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ID PMID Title PublicationDate abstract
21954634 [Relationship of silent myocardial ischiemia with the course of rheumatoid arthritis and h 2011 Jan The aim of this investigation was to study the frequency and duration of silent myocardial ischemnia (SMI) and to evaluate its relationship with the duration of rheumatoid arthritis (RA) and hyperhomocysteinemia. 63 patients with rheumatoid arthritis were observed, during this study we investigated homocysteine blood level, markers of an inflammation and episodes of SMI using daily (cholter) ECG monitoring. It was often recorded "silent" myocardial ischemia in patients with the RA, which was associated with high activity of inflammatory process (high C-reactive protein, the disease activity score, HAQ, number of swollen and painful joints) and hyperhomocysteinemia, whereas disease duration was less important in formation of SMI.
20974296 The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab 2012 Mar Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. Being IL-6 a key cytokine for B cell survival, the interleukin-6 (IL-6) -174G>C and the IL-6 receptor (IL-6R) D358A gene polymorphisms were investigated in 158 RA patients treated with rituximab (RTX). One hundred and twenty-eight (81.0%) were RF positive and 126 (79.7%) were anti-CCP positive. Response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR and the ACR criteria. The possible relationship with IL-6 serum levels was also studied. By univariate analysis, lack of response by the EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (39.1%), than in the GC/GG patients (18.5%) (OR 2.83; 95%CI=1.10-7.27; p=0.031). A good response was noticed in only one patient (4.3%) with the IL-6 -174 CC genotype, while it was present in 24.4% of GG/GC cases (p=0.06). By stepwise multivariate analysis (including RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status and IL-6 genotype as covariates), the IL-6 -174CC genotype was selected as an independent predictor of no response to RTX by both EULAR and ACR≥50 criteria, while the IL-6R polymorphism resulted as not associated. No definite association between gene polymorphisms and IL-6 serum levels was noticed. Present results suggest a possible role for IL-6 genotyping to better plan treatment with RTX in RA, and larger studies are worthwhile.
22808986 Inflammation, endothelial function and atherosclerosis in rheumatoid arthritis. 2012 Jul 19 Different techniques have proven to be useful in determining the presence of subclinical cardiovascular disease in patients with rheumatoid arthritis (RA). Doppler imaging with iontophoresis of acetylcholine and flow-mediated, endothelium-dependent vasodilation give information on endothelial dysfunction, an early step in the atherogenesis process. However, there is no good correlation between these two surrogate markers of cardiovascular disease in RA. A single determination of routine laboratory markers of inflammation does not seem to relate to endothelial function in RA. Further research is needed to determine whether microvascular endothelial function is a better predictor of cardiovascular outcome than macrovascular endothelial function in patients with RA.
23179262 Impact of modified-release prednisone on functional ability in patients with rheumatoid ar 2013 Jun This observational study assessed functional ability in patients treated with modified-release prednisone under conditions of normal clinical practice. Patients treated with modified-release prednisone were observed over 9 months. The primary outcome measure was the change from baseline total score using the Questionnaire on Activity Status (QAS); total QAS score ranges from 0 (severely impaired) to 100 (completely unimpaired). Other measures included Visual Analogue Scale (VAS) from 0 to 10 (where 10 = full daily performance) and Health Assessment Questionnaire Disability Index (HAQ-DI). There were no restrictions on dose of modified-release prednisone or use of concomitant therapy. A total of 1,733 patients were included in the study, with valid observations at baseline and study end for 1,185 patients (thereof 74 % female, median age 59 years, median disease duration 5 years). Mean total QAS score improved significantly after 9 months of treatment with modified-release prednisone from 54.3 to 70.2 (p < 0.001). There were also significant (p < 0.001) improvements in all three QAS dimensions (occupational performance: 66.6-78.9; household duties: 55.6-70.9; leisure activities: 51.6-69.4), daily performance (mean VAS 5.1-7.0; p < 0.001) and mean HAQ-DI score (1.35-1.00; p < 0.001). Dose of modified-release prednisone was significantly reduced (from 5.0 to 4.4 mg/day, p < 0.001) and fewer patients required biological rheumatoid arthritis (RA) treatments, analgesia and gastroprotectants. Functional ability in patients with RA improved significantly from baseline after 9 months of treatment with modified-release prednisone. This observational study, conducted under daily-practice conditions, confirms the beneficial effects of modified-release prednisone shown previously in randomised controlled trials.
21454308 The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of 2011 Aug OBJECTIVE: It remains unclear whether autoantibodies are useful biomarkers to tailor the choice of biological treatment in RA. We investigated the relationship between the presence and levels of different RF and ACPA isotypes and the response to TNF blockade in an exploratory study. METHODS: A total of 101 active RA patients were prospectively treated with infliximab (3 mg/kg). Changes in disease activity were monitored by the 28-joint DAS (DAS-28). Serum levels of different isotypes [immunoglobulins M, G and A (IgM, IgG and IgA)] of RF and anti-citrullinated peptide antibodies were measured by ELISA. RESULTS: The mean DAS-28 decreased from 5.9 (1.1) at baseline to 4.0 (1.3) at Week 16 of infliximab treatment (P < 0.001). High baseline levels of different isotypes of RF (all P < 0.008), ACPA IgM (P = 0.008) and ACPA IgG (P = 0.07) were associated with an absolute decrease in DAS-28 after TNF blockade. This relationship persisted after adjusting for DAS-28 at baseline. However, the different isotypes of baseline RF and ACPA levels accounted for only a small proportion of variance in treatment response (RF: R² between 7 and 12% and ACPA: R² between 4 and 7%). The simultaneous presence of all three isotypes of RF or ACPA had no additive value. CONCLUSION: Presence as well as the titres of RF and IgM ACPA at baseline are significantly correlated with better response to infliximab treatment. However, this correlation is not strong enough to allow a reliable prediction in individual patients. Trial Registration. ISRCTN Register, http://www.controlled-trials.com/isrctn/, ISRCTN36847425.
22880708 Good long-term outcome of synovectomy in advanced stages of the rheumatoid elbow. 2012 Aug BACKGROUND AND PURPOSE: Synovectomy is an effective procedure for management of the rheumatoid elbow at radiographically early stages (Larsen grades 1 and 2). However, its efficacy for advanced stages (Larsen grades 3-5) is controversial. We investigated the outcome of synovectomy for advanced stages of the rheumatoid elbow. METHODS: Between May 1985 and September 1994, synovectomy was performed for 67 rheumatoid elbows in 59 patients (mean age 52 (26-72) years, 54 women). 3 elbows (3 patients) were lost to follow-up after mean 15 (10-23) years. Thus, 64 elbows were evaluated clinically and radiographically. RESULTS: The mean Mayo elbow performance score (MEPS) improved from 42 (15-75) points preoperatively to 78 (45-100) points at the final follow-up examination. In cases of Larsen grade 5, the mean MEPS at final follow-up examination (69 points) was lower than those of Larsen grade 3 and 4 cases (80 and 79 points, respectively) (p < 0.01). Recurrence of synovitis was obvious in 20/67 elbows. 12 cases had a total elbow arthroplasty mean 13 years after the synovectomy. The 10-year, 15-year, and 20-year survival rates were 97%, 75%, and 70%, respectively. INTERPRETATION: Our findings suggest that synovectomy for the rheumatoid elbow gives a good long-term outcome for radiographically judged destroyed joints of Larsen grades 3-4.
21367760 Antibodies to citrullinated α-enolase peptide 1 and clinical and radiological outcomes in 2011 Jun INTRODUCTION: The anticyclic citrullinated peptide 2 (anti-CCP2) assay is a generic test for antibodies to citrullinated proteins, among which there is a subset of about 50% with antibodies to citrullinated enolase peptide 1 (CEP-1). The anti-CEP-1 positive subset is strongly associated with the HLA-DRB1 shared epitope and its interaction with smoking. OBJECTIVE: To investigate whether anti-CEP-1 antibodies may be helpful in predicting outcome. METHODS: Anti-CEP-1 and anti-CCP2 antibodies were measured in two prospective cohorts of patients (Karolinska n=272, Norfolk Arthritis Register (NOAR) n=408) with early rheumatoid arthritis (RA). Outcomes measured were C-reactive protein, erythrocyte sedimentation rate, visual analogue scales for pain and global assessment of disease activity, Health Assessment Questionnaire, physician's assessment, swollen and tender joint counts and radiological progression. RESULTS: Anti-CCP2 antibodies were present in 57% and 50%, and anti-CEP-1 in 27% and 24% of the Karolinska and NOAR cohorts, respectively. Importantly, no statistically significant differences in clinical outcomes were demonstrated between the anti-CEP-1-/CCP2+ and the anti-CEP-1+/CCP2+ subsets in either cohort, or in radiological outcomes in the Karolinska cohort. CONCLUSION: Although antibodies to specific citrullinated proteins may have distinct genetic and environmental risk factors, the similarity in clinical phenotype suggests that they share common pathways in the pathogenesis of joint disease in RA.
21510883 A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease 2011 Apr 21 INTRODUCTION: Janus kinase 2 (JAK2) is involved in the downstream activation of signal transducer and activator of transcription 3 (STAT3) and STAT5 and is responsible for transducing signals for several proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), including interleukin (IL)-6, interferon γ (IFNγ) and IL-12. In this paper, we describe the efficacy profile of CEP-33779, a highly selective, orally active, small-molecule inhibitor of JAK2 evaluated in two mouse models of RA. METHODS: Collagen antibody-induced arthritis (CAIA) and collagen type II (CII)-induced arthritis (CIA) were established before the oral administration of a small-molecule JAK2 inhibitor, CEP-33779, twice daily at 10 mg/kg, 30 mg/kg, 55 mg/kg or 100 mg/kg over a period of 4 to 8 weeks. RESULTS: Pharmacodynamic inhibition of JAK2 reduced mean paw edema and clinical scores in both CIA and CAIA models of arthritis. Reduction in paw cytokines (IL-12, IFNγ and tumor necrosis factor α) and serum cytokines (IL-12 and IL-2) correlated with reduced spleen CII-specific T helper 1 cell frequencies as measured by ex vivo IFNγ enzyme-linked immunosorbent spot assay. Both models demonstrated histological evidence of disease amelioration upon treatment (for example, reduced matrix erosion, subchondral osteolysis, pannus formation and synovial inflammation) and reduced paw phosphorylated STAT3 levels. No changes in body weight or serum anti-CII autoantibody titers were observed in either RA model. CONCLUSIONS: This study demonstrates the utility of using a potent and highly selective, orally bioavailable JAK2 inhibitor for the treatment of RA. Using a selective inhibitor of JAK2 rather than pan-JAK inhibitors avoids the potential complication of immunosuppression while targeting critical signaling pathways involved in autoimmune disease progression.
22539217 Methotrexate (MTX)-cIBR conjugate for targeting MTX to leukocytes: conjugate stability and 2012 Sep Methotrexate (MTX) has been used to treat rheumatoid arthritis at low doses and leukemia at high doses; however, this drug can produce severe side effects. Our hypothesis is that MTX side effects can be attenuated by directing the drug to the target cells (i.e., leukocytes) using (cyclo(1,12)PenPRGGSVLVTGC) peptide (cIBR). To test this hypothesis, MTX was conjugated to the N-terminus of cIBR peptide to give MTX-cIBR conjugate. MTX-cIBR (5.0 mg/kg) suppressed joint arthritis in adjuvant arthritis rats and prevented periarticular inflammation and bone resorption of the limb joints. In vitro, the toxicity of MTX-cIBR peptide against Molt-3 T cells was inhibited by anti-lymphocyte function-associated antigen-1 (LFA-1) antibody and cIBR peptide in a concentration-dependent manner, suggesting that the uptake of MTX-cIBR was partially mediated by LFA-1. Chemical stability studies indicated that MTX-cIBR was most stable at pH 6.0. The MTX portion of MTX-cIBR was unstable under acidic conditions, whereas the cIBR portion was unstable under basic conditions. In biological media, MTX-cIBR had short half lives in rat plasma (44 min) and homogenized rat heart tissue (38 min). This low plasma stability may contribute to the low in vivo efficacy of MTX-cIBR; therefore, there is a need to design a more stable conjugate to improve the in vivo efficacy.
22942325 The efficacy and safety of antidepressants in inflammatory arthritis: a Cochrane systemati 2012 Sep OBJECTIVES: To determine the efficacy and safety of antidepressants in pain management in patients with inflammatory arthritis (IA). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any antidepressants (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. A risk of bias assessment was performed using methods recommended by the Cochrane Collaboration. RESULTS: Eight trials (652 participants) in patients with rheumatoid arthritis (RA) and 1 trial in patients with ankylosing spondylitis (100 participants) were included in this review. The majority of studies were published in the late 1980s in patients with active disease receiving minimal disease-modifying antirheumatic drug therapy. All trials evaluated tricyclic antidepressants (TCA) and 2 studies included a selective serotonin uptake inhibitor. Seven of the 9 trials had high risk of bias, 2 were unclear, and metaanalysis was not performed due to trial heterogeneity. RA trials with short-term outcome (< 1 week) found no significant benefit of amitriptyline 25 mg in combination with dextropropoxyphene (DXP) 65 mg over placebo, and inferiority of amitriptyline + DXP versus DXP 130 mg [mean difference (MD) 10.0, 95% CI 0.4 to 19.6]. There was conflicting evidence regarding medium (1-6 wks) or longer-term (> 6 wks) benefits on pain. One trial in depressed patients with RA showed no significant difference between amitriptyline and paroxetine given for 8 weeks (65% vs 56% much or very much improved; RR 1.2, 95% CI 0.9 to 1.5). One trial found that amitriptyline was no better than placebo in reducing pain in patients with active AS over 2 weeks (MD -0.2, 95% CI -1.2 to 0.8). From 5 trials, withdrawals due to adverse events were not significantly different from placebo. However, there were significantly more minor adverse events in patients receiving TCA compared with those receiving a placebo (RR 2.3, 95% CI 1.2 to 4.4). These included somnolence, dizziness, dry mouth, and nausea. CONCLUSION: Based upon 9 trials of high or unclear risk of bias, it is not possible to draw firm conclusions about the efficacy of TCA as analgesics for patients with IA. The use of these agents may be associated with adverse events that are generally mild and do not lead to cessation of treatment. High-quality trials are needed in this area.
22103436 Towards personalized treatment: predictors of short-term HAQ response in recent-onset acti 2012 Feb OBJECTIVE: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients this outcome is less relevant, whereas short-term functional ability is relevant to all. Do these various treatment goals share the same predictors? METHODS: Data for 497 patients from the Dutch Behandel Strategieen (BeSt) study of treatment strategies for early rheumatoid arthritis (RA), randomized to initial monotherapy or combination therapy, were used. Predictors of short-term functional disability [Health Assessment Questionnaire (HAQ) score ≥ 1 after 3 months of treatment] were identified with logistic regression analyses. Predicted risks of a HAQ score ≥ 1 were determined for each treatment group and for each subpopulation. RESULTS: At baseline, 76% of patients had a HAQ score ≥ 1 (mean 1.7 ± 0.5). After 3 months of treatment this score was achieved by 40% (mean HAQ score 1.5 ± 0.5). Baseline HAQ score, pain, the Ritchie Articular Index (RAI), and treatment group were significant independent predictors for a HAQ score ≥ 1; the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and baseline radiological damage were not. With cut-offs of 35% and 60%, the risk of a HAQ score ≥ 1 was high for 47% and low for 20% of the patients treated with initial monotherapy. Risks were markedly reduced in the combination therapy groups, also in unfavourable risk profiles. CONCLUSION: In recent-onset active RA, baseline HAQ score, pain, and initial treatment are predictors for a HAQ score ≥ 1 after 3 months. Known predictors of radiological damage were not predictive of short-term functional disability. The choice of the best initial treatment thus depends on the relevance of various outcome measures for an individual patient.
22483660 Large granular lymphocyte leukemia as a complication of rheumatoid arthritis. 2012 Nov Large granular lymphocyte leukemia is a rare entity belonging to same spectrum of diseases than Felty's syndrome, which might occur in patients with long-standing rheumatoid arthritis. It is clinically characterized by persistent neutropenia and recurrent bacterial infections associated with the presence in both peripheral blood and bone marrow of clonal expansion of atypic lymphocytes with a cytotoxic T cell phenotype, or less frequently an NK-cell phenotype, as well as splenomegaly. It is more frequently diagnosed in seropositive rheumatoid arthritis, with significant structural damage, extra-articular manifestations and persistently elevated values of ESR, despite them havubg low inflammatory joint activity. We report the case of a 70 year old male with a long-standing rheumatoid arthritis, who developed septic shock secondary to prosthetic hip infection by Salmonella spp. He showed persistent neutropenia, and an aberrant monoclonal T cell population was detected in both peripheral blood and bone marrow, consistent with large granular lymphocyte leukemia.
22615458 Positivity for anti-cyclic citrullinated peptide is associated with a better response to a 2012 Nov OBJECTIVES: Very limited data are available regarding the efficacy of abatacept (ABA) in real life. The aims of this study were to determine the efficacy of ABA in rheumatoid arthritis and predicting factors of efficacy in common practice. METHODS: The Orencia and Rheumatoid Arthritis" (ORA) prospective registry, promoted by the French Society of Rheumatology, has included 1003 patients with RA. RESULTS: 773 patients had already fulfilled the 6-month follow-up visit. Only 21.3% of patients would have fulfilled inclusion criteria used in pivotal controlled trials. The European League Against Rheumatism (EULAR) response, was observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%, moderate response: 38.7%) and was similar in patients who did and in patients who did not fulfill inclusion criteria of controlled trials. Among EULAR responders, initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0-6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs 66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In multivariate analysis adjusted on initial 28-joint disease activity score and CRP, anti-CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to 2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti-CCP positivity was also significantly associated with a higher ABA retention rate at 6 months. CONCLUSIONS: Real life efficacy of ABA in the ORA registry was similar as that reported in clinical trials. Anti-CCP positivity was associated with a better response to ABA, independently from disease activity.
23044789 [Disorders of the larynx and chronic inflammatory diseases]. 2012 Dec Chronic inflammatory diseases including tuberculosis, rheumatic disorders (rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Wegeners's granulomatosis, relapsing polychondritis) and reflux disease are considered as systemic diseases, and may affect the larynx. The clinical symptoms are often unspecific, leading to prolonged intervals to diagnosis. Solid and haematological tumours should be considered in differential diagnosis and may require bioptic sampling. Treatment may require interdisciplinary approach.
22286641 Switching between anti-TNF-alpha agents does not improve functional capacity in patients w 2012 Jan OBJECTIVES: To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This study included 99 patients diagnosed with RA American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defined as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05. RESULTS: Switching was performed in 39 (39.4%) patients, especially due to PF (24.3%), SF (35.1%) and T (40.5%). The retention rate of the first agent was 60.1%, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43% of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity. CONCLUSION: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no significant improvement in functional capacity.
22807020 Demodex mite infestation in patients with and without rheumatoid arthritis. 2012 Mar In the present study we compared the prevalence of Demodex mites in patients with rheumatoid arthritis and in one control group involving individuals of similar mean age. From each person we epilated 3-4 lashes from each eyelid and examined them under a microscope to find Demodex mites. In total 147 patients were examined. The prevalence of Demodex mites was 33% in rheumatoid arthritis (RA) patients and 31% in the control group. Our results demonstrated that the prevalence of Demodex mites was similar in RA patients as compared to the control group.
23399842 Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activati 2012 Dec Total glucoside of paeony (TGP), an active compound extracted from paeony root, has been used in therapy for rheumatoid arthritis (RA). Th1 and Th17 cells are now believed to play crucial roles in the lesions of RA. However, the molecular mechanism of TGP in inhibition of Th1 and Th17 cells remains unclear. In this study, we found that TGP treatment significantly decreased percentage and number of Th1 and Th17 cells in collagen induced arthritis (CIA) mice. Consistently, treatment with TGP decreased expression of T-bet and RORγt as well as phosphorylation of STAT1 and STAT3. In particular, TGP treatment inhibited dendritic cells (DCs) maturation and reduced production of IL-12 and IL-6. Moreover, TGP-treatment RA patients showed shank population of matured DCs and IFN-γ-, IL-17-producing cells. Taken together, our results demonstrated that TGP inhibited maturation and activation of DCs, which led to impaired Th1 and Th17 differentiation in vivo.
22839595 Physical inactivity and arterial dysfunction in patients with rheumatoid arthritis. 2013 OBJECTIVES: The increased risk of cardiovascular (CV) disease associated with rheumatoid arthritis (RA) is partly attributable to chronic inflammation, but traditional CV risk factors such as physical inactivity are also likely to be important. This study assessed the cross-sectional relationship between physical activity (PA) and arterial dysfunction in patients with RA. METHODS: Participants free of overt arterial disease aged 40-65 years were recruited from a consecutive series of RA patients attending a rheumatology clinic. A research nurse measured the 'augmentation index' (AIX%) on a single occasion (a higher AIX% indicates arterial dysfunction) using SphygmoCor radial pulse wave analysis (PWA) according to current recommendations. Participants provided a fasting blood sample and self-completed a patient questionnaire that included the modified Godin PA score (mGPAS). Analysis was adjusted for age, sex, CV and rheumatological factors using multiple linear regression. RESULTS: Among 114 patients (mean age 54 years, median arthritis duration 10 years, 82% women), mean AIX% was 31.5 (SD 7.7) and median mGPAS 15 (IQR 10-35). AIX% was correlated with mGPAS (rho -0.21, p = 0.02). AIX% decreased with more frequent vigorous PA. On unadjusted analysis, a 10-point higher mGPAS was associated with a -0.9 [95% confidence interval (CI) -1.3 to -0.4, p = 0.0005] lower AIX%. On adjusted analysis, the reduction was attenuated to -0.5 (95% CI -0.8 to -0.1, p = 0.03). CONCLUSIONS: A higher level of self-reported PA in RA patients is associated with a lower level of arterial dysfunction independently of other CV and rheumatological factors. Longitudinal studies are required to demonstrate that increased PA improves arterial dysfunction in RA patients.
22851506 Combining family and twin data in association studies to estimate the noninherited materna 2012 Dec It is hypothesized that certain alleles can have a protective effect not only when inherited by the offspring but also as noninherited maternal antigens (NIMA). To estimate the NIMA effect, large samples of families are needed. When large samples are not available, we propose a combined approach to estimate the NIMA effect from ascertained nuclear families and twin pairs. We develop a likelihood-based approach allowing for several ascertainment schemes, to accommodate for the outcome-dependent sampling scheme, and a family-specific random term, to take into account the correlation between family members. We estimate the parameters using maximum likelihood based on the combined joint likelihood (CJL) approach. Simulations show that the CJL is more efficient for estimating the NIMA odds ratios as compared to a families-only approach. To illustrate our approach, we used data from a family and a twin study from the United Kingdom on rheumatoid arthritis, and confirmed the protective NIMA effect, with an odds ratio of 0.477 (95% CI 0.264-0.864).
22127818 Cellular response to prosthetic wear debris differs in patients with and without rheumatoi 2012 Apr OBJECTIVE: To examine whether patients with rheumatoid arthritis (RA) demonstrate patterns of prosthetic wear or cellular responses to implant wear debris different from those demonstrated by patients without inflammatory joint disease. METHODS: Thirty-eight patients who had undergone a primary revision of a total elbow arthroplasty for aseptic loosening between 1996 and 2008 were identified. Twenty-five of these patients had RA, and 13 did not have inflammatory arthritis. Clinical data, gross wear patterns of the removed prostheses, and histopathologic analyses of peri-implant tissue were compared between the patients with RA and those without RA. RESULTS: Evaluation of the retrieved prostheses showed that conformational change of the humeral polyethylene bushing was associated with the generation of polyethylene and metal particles. The amount and type of wear debris in periprosthetic tissues were similar in patients with and those without RA. Patients with RA who were not receiving anti-tumor necrosis factor (anti-TNF) therapy exhibited a histologic pattern of interstitial and sheet-like lymphocytic infiltrates associated with a high plasma cell composition, which was different from the predominantly perivascular infiltrates with few plasma cells seen in non-RA patients (P = 0.04). Patients with RA who were receiving anti-TNF therapy showed a mixed perivascular and interstitial pattern of infiltrates with variable cell composition. CONCLUSION: Patients with RA exhibited a distinct cellular response to implant wear debris compared with patients without RA. This reaction was unrelated to differences in the type or amount of wear debris and was mitigated by anti-TNF therapy. These results suggest an intrinsic alteration in immunoregulation in RA and have implications for potential immunologic treatment of osteolysis in these patients.