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ID PMID Title PublicationDate abstract
27793171 Evaluation of a patient decision aid for initiating disease modifying anti-rheumatic drugs 2016 Oct 28 BACKGROUND: According to international guidelines, treatment of inflammatory arthritis should be based on a shared decision between patient and rheumatologist. Furthermore, patients with inflammatory arthritis have high need of information and want to be more actively involved in medical decision-making. To facilitate shared decision-making and support patients in choosing between disease modifying anti-rheumatic drugs (DMARDs), a web-based patient decision aid (PtDA) was developed. This study evaluated use, appreciation and effect of this PtDA. METHODS: A post-test only study with a historical comparison group was conducted. In a two-year period, all patients diagnosed with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis, who were deciding whether to start a (different) DMARD were invited to participate. In the first year, patients received standard information (comparison group). In the second year, patients were referred to the PtDA (intervention group). In both groups, a questionnaire was sent four weeks after consulting the rheumatologist. Patient characteristics included sociodemographic, health-related and preference-related variables. Process measures were for use and appraisal of the PtDA (intervention group only). The primary outcome measure was patients' perceived role in medical decision-making. Secondary outcome measures comprised satisfaction with the decision-making process and the decision, beliefs about medication, adherence to medication and trust in the physician. RESULTS: We received 158/232 questionnaires (68 %) from the comparison group and 123/200 (61 %) from the intervention group. The PtDA was used by 69/123 patients (57 %) in the intervention group. Patients who used the PtDA highly appreciated it and perceived it as easy to use and helpful. Relative to the comparison group, patients in the intervention group perceived a more active role in medical decision-making and decisions were more in line with patients' personal preferences. Other outcomes showed no significant difference between the two groups. CONCLUSION: The web-based PtDA was highly appreciated and perceived as helpful for decision-making. Implementation of the PtDA in rheumatology practice was associated with a significantly larger proportion of patients perceiving an active role in medical decision-making and decisions were more in line with patients' personal preferences. The PtDA can be a valuable aid in improving patient participation in decision-making about DMARDs.
26272937 HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid. 2015 Oct Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases.
26633038 Invariant NKT cells are expanded in peripheral blood but are undetectable in salivary glan 2016 Jan OBJECTIVES: Invariant NKT (iNKT) cells play a role in regulating the function of autoreactive B cells before their entry into germinal centres. Absence and/or reduction of iNKT cells have been demonstrated in patients with systemic lupus erythematosus (SLE) together with an increase of autoreactive B cell activity. Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease in which lymphocyte infiltration and organisation in lymphoid structures of inflamed salivary glands occurs. The aim of the study was to investigate the percentage and function of iNKT in the salivary glands and peripheral blood of patients with pSS. METHODS: Minor salivary gland biopsies were obtained from patients with pSS and with non-specific chronic sialoadenitis (nSS). Flow cytometry analysis of CD1d/α-GalactosylCeramide (α-GalCer) tetramer positive cells, producing IFN-γ and IL-17, and quantitative gene expression analysis by TaqMan real-time PCR for Vα24 were performed on salivary glands biopsies and peripheral blood samples obtained from patients and controls. Flow cytometry and immunofluorescence analysis for autoreactive B lymphocytes and ELISA for anti-SSA antibodies (Ab) detection were also performed. RESULTS: An increase of iNKT was detected ex vivo in peripheral blood of pSS patients; after α-GalCer stimulation this subset produce IL-17 and IFN-iNKT were undetectable in the salivary glands of pSS patients and anti-SSA specific B cells were found in target tissue. Invariant NKT cells were able to inhibit autoantibody production by B cells obtained from salivary glands of pSS. CONCLUSIONS: Impaired iNKT migration to inflamed sites might induce the activation of autoreactive B cells specific for SSA-antigen in salivary glands of pSS patients.
25476830 Antinociceptive and anti-arthritic effects of kramecyne. 2015 Jan 15 AIMS: The aim of this study was to evaluate the antinociceptive (acute assays) and anti-inflammatory (chronic assays) effects of kramecyne (KACY), a peroxide isolated from Krameria cytisoides. MAIN METHODS: The antinociceptive activity of KACY was evaluated using the hot plate, acetic acid and formalin tests. The effects of KACY on heat-induced hemolysis in rat erythrocytes were also evaluated. The in vivo anti-inflammatory assays were performed using the chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema and carrageenan-kaolin induced arthritis (CKIA). In the CKIA model, the hot plate test was performed, serum samples were obtained for the quantitation of pro-inflammatory (IL-1β, IL-6, IL-12 and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines. KEY FINDINGS: KACY possess antinociceptive effects with comparable activity to naproxen (NPX). KACY inhibited hemolysis (EC50 = 180 μg/mL), in comparison to the untreated group and with a higher potency than NPX (EC50 = 263 μg/mL). KACY at 50 mg/kg decreased inflammation by 38% (chronic TPA-induced edema model) and by 26% (CKIA model), in comparison with the vehicle group and with similar activity to the positive controls 8 mg/kg indomethacin (IND) and 1 mg/kg methotrexate (MTX), respectively. In the CKIA model, KACY increased the release of anti-inflammatory (IL-4 and IL-10) cytokines but reduced the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 and TNF-α). KACY at 50 and 100 mg/kg showed antinociceptive effects by 27% and 23%, respectively, in mice with mono-arthritis. SIGNIFICANCE: KACY might be a good alternative for the treatment of rheumatoid arthritis (RA) due its antinociceptive and anti-inflammatory activities.
26904697 Association of Sicca Syndrome with Proviral Load and Proinflammatory Cytokines in HTLV-1 I 2016 The Sjögren syndrome has been diagnosed in patients with HTLV-1 associated myelopathy and dry mouth and dry eyes are documented in HTLV-1 carriers. However the diagnosis of Sjögren syndrome in these subjects has been contested. In this cross-sectional study, we evaluated the role of immunological factors and proviral load, in sicca syndrome associated with HTLV-1 in patients without myelopathy. Subjects were recruited in the HTLV-1 Clinic, from 2009 to 2011. The proviral load and cytokine levels (IFN-γ, TNF-α, IL-5, and IL-10) were obtained from a database containing the values presented by the subjects at admission in the clinic. Of the 272 participants, 59 (21.7%) had sicca syndrome and in all of them anti-Sjögren syndrome related antigen A (SSA) and antigen B (SSB) were negatives. The production of TNF-α and IFN-γ was higher in the group with sicca syndrome (P < 0.05) than in HTLV-1 infected subjects without sicca syndrome. Our data indicates that patients with sicca syndrome associated with HTLV-1 do not have Sjögren syndrome. However the increased production of TNF-α and IFN-γ in this group of patients may contribute to the pathogenesis of sicca syndrome associated with HTLV-1.
26934448 Development of a specific affinity-matured exosite inhibitor to MT1-MMP that efficiently i 2016 Mar 29 The membrane-associated matrix metalloproteinase-14, MT1-MMP, has been implicated in pericellular proteolysis with an important role in cellular invasion of collagenous tissues. It is substantially upregulated in various cancers and rheumatoid arthritis, and has been considered as a potential therapeutic target. Here, we report the identification of antibody fragments to MT1-MMP that potently and specifically inhibit its cell surface functions. Lead antibody clones displayed inhibitory activity towards pro-MMP-2 activation, collagen-film degradation and gelatin-film degradation, and were shown to bind to the MT1-MMP catalytic domain outside the active site cleft, inhibiting binding to triple helical collagen. Affinity maturation using CDR3 randomization created a second generation of antibody fragments with dissociation constants down to 0.11 nM, corresponding to an improved affinity of 332-fold with the ability to interfere with cell-surface MT1-MMP functions, displaying IC50 values down to 5 nM. Importantly, the new inhibitors were able to inhibit collagen invasion by tumor-cells in vitro and in vivo primary tumor growth and metastasis of MDA-MB-231 cells in a mouse orthotopic xenograft model. Herein is the first demonstration that an inhibitory antibody targeting sites outside the catalytic cleft of MT1-MMP can effectively abrogate its in vivo activity during tumorigenesis and metastasis.
26667304 No association of IL-12p40 pro1.1 polymorphism with juvenile idiopathic arthritis. 2015 Dec 15 BACKGROUND: IL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population. METHODS: In 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR. RESULTS: There is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4%) and in rheumatoid factor negative polyarthritis (30.5%) and a lower pro1.1 genotype in persistent oligoarthritis (20.7%) and in enthesitis-related arthritis (17%). Likelihood of the occurrence of genotype IL12-p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95% 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95% 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 % 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant. CONCLUSION: A tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL-12p40 in the different subtypes of JIA.
26433318 Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multic 2015 Dec 19 BACKGROUND: Early intervention and tight control of inflammation optimise outcomes in rheumatoid arthritis but these approaches have not yet been studied in psoriatic arthritis. We aimed to assess the effect of tight control on early psoriatic arthritis using a treat-to-target approach. METHODS: For this open-label multicentre randomised controlled trial, adult patients (aged ≥18 years) with early psoriatic arthritis (<24 months symptom duration), who had not previously received treatment with any disease-modifying anti-rheumatic drugs, were enrolled from eight secondary care rheumatology centres in the UK. Enrolled patients were randomly assigned in a 1:1 ratio to receive either tight control (with review every 4 weeks and with escalation of treatment if minimal disease activity criteria not met) or standard care (standard therapy according to the treating clinician, with review every 12 weeks) for 48 weeks. Randomisation was done by minimisation incorporating a random element, to ensure treatment groups were balanced for randomising centre and pattern of arthritis (oligoarticular vs polyarticular). The randomisation procedure was done through a central 24-h automated telephone system based at the Leeds Institute of Clinical Trials Research (Leeds, UK). This was an open-label study in which patients and clinicians were aware of treatment group assignment. Clinical outcomes were recorded by a masked assessor every 12 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology (ACR) 20% (ACR20) response at 48 weeks, analysed by intention to treat with multiple imputation for missing ACR components. Cost-effectiveness was also assessed. This trial is registered with ClinicalTrials.gov, number NCT01106079, and the ISCRCTN registry, number ISCRCTN30147736. FINDINGS: Between May 28, 2008, and March 21, 2012, 206 eligible patients were enrolled and randomly assigned to receive tight control (n=101) or standard care (n=105). In the intention-to-treat patient population, the odds of achieving an ACR20 response at 48 weeks were higher in the tight control group than in the standard care group (odds ratio 1·91, 95% CI 1·03-3·55; p=0·0392). Serious adverse events were reported by 20 (10%) patients (25 events in 14 [14%] patients in the tight control group and eight events in six [6%] patients in the standard care group) during the course of the study. No unexpected serious adverse events or deaths occurred. INTERPRETATION: Tight control of psoriatic arthritis disease activity through a treat-to-target approach significantly improves joint outcomes for newly diagnosed patients, with no unexpected serious adverse events reported. FUNDING: Arthritis Research UK and Pfizer.
27783083 Extra virgin olive oil: a key functional food for prevention of immune-inflammatory diseas 2016 Nov 9 Nowadays, it is clear that an unhealthy diet is one of the prime factors that contributes to the rise of inflammatory diseases and autoimmunity in the populations of both developed and developing countries. The Mediterranean diet has been associated with a reduced incidence of certain pathologies related to chronic inflammation and the immune system. Olive oil, the principal source of dietary lipids of the Mediterranean diet, possesses a high nutritional quality and a particular composition, which is especially relevant in the case of Extra Virgin Olive Oil (EVOO). EVOO is obtained from olives solely by mechanical or other physical preparation methods, under conditions that do not alter the natural composition. EVOO is described as a key bioactive food with multiple beneficial properties and it may be effective in the management of some immune-inflammatory diseases. In this review, the key research is summarised which provides evidence of the beneficial effects of EVOO and its minor components focusing on their mechanisms on immune-inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and sclerosis.
27704870 Commercial biomarker assays: friend and foe. 2016 Nov AIM: Commercial kits can provide a convenient solution for measuring circulating biomarkers to support drug development. However, their suitability should be assessed in the disease matrix of interest. METHODOLOGY: Twelve biomarkers were evaluated in samples from patients with rheumatoid arthritis. We used immunoassay kits from five vendors on three multiplexed platforms. Kit suitability was evaluated on the basis of detectability and prespecified performance acceptance criteria. RESULTS: Assays had varying levels of sensitivity and susceptibility to interference by matrix components. Only a few assays in the multiplexed kits were found to be suitable. In general, kits for analytes that passed our assay criteria showed good correlation between vendors. CONCLUSION: The data from this study demonstrate that the majority of assays on multiplexed kits evaluated either lacked sensitivity and/or had poor performance, which diminishes the utility of the multiplexing approach.
27215115 [MEDICAL CANNABIS]. 2016 Feb The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing. Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.
27159947 Efficacy and Safety of Infliximab for Ankylosing Spondylitis in Japanese Patients: A Retro 2015 Dec PURPOSE: Tumor necrosis factor inhibitors (TNFi) such as infliximab (IFX) and adalimumab have been shown to be efficacious not only for rheumatoid arthritis but also for Ankylosing Spondylitis (AS). However, only a limited number of reports regarding the effect of TNFi on AS in Japanese population have been published. MATERIALS AND METHODS: We retrospectively evaluated all 11 patients (8 males and 3 females) with AS who were treated with IFX. RESULTS: After a mean follow-up period of 19 months, the mean BASDAI decreased from 4.7 ± 2.2 to 1.7 ± 1.2 and the serum CRP level decreased from 1.62 ± 1.94 mg/dl to 0.23 ± 0.45 mg/dl. There was no case of serious infection or anaphylaxis. CONCLUSIONS: Our results indicate that IFX is efficacious and safe for AS in Japanese patients.
27103910 Periodontal Systemic Connections-Novel Associations-A Review of the Evidence with Implicat 2016 Apr Periodontal diseases, considered as inflammatory diseases have proved to have a spectrum of systemic implications. Earliest research has associated periodontal disease with common systemic aliments such as hypertension, diabetes, osteoporosis, rheumatoid arthritis to name a few. The evolution of advanced diagnostic aids let researchers make vast inroads in linking periodontal diseases to systemic diseases like Alzheimer's disease (AD) and even Schizophrenia. Our aim was to review and critically evaluate comprehensive literature and provide knowledge to medical practitioners on these associations so as to pave way for closer interactions between medical and dental practitioners in implementing better health care. Electronic databases such as PubMed, Google Scholar and Cochrane databases were used as source of the data for relevant studies published from 2005 up to 2015 with the following keywords, "'Periodontal disease", "systemic conditions", "periodontal disease and Alzheimer's", "Periodontal disease and Schizophrenia", "Periodontal disease and Psoriasis" and "Periodontal disease and erectile dysfunction". The evidence presented ascertains that a reasonable and modest association does exist between Periodontal disease and Alzheimer's, Schizophrenia, Erectile dysfunction, as well as Psoriasis and thus establishes periodontal disease as a potential risk factor.
26666335 Causes of changes in carotid intima-media thickness: a literature review. 2015 Dec 15 Atherosclerosis causes significant morbidity and mortality. Carotid intima-media thickness (CIMT) predicts future cardiovascular and ischaemic stroke incidence. CIMT, a measure of atherosclerotic disease, can be reliably determined in vivo by carotid ultrasound. In this review, we determined that CIMT is associated with traditional cardiovascular risk factors such as age, sex, race, smoking, alcohol consumption, habitual endurance exercise, blood pressure, dyslipidemia, dietary patterns, risk-lowering drug therapy, glycemia, hyperuricemia, obesity-related anthropometric parameters, obesity and obesity-related diseases. We also found that CIMT is associated with novel risk factors, including heredity, certain genotypic indices, anthropometric cardiovascular parameters, rheumatoid arthritis, immunological diseases, inflammatory cytokines, lipid peroxidation, anthropometric hemocyte parameters, infectious diseases, vitamin D, matrix metalloproteinases, and other novel factors and diseases. However, the conclusions are inconsonant; the underlying causes of these associations remain to be further explored.
26082907 Base of Tongue Tuberculosis: A Case Report. 2015 May INTRODUCTION: Tuberculosis is an infectious disease that has displayed increasing incidence in the last decades. It is estimated that up to 20% of tuberculosis cases affect extra-pulmonary organs. In the ENT area, soft palate and tongue are the least probable locations. CASE REPORT: A 62-year-old female with a history of rheumatoid arthritis and treatment with corticosteroids and Adalimumab, developed a foreign body sensation in the pharynx accompanied by a sore throat and halitosis. The laryngoscopy with a 70 degree rigid telescope showed an ulcerated hypertrophic lesion in the right vallecula of about 2-3 cm in the base of the tongue. Acid-alcohol resistant bacilli were found positive for M. tuberculosis, through the Ziehl Neelsen method and Löwenstein culture the patient was treated with tuberculostatic medication. CONCLUSION: TB is a possible diagnosis when in the presence of an ulcerated lesion at the base of the tongue, accompanied by sore throat, dysphagia, or foreign body sensation.
25813714 Prelude to oral microbes and chronic diseases: past, present and future. 2015 Jul Associations between oral and systemic health are ancient. Oral opportunistic bacteria, particularly, Porphyromonas gingivalis and Fusobacterium nucleatum, have recently been deviated from their traditional roles as periodontal pathogens and arguably ascended to central players based on their participations in complex co-dependent mechanisms of diverse systemic chronic diseases risk and pathogenesis, including cancers, rheumatoid-arthritis, and diabetes.
25658079 Periprosthetic supracondylar femur fracture treated with spanning external fixation. 2015 Feb Periprosthetic supracondylar fractures of the femur after total knee arthroplasty represent a devastating complication for the patient and a technical challenge for the surgeon. Treatment is often complicated by advanced patient age, retained cement, and accompanying osteoporosis. We present the case of a 54-year-old woman with a comminuted fracture of the distal femur just above a total knee prosthesis. She had a complex past medical history, including extensive coronary artery disease, morbid obesity, chronic osteoporosis, anemia, diabetes, and rheumatoid arthritis. She was a Jehovah's Witness and thus refused all blood products. Given her medical history, religious preferences, and fracture comminution, a spanning external fixator was used. She completed fracture union with an excellent clinical and radiographic result at 2 years.
24998041 Medial Column Arthrodesis Using an Anatomic Distal Fibular Locking Plate. 2015 Jul The medial column fusion is performed for a multitude of etiologies, including peritalar subluxation deformity, Charcot arthropathy, trauma, post-traumatic degenerative joint disease, and rheumatoid arthritis. Various surgical techniques have been described for medial column arthrodesis. We describe a new fixation method using an anatomic distal fibular locking plate for medial column arthrodesis. This technique provides a rigid construct in compromised or at risk bone. After a review of the surgical technique, we outline 2 case examples of patients with peritalar subluxation and Charcot arthropathy.
27785332 Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Involving the Colon in a Patient 2016 Oct The link between immunosuppressive therapy and increased lymphoma risk is well established in patients with solid organ transplantation. Epstein-Barr virus-positive (EBV) diffuse large B-cell lymphoma (DLBCL) is known to be a complication in patients receiving methotrexate for rheumatoid arthritis, and the risk of lymphoma in inflammatory bowel disease (IBD) has raised concerns regarding the lymphoproliferative potential of immunomodulatory therapy. In this report, we describe a case of EBV-positive DLBCL arising within the colon of a patient affected by ulcerative pancolitis. The patient is a 73-year-old man with a history of IBD and polymyositis on long-term methotrexate therapy. Increasing age and long-term methotrexate therapy may simulate post-transplantation immunosuppression and contribute to lymphoma tumorigenesis in a segment of chronically inflamed colon.
27586383 Therapy: Paradoxical effects of targeting TNF signalling in the treatment of autoimmunity. 2016 Nov Adalimumab, an anti-TNF monoclonal antibody used to treat rheumatoid arthritis and other autoimmune disorders, paradoxically enhances the capacity of TNF to expand TNF receptor type II-expressing regulatory T cells. This provocative finding opens a new avenue for exploring the mechanisms that underlie efficacy, non-responsiveness and adverse effects associated with therapeutic targeting of TNF signalling.