3-month-old guinea pigs (control group) as well as 5- to 8-month-old guinea pigs with OA changes (OA group). Chondrocytes were isolated enzymatically and maintained in suspension culture. Growth factor addition groups were then prepared from both the OA group and the control group, using the factors TGF-β, bFGF, and IGF-1 (1.25 ng/ml each). Cytokine addition groups were also prepared using IL-1α and IL-1β (10 ng/ml each). An addition group was also prepared for sodium hyaluronate (HA) (500 μg/ml). In each group, (35)S was added as a PG metabolic marker, (3)H-proline was added as a collagen metabolic marker, and the groups were cultured. Next, (35)S and (3)H-proline uptake was measured by a liquid scintillation counter. The results revealed that (1) both PG synthesis and collagen synthesis were promoted significantly more in OA chondrocytes than in normal chondrocytes; (2) with the addition of growth factors, PG and collagen synthesis was enhanced in OA chondrocytes; and (3) PG synthesis and collagen synthesis were inhibited in both normal and OA chondrocytes with the addition of IL-1α and -β. This result suggests that the repair function is activated more in OA chondrocytes than in normal chondrocytes, thereby promoting the synthesis of the cartilage matrix by chondrocytes. This synthesizing capability is enhanced and acts to effectively repair degenerative articular cartilage further through the addition of growth factors.

A longitudinal osteotomy of lateral sacrum for malignant iliac tumors using modified threadwire saw is conducted. This procedure issignificantly wide, rapid and safe. J. Surg. Oncol. 2007;95:258–260. © 2007 Wiley-Liss, Inc.

The effectiveness of surgical synovectomy of finger joints were clinically and radiologically evaluated. One hundred and sixty-one finger joints (MP 72, PIP 70, DIP 10 and IP 9) of 64 hands of 52 patients with rheumatoid arthritis who had a surgical synovectomy were examined at an average of 6.7 years follow-up (range 5.2–17 years). The results of synovectomy in these patients were evaluated according to five factors: recurrence of synovial swelling, relief of pain progression of deformity, progression of radiological change, and changes in range of motion after surgery. Un-operated fingers which were not swollen at the time of surgery were used as the controls. Recurrence of synovial swelling was seen in 12% of the patients at the follow-up examination and pain in the finger joints had developed in 6%. In almost all patients, the anti-inflammatory effects of surgery persisted for more than 5 years. Twenty-two (14%) PIP and MP joints showed postoperative progression of clinical deformity. Fifty-seven joints (35%) showed progression of bone change or articular rheumatoid lesion upon radiological examination. Each of the four clinical factors (pain, swelling, deformity and motion) improved more in the treated fingers than the un-operated control fingers. Although only 33% of the MP and PIP joints experienced no loss of motion in the operated joints after surgery, loss of motion occurred to only a small extent (10–15°) and few patients experienced difficulties with daily activities. The results of this clinical study suggest that surgical synovectomy for rheumatoid finger joints has anti-inflammatory effects as well as a prophylactic effect on the development of deformity and the progression of bony change after surgery.

The effects of total knee arthroplasty (TKA) on the disease activity of rheumatoid arthritis (RA) was investigated in the present study. The disease activity of RA in 58 patients who had undergone simultaneous bilateral TKA (116 knee joints) was examined before, and 1, 6 and 12 months and 3 and 5 years after the operation. The disease activity was assessed using the simplified Lansbury index according to the duration of morning stiffness, grip strength, joint count and erythrocyte sedimentation rate. In addition, C-reactive protein (CRP) and rheumatoid factor were also measured. The mean simplified Lansbury index and CRP significantly improved 1, 6 and 12 months after TKA surgery compared to preoperative levels. However, 3 and 5 years after TKA, the mean simplified Lansbury index indicated that the disease activity remained lower than the preoperative level in only 21 (36%) patients. The results of the present study demonstrate that TKA lowers RA activity for at least 1 year after surgery, and thus synovectomy and surgical resection of articular cartilage in the knee joint appear to have an anti-rheumatoid effect.

Several investigators have demonstrated an association between Epstein-Barr virus (EBV) and the pathogenesis of rheumatoid arthritis (RA). However, there is no direct evidence that this virus exists in the synovial cells of patients with RA. We attempted to detect EBV in synovial cells from RA patients. Specimens of synovial tissues from 34 patients with RA and from 20 patients with osteoarthritis (OA), and from one patient with psoriatic arthritis as controls, were examined for evidence of the EBV by in situ hybridization. The specimens were also tested by immunoperoxidase staining for expression of the CD21 molecule (EBV receptor), EBV nuclear antigen (EBNA)-2 and latent membrane protein (LMP)-1. EBV-encoded small RNA-1 (EBER) was demonstrated in synovial lining cells from eight (23.5%) out of 34 RA patients but in none of 20 OA patients (P < 0.05) nor in the one psoriatic arthritis patient. Interestingly, EBER localized in synovial lining cells that were located at the apex of villus proliferating lesions. Furthermore, LMP-1 was also detected in synovial lining cells at the top of villus lesions. Nevertheless, CD19 and CD21 molecules, and EBNA-2 were not demonstrated in such lesions. The incidence of EBV-positive in synovial lining cells with severely infiltrated lymphocytes tended to be higher than that in moderately infiltrated ones. This is the first evidence that EBV exists in chronically inflamed synovial lining cells of human joints in RA.

Total knee arthroplasty (TKA) was performed simultaneously on both knees by two teams in a single procedure. The study population consisted of 74 patients (148 knee joints) with osteoarthritis (OA) or rheumatoid arthritis (RA). The peri- and postoperative results were compared with those in a group of 22 OA and RA patients (44 knee joints) who underwent staged operation during one hospital stay. Comparisons were made of functional score and range of motion (ROM) before and after operation, mean total blood loss, operative time, duration of hospital stay, and operative and postoperative complications. The simultaneous performance of bilateral procedures did not influence the functional score, ROM after operation, or mean intra- and postoperative blood loss. Nor was incidence of operative and postoperative complications increased compared with that in the staged operation group. The operative time in the simultaneous TKA group was significantly shorter than the time that would have been required had separate procedures been performed on both knees. Simultaneous bilateral TKA is beneficial for the patient.

To clarify the effects of hyaluronic acid (HA) on cartilage metabolism, we examined proteoglycan (PG) and collagen metabolism by chondrocytes by allowing porcine free articular chondrocytes to react in vitro with HA. The involvement of protein kinase C (PKC) and CD44, an HA receptor, in the mechanisms whereby HA exerted its effects on PG and collagen metabolism was also investigated. HA increased the synthesis of PG and collagen by porcine chondrocytes. On immunostaining with anti-PKC serum, the chondrocytes to which HA was added showed more chromatic features than the group not administered HA (control). The increased synthesis of PG and collagen induced by HA was suppressed by a protein kinase inhibitor, H-7. CD44 was localized in the chondrocyte membrane, and was transferred from the cell membrane to the cytoplasm on the addition of HA. These findings suggest that HA binds to CD44 and acts on intracellular signal transduction via PKC as a result of the transmission of the bound HA to the cytoplasm. HA was speculated to exert both mechanical and chemical effects in activating cartilage metabolism.

The type of osteoarthritis and the degree of severity which causes restriction of knee range of motion (ROM) is still largely unknown. The objective of this study was to analyse the location and the degree of cartilage degeneration that affect knee range of motion and the connection, if any, between femorotibial angle (FTA) and knee ROM restriction. Four hundreds and fifty-six knees in 230 subjects with knee osteoarthritis undergoing knee arthroplasty were included. Articular surface was divided into eight sections, and cartilage degeneration was evaluated macroscopically during the operation. Cartilage degeneration was classified into four grades based on the degree of exposure of subchondral bone. A Pearson correlation was conducted between FTA and knee flexion angle to determine whether high a degree of FTA caused knee flexion restriction. A logistic regression analysis was also conducted to detect the locations and levels of cartilage degeneration causing knee flexion restriction. No correlation was found between FTA and flexion angle (r = −0.08). Flexion angle was not restricted with increasing FTA. Logistic regression analysis showed significant correlation between restricted knee ROM and levels of knee cartilage degeneration in the patella (odds ratio (OR) = 1.77; P = 0.01), the lateral femoral condyle (OR = 1.62; P = 0.03) and the posterior medial femoral condyle (OR = 1.80; P = 0.03). For clinical relevance, soft tissue release and osteophyte resection around the patella, lateral femoral condyle and posterior medial femoral condyle might be indicated to obtain a higher degree of knee flexion angle. Case–control study, Level III.

Histological and molecular changes were examined to investigate the effects of long-term administration of glucosamine (GlcN) and chondroitin sulfate (CS) in a model of spontaneous osteoarthritis (OA) in Hartley guinea pigs. Three groups of female 3-week-old Hartley guinea pigs received GlcN, CS, and neither agent, respectively. Five animals in each group were sacrificed at 8, 12, and 18 months of age. At 8 months of age, Hartley guinea pigs had severe degeneration of knee joint cartilage, chondrocyte apoptosis, marked reduction of tissue total RNA, decreases of aggrecan and collagen type 2 mRNAs, and increases in MMP-3 and MMP-8 mRNAs. Long-term administration of GlcN and CS reduced cartilage degeneration at 8 months of age. The marked loss of total RNA and the increase in MMP-3 mRNA were also inhibited by GlcN and CS. Thus, long-term oral administration of GlcN or CS inhibits OA progression, maintains total RNA and down-regulates MMP-3 mRNA in a spontaneous OA model in Hartley guinea pigs.

Finding an effective treatment strategy for rheumatoid arthritis (RA) patients who have not benefited from previous tumor necrosis factor-α antagonist treatment is important for minimizing RA disease activity and improving patient outcomes. The aim of this study was to compare the safety and effectiveness of etanercept in patients with and without infliximab (IFX) treatment experience. Patients (n = 7,099) from a large postmarketing observational study of etanercept use in Japan were divided into 2 cohorts based on previous IFX use (pre-IFX and non-IFX). Baseline characteristics were assessed in each cohort. Adverse events (AEs) and European League Against Rheumatism (EULAR) responses were monitored every 4 weeks for 24 weeks. At baseline, pre-IFX patients were younger and had fewer comorbidities and a shorter RA duration than non-IFX patients. During the study, pre-IFX patients received concomitant methotrexate more often than non-IFX patients. The incidence of AEs and serious AEs were significantly lower in pre-IFX patients, as was the percentage of patients who discontinued treatment. Both cohorts had significant improvement (P < 0.001) in EULAR responses at the end of the treatment period. This study demonstrated that etanercept was effective and well tolerated in active RA patients with and without prior IFX treatment.

Precise mechanism of developing neuropathic arthropathy known as Charcot's joint is not fully understood.A 55-year-old Japanese woman with neurofibromatosis-1 complained of right gonalgia in December 2001. Physical examination revealed a huge tumor in the right lower leg without signs of inflammation. Laboratory findings were unremarkable. Radiographic examination disclosed the presence of osteoarthropathy in the right knee joint. In contrast, radiologic findings of the right foot and ankle were compatible with neuropathic arthropathy. Further investigations could not reveal abnormal findings in the nervous system. To improve patient's quality of life, partial resection of the tumor was performed. The resected tissues were compatible with neurofibromatosis without malignant transformation. The patient newly noticed pains in the right ankle and tarsal joints one year after the operation. Restricted mobility and insufficient blood supply in the right knee arising from the huge tumor might accelerate development of osteoarthropathy through malnutrition of the chondrocytes. Because the patient did not experience the arthralgia before the operation, the tumor might damage the peripheral nerves unabling to receive afferent signals from such joints resulting in neuropathic arthropathy.The damaged peripheral nerves might be contributory to developing or accelerating neuropathic arthropathy.

Scaphocapitate fracture refers to a combination of fractures in the scaphoid and capitate. In 1956, Fenton reported two cases of scaphocapitate fracture that he termed “naviculocapitate fracture syndrome.” Fortythree cases have been reported since then. However, scaphocapitate fracture associated with median nerve palsy is rare. Our report concerns a case of scaphocapitate fracture associated with median nerve palsy. Treatment involved open reduction and internal fi xation using a Herbert screw.

In this study, we examined the effect of photodynamic therapy (PDT) using Na-pheophorbide a (Na-Phde a) on normal joint tissue.The treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection is a serious issue. Recently, an experimental in vivo and in vitro model for the inactivation of MRSA by PDT using a photosensitizer, Na-Phde a, has been developed.The knee joints of mice were injected with 560 or 280 micromol/L of Na-Phde a. Thirty minutes after injection, percutaneous laser irradiation was applied for 5 min using a semiconductor laser (power: 125 mW; wavelength: 664 nm; total energy: 12 J/cm2). The joint perimeter and body weight of the treated mice were monitored, and histological evaluation was also done.Joint swelling was observed up to 3 wk after PDT (p0.05). On histology 1 wk post-PDT, the treated knees were found to have inflammatory changes, primarily in synovial tissue. Eight weeks after PDT, the synovitis was no longer present. No significant effects were observed on cartilage, bone marrow, or menisci.The results of this experiment showed that PDT with Na-Phde a induced arthritis for a short time after treatment. However, this arthritis was reversible, and the PDT did not appear to induce osteoarthritic changes in normal joint tissue. These findings indicate that PDT using Na-Phde a caused minimal but reversible changes in joint tissue, suggesting that it would be a safe and useful treatment for bacterial septic arthritis.

Summary With the cooperation of the Japanese Musculoskeletal Oncology Group (JMOG), we conducted a questionnaire survey to assess the status of extendable prosthesis use after resection of malignant bone tumors in children. The subjects were 28 patients (mean age, 10.1 years). Osteosarcoma was the most frequent tumor, and all patients had undergone preoperative chemotherapy and wide resection. The prosthesis was the Growing Kotz-type in 26 patients. The mean predicted leg length discrepancy was 67.7mm, mean stem diameter 10mm, mean number of elongations 2.1, and mean total elongation 35.4mm. Infection was observed in one patient with a mean functional assessment of 75%. In Japan, extendable prostheses, as represented by the Growing Kotz-type, provide a useful limb reconstruction method, with a minimum of major complications and with good function of the affected limb. However, a long-term follow-up survey is necessary.

Survivin expression has been detected in various cancers and correlations have been recognized between the level of expression of this gene in tumors and prognosis. However, the aforementioned authors did not evaluate correlations between prognosis and survivin expression levels using surgically resected samples. In this study, we retrospectively investigated outcomes by examining the correlations between expression of this gene and clinicopathological parameters. Biopsy and resected specimens from which paraffin-embedded tissues could be extracted, were available from 16 patients in our hospital. We used the RT-PCR method and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker. Expression of survivin mRNA was detected in all samples. There was a significant negative correlation between survivin expression levels and duration of follow up, in months, using the Spearman's rank for the initial biopsy samples (rho=-0.775, p

The Harris-Galante I modular acetabular components (Zimmer, Warsaw, Ind) were most widely used in the 1980s in primary and revision total hip arthroplasty. We assessed 76 primary total hip arthroplasties performed using Harris-Galante I modular acetabular components. Dissociation of the polyethylene liner occurred in 5 patients and required revision surgery. None of the 76 hips had fractures of the metal locking tines on the metal shell. Liner dissociation was attributed to fatigue fracture of the polyethylene, a result of a gap between the liner and the metal shell. The thin polyethylene liner rim aggravated failure. The revision technique was to cement the polyethylene liner into the well-fixed Harris-Galante metal shell. The average follow-up observation period after revision surgery was 6.4 years; and there was no recurrence of dissociation, which supports the use of our revision technique.