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ID PMID Title PublicationDate abstract
29409929 Cysteine cathepsins in extracellular matrix remodeling: Extracellular matrix degradation a 2019 Jan Cysteine cathepsins have been for a long time considered to execute mainly nonspecific bulk proteolysis in the endolysosomal system. However, this view has been changing profoundly over the last decade as cathepsins were found in the cytoplasm, nucleus and in the extracellular milieu. Cathepsins are currently gaining increased attention largely because of their extracellular roles associated with disease development and progression. While kept under tight control under physiological conditions, their dysregulated and elevated activity in the extracellular milieu are distinctive hallmarks of numerous diseases such as various cancers, inflammatory disorders, rheumatoid arthritis, bone disorders and heart diseases. In this review, we discuss cysteine cathepsins with a major focus on their extracellular roles and extracellular proteolytic targets beyond degradation of the extracellular matrix. We further highlight the perspectives of cathepsin research and novel avenues in cathepsin-based diagnostic and therapeutic applications.
30206094 What evidence is used to underpin the design of strength-based exercise interventions eval 2018 Sep 10 INTRODUCTION: Healthcare researchers designing strength-based exercise interventions must choose an appropriate dose to test before evaluating its effect using a definitive/phase-III randomised controlled trial (RCT). Compared with early phase testing employed by pharmaceutical trials, it is questionable whether exercise-based trials employ the same rigour for establishing tolerated dosage. Consequently, it is unclear if participants are initially prescribed optimal doses of exercise, which may potentially impact on study outcomes. Using trials of strength-based exercise interventions in adults with rheumatoid arthritis (RA) as an exemplar, the aims of this review are to (1) identify the proportion of RCTs that use phase I/II trials with dose escalation methodology for setting prescription parameters, (2) determine type and level of evidence used to justify prescription parameters of strength-based exercise interventions evaluated by RCTs, (3) explore consistency and applicability of the evidence underpinning prescription parameters in RCTs and (4) explore if a relationship exists between risk of bias for RCTs evaluating strength-based interventions and the level of evidence used to underpin prescription parameters. METHODS AND ANALYSIS: Focusing on RCT's evaluating strength-based exercise interventions in adults with RA published after 2000, the following databases will be searched: Allied and Complementary Medicine Database, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, Medline and Physiotherapy Evidence Database. For each RCT, we will identify the evidence used to underpin prescription parameters. Both trial and underpinning evidence will have key information about the intervention extracted using the template for intervention description and replication checklist. Risk of bias will be assessed according to Cochrane. Levels of evidence will be assessed against the Oxford Centre for Evidence-Based Medicine and relationships between RCT and underpinning evidence explored and described narratively. Two independent assessors will be involved throughout data selection and extraction with recourse to a third reviewer should agreement not be reached. ETHICS AND DISSEMINATION: No ethical issues are identified. Dissemination will be via publication. PROSPERO REGISTRATION NUMBER: CRD42018090963.
29552837 [Meta-analysis on efficacy and safety of combination therapy of Aconitum and Western medic 2018 Jan To analyze the efficacy and safety of the combination therapy of Aconitum and Western medicine in the treatment of rheumatoid arthritis (RA) by Meta-analysis, and provide evidence for its clinic application for RA. The random clinical trials (RCTs) regarding the combination therapy for treating RA were retrieved in the database of China National Knowledge Infrastructure database, China Science and Technology Journal database, WanFang, Chinese Biomedical Medical Database, PubMed, and Cochrane Library up to July 2017. According to the given inclusion criteria, 8 RCTs involving 659 participants were included, and the included RCTs could be further divided into three subgroups according to the herb type, which were Aconiti Radix (Chuanwu) subgroup (6RCTs), Aconiti Kusnezoffii Radix (Caowu) subgroup (1RCT), and Chuanwu-Caowu subgroup (1RCT). The Meta-analysis results indicated that as compared with Western medicine, the combined use of Aconitum and Western medicine, no matter Chuanwu, Caowu or Chuanwu-Caowu subgroups, could improve the total effective rate of RA (6RCTs, RR=1.19, 95%CI [1.10, 1.28], P<0.000 01), (1 RCT, RR=1.43, 95%CI [1.18, 1.73], P=0.000 2), (1 RCT, RR=1.27, 95%CI [1.02, 1.58], P=0.03) respectively. The combined use of Aconitum and Western medicine was also effective on the number of joint swelling, duration of morning stiffness, patients' handgrip, and the erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor. However, its action was not significant on joint tenderness. And also, in the included RCTs, there were 34 cases of adverse drug reactions/events (ADR/ADE) in the Chuanwu subgroup, while 86 cases in the Western medicine control group. The ADR/ADE incidence was even more lower in Chuanwu-Caowu subgroup, but no difference between Caowu subgroup and Western medicine group. Based on the included RCTs, the combined use of Aconitum and Western medicine could achieve more satisfying efficacy and lower ADRs incidence for RA as compared with Western medicine alone. However, due to the limitation in the not-high quality of included RCTs and the lack of large-scale multi-center research, the results still need to be further validated in the clinic application.
30196044 Assessing treatment tolerability for rheumatoid arthritis. Validation and practical applic 2020 Mar INTRODUCTION: Given the lack of standardized tools to assess tolerability from patient's perspective, we carried out the validation of a questionnaire to asses treatment tolerability for rheumatoid arthritis (RA): TOL-AR-18. METHODS: The TOL-AR-18 was validated in the cross-sectional observational study in adult patients with RA. Socio-demographic and clinical variables were collected. Patients completed the TOL-AR-18 and ARTS questionnaires and a question about their general health status. RESULTS: Data of 66 patients with a mean age (standard deviation; SD) of 56.71 (10.50) years were analyzed; 66.7% were women. Mean (SD) time to disease progression was 10.76 (8.23) years, and time from first treatment initiation was 9.24 (7.70) years. Patients did not report other adverse events rather than those included in the TOL-AR-18. The questionnaire was feasible with high internal consistency (Cronbach's α >0.90). Discriminant validity was moderate, with significant differences between patients in remission and all other, and between patients who did not report adverse events and the rest (P<.05). Convergent validity was moderate-low when correlated with the ARTS questionnaire. CONCLUSION: The TOL-AR-18 is valid for use in a clinical setting and useful as an additional tool for all professionals to manage and assess tolerability in RA.
29925726 Methotrexate-associated lymphoproliferative disorder complicated by severe acute respirato 2018 Aug 29 Lymphoproliferative disorder (LPD) is a potentially severe adverse effect of methotrexate (MTX) administration in patients with rheumatoid arthritis (RA). We report a case of MTX-associated LPD (MTX-LPD) in a patient with RA who developed severe pulmonary failure complicated by perforation of the terminal ileum. A 61-year-old woman with RA receiving MTX complained of dyspnea and abdominal pain. She was diagnosed with intestinal perforation and peritonitis, and underwent immediate abdominal surgery. Pathological examinations of the specimen obtained from the resected ileum and a bone marrow aspirate revealed diffuse large B-cell lymphoma. Steroid therapy failed to improve her respiratory failure, but her condition improved after abdominal surgery and suspension of MTX. MTX-LPD can result in multiple life-threatening conditions; however, the symptoms are highly variable. RA patients receiving MTX should thus be monitored carefully, and MTX administration should be stopped immediately on suspicion of MTX-LPD.
29543214 [Rheumatoid atlanto-axial dislocation: a surgical approach]. 2018 Pathological processes in the craniovertebral region (CVR) are usually accompanied by dislocation complications leading to gross neurological disorders. One of the diseases that affect the CVR and lead to atlanto-axial dislocation (AAD) is rheumatoid arthritis. Errors in the diagnosis of rheumatoid disease and in the choice of a treatment approach may cause adverse outcomes. OBJECTIVE: To define the approach for surgical treatment of AAD associated with rheumatoid disease of the CVR, with allowance for the rigidity of deformity. MATERIAL AND METHODS: Five patients with rheumatoid AAD, 4 females and 1 male, aged 54 to 73 years underwent surgery. All dislocations were anterior ones. Three patients had mobile pannus-associated dislocation. In 2 cases, AAD was rigid and combined with odontoid invagination into the foramen magnum (FM). RESULTS: In all mobile AAD cases, decompression of the brainstem and restoration of the normal anatomical relationships in the CVR were achieved by dislocation correction and atlanto-axial fusion performed from the posterior approach, avoiding transoral interventions. In this case, spontaneous resorption of the pannus occurred within several months after surgery. In the postoperative period, all patients achieved significant regression of pain and neurological disorders. Complications in the form of wound infection developed in 1 case. CONCLUSION: A decision algorithm for choosing a surgical treatment option was based on the degree of deformity stability. Mobile AADs serve as an indication for indirect decompression using instrumental correction of dislocation and atlantoaxial fixation from the posterior approach. In the case of fixed AAD, posterior fixation is complemented by anterior decompression via the transoral approach.
29249429 Discrepancies in risk age and relative risk estimations of cardiovascular disease in patie 2018 Feb 1 OBJECTIVE: The European guidelines on cardiovascular disease (CVD) prevention advise use of relative risk and risk age algorithms for estimating CVD risk in patients with low estimated absolute risk. Patients with inflammatory joint diseases (IJD) are associated with increased risk of CVD. We aimed to estimate relative risk and risk age across IJD entities and evaluate the agreement between 'cardiovascular risk age' and 'vascular age models'. METHODS: Using cross-sectional data from a nationwide project on CVD risk assessment in IJD, risk age estimations were performed in patients with low/moderate absolute risk of fatal CVD. Risk age was calculated according to the cardiovascular risk age and vascular age model, and risk age estimations were compared using regression analysis and calculating percentage of risk age estimations differing ≥5years. RESULTS: Relative risk was increased in 53% and 20% had three times or higher risk compared to individuals with optimal CVD risk factor levels. Furthermore, 20-42% had a risk age ≥5years higher than their actual age, according to the specific risk age model. There were only minor differences between IJD entities regarding relative risk and risk age. Discrepancies ≥5years in estimated risk age were observed in 14-43% of patients. The largest observed difference in calculated risk age was 24years. CONCLUSION: In patients with low estimated absolute risk, estimation of relative CVD risk and risk age may identify additional patients at need of intensive CVD preventive efforts. However, there is a substantial discrepancy between the risk age models.
30712718 The effectiveness of Mindfulness-Based Cognitive Therapy on the illness perception and Psy 2019 Feb This study was conducted to evaluate the Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) on the Illness Perception (IP) and Psychological Symptoms (PS) for Patients in primary care with an active symptom of Rheumatoid Arthritis (RA). The present design is a clinical trial that uses the pre-test and post-test design with a control group. MBCT as an evidence-based psychotherapeutic intervention and Mindfulness-Based Intervention (MBI), is an 8-week course developed for patients with relapsing depression that integrates mindfulness meditation practices and cognitive therapy. This semi-experimental study was conducted using a pretest-posttest and control group. Diagnostic criteria for the diagnosis of patients with RA were all patients with RA who visited the clinic of Jam Rheumatology Centers and met other inclusion criteria in Mashhad in the spring of 2018. Therefore, 28 patients were randomly selected from the diagnostic group. They were randomly assigned to an experimental group and a control group (14 individuals in each group) and then were post-tested after two months. The data were collected using the revised Illness Perception Questionnaire (IPQ-R) and Depression Anxiety Stress Scales (DASS-21 scores) which were completed by the participants. The data were analyzed using repeated measures MANOVA. The results showed that there was a significant difference between the mean scores of pre-test (before MBI) and post-test (after MBI) in the experimental group compared to the control group, and MBCT had a significant effect on the perception of the disease and the psychological syndrome in the experimental group compared to the control group. Therefore, it can be concluded that MBCT is effective on IP and psychological syndrome and can be used as an MBI method to reduce the illness perceptions in people with RA. The future researches with longer pursuing period's efficacy continuation are suggested.
29734345 Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthrit 2018 Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.
30596535 Quercetin, a Plant Polyphenol, Has Potential for the Prevention of Bone Destruction in Rhe 2019 Feb We investigated the immune-regulatory function of quercetin, in interleukin (IL)-17-produced osteoclastogenesis in rheumatoid arthritis (RA). RA fibroblasts-like synoviocytes (RA-FLS) were stimulated with IL-17, and the mRNA expression and secretion of receptor activator of nuclear factor kappa-B ligand (RANKL) were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. CD14(+) monocytes (osteoclast precursors) were stimulated with IL-17, RANKL, with/without quercetin, and tartrate-resistant acid phosphatase activity was evaluated to assess osteoclast differentiation. Osteoclast differentiation was investigated after coculturing IL-17-stimulated RA-FLS and Th17 cells with monocytes. CD4(+) T cells were cocultured with quercetin under Th17-inducing conditions, and their differentiation to Th17 cells and Treg cells was determined by flow cytometry analysis. We found that IL-17 stimulated RA-FLS to produce RANKL and quercetin decreased the IL-17-induced RANKL protein levels. Quercetin decreased the IL-17-produced activation of mammalian target of rapamycin, extracellular signal-regulated kinase and inhibitor of kappa B-alpha. When monocytes were stimulated with IL-17, macrophage colony-stimulating factor or RANKL, mature osteoclasts were formed, and quercetin decreased this osteoclastogenesis. When monocytes were cultured with IL-17-prestimulated RA-FLS or Th17 cells, osteoclasts were produced, and quercetin decreased this osteoclast differentiation. In Th17-differentiation conditions, quercetin suppressed Th17 cell and the production of IL-17, but quercetin did not affect Treg cells. Quercetin inhibits IL-17-stimulated RANKL production in RA-FLS and IL-17-stimulated osteoclast formation. Quercetin reduces Th17 differentiation. Quercetin could be an additional therapeutic option for bone destructive processes in RA.
30102390 Progression of subclinical atherosclerosis in systemic lupus erythematosus versus rheumato 2018 Dec 1 OBJECTIVES: The progression of subclinical atherosclerosis in SLE and RA has not been comparatively assessed. We sought to investigate the impact of low disease activity and other disease-related factors on atherosclerosis progression in SLE vs RA. METHODS: We performed a 3-year follow-up carotid and femoral artery ultrasound in 101 patients with SLE, 85 with RA and 85 controls after a baseline examination in 115 SLE and 1:1 age- and gender-matched RA patients and controls. We used logistic regression to compare atherosclerosis progression (new plaque development) between SLE and RA vs controls, and assess determinants of progression in SLE patients with different lupus low disease activity state (LLDAS) durations, adjusting for disease-related factors, antihypertensives, antiplatelets, statins and the Systemic Coronary Risk Evaluation 10-year cardiovascular risk. RESULTS: The odds ratio (OR) of plaque progression vs controls was significantly higher in SLE (OR = 2.81, P = 0.043), but not in RA (OR = 2.22, P = 0.109). Results were similar in patients with low disease activity (88% of SLE, 74% of RA). Multivariate determinants of progression in SLE included antiphospholipid antibodies (OR = 2.00, P = 0.043) and Systemic Coronary Risk Evaluation (OR = 2.87, P = 0.019) for all patients, and additionally cumulative corticosteroid dose during follow-up (OR = 1.38, P = 0.013) and disease duration (OR = 1.20, P = 0.022) for patients in LLDAS over entire follow-up. Results were similar for patients with shorter LLDAS durations (>75% or >50% of follow-up). CONCLUSION: Plaque progression is accelerated in SLE regardless of disease activity, and is associated with antiphospholipid antibodies and the Systemic Coronary Risk Evaluation. In LLDAS, cumulative corticosteroid dose and disease duration are additional determinants of progression.
29341125 Gut microbiota and probiotics: novel immune system modulators in myasthenia gravis? 2018 Feb Gut microorganisms (microbiota) live in symbiosis with the host and influence human nutrition, metabolism, physiology, and immune development and function. The microbiota prevents pathogen infection to the host, and in turn the host provides a niche for survival. The alteration of gut bacteria composition (dysbiosis) could contribute to the development of immune-mediated diseases by influencing the immune system activation and driving the pro- and anti-inflammatory responses in order to promote or counteract immune reactions. Probiotics are nonpathogenic microorganisms able to interact with the gut microbiota and provide health benefits; their use has recently been exploited to dampen immunological response in several experimental models of autoimmune diseases. Here, we focus on the relationships among commensal bacteria, probiotics, and the gut, describing the main interactions occurring with the immune system and recent data supporting the clinical efficacy of probiotic administration in rheumatoid arthritis, multiple sclerosis, and myasthenia gravis (MG) animal models. The encouraging results suggest that selected strains of probiotics should be evaluated in clinical trials as adjuvant therapy to restore the disrupted tolerance in myasthenia gravis.
29776427 Rheumatoid meningitis developed in patient with stable rheumatoid arthritis and myasthenia 2018 May 18 BACKGROUND: Rheumatoid meningitis (RM) is a rare disorder that often develops during a remission phase of rheumatoid arthritis (RA). This is the first study to demonstrate differences in regard to immunological disturbance between blood and cerebrospinal fluid (CSF) samples obtained from a patient with RM using flow cytometry. CASE PRESENTATION: A 36-year-old woman with RA and generalized myasthenia gravis (MG) developed RM during a remission phase. Although both RA and MG were stable and well controlled, she noticed fever, headache, and transient sensory disturbance. Blood and CSF examination findings suggested aseptic meningitis, while brain magnetic resonance imaging revealed restricted portions of meningitis and associated cortical lesions, compatible with a diagnosis of RM. The dose of oral prednisolone was increased, which ameliorated the symptoms within 1 week along with improvement in CSF findings. This patient exhibited features of RM that were manifested in a manner independent of the activity of RA. An investigation of cellular immunity using CSF specimens with flow cytometry showed differences in regard to the pathogenesis of inflammation in the CSF as compared to outside of the central nervous system. In contrast to results obtained with paired blood samples, CSF cells at the peak stage of RM showed a marked increase in CCR3(+) Th2 cells and marked decrease in CD8(+) cells, suggesting an immunoregulatory disturbance in the CSF. Those findings indicated a CSF-specific activation of humoral immunity, resulting in augmentation of meningeal inflammation, as shown by excess synthesis of intrathecal IgG and markedly elevated interleukin-6 level. Results of the present detailed investigation of lymphocyte subsets revealed a discrepancy regarding the process of inflammation in this RM patient between CSF and blood samples. CONCLUSIONS: RM is not a simple reflection of the immune status of RA, as the pathogenesis seems related to, at least in part, CSF-specific immunological dysregulation.
29558346 [Methods of efficacy assessment of the knee joint radiosynoviorthesis- personal experience 2018 OBJECTIVE: Introduction: Radiosynoviorthesis (RS) is local method of treatment of remittent joint effusions among patients who obtained general improvement after disease modifying anti-rheumatic drugs therapy but one or a few joints stay resistant to this treatment and intraarticular corticosteroids injections. The aim: The attempt to identification methods of efficacy assessment of the 90yttrium knee joint RS. PATIENTS AND METHODS: Material and methods: The study group consisted of 43 patients with rheumatoid arthritis (RA) and 19 patients with inflammatory spondyloarthropaties (SPA) where 8 patients were treated for ankylosing spondylitis (AS), 4 for psoriatic arthritis (PsA) and 7 due to undifferentiated inflammatory spondyloarthropaties (USPA). The efficacy of RS was measured subjectively by the patient, physically by the physician and with the help of chosen scores (DAS28), questionnaires (HAQ), laboratory parameters [ESR, level of CRP, osteoprotegerin (OPG), serum amyloid A (SAA), hialuronic acid (HA)] and three-phase bone scintigraphy of affected knee joints. RESULTS: Results: In RA patients very good results - no knee effusion were obtained in 25 (58,1%) joints, good results - minimal effusion in 10 (23,3%) knees and lack of improvement in 8 (18,6%) patients. Cumulatively very good and good results were obtained in 35 (81,4%) treated knee joints. In SPA patients very good results were noted in 12 (63,2%), good in 5 (26,3%), lack of improvement in 2 (10,5%) patients. Cumulatively very good and good results were obtained in 17 (89,5%) treated knee joints. We observed favorable profile changes of chosen scores (DAS28), questionnaires (HAQ), laboratory parameters (ESR, CRP, OPG, SAA, HA) and results of three-phase bone scintigraphy of knee joints. CONCLUSION: Conclusions: 90Yttrium RS is effective treatment of recurrent knee joints effusion in patients with RA i SPA. RS despite being local treatment decreases unspecific inflammatory process and systemic disease activity among patients with RA i SPA. The anatomic period of affected knee joints has negative correlation with treatment efficacy. 90Yttrium RS is safe procedure, favourable profile changes of cartilage and bone turn-over markers after therapy indicates protective influence of RS on these structures. The treatment response based on physical examination, subjective patient's evaluation, acute phase laboratory parameter levels and appropriate scores, questionnaires and imaging exams is fast and long-lasting.
29483841 Prevalence and Determinants of Peripheral Microvascular Endothelial Dysfunction in Rheumat 2018 OBJECTIVES: To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events. MATERIALS AND METHODS: Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis-ClinicalTrials.gov: NCT02341066) were analyzed. Log-transformed reactive hyperemia index (Ln-RHI) was evaluated by peripheral arterial tonometry (PAT) using the EndoPAT2000 device: values of Ln-RHI < 0.51 were considered indicative of peripheral ED. RESULTS: Peripheral microvascular ED was documented in one-third of RA patients (33.5%); in multiple logistic regression analysis, ACPA negativity and higher triglycerides concentrations were independently associated with the presence of peripheral ED [OR (95% CI) = 1.708 (1.218-2.396), p < 0.01 and OR (95% CI) = 1.005 (1.002-1.009), p < 0.01, respectively]. Multiple regression analysis showed a positive correlation between Ln-RHI values and systolic blood pressure and HDL cholesterol levels; furthermore, higher values of Ln-RHI were associated with ACPA positivity, while smoking habit was associated with lower Ln-RHI values. CONCLUSIONS: This study demonstrates for the first time a high prevalence of peripheral microvascular ED in patients with RA free of previous cardiovascular events that appear to be only partially driven by traditional cardiovascular risk factors. The association between ACPA negativity and ED warrants further exploration.
29101672 Association between leptin and IL-6 concentrations with cardiovascular risk in patients wi 2018 Mar Pro-inflammatory cytokines such as leptin and IL-6 play an important role in the development of cardiovascular risk. Determine the relationship between leptin and IL-6 concentrations with cardiovascular risk in patients with rheumatoid arthritis. We determined IL-6 and leptin levels in 77 patients with the diagnosis of rheumatoid arthritis. The cardiovascular risk was calculated using the modified Framingham scale. Statistical analysis was performed using SPSS 22 considering a significant p < 0.05. Serum leptin concentrations and cardiovascular risk (CVR) factors were compared and found that there was a significant difference between higher leptin values and disease activity (p 0.047), obesity (p 0.038), positive rheumatoid factor (p 0.009), tobacco (p 0.009), and metabolic syndrome (p 0.001). Likewise, a significant relationship was found between lower leptin concentrations and hydroxychloroquine consumption (p = 0.023). We found significant difference between IL-6 concentrations and disease activity (p 0.028), hypertriglyceridemia (p 0.023), LDL-C (p 0.029), and smoking (0.005). Similarly, an association between hydroxychloroquine consumption and low concentrations of IL-6 was found (p 0.005). Framingham CVR was calculated and the result obtained was multiplied by 1.5. The 35.2% of the population studied had a low Framingham CVR, 38.9% moderate, and 25.9% presented a high risk. We compared the level of CVR and serum leptin and IL-6 concentrations, finding that the highest CVR was the leptin and IL-6 values. There is a positive association between CVR and serum leptin concentrations. It is also significantly associated with traditional and non-traditional risk factors.
30566451 Epidemiology and treatment patterns of rheumatoid arthritis in a large cohort of Arab pati 2018 OBJECTIVES: There is limited information on the epidemiology and treatment patterns of rheumatoid arthritis (RA) across the Arab region. We aim in this study to describe the demographic characteristics, clinical profile, and treatment patterns of patients of Arab ancestry with RA. METHODS: This is a cross sectional study of 895 patients with established rheumatoid arthritis enrolled from five sites (Jordan, Lebanon, Qatar, Kingdom of Saudi Arabia (KSA), and United Arab Emirates). Demographic characteristics, clinical profile, and treatment patterns are compared between the five countries. RESULTS: The majority of our patients are women, have an average disease duration of 10 years, are married and non-smokers, with completed secondary education. We report a high (>80%) ever-use of methotrexate (MTX) and steroids among our RA population, while the ever-use of disease modifying anti-rheumatic drugs (DMARDs) and TNF-inhibitors average around 67% and 33%, respectively. There are variations in RA treatment use between the five country sites. Highest utilization of steroids is identified in Jordan and KSA (p-value < 0.001), while the highest ever-use of TNF-inhibitors is reported in KSA (p-value < 0.001). CONCLUSION: Disparities in usage of RA treatments among Arab patients are noted across the five countries. National gross domestic product (GDP), as well as some other unique features in each country likely affect these. Developing treatment guidelines specific to this region could contribute in delivering standardized therapies to RA patients.
30412852 The renin-angiotensin system in the synovium promotes periarticular osteopenia in a rat mo 2018 Dec Periarticular osteopenia is the most specific hallmark of rheumatoid arthritis (RA). The renin-angiotensin system (RAS) in the synovium has been found to participate in the pathogenic process of RA. This study examined whether and how RAS regulates periarticular osteopenia in RA. The synovial tissues from patients with RA and osteoarthritis (OA) were prepared. Female Sprague-Dawley rats were treated with either saline, bovine type II collagen (CII) to induce arthritis (CIA), or CII combined with perindopril, an inhibitor of angiotensin-converting enzyme (ACE). Expressions of RAS components, including AT1R, AT2R and ACE, in human and rat synovial tissues were detected. Bone mass of rat joints was examined. Levels of RANKL, OPG and DKK-1 in rat synovium and expressions of TRAF6 and β-catenin in rat bone were examined. The results showed that AT1R, AT2R and ACE in human and rat synovium were up-regulated, but the increased ACE in rat synovial tissues was abrogated by perindopril. While CIA rats displayed increased bone resorption and decreased bone formation, perindopril treatment almost completely abrogated the RAS-mediated osteopenia, indicating that inhibition of ACE reduced the joint damages in rats. The expressions of RANKL and DKK-1 increased in CIA rats as compared with those in the control; TRAF6 was up-regulated and β-catenin was down-regulated in the bone tissues of CIA rats. The changes were then reversed by the use of perindopril. Our findings demonstrate that RAS in the synovium promotes periarticular osteopenia by increasing bone resorption and decreasing bone formation through modulating the RANKL/RANK/TRAF6 and Wnt/β-catenin pathways.
30541951 MiR-92a inhibits fibroblast-like synoviocyte proliferation and migration in rheumatoid art 2018 Dec Growing data have indicated that the miR-17-92 cluster is implicated in inflammatory response and rheumatoid arthritis (RA). This study was aimed to investigate the effects of miR-92a on the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Our results showed that miR-92a was significantly down-regulated in RA synovial tissue and RA-FLSs, whereas the protein level of AKT2 is increased. Restoration of miR-92a suppressed the proliferation and migration of RA-FLSs. Down-regulation of miR-92a promotes proliferation and migration of normal human FLSs. Dual luciferase reporter gene assay showed that miR-92a could specifically bind with the 30UTR of AKT2 and significantly repressed the luciferase activity. Down-regulation or up-regulation of miR-92a significantly increased or decreased the protein and phosphorylation levels of AKT2. siRNA-mediated down-regulation of AKT2 significantly prevented cell proliferation and migration of RA-FLSs, which were similar to the effects induced by overexpression of miR-92a. Moreover, AKT2 overexpression rescued miR-92a-mediated suppressive effect on proliferation and migration of RA-FLS. Thus, miR-92a could inhibit the proliferation and migration of RA-FLSs through regulation of AKT2 expression.
30515171 Autoantibodies to Peptidylarginine Deiminase 2 Are Associated With Less Severe Disease in 2018 Objective: Peptidylarginine deiminases (PAD) 2 and 4 are key enzymes in rheumatoid arthritis (RA) pathogenesis due to their ability to generate the protein targets of anti-citrullinated protein antibodies (ACPA). Anti-PAD4 antibodies that cross-react with PAD3 (anti-PAD3/4) have been identified and are associated with severe joint and lung disease. Here, we examined whether anti-PAD2 antibodies were present in patients with RA and defined their clinical significance. Patients and Methods: A PAD2 ELISA was established to screen for anti-PAD2 IgG in sera from RA patients from a prospective observational cohort study (n = 184) and healthy controls (n = 100). RA patient characteristics were compared according to anti-PAD2 antibody status. Multivariable models were constructed to explore the independent associations of anti-PAD2 antibodies with clinical variables. Results: Anti-PAD2 antibodies were found in 18.5% of RA patients and 3% of healthy controls (p < 0.001). Among RA patients, anti-PAD2 antibodies were not associated with traditional genetic or serologic RA risk factors, including HLA-DRβ1 shared epitope alleles, ACPA, rheumatoid factor (RF), or anti-PAD3/4 antibodies. In addition, antibodies to PAD2 were associated with fewer swollen joints, a lower prevalence of interstitial lung disease, and less progression of joint damage. In subset analyses in which patients were stratified by the baseline presence of ACPA/RF or anti-PAD3/4 antibodies, anti-PAD2 antibodies provided additional value in identifying patients with the least progressive joint disease. Conclusions: Anti-PAD2 antibodies represent a novel serologic marker in RA that identifies a genetically and clinically unique subset of patients with less severe joint and lung disease.