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ID PMID Title PublicationDate abstract
23002032 Diastolic dysfunction in rheumatoid arthritis: a meta-analysis and systematic review. 2013 Apr OBJECTIVE: To determine if the prevalence of diastolic dysfunction is increased in rheumatoid arthritis (RA) patients. METHODS: We conducted a time- and language-restricted literature search to identify studies conducted to compare echocardiographic parameters in patients with RA and controls. The mean difference for echocardiographic variables of interest was calculated using a random-effects model. A systematic review of the literature was performed. RESULTS: A total of 25 studies reporting on 5,836 subjects (1,614 with RA) were included. Results reflect mean differences, with positive values denoting higher values in RA patients. Patients with RA had larger mean left atrial dimension (mean difference 0.09 cm [95% confidence interval (95% CI) 0.01, 0.17]; P = 0.02), higher left ventricular mass index (mean difference 6.2 gm/m(2) [95% CI 1.08, 11.33]; P = 0.02), higher mean systolic pulmonary artery pressure (mean difference 5.87 mm Hg [95% CI 4.36, 7.38]; P < 0.00001), prolonged isovolumetric relaxation time (mean difference 9.67 msec [95% CI 5.78, 13.56]; P < 0.00001), and higher transmitral A wave velocity (mean difference 0.13 meters/second [95% CI 0.07, 0.18]; P < 0.00001) compared to controls. A subanalysis of 2,183 subjects excluding 2 large unmatched studies showed the same results, with the exception that patients with RA had a lower mitral E/A ratio (mean difference -0.17 [95% CI -0.25, -0.09]; P < 0.00001), suggestive of diastolic dysfunction. There were no differences in left ventricular ejection fraction (%), transmitral E wave velocity (meters/second), and mitral deceleration time (msec). CONCLUSION: Patients with RA were more likely to have echocardiographic parameters of diastolic dysfunction, and have higher systolic pulmonary artery pressures and larger left atrial sizes.
24792438 Lysophosphatidic acid-induced IL-8 secretion involves MSK1 and MSK2 mediated activation of 2014 Jul 1 Lysophosphatidic acid (LPA) is a pleiotropic lipid mediator that promotes motility, survival, and the synthesis of chemokines/cytokines such as interleukin-8 (IL-8) and interleukin-6 by human fibroblast-like synoviocytes from patients with rheumatoid arthritis (RAFLS). In those cells LPA was reported to induce IL-8 secretion through activation of various signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK), p42/44 MAPK, and Rho kinase. In addition to those pathways we report that mitogen- and stress-activated protein kinases (MSKs) known to be activated downstream of the ERK1/2 and p38 MAPK cascades and CREB are phosphorylated in response to LPA. The silencing of MSKs with small-interfering RNAs and the pharmacological inhibitor of MSKs SB747651A shows a role for both MSK1 and MSK2 in LPA-mediated phosphorylation of CREB at Ser-133 and secretion of IL-8 and MCP-1. Whereas CREB inhibitors have off target effects and increased LPA-mediated IL-8 secretion, the silencing of CREB1 with short hairpin RNA significantly reduced LPA-induced chemokine production in RAFLS. Taken together the data clearly suggest that MSK1 and MSK2 are the major CREB kinases in RAFLS stimulated with LPA and that phosphorylation of CREB1 at Ser-133 downstream of MSKs plays a significant role in chemokine production.
25509766 [Short- and medium-term effectivenesses of stemless hip arthroplasty for treating hip join 2014 Sep OBJECTIVE: To summarize the short- and medium-term effectivenesses of stemless hip arthroplasty for treating hip joint disease in young and middle-aged patients. METHODS: Between June 2005 and December 2010, 25 cases (27 hips) of hip joint disease were treated with stemless hip arthroplasty. There were 17 males (19 hips) and 8 females (8 hips) with an average age of 45.6 years (range, 30-57 years), including 13 left hips, 10 right hips, and 2 bilateral hips. The causes included avascular necrosis of the femoral head (ANFH) secondary to femoral neck fracture in 5 cases (5 hips), ANFH in 15 cases (16 hips), osteoarthritis of the hip joint caused by ankylosing spondylitis in 2 cases (3 hips), osteoarthritis of the hip joint caused by dysplasia of acetabular in 2 cases (2 hips), and rheumatoid arthritis in 1 case (1 hip). The disease duration was 1-17 years (mean, 6.1 years). Before operation, the Harris score was 47.6 ± 14.2. RESULTS: The incision healed by first intention in all patients, and no complications occurred, such as infection, periprosthetic fracture, and deep vein thrombosis of lower extremity. Twenty-five patients (27 hips) were followed up 36-96 months (mean, 51 months). One case (1 hip) had sciatic nerve injury after operation, which was relieved by symptomatic treatment. One case (1 hip) had prosthesis loosening, which was relieved after revision. The survival rate of prosthesis was 96.3% (26/27). At last follow-up, the Harris score was 92.1 ± 3.6, which was significantly better than preoperative score (t = 18.241, P = 0.000). The excellent and good rate was 88.9% (excellent in 19 hips, good in 5 hips, fair in 2 hips, and poor in 1 hip). The X-ray films showed good location of prosthesis, and no evidence of dislocation, bone resorption, osteolysis, and heterotopic ossification. CONCLUSION: Because of reserving femoral neck, biomechanics conduction and distribute of the proximal femur achieve natural biomechanics state of the human body. The short- and medium-term effectivenesses of stemless hip arthroplasty for treating hip joint disease in young and middle-aged patients are satisfactory, but the long-term effectiveness need further observation.
23982537 Comparative efficacy of subcutaneous versus oral methotrexate in active rheumatoid arthrit 2013 Jul This prospective study was conducted in rheumatology clinic under the department of medicine of Bangabandhu Sheikh Mujib Medical University from December 2004 to December 2005 to asses the efficacy, safety and compliance of subcutaneous methotrexate (MTX) in active rheumatoid arthritis (RA) patients. A total of 92 active rheumatoid arthritis patients according to American College of Rheumatology (ACR) criteria were recruited for the trial for six months. Among them 46 cases belonged to injectable MTX group and 46 cases belonged to oral MTX group. Mean±SD age of patients was 45.54±12.42 vs. 44.63±13.99 years in subcutaneous group and oral group respectively. In the subcutaneous group 41 were female and 5 male; in the oral group 34 were female and 12 male. Mean duration of the disease was 49.74 months in subcutaneous group and 49 months in oral group. RA test was positive in 35 cases in both groups whereas Rose Waaler test was positive in 19 patients in subcutaneous group and 14 patients in oral group. At 24 week, response rate of ACR 20 was significantly higher in subcutaneous MTX than oral MTX group (93% vs. 80%, p=0.02). Similarly ACR 50 response was significantly higher in subcutaneous MTX than in oral group (89% vs. 72%, p=0.03). ACR 70 response was not significantly higher in SCMTX group then oral group (11% vs. 9 %, p=0.72). Adverse effects were relatively less in subcutaneous MTX and most common side effects were nausea (37% vs. 63%), vomiting (11% vs. 30%), dyspepsia (29% vs. 48%), dizziness (4l% vs. 52%) and alopecia (72% vs. 85%). The results of the study demonstrated that subcutaneous MTX was significantly more effective than oral MTX at the same dosage in active Rheumatoid arthritis patients with no increase in side effects.
23968403 Association of HLA-DRB1 and -DQB1alleles and haplotypes with rheumatoid arthritis in a Pak 2013 Aug 22 INTRODUCTION: Rheumatoid arthritis is an autoimmune disease with poorly understood pathophysiology. Genetic components of disease etiology, especially human leukocyte antigen (HLA) associations, are well known. Ethnic differences account for a number of variations in disease association with the HLA locus and there seem to be differences in various studies regarding its genetic predisposition. This study was aimed at determining the contribution of DRB1 and DQB1 components of HLA class II in rheumatoid arthritis in a Pakistani cohort. METHOD: For this study, 110 patients and 120 healthy controls from the same geographical area and matched ethnicity were enrolled. Blood DNA was isolated from all the subjects and HLA alleles were typed following allele specific amplification. Subsequently, haplotypes were generated and allelic and haplotype distribution frequencies were compared among the patients and controls using χ² and Arlequin software. The data obtained by this analysis were also compared with other reported associations found in the Pakistani population by meta-analysis. RESULTS: HLA allelic status was determined among the patients and controls from the same geographical area to account for differences in ethnicity and environmental factors. Significant associations were found for alleles as well as haplotypes among the patients of rheumatoid arthritis. DRB1*10, DQB1*05 and DQB1*602 were found to be associated with disease susceptibility, whereas DRB1*11 and DQB1*02 had protective effect against the disease. Similarly, haplotype DRB1*10-DQB1*05 was associated disease risk, whereas DRB1*07-DQB1*02 and DRB1*11-DQB1*0301 had a protective effect. CONCLUSION: There is a significant DRB1and DQB1 allele and haplotype association with rheumatoid arthritis susceptibility and protection.
23686414 Validation of the methotrexate-first strategy in patients with early, poor-prognosis rheum 2013 Aug OBJECTIVE: Methotrexate (MTX) taken as monotherapy is recommended as the initial disease-modifying antirheumatic drug for rheumatoid arthritis (RA). The purpose of this study was to examine outcomes of a blinded trial of initial MTX monotherapy with the option to step-up to combination therapy as compared to immediate combination therapy in patients with early, poor-prognosis RA. METHODS: In the Treatment of Early Rheumatoid Arthritis (TEAR) trial, 755 participants with early, poor-prognosis RA were randomized to receive MTX monotherapy or combination therapy (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine). Participants randomized to receive MTX monotherapy stepped-up to combination therapy at 24 weeks if the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was ≥3.2. RESULTS: Attrition at 24 weeks was similar in the MTX monotherapy and combination groups. Of the 370 evaluable participants in the initial MTX group, 28% achieved low levels of disease activity and did not step-up to combination therapy (MTX monotherapy group). The mean ± SD DAS28-ESR in participants continuing to take MTX monotherapy at week 102 was 2.7 ± 1.2, which is similar to that in participants who were randomized to immediate combination therapy (2.9 ± 1.2). Participants who received MTX monotherapy had less radiographic progression at week 102 as compared to those who received immediate combination therapy (mean ± SD change in modified Sharp score 0.2 ± 1.1 versus 1.1 ± 6.4). Participants assigned to initial MTX who required step-up to combination therapy at 24 weeks (72%) demonstrated similar DAS28-ESR values (3.5 ± 1.3 versus 3.2 ± 1.3 at week 48) and radiographic progression (change in modified Sharp score 1.2 ± 4.1 versus 1.1 ± 6.4 at week 102) as those assigned to immediate combination therapy. The results for either of the immediate combination approaches, whether triple therapy or MTX plus etanercept, were similar. CONCLUSION: These results in patients with early, poor prognosis RA validate the strategy of starting with MTX monotherapy. This study is the first to demonstrate in a blinded trial that initial MTX monotherapy with the option to step-up to combination therapy results in similar outcomes to immediate combination therapy. Approximately 30% of patients will not need combination therapy, and the 70% who will need it are clinically and radiographically indistinguishable from those who were randomized to receive immediate combination therapy.
24626274 Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis. 2014 Jan The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.
23379428 Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T 2013 Mar A new paradigm has emerged relating the pathogenesis of rheumatoid arthritis (RA), focused on the balance between T helper type 17 cells and regulatory T cells (T(regs) ). In humans, both subpopulations depend on transforming growth factor (TGF)-β for their induction, but in the presence of inflammatory cytokines, such as interleukin (IL)-6, the generation of Th17 is favoured. Tocilizumab is a therapeutic antibody targeting the IL-6 receptor (IL-6R), which has demonstrated encouraging results in RA. The aim of this study was to evaluate the effect of tocilizumab on Th1 cells, Th17 cells, IL-17 and interferon (IFN)-γ double secretors Th17/Th1 cells, and T(regs) in RA patients. Eight RA patients received tocilizumab monthly for 24 weeks and blood samples were obtained every 8 weeks to study T cell populations by flow cytometry. The frequency of Th17 cells, Th1 cells and Th17/Th1 cells was evaluated in peripheral blood mononuclear cells (PBMCs) activated in vitro with a polyclonal stimulus. T(regs) were identified by their expression of forkhead box protein 3 (FoxP3) and CD25 by direct staining of PBMCs. Although no changes were detected in the frequency of Th1 or Th17 cells, the percentages of peripheral T(regs) increased after therapy. In addition, the infrequent Th17/Th1 subpopulation showed a significant increment in tocilizumab-treated patients. In conclusion, tocilizumab was able to skew the balance between Th17 cells and T(regs) towards a more protective status, which may contribute to the clinical improvement observed in RA patients.
25054600 Rituximab for rheumatoid arthrits treatment: a systematic review. 2014 May INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation that often leads to significant disability. Several effective anti-TNF agents have been used, but some patients have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody indicated in such cases. METHODS: We conducted a systematic review to access efficacy and safety of rituximab in patients with active RA which have or have not been treated with anti-TNF agents before, and to relate outcome with RF and anti-CCP serology. We searched major electronics databases, grey literature and searched for references manually. We used Review Manager(r)5.1 for meta-analysis. RESULTS: We included six RCTs comparing rituximab 1000 mg with placebo. Methotrexate was used by both groups. Treatment with rituximab was more effective in naïve and in anti-TNF treatment failure patients - ACR20/50/70 and EULAR response. We observed lower changes in Total Genant-modified Sharp score, erosion score and joint narrowing scores in the rituximab group, and SF-36, FACIT-T and HAQ-DI scores were also better in this group. There were no differences between groups regarding safety outcomes, with exception of acute injection reactions, which were more common on rituximab group. More RF/anti-CCP seropositive patients achieved ACR20 than RF/anti-CP negative patients in rituximab group. CONCLUSION: Available data support the use of rituximab for the treatment of RA, as it is an effective and safe option for naïve and anti-TNF treatment failure patients. RF and anti-CCP seam to influence treatment results, but this inference needs further research.
24313444 Etanercept decreases synovial expression of tumour necrosis factor-α and lymphotoxin-α i 2014 OBJECTIVES: Etanercept is an effective tumour necrosis factor (TNF)-α inhibitor drug with the unique ability to block not only TNF-α but also lymphotoxin (LT)-α, at least in vitro. We aimed to investigate the in vivo effect of etanercept on synovial expression of TNF-α and LT-α. METHOD: Synovial biopsies from 12 rheumatoid arthritis (RA) patients started on etanercept and 11 RA patients started on infliximab were obtained at baseline and 8 weeks after treatment initiation. Synovial expression of TNF-α and LT-α was evaluated by immunohistochemistry followed by computer-assisted image analysis. Differences between paired samples were analysed by the Wilcoxon test and between groups by the Mann-Whitney test. A p-value < 0.05 was considered statistically significant. RESULTS: Six out of the 12 of the patients started on etanercept achieved an American College of Rheumatology (ACR)50 response. Macroscopic evaluation of the joints during arthroscopy revealed a significant decrease of local inflammation mainly in good ACR50 responders. Synovial expression of both LT-α and TNF-α decreased but the differences did not reach statistical significance at a group level. By contrast, a significant decrease in both LT-α and TNF-α was observed when only good ACR50 responders were analysed. Despite higher levels of baseline synovial TNF-α in the good responders, neither baseline LT-α nor TNF-α could predict clinical response after 8 weeks. A decreasing trend of the synovial levels of LT-α was also observed in good responders to infliximab, but the difference did not reach statistical significance. CONCLUSIONS: Etanercept treatment modulates the synovial expression of both TNF-α and LT-α in vivo, a mechanism that might partly explain its clinical efficacy in RA.
24393164 Th1 and Th2 polymorphisms in Sjögren's syndrome and rheumatoid arthritis. 2014 Jul BACKGROUND: Sjogren's syndrome is characterized by T-cell infiltration of exocrine glands leading to parenchymal destruction and impaired glandular function. This process is orchestrated by cytokines, whose secretion can be regulated by genetic polymorphisms. MATERIALS AND METHODS: The aim of this study was to investigate the influence of interleukin-6 -174G/C, interleukin-10 -1082G/A, tumor necrosis factor-α -308G/A, interferon-γ +874A/T gene polymorphisms in (RA) and secondary Sjögren's syndrome (sSS). A study sample that comprised of 138 Brazilian patients was divided into three groups: RA (n = 66), sSS (n = 20), and healthy controls - C (n = 52). Patients were subjected to Schirmer's test, unstimulated salivary flow rate, biopsy of minor salivary glands, and serological tests for diagnosing SS. Genomic DNA was obtained from saliva samples and submitted to genotyping. The association between genotypes/alelle frequency and SS susceptibility was tested, as well as their association with clinical features of SS. RESULTS: Tumor necrosis factorα (TNFα)-308GA polymorphisms differed significantly between AR, SS, and C patients (P = 0.008). IL-6 overall G carriers and TNFα A carriers had a higher risk of presenting SS (P = 0.021). IL-6 polymorphism distribution was also distinctive regarding lymphocytic infiltration at the minor salivary glands (P = 0.026) and Schirmer's test (P = 0.035). CONCLUSION: These results suggest that IL-6 -174GC and TNFα-308GA gene polymorphisms are associated with susceptibility to SS. Additionally, IL-6 polymorphism could influence lymphocytic infiltration of salivary glands and diminish lachrymal gland function.
25270355 Diagnostic utility of musculoskeletal ultrasound in patients with suspected arthritis--a p 2014 Oct 1 INTRODUCTION: This study aimed to assess the utility of musculoskeletal ultrasound (MSUS) in patients with joint symptoms using a probabilistic approach. METHODS: One hundred and three patients without prior rheumatologic diagnosis and referred to our clinic for evaluation of inflammatory arthritis were included. Patients were assessed clinically including joint examination, laboratory testing including acute-phase reactants, rheumatoid factor (RF) and anti citrulinated protein antibody (ACPA), and radiographs of hands and feet if clinically indicated. A diagnostic assessment was then performed by the responsible rheumatologist where the probability of a) any inflammatory arthritis and b) rheumatoid arthritis was given on a 5-point scale ranging from 0 to 20% up to 80 to 100% probability. Subsequently, an ultrasound examination of the wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP) joints 2 to 5 in both hands, metatarsophalangeal (MTP) joints 2 to 5 in both feet and any symptomatic joints was performed and the results presented to the same rheumatologist. The latter then assessed the diagnostic probabilities again, using the same scale. RESULTS: The rheumatologists' certainty for presence/absence of inflammatory arthritis and rheumatoid arthritis was increased significantly following ultrasound performance. The proportion of patient for whom diagnostic certainty for inflammatory arthritis was maximal was 33.0% before and 71.8% after musculoskeletal ultrasound (P <0.001). With regard to a diagnosis of RA, the proportions were 31.1% pre-test and 61.2% post-test (P <0.001). MSUS findings agreed with the final diagnosis in 95% of patients. CONCLUSION: Musculoskeletal ultrasound, when added to routine rheumatologic investigation, greatly increases the diagnostic certainty in patients referred for the evaluation of inflammatory arthritis. The changes from pre-test to post-test probability quantify the diagnostic utility of musculoskeletal ultrasound in probabilistic terms.
23908006 Induced abortions in women with rheumatoid arthritis receiving methotrexate. 2013 Aug OBJECTIVE: To determine the rate of induced abortions in women with rheumatoid arthritis (RA) exposed to methotrexate (MTX) compared with women with RA unexposed to this medication. METHODS: We performed a nested case-control study using administrative databases from Quebec. All women with RA ages 15-45 years were identified and cases were defined as women having an induced abortion. Each case was matched to ≥1 controls for age, calendar time, and cohort entry. Exposure was defined as having filled ≥1 prescriptions of MTX ≤16 weeks prior to the index date. RESULTS: We identified 112 cases of induced abortions in women with RA and 5,855 RA controls. Exposure to MTX occurred in 10.7% of cases and 21.7% of controls. Women exposed to MTX had a lower rate of induced abortions compared with unexposed women (rate ratio [RR] 0.47 [95% confidence interval (95% CI) 0.25-0.89]). In the multivariate analysis, there was a trend toward an increased rate of induced abortions among women exposed to anti-tumor necrosis factor (anti-TNF) agents (RR 2.07 [95% CI 0.81-5.27]). CONCLUSION: Women with RA exposed to MTX have a lower rate of induced abortions than unexposed women. Women with RA exposed to anti-TNF agents may have an increased rate of induced abortions compared to unexposed women.
23729806 Bilateral evaluation of the hand and wrist in untreated early inflammatory arthritis: a co 2013 Aug OBJECTIVE: To compare Doppler ultrasound (US) and 3.0-Tesla magnetic resonance imaging (3.0-T MRI) findings of synovial inflammation in the tendons and joints in an early polyarthritis cohort (patients who presented < 1 year after arthritis onset) using a bilateral hand and wrist evaluation. Also, to evaluate the diagnostic performance of US and MRI findings for rheumatoid arthritis (RA), their ability to predict RA as a diagnostic outcome, and their capacity to improve the accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria in early arthritis. METHODS: Forty-five patients (40 women, 5 men; mean age 45.6 yrs) with untreated recent-onset polyarthritis participated in this prospective study and were examined using an US and MRI approach including both wrists and hands. After a followup of 12 months, patients were classified as having RA if they fulfilled the criteria for RA. The proportion of synovitis identified by US and MRI for each joint and tendon region was compared by chi-square test. The diagnostic performance of US and MRI for RA identification was evaluated using receiver-operating curve (ROC) analysis. Possible associations between synovitis for each joint and tendon region as identified by US or MRI and RA diagnosis at 12 months were tested by logistic regression analysis. The diagnostic performance of the ACR/EULAR RA classification criteria corrected by US and MRI joint and tendon counts was evaluated using ROC analysis. RESULTS: Thirty patients fulfilled the ACR/EULAR criteria [early RA (ERA) patients] and the remaining 15 failed to meet these criteria (non-RA). Carpal joint synovitis and tenosynovitis of the flexor tendons was found in 86.7% and 86.7% of patients with ERA on MRI compared with 63.3% and 50% on US, respectively (p < 0.05). The global MRI and US counts revealed a good diagnostic performance for RA diagnosis of both techniques, although MRI was statistically significantly better [area under the curve (AUC) = 0.959 and AUC = 0.853, respectively; z statistic = 2.210, p < 0.05]. MRI identification of carpal joint synovitis (OR 3.64, 95% CI 1.119-11.841), tenosynovitis of the flexor tendons (OR 5.09, 95% CI 1.620-16.051), and global joint and tendon count (OR 2.77, 95% CI 1.249-6.139) were in the multivariate logistic regression model the most powerful predictors of progression toward RA. In the group of ERA patients with US joint and tendon counts ≤ 10, a statistically significant difference was found between the diagnostic performance for RA of the ACR/EULAR criteria as previously described and the diagnostic performance of the MRI-corrected ACR/EULAR criteria (AUC = 0.898 and AUC = 0.986, respectively; z statistic = 2.181, p < 0.05). CONCLUSION: 3.0-T MRI identified a higher prevalence of synovitis in comparison to US in an early polyarthritis cohort. Both techniques have good diagnostic performance for RA although MRI reveals a significantly higher diagnostic capability. Synovitis of carpal joints and of flexor tendons as identified by MRI were the most powerful predictors of progression toward RA. In patients with US joint and tendon counts ≤ 10, MRI can significantly improve the diagnostic performance of the 2010 ACR/EULAR classification criteria.
23827841 Reverse shoulder arthroplasty. 2013 Jul The reverse shoulder arthroplasty is considered to be one of the most significant technological advancements in shoulder reconstructive surgery over the past 30 years. It is able to successfully decrease pain and improve function for patients with rotator cuff-deficient shoulders. The glenoid is transformed into a sphere that articulates with a humeral socket. The current reverse prosthesis shifts the center of rotation more medial and distal, improving the deltoid's mechanical advantage. This design has resulted in successful improvement in both active shoulder elevation and in quality of life.
25359291 Soluble OX40L is associated with presence of autoantibodies in early rheumatoid arthritis. 2014 Oct 30 INTRODUCTION: OX40 and its ligand OX40L are key components in the generation of adaptive memory response and provide necessary co-stimulatory signals for activated effector T cells. Here we investigate the dual roles of the membrane and soluble (s) forms of OX40 and OX40L in plasma and synovial fluid and their association with autoantibodies and disease activity in rheumatoid arthritis (RA). METHODS: Soluble OX40 and sOX40L plasma levels were measured in treatment-naïve early RA patients (eRA) at baseline and after 3, 6, and 12 months of treatment with methotrexate and adalimumab (n = 39) and with methotrexate alone (n = 37). Adalimumab was discontinued after the first year, and patients were followed for additional 12 months. For comparison, sOX40 and sOX40L were measured in patients with chronic RA (cRA, n = 15) and healthy volunteers (HV, n = 34). Membrane-bound OX40 and OX40L expression on T cells, B cells and monocytes were quantified. RESULTS: Soluble OX40 plasma levels of eRA patients were not different at the time of treatment initiation, but were significantly higher after 12 months of treatment, compared with HV or cRA patients. Soluble OX40L was significantly elevated throughout the first 12 months of treatment compared with HVs and patients with cRA. Adalimumab treatment did not influence sOX40 or sOX40L plasma levels. At baseline, sOX40L levels were strongly associated with the presence of anti-citrullinated protein antibodies (ACPA) (P <0.001) and IgM-RF (P <0.0001). The sOX40/sOX40L ratio was decreased in eRA, and a low ratio at the time of adalimumab discontinuation was associated with increased DAS28CRP and risk of flare the following year. T cells in the synovial fluid had the highest expression of OX40, while monocytes and B cells were the main expressers of OX40L in the joint. CONCLUSIONS: Plasma levels of sOX40 and sOX40L were increased in eRA and sOX40L was correlated with ACPA and IgM-RF. Further, expression of membrane-bound OX40 and OX40L was increased in eRA and cRA. Combined, these findings could reflect that increased activity in the OX40 systems facilitate to drive disease activity and autoantibody production in RA. TRIAL REGISTRATION: Clincaltrials.gov NCT00660647, 10 April 2008.
25134301 Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA): a case report with 2014 Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA) is reported here. A 33-year-old nulliparous woman with a 16-year history of RA who had been treated with corticosteroid and immunosuppressive drugs was diagnosed as having a non-typhoidal Salmonella ovarian abscess which might have been preceded by an occurrence of endometriotic cyst. Multidisciplinary therapy including surgical intervention was required to complete the eradication of infection. Although Salmonella ovarian abscess is rare, it may cause a serious complication in the ovary harboring endometriotic cyst through sustained presence of Salmonella bacteraemia.
24075961 Synthesis and evaluation of cyclosporine A-loaded polysialic acid-polycaprolactone micelle 2014 Jan 23 Polysialic acid (PSA) has been identified as a natural, hydrophilic polymer that can be used to extend circulation time and improve therapeutic efficacy when used as the basis of drug carrier systems. Here, to further investigate the potential of PSA to alter the pharmacokinetic and pharmacodynamic profiles of associated therapeutics, PSA-based micelles were formed via self-assembly of PSA grafted with polycaprolactone (PCL) at a critical micelle concentration of 84.7±13.2 μg/ml. Cyclosporine A (CyA), a therapeutic used in the treatment of rheumatoid arthritis, was loaded into the PSA-PCL micelles with a loading capacity and loading efficiency of 0.09±0.02 mg CyA/mg PSA-PCL and 29.3±6.4%, respectively. CyA loading resulted in a size increase from 73.8±12.4 nm to 107.5±9.3 nm at 25 °C and from 138.4±40.7 nm to 195.3±52.1 nm at 37 °C, favorable size ranges for drug delivery to inflamed tissue characterized by leaky vasculature, as occurs during rheumatoid arthritis pathogenesis. As an indicator of the stealth nature the micelles are expected to exhibit in vivo, the fixed aqueous layer thickness of the PSA-PCL micelles was determined to be 0.63±0.02 nm, comparable to that obtained for traditionally utilized poly(ethylene glycol) coated liposomes. The PSA-PCL micelles had a negligible effect on the viability of the SW982 synovial fibroblast cell line. Fluorescent microscopy was utilized to demonstrate uptake by the synovial fibroblasts through a non-receptor mediated form of endocytosis and partitioning of CyA into the membrane.
23319018 The effect of snuff (smokeless tobacco) on disease activity and function in rheumatoid art 2013 Jan BACKGROUND: It is not known whether snuff (moist smokeless tobacco) affects disease activity in rheumatoid arthritis (RA). OBJECTIVE: This study aims to study the effect of snuff on disease activity and function in Swedish patients with early RA. METHODS: Between 1992 and 2005, 2800 adult patients were included in the Better Anti-Rheumatic FarmacOTherapy (BARFOT) early RA study in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire, visual analog scale for general health, and drug treatment were registered at inclusion and at follow-up after 1, 2, and 5 years. European League Against Rheumatism response and remission criteria were applied at 1 year. In 2010, a self-completed postal questionnaire was sent to 2102 patients in the BARFOT study enquiring about lifestyle factors such as smoking and use of snuff. Three controls for each patient using snuff were identified. RESULTS: Fifty-one patients who used snuff were identified, together with 145 controls. When we adjusted for socioeconomic class, disease duration, and previous antirheumatic medication, the snuff users had lower DAS28 values at up to 6 months of follow-up than patients who had never smoked, and they had lower DAS28 values than previous smokers at up to 2 years of follow-up. No effect of snuff use on European League Against Rheumatism response was seen at up to 1 year. CONCLUSIONS: Snuff users initially had lower DAS28 levels than never smokers and previous smokers.
25437282 Genetics, environment, and gene-environment interactions in the development of systemic rh 2014 Nov Rheumatic diseases offer distinct challenges to researchers because of heterogeneity in disease phenotypes, low disease incidence, and geographic variation in genetic and environmental factors. Emerging research areas, including epigenetics, metabolomics, and the microbiome, may provide additional links between genetic and environmental risk factors in the pathogenesis of rheumatic disease. This article reviews the methods used to establish genetic and environmental risk factors and studies gene-environment interactions in rheumatic diseases, and provides specific examples of successes and challenges in identifying gene-environment interactions in rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Emerging research strategies and future challenges are discussed.