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ID PMID Title PublicationDate abstract
24418764 Rheumatoid arthritis in 2013. Translational medicine in RA: time for change. 2014 Feb With every passing year, research on the pathogenesis of rheumatoid arthritis benefits from discoveries in other scientific fields. Three of the best examples that illustrate the benefit of such interdisciplinary bridges and the effects they have on our understanding of rheumatoid arthritis are presented here.
24396598 Capillaroscopy in psoriatic and rheumatoid arthritis: a useful tool for differential diagn 2013 Impairment of capillaries permeability and changes of microcirculation are associated with inflammatory arthritis. In order to demonstrate microvascular differences between psoriatic arthritis (PsA) and rheumatoid arthritis (RA) we analyzed capillaroscopic abnormalities such as megacapillaries, haemorrhages, ramifications, and avascular areas in patients affected by these two rheumatic disorders. Moreover to identify specific capillaroscopy patterns we analyzed the following parameters: venous limb diameter, arterial limb diameter, capillary loop diameter, amplitude of the capillary loop, linear density of capillaries (on 2 mm), and number of twisted capillaries (on 4 mm). Through a comparative morphometric analysis of capillaroscopy, our study demonstrated the presence of specific microvascular differences between PsA and RA providing an additional diagnostic tool for the differential diagnosis. We also suggest that capillaries structural abnormalities might reflect endothelial injury due to systemic inflammation during chronic arthritis.
24876781 Rheumatoid arthritis in Jordan: a cross sectional study of disease severity and associated 2014 Treating rheumatoid arthritis (RA) to target is advocated using disease activity measures. The impact of RA on the general health status of affected patients in Jordan is not well described. This study reported the severity of RA in Jordan and its association with consequent disabilities and comorbidities. A cross-sectional, observational study was conducted at King Abdullah University Hospital in the north of Jordan. All patients who were diagnosed with RA were included. Patients' demographics, comorbidities, disease activity score (DAS 28), and clinical disease activity index (CDAI) were collected. Both DAS 28 and CDAI were utilized to categorize RA disease activity. A total of 465 patients with RA were included: 82% were females; mean age ± standard deviation (SD) was 47.62±14.6 years; and mean disease duration ± SD was 6±4.45 years. The mean ± SD for the DAS 28 and CDAI was 5.1±1.5 and 23±14.2, respectively. According to the DAS 28, 51% of the patients were in the high disease activity category and only 5% were in remission. On the other hand, according to the CDAI, 44% were in the high disease activity category and only 1% were in remission. In Jordan, patients with RA have a high severe disease rate and a low remission rate. The disease is often progressive and associated with comorbidities that need to be managed.
24855620 Assessment of peripheral neuropathy in patients with rheumatoid arthritis who complain of 2014 Apr OBJECTIVE: To assess the prevalence of peripheral neuropathy in patients with rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the relationship between electrophysiological findings of peripheral neuropathy and clinical findings of RA. METHODS: Patients with a clinical diagnosis of RA and who had tingling or burning sensation in any extremity were electrophysiologically examined for evidence of peripheral neuropathy. Study parameters, including age, gender, laboratory parameters, duration of RA, and medication, were recorded. The symptoms and signs of neuropathy were quantified with the neuropathy symptom score, and the functional statuses of these patients were assessed. RESULTS: Out of a total of 30 RA patients, 10 (33%) had peripheral neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1 had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages of the patients with and without peripheral neuropathy were 69.4 and 56.5 years, respectively (p<0.05). A significant relationship was found between peripheral neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no relationship was found between peripheral neuropathy and the type of medication, RA duration, the patients' functional status, neuropathic symptoms, erythrocyte sedimentation rate, and C-reactive protein values. CONCLUSION: Neuropathic symptoms are common in RA patients, and it is difficult to distinguish peripheral neuropathy symptoms from those of arthritis. Patients with RA, particularly elderly patients and anti-CCP antibody positive patients who complain of neuropathic symptoms should undergo electrophysiological examination.
25414636 New insights into the impact of neuro-inflammation in rheumatoid arthritis. 2014 Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA.
25246804 Cost of tumor necrosis factor blockers per patient with rheumatoid arthritis in a multista 2014 BACKGROUND: The purpose of this study was to estimate the annual cost per treated patient for the tumor necrosis factor (TNF) blockers, etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA) patients covered by Medicaid. METHODS: The MarketScan Medicaid Multistate Database was used to identify adult RA patients who used etanercept, adalimumab, or infliximab (index agents) from 2007 to 2011. The index date was the first claim preceded by 180 days and followed by 360 days of continuous enrollment. Patients with other conditions for which these agents are approved by the US Food and Drug Administration were excluded. "Continuing" patients had one or more pre-index claim for their index biologic, and "new" patients did not. Cost per treated patient was calculated in the 360 day post-index period for each index agent as the total index drug and administration cost to the payer and the costs of switched-to agents divided by the number of patients who received the index agent. RESULTS: A total of 1,085 patients met the study criteria. Forty-eight percent received etanercept (n=521); 37% received adalimumab (n=405); and 15% received infliximab (n=159). Patient characteristics were similar across groups (mean age 47.4 years, 83% female). The annual cost per treated patient was lowest for etanercept ($18,466), followed by adalimumab ($20,983) and infliximab ($26,516). For all agents, annual costs were lower for new patients ($17,996 for etanercept, $18,992 for adalimumab, and $24,756 for infliximab) than for continuing patients ($19,004 for etanercept, $24,438 for adalimumab, and $28,127 for infliximab). CONCLUSION: Etanercept had lower costs per treated patient than adalimumab or infliximab in both new and continuing Medicaid enrollees with RA.
25035834 Rheumatoid arthritis: Nuclear Medicine state-of-the-art imaging. 2014 Jul 18 Rheumatoid arthritis (RA) is an autoimmune disease, which is associated with systemic and chronic inflammation of the joints, resulting in synovitis and pannus formation. For several decades, the assessment of RA has been limited to conventional radiography, assisting in the diagnosis and monitoring of disease. Nevertheless, conventional radiography has poor sensitivity in the detection of the inflammatory process that happens in the initial stages of RA. In the past years, new drugs that significantly decrease the progression of RA have allowed a more efficient treatment. Nuclear Medicine provides functional assessment of physiological processes and therefore has significant potential for timely diagnosis and adequate follow-up of RA. Several single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals have been developed and applied in this field. The use of hybrid imaging, which permits computed tomography (CT) and nuclear medicine data to be acquired and fused, has increased even more the diagnostic accuracy of Nuclear Medicine by providing anatomical localization in SPECT/CT and PET/CT studies. More recently, fusion of PET with magnetic resonance imaging (PET/MRI) was introduced in some centers and demonstrated great potential. In this article, we will review studies that have been published using Nuclear Medicine for RA and examine key topics in the area.
24765541 Yoga and Physical Rehabilitation Medicine: A Research Partnership in Integrative Care. 2013 Dec 7 Mind-body interventions, such as yoga, that teach stress management with physical activity may be well suited for investigation in both osteoarthritis and rheumatoid arthritis. In order to be considered as viable care options integrative studies need to offer a comprehensive design and include clinicians familiar with the disease process of the study populations. A review of the literature reveals a dearth of information related to the collaboration between yoga and physical rehabilitation medicine. This article discusses the collaboration with physical rehabilitation medicine to collect relevant pre- and post-intervention measures for an on-going pilot acceptability/feasibility yoga study for minority patients with osteoarthritis or rheumatoid arthritis. An interdisciplinary clinical research team selected psychosocial and physical measures for a community sample of bilingual minority patients, not typically identified as practicing yoga. Sixteen female adults aged 40-63 years (mean =51) completed baseline physical assessments using single leg stance, functional reach test, time up and go test, timed up from the floor test and the Disabilities of the Arm, Shoulder and Hand measures. Baseline values show an average level of functional ability prior to beginning the intervention. Preliminary results indicate some improvement; however, selected measures may not have the sensitivity and specificity needed to identify significant change. In this study, combining interdisciplinary perspectives enhanced the quality of the research study design. The experience of this interdisciplinary clinical research team opens the discussion for future collaborations.
24023512 Comparison of drug survival rates for tumor necrosis factor antagonists in rheumatoid arth 2013 BACKGROUND: Persistence of anti-tumor necrosis factor (TNF) therapy in rheumatoid arthritis (RA) is an overall marker of treatment success. OBJECTIVE: To assess the survival of anti-TNF treatment and to define the potential predictors of drug discontinuation in RA, in order to verify the adequacy of current practices. DESIGN: An observational, descriptive, longitudinal, retrospective study. SETTING: The Hospital Clínico Universitario de Valladolid, Valladolid, Spain. PATIENTS: RA patients treated with anti-TNF therapy between January 2011 and January 2012. MEASUREMENTS: Demographic information and therapy assessments were gathered from medical and pharmaceutical records. Data is expressed as means (standard deviations) for quantitative variables and frequency distribution for qualitative variables. Kaplan-Meier survival analysis was used to assess persistence, and Cox multivariate regression models were used to assess potential predictors of treatment discontinuation. RESULTS: In total, 126 treatment series with infliximab (n = 53), etanercept (n = 51) or adalimumab (n = 22) were administered to 91 patients. Infliximab has mostly been used as a first-line treatment, but it was the drug with the shortest time until a change of treatment. Significant predictors of drug survival were: age; the anti-TNF agent; and the previous response to an anti-TNF drug. LIMITATION: The small sample size. CONCLUSION: The overall efficacy of anti-TNF drugs diminishes with time, with infliximab having the shortest time until a change of treatment. The management of biologic therapy in patients with RA should be reconsidered in order to achieve disease control with a reduction in costs.
23223871 [Personalized medicine for rheumatoid arthritis : serological and clinical patient profile 2013 Feb Nowadays B and T-cell directed biologics in addition to TNF inhibitors are established as effective and safe treatment options for rheumatoid arthritis. As shown by the approval of rituximab for the treatment of systemic vasculitis, these drugs can also be useful for the treatment of other systemic autoimmune diseases; however, to optimize therapeutic strategies, predictive factors for treatment response as well as a good characterized safety profile are essential. So far implementation of real personalized medicine is not feasible in the field of rheumatology, but first biomarkers have already been identified and provide promising results. In this context, it has been shown that a B-cell directed therapy with rituximab is more effective in seropositive patients with rheumatoid arthritis. In addition, characterization of the cytokine milieu as well as of circulating and tissue infiltrating B and T-cell subsets might be useful for prediction of treatment response in the near future.
25481552 Mesenchymal stromal cells for treatment of arthritis. 2014 Aug Patients with refractory inflammatory arthritis can still respond favourable to autologous haematopoietic stem cell transplantation. However, this treatment has a high morbidity and even 5% mortality. Mesenchymal stromal cells (MSC), a subset of the non-haematopoietic stromal cells obtained from bone marrow, were found to have a strong immunosuppressive effect. MSC treatment is explored in many diseases like diabetes, SLE, MS and RA. This review covers all relevant literature regarding MSC treatment of inflammatory arthritis (RA and JIA). This review contains data of in vitro studies, animal studies and clinical studies. The following subjects will be discussed in detail: properties of MSC, presence of MSC in the joint, intra-articular versus intravenous route, autologous versus allogeneic, ideal source of MSC, distribution, transdifferentiation, engraftment, rejection, efficacy and toxicology. After reading this review the reader will be totally updated in this quickly evolving field of MSC therapy.
24126456 The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models o 2014 Mar OBJECTIVE: The histamine H4 receptor (H4R) has been shown to drive inflammatory responses in models of asthma, colitis and dermatitis, and in these models it appears to affect both innate and adaptive immune responses. In this study, we used both H4R-deficient mice and a specific H4R antagonist, JNJ 28307474, to investigate the involvement of the H4R in mouse arthritis models. METHODS: H4R-deficient mice and wild-type mice administered the H4R antagonist were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The impact on Th17 cells was assessed by restimulation of inguinal lymphocytes in the disease or immunisation models and with in vitro stimulation of whole blood. RESULTS: Both H4R-deficient mice and mice treated with the H4R antagonist exhibited reduced arthritis disease severity in both CAIA and CIA models. This was evident from the reduction in disease score and in joint histology. In the CIA model, treatment with the H4R antagonist reduced the number of interleukin (IL)-17 positive cells in the lymph node and the total production of IL-17. Th17 cell development in vivo was reduced in H4R-deficient mice or in mice treated with an H4R antagonist. Finally, treatment of both mouse and human blood with an H4R antagonist reduced the production of IL-17 when cells were stimulated in vitro. CONCLUSIONS: These results implicate the H4R in disease progression in arthritis and in the production of IL-17 from Th17 cells. This work supports future clinical exploration of H4R antagonists for the treatment of rheumatoid arthritis.
25442029 MR imaging assessment of arthritis of the knee. 2014 Nov The magnetic resonance (MR) imaging presentations of arthritis of the knee are important for radiologists to recognize because these disorders are often clinically unsuspected. When they are known or clinically suspected, knowledge of imaging features allows for the confirmation and characterization of the extent of disease. This article reviews the fundamental MR imaging manifestations of rheumatologic disorders of the knee and their presentation in specific arthropathies.
23763801 Juvenile rheumatoid arthritis. 2013 Jun OBJECTIVE: To determine the spectrum of clinical presentation, laboratory parameters and drug therapy in patients with Juvenile Rheumatoid Arthritis (JRA). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The Children's Hospital and The Institute of Child Health, Lahore, from October 2008 to October 2011. METHODOLOGY: All patients who fulfilled the American College of Rheumatology criteria for JRA were enrolled. Their clinical features, investigations done and treatment received for JRA were noted. Statistical analysis of data was done on SPSS version 16.0 for obtaining descriptive statistics. RESULTS: Out of 185 patients, 50.3% (n = 93) were females; 54% (n = 100) were between 10 - 15 years of age. Polyarthritis was found in 71.9% (n = 133) followed by oligoarthritis (22.7%, n = 42) and systemic onset disease (5.4%, n = 10). Morning stiffness (78%) and fever (68%) were the most common clinical presentations. All patients with systemic onset disease had fever (n = 10) followed by skin rash, hepatosplenomegaly and lymphadenopathy. Uveitis was found in 2 patients, and both belonged to the oligoarticular group. Rheumatoid factor was found in 10.27% (n = 19) of all patients. All patients were given non-steroidal anti-inflammatory drugs (NSAIDs). Disease modifying agents (methotrexate) were given to 43.8% (n = 81). Steroids were used in 61% (n = 113) of patients either with NSAIDs alone or NSAIDs plus methotrexate. CONCLUSION: Disease profile of JRA at the study centre showed that polyarthritis is the commonest type. Recognition of subtypes will help in planning the management of these patients.
23935647 Correlation of increased blood levels of GITR and GITRL with disease severity in patients 2013 Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is a type I transmembrane protein belonging to the TNFR superfamily. After activated by its ligand GITRL, GITR could influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases included rheumatoid arthritis and autoimmune thyroid disease. We previously reported that serum GITRL levels are increased in systemic lupus erythematosus (SLE) patients compared with healthy controls (HC). Here, we tested serum soluble GITR (sGITR) and GITRL levels in 41 primary Sjögren's syndrome (pSS) patients and 29 HC by ELISA and correlated sGITR and GITRL levels with clinical and laboratory variables. GITR and GITRL expression in labial salivary glands was detected by immunohistochemistry. pSS patients had significantly increased serum levels of sGITR and GITRL compared with controls (GITR: 5.66 ± 3.56 ng/mL versus 0.50 ± 0.31 ng/mL; P < 0.0001; GITRL: 6.17 ± 7.10 ng/mL versus 0.36 ± 0.28 ng/mL; P < 0.0001). Serum sGITR and GITRL levels were positively correlated with IgG (GITRL: r = 0.6084, P < 0.0001; sGITR: r = 0.6820, P < 0.0001) and ESR (GITRL: r = 0.8315, P < 0.0001; sGITR: r = 0.7448, P < 0.0001). Moreover, GITR and GITRL are readily detected in the lymphocytic foci and periductal areas of the LSGs. In contrast, the LSGs of HC subjects did not express GITR or GITRL. Our findings indicate the possible involvement of GITR-GITRL pathway in the pathogenesis of pSS. Further studies may facilitate the development of targeting this molecule pathway for the treatment of pSS.
26251760 Bifunctional Peptide Inhibitors Suppress Interleukin-6 Proliferation and Ameliorates Murin 2014 Dec The objective of this study is to evaluate the efficacy and potential mechanism of action of type-II collagen bifunctional peptide inhibitor (CII-BPI) molecules in suppressing rheumatoid arthritis in the collagen-induced arthritis (CIA) mouse model. CII-BPI molecules (CII-BPI-1, CII-BPI-2, and CII-BPI-3) were formed through conjugation between an antigenic peptide derived from type-II collagen and a cell adhesion peptide LABL (CD11a(237-246)) from the I-domain of LFA-1 via a linker molecule. The hypothesis is that the CII-BPI molecules simultaneously bind to MHC-II and ICAM-1 on the surface of APC and block maturation of the immunological synapse. As a result, the differentiation of naïve T cells is altered from inflammatory to regulatory and/or suppressor T cells. The efficacies of CII-BPI molecules were evaluated upon intravenous injections in CIA mice. Results showed that CII-BPI-1 and CIIBPI-2 suppressed the joint inflammations in CIA mice in a dose-dependent manner and were more potent than the respective antigenic peptides alone. CII-BPI-3 was not as efficacious as CII-BPI-1 and CII-BPI-2. Significantly less joint damage was observed in CII-BPI-2 and CII-2 treated mice than in the control. The production of IL-6 was significantly lower at the peak of disease in mice treated with CII-BPI-2 compared to those treated with CII-2 and control. In conclusion, this is the first proof-of-concept study showing that BPI molecules can be used to suppress RA and may be a potential therapeutic strategy for the treatment of rheumatoid arthritis.
24348792 UPLC-PDA determination of paeoniflorin in rat plasma following the oral administration of 2014 Jan Rheumatoid arthritis (RA) is a chronic disabling autoimmune disease with characteristics of chronic, progressive inflammatory joint synovial damage, which mainly encroaches upon the synovium of the joint. The use of traditional medicine to treat RA slows the development of RA to a certain extent; however, it often has numerous side-effects. Therefore, the focus of RA research is the identification of a new, safe and effective medicine. The aim of the present study was to use an ultra performance liquid chromatography and photo diode array (UPLC-PDA) method to detect the paeoniflorin component in a Radix Paeoniae Alba decoction and in rat plasma following the oral administration of Radix Paeoniae Alba decoction. In addition, the effects of paeoniflorin on collagen-induced arthritis (CIA) in rats were investigated. The results indicate that a UPLC-PDA method for determining the presence of paeoniflorin in the Radix Paeoniae Alba decoction was successfully established. The method was fast, simple, sensitive, precise and valid. Paeoniflorin was shown to be a bioactive component of the Radix Paeoniae Alba decoction that was absorbed into rat plasma. Paeoniflorin significantly improved the disease resistant ability of RA rats and reduced the levels of the inflammatory cytokines, IL-1β and TNF-α, thereby inhibiting inflammation and bone erosion in the rats with CIA. The observations are likely to lay the foundation for further study of the mechanism of paeoniflorin in the treatment of RA.
22527139 Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radica 2013 Mar Rheumatoid arthritis is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone in a chronic phase. Pathology of rheumatoid arthritis suggests autoimmunity linked to inflammation. In our study, rheumatoid arthritis was induced in Wistar rats by intradermal injections of 100 μl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail. Disease developed about 13 ± 1 days after immunization and treatment with hesperidin (HES) at a dose of 160 mg kg(-1) body weight was given after onset of disease daily until 20th day. The effect of treatment in the rats was monitored by clinical scoring, biochemical parameters and histological evaluations in joints. A steady increase in the articular elastase, nitric oxide and lipid peroxidation was observed in joints of arthritic rats as compared to control, whereas a significant decrease in reduced glutathione, superoxide dismutase activity and catalase was observed in collagen-induced arthritis rats as compared to control group. The results from the present work indicate that the treatment with hesperidin was effective in bringing about significant changes on all the parameters studied in collagen-induced arthritis rats. These data confirm that erosive destruction of the joint cartilage in collagen-induced arthritis is due free radicals released by activated neutrophils and produced by other biochemical pathways. In the present study, an attempt has been made to amelioration of the disease process by a natural product. These results suggest that oral administration of HES could be effective for treating human RA patients.
22147111 Hepatitis B virus reactivation in a juvenile rheumatoid arthritis patient under treatment 2013 May Juvenile rheumatoid arthritis is a common chronic inflammatory disease in the childhood and it can differentiate rarely into spondiloarthropaties. It is one of the important causes of chronic pain and disability. Some of the drugs used for the treatment have immunosupressive activity. One of the serious side-effects of immunosupressive treatment is activation of opportunistic pathogens. Hepatitis B virus (HBV) is one of these pathogens, and the rate of carriers in the population is considerably high. It can cause liver damage and death if reactivated. Thus, the management of oppotunistic pathogens becomes a complex issue when treating rheumatic diseases with immunosupressive drugs. In this case report, we present a juvenile rheumatoid arthritis patient whose liver enzymes raised while he was under treatment and afterwards HBV reactivation was determined as the cause. When reactivation was detected, we started controlled antiviral therapy. We achieved successful clinical and laboratory results after adding biological agents to the treatment. Careful evaluation of the patients who have indication for immunosuppressive agents and regular follow-up in case of infection may be protective from severe morbidity and/or mortality.
24565889 Endothelial dysfunction in joint disease. 2014 Oct Inflammatory joint diseases and autoimmune diseases with joint manifestations are associated with premature and accelerated atherogenesis. Patients with rheumatoid arthritis (RA) have a 5- to 10-year decrease in life expectancy compared to the general population, and those exhibiting extraarticular manifestations have the greatest excess mortality. RA is now established as an independent cardiovascular risk factor. Complex interactions linking conventional cardiovascular risk factors, systemic inflammation, and vascular function may explain the increased cardiovascular risk among RA patients. Endothelial dysfunction is now recognized as both the key step in early atherogenesis and a contributor to atheroma plaque progression at later stages. Endothelial dysfunction is defined as impaired endothelium-dependent blood-vessel dilation in response to a stimulus. The underlying mechanisms remain speculative. Over the last decade, a role for endothelial dysfunction in the cardiovascular complications of inflammatory joint disease has been hypothesized and several maintenance drugs targeting this phenomenon have been tested, with promising results.