Browse

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

ID PMID Title PublicationDate abstract
22669596 Significant improvement in MRI-proven bone edema is associated with protection from struct 2013 Mar OBJECTIVE: To identify the value of magnetic resonance imaging (MRI)-proven bone edema in patients with very early rheumatoid arthritis (RA). METHODS: All of the 13 patients included in the study were positive at entry for MRI-proven bone edema of the wrist and finger joints and anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. A tight control approach was applied for 12 months. Plain MRI and radiographs of both wrist and finger joints were examined every 6 months. MRI was scored by the RA MRI scoring (RAMRIS) technique and plain radiographs were scored using the Genant-modified Sharp score. Variables that were correlated with plain radiographic changes at 12 months were examined. RESULTS: Simplified disease activity index (SDAI) remission was achieved in 7 patients, and a significant reduction in the RAMRIS bone edema score, which declined to <33 % as compared with the baseline, was achieved in 8 out of 13 patients. Four patients showed plain radiographic progression while 9 patients did not. Significant reductions in the RAMRIS bone edema score (p = 0.007) and the time-integrated SDAI (p = 0.031) were the variables involved in plain radiographic progression. CONCLUSIONS: Improvement in bone edema may be associated with protection against structural damage in very early RA patients managed using the tight control approach.
21327436 Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: a sub- 2012 Jun The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2-5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pre-treatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for <2 years. Less AEs and SAEs were observed among patients with shorter duration of RA. These results suggest that RA treatment in Japan in the era pre-biologics may not have been adequate to control disease activity and prevent joint destruction. Patients with shorter duration of RA may have better physical status which allows the opportunity to treat more intensively putting a higher percentage of patients in remission and possibly decreasing exposure to SAEs.
22183834 Development and evaluation of a novel ultrasound score for large joints in rheumatoid arth 2012 May OBJECTIVE: To introduce and evaluate a new standardized ultrasound (US) score developed for large joints in patients with rheumatoid arthritis (RA). METHODS: A US score was designed to determine the degree of inflammation in the shoulder, the elbow, the hip, and the knee joint in patients with RA (Sonography of Large Joints in Rheumatology [SOLAR] score). Synovitis and synovial vascularity were scored semiquantitatively (grade 0-3) by gray-scale US (GSUS) and power Doppler US (PDUS). Patients with RA were examined at baseline and 3, 6, and 12 months after initiation of local or systemic therapy (disease-modifying antirheumatic drugs [DMARDs]/biologic agents). Erythrocyte sedimentation rate, anti-cyclic citrullinated peptide antibodies, and the clinical Disease Activity Score in 28 joints (DAS28) were determined. RESULTS: A cohort of 199 patients were analyzed and followed up over 12 months. At baseline, before modification of the therapy, patients received either DMARDs (n = 131), DMARDs plus biologic agents (n = 46), biologic monotherapy (n = 8), or no DMARD therapy (n = 14). At baseline, the mean DAS28 score was 4.6 and decreased to 3.2 after 1 year of therapy (P < 0.001). All US scores demonstrated a statistically significant improvement except for the PDUS scores for the shoulder and the hip. In detail, the mean synovitis GSUS score for the knee decreased from 5.2 at baseline to 2.2 after 12 months of followup. The mean GSUS score for the shoulder fell from 2.6 to 1.6, for the elbow fell from 5.2 to 2.6, and for the hip fell from 2.2 to 0.4 (P < 0.05 for each). CONCLUSION: The SOLAR score is a feasible tool for the qualitative and quantitative evaluation of large joint involvement in patients with RA using US.
21362334 p53 in fibroblast-like synoviocytes can regulate T helper cell functions in patients with 2011 Feb BACKGROUND: p53 is a tumor suppressor and plays a key role in regulating cell hyperplasia, repairing DNA and inducing apoptosis. This study was to investigate p53 expression in fibroblast-like synoviocytes (FLS) and its effect on CD4(+) T lymphocytes from patients with active rheumatoid arthritis (RA). METHODS: Human FLS were transfected with p53 siRNA and cocultured with CD4(+) T lymphocytes from patients with active RA. The expressions of osteoprotegerin and interleukin (IL)-6 were detected in p53 siRNA and scramble siRNA-transfected FLS. In addition, protein levels of interferon (IFN)-γ, IL-17, IL-4 and CD25 as well as mRNAs of IFN-γ, retinoic acid-related orphan receptor (ROR)-γt, IL-17 and Foxp3 in cocultured CD4(+) T lymphocytes were also measured. RESULTS: IL-6 decreased in p53-knockdown FLS while osteoprotegerin expression was not altered. FLS with p53 deletion significantly increased the production of IL-17 and IFN-γ by CD4(+) T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4(+)CD25(high) T lymphocytes. CONCLUSION: p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.
21286723 The CD226 gene in susceptibility of rheumatoid arthritis in the Chinese Han population. 2012 May Recent case-control studies have identified some loci that are associated with rheumatoid arthritis (RA). Among these, a single nucleotide polymorphism (SNP), Gly307Ser (rs763361), in the CD226 gene was first discovered to confer the risk of RA in populations with European and Colombian ancestry. Because the effect of genetic factors varies in different races, the association between RA and CD226 is yet to be evaluated in other non-European populations. Here, we report the significant association between CD226 and RA in a Chinese population of 423 randomly enrolled individuals. The statistical results show that the rs763361 SNP in the CD226 gene is significantly associated with RA in the Chinese population group (P (obs) = 0.005, odds ratio = 1.52). After adjusting for sex and age using multivariate logistics regression analysis, the association is still positive (P (adj) = 0.029, odds ratio = 1.45). Meta-analysis confirms the association between rs763361 and RA (overall P < 0.001, overall odds ratio = 1.12). The test of odds ratio heterogeneity also suggests that the rs763361 SNP confers the same risk of RA in both the Chinese and the Colombian populations, and indicates that rs763361 may play a more important role in non-European populations compared with the European population (P = 0.031). These results demonstrate a genetic association between the CD226 gene and RA in a Chinese Han population with a potentially greater genetic effect than in the European population.
22992031 Effects of shark cartilage polysaccharides on the secretion of IL-6 and IL-12 in rheumatoi 2012 Dec CONTEXT: Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by inflammation of the synovial membrane, leading to articular cartilage destruction. Shark cartilage polysaccharide (SCP) is a biodegradable, biocompatible, nontoxic, non-immunogenic and non-inflammatory polysaccharide that may be used in treating RA. OBJECTIVE: The anti-RA activities of SCP given orally to rats are investigated here for the first time. MATERIALS AND METHODS: SCP treatment group were administered with SCP-1, SCP-2 in the dosage of 9 mg/day for 24 days. The effect of SCP-1 and SCP-2 on the body weight, paw swelling, morphological changes of ankle and IL-6, IL-12 secretion in RA rats are examined. RESULTS: On day 24, there were no obvious differences in BMI between positive, SCP-1 and SCP-2 group. The swelling degree of SCP-1 and SCP-2 group was less serious than model group. X-ray revealed that SCP-1, SCP-2 group owned normal joint alignment and more smooth and tidy articular surface. The SCP-1 and SCP-2 have inhibitory effect on IL-6 (430.3 ± 25.6 pg/mL, 439.1 ± 35.9 pg/mL) and IL-12 (63.9 ± 20.1 pg/mL, 64.9 ± 14.1 pg/mL) secretion, which showed significant differences with model group (612 ± 72.3 pg/mL, 230.1 ± 29.2 pg/mL), but still higher than normal group (361.8 ± 47.1 pg/mL, 34.2 ± 15.1 pg/mL) and lower than positive group (418.1 ± 42.5 pg/mL, 90.2 ± 17.8 pg/mL). Especially, when the concentration of SCP was 125 μg/mL, the contents of IL-6 (431.1 ± 43.3 pg/mL, 401.7 ± 55.7 pg/mL) and IL-12 (63.2 ± 12.3 pg/mL, 52.3 ± 8.7 pg/mL) were lowest. DISCUSSION AND CONCLUSION: These findings demonstrate that SCP have excellent anti-RA activities and thus have great potential as a drug for treating RA diseases.
22203216 Magnetic resonance imaging (MRI) detection of synovitis and bone lesions of the wrists and 2012 Sep OBJECTIVE: To explore whether synovitis and bone lesions in the wrists and finger joints visualized by plain magnetic resonance imaging (MRI)-based findings correspond exactly or not to those judged by gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI-based findings. METHODS: Magnetic resonance imaging of the wrists and finger joints of both hands were examined in 51 early-stage rheumatoid arthritis (RA) patients whose median disease duration from the onset of articular manifestations to entry was 5 months, by both plain (T1 and short-time inversion recovery images) and Gd-DTPA-enhanced MRI (post-contrast fat-suppressed T1-weighted images) simultaneously. We focused on 15 sites per hand, to examine the presence of synovitis and bone lesions (bone edema and bone erosion). Gd-DTPA-enhanced MRI-based findings were considered "true" lesions, and we evaluated the accuracy of plain MRI-based findings in comparison to Gd-DTPA-enhanced MRI-based findings. RESULTS: Synovitis, judged by plain MRI-based findings, appeared as false-positive at pretty frequency; thus, the specificity, positive predictive value and accuracy of the findings were low. The rate of enhancement (E-rate) in false-positive synovitis sites was significantly low compared with true-positive synovitis sites where Gd-DTPA enhancement appears. In contrast to synovitis, the false-positivity of bone lesions, judged by plain MRI-based findings, was very low compared with Gd-DTPA-enhanced MRI-based findings. CONCLUSION: Synovitis judged by plain MRI-based findings is sometimes considered false-positive especially in sites where synovitis is mild. However, plain MRI is effective in identifying bone lesions in the wrist and finger joints in early-stage RA.
22618411 Major depressive disorder in patients with rheumatoid arthritis. 2013 Mar OBJECTIVE: To investigate the point prevalence of major depressive disorder (MDD) as diagnosed by the Mini-International Neuropsychiatric Interview (M.I.N.I) in patients with rheumatoid arthritis (RA) and to determine whether MDD is related to features of RA disease, such as disease activity or physical dysfunction. METHODS: Of the patients with RA who participated in the IORRA survey conducted in October 2005, 162 were evaluated using the M.I.N.I., the Center for Epidemiologic Studies-Depression (CES-D) scale, and the two-question depression screen for MDD. RA clinical features were obtained from the concomitant IORRA cohort database. Relationships between MDD and RA disease features were analyzed by the Wilcoxon rank sum test and Pearson's chi-square test. RESULTS: The point prevalence of MDD as diagnosed by the M.I.N.I. was 6.8 % in our Japanese patients with RA. The percentage of depressive patients was determined to be 23.5, 17.3, or 7.4 % according to the CES-D scale with cut-off points of 16, 19, or 27, respectively, and 14.2 % according to the two-question depression screen. The best cut-off point for CES-D for risk of MDD diagnosed by M.I.N.I. in this study was determined to be 23, with 11.7 % depressive patients having the highest sum of sensitivity and specificity. No relationship between MDD and RA disease activity was detected. CONCLUSION: By using the well-established structural interview instrument M.I.N.I., we determined the point prevalence of MDD in the RA patients enrolled in this study to be 6.8 %, leading to the conclusion that concomitant MDD does not seem to influence disease activity in RA patients.
23164236 Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse 2012 Nov 19 INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations. METHODS: A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations. RESULTS: The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)). CONCLUSION: Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests additional association with a PADI2 gene. The study thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to RA development in multiple populations of Asian descent.
20401724 Pulmonary non-Hodgkin's lymphoma developed during long-term methotrexate therapy for rheum 2012 Nov Methotrexate is effective in treating rheumatoid arthritis (RA). Some reports have discussed the possible association between methotrexate and lymphoma. Here, we report a case of pulmonary non-Hodgkin's lymphoma (NHL) developed after 11 years' methotrexate therapy for RA. Biopsy of the pulmonary mass demonstrated a diffuse large B-cell lymphoma. After withdrawal of methotrexate without any other intervention for 4 weeks, a significant reduction in the size of the lymphoma was observed. The causative relationship between methotrexate and pulmonary lymphoma is suggested by the persistent remission after stopping methotrexate therapy.
22392349 Relationship between CDT and disease activity in rheumatoid arthritis. 2012 Apr The aim of this study was to estimate the serum concentration of carbohydrate-deficient transferrin (CDT) in patients with rheumatoid arthritis (RA) and the relationship between the CDT level and disease activity in RA patients. Studies were carried out in 47 female patients with RA and 32 healthy women. Disease activity of RA was evaluated using the 28-joint count Disease Activity Score (DAS 28). Serum CDT was determined by particle-enhanced immunononephelometry using the N Latex CDT test. Patients with RA had significantly lower serum concentrations of CDT compared with controls. The correlation study showed the significant negative relationship between CDT and DAS 28 (r = - 0.483, p = 0.011). There were no correlations between serum CDT level and patient's age, disease duration, number of tender and swollen joints, and degree of disability evaluated by the Health Assessment Questionnaire. The level of CDT in patients with RA was significantly decreased and confirms the changes in transferrin glycosylation which are dependent on the disease activity. Therefore, measurement of CDT in the sera of patients with RA can be useful for the evaluation of disease activity in these patients.
22029973 The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic syn 2011 INTRODUCTION: Calprotectin (MRP8/MRP14, S100A8/A9) is associated with disease activity in patients with rheumatoid arthritis (RA). Ultrasonography (US) is a reliable method for evaluation of synovitis (B-mode (BM) and power Doppler (PD)). The present objectives were to explore in RA patients the associations between calprotectin and a comprehensive US examination, as well as the responsiveness of calprotectin compared to other inflammatory markers during anti-TNF treatment. METHODS: A total of 20 RA patients starting treatment with adalimumab were examined longitudinally by US (BM and PD (semi-quantitative scores 0 to 3) of 78 joints, 36 tendons/tendon groups and 2 bursae) and clinically at baseline and after 1, 3, 6 and 12 months. Associations between the US sum scores and the inflammatory markers calprotectin, serum amyloid A (SAA), CRP and ESR were explored by correlation and linear regression analyses, and the response to treatment was assessed by Standardized Response Mean (SRM). RESULTS: The inflammatory markers, clinical examinations and US sum scores improved during treatment (P < 0.001). Of the inflammatory markers, calprotectin had the highest correlation coefficients with the total BM and PD sum scores (median (range) 0.59 (0.37 to 0.76) for BM and 0.56 (0.38 to 0.72) for PD). Even higher correlations were found between calprotectin and sum US scores of reduced number of joint counts. Calprotectin made a considerable contribution to total US sum scores in the linear regression analyses (P = 0.001 to 0.031) and among the inflammatory markers, calprotectin had the highest SRM (0.84 at one month). CONCLUSIONS: Calprotectin was associated with the sum scores from a comprehensive US assessment and was responsive to change during anti-TNF treatment. Thus, examination of this leukocyte protein could be of additional value in the assessment of RA patients on biologic treatment.
21080353 Comparative study of the detection of joint injury in early-stage rheumatoid arthritis by 2011 Mar OBJECTIVE: To verify whether magnetic resonance imaging (MRI)-proven joint injury is sensitive as compared with joint injury determined by physical examination. METHODS: MRI of the wrist and finger joints of both hands was examined in 51 early-stage rheumatoid arthritis (RA) patients by both plain and gadolinium diethylenetriaminepentaacetic acid-enhanced MRI. Synovitis, bone edema, and bone erosion (the latter two included as bone lesions at the wrist joints); metacarpophalangeal joints; and proximal interphalangeal joints were considered as MRI-proven joint injury. Japan College of Rheumatology-certified rheumatologists had given a physical examination just before the MRI study. The presence of tender and/or swollen joints in the same fields as MRI was considered as joint injury on physical examination. The association of MRI-proven joint injury with physical examination-proven joint injury was examined. RESULTS: A total of 1,110 sites were available to be examined. MRI-proven joint injury was found in 521 sites, whereas the other 589 sites were normal. Physical examination-proven joint injury was found in 305 sites, which was significantly low as compared with MRI-proven joint injury (P = 1.1 × 10(-12) versus MRI). Joint injury on physical examination was not found in 81.5% of the sites where MRI findings were normal. Furthermore, an association of the severity of MRI-proven joint injury with that of joint injury on physical examination was clearly demonstrated (P = 1.6 × 10(-15), r(s) = 0.469). CONCLUSION: Our present data suggest that MRI is not only sensitive but accurately reflects the joint injury in patients with early-stage RA.
22116525 Undifferentiated connective tissue disease in a rheumatology center in Cali, Colombia: cli 2013 Apr The aim of the study is to evaluate the clinical and serological features of patients with undifferentiated connective tissue disease (UCTD) of a rheumatology referral center in Cali, Colombia, who were followed for a year. A retrospective analysis of a cohort of patients with an initial diagnosis of UCTD and monitoring for at least 12 months was carried out. A total of 94 patients with UCTD (97.9% women) were evaluated, with an average follow-up of 51 ± 35.7 months. Only 13 patients (13.8%) evolved into a defined connective tissue disease (CTD), of which 8.5% (n:8) developed systemic lupus erythematosus (SLE), 4.2% (n:4) Sjögren syndrome (SS) and 1.1% (n:1) rheumatoid arthritis (RA). A mean period of 35.8 ± 29.2 months between UCTD diagnosis and definite develop of a CTD was found. Arthritis, Raynaud's phenomenon and photosensitivity were statistically significant (<0.001) for development of CTD. After a mean follow-up of 4.25 years, most of the patients with UCTD showed a favorable evolution. Arthritis, Raynaud's phenomenon and the presence of photosensitivity were predictors for the development of CTD. It requires a consensus to establish criteria for the classification of UCTD.
21947370 Mechanistic modeling of antigen sink effect for mavrilimumab following intravenous adminis 2012 Aug Mavrilimumab is a fully human monoclonal antibody that binds to granulocyte-macrophage colony stimulating factor receptor α (GM-CSFRα) with high affinity and specificity and has potential application in various inflammatory diseases. The objective of this investigation was to develop a mechanistic population model to characterize the pharmacokinetics of mavrilimumab, the GM-CSFRα-mediated clearance, and receptor occupancy following single intravenous dosing to patients with rheumatoid arthritis. The internalization rate of mavrilimumab-GM-CSFRα complex was fixed to a value determined from quantitative confocal fluorescent imaging. The estimated typical first-order clearance and the central and peripheral distribution volumes were 3.79 mL/kg/d, 39.6 mL/kg, and 50.3 mL/kg, respectively. The systemic GM-CSFRα expression level was estimated to be 0.0782 nM, and the equilibrium dissociation constant (0.103 nM) was in good agreement with the monovalent affinity determined by surface plasmon resonance. By fitting to the observed pharmacokinetic data, the mechanistic model predicted that systemically greater than 90% GM-CSFRα blockade by mavrilimumab was achieved and maintained up to 4, 7, and 11 weeks following single 1-, 3-, and 10-mg/kg administrations, respectively. Posterior visual predictive check and bootstrapping suggest that the mechanistic model is reasonably robust and can be used to predict mavrilimumab exposure under various scenarios for future clinical trial design.
22193331 Multi-response model for rheumatoid arthritis based on delay differential equations in col 2012 Feb Collagen-induced arthritis (CIA) in mice is an experimental model for rheumatoid arthritis, a human chronic inflammatory destructive disease. The therapeutic effect of neutralizing the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) by an antibody was examined in the mouse disease in a view of deriving a pharmacokinetic/pharmacodynamic (PKPD) model. In CIA mice the development of disease is measured by a total arthritic score (TAS) and an ankylosis score (AKS). We present a multi-response PKPD model which describes the time course of the unperturbed and perturbed TAS and AKS. The antibody acts directly on GM-CSF by binding to it. Therefore, a compartment for the cytokine GM-CSF is an essential component of the mathematical model. This compartment drives the disease development in the PKPD model. Different known properties of arthritis development in the CIA model are included in the PKPD model. Firstly, the inflammation, driven by GM-CSF, dominates at the beginning of the disease and decreases after some time. Secondly, a destructive (ankylosis) part evolves in the TAS that is delayed in time. In order to model these two properties a delay differential equation was used. The PKPD model was applied to different experiments with doses ranging from 0.1 to 100 mg/kg. The influence of the drug was modeled by a non-linear approach. The final mathematical model consists of three differential equations representing the compartments for GM-CSF, inflammation and destruction. Our mathematical model described well all available dosing schedules by a simultaneous fit. We also present an equivalent and easy reformulation as ordinary differential equation which grants the use of standard PKPD software.
21660511 [Primary treatment of complicated flexor tendon injuries of the hand]. 2011 Jun Complicated flexor tendon injuries are classified into lacerations, avulsions, ruptures, and defects. They are often a challenge for hand surgeons and frequently they present unsatisfactory functional results postoperatively. Lacerations and avulsions are usually treated by pull-out sutures and suture anchors. In ruptures, the causality should be sought. Tendon-linking, transposition and tenodesis/arthrodesis are the domain of rheumatoid arthritis. The primary transplantation of tendons is rarely indicated, ideally in non-contaminated flexor tendon defects in zones III-V with an uninjured surrounding soft tissue situation. Postoperative rehabilitation programs are very the same as in normal flexor tendon injuries.
21665247 The effect of TNF-alpha blocking therapy on lipid levels in rheumatoid arthritis: a meta-a 2011 Dec OBJECTIVES: Changes in the lipid profile have been described in patients with rheumatoid arthritis (RA) following therapy with tumor necrosis factor (TNF)-alpha blocking agents. However, thus far, results have been inconsistent. Therefore, we investigated changes in lipid levels after TNF-alpha blocking therapy using meta-analysis of published data. METHODS: The literature was searched to identify studies assessing changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, triglycerides, atherogenic index (ie, TC/HDLc ratio), and apolipoprotein levels in response to TNF-alpha blocking therapy. Weighted mean levels of lipids at different time points and subsequent changes in these lipid levels between these time points were calculated with multivariate linear mixed models. RESULTS: Data were available on TC in 15 studies encompassing 766 RA patients and on HDLc in 14 studies encompassing 736 RA patients. TC increased significantly (maximum increase of 10%) and HDLc increased significantly in the first 2 to 6 weeks of therapy (maximum increase of 7%), after which it remained more or less stable. The atherogenic index did not significantly change over time. There was too limited information to evaluate changes in other lipids and apolipoproteins. CONCLUSIONS: TNF-alpha blocking therapy has a modest effect on TC and HDLc levels in RA patients with no significant overall effect on the atherogenic index. Whether TNF-alpha blocking effects on qualitative lipid changes (structure and function) are more relevant to their presumed vascular benefits requires further study.
22127333 Arterial dysfunction in patients with rheumatoid arthritis and the consumption of daily fr 2012 Mar BACKGROUND/OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased arterial dysfunction and increased risk of cardiovascular disease. Regular fruit and vegetable consumption prevents cardiovascular disease, but their influence on arterial dysfunction in RA has not been investigated. We assessed the relationship between daily fruit-vegetable consumption and arterial dysfunction in this high-risk group. SUBJECTS/METHODS: Participants were recruited from a consecutive series of RA patients aged 40-65 years without overt cardiovascular disease attending rheumatology clinics. Standardised research nurse assessment included SphygmoCor pulse wave analysis using radial applanation tonometry (a higher augmentation index (AIX%) indicates arterial dysfunction), fasting blood sample, patient questionnaire and medical record review. Multivariable analysis was used to adjust for age, sex, cholesterol, mean arterial blood pressure, smoking habit, alcohol consumption, physical activity, cumulative inflammatory burden, rheumatoid nodules, disability and education. RESULTS: We recruited 114 RA patients: 81% female, mean age 54 years, median arthritis duration 10 years and mean AIX% 31.5 (s.d. 7.7). Fruit and vegetable consumption were significantly correlated (Spearman's rho 0.54, P≪0.0001) and on unadjusted analysis daily fruit and vegetable consumption was associated with a lower AIX% (-3.2; 95% CI -6.4 to -0.1, P=0.05). On adjusted analysis AIX% was lower with daily vegetable (-4.2; 95% CI -7.9 to -0.5; P=0.003), but not with daily fruit (-0.02; 95% CI -3.9 to 3.8; P=0.99) consumption. CONCLUSIONS: Daily vegetable consumption, but not daily fruit consumption, was independently associated with more favourable arterial function in patients with RA. These findings are consistent with the enterosalivary circulation of nitrate having an influence on arterial function.
21501790 Elbow interposition arthroplasty. 2011 May End-stage elbow arthritis in young, active patients presents a challenging problem to the upper extremity surgeon. Total elbow arthroplasty is not a viable option in this population because of functional restrictions, limited implant survivorship, and the lack of an adequate salvage option. With the appropriate surgical indication, interposition arthroplasty can relieve severe pain, affording a functional elbow without severely proscribing permitted activities. In addition, bone stock is preserved, as are other reconstructive options for the future.