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ID PMID Title PublicationDate abstract
21371351 What have we learned from clinical trials in primary Sjögren's syndrome about pathogenesi 2011 Feb 28 In vitro and in vivo experimental data have pointed to new immunopathogenic mechanisms in primary Sjögren's syndrome (pSS). The availability of targeted treatment modalities has opened new ways to selectively target these mechanistic pathways in vivo. This has taught us that the role of proinflammatory cytokines, in particular TNFα, is not crucial in the immunopathogenesis of pSS. B cells appear to play a major role, as depletion of B cells leads to restoration of salivary flow and is efficacious for treatment of extraglandular manifestations and mucosa-associated lymphoid tissue lymphoma. B cells also orchestrate T-cell infiltration and ductal epithelial dearrangement in the salivary glands. Gene profiling of salivary gland tissue in relation to B-cell depletion confirms that the axis of IFNα, B-cell activating factor, B-cell activation, proliferation and survival constitutes a major pathogenic route in pSS.
21573036 Clinical, laboratory, and ultrasound assessment of the knee in juvenile rheumatoid arthrit 2011 Apr 25 BACKGROUND: The aim of this work was to study the ultrasonographic (USG) features of knee joints in relation to clinical and laboratory measures in patients with juvenile rheumatoid arthritis (JRA), and also to evaluate the accuracy of ultrasound in the diagnosis of local joint activity. METHODS: This study included 20 with JRA and 20 matched and apparently healthy controls. All patients were subjected to full history taking, careful clinical examination and laboratory investigation. The knee joints of all patients and control were examined with plain radiography and ultrasonography on the same day of clinical examination using ultrasound to detect synovial thickness and effusion at the knee. RESULTS: Mean USG knee synovial thickness was significantly greater in JRA patients versus controls (4.2 ± 2.4 mm versus 1.7 ± 0.3 mm, P < 0.001). Although knee effusion was not detected in any of the controls, it was demonstrated in 90% of JRA patients, with a mean effusion volume of 3.8 ± 3.1 mL. There was a statistically significant difference (P < 0.001) between clinically active and inactive knees with regard to knee synovial thickness. Mean knee effusion volume was significantly (P < 0.05) higher in the clinically active than in the clinically inactive knees. Patients with high disease activity had a significantly (P < 0.05) higher knee synovial thickness and knee effusion volume than patients with low and moderate disease activity. Significantly (P < 0.05) positive correlations were found between knee synovial thickness and articular index (AI) scores, disease activity score, clinical knee scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Significant positive correlations (P < 0.05) were found between knee effusion volume and AI scores, visual analog scores, disease activity scores, clinical knee scores, ESR, and CRP levels. Significant negative correlations (P < 0.05) were found between knee effusion volumes and hemoglobin levels. CONCLUSION: UGS-detected parameters represent a reliable index of JRA disease activity with a higher sensitivity for knee synovial thickness and higher specificity for knee effusion.
22469408 Magnetic resonance imaging of shoulder arthropathies. 2012 May The role of magnetic resonance imaging in evaluating shoulder arthropathies is evolving. This article reviews 4 of the major arthropathies: septic arthritis, rheumatoid arthritis, calcium pyrophosphate dihydrate (CPPD) deposition disease, and hydroxyapatite disease (HAD), with special attention to their magnetic resonance imaging features. Comfort with identifying these entities allows appropriate and prompt treatment, which is critical for joint preservation in the case of infection, for maximal therapeutic efficacy of disease-modifying drugs in the case of rheumatoid arthritis, and for expediting symptomatic relief in the cases of CPPD deposition disease and HAD.
23487410 The Agreement Between Blood Pool - Delayed Bone Scintigraphy and Tc-99m Human Immunoglobul 2011 Aug OBJECTIVE: In this study, it was aimed to investigate the agreement between early phase of bone scintigraphy - human immunoglobulin scintigraphy (EPBS-HIG) and late phase bone scintigraphy - HIG (LPBS-HIG) in the determination of the presence and also the severity of inflammatory arthritis. MATERIAL AND METHODS: Twenty-eight patients (23 female, 5 male; between 19 to 80 years of age) with inflammatory arthritis were included in the study. Tc-99m HIG and blood pool/late phase bone scintigraphies were performed in all patients. In scintigraphic examinations, the joints were scored with the degree of accumulation of the radiopharmaceutical by the semiquantitative analysis (0=Background activity, 1=Faint uptake, 2=Moderate uptake, 3=Marked uptake) which is called as visually active joint score as severity index of the disease. To estimate the agreement between EPBS - HIG and LPBS - HIG in the determination of the presence and severity of inflammatory arthritis, 2x2 kappa coefficients were calculated. RESULTS: Our results showed good agreement between EPBS - HIG for the presence of inflammation (kappa: 0.72) but not for the severity of the disease (kappa: 0.29), poor agreement between LPBS - HIG for both the presence (kappa: 0.51) and severity (kappa: 0.01) of inflammatory arthritis. CONCLUSION: The blood pool scintigraphy could be used in the investigation of the presence of inflammatory arthritis because the good agreement with HIG and the lower cost but not for the severity of the disease Conflict of interest:None declared.
22475284 Is it time for hepcidin to join the diagnostic toolkit for iron deficiency? 2012 Apr The diagnostic value of hepcidin, the master regulator of iron metabolism, as an index of iron status is being intensively investigated. van Santen et al. have reported the value of hepcidin as a test for iron deficiency in both noninflamed and inflamed anemic patients with rheumatoid arthritis. Their data show that serum hepcidin identifies iron deficiency in anemic rheumatoid arthritis patients. Based on these results, the authors offer cutoffs for hepcidin and propose an algorithm to diagnose iron deficiency in this setting. This study provides insight into the physiology of hepcidin regulation in patients with coexisting iron deficiency and inflammation.
22039306 α9β1 integrin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cel 2011 Dec 1 The interaction between matricellular proteins such as tenascin-C (TN-C) and osteopontin (OPN) and integrins has been implicated in the pathology of rheumatoid arthritis in which Th17 cells are recognized as primary pathogenic cells. The differentiation of Th17 cells is tightly regulated by cytokines derived from APCs, receiving various signals including TLR stimuli. In this study, we used a collagen-induced arthritis model and found that increased numbers of α(9) integrin-positive conventional dendritic cells and macrophage were detectable in the draining lymph node (dLN) shortly following first immunization, and these cells produced both TN-C and OPN, ligands for α(9) integrin. α(9) integrin-mediated signaling, induced by TN-C and OPN, promoted the production of Th17-related cytokines by conventional dendritic cells and macrophages in synergy with TLR2 and 4 signaling. This led to the Th17 cell differentiation and arthritis development. Moreover, Th17 cells generated under blocking of α(9) integrin-mediated signaling showed low level of CCR6 expression and impaired migration ability toward CCL20. Thus, we have identified α(9) integrin-mediated signaling by TN-C and OPN as a novel intrinsic regulator of pathogenic Th17 cell generation that contributes to the development of rheumatoid arthritis.
29539374 Ankylosis of wrist and small joints of the hand occurs in rheumatoid arthritis: Diagnostic 2012 Dec There are no universally accepted criteria for the paleopathological diagnosis of rheumatoid arthritis (RA). Recent clinical studies show that small joint ankylosis occur in RA at a low frequency (2%). Presence of small joint ankylosis in paleopathological material does therefore not allow one to exclude a diagnosis of RA provided no other bone changes suggestive of spondyloarthropathy are present.
21760803 Randomised double-blind trial of combination antibiotic therapy in rheumatoid arthritis. 2011 Objective. A combination of intravenous clindamycin and oral tetracycline has been used for many years as a treatment for active rheumatoid arthritis (RA), despite the absence of good evidence for its efficacy. A single-blind pilot study of this therapy suggested that a double-blind placebo-controlled trial was warranted. Methods. Patients with active RA were randomised in a 2 : 1 ratio to receive active treatment or placebo for 25 weeks. The active treatment consisted of intravenous clindamycin in a reducing regime, and oral tetracycline twice daily three times a week. 50 patients were to be recruited. The primary outcome measure was the proportion of patients achieving an ACR20 response. Results. An interim statistical analysis was performed after 20 patients had completed the study. Two patients in the active group achieved an ACR20 response, with none in the placebo group (NS). There was a better ESR20 response in the placebo group (P = .02). There were no other significant differences between the groups. The results indicated that it was unlikely that a significant difference in ACR20 response would emerge if the remaining 30 patients were recruited. The trial was therefore halted. Conclusion. This antibiotic regime is unlikely to be a valuable therapy for active rheumatoid arthritis.
23066434 Foot problems in a group of patients with rheumatoid arthritis: an unmet need for foot car 2012 OBJECTIVES: The aim of this study was to evaluate the foot involvement in a group of RA patients in regard to symptoms, type and frequency of deformities, location, radiological changes, and foot care. PATIENTS AND METHODS: A randomized selected 100 rheumatoid arthritis (RA) patients were recruited to the study. Data about foot symptoms, duration and location of foot pain, pain intensity, access to services related to foot, treatment, orthoses and assistive devices, and usefulness of therapies were determined by the questionnaire. Radiological changes were assessed according to modified Larsen scoring system. The scores of disease activity scale of 28 joints and Health Assessment Questionnaire indicating the functional status of RA patients were collected from patient files. RESULTS: A total of 100 RA patients (90 female, 10 male) with a mean age of 52.5 ±10.9 years were enrolled to the study. Eighty-nine of the 100 patients had experienced foot complaints/symptoms in the past or currently. Foot pain and foot symptoms were reported as the first site of involvement in 14 patients. Thirty-six patients had ankle pain and the most common sites of the foot symptoms were ankle (36%) and forefoot (30%) followed by hindfoot (17%) and midfoot (7%) currently. Forty-nine of the patients described that they had difficulty in performing their foot care. Insoles and orthopedic shoes were prescribed in 39 patients, but only 14 of them continued to use them. The main reasons for not wearing them were; 17 not helpful (43%), 5 made foot pain worse (12.8%), and 3 did not fit (7.6%). Foot symptoms were reported to be decreased in 24 % of the subjects after the medical treatment and 6 patients indicated that they had underwent foot surgery. Current foot pain was significantly associated with higher body mass index and longer disease duration, and duration of morning stiffness. The radiological scores did not correlate with duration of foot symptoms and current foot pain (p>0.05) but the total number of foot deformities was found to be correlated with Larsen scores (p<0.05). CONCLUSION: In our study, foot involvement and foot symptoms were seen frequently in RA but there is an unmet need for provision and monitoring of foot care in patients suffering from this chronic disease.
22474556 Fiberoptic intubation through a laryngeal mask airway as a management of difficult airwary 2012 Mar Patients with cervical spine instability and limited range of motion are challenge to anesthesiologists. It is important to consider alternatetive methods for securing the airway while maintaining neutral position and minimizing neck motion, because these patients are at increased risk for tracheal intubation failure and neurologic injury during airway management or position change. We experienced two cases that patients had cervical spine instability and severe limited range of motion due to the fusion of the entire cervical spine. One patient was a 6-year-old girl weighing 12.7 kg and had Klippel-Feil syndrome with Arnold-Chiari malformation, the other was a 24-year-old female weighing 31 kg and had juvenile rheumatoid arthritis. We successfully performed the intubation by using the fiberoptic intubation though a laryngeal mask airway in these two cases.
22279510 Synovial tissue response to treatment in rheumatoid arthritis. 2011 The recognition of the synovial tissue, as the primary target of inflammation in RA, has driven research in this field, not only to clarify the disease pathogenesis but also to evaluate local changes in response to treatment. Special interest has been given to the identification of sensitive synovial biomarkers that could be of help in demonstrating proof of principle in early stages of drug development. Synovial sublining macrophages have been shown to correlate with scores for disease activity in cross-sectional studies. Moreover, decreased disease activity as measured by the disease activity score evaluated in 28 joints (DAS28) after effective treatment, has consistently been associated with a reduction of the number of CD68+ synovial sublining macrophages across different therapies. This observation highlights a possible final common pathway in the mechanism of action of various therapies and supports the notion that macrophages have a central role in RA pathogenesis.When considering experimental therapies, the study of serial synovial biopsies in relatively small numbers of patients, in the context of proof of principle trials, successfully distinguished between effective and ineffective treatments. This attractive approach can be used during early drug development for screening proposes, supporting which new treatments have higher probability to be beneficial in a large scale clinical trial.In this paper we review the effects of RA treatments on the synovial tissue, including targeted therapies, with particular attention to their effect on synovial biomarkers.
22053161 "Delivering knowledge and advice": Healthcare providers' experiences of their interaction 2011 Rheumatic diseases are often chronic and involve a lifetime of suffering. The focus of rheumatology care is to support patients to manage their lives and master their disease. Healthcare providers and patients have different views on the consequences of living with rheumatic diseases and patients are reporting unmet healthcare needs. There is a need to integrate providers' perspective to develop the quality of rheumatology care. The aim was to explore healthcare providers' experiences of their interaction with patients in their management of RA. Interviews with 18 providers from different clinical settings were analysed in accordance with the grounded theory method. A core category; Delivering knowledge and advice was found to be the most important task and involved providing the patient with information about the disease and appropriate forms of treatment. Healthcare providers' attitudes and patients' responses influenced the outcome of the delivery of knowledge and advice and three dimensions emerged; completed delivery, adjusted delivery and failed delivery. There were differences in the providers' experiences in their interaction with patients as well as in reflections on their role as the delivering part. There could be difficulties in the interaction when patients' expectations and preferences were not taken into account when giving advice. These findings highlight the importance of developing rheumatology care, as no provider or patient benefits if the delivery of knowledge and advice becomes a failed delivery. The healthcare organization must acknowledge the difficulties involved in the interaction with patients in their management of RA and find methods to develop a more person-centred approach to care.
21403892 Rapidly evolving coronary aneurysm in a patient with rheumatoid arthritis. 2011 Feb 21 Coronary artery aneurysm (CAA) formation in the setting of an acute inflammatory state due to connective tissue disease is rare. We report a case of rapid progression from an ectatic to an aneursymatic left circumflex coronary artery leading to an acute coronary event in a patient with rheumatoid arthritis (RA). We report the accelerated growth of the aneurysm as it was temporally related to the lapse in treatment and the management strategies involved with this entity.
24653514 Clinical analysis of chinese patients with rheumatoid arthritis treated with leflunomide a 2012 Sep OBJECTIVE: To analyze the safety of combined leflunomide (LEF), methotrexate (MTX), and glucocorticoid (GC) therapy, we investigated the adverse effects of such combination therapy in patients with early active rheumatoid arthritis (RA). METHODS: Two hundred sixty-six patients with RA who were receiving LEF and MTX therapy were randomly assigned to 3 groups, as follows: group 1 received no GC, group 2 received 7.5 mg prednisone, and group 3 received 15 mg prednisone. Adverse effects were analyzed using the χ(2) test at week 4 or the Fisher exact test at week 12. RESULTS: Patients in group 1 had a higher incidence of skin rash, oral ulcers, leukopenia, and liver damage than did those in groups 2 and 3 (all, P ≤ 0.05). However, the rates of osteoporosis, diabetes, hyperlipidemia, and hypertension in group 3 were statistically higher than in groups 1 and 2 (P ≤ 0.05). CONCLUSION: In the treatment of RA, the incidence of skin rash, liver dysfunction, and oral ulcers may be decreased with combination therapy using LEF, MTX, and 7.5 mg prednisone, and blood pressure, blood glucose concentration, and bone density are not increased. Most important, 7.5 mg prednisone was synergistic with LEF and MTX, and such combination therapy could be a useful option as initial treatment of early active RA.
22279343 ANCA-associated Goodpasture's syndrome in a patient with rheumatoid arthritis on penicilla 2012 Jan Although penicillamine has been used effectively in the management of a variety of diseases, several adverse reactions have been observed with prolonged administration of this agent. We report a case of Goodpasture's syndrome, as a result of induction of anti-myeloperoxidase antineutrophil cytoplasmic antibodies in a 51 year old man who was being treated with this drug for rheumatoid arthritis. This pulmonary-renal syndrome has been described on rare occasions in patients receiving penicillamine. Treatment with steroids and cyclophosphamide resulted in pulmonary and renal functional recovery.
22081766 Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspecti 2011 Feb Biologicals revolutionized the treatment of Rheumatoid Arthritis (RA). The targeted suppression of key inflammatory pathways involved in joint inflammation and destruction allows better disease control, which, however, comes at the price of an elevated infection risk due to relative immunosuppression. The disease-related infection risk and the infection risk associated with the use of TNF-α inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol), rituximab, abatacept and tocilizumab are discussed. Risk factors clinicians need to take into account when selecting the most appropriate biologic therapy for RA patients, as well as precautions and screening concerning a number of specific infections, such as tuberculosis, intracellular bacterial infections, reactivation of chronic viral infections and HIV are reviewed.
22137029 A cholesterol and actinide dependent shadow biosphere of archaea and viroids in autoimmune 2012 Mar Endogenous digoxin has been related to the pathogenesis of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis. The possibility of endogenous digoxin synthesis by archaea with a mevalonate pathway and cholesterol catabolism was considered. 10 cases each of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis before starting treatment and 10 age and sex matched healthy controls from general population were chosen for the study. Cholesterol substrate was added to the plasma of the patients and the generation of cytochrome F420, free RNA, free DNA, polycyclic aromatic hydrocarbon, hydrogen peroxide, serotonin, pyruvate, ammonia, glutamate, cytochrome C, hexokinase, ATP synthase, HMG CoA reductase, digoxin and bile acids were studied. The changes with the addition of antibiotics and cerium to the patient's plasma were also studied. The statistical analysis was done by ANOVA. The parameters mentioned above were increased the patient's plasma with addition of cholesterol substrate. The addition of antibiotics to the patient's plasma caused a decrease in all the parameters while addition of cerium increased their levels. An actinide dependent shadow biosphere of archaea and viroids is described in multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis contributing to their pathogenesis.
22209352 Classification criteria for Sjogren's syndrome: a critical review. 2012 Aug Over the years, several different criteria sets have been proposed for the classification of Sjögren's syndrome (SS), but none of them has been widely adopted by the scientific community until the publication of the 1993 Preliminary European Classification criteria. These Classification criteria have been largely employed both in clinical practice and in observational and interventional studies for many years. In 2002 the Preliminary European Criteria were re-examined by a joint American and European Committee. The result of this revision were the American and European Consensus Group classification criteria (AECG-criteria) which introduced more clearly defined rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria. These AECG-criteria set is now considered to be valid to ensure a specific diagnosis of SS by the vast majority of the expert in the field. To date, the AECG-criteria have been cited more than 1.304 in literature and have been used to estimate the point prevalence of the disease in several studies conducted in Greece, UK, Turkey and Norway. However, when employed in epidemiologic studies or in daily practice, the AECG-criteria have demonstrated a higher specificity (75%), but a lesser sensitivity (65.7%) in comparison to the previous Preliminary European criteria, indicating an average prevalence of pSS at ~ 0.2% in the adult population, which is far lower than previously reported. In this paper we will critically analyse the "pro and cons" of the current AECG-criteria and of the potential usefulness of some potential revisions.
22859920 The role of biologic agents in damage progression in rheumatoid arthritis: indirect compar 2012 Aug OBJECTIVES: All biologic agents approved for the treatment of rheumatoid arthritis (RA) have been tested versus methotrexate (MTX) for efficacy on damage progression in several randomized clinical trials (RCTs), but direct head-to-head comparisons have never been conducted. The purpose of this investigation is to analyse data coming from main RA RCTs and to perform an indirect comparison. METHODS: A systematic review of literature from 1988 to 2011 was conducted. Only randomized, double-blind, controlled, comparative trials, with evaluation of radiographic progression were included. The radiographic score was standardized and mean difference in the percentage of the annual radiographic progression rate was used as the effect measure. Heterogeneity between studies was estimated by I(2) test. For each trial, the effect was plotted according to its standard error in a funnel plot. RESULTS: Of 44 potentially relevant trials, 12 RCTs were included in the study. In order to optimize RCTs comparison, studies were stratified in early and late RA group. Main population characteristics were similar in both early and late RA groups, whereas the standardized baseline radiographic score value significantly differs among trials in both early (range 2.7-21.9) and late (range 23.46-75) RA groups. The standardized annual estimated progression is similar across the late RA group. Strong evidence of heterogeneity (I(2) = 97%, p = 0.00001) but no asymmetry of the funnel plot was observed in the early RA group. Total mean difference was -16.28 (95% confidence interval [CI] -24.42 to -8.14). For the late RA group a random model was used (I(2) = 99%, p = 0.00001) and a total mean difference of -39.25 (95% CI -53.77 to -24.73) was found. CONCLUSIONS: All biologic agents provide a favourable effect on disease progression both in early and late RA. The significant heterogeneity among various RCTs did not allow an effective comparison of the performance of biologic agents in each study.
21607034 Radionuclide imaging with human polyclonal immunoglobulin (Tc-HIG) and bone scan in patien 2011 Jan BACKGROUND AND AIM: Rheumatoid arthritis (RA) is a chronic polyarthritic syndrome in which actively inflamed joints coexist with others being in remission. Compatible bone scan (BS) reveals joints with increased activity due to degenerative alterations, whilst scanning with human polyclonal immunoglobulin (HIG) is capable to show which of the joints present active inflammation of the synovial membrane. The aim of the study is to investigate the utility of molecular imaging with HIG in patients suffering from RA. PATIENTS AND METHODS: Forty patients (9 males plus 31 females), suffering from painful polyarthritic syndrome, with a mean age 45.3±7 years and a duration of disease 18.3±4.2 months were enrolled in the study. Twenty-six of the patients were serum positive to RA factor, considered as suffering from RA, whilst fourteen of them were RA factor negatives and they were considered as patients with serum-negative polyarthritis. All patients were submitted to x-rays and ultrasound examination (US) in joints of interest, plus whole body BS with (99m)Tc-MDP and finally scan with (99m)Tc-HIG. RESULTS: A total of 1680 joints have been evaluated. In 6 of the patients-two with serum negative RA (252 joints), radionuclide imaging with HIG was within normal limits, despite the fact that in compatible bone scan degenerative alterations have been mentioned in 30 joints. In all these patients disease was evaluated as inactive ("arthrotic changes"). In the remaining 34 patients-12 with serum negative RA (1428 joints), increased accumulation of HIG, concerning serum positive patients, has been mentioned to 163 joints ("arthritic changes"), whilst in the same group, BS revealed degenerative changes to 265 joints. Concerning serum negative patients, the respective results were 64 versus 190 joints. Increased uptake of HIG has been found in 189/226 swollen and painful joints (overall sensitivity according to clinical criteria 83.3%) and in 38 joints without any clinical evidence of inflammation, with clinical active inflammation presented after follow-up to 35 of them, yielding thus specificity at the level of 92%. Matched findings between these two methods have been mentioned to 185 out of 227 joints with an abnormal scan with HIG. Abnormal x-rays and US findings have been mentioned in 67 of the joints. CONCLUSIONS: According to the above mentioned, BS in RA reveals joints being actively inflamed or not, whilst radionuclide study with HIG is capable to distinguish actively inflamed joints, even in patients with serum negative RA, in a greater extent than anatomical imaging modalities.