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ID PMID Title PublicationDate abstract
21110028 A proposal of simple calculation (ERI calculator) to predict the early response to TNF-α 2012 Feb Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-α blocking agents. The formulation and definition of an early indicator of patient's reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.
19924229 Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immun 2009 Nov 17 BACKGROUND: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man. METHODS/PRINCIPAL FINDINGS: We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT). We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO). Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3) (0.95-5.1 x 10(-3)) % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion. CONCLUSIONS/SIGNIFICANCE: The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.
20559831 Birmingham hip resurfacing: five to eight year results. 2011 Aug Hip resurfacings have been performed in our hospital since May 2001, and in this retrospective study, we analysed the clinical and radiological outcome of the first 144 prostheses (126 patients). One hundred and seven patients have visited our hospital for regular follow-up examination; 16 are not in regular follow-up and were sent a Harris Hip Score (HHS) questionnaire. Three patients live abroad. Mean follow-up was six years. One patient was lost during follow-up. Four prostheses have been revised. The six year cumulative survival rate was 96.7%. Two female patients required revision for aseptic lymphocyte-dominated vascular associated lesions (ALVAL) and two male patients due for femoral head necrosis. Both reoperated female patients had cup inclination > 60°. Mean HHS in the follow-up was 95.3, and mean patient satisfaction 2.53 on a scale 0-3. Neck thinning > 10% was seen in seven hips and impingement in 12 hips.
21038033 Chemotherapy in severe nasal polyposis--a possible beneficial effect? A report of three ca 2010 Sep BACKGROUND: Nasal polyposis is an inflammatory process of the nasal mucosa. Treatment has changed from surgery to an anti-inflammatory approach, but neither of these treatments addresses the underlying cause. Topical steroids and occasional use of systemic steroids in patients with nasal polyposis can frequently control the polypoid disease. In a few cases, when the disease is more aggressive, the repeated application of systemic steroids together with sinus surgery is required. MATERIAL AND METHODS: We present our experience with one case of rheumatoid arthritis and two cases with malignant diseases, all of which were treated with chemotherapy and were also accompanied by severe nasal polyposis. All of our patients had eosinophilic polypoid disease. Various chemotherapeutic treatment schemes were utilized. RESULTS: During chemotherapy all three patients were markedly improved symptomatically including olfaction along with a significant reduction in their nasal polyposis. Duration of remission lasted for a few months in two cases and for three years, in a third case. CONCLUSION: This is the first report describing the successful treatment of severe nasal polyposis with chemotherapy. Based on this experience, we suggest a phase II trial with chemotherapy, preferably "low dose" methotrexate, in patients with severe nasal polyposis.
19473557 Ultrasound imaging for the rheumatologist. XX. Sonographic assessment of hand and wrist jo 2009 Mar In the rheumatology literature, most of the available evidence on three-dimensional ultrasound (3D US) is related to the acquisition process and highlights the virtual operator independence and shortening of the US examination time. The main aim of this study was to compare 3D US using a high-frequency volumetric probe and conventional 2D US at the wrist and hand in patients with rheumatoid arthritis (RA). The 3D US examinations were performed using a Logiq 9 (General Electrics Medical Systems, Milwaukee, WI) with a high-frequency (8-15 MHz) volumetric probe. Overall, there is good-to-excellent agreement between the two modalities relating to both joint inflammation and bone erosion. This study is an initial step towards establishing a methodology necessary for developing multi-centre US studies which are aimed at assessing hand involvement in patients with RA.
20386493 Polymorphisms within the folate pathway predict folate concentrations but are not associat 2010 Jun OBJECTIVES: To determine whether genetic polymorphisms within the folate pathway are associated with red blood cell (RBC) methotrexate (MTX) polyglutamate concentrations, RBC folate concentrations and MTX efficacy/toxicity. METHODS: Disease activity in 200 rheumatoid arthritis patients on MTX was assessed by swollen and tender joint counts and Disease Activity Score 28. Genetic polymorphisms shown to have an effect on gene expression or protein function were examined. RESULTS: RBC folate concentrations were significantly associated with MTHFR 677C>T (P=0.002), MTRR 66A>G (P<0.0001), MTHFD1 1958G>A (P=0.001) and SHMT 1420C>T (P=0.012), whereas no association of these polymorphisms with disease activity was observed. None of the polymorphisms tested predicted RBC MTX polyglutamate concentrations. There were weak associations between central nervous system adverse effects and AMPD1 34C>T (P=0.04) and between gastrointestinal adverse effects and MTHFD1 1958G>A (P=0.03) and ABCC2 IVS23+56T>C (P=0.045). There was a stronger association between any adverse effect and ABCG2 914C>A (P=0.004). CONCLUSION: Although RBC folate concentrations are associated with genetic polymorphisms within the folate pathway, these variants do not predict disease activity. To accurately evaluate whether any polymorphisms are reliable predictors of MTX efficacy or toxicity, large prospective clinical trials are required. Furthermore, application of a genome-wide association strategy is likely to uncover novel predictors of MTX response.
20472589 Assessment of cartilage loss at the wrist in rheumatoid arthritis using a new MRI scoring 2010 Nov OBJECTIVES: To develop and test an MRI cartilage scoring system for use at the wrist in rheumatoid arthritis (RA). METHODS: MRI scans were obtained using a 3T MRI scanner with dedicated wrist coil in 22 early and 16 established RA patients plus 22 controls. Axial and coronal T1-weighted (precontrast and postcontrast) and T2-weighted turbo spin echo sequences were obtained. Eight wrist joints were scored for cartilage narrowing: distal radioulnar, radiolunate, radioscaphoid, triquetrum-hamate, capitate-lunate, scaphotrapezoid, second metacarpal base-trapezoid and third metacarpal base-capitate, using a system based on the Sharp van der Heijde x-ray joint space narrowing (JSN) score by three radiologists. Fifteen sites at the wrist were also scored for synovitis, bone oedema and erosion using the RA MRI score. RESULTS: Interobserver (three-reader) and intraobserver reliability (readers 1 and 2) for the cartilage score were excellent: intraclass correlations (ICC (95% CI)) 0.91, (0.86 to 0.94), 0.98 (0.96 to 1.00) and 0.94 (0.87 to 1.00), respectively. Cartilage scores (median, range) were higher in the established RA group (11.9, 2.3-27.3) than the early RA group (2.15, 0-6) (p≤0.001) but early RA scores did not differ from healthy controls (2.3, 1-8.7). Cartilage scores correlated with synovitis (R=0.52), bone oedema (R=0.63) and erosion scores (R=0.66), p<0.001 for all, and with x-ray JSN scores (R=0.68 to 0.78). CONCLUSION: This MRI cartilage score demonstrated excellent reliability when tested in a three-reader system. However, cartilage loss in early RA could not be distinguished from that seen in healthy controls.
20570414 Epitrochlear and axillary lymph node visualization on FDG-PET/CT imaging in a patient with 2011 May An 38 year-old female with oral tongue cancer was referred for FDG-PET/CT scan for evaluating axillary lymph nodes and restaging malignancy. Bilateral uptake of axillary and epitrochlear lymph nodes were observed on PET/CT imaging. The uptake pattern was unexpected for the patient with this malignancy and she had a history of rheumatoid arthritis. Additionally, the wrists were included in the field of view and showed elevated FDG uptake. In this case report, we report benign axillary and epitrochlear tracer uptake on FDG-PET/CT scan in a patient with a history of rheumatoid arthritis.
20100795 Fibromyalgic rheumatoid arthritis and disease assessment. 2010 May OBJECTIVE: We evaluated fibromyalgic RA to determine its clinical impact, identification using core clinical assessments and influence identifying active disease using disease activity scores (DAS-28). METHODS: We examined the impact and identification using core clinical assessments (tender minus swollen joint counts) of fibromyalgic RA (> or =11 tender points) in initial (105 patients) and replicate (100 patients) cohorts. Receiver operator characteristic (ROC) curves optimized the cut-off points using tender minus swollen joint counts; their validity was confirmed in a routine practice cohort (321 patients). We evaluated whether fibromyalgic RA affected the identification of active disease using DAS-28 (> or =5.1) and the clinical disease activity index (CDAI). RESULTS: A total of 18/105 and 12/100 patients in initial and replicate cohorts, respectively, had fibromyalgic RA. This was identified by > or =7 tender minus swollen joint counts with 83% sensitivity and 80% specificity in the initial cohort (72 and 98% in replicate, respectively) and ROC area under the curve 0.80 (0.94 in replicate). 'Fibromyalgic' RA (tender point scores in initial and tender minus swollen joints in clinical practice cohorts) had higher DAS-28, pain, fatigue and HAQ scores. More fibromyalgic RA patients had active disease by DAS-28 (odds ratio 14.3; 95% CI 5.5, 37.1; and CDAI 17.2; 95% CI 6.1, 48.5); conventional assessments (three or more tender joints; three or more swollen joints; ESR > or =28 mm/h) showed no difference (1.75; 95% CI 0.72, 4.3). CONCLUSION: Fibromyalgic RA affects 12-17% of RA outpatients and results in worse functional outcomes. DAS-28 scores over-interpret active disease in fibromyalgic RA.
19551384 Successful resolution of pneumonia developed in a patient affected by Crohn's disease, rhe 2010 May Tumour necrosis factor alpha inhibitors, both infliximab and adalimumab, have been approved for the treatment of both rheumatoid arthritis and Crohn's disease. A slight increase in the risk of infections in patients receiving immunosuppressants and/or biological agents has been reported. Here, we present the case of a 68-year-old woman affected by Crohn's disease, myasthenia gravis, recurrent uveitis and rheumatoid arthritis who developed pneumonia during concomitant treatment with biological agents and conventional immunosuppressive drugs.
19118870 HLA class II and autoimmunity: epitope selection vs differential expression. 2009 Autoimmune diseases like rheumatoid arthritis (RA), multiple sclerosis, psoriasis and insulin-dependent diabetes mellitus are subject to a complex pathogenesis controlled by multiple genes and numerous environmental factors. The strongest genetic association is with certain HLA class II haplotypes and we here summarize the evidence supporting differential expression as a mechanism supporting the autoimmune process.
20067641 Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthriti 2010 Jan 12 BACKGROUND: Lactic acid-producing bacteria (LAB) probiotics demonstrate immunomodulating and anti-inflammatory effects and the ability to lessen the symptoms of arthritis in both animals and humans. This randomized, double-blind, placebo-controlled, parallel-design, clinical pilot trial was conducted to evaluate the effects of the LAB probiotic preparation, Bacillus coagulans GBI-30, 6086, on symptoms and measures of functional capacity in patients with rheumatoid arthritis (RA) in combination with pharmacological anti-arthritic medications. METHODS: Forty-five adult men and women with symptoms of RA were randomly assigned to receive Bacillus coagulans GBI-30, 6086 or placebo once a day in a double-blind fashion for 60 days in addition to their standard anti-arthritic medications. Arthritis activity was evaluated by clinical examination, the American College of Rheumatology (ACR) criteria, the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), and laboratory tests for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: Subjects who received Bacillus coagulans GBI-30, 6086 experienced borderline statistically significant improvement in the Patient Pain Assessment score (P = .052) and statistically significant improvement in Pain Scale (P = .046) vs placebo. Compared with placebo, Bacillus coagulans GBI-30, 6086 treatment resulted in greater improvement in patient global assessment and self-assessed disability; reduction in CRP; as well as the ability to walk 2 miles, reach, and participate in daily activities. There were no treatment-related adverse events reported throughout this study. CONCLUSIONS: Results of this pilot study suggest that adjunctive treatment with Bacillus coagulans GBI-30, 6086 LAB probiotic appeared to be a safe and effective for patients suffering from RA. Because of the low study population size, larger trials are needed to verify these results. TRIAL REGISTRATION: ACTRN12609000435280.
19877107 Out-of-pocket expenses and their burden in patients with rheumatoid arthritis. 2009 Nov 15 OBJECTIVE: To describe and understand the burden of out-of-pocket expenses in patients with rheumatoid arthritis (RA). METHODS: We studied out-of-pocket expenses and their burden in 8,545 US patients with RA. We determined direct medical costs, out-of-pocket expenses, the burden of out-of-pocket expenses, household income, and measures of RA severity and outcome. In addition, patients were classified into 3 groups based on the level of burden caused by out-of-pocket expenses: no or limited problem (I am able to pay the bills without much problem); moderate problem (paying the bills takes away some money I need for other activities); and a great problem (I can't purchase all of the medications or medical care that I need). RESULTS: A total of 43.6% of patients reported problems paying medical bills after insurance payments and 9.0% reported severe or great problems. Problems with expenses were associated with measures of RA severity, but also and particularly with lower household income and absence of health insurance. The proportion of household income that was consumed by out-of-pocket spending for the 3 groups was 2.4%, 7.2%, and 19.2%, respectively, and the percentage of patients meeting the 185% poverty level for these groups was 12.3%, 24.4%, and 51.3%, respectively. CONCLUSION: The out-of-pocket burden is substantial, particularly in those <65 years of age. Out-of-pocket expenses exert their severity predominantly on those with the most severe RA who have the least ability to pay. Household income is the primary determinant of out-of-pocket burden, followed by RA severity, and type of health insurance.
20736134 Paricalcitol, a synthetic vitamin D analog: a candidate for combination therapy with biolo 2010 Dec Biologic agents, especially TNFα inhibitors, appear to be very effective in treatment of rheumatoid arthritis (RA). Although the use of biologic agents has greatly improved the therapeutic efficacy in management of RA, biologic therapies for RA treatment have several limitations. These agents fail to achieve complete remission in substantial portion of RA patients. Also certain adverse events have been observed, including serious bacterial infections and reactivation of latent tuberculosis. Previous reports demonstrated that TNFα inhibitors are more efficacious in combination with other drugs such as methotrexate. In this report, we suggest that paricalcitol, a synthetic vitamin D analog is another candidate molecule for combination therapy with TNFα inhibitors in RA.
20444756 Explaining the cardiovascular risk associated with rheumatoid arthritis: traditional risk 2010 Nov BACKGROUND: Cardiovascular (CV) disease has a major impact on patients with rheumatoid arthritis (RA), however, the relative contributions of traditional CV risk factors and markers of RA severity are unclear. The authors examined the relative importance of traditional CV risk factors and RA markers in predicting CV events. METHODS: A prospective longitudinal cohort study was conducted in the setting of the CORRONA registry in the USA. Baseline data from subjects with RA enrolled in the CORRONA registry were examined to determine predictors of CV outcomes, including myocardial infarction, stroke or transient ischemic attack. Possible predictors were of two types: traditional CV risk factors and markers of RA severity. The discriminatory value of these variables was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) in logistic regression. The authors then assessed the incidence rate for CV events among subjects with an increasing number of traditional CV risk factors and/or RA severity markers. RESULTS: The cohort consisted of 10 156 patients with RA followed for a median of 22 months. The authors observed 76 primary CV events during follow-up for a composite event rate of 3.98 (95% CI 3.08 to 4.88) per 1000 patient-years. The c-statistic improved from 0.57 for models with only CV risk factors to 0.67 for models with CV risk factors plus age and gender. The c-statistic improved further to 0.71 when markers of RA severity were also added. The incidence rate for CV events was 0 (95% CI 0 to 5.98) for persons without any CV risk factors or markers of RA severity, while in the group with two or more CV risk factors and three or more markers of RA severity the incidence was 7.47 (95% CI 4.21 to 10.73) per 1000 person-years. CONCLUSIONS: Traditional CV risk factors and markers of RA severity both contribute to models predicting CV events. Increasing numbers of both types of factors are associated with greater risk.
19194706 Expression and citrullination of keratin in synovial tissue of rheumatoid arthritis. 2009 Sep Keratin is the main component of cellular intermediate filaments, and its post-translational modification plays an important role in cell differentiation and apoptosis, as well as disease states. The conversion of peptidylarginine to citrulline, termed citrullination, is particularly involved in the pathogenesis of rheumatoid arthritis (RA). Immunohistochemistry using an antibody mixture that broadly recognized various keratin forms detected cytokeratin in many cells in the area lining the synovial membrane of RA. Furthermore, double immuno-florescent labeling showed that the cells expressing cytokeratin were also positive for citrulline when they were in the vicinity of extracellular deposits or approached the exterior of the synovial membrane. Western blot analysis demonstrated citrullination of keratin purified from RA synovial tissue by immuno-precipitation. The above results indicate the presence of citrullinated cytokeratin in synovial membranes in RA.
19404004 [Application of NFkappaB inhibitor for arthritis]. 2009 Apr Recent progress in DNA technologies has provided the strategies to regulate the transcription of disease-related genes in vivo using antisense oligodeoxynucleotide (ODN). Transfection of cis-element double-stranded oligodeoxynucleotides (decoy ODNs) has been reported as a new therapeutic tool of anti-gene strategies for gene therapy. In the field of arthritis, decoy ODNs strategies have been significant therapeutic potential. The concept of regulation the disease related gene expression at the level of transcriptional factor may be more therapeutic effects compared with monotherapy in arthritis. Injection of NFkappaB decoy ODN into the affected joint resulted in marked suppression of joint destruction in CIA models. In vitro studies demonstrated that the inhibitory effect on inflammatory cytokines and matrix metalloproteinase production from stimulated synovial cells derived from rheumatoid arthritis patients. NFkappaB decoy ODN inhibited induction of osteoclasts and bone resorption ability. Parthenolide is one of the main sesquiterpense lactones responsible for the bioactivities of feverfew and recently reported to inhibit NFkappaB activation. Parthenolide has ameliorated the severity of joint destruction in experimental animal model. Based upon these findings, NFkappaB may be one of important therapeutic target for arthritis.
20806736 Evaluation of the stomatognathic system in patients with rheumatoid arthritis according to 2010 Jul The aim of this study was to investigate the clinical features of stomatognathic dysfunction in patients with rheumatoid arthritis (RA). The study sample consisted of 40 patients with RA (34 female, 6 male), mean age 44 years, recruited at the Rheumatology Division of the Department of Internal Medicine, University of Pisa, Italy. The inclusion criteria were diagnosis of RA according to the criteria of the American Rheumatism Association (ARA). In the study, 82.5% (n=33) of patients affected by RA satisfied at least the criteria of one diagnosis of temporomandibular disorders (TMD), according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The results are in agreement with the literature and the prevalence of such involvement ranges between 53% and 94% of patients. Several studies reported an involvement of the stomatognathic system in RA. In fact, RA can affect the temporomandibular joint as much as any other synovial joint. A more thorough analysis is required for a multidisciplinary approach to gnathological patients, including assessment by a rheumatologist. This issue and its epidemiologic relevance need further scientific research. Dentistry has a fundamental role in this process since patients who present with a systemic disease such as RA can be recognized and intercepted and referred to medical specialists, i.e., rheumatologists, to provide a diagnosis and therapy.
20505635 Portuguese guidelines for the use of biological agents in rheumatoid arthritis - March 201 2010 Jan The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).
19797510 Proinflammatory cytokines synergistically enhance the production of chemokine ligand 20 (C 2009 Nov OBJECTIVE: Chemokine ligand 20 (CCL20) is a selective ligand for chemokine receptor 6 (CCR6). We investigated, both in vitro and in vivo, whether CCL20 is critically involved in the disease process of rheumatoid arthritis (RA). METHODS: In vitro study investigated the effect of proinflammatory cytokines and biologic disease-modifying antirheumatic drugs (DMARD) on the production of CCL20 by rheumatoid fibroblast-like synovial cells (FLS). The in vivo role of CCL20 was studied by screening for serum CCL20 concentration in patients with RA during the therapeutic course of biologic DMARD, i.e., infliximab, etanercept, and tocilizumab. RESULTS: Spontaneous CCL20 production from rheumatoid FLS was minimal; however, its production was significantly stimulated by interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), or IL-17. IL-1beta was the most potent for stimulating the production of CCL20. CCL20 production was synergistically augmented by a combination of IL-1beta, TNF-alpha, and IL-17. In contrast, interferon-gamma suppressed IL-1beta-induced CCL20 production. IL-6, in combination with soluble IL-6 receptor (sIL-6R), did not modulate CCL20 production, whereas IL-1beta-induced, TNF-alpha-induced, and IL-17-induced production were increased by IL-6. These production levels were clearly suppressed by biologic DMARD in vitro. Serum CCL20 was significantly higher in RA than in control subjects, and was clearly decreased by the treatment with infliximab, etanercept, and tocilizumab. CONCLUSION: Proinflammatory cytokines modulate the production of CCL20 from FLS. Our data suggest that therapeutic efficacy of biologic DMARD may result from the inhibition of CCL20 production in rheumatoid synovium.