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ID PMID Title PublicationDate abstract
23678159 Cholesteryl ester transfer protein in patients with rheumatoid arthritis. 2013 Jul OBJECTIVE: To investigate how cholesteryl ester transfer protein (CETP), one of the enzymes involved in the reverse cholesterol transfer, is expressed in patients with rheumatoid arthritis (RA) and its potential relationship with both dyslipidemia and the risk of cardiovascular mortality observed in these patients. METHODS: Plasma CETP concentrations and CETP activity were measured in 101 patients with RA and 115 sex- and age-matched controls. A multivariable analysis adjusted for standard cardiovascular risk factors, including high-density lipoprotein cholesterol, was performed to evaluate the influence of CETP on dyslipidemia and cardiovascular mortality risk, as assessed by the Systematic Coronary Risk Evaluation (SCORE) risk function. RESULTS: Patients with RA showed lower CETP activity [beta coefficient = -10.82 (95% CI -19.56 to 2.07) pmol/3 h; p = 0.02] and an inferior CETP mass [β = -0.85 (95% CI -1.64 to 0.05) μg/ml; p = 0.03] versus controls. Divided into those taking and those not taking glucocorticoids, patients taking glucocorticoids revealed lower CETP activity and mass [β = -8.98 (95% CI -14.55 to 3.41) pmol/3 h; p = 0.00, for CETP activity; and β = -0.77 (95% CI -1.46 to 0.08) μg/ml; p = 0.03, for CETP mass]. Patients with RA not taking glucocorticoids showed no differences versus controls in either CETP activity or mass. Both current prednisone intake [β = -16.14 (95% CI -24.87 to 7.41) pmol/3 h; p = 0.00] and average daily prednisone intake during the last 3 months [β = -0.36 (95% CI -0.54 to 0.18) μg/ml; p = 0.01] were strongly and inversely correlated with CETP activity and mass, respectively. CETP activity showed an inverse trend compared to SCORE risk, demonstrating that lower levels were effective predictors of total mortality when a higher SCORE risk was found [β = -4.7 (95% CI -9.3 to 0.02) pmol/3 h; p = 0.04] in patients with RA. CONCLUSION: CETP is downregulated in patients with RA who are taking glucocorticoids. Low CETP activity is associated with an increased level of cardiovascular risk in patients with RA.
24315477 Shoulder arthroplasty for rheumatoid arthritis: 303 consecutive cases with minimum 5-year 2014 Jun BACKGROUND: This is an update on a previously documented cohort of patients who underwent shoulder arthroplasty for rheumatoid arthritis, with a minimum 5-year clinical follow-up. METHODS: The survivorship of 303 consecutive shoulder arthroplasties (108 hemiarthroplasties, 195 total shoulder arthroplasties) for rheumatoid arthritis at one institution was assessed. There were 255 arthroplasties in the clinical analysis and 188 in the radiographic analysis. RESULTS: Kaplan-Meier survivorship free of revision at 5 years and 10 years was 96.1% and 92.9% for total shoulder arthroplasty (TSA) and 89.2% and 87.9% for hemiarthroplasty (HA). The most common indications were glenoid loosening (5%) and infection (2%) for TSA revision and glenoid arthrosis (7%) for HA revision. Pain relief was greater with TSA than with HA. In patients with an intact rotator cuff, in comparing TSA with HA, those with a TSA had greater improvements in pain scores (-2.7 vs. -1.8 on a 5-point scale) and degrees of elevation (45 versus 24) (P = .08). Approximately 30% of humeral components and 73% of glenoid components had periprosthetic lucencies. There was a shift in position of the glenoid in 33% of TSAs, and 36% were "at risk." Eighty-one percent of HAs had moderate or severe glenoid erosion. DISCUSSION/CONCLUSION: Both HA and TSA provide pain relief and improved motion in patients with rheumatoid arthritis. In patients with an intact rotator cuff, pain relief and range of motion are more improved with TSA compared with HA. There is a high rate of component lucency, but component revision is uncommon. LEVEL OF EVIDENCE: Level IV, case series, treatment study.
25440525 Does non-erosive rheumatoid arthritis exist? A cross-sectional analysis and a systematic l 2015 Apr OBJECTIVE: To evaluate the prevalence and factors associated with non-erosive rheumatoid arthritis (RA). METHODS: First, a cross-sectional analytical study was performed. Non-erosive disease, defined as the absence of any erosion on X-rays after 5 years of RA, was evaluated in 500 patients. Further and additional evaluations including ultrasonography (US) and computed tomography (CT) were performed in those patients meeting the eligibility criteria. The Spearman correlation coefficient, kappa analysis, and Kendall׳s W test were used to analyze the data. Second, a systematic literature review (SLR) was performed following the PRISMA guidelines. RESULTS: Of a total of 40 patients meeting the eligibility criteria for non-erosive RA, eight patients were confirmed to have non-erosive RA by the three methods. A positive correlation between non-erosive RA and shorter disease duration, antinuclear antibodies positivity, lower rheumatoid factor (RF) and C-reactive protein titers, lower global visual analog scale values, toxic exposures, and lower disease activity-(RAPID3) was found. In addition, an inverse correlation with anticyclic citrullinated peptide antibodies (ACPA) positivity and medication use was observed. From the SLR, it was corroborated that factors associated with this subphenotype were shorter disease duration, younger disease onset, negative ACPA and RF titers, low cytokine levels, and some genetic markers. CONCLUSION: Non-erosive RA is rare, occurring in less than 2% of cases. These findings improve on the understanding of RA patients who present without erosions and are likely to have less severe disease.
24247114 Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis a 2014 Jan PURPOSE OF REVIEW: Despite the progress toward understanding the molecular pathogenesis of rheumatoid arthritis (RA), its cause remains elusive. Genes are important but rather insufficient to explain the majority of RA cases. This review describes the novel data supporting the microbiome and its interactions with the human host as potential en('in')vironmental factors in RA pathogenesis. RECENT FINDINGS: Animal models of inflammatory arthritis have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses and elicit joint inflammation. Human RA studies have focused on three mucosal sites: the gut, the gingiva, and the respiratory tree. The oral microbiome, and specifically Porphyromonas gingivalis, has long been implicated. Novel sequencing technologies have allowed investigations into the role of the gut microbiome in the development of autoimmune arthritis. Most recently, the pulmonary parenchyma has also been described as yet another possible mucosal site of initiation of autoimmunity in RA. SUMMARY: Emerging data implicate the microbiome in RA pathogenesis. Mucosal sites exposed to a high load of bacterial antigens--such as the periodontium, lung, and gut--may represent the initial site of autoimmune generation. If validated, these findings could lead to the discovery of potential biomarkers and therapeutic approaches in the preclinical and clinical phases of RA.
23393145 Defining erosive disease typical of RA in the light of the ACR/EULAR 2010 criteria for rhe 2013 Apr BACKGROUND: According to the 2010 criteria, rheumatoid arthritis (RA) can be classified in the presence of ≥6 points on the criteria or 'typical' erosive disease. RA-specific erosiveness however has not been defined yet. This study reports the results of the data driven phase of a European League Against Rheumatism (EULAR) taskforce aiming to define RA-specific erosiveness. METHODS: Baseline radiographs of hands and feet of 980 Dutch and 811 French early arthritis patients were studied on the number and site of erosive joints. Test characteristics were determined, with the outcome measures being initiation of methotrexate (MTX) therapy or any disease modifying antirheumatic drug (DMARD) therapy within the first year of disease and arthritis persistency over 5 years. Analyses were repeated in the patients with <6 points on the American College of Rheumatology/EULAR 2010 criteria. RESULTS: In both cohorts comparable test characteristics were observed for the outcomes MTX therapy, any DMARD therapy and arthritis persistency. Test characteristics were not influenced by the site of erosiveness. The specificity observed was >50% for ≥1 erosive joint, >80% for ≥3 erosive joints and >90% for ≥5 erosive joints. When analysing the patients not fulfilling the 2010 criteria (n=308 and 149), specificity was >60% for ≥1 erosive joint, >90% for ≥3 erosive joints and >95% for ≥5 erosive joints. Few of these patients fulfilled the radiological criterion; 27-36 patients had ≥3 erosive joints and 13-14 patients had ≥5 erosive joints. CONCLUSIONS: RA-specific erosiveness can be defined with high specificity at several cut-offs for the number of erosive joints in two independent cohorts with multiple different outcomes. The final radiological criterion will be established in the next phase.
25399601 Immunoglobulin heavy-chain-binding protein (BiP): a stress protein that has the potential 2014 Dec Immunoglobulin heavy-chain-binding protein (BiP) or glucose-regulated protein 78 (Grp78) is a vital ubiquitous resident of the endoplasmic reticulum (ER). As an intracellular chaperone, BiP correctly folds nascent polypeptides within the ER and regulates the unfolded protein response ensuring protection of the cell from denatured protein and reinforcing its anti-apoptotic role, when the cell is under stress. Additionally, BiP is a member of the heat-shock protein (HSP) 70 family and, as a stress protein, is up-regulated by conditions of reduced oxygen and glucose. Cell stress induces surface expression and secretion of BiP. Consequently, BiP is detectable in several bodily fluids including serum, synovial fluid (SF) and oviductal fluid. However, as an extracellular protein, BiP has additional properties that are quite distinct from the intracellular functions. Extracellular BiP is immunoregulatory and anti-inflammatory causing development of tolerogenic dendritic cells (DCs), induction of regulatory T-cells, abrogation of osteoclast development and function, induction of anti-inflammatory cytokine production, including interleukin (IL)-10, IL-1 receptor antagonist and soluble tumour necrosis factor (TNF)-receptor type II, and attenuation of TNFα and IL-6. Together, these functions help drive the resolution of inflammation. Disease models of inflammatory arthritis have helped to demonstrate the novel mode of action of BiP in which the pharmacokinetics and pharmacodynamics are dissociated. The three murine models to be discussed each show BiP induced long-term therapeutic protection and therefore has potential for long-lasting drug-free therapy in rheumatoid arthritis (RA).
24157091 Th17 cells and IL-17 a--focus on immunopathogenesis and immunotherapeutics. 2013 Oct IMPORTANCE: Accumulating evidence suggests that IL-17 A has broad pathogenic roles in multiple autoimmune and immune-mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). The development of new therapies that inhibit IL-17 pathway signaling is of clinical significance. OBJECTIVES: This review aims to summarize the current preclinical evidence on the role of Th17 cells and IL-17 and related cytokines in immune-mediated disease pathophysiology, with a focus on psoriasis and rheumatoid arthritis, as well as to summarize recent clinical trials in these indications with newly developed IL-17 pathway inhibitors. METHODS: A systematic literature search was conducted of PubMed using relevant keywords. Studies were assessed according to recent relevance to IL-17-mediated pathophysiology and clinical IL-17 inhibition. Experimental animal models of autoimmune disease and clinical studies that focused on IL-17 pathway inhibitors were included. RESULTS: Preclinical studies suggest that IL-17A is an attractive therapeutic target. Several IL-17A inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibodies, secukinumab and ixekizumab, and the anti-17RA monoclonal antibody brodalumab. Each has shown variable and sometimes favorable results in proof-of-concept and phase II clinical trials and is currently undergoing further clinical evaluation in a range of immune-mediated diseases. CONCLUSION: Targeting the IL-17 pathway shows promise as strategy to treat immune-mediated diseases ranging from skin to joints.
24156821 Systematic review of tumor necrosis factor inhibitor discontinuation studies in rheumatoid 2013 Nov BACKGROUND: Anti-tumor necrosis factor agents (anti-TNFs) have changed the course of rheumatoid arthritis (RA) for more than a decade. Use of these medications often results in remission, or at least low disease activity (LDA), but at a substantial cost. It has been postulated that discontinuation of these medications among patients with RA in remission or LDA may be possible without an associated increase in RA disease activity. OBJECTIVE: The goal of this systematic literature review was to summarize published articles regarding discontinuation of anti-TNFs in patients with RA. METHODS: A systematic literature review was conducted to identify English-language articles indexed in PubMed from July 1999 through June 2013 reporting results regarding anti-TNF discontinuation in patients with RA. Study designs included observational longitudinal studies and clinical trials. Outcomes had to include 1 of the following: time to flare after anti-TNF discontinuation, failure to remain in remission, or proportion of patients in LDA or remission at the end of the study. RESULTS: Ten studies examined discontinuation of anti-TNF therapies in RA. Inclusion criteria varied significantly across studies in terms of disease activity status (remission or LDA) and duration of this disease status (1 year or 1 month) before discontinuation being attempted. Results from larger studies (eg, >100 patients) suggest that the proportion of patients who discontinued anti-TNF and did not have an increase in disease activity ranged from 24% to 81%. In 3 studies that evaluated durability of LDA or remission after anti-TNF discontinuation, the mean time to relapse varied from 15 weeks to 17 months. In studies that analyzed radiographic data, once therapies were reinitiated after an increase in disease activity was detected, patients generally did not experience progression in structural damage. CONCLUSIONS: Discontinuation of anti-TNF therapy is achievable for many RA patients who start in clinical remission or LDA. However, heterogeneous inclusion criteria and highly variable outcome definitions across studies make it difficult to efficiently summarize the literature on this topic or to conduct a meta-analysis. There is a lack of evidence regarding how to best predict which patients have the greatest likelihood of continuing to do well after discontinuation of anti-TNF therapy.
24164120 Short to medium results using the remotion total wrist replacement for rheumatoid arthriti 2013 We present the clinical outcome of patients who underwent RE-MOTION Total Wrist Replacement (TWR) for the treatment of Rheumatoid arthritis involving the wrist. Ten patients were available for follow-up, ranging from one to five years after index surgery. Two patients required surgical intervention for wound breakdown, including one patient who required a radial forearm flap for skin coverage. No patients required revision surgery or conversion to fusion. Patients who did not have complications gained statistically significant pain relief and improvement in mean overall flexion. In this small case series with short to medium results patients reported an improvement in terms of flexion and pain. Despite this, the question of efficacy of TWR compared to fusion in the long term remains unanswered due to the high rate of complications.
23948414 [Analysis of CD4(+);T cell subsets in peripheral blood of patients with rheumatoid arthrit 2013 Aug OBJECTIVE: To investigate the percentages of Treg, Th1, Th2, Th17 cells in peripheral blood of patients with rheumatoid arthritis (RA) of different stages and their roles in the disease process to explore their associations with the disease activity markers and antibody markers. METHODS: We enrolled 78 RA patients and 21 healthy controls in this study. Percentages of Treg, Th1, Th2, Th17 cells were analyzed by flow cytometry. RESULTS: Percentages of CD3(+);CD4(+);T cells and CD4(+);CD25(+);T cells increased in RA groups; compared with non-active RA group and control group, active RA group had the higher percentage of Treg; Th2 cells were less in non-active RA group compared with controls, but Th1, Th17 cells were not significantly different in the three groups. Correlation analysis showed that no relationship was observed between Th1, Th2, Th17, Treg cells and RA activity markers (ESR, CRP and PLT). CONCLUSION: The abnormality of CD4(+);T cell subsets may contribute to the development of RA disease.
23867949 Is there a therapeutic window of opportunity in early inflammatory bowel disease? Early st 2013 Sep Traditionally therapy for inflammatory bowel disease (IBD) encompassed a sequential approach with subjects treated with 5-ASA products and/or corticosteroids initially, and only where failing such treatment, moving on to immunomodulator or biologic therapy. In the rheumatologic literature the importance of the early introduction of immunosuppressive therapies for inflammatory arthropathies has been increasingly recognized, however this concept remains much debated in IBD with no clear consensus on the optimal therapeutic approach. In this review we discuss how the natural history of IBD provides a rationale for the early introduction of the most effective therapy. We outline how the experience of early immunosuppressive therapy in rheumatoid arthritis informs therapeutic decision making in IBD. We review the evolving treatment strategies in IBD and the current evidence supporting the introduction of immunosuppressive treatment soon after IBD diagnosis. Finally we discuss the importance of selecting appropriate therapeutic endpoints in IBD and review the potential risks and benefits of early immunosuppressive treatment strategies in IBD.
23697938 The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes. 2013 Jun RA (rheumatoid arthritis) is an inflammatory disease of synovial joints affecting approximately 1% of the population. One of the main cell types involved in damage to RA joint tissue is the FLSs (fibroblast-like synoviocytes). These have a semi-transformed, auto-aggressive phenotype typified by loss of contact inhibition, reduced apoptosis and the production of matrix-degrading enzymes. The mechanisms involved in the development of this phenotype are unclear; however, increasing evidence implicates alterations in the epigenetic regulation of gene expression. Reduced acetylation of amino acids in the tails of histone proteins is an epigenetic mark associated with transcriptional repression and is controlled by the HDAC (histone deacetylase) enzyme family. To date, evidence has implicated HDACs in the auto-aggressive phenotype of FLSs, and administration of HDAC inhibitors to both animal models of RA and individuals with juvenile arthritis has shown efficacy in attenuating inflammation and tissue damage. This highlights a role for HDACs in disease pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.
22878378 Characteristics of idiopathic atlanto-axial subluxation: a comparative radiographic study 2013 Jan OBJECTIVE: Atlanto-axial subluxation (AAS) is caused by multiple conditions; however, idiopathic AAS patients without RA, upper-cervical spine anomalies or any other disorder are rarely encountered. This study retrospectively investigated the radiographic findings in idiopathic AAS patients, and clarified the differences between those AAS patients and those due to RA. METHODS: Fifty-three patients with AAS treated by transarticular screw fixation were reviewed. The subjects included 8 idiopathic patients (ID group) and 45 RA patients (RA group). The study investigated the atlanto-dental interval (ADI) value and space available for spinal cord (SAC) at the neutral and maximal flexion position. RESULTS: The average ADI value at the neutral position in the ID and RA groups before surgery was 7.8 and 7.2 mm, respectively (p > 0.74). The average ADI value at the flexion position in the two groups was 10.3 and 11.7 mm, respectively (p > 0.06). The average SAC value at the neutral position in the two groups was 12.0 and 17.1 mm, respectively (p < 0.01). Finally, the average SAC value at the flexion position in the two groups was 10.7 and 13.5 mm, respectively (p < 0.01). CONCLUSIONS: The SAC value at both the neutral and flexion positions in idiopathic AAS patients was significantly smaller than those values in RA-AAS patients. This may be because the narrowing of the SAC in the idiopathic group easily induces cervical myelopathy. Furthermore, surgery was often recommended to RA patients, because of the neck pain induced by RA-related inflammation of the atlanto-axial joint, regardless of any underlying myelopathy.
23116710 Mast cells and inflammation. 2013 Mar The prominent role for mast cells in the inflammatory response has been increasingly well documented in recent years. Mast cells not only contribute to maintain homeostasis via degranulation and to generate IgE-mediated allergic reactions, but also sit at a major crossroads for both innate and adaptive immune responses. The part played by mast cells in chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis identifies mast cells as a valuable treatment target in these diseases. Tyrosine-kinase inhibitors targeting the c-Kit mast cell receptor have been found effective in treating rheumatoid arthritis, asthma, and multiple sclerosis. When used in combination with other available drugs, tyrosine-kinase inhibitors may improve the therapeutic management of these diseases.
24289729 Motivations for inadequate persistence with disease modifying anti-rheumatic drugs in earl 2013 Dec 1 BACKGROUND: Knowledge of factors that contribute to non-persistence with disease modifying anti-rheumatic drugs (NP) is essential to improve rheumatoid arthritis (RA) outcomes. Aims of the study were to investigate patient's motivations and risk factors for NP in a cohort of early RA patients. METHODS: Up to September 2012, data from 149 patients, who had at least 1 year of follow-up, at least one drug indication, and at least 2 consecutive six-months-apart rheumatic evaluations that included assessment of compliance were reviewed. NP and patient's motivations of NP were evaluated according to a questionnaire. NP was defined when patients referred that they had completely stop RA medication, "Sometimes", "Almost always" or "Always". Patients had to pay for their medication.Descriptive statistics and logistic regression models were used. Statistical significance was set at a p value of less than 0.05. The study was approved by the internal review board. RESULTS: Up to cut-off, 715 questionnaires were applied to 149 patients, who had follow-up of 58.7 ± 27.9 months and were indicated 2.4 ± 0.7 DMARDs/patient/follow-up.Patients were most frequently female (88.6%), middle-aged ([mean ± SD] age of 38.5 ± 12.8 years) with lower-middle/lower socio-economic status (87.9%) and scholarship of 11 ± 3.9 years.Ninety-nine (66.4%) patients were NP and filled 330 questionnaires. Multivariate analysis showed that years of formal education (OR: 1.12, 95% CI: 1.1-1.24, p = 0.03), perception of at least some difficulty to find arthritis medication (OR: 5.68, 95% CI: 2.48-13, p = 0.000) and perception that arthritis medication is expensive (OR: 5.27, 95% CI: 2.1-13.84, p = 0.001) at the first evaluation of patient's compliance were all predictors of NP.Among the 99 NP patients, 25 (25.3%) were recurrent-NP and accumulated more disease activity. The combination of both reasons of NP ("Because it was not available at the drugstore" and "Because the medication is very expensive") when selected at the first evaluation of compliance was the only variable to predict recurrent NP, OR: 4.8, 95% CI: 1.1-20.8, p = 0.04. CONCLUSIONS: Health systems should provide (first line) treatment for RA as a strategy to improve compliance with therapy and clinical outcomes, particularly in vulnerable populations.
24286543 ACPA fine-specificity profiles in early rheumatoid arthritis patients do not correlate wit 2013 Oct 1 INTRODUCTION: Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients. METHODS: Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip. RESULTS: Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations. CONCLUSIONS: Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores.
23565635 Will antirheumatic treatment improve cardiovascular outcomes in patients with rheumatoid a 2014 In recent years, the scientific community has gained significant insight into the complex interaction between inflammation and the cardiovascular system in patients with rheumatoid arthritis (RA), which leads to increased cardiovascular (CV) morbidity and mortality in these patients. Our common understanding of this association is that persistent inflammation contributes to the development of premature atherosclerosis. Consequently, the question arises whether control of inflammation with antirheumatic treatment will be able to improve CV outcome. While there are a lot of data that demonstrate improvement of numerous CV surrogate markers in patients treated with virtually all antirheumatic drug classes, there is much less information about the possible translation of these beneficial effects into improved CV outcome. In summary, the published evidence suggests that tumor necrosis factor (TNF) alpha inhibitors may improve CV outcome. The same is true for methotrexate (MTX). However, it is not clear whether MTX works via suppression of inflammation or through drug specific mechanisms. For other traditional disease-modifying antirheumatic drugs and biologic therapies, there are no convincing data for improved CV outcome. Only a few drugs (glucocorticoids and NSAIDs) have been associated with increased CV risk. Treating RA aggressively, as recommended by current guidelines, is likely to have a beneficial effect on CV outcomes.
25481189 [Expression of cadherin-11 in rheumatoid arthritis synovium and its correlation with infla 2014 Dec OBJECTIVE: To explore the pattern of cadherin-11 expression and its relationship with synovial inflammation in rheumatoid arthritis (RA), and study the regulatory effects of cytokines on cadherin-11 expression on RA fibroblast-like synoviocytes (RAFLS). METHODS: Synovium samples were obtained from 28 RA patients who were undergoing total knee replacement. After HE staining, synovitis score was determined according to Rooney's inflammation score system. The expression of cadherin-11 in RA synovium was semi-quantified by immunohistochemical staining, and its correlations with Rooney's inflammation score and systematic inflammatory markers were analyzed statistically. After induction with transforming growth factor β (TGF-β) or interleukin 17 (IL-17) at a series of concentrations, the expression of cadherin-11 on RAFLS was assessed by real time guantitative-PCR and Western blotting. RESULTS: There was no significant difference in cadherin-11 expression in RA synovium among different levels of C-reactive protein. Cadherin-11 in the lining and sublining layers were positively correlated with D-dimer, synovial lining layer hyperplasia, proliferating blood vessels, perivascular infiltration of lymphocytes, focal aggregation of lymphocytes and diffuse infiltration of lymphocytes; cadherin-11 in the lining layer was negatively correlated with interstitial fibrosis. TGF-β or IL-17 stimulation could up-regulate cadherin-11 expression on RAFLS at mRNA and protein levels. CONCLUSION: The over-expression of cadherin-11 in RA was correlated with synovial lining layer hyperplasia, proliferating blood vessels and infiltration of lymphocytes. Cadherin-11 expression on RAFLS could be induced by TGF-β and IL-17 induction.
24613586 Trabecular metal patella--is it really doomed to fail in the totally patellar-deficient kn 2014 Jun Reconstruction of the patella poses real problems for the revision TKR surgeon, particularly when the patella is absent, fractured or profoundly deficient. The trabecular metal patella was introduced in an attempt to address these issues. However the largest series of such cases published to date cast serious doubts on the validity of using Trabecular Metal (TM) in cases where there is no residual patellar bone stock at all. We present a case where the TM Patellar implant has survived satisfactorily for 8 years post reconstruction in a knee with no residual patella bone, resulting in greatly improved symptoms and function. We believe that this success might be related to specific technical details in the reconstruction and we present the technique.
24302705 Change of psychological distress and physical disability in patients with rheumatoid arthr 2014 May OBJECTIVE: During the past decades, a more cautious approach with respect to prescribing medication and physical exercise progressed toward evidence-based guidelines regarding the management of rheumatoid arthritis (RA). Currently, physical activity and other means to improve well-being and functioning are encouraged, and the disease is targeted earlier with more intensive and aggressive pharmacologic treatment. The current study examined whether psychological distress and physical disability in patients with RA reduced over the last 2 decades and whether this is explained by a reduction of disease activity. METHODS: From 1990-2011, consecutive patients with RA (n = 1,151, age range 17-86 years, 68% female, 62% rheumatoid factor positive) were monitored at diagnosis and after 3-5 years of treatment (followup). Depressed mood, anxiety, and physical disability were predicted in multiple linear regression analyses by year of assessment, disease activity, and patient demographics. RESULTS: Over the decades, depressed mood (P = 0.01), anxiety (P = 0.001), and physical disability (P = 0.02) reduced at diagnosis and within-treatment improvement of anxiety (P = 0.04) and physical disability (P < 0.001) increased. Percentages of patients with depressed mood, anxiety, and physical disability at followup changed from 25%, 23%, and 53%, respectively, 2 decades ago to 14%, 12%, and 31%, respectively, currently. After taking account of reduction in disease activity, the decrease in physical disability remained significant (P < 0.001). CONCLUSION: Over the last 2 decades, psychological distress and physical disability decreased. This favorable trend might partly be due to reduced disease activity. The results indicate that patients with RA have a better opportunity to live a valued life currently than 20 years ago.