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

ID PMID Title PublicationDate abstract
25550338 Changes in the anticitrullinated peptide antibody response in relation to therapeutic outc 2016 Feb OBJECTIVE: To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA). METHODS: Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression. RESULTS: During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression. CONCLUSIONS: The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA. TRIAL REGISTRATION NUMBER: WHO database at the Karolinska institute: CT20080004; and clinicaltrials.gov: NCT00764725.
23093721 Who are the patients with early arthritis with worse than death scores on the EQ-5D? Resul 2013 May OBJECTIVES: The EQ-5D is a five-dimension multi-attribute questionnaire widely used to calculate quality-adjusted life-year scores. We aimed to describe patients with early arthritis (EA) and EQ-5D < 0, a state worse than death, at baseline and over 2 years and determine aspects of EA associated with a negative score. METHODS: EQ-5D scores for 813 patients were longitudinally assessed over 24 months. Characteristics and health status of patients with EQ-5D < 0 were analysed. Multivariate logistic regression was used to determine aspects of EA associated with a negative score. RESULTS: At baseline, 90 (11%) patients had a negative EQ-5D score (median EQ-5D -0.052; range -0.530 to -0.011). Almost all patients had extreme pain/discomfort and at least moderate problems in anxiety/depression domain. These patients had lower educational level, greater disease activity, higher HAQ score (greater functional disability), greater pain and fatigue, lower Short Form 36 (SF-36) mental component scores and higher CRP levels than patients with EQ-5D ≥ 0 (all P < 0.001). In the logistic regression model, worse HAQ and SF-36 mental component scores were associated with EQ-5D < 0. Results were similar at 6, 12 and 24 months, with 25, 23 and 24 patients, respectively, in a state worse than death. CONCLUSION: Pain or discomfort, often severe, is a key domain of the EQ-5D for patients with EA in a health state worse than death, and poor HAQ and SF-36 mental component scores were always independently associated with a state worse than death. EA patients may have specific needs necessitating better management of pain and psychological state.
24685296 Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid ar 2014 May Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis.
22807318 Adalimumab treatment in patients with rheumatoid arthritis with renal insufficiency. 2013 Mar OBJECTIVE: To elucidate the safety of adalimumab for rheumatoid arthritis (RA) patients with renal insufficiency, including those with end-stage renal disease undergoing hemodialysis. METHODS: Sixty-five RA patients, including 2 patients undergoing hemodialysis, treated with adalimumab in our hospital from December 1, 2008 to June 30, 2011 were retrospectively analyzed. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated from the Cockcroft-Gault formula at the start and end of followup after adalimumab treatment. The proportion of the patients who discontinued or switched adalimumab treatment and the change of the eGFR were compared between patients with (n = 39) and without (n = 26) renal insufficiency, defined as an eGFR <60 ml/minute/1.73 m(2) . RESULTS: There was no significant difference between the 2 groups in the proportion of the patients who discontinued or switched adalimumab treatment (51.3% versus 50.0%; P = 0.53). The mean ± SD changes of eGFR were from 41.6 ± 13.3 to 43.4 ± 17.9 ml/minute/1.73 m(2) in patients with renal insufficiency and from 83.6 ± 17.5 to 83.0 ± 16.8 ml/minute/1.73 m(2) in patients without renal insufficiency, and the differences in each group were not statistically significant (P = 0.92 and P = 0.78, respectively). No severe infections or other severe adverse events were observed in either group during adalimumab treatment. CONCLUSION: Our data indicate that adalimumab does not worsen renal function and has no serious adverse events even for RA patients with renal insufficiency, including those undergoing hemodialysis, and suggest that it could be a potential therapeutic option for them.
24659755 Synovial inflammation assessed by ultrasonography correlates with MRI-proven osteitis in p 2014 Aug OBJECTIVE: The aim of this study was to explore whether assessment of synovial inflammation by ultrasonography correlates with MRI-proven osteitis in patients with RA. METHODS: Thirty RA patients who fulfilled 2010 RA classification criteria and were naive to DMARDs, including biologics and glucocorticoids, were consecutively enrolled in this study. Grey scale (GS) and power Doppler (PD) images of articular synovitis and bone erosion in both wrist and MCP joints were evaluated by the method proposed by the European League Against Rheumatism. MRI-proven osteitis of the identical sites was also evaluated within 3 days using the RA MRI scoring system (RAMRIS). The Cochran-Armitage test and Spearman's correlation coefficient were used to investigate the correlation of each US finding with MRI-proven osteitis. RESULTS: MRI-proven osteitis was found in 8.3% of MCP joints and 48.3% of wrist joints. Its prevalence was increased in the joints where the GS or PD grade of articular synovitis was 2 or 3. In addition, MRI-proven osteitis was found preferentially in the joints positive for bone erosion on US. A clear correlation was demonstrated between the GS or PD grade of articular synovitis or the presence of US bone erosion and RAMRIS osteitis score in both MCP joints and wrist joints. CONCLUSION: Our data indicate that joint injury assessed by US correlates with MRI-proven osteitis in patients with RA.
23857661 Temporomandibular joints in patients with rheumatoid arthritis using magnetic resonance im 2013 Nov The aim of this study was to determine the relationship between the pathogenic duration of rheumatoid arthritis in joints other than the temporomandibular joint and bone and soft tissue involvement of the temporomandibular joint using magnetic resonance imaging. Twenty-six symptomatic patients diagnosed with rheumatoid arthritis were enrolled in this study. All patients were classified according to the duration of rheumatoid arthritis in joints other than the temporomandibular joint. The relationships between the duration of rheumatoid arthritis in these various joints and magnetic resonance findings in the temporomandibular joint were analyzed using the chi-square test. Bony changes in the mandibular condyle were observed in 43 of 52 (82.7 %) temporomandibular joints, but the frequency of such changes was not significantly correlated with the duration of rheumatoid arthritis in other joints. We found a significant correlation between the duration of rheumatoid arthritis in other joints and the type and number of bony changes in the mandibular condyle (P < 0.05). Superior disc positions were observed in 27 of 52 (51.9 %) temporomandibular joints. T2-weighted images demonstrated effusion in the joint space in 38 of 52 (73.1 %) temporomandibular joints. A biplanar disc configuration was the most frequent configuration in all groups. The duration of rheumatoid arthritis in other joints was significantly correlated with the mobility of the mandibular condyle (P < 0.05). The type and number of bony changes and mobility of the mandibular condyle showed significant relationships with the duration of rheumatoid arthritis in other joints in the body (P < 0.05).
24568777 Diagnosis and classification of rheumatoid arthritis. 2014 Feb Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear etiology that is manifested in by a progressive and destructive polyarthritis in association with serological evidence of autoreactivity. Its diagnosis is based on the classification criteria that involve four parameters: joint involvement, serology (rheumatoid factor and anti-cyclic citrullinated peptide--anti-CCP), levels of acute phase reactants and the duration of the symptoms Aletaha, et al. [1]. This classification simplifies the categorization of the patients with early RA; however, the diagnosis requires highly trained specialists who are able to differentiate early symptoms of RA from other pathologies.
24881423 The acutely swollen knee. Part 1: Management of atraumatic pathology. 2014 The acutely swollen knee is a common presentation of knee pathology in the Emergency Department and the primary care setting whether on board ship, a Regimental Aid Post or Medical Centre. The swollen knee has both traumatic and atraumatic (systemic) causes, all of which can be accurately diagnosed with an understanding of the underlying injury patterns and patho-anatomy. In Part One, we will be examining the management of non-traumatic causes, followed by Part Two, looking at traumatic causes, in the next issue of the Journal. A detailed clinical history combined with thorough clinical examination will establish the diagnosis, or at least the narrow differential diagnosis in the majority of cases. The uses of specialist examination techniques, diagnostic imaging and arthrocentesis can further assist the clinician in confirming the correct diagnosis and thus prescribing the appropriate treatment. This review will endeavour to give a consensus of opinion and structured guidelines in the diagnosis and initial management of patients presenting with acute or recent-onset swelling of the knee related to atraumatic pathology.
24682873 Identification of potential serum biomarkers for rheumatoid arthritis by high-resolution q 2014 Oct The aim of this study was to find serum biomarkers of rheumatoid arthritis (RA) by high-resolution proteomic analysis. Low-abundance proteins from pooling serum sample of early RA patients and healthy controls were enriched using ProteoMiner™ enrichment kits. The enriched proteins were separated on SDS-PAGE, digested by trypsin, labeled with tandem mass tag (TMT) reagents, and desalted by C18 stage tip column. Then, the labeled peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with nano-LC combined with Orbitrap Q Exactive mass spectrometer, and experiments were carried out three times using different specimens, and differentially expressed proteins were screened by intensity ratios of identified peptides. Enzyme-linked immunosorbent assays (ELISAs) were performed to confirm differentially expressed proteins. Twenty-six proteins were found differentially expressed in RA serum by high-resolution proteomic analysis. Among them, levels of thrombospondin-1, ficolin-2, isoform 10 of fibronectin, and apolipoprotein E were higher in RA patients than in healthy controls (RA/healthy control (HC) ≥ 1.5, p<0.05), while levels of angiotensinogen, paraoxonase/arylesterase 1, isoform E of proteoglycan 4, and plasminogen were significantly lower (RA/HC ≤ 0.67, p<0.05). Further study by ELISA showed a higher level of ficolin-2 in the serum of RA patients compared to healthy controls; the level of ficolin-2 was found to be positively correlated with swollen joint counts (SJCs), disease activity score (DAS28), rheumatoid factor, and IgM in RA patients and with DAS28 and IgM in early RA patients through statistical analysis. The results of this study suggest that ficolin-2, as a newly screened biomarker by high-resolution quantitative proteomic analysis, offers the potentiality to become a diagnostic or disease evaluation tool in RA.
25326335 Meta-analysis of associations between functional HLA-G polymorphisms and susceptibility to 2015 Jun The aim of this study was to determine whether the functional HLA-G 14 bp insertion (I)/deletion (D) and +3142 G/C polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the HLA-G 14 bp I/D, and +3142 G/C polymorphisms and SLE or RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of 14 comparison studies from 11 articles met our inclusion criteria, comprising eight on SLE (1,284 patients and 1,885 controls) and four on RA (820 patients and 772 controls), and three studies investigated response to methotrexate (MTX) in RA according to the HLA-G 14 bp I/D polymorphisms (249 responders and 205 nonresponders). Meta-analysis revealed an association between the II + ID genotype of the HLA-G 14 bp I/D polymorphism in overall group (OR = 1.205, 95% CI = 1.036-1.403, P = 0.016). Ethnicity-specific meta-analysis showed no association between the II + ID genotype and SLE in the South American, European, and Asian population. Meta-analysis revealed a significant association between SLE and the HLA-G +3142 G allele in all study subjects (OR = 1.367, 95% CI = 1.158-1.613, P = 2.2 × 10(-5)) and in the South American group (OR = 1.531, 95% CI = 1.242-1.888, P = 6.7 × 10(-5)). However, no association between HLA-G 14 bp I/D, and +3142 G/C polymorphisms and RA was found (OR for HLA-G I allele = 1.013, 95 % CI = 0.879-1.167, P = 0.859; OR for +3142 G allele = 0.980, 95% CI = 0.742-1.294, P = 0.888). Furthermore, HLA-G 14 bp I/D polymorphism was not found to be associated with response to MTX in RA. This meta-analysis demonstrates that the HLA-G 14 bp I/D polymorphism is associated with susceptibility to SLE, and HLA-G +3142 G/C polymorphisms are associated with susceptibility to SLE in South Americans.
23696630 A genetic variant in the region of MMP-9 is associated with serum levels and progression o 2014 Jun OBJECTIVES: The severity of joint destruction is highly variable between rheumatoid arthritis (RA) patients. The majority of its heritability is still unexplained. Several autoimmune diseases share genetic risk variants that may also influence disease progression. We aimed to identify genetic risk factors for the severity of joint damage in RA by studying genetic susceptibility loci of several autoimmune diseases. METHODS: In phase 1, 3143 sets of x-rays of 646 Dutch RA patients taken over 7 years (Sharp van der Heijde (SHS) scored) were studied. Genotyping was done by Immunochip. Associations of single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >0.01 and joint destruction were analysed. In phase 2, 686 North American RA patients with 926 SHS-scored x-rays over 15 years of follow-up were evaluated. In both phases multiple testing corrections were done for the number of uncorrelated SNPs; the thresholds for significance were p<1.1×10(-6) and p<0.0036. Matrix metalloproteinase 9 (MMP-9) levels were measured with ELISA in baseline serum samples. RESULTS: In phase 1, 109 SNPs associated significantly with joint destruction (p<1.1×10(-6)). Of these, 76 were located in the HLA region; the 33 non-HLA variants were studied in phase 2. Here two variants were associated with the severity of joint destruction: rs451066 on chromosome 14 (p=0.002, MAF=0.20) and rs11908352 on chromosome 20 (p=0.002, MAF=0.21). Rs11908352 is located near the gene encoding MMP-9. Serum levels of MMP-9 were significantly associated with the rs11908352 genotypes (p=0.007). CONCLUSIONS: These data indicate that two loci that confer risk to other autoimmune diseases also affect the severity of joint destruction in RA. Rs11908352 may influence joint destruction via MMP-9 production.
23783062 Applying evidence in the care of patients with rheumatoid hand and wrist deformities. 2013 Oct The traditional approach in managing rheumatoid hand deformities is based on the individual surgeon's experiences. In the current era of evidence-based medicine, formulating treatment for the rheumatoid hand fits perfectly within the framework of evidence-based medicine by leveraging the best evidence from the literature, incorporating surgeons' experience and considering patients' preferences. In this Special Topic article, we use a case example to illustrate how evidence-based medicine can be practiced within the framework of treating rheumatoid hand deformities by distilling the best evidence from the literature to guide surgeons in a rational approach for treating this common condition.
24387883 Inflammation and vascularisation markers of arthroscopically-guided finger joint synovial 2014 Jan OBJECTIVES: To analyse whether synovial markers of the clinically dominant metacarpophalangeal (MCP) joint reflect global disease activity measures in rheumatoid arthritis (RA). METHODS: Arthroscopically-guided synovial biopsies from the dominant metacarpophalangeal (MCP) joint of 10 patients with RA (DAS28 >3.2) were stained for determination of the synovitis score, CD68, vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α). MRI and ultrasound were used to calculate the RAMRIS and US7 score respectively. Arthroscopy of the same joint was repeated in 6 patients after 6 months. RESULTS: The synovitis score significantly correlated to DAS28 (Spearman r=0.74), CRP (r=0.69), and US7 (r=0.66); sublining CD68 macrophages to CRP (r=0.6); HIF-1α to DAS28 (r=0.77), CRP (r=0.73); and VEGF to DAS28 (r=0.753) and RAMRIS (r=0.663). All patients showed a reduction of the DAS28 after 6 months (mean±SD: 5.2±1.5 vs. 2.75±1.1; p<0.05). There were three patients with a good EULAR response, and only these showed declining sublining CD68 macrophages in the control biopsy (χ2 test: LR 8.3, p=0.05). Two of the remaining patients with increasing CD68 sublining macrophages showed a deterioration of the RAMRIS. CONCLUSIONS: Some histological findings in arthroscopically-guided biopsies of the dominantly affected MCP joint reflect global disease activity measures and their changes in RA patients. Moreover, repeated MCP synovial biopsy may distinguish true responders from individuals with residual disease activity, who are not readily recognized by clinical means.
24659148 [Outpatient rheumatologic treatment in Germany]. 2014 Mar Outpatient rheumatologic treatment in Germany is managed by rheumatologists in private practice (n = 557), by authorized rheumatism outpatient centers (n = 116), by rheumatism centers according to §116b (n = 43) and by university outpatient departments. A total number of 975 rheumatologists were registered by the end of 2012 of whom approximately 830 were active in outpatient care. With this number of rheumatologists Germany is in the middle range in comparison to eight industrial nations including the USA. This number is not sufficient to provide adequate medical care and the consequences are too long waiting times for an appointment with a rheumatologist. Statistical data of the Kassenärztliche Bundesvereinigung (KBV, National Association of Statutory Health Insurance Physicians) showed 688,000 general insurance patients with rheumatoid arthritis (RA). As some 68.9 % of the population are in this insurance scheme there are some 770,000 RA patients in Germany (almost 1 % of the population). One way to improve rheumatology care in spite of the lack of rheumatologists could be special agreements with the general health insurance providers to improve cooperation and division of responsibilities between rheumatologists and general practitioners, to implement patient education, tighter control and treat to target in rheumatology care. Another way could be a new treatment level called "ambulant specialist care", with no budget for medical care and no budget for the number of patients treated and therefore the chance for rheumatologists to treat more patients and have a better income. To achieve that more young doctors receive approval as a specialist in rheumatology, more chairs of rheumatology at universities and a nationwide stipendium for training assistants are needed.
24136064 Costs of rheumatoid arthritis during the period 1990-2010: a register-based cost-of-illnes 2014 Jan OBJECTIVES: The objectives of this study were to analyse the total socio-economic impact of RA in Sweden during the period 1990-2010 and to analyse possible changes in costs during this period. The period was deliberately chosen to cover 10 years before and 10 years after the introduction of biologic drugs. METHODS: A prevalence-based cost-of-illness study was conducted based on data from national and regional registries. RESULTS: There was a decrease in the utilization of RA-related inpatient care as well as sick leave and disability pension during 1990-2010 in Sweden. Total costs for RA are presented in current prices as well as inflation-adjusted with the consumer price index (CPI) and a healthcare price index. The total fixed cost of RA was €454 million in 1990, adjusted to the price level of 2010 with the CPI. This cost increased to €600 million in 2010 and the increase was mainly due to the substantially increasing costs for pharmaceuticals. Of the total costs, drug costs increased from 3% to 33% between 1990 and 2010. Consequently the portion of total costs accounting for indirect costs for RA is lowered from 75% in 1990 to 58% in 2010. CONCLUSION: By inflation adjusting with the CPI, which is reasonable from a societal perspective, there was a 32% increase in the total fixed cost of RA between 1990 and 2010. This suggests that decreased hospitalization and indirect costs have not fallen enough to offset the increasing cost of drug treatment.
24676467 Anti-inflammatory effect of resveratrol on adjuvant arthritis rats with abnormal immunolog 2014 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease with unknown etiology. The present study investigated the anti-inflammatory effect of resveratrol on rats with adjuvant arthritis (AA) with abnormal immunological function via the reduction of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). AA model rats were established by injection of complete Freund's adjuvant and alterations in the rats secondary paw swelling and the polyarthritic scores were observed. Pathological examination of joint tissues was observed by hematoxylin and eosin staining. The proliferation of spleen cells was examined using a 3-(4,5-dimethylthiazol-2‑yl)-2,5-diphenyltetrazolium bromide assay in vitro. The protein expression of COX-2 in the synovial tissues was detected by western blotting. The level of PGE2 in the serum was assayed using an ELISA kit. The results demonstrated that resveratrol (10 or 50 mg/kg) was able to significantly reduce paw swelling and decrease the arthritis scores. Compared with the AA model rats, a significant reduction in the proliferation of concanavalin A-stimulated spleen cells was observed, articular cartilage degeneration with synovial hyperplasia and inflammatory cell infiltration was suppressed and the production of COX-2 and PGE2 in AA rats was reduced by treatment with resveratrol. These results suggest that resveratrol has significant anti-inflammatory effects on AA rats, which may be associated with the reduction of COX-2 and PGE2 inflammatory mediators.
23412262 Lateral approach is advantageous in total knee arthroplasty for valgus deformed knee. 2014 Jan INTRODUCTION: For the total knee arthroplasty in valgus deformed knee, superiority of the medial or lateral approach is still controversial. We compared the short-term result of two approach groups. MATERIALS AND METHODS: Forty-seven knees in rheumatoid arthritis with valgus deformity from 6° to 24° were randomly divided into two group; medial approach (24 knees) and lateral approach (24 knees). We used Scorpio NRG PS for all knees. Median postoperative periods were 43 months in both groups. We compared the surgical time, and alignment on standing radiograph, range of motion (ROM) pre/postoperatively, and degrees of soft-tissue release procedure, and lateral laxity measured by stress radiograph immediately after operation and at final follow-up. RESULT: Pre/postoperative alignment, surgical time, lateral laxity, and preoperative ROM had no significant in two groups; however, postoperative flexion was superior in lateral approach group 123.8°, 109° in medial approach group. All cases required iliotibial band (ITB) release at Gerdy's tubercle, 83 % ITB at joint level, 21 % lateral collateral ligament (LCL), 17 % popliteus tendon (PT) in medial approach group, and 88 % ITB at Gerdy's tubercle, 46 % ITB at joint level, 13 % LCL, 4 % PT in lateral approach group. DISCUSSION: In the valgus knee, lateral structures are tight. Lateral approach can directly adjust the tight structure, and also less vascular compromise to the patella than medial approach with lateral patellar release. Less invasiveness to the quadriceps muscle in lateral approach could result into better range of motion after the surgery.
25184828 Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP 2014 INTRODUCTION: Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis. METHODS: Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression. RESULTS: No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively). CONCLUSION: Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.
24782174 Hand and foot surgery rates in rheumatoid arthritis have declined from 1986 to 2011, but l 2014 May OBJECTIVE: To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup. METHODS: The study examined orthopedic data from the UK Early RA Study (1986-1999, 9 centers; n = 1,465) and the UK Early RA Network (2002-2012, 23 centers; n = 1,236) with linkage to national data sets (Hospital Episode Statistics, National Joint Registry, and Office of National Statistics). Clinical and laboratory measures and hand and foot radiographs were standardized and obtained yearly in both cohorts. The use of disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologic therapies reflected the contemporary conventional practices and guidelines of the time frames examined. Recruitment years were grouped into 6 periods, and interventions were classified into major, intermediate, and minor categories. RESULTS: A total of 1,602 orthopedic surgical procedures were performed in 770 patients (29%) over a maximum of 25 years of followup. The 25-year cumulative incidence rate of major interventions was 21.7% (range 19.4-24.0%), and that of intermediate interventions was 21.5% (range 17.8-25.5%). There was a decline in the 10-year cumulative incidence of intermediate surgeries over time (P < 0.001), but not of major/minor surgery. This decline coincided with a gradual shift from sequential monotherapy to combination DMARD therapies and biologic agents in recent recruitment periods. CONCLUSION: Orthopedic surgery is an important and common outcome in RA. Only the rates of hand/foot surgery showed a consistent decline from 1986 to 2011. Possible explanations include differences in the pathophysiologic processes affecting the joints, variations in the responses to therapy between large-joint and small-joint destructive processes, and changes in service provision and thresholds for surgery over time.
24146468 Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis. 2013 Rheumatoid arthritis (RA) is the rheumatism mainly manifested as disabling joint disease and mainly involves hands, wrists, feet and other small joints. Recurrent arthritis attacks, synovial cell hypertrophy and hyperplasia and bone and cartilage damages eventually lead to joint dysfunction and other complications, and there is no cure. Quercetin (QU) is a kind of natural flavonoids, with lipid-lowering, anti-inflammatory and other pharmacological activities, and minor toxic side effects. Thus, we assume that QU may be an adjuvant natural drug for treatment of RA. The possible mechanism is through regulation of NF-κB, to inhibit the transcription of joint synovitis factors, hinder the generation of inflammatory factors, and inhibit the inflammatory reaction; through inhibiting the activities of VEGF, bFGF, MMP-2 and other cytokines, to inhibit angiogenesis in multiple links and inhibit synovial pannus formation. QU may be an adjuvant natural drug for treatment of RA.