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ID PMID Title PublicationDate abstract
25009076 Anti-cyclic citrullinated peptide (CCP) antibody in patients with wood-smoke-induced chron 2015 Jan Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group (p = 0.03) and controls (p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls.
25267259 Targeted exon sequencing fails to identify rare coding variants with large effect in rheum 2014 Sep 30 INTRODUCTION: Although it has been suggested that rare coding variants could explain the substantial missing heritability, very few sequencing studies have been performed in rheumatoid arthritis (RA). We aimed to identify novel functional variants with rare to low frequency using targeted exon sequencing of RA in Korea. METHODS: We analyzed targeted exon sequencing data of 398 genes selected from a multifaceted approach in Korean RA patients (n = 1,217) and controls (n = 717). We conducted a single-marker association test and a gene-based analysis of rare variants. For meta-analysis or enrichment tests, we also used ethnically matched independent samples of Korean genome-wide association studies (GWAS) (n = 4,799) or immunochip data (n = 4,722). RESULTS: After stringent quality control, we analyzed 10,588 variants of 398 genes from 1,934 Korean RA case controls. We identified 13 nonsynonymous variants with nominal association in single-variant association tests. In a meta-analysis, we did not find any novel variant with genome-wide significance for RA risk. Using a gene-based approach, we identified 17 genes with nominal burden signals. Among them, VSTM1 showed the greatest association with RA (P = 7.80 × 10-4). In the enrichment test using Korean GWAS, although the significant signal appeared to be driven by total genic variants, we found no evidence for enriched association of coding variants only with RA. CONCLUSIONS: We were unable to identify rare coding variants with large effect to explain the missing heritability for RA in the current targeted resequencing study. Our study raises skepticism about exon sequencing of targeted genes for complex diseases like RA.
23836530 Prophylaxis for latent tuberculosis infection prior to anti–tumor necrosis factor therap 2013 Nov OBJECTIVE: To determine if low-risk elderly patients with rheumatoid arthritis (RA) who screen positive for latent tuberculosis (TB) infection prior to anti–tumor necrosis factor (anti-TNF) therapy should be given isoniazid (INH). METHODS: A Markov model was developed. The base case was a patient age 65 years with RA starting anti-TNF therapy with a positive tuberculin skin test (TST) finding of 5–9 mm, who was born in a country with low TB prevalence and had no other TB risk factors. The decision was 9 months of INH or not. The primary outcome was quality-adjusted life expectancy. Multiple sensitivity analyses were performed. RESULTS: No prophylaxis was favored, with a gain of 1.1 quality-adjusted life days, but the decision was sensitive to several variables. Prophylaxis was favored for patients ages <61 years, if the relative risk (RR) of TB reactivation with RA alone was >2.5, if the RR with anti-TNF therapy was >5.8, or if the utility associated with INH therapy was >0.98. Prophylaxis was also preferred for patients with a TST result >10 mm and for patients from higher risk countries. If 6 months of INH or 4 months of rifampin were used, prophylaxis was preferred, providing that therapy reduced the risk of TB reactivation by >47% and >27%, respectively. CONCLUSION: Withholding prophylaxis prior to anti-TNF therapy may be reasonable for low-risk elderly RA patients with a TST finding of 5–9 mm, although the decision is sensitive to patient preferences. For patients age <61 years from a higher risk country, or with a TST finding >10 mm, prophylaxis is preferred.
24200293 Pomegranate use to attenuate bone loss in major musculoskeletal diseases: an evidence-base 2013 Dec This review explores the effects of pomegranate on the pathogenesis of bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. A systematic review of the literature was conducted to identify the relevant studies on pomegranate and osteoporosis/osteoarthritis/rheumatoid arthritis. A comprehensive search was conducted in Medline and CINAHL for relevant studies published between the years 1946 to 2012. The main inclusion criteria were research articles published in English, studies had to report the association or effect of pomegranate and these bone and joint diseases: osteoporosis, osteoarthritis or rheumatoid arthritis. The literature search identified 35 potentially relevant articles, whereby 8 met the inclusion criteria. Two animal studies, two combinations of animal and in vitro studies, three in vitro studies and one human study were included in this review. All the studies reported positive effects of pomegranate extract or juice on osteoporosis, osteoarthritis and rheumatoid arthritis. This evidence-based review highlighted the potential of pomegranate extract being used for treating bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. Further studies are required to identify the active ingredients and molecular mechanisms before controlled human observational studies are conducted to provide stronger evidence.
24929023 Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a ra 2014 Aug The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Patients were randomized 1:1 to receive 500 ml of either H2-saline or placebo-saline, which was drop infused intravenously (DIV) daily for 5 days. The disease activity score in 28 joints (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks. Therapeutic effects of H2-saline on joint inflammation were estimated by measuring serum biomarkers for RA, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8-hydroxydeoxyguanosine (8-OHdG). In the H2-infused group, average DAS28 decreased from 5.18 ± 1.16 to 4.02 ± 1.25 immediately post infusion and reached 3.74 ± 1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo group throughout the study. IL-6 levels in the H2 group significantly decreased in 4 weeks by 37.3 ± 62.0% compared to baseline, whereas it increased by 33.6 ± 34.4% in the placebo group. TNFα levels did not change remarkably in the H2 or placebo groups in 4 weeks post-infusion compared to baseline. The relative ratio of 8-OHdG in the H2 group also significantly decreased by 4.7%. After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H2 group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H2 safely and effectively reduced RA disease activity.
24515410 Prediction of relapse after discontinuation of biologic agents by ultrasonographic assessm 2014 Oct OBJECTIVE: This prospective study aimed to determine whether the comprehensive ultrasonographic assessment of synovial inflammation predicts relapse after discontinuation of treatment with a biologic agent in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: RA patients in clinical remission (Disease Activity Score in 28 joints [DAS28] <2.6) receiving treatment with a biologic agent who agreed to discontinue the treatment were recruited. Patients underwent a comprehensive ultrasound scan on 134 synovial sites in 40 joints and were prospectively followed up for 6 months. Physicians who evaluated the patients during the study period were blinded to the baseline ultrasound findings. RESULTS: Forty-two patients receiving either a tumor necrosis factor antagonist or tocilizumab were enrolled. Using the optimal cutoff values determined by receiver operating characteristic curve analysis, relapse rates were significantly higher in patients whose total ultrasound scores at discontinuation were high than in those whose total ultrasound scores were low (P < 0.001 for both total gray-scale and power Doppler scores), whereas the difference between high and low DAS28 was not statistically significant (P = 0.158 by log rank test). Positive and negative predictive values were 80.0% and 73.3% for the total gray-scale score and 88.9% and 74.2% for the total power Doppler score, respectively. CONCLUSION: In RA patients in clinical remission receiving treatment with a biologic agent, residual synovial inflammation determined by comprehensive ultrasound assessment predicted relapse within a short term after discontinuation of the treatment. Our data provide a rationale and groundwork to conduct a large-scale study for establishment of ultrasound-based strategies to optimize the period of treatment with a biologic agent.
23669798 Assessing process of care in rheumatoid arthritis at McGill University hospitals. 2013 Jun OBJECTIVE: In rheumatoid arthritis (RA), quality indicators (QIs) are tools used to measure process of care. This study aimed to assess performance of selected QIs from the 2004 Arthritis Foundation's QI Set at 2 major sites of a university network of teaching hospitals. METHODS: The charts and electronic hospital records of 76 RA patients were audited to determine adherence to QIs. Logistic multivariate regression analyses were performed to investigate potential determinants of nonadherence and propose measures to facilitate better QI compliance, as a potential strategy towards RA care improvement. RESULTS: We identified consistent observance of QIs mandating prescription of disease-modifying antirheumatic drug therapy for all patients, drug adjustment with disease activity, prednisone tapering, and bisphosphonate therapy if indicated for patients on glucocorticoids. However, there was either lack of documentation or true inconsistent adherence to QIs dealing with radiograph performance, functional capacity assessment, and screening for hepatitis and tuberculosis before commencement of methotrexate and biologic agents, respectively. For the specific QIs analyzed, we did not find any definite independent associations with the studied variables. CONCLUSIONS: Our findings indicate that while there is frequent evidence for adherence to certain RA quality care standards at our centers, there is less compliance to others. Strategies to optimize the performance or documentation of those found most lacking, namely, functional capacity and screening for specific drug contraindications, could improve patient care. Radiographic disease monitoring, while lacking, may represent a move toward other more sensitive methods of RA progression detection, such as joint ultrasound. The inclusion of patient- and physician-derived information could help elucidate the reasons underlying nonadherence.
24042266 Acquired hemophilia in the patient suffering from rheumatoid arthritis: case report. 2013 Dec Acquired hemophilia is a severe bleeding diathesis caused by autoantibodies against a coagulation factor VIII (FVIII inhibitor). Massive bleeding diathesis, often life threatening are observed in almost 90% of patients. In 50-60% of cases, inhibitor emerges spontaneously. However, there are some conditions like pregnancy, puerperium, autoimmune disorders or cancers that seem to induce acquired hemophilia. We report a case of a 49-year-old woman suffering from rheumatoid arthritis (RA) for several years, who was diagnosed with acquired hemophilia in September 2011. The patient had been treated by steroids and leflunomide during the last few months. At the time of diagnosis, diffuse bruising of the forearms and the trunk was observed. The patient was treated with recombinant activated factor VII, and the first-line immunosuppressive therapy was introduced (cyclophosphamide and prednisone). We observed the elimination of symptoms and the disappearance of diathesis. Significant reduction of the titer of inhibitor was achieved, but only partial remission was obtained. It lasted until the beginning of December 2011, when the titer of the inhibitor increased again and massive bleeding to the left lower limb occurred. It was necessary to administer recombinant factor VIIa together with the second-line immunosuppressive therapy based on the Budapest protocol. The rapid reduction of the diathesis and improvement of the patient's general condition was achieved as previously. However, still there was no complete remission. After 2 weeks of treatment, the titer of inhibitor diminished, and factor VIII activity increased slightly. Because of RA, the patient was treated with methylprednisolone in maintenance doses during the next few weeks. Unfortunately, after over a month, the increase of inhibitor titer and the decrease of FVIII level were observed again. Some bruises appeared. It was necessary to increase doses of corticosteroids to therapeutic levels and add cyclophosphamide in low doses to prevent the appearance of more hemorrhagic diathesis. Partial remission was achieved a second time at the end of April 2012. The patient was given methylprednisolone with chloroquine as a maintenance treatment and the control of RA. The titer of the inhibitor increased again in June 2012, but there were no signs of diathesis. In August 2012, some bruises were detected, and we decided to add cyclophosphamide again instead of escalating the doses of methylprednisolone to prevent the occurrence of side-effects of corticosteroids. Cyclophosphamide was given with intervals only depending on activated partial thromboplastin time. No further diathesis was observed in spite of the lack of remission. We were forced to withdrawn cyclophosphamide completely in October 2012 because of signs of hematuria. Fortunately, right nephrolithiasis and urinary tract infection were the cause of that condition. These symptoms vanished after standard supportive treatment. Maintenance doses of corticosteroids and chloroquine were continued as the main treatment. The patient's condition was good, but the titer of inhibitor increased over the value that had been detected at the time of diagnosis, and some bruises appeared again at the end of January 2013. The decision to use rituximab as the next-line therapy was made. This anti-CD20 monoclonal antibody is primarily used in the management of lymphomas. However, it has been successfully applied in the management of various autoimmune conditions. The usual treatment regime involves four separate intravenous infusions of 375 mg/m each, administered at weekly intervals. At the time of admission to the hospital in the second half of February 2013, the titer of inhibitor was dangerously high, almost three times more than the initial level. Fortunately, only a few bruises were observed, and no bypassing agents were needed. The patient was given the whole-planned therapy. Concomitant continuation of maintenance doses of corticosteroids was necessary to enforce the effect of eradication of inhibitor because of high levels of its titer during rituximab administration. It prevented the patient from massive diathesis that might occur. The laboratory tests were improving during the next subsequent weeks after the last dose of rituximab. Over a month later, a significant decrease of the titer of inhibitor and an increase of factor VIII activity was observed. Probably, the laboratory tests will be improving during the next few weeks. The patient is in outpatient care now. She is treated with maintenance doses of corticosteroids and chloroquine as the main treatment of RA. We will try to withdraw corticosteroids unless it is not feasible to achieve complete remission. We will have to introduce another kind of immunosuppressive agent in case of recurrence.
24257366 Adaptive immunity in rheumatoid arthritis: anticitrulline and other antibodies in the path 2014 Jan PURPOSE OF REVIEW: To describe recent progress concerning rheumatoid arthritis (RA)-associated autoantibodies, in particular antibodies to citrullinated proteins antigens. RECENT FINDINGS: An increasingly diverse and RA-associated repertoire of antibodies has been defined over the last few years. These antibodies are preferentially, but not exclusively, reactive with posttranslationally modified antigens. Citrullinated antigens are the most common targets, but also other modifications including homocitrullination (carbamylation) are recognized. These antibodies display varying degrees of cross-reactivity, and both broadly cross-reactive and monoreactive antibodies are present. Progress, described in this review, has been made both concerning mechanisms behind the generation of these antibodies and concerning their effector functions. SUMMARY: Several different triggering mechanisms are involved in forming an antibody repertoire that evolves before the onset of clinical disease, and where antibodies with different specificities may interact directly or indirectly with target organs in causing different arthritis-associated symptoms. The increasing understanding of the role of adaptive and specific immunity in RA creates opportunities for a new generation of interventions.
25180052 A transient peak of infections during onset of rheumatoid arthritis: a 10-year prospective 2014 Sep 1 OBJECTIVES: The role of infection in rheumatoid arthritis (RA) has not been determined. We aimed to document the infectious burden and some aspects of antibacterial immunity in a large and prospective cohort study of RA patients in the early and late stages of the disease and in their relatives predisposed to RA. SETTING: Clinical and laboratory examination of all individuals enrolled in the study was performed in the Republican Clinical Hospital, Kazan, Russia. PARTICIPANTS: 376 patients with RA, 251 healthy first-degree relatives and 227 healthy controls without a family history of autoimmune disease (all females) were examined twice annually over more than 10 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The following parameters were investigated: type, duration and frequency of infections, bacterial colonisation and serum levels of IgG to bacteria, serum levels of total Ig, plasma cytokine levels, granulocyte reactive oxygen species production, lysozyme activity and phagocytosis. RESULTS: There were no significant differences in infection rate between healthy controls (median 14 days/year) and RA patients (13). However, infection rates were higher (p<0.001) in healthy relatives (53) and early stage patients (62), which groups also showed heavy bacterial skin colonisation. In contrast, late stage patients had fewer infection days (12; p<0.001) than healthy controls, although bacterial colonisation was still heavy. Phagocyte function and antibacterial antibody generation, together with compensatory cytokine production, were observed to be subnormal in the healthy relatives as well as in RA patients. CONCLUSIONS: We observed a marked increase in overall infections at the time of RA onset, and signs of a defective antibacterial defence mechanism, contrasting with fewer infections in the late RA stage. It can be speculated that frequent early infections initiate a compensatory immune hyper-reactivity which reduces the infection load while stimulating the development of RA in predisposed individuals.
25274241 Successful treatment with tocilizumab in a case of intralymphatic histiocytosis associated 2014 A 75-year-old woman with rheumatoid arthritis (RA) presented with long-term painful erythema on the right upper arm and left elbow. The patient was diagnosed with intralymphatic histiocytosis (ILH) based on the biopsy findings. Because the patient was unresponsive to single-agent treatment with methotrexate, infliximab and etanercept, we switched to tocilizumab (TCZ) treatment, which induced remission of the ILH. Our case suggests that TCZ may be a treatment option for ILH in patients with RA.
24163052 Headaches related to rheumatologic disease. 2013 Dec Headaches are a common, but under-recognized and understudied symptom in the context of the rheumatic diseases. They can result from intracranial pathology, such as parenchymal and meningeal inflammation, thrombosis, space-occupying lesions, and more. Inflammation, irritation, or degeneration of anatomically related structures such as the eyes, neck, and sinuses can equally cause headaches. In addition, patients with rheumatologic disorders have the same tendencies as the general population to develop primary headaches. While the latter are benign in nature, and generally require only symptomatic relief, the former type of headaches may signal disease manifestation, progression, or complication. Thus, familiarity with common and uncommon headache syndromes related to rheumatologic disorders as well as with their possible underlying disease processes and mechanisms is important. This will help to successfully develop an effective approach toward the evaluation of patients presenting with headaches in a rheumatologic context, and, ultimately, diagnose and treat potentially severe underlying disease.
25274902 Earlier time to remission predicts sustained clinical remission in early rheumatoid arthri 2014 Nov OBJECTIVE: To evaluate the prevalence and predictive factors of sustained remission in an early rheumatoid arthritis (ERA) population. Predictive factors of sustained remission in ERA are unknown. We hypothesized that a short time to remission is an important predictor of sustained clinical remission. METHODS: Patients in the Canadian Early Arthritis Cohort were included. Remission was defined by Boolean-based American College of Rheumatology/European League Against Rheumatism clinical trial and clinical practice definitions and Simplified Disease Activity Index (SDAI). Logistic regression analysis identified predictors of sustained remission and influence of time to remission. RESULTS: Of 1840 patients, 633 (34%) achieved clinical trial remission, 759 (41%) clinical practice remission, and 727 (39%) SDAI remission. Over half of those meeting remission criteria achieved sustained remission based on clinical trial (55%), clinical practice (60%), and/or SDAI (58%). Corticosteroid use and lack of initial disease-modifying antirheumatic drug (DMARD) were associated with decreased probability of sustained remission, while initial combination DMARD increased this probability. Female sex, greater pain, and longer time to first remission made sustained remission less likely. CONCLUSION: Female sex, greater pain, and lack of initial DMARD therapy reduced the probability of sustained remission. A shorter time to remission is related to sustainability and supports striving for early remission.
24562503 Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg phenotype in 2015 Jun OBJECTIVES: MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of patients with RA and their possible impact on Treg function and disease activity. METHODS: Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA expression was correlated with disease activity and expression of target genes. Interference with biological activity of miRNAs was evaluated in functional Treg assays. RESULTS: Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation was found in Tregs of RA patients. Diminution of miR-146a expression was observed in particular in patients with active disease, and correlated with joint inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory phenotype characterised by inflammatory cytokine expression. This was due to an augmented expression and activation of signal transducer and activator transcription 1 (STAT1), a direct target of miR-146a. CONCLUSIONS: Our results suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via increased STAT1 activation, and contributes thereby to RA pathogenesis.
23275019 Latent variable indirect response modeling of categorical endpoints representing change fr 2013 Feb Accurate exposure-response modeling is important in drug development. Methods are still evolving in the use of mechanistic, e.g., indirect response (IDR) models to relate discrete endpoints, mostly of the ordered categorical form, to placebo/co-medication effect and drug exposure. When the discrete endpoint is derived using change-from-baseline measurements, a mechanistic exposure-response modeling approach requires adjustment to maintain appropriate interpretation. This manuscript describes a new modeling method that integrates a latent-variable representation of IDR models with standard logistic regression. The new method also extends to general link functions that cover probit regression or continuous clinical endpoint modeling. Compared to an earlier latent variable approach that constrained the baseline probability of response to be 0, placebo effect parameters in the new model formulation are more readily interpretable and can be separately estimated from placebo data, thus allowing convenient and robust model estimation. A general inherent connection of some latent variable representations with baseline-normalized standard IDR models is derived. For describing clinical response endpoints, Type I and Type III IDR models are shown to be equivalent, therefore there are only three identifiable IDR models. This approach was applied to data from two phase III clinical trials of intravenously administered golimumab for the treatment of rheumatoid arthritis, where 20, 50, and 70% improvement in the American College of Rheumatology disease severity criteria were used as efficacy endpoints. Likelihood profiling and visual predictive checks showed reasonable parameter estimation precision and model performance.
23111637 Roles of Wnt signals in bone resorption during physiological and pathological states. 2013 Jan Osteoclasts, multinucleated giant cells, are responsible for bone resorption in physiological and pathological conditions such as osteoporosis and rheumatoid arthritis. Osteoclasts develop from the monocyte/macrophage lineage under the strict control of bone-forming osteoblasts. Osteoblast-lineage cells express two cytokines essential for osteoclast differentiation, colony-stimulating factor-1, and receptor activator of nuclear factor κB ligand (RANKL) and also express osteoprotegerin, a soluble decoy receptor for RANKL. The signaling molecule Wnt has been shown to be important for the differentiation of osteoblasts through β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. Recent studies have established that Wnt-mediated signals are also crucial for bone resorption in both physiological and pathological conditions. In this review, we introduce recent advances in roles of Wnt signaling in bone formation and bone resorption.
24659203 Factors affecting choice of open surgical techniques in elbow stiffness. 2014 Apr BACKGROUND: We analyzed the clinical outcomes of stiff elbow open treatment to assess factors affecting the choice of surgical procedures in a consecutive series of patients followed up prospectively. MATERIALS AND METHODS: Forty-one patients, mean aged 48 years, were evaluated. Elbow stiffness was caused by post-traumatic osteoarthritis in 32 patients, primary osteoarthritis in seven and rheumatoid arthritis in two. Stiffness was classified as mixed and extrinsic in 28 and 13 cases, respectively. Seventeen ulno-humeral arthroplasties (UHA), seven UHA with radiocapitellar replacement, six UHA with radial head replacement, ten total elbow replacement and one UHA with anconeus interposition were performed. Mayo Elbow Performance Score (MEPS), modified-American Shoulder and Elbow Surgeons (m-ASES) and Q-DASH scores were used for the pre- and post-operative evaluation. RESULTS: Mean follow-up was 25 months. The average increase in MEPS and m-ASES was 45 and 41, respectively. The average decrease in Q-DASH and the average increase in m-ASES pain were 43 and 21, respectively. The mean increase in flection, extension, pronation and supination was 29°, 25°, 18° and 17°, respectively. All the differences were statistically significant. CONCLUSIONS: Strictly customized open surgery of elbow stiffness, by taking into account the clinical value of each patient's pathoanatomical conditions, yields satisfactory functional results in majority of cases. In particular, the degree and site of elbow cartilage wear proved to be the factors affecting the choice of treatment most. Treatment should be aimed at removing the causes of pain and at recovering range of motion.
24499541 Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher co 2014 Feb 6 INTRODUCTION: Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease. METHODS: FC was measured in consecutive patients with SSc, primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and κ statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated. RESULTS: FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and κ = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects. CONCLUSIONS: FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced.
23515604 Is rheumatoid factor useful in primary care? A retrospective cross-sectional study. 2013 Jul Rheumatoid factor (RF) is frequently tested in general practice where its utility as a diagnostic test for rheumatoid arthritis (RA) is not known. We undertook a retrospective cross-sectioal study to determine the utility and cost of RF in a primary care population. We compared RF with recorded clinical features based on the American College of Rheumatology (ACR) criteria as a diagnostic test for RA in 235 patients in general practice using receiver operating characteristic curves and calculated the cost of testing per case of RA. We analysed 36,191 RF requests made to one laboratory from 2003-2009 at a mean annual cost of £58,164 and the variation and annual cost of RF testing between 77 practices. The sensitivity and specificity of RF at the optimal cut-off value of 20 U/ml were 0.6 and 0.96 and that of two documented clinical ACR criteria were 0.9 and 0.92, respectively. No ACR criteria were documented in 150 (63.8%) patients who had RF tested. The overall cost of RF testing per case of seropositive RA was £708.75. Of all RF requests, 66.6% was made by GPs, 7.0% by rheumatologists and 26.4% by other hospital departments. The proportion of positive tests was 5.8% in primary care and 17.7% in rheumatology. The mean number of tests performed annually in primary care was 4.65 (SD 2.7) per 1,000 patients. RF is less sensitive for RA than clinical features in primary care and is frequently requested in cases without clinical evidence of the disease, adding to the overall cost.
23532497 Serum levels of calreticulin in correlation with disease activity in patients with rheumat 2013 Jul OBJECTIVE: The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA). METHODS: Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative. RESULTS: Serum CRT levels in RA patients (4.817 ± 2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574 ± 0.942 ng/ml), SLE (4.013 ± 1.536 ng/ml), other autoimmune diseases (3.882 ± 0.837 ng/ml) and HC (3.726 ± 0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P < 0.01). CONCLUSION: Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.