Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18666381 Persistent clinical response of infliximab therapy in patients with refractory rheumatoid 2006 Jan Infliximab, a chimeric monoclonal anti-tumor necrosis factor alpha antibody is approved for the treatment of patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) therapy. This report provides analyses by using infliximab in combination with various disease modifying anti-rheumatic drugs, infliximab "survival" over a period of three years, and its effectiveness on synovial tissue damage using magnetic resonance (MR) imaging. The study was started in 1999 as an open label study using infliximab in combination with cyclosporin A (CsA) in refractory RA patients who were unable to tolerate MTX. A total of 18 RA patients were investigated. After a year of treatment, 80% of patients achieved the 20% American College of Rheumatology Response criteria. Two patients dropped out; one because of an immediate hypersensitivity reaction and the other because of the development of pulmonary tuberculosis. In a subsequent study we investigated infliximab "survival" over a period of 3 years. A total of 84 RA patients were included in the study. After 3 years of therapy, 59% of patients still continued receiving infliximab. The factor that was associated with infliximab "survival" was the concomitant use of MTX. A total of 28 (33%) patients discontinued this study. More specifically, 16 (19%) presented adverse drug reactions, 9 (11%) had drug failure, and 3 (3%) were lost from follow-up. Finally, to evaluate by MR imaging the inflammatory tissue changes in refractory RA patients treated with infliximab, 16 patients were examined with MR imaging of the dominant affected wrist and hand before and one year after therapy. The volume of the enhancing inflammatory tissue (VEIT) was evaluated. A significant decrease of VEIT was observed in 88% of patients after therapy. We conclude that in refractory RA patients infliximab was proved to be efficacious and well tolerated in combination with CsA. The clinical response of infliximab was persistent over a 3-year period and was associated with the concomitant use of MTX. This clinical improvement was also associated with the reduction of inflammatory disease tissue damage.
17170051 Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumat 2007 May BACKGROUND: Several clinical and experimental lines of evidence suggest that leucotriene B4 (LTB4), an arachidonic acid derivative with potent proinflammatory properties, plays a key role in the pathophysiology of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the efficacy and safety of BIIL 284, an oral long-acting LTB4 receptor antagonist, as monotherapy for the treatment of patients with active RA. METHODS: This was a multi-centre, randomised, double-blind, placebo-controlled trial of patients with active RA of 3 months' duration. A total of 342 patients were randomised to receive 5 mg, 25 mg or 75 mg of BIIL 284 or placebo. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR) 20. RESULTS: Although a higher percentage of ACR 20 responders was observed in the groups treated with 25 mg and 75 mg of BIIL 284 compared with those treated with placebo, no statistically significant differences were found between any of the three active treatment groups compared with the placebo group with regard to the primary or secondary end points. All trial treatments were safe and well tolerated. CONCLUSIONS: This clinical trial demonstrates that treatment of patients with active RA with a potent oral long-acting LTB4 receptor antagonist produced only modest improvements in disease activity. The results of this trial support the conclusion that LTB4 is not a major contributor to the inflammatory process in RA.
17100028 Serum leptin levels in rheumatoid arthritis and relationship with disease activity. 2006 Oct OBJECTIVES: This study was performed to evaluate serum leptin levels in rheumatoid arthritis (RA) patients and investigate the correlation with serum tumor necrosis factor alpha (TNF-alpha) levels and clinical and laboratory parameters of disease activity. METHODS: Fifty patients with RA and 34 control subjects were included. Disease activity score 28 (DAS28) was calculated for each patient. Laboratory activity was assessed by examining erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Immunoradiometric assay was used for measuring serum leptin levels (ng/mL). Serum TNF-alpha levels (pg/mL) were measured by sandwich enzyme-linked immunosorbent assay method in 41 of 50 RA patients and in 24 control subjects. RESULTS: Age, sex and body mass index (BMI) did not show a statistically significant difference between RA and control subjects (P > 0.05). Serum leptin levels were higher in RA (P = 0.000). In RA patients, there were no correlations between serum leptin levels and disease duration, swollen and tender joint counts, DAS28, CRP, ESR, serum TNF-alpha levels, oral glucocorticoid and methotrexate usage (P > 0.05). There was no statistically significant serum leptin level difference between patients with high disease activity and mild and low disease activity (P = 0.892). Serum leptin levels positively correlated with BMI in both patient and control groups (P < 0.05). In both groups, mean serum leptin levels were higher in women than men. CONCLUSIONS: Even though serum leptin levels were found to be significantly higher in RA patients than in control subjects in this study, there was no correlation between serum leptin levels and TNF-alpha levels, clinical and laboratory parameters of disease activity. However serum leptin levels positively correlated with BMI in both patient and control groups. In RA, circulating leptin levels do not seem to reflect disease activity.
15674392 Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequen 2005 May T-lymphocytes play an important role in rheumatoid arthritis (RA). In this study, we evaluated the hypothesis that common T-cell receptor (TCR) structural features may exist among infiltrating T cells of different RA patients, if the TCR repertoire is shaped by interaction with common self or microbial antigens in the context of susceptible HLA genes in RA. Synovial lesion tissue (ST), synovial fluid (SF) and blood specimens from RA patients and controls were analyzed for TCR V gene repertoire by real-time PCR. There was highly skewed BV14 and BV16 usage in synovial T cells of RA as opposed to those of controls, which was accompanied with a trend for correlation between skewed BV16 and DRB1(*)0405. Immunoscope analysis of the V-D-J region of ST-derived T cells demonstrated oligoclonal and polyclonal expansion of BV14(+) and BV16(+) T cells. Detailed characterization using specific BV and BJ primers further revealed common clonotypes combining the same BV14/BV16, BJ and CDR3 length. DNA cloning and sequence analysis of the clonotypes confirmed identical CDR3 sequences and common CDR3 sequence motifs among different RA patients. The findings are important in the understanding of BV gene skewing and CDR3 structural characteristics among synovial infiltrating T cells of RA.
16985251 Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study 2006 Sep 20 BACKGROUND: Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. METHODS: Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18,573 matched control subjects, and more than 86,000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. RESULTS: We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). CONCLUSIONS: Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions.
16505601 [The role of CD4+CD25+ regulatory T cells in patients with Rheumatoid Arthritis]. 2006 Feb CD4(+)CD25(+) regulatory T cells play an important role in preventing autoimmunity. We investigated the presence of CD4(+)CD25(+) regulatory T cells in the peripheral blood of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc), using flow cytometry. The percentage of CD4(+)CD25(+) regulatory T cells was significantly decreased in RA, especially in patients with high serum levels of either CRP or MMP-3. In SSc and SLE, the percentage of CD4(+)CD25(+) regulatory T cells was higher in patients than in controls, but not significant. We also investigated the serum levels of IL-10, which influences the function of CD4(+)CD25(+) regulatory T cells and other regulatory T cells. In RA, on contrast to CD4(+)CD25(+) regulatory T cells, the serum levels of IL-10 increased in patients with higher serum levels of CRP, or MMP-3. In SLE and SSc, the serum level of IL-10 increased significantly in patients than in controls. These data thus indicated that CD4(+)CD25(+) regulatory T cells contributes to occurrence and progression of RA, and other regulatory T cells or cytokines contribute to occurrence and progression of SSc and SLE.
16126971 Prevalence of antiphospholipid and antioxidized low-density lipoprotein antibodies in rheu 2005 Jun Antiphospholipid antibodies characterize the antiphospholipid syndrome (APS), but they can also be found in various autoimmune, infectious, and malignant conditions. This study's objectives were to detect the prevalence of antiphospholipid and antioxidized low-density lipoprotein (anti-oxLDL) antibodies among patients with rheumatoid arthritis (RA) who did not have clinical manifestations of APS. Using a standard enzyme-linked immunosorbent assay (ELISA), we evaluated the levels of immunoglobulin G (IgG) and IgM anticardiolipin, IgG, and IgM anti-beta-2-glycoprotein-I (anti-beta(2)GPI), and anti-oxLDL autoantibodies in 82 patients with RA. The cutoff levels for detecting these autoantibodies were 15 IgG phospholipid units (GPL), 15 IgM phospholipid units (MPL), and 25 ELISA units (EU)/mL, respectively. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 10 with low levels of IgG anticardiolipin and 7 with medium to high levels of anticardiolipin autoantibodies. IgM anticardiolipin was found in only 1 (1%) patient, and both IgG and IgM anti-beta(2)GPI were found in 3 (4%) patients with RA. Elevated levels of anti-oxLDL antibodies were found in 8 (10%) patients, 4 of whom also had elevated levels of IgG anticardiolipin. We conclude that IgG anticardiolipin autoantibodies can be found in about one-fifth of RA patients who do not have clinical manifestations of APS. Whether the presence of anticardiolipin signifies increased risk for thrombosis and atherosclerosis in these patients should be studied further.
17032600 [Life-threatening liver failure and severe dyscrasias in blood and lymph nodes caused by s 2006 Sep 25 We report a case of sulphasalazine-related drug-induced hypersensitivity syndrome (the "three-week sulphasalazine syndrome") in which periferal T-cell lymphoma was a provisory diagnosis. A 40-year-old woman with seropositive rheumatoid arthritis was admitted to a local hospital 26 days after initiation of sulphasalazine treatment. She had fever, lymphadenopathy, dermatitis and facial oedema and showed biochemical signs of progressive hepatitis. Peripheral blood counts showed elevated leucocyte count with 15% atypical plasmacytes. Lymph node biopsy showed altered follicular architecture, a diffuse CD 4 positive predominance and histiocytes with erythrophagocytosis. Investigation by gene rearrangement for clonality of B- and T-lymphocytes ruled out the suspicion of lymphoma. Haematological and near-fatal hepatological changes resolved following discontinuation of sulphasalazine and a three-week course of glucocorticoid therapy. Early awareness of this syndrome via measuring liver function tests on, e.g., days 14-35 in patients started on sulphasalazine is recommended.
17127204 Infection and musculoskeletal conditions: Imaging of musculoskeletal infections. 2006 Dec Imaging procedures are routinely used to evaluate patients suspected of having musculoskeletal infection. Radiographs should be performed whenever musculoskeletal infection is suspected. Even when not diagnostic, radiographs are useful. They provide an anatomic overview of the region of interest, including pre-existing conditions that could influence the selection and interpretation of subsequent procedures. Magnetic resonance imaging (MRI) is sensitive, provides superb anatomic detail, does not use ionizing radiation, and is rapidly completed. This technique is especially valuable for septic arthritis, spinal osteomyelitis, and diabetic foot infections. Among the radionuclide procedures, three-phase bone imaging is readily available, and very accurate in unviolated bone. Labeled leukocyte imaging should be used in cases of 'complicating osteomyelitis' such as prosthetic joint infections. This test is also useful in unsuspected diabetic pedal osteomyelitis and the neuropathic joint. Gallium imaging is a useful adjunct to MIR in spinal infection. 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) will likely play an important role, especially in the evaluation of spinal infection.
17143972 Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis suscep 2007 Jan OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) promoter -308 A/G polymorphism has been reported to be associated with rheumatoid arthritis (RA) with inconsistent results. We investigated whether TNF-alpha -308 A/G polymorphism confers susceptibility to RA. METHODS: We conducted a random effect metaanalysis on the association of genotypes A/A (recessive effect), A/A + A/G (dominant effect), A allele, and A/A vs G/G genotypes of the TNF-alpha -308 polymorphisms with RA overall and within different ethnic populations. RESULTS: Fourteen studies, 10 of Europeans, 3 of Latin Americans, and one Asian, were included in this metaanalysis. An association between RA and the TNF-alpha -308 A allele was not found in the overall population (OR 1.005, 95% CI 0.715-1.412, p = 0.976). However, stratification by ethnicity indicated that the TNF-alpha A allele was significantly associated with RA in Latin Americans (OR 2.004, 95% CI 1.158-3.467, p = 0.013). Conversely, there was no association detected for the TNF-alpha A allele with RA patients from the European samples (OR 0.911, 95% CI 0.684-1.212, p = 0.520). The OR for the A/A + A/G genotype, the A/A genotypes, and the A/A vs G/G genotypes in samples overall and in each ethnic group showed a similar trend to those for the TNF-alpha A allele. CONCLUSION: This metaanalysis demonstrates that the TNF-alpha -308 A/G polymorphism may represent a significant risk factor for RA in Latin Americans, but not in Europeans.
16038842 Infliximab continuation rates in patients with rheumatoid arthritis in everyday practice. 2005 Jul Infliximab is a major breakthrough in the management of rheumatoid arthritis (RA). We evaluated infliximab continuation rates and reasons for discontinuation in patients with RA. PATIENTS AND METHODS: We studied patients with RA started on infliximab at any time between March 2000 and December 2002, under the conditions of everyday practice (as opposed to clinical trial settings), as recommended by the French marketing license (3 mg/kg as an intravenous infusion at weeks 0, 2, and 6 then at 8-week intervals). The number of infliximab infusions, side effects, and nonresponse rates was recorded. The Kaplan-Meier method was used to evaluate treatment continuation. Reasons for discontinuation were studied. RESULTS: We included 41 patients, with a mean age of 54 years, a mean RA duration of 9 years, and a mean of three previous disease-modifying antirheumatic drug treatments. The total number of infliximab infusions was 461 with a mean of 10.8 per patient and a mean follow-up under treatment of 15.3 months. The proportions of patients still on infliximab were 82%, 74%, and 67% after 6, 12, and 24 months, respectively. The main reasons for discontinuation were escape phenomenon (n = 6, 42.8% of discontinuations) and allergy (n = 3); in one case each, the reason was primary ineffectiveness, severe infection, plans to start a pregnancy, poor compliance, and unavailability for follow-up. There were 59 recorded episodes of side effects, with a profile similar to that in the literature and in postmarketing databases. CONCLUSION: The infliximab continuation rate in everyday practice in patients with RA (67% after 2 years) was consistent with published data and with the results of controlled trials.
16248997 The CTLA4+49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern 2006 Apr Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2%; P=0.02; OR=1.28; 95% C.I.=1.04-1.58) and JIA (61.8%; P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value<0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively). Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population.
16982117 [Aspergillosis in systemic diseases treated with steroids and/or immunosuppressive drugs: 2006 Nov This is a multicentric retrospective study of aspergillosis in patients treated by corticosteroids and/or immunosuppressive drugs for systemic diseases and a review of the literature. Nine patients, 5 men and 4 women, mean age of 62.8 years old were included among which Horton's diseases (3 cases), systemic lupus erythematosus (2), polymyositis (1), microscopic polyangiitis (1), idiopathic thrombocytopenic purpura (1), rheumatoid polyarthritis (1). Aspergillosis occurred in average 28.4 month after the diagnosis of systemic disease, and 28 months after the beginning of its treatment: corticosteroids in all cases, at a dose of 50.8 mg/day (equivalent prednisone) in average, cyclophosphamide (2 cases), methotrexate (1), intravenous immunoglobulins (1), leflunomide (1). All cases were invasive or chronic pulmonary aspergillosis located in the lungs (6 cases), or in the brain (3). Revealing symptoms were mild and non specific. Lymphopenia was severe in most cases, in average 472 lymphocytes/mm3 and 283 CD4+/mm3. The diagnosis was confirmed 20.75 days after the first symptoms in invasive aspergillosis, and 18.5 months in the chronic pulmonary cases, by cultures in 7 cases (broncho-alveolar lavage: 4; cerebral biopsy: 3), and direct microscopy examination of broncho-alveolar lavage in 2 cases. Specific serology was positive in 4 cases. Patients were treated by voriconazole (4 cases), itraconazole (2), amphotericin B (1), association of caspofungin and voriconazole (1), successive voriconazole and itraconazole (1). Six patients recovered from aspergillosis with 10.8 months of following time, 3 patients died a few days after confirmation of the diagnosis. Fifty-four cases of the literature are analysed.
15208176 Long term safety of methotrexate in routine clinical care: discontinuation is unusual and 2005 Feb OBJECTIVE: To analyse patients with rheumatoid arthritis, treated with methotrexate in a weekly academic rheumatology clinic over 13 years, for continuation of courses and reasons for discontinuation. METHODS: All 248 patients with an analysable longitudinal course who took methotrexate in standard care between 1990 and 2003 were studied. Continuation of courses was analysed using life tables. All abnormal and severely abnormal values for aspartate aminotransferase (AST) >40 U/l, >80 U/l, albumin <35 g/l, <30 g/l, white blood cell (WBC) count <4.0 x 10(9)/l, <3.0 x 10(9)/l, and platelet count <150 x 10(9)/l, <100 x 10(9)/l, were identified. Responses of the clinician and subsequent laboratory values were reviewed. RESULTS: Over 1007 person-years, the probability of continuing methotrexate over five years was 79% (95% confidence interval, 72% to 84%). Severe laboratory abnormalities occurred in 2.9 per 100 person-years, specifically 0.9 for AST >80 U/l, 1.1 for albumin <30 g/l, 0.7 for WBC <3.0 x 10(9)/l, and 0.3 for platelets <100 x 10(9)/l. No severe laboratory abnormality progressed to further severity or clinical disease. Permanent discontinuations of methotrexate occurred in 46 patients (19%), 26 (10% of all patients) for adverse effects, 15 (32.6%) for inefficacy; only two discontinuations resulted from laboratory abnormalities, both of WBC, possibly from other sources. CONCLUSIONS: Methotrexate was associated with a high rate of continuation, and few clinically significant laboratory abnormalities. Discontinuation primarily reflected clinical rather than laboratory findings. Vigilance for methotrexate toxicity is required but methotrexate appears among the safest treatments for rheumatoid arthritis.
16156465 Conversion of knee fusion to total arthroplasty: complications in 8 patients. 2005 Jun BACKGROUND: There are no clear indications for conversion of knee fusion to total arthroplasty. In this paper we report outcome and complications in 8 patients. PATIENTS AND METHODS: We reviewed 8 total knee arthroplasties after takedown of previous fusion 24-55 months after the conversion. The original diagnoses were complications following injury in 3 patients, rheumatoid arthritis in 3, complication after chondromalacia in 1 patient and tuberculous arthritis in 1 patient. The age at operation ranged from 31 to 67 years. The time since arthrodesis ranged from 1 to 49 years. RESULTS: 5 patients had to undergo reoperation for postoperative complications. 2 patients experienced recurrence of previous deep infection, which led to thigh amputation in one and chronic fistulation in the other. Only 1 patient had an uneventful course after the conversion procedure, but he died later on due to a heart attack. As another patient also died of cardiovascular disease, 5 of the 8 patients were available for evaluation of knee function. In these patients the knee flexion ranged from 90 to 120 degrees, extension lag ranged from 10 to 40 degrees, and all knees were aligned at 6 to 8 degrees of valgus. The Knee Society clinical scores ranged from 47 to 74, the Womac scores ranged from 9 to 47, and EuroQol ranged from 0.1 to 0.8. INTERPRETATION: Our findings indicate that conversion of knee arthrodesis to total arthroplasty should only be performed in selected cases, and after giving the patient extensive information about the high risk of rather serious complications.
15888916 Interaction between HSP73 and HLA-DRB1*0401: implications for the development of rheumatoi 2005 The amino acid motif QKRAA on HLA-DRB1*0401 carries susceptibility to develop rheumatoid arthritis through unknown mechanisms. We identified the original functions of this motif. In B-cells, HSP73, the constitutive 70-kDa heat-shock protein (HSP), associates with HLA-DRB1*0401. This interaction causes abnormal trafficking of HLA-DRB1*0401. Indeed, HSP73 targets HLA-DRB1*0401 from endoplasmic reticulum to lysosomes bypassing the normal route through the Golgi apparatus and endosomes. In this article, we propose mechanisms to explain how 70-kDa HSPs might contribute to rheumatoid arthritis.
17144481 [Diagnostic problems in pleural involvement in systemic diseases]. 2006 Jul Pleuropulmonary manifestations in connective tissue diseases are frequent and variable. Pleural involvement is due especially to autoimmune inflammation and vasculitis, causing increased capillary permeability. Many of pleural effusions are asymptomatic, but with advancement in chest scanning techniques and immunohistology, pleuropulmonary abnormalities are increasingly being recognized in the early stages of a variety of connective tissue disease. The purpose of this article is to provide comprehensive information about incidence, pathophysiology, clinical manifestation and treatment for pleural diseases associated with connective tissue diseases.
15972905 Natural history of fixed flexion deformity following total knee replacement: a prospective 2005 Jul We investigated fixed flexion deformity (FFD) after total knee replacement (TKR). Data relating to 369 cruciate-retaining unilateral TKRs performed at a single institution were collected prospectively. Fixed flexion was measured pre-operatively and at one week, six months, 18 months, three years and five years after surgery. Using binary logistic regression, pre-operative FFD was a predictor of post-operative FFD > 10 degrees at one week (p = 0.006) and six months (p = 0.003) following surgery. Gender was a predictor at one week (p = 0.0073) with 24% of women showing a FFD > 10 degrees compared with 37% of men. We have shown that a gradual improvement in knee extension can be expected up to three years after surgery in knees with FFD. By this time residual FFD is mild or absent in the majority of patients, including those who had a severe pre-operative FFD.
16235383 Retention versus sacrifice of the posterior cruciate ligament in total knee replacement fo 2005 Oct 19 BACKGROUND: The functional and clinical results to support the choice whether or not to retain the posterior cruciate ligament (PCL) during total knee arthroplasty have not been gathered and analysed so far. There are at least some trials showing no difference. OBJECTIVES: To identify the difference in functional, clinical, and radiological outcome between retention and sacrifice of the PCL in total knee arthroplasty in patients with osteoarthrosis and other non-traumatic diseases. SEARCH STRATEGY: A search was conducted in MEDLINE(Through PubMed; 1966 - March 2004), EMBASE (1980 - March 2004), Cochrane Central Register of Controlled Trials (CENTRAL Issue 2004 - 1), and Current Contents (1996 - March 2004). Also, references of selected articles were checked and citation tracking on the articles selected was performed. SELECTION CRITERIA: Randomised controlled trials comparing retention to sacrifice of the PCL during total knee arthroplasty with regard to functional, radiological and clinical outcome in patients with osteoarthritis and other non-traumatic diseases were selected by two independent reviewers. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed with the checklist by van Tulder and the Jadad list. Data was collected with a predeveloped form. Meta-analysis was performed with subgroup analyses on age, gender, disease severity, and follow-up time, if allowed by adequate power. MAIN RESULTS: Eight randomised controlled trials were found. Two treatment options were compared against PCL retention: PCL sacrifice without additional stabilisation (post and cam mechanism) (2 studies), and PCL sacrifice with posterior stabilized design (5 studies). One study included all three options. Range of motion was found to be 8.1 degrees higher in the posterior stabilized group compared to the PCL retention group (p=0.01, 95% confidence interval [1.7, 14.5]), although the heterogeneity was high (I(2 )= 66.3%). PCL resection without substituting the PCL with a posterior stabilised prosthesis showed no difference compared to PCL retention (p=0.31, I(2) = 83.2%). On clinical scores, only Hospital for Special Surgery score revealed a significant difference of 1.6 points (p=0.03, 95% confidence interval [-3.1, -0.1]) between PCL retention versus PCL sacrifice and substitution combined favouring the latter group. The necessary subgroup analyses could not be performed for the clinical scores. AUTHORS' CONCLUSIONS: These results should be interpreted with caution as the methodological quality of the studies was highly variable. We conclude that there is, so far, no solid base for the decision to either retain or sacrifice the PCL with or without use of a posterior stabilized design during total knee arthroplasty. The technique of PCL retention is difficult because the normal configuration and tension need to be reproduced with ligament tensioners. Knowledge of the technique needs to be improved before it can yield superior results compared to the more straightforward techniques of PCL sacrifice or use of a posterior stabilized design. Also, studies evaluating the effect of both techniques should address the right outcome parameters such as range of motion, contact position, and anterior-posterior stability. Suggestions are given to improve future research on this specific topic of knee arthroplasty.
16034643 Bilateral simultaneous extensor mechanism disruption following simultaneous bilateral tota 2005 Jul Extensor disruptions of the knee following the total knee replacements are uncommon. We describe a case of postoperative bilateral simultaneous extensor mechanism disruption following simultaneous bilateral total knee replacement. On both sides, the patient sustained open wounds. The extensor mechanism was successfully repaired on both sides, but the outcome is less than satisfactory.