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ID PMID Title PublicationDate abstract
29367417 Comparative Cardiovascular Risk of Abatacept and Tumor Necrosis Factor Inhibitors in Patie 2018 Jan 24 BACKGROUND: We examined the cardiovascular risk of abatacept compared with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis with and without diabetes mellitus (DM). METHODS AND RESULTS: We conducted a cohort study of patients with rheumatoid arthritis who newly started abatacept or TNF inhibitors using claims data from Medicare and MarketScan. The primary outcome was a composite cardiovascular end point of myocardial infarction (MI), stroke/transient ischemic attack, and coronary revascularization. To account for >60 baseline characteristics, abatacept initiators were 1:1 propensity score (PS) matched to TNF initiators in each database. Cox proportional hazards models estimated hazard ratio (HR) and 95% confidence interval (CI) in the PS-matched cohort per database. A fixed-effects meta-analysis pooled database-specific HRs. We included a total of 13 039 PS-matched pairs of abatacept and TNF inhibitor initiators (6103 pairs in Medicare and 6936 pairs in MarketScan). A total of 34.7% in Medicare and 19.8% in MarketScan had baseline DM. The HR (95% CI) for the primary outcome associated with abatacept use versus TNF inhibitor was 0.81 (0.66-0.99) in Medicare and 0.95 (0.74-1.23) in MarketScan, with a pooled HR of 0.86 (95% CI, 0.73-1.01; P=0.3 for heterogeneity). The risk of the primary outcome was lower in abatacept initiators versus TNF inhibitors in the DM subgroup, with a pooled HR of 0.74 (95% CI, 0.57-0.96; P=0.7 for heterogeneity), but not in the non-DM subgroup, with a pooled HR of 0.94 (95% CI, 0.77-1.14; P=0.4 for heterogeneity). CONCLUSIONS: In this large population-based cohort of patients with rheumatoid arthritis, abatacept use appeared to be associated with a modestly reduced cardiovascular risk when compared with TNF inhibitor use, particularly in patients with DM.
29906533 Methylglyoxal modified IgG generates autoimmune response in rheumatoid arthritis. 2018 Oct 15 The detection of autoantibodies generated against modified proteins that stimulate cellular and humoral immune response has developed a lot of interest in the recent years and a search for biomarkers for the early detection of diseases has increased. IgG protein has earned attention for its possible modifications under hyperglycaemic conditions in rheumatoid arthritis, wherein dicarbonyl stress has been reported to alter the structural integrity of the protein. This report suggests that the interaction of the methylglyoxal with the IgG has consequences in the autoimmunopathology of rheumatoid arthritis. Our molecular docking analysis of methylglyoxal and IgG revealed a close interaction between the two molecules. TNBS studies confirmed the interaction by showing a decline in free lysine-arginine content post-MG modifications in IgG. The modified IgG was thermally more stable and showed the generation of glycation adducts N-epsilon-carboxyethyllysine. Rheumatoid arthritis patients showed enhanced carbonyl stress which was expected to induce structural changes in the epitope makeup of IgG. The ELISA studies and gel retardation assay confirmed auto-antibodies against MG modified IgG (MG-IgG) pointing towards the generation of neoepitopes upon IgG after interaction with MG. This study establishes the IgG modification in RA patients under alter carbonyl concentrations.
30107253 Evaluation of anti-arthritic potential of Trigonella foenum graecum L. (Fenugreek) mucilag 2018 Sep Rheumatoid arthritis is a chronic inflammatory joint disease characterized by synovial proliferation and tissue destruction. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play a key role in the disease process and elevate energy expenditure, which further increases the joint pain and stiffness. The present study was undertaken to explore the anti-arthritic potential of fenugreek mucilage in adjuvant induced arthritic rats. In the present study, paw volume was measured on the 7(th), 14(th) and 21(st) day. Finally, animals were anaesthetized; blood samples and tissues were collected for the assay of inflammatory enzymes like cyclooxygenase, lipoxygenase; evaluated the level of cytokines like IL-6, TNF-α, arthritic index and rheumatoid factor. Fenugreek mucilage exhibited maximum percentage of edema inhibition at a dose of 75 mg/kg on 21st day of adjuvant arthritis. The effect was higher than that of standard drug, indomethacin. The activities of inflammatory enzymes and concentration of mediators were decreased on treatment with fenugreek mucilage. Cytology of synovial fluid showed mild inflammation with normal synoviocytes (mesothelial cells) tried to bring back to normal characteristics on supplementation with fenugreek mucilage. Based on the observations, it can be suggested that fenugreek mucilage possesses promising anti-arthritic property and it can be used as a therapeutic agent for arthritis.
29106028 Association of High Anti-Cyclic Citrullinated Peptide Seropositivity and Lean Mass Index W 2018 Jul OBJECTIVE: Osteoporotic fractures are associated with high morbidity and mortality. Persons with rheumatoid arthritis (RA) have twice the risk of osteoporosis-related fracture than age-matched controls, the causes for which remain unknown. We investigated contributions of RA characteristics, medication use, and body composition to low bone mineral density (BMD) in patients with RA. METHODS: Data were from the Arthritis, Body Composition, and Disability Study (n = 138; 82 women, 56 men). Demographic, clinical, laboratory, and functional variables were collected at study visits. Body composition (fat, lean muscle, and BMD) was measured by dual x-ray absorptiometry. Linear regression analyses evaluated the association between predictors and femoral neck BMD. RESULTS: Average disease duration was 19 years, 70% of patients were rheumatoid factor positive, and 55% were high-positive anti-cyclic citrullinated peptide (anti-CCP). Age and high anti-CCP positivity were negatively associated with BMD after controlling for other variables (β = -0.003 and -0.055, respectively, P < 0.05). Appendicular lean mass index (ALMI) was positively associated with BMD (β = 0.053, P < 0.0001). In high anti-CCP positivity participants, increasing anti-CCP levels were associated with a negative linear trend in BMD (β = -0.011, P = 0.026). CONCLUSION: High anti-CCP positivity and ALMI were strongly associated with BMD in patients with RA. The linear relationship of anti-CCP levels with lower BMD supports the hypothesis that processes specific to RA negatively impact BMD. In contrast, ALMI was positively associated with BMD, emphasizing the importance of this potentially modifiable risk factor. Our findings highlight the complicated interplay of RA disease-specific and functional factors and their impact on bone mass.
29496215 A recording form for differential diagnosis of arthropathies. 2018 Mar The present study is focused on a group of arthropathies that may have very similar bone manifestations (rheumatoid arthritis, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, osteoarthritis and diffuse idiopathic skeletal hyperostosis), which makes it more difficult to diagnose them in human remains from archaeological contexts. A stepwise recording form was designed in order to improve the identification and differential diagnosis of these pathological conditions in bone remains, particularly in joint manifestations of the spine, pelvis, hands, feet and other limb joints. This recording form was applied in the analysis of two medieval individuals from the Basque Country (Spain) who presented very severe arthropathic manifestations. The use of this recording form allowed the researchers the diagnosis of ankylosing spondylitis in one of them and diffuse idiopathic skeletal hyperostosis in the other.
29258867 Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis 2018 Feb 1 There are numerous extra- and intra-cellular processes involved in the production of reactive oxygen species (ROS). Augmented ROS generation can cause the damage of biomolecules such as proteins, nucleic acid and lipids. ROS act as an intracellular signaling component and is associated with various inflammatory responses, chronic arthropathies, including rheumatoid arthritis (RA). It is well documented that ROS can activate different signaling pathways having a vital importance in the patho-physiology of RA. Hence, understanding of the molecular pathways and their interaction might be advantageous in the development of novel therapeutic approaches for RA.
30394138 Upadacitinib for the treatment of rheumatoid arthritis. 2019 Jan Introduction: Tofacitinib and baricitinib have recently been approved as second-line treatments for Rheumatoid arthritis (RA) though their maximum expected efficacy may be limited by dose-related toxicities. Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects. Areas covered: In this paper, we review a newly developed oral selective JAK inhibitor, upadacitinib for the treatment of RA. The doses of upadacitinib extended-release 15 and 30 mg daily selected in phase III RA studies have shown a near-maximum efficacy in phase II studies. Upadacitinib inhibited radiographic progression and displayed rapid and sustained clinical and functional efficacy in RA when in combination with methotrexate (MTX), upadacitinib was superior to placebo in MTX-Inadequate Responders (IRs) and biologic disease modifying antirheumatic drugs-IRs while as monotherapy, it was superior to MTX in MTX-IRs and MTX-naïve patients. Upadacitinib was superior to adalimumab using ACR70, reduction of pain-VAS and improvement of HAQ-DI. The comparison with abatacept is still ongoing. Expert commentary: Upadacitinib has displayed a rapid and favorable efficacy profile in RA but despite being a selective JAK1 inhibitor appears to have a similar safety profile to less-selective Jakinibs. Longer term safety data are awaited.
29542422 The Emerging Role of IL-1 Inhibition in Patients Affected by Rheumatoid Arthritis and Diab 2018 BACKGROUND: Although in the past, prevention of the joint destruction and disability was strongly emphasised in Rheumatoid Arthritis (RA), at present, a growing body of evidence is focused at identifying the best management of associated comorbidities, such as Type 2 Diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients. OBJECTIVE: We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process. METHOD: After literature search, the available evidence has been selected and commented in the text. RESULTS: During RA, it is well known that different inflammatory cytokines, such as interleukin-1β (IL-1β), are pivotal pathogenic mediators and their role has been largely confirmed in clinical settings. Similarly, it has been shown that the excess of nutrients, secondary to over-nutrition, may activate the immune system, leading to an increased production of inflammatory cytokines, including IL-1β, suggesting new possible therapeutic targets. CONCLUSION: Although further studies are needed to fully investigate the pathogenic interplay between inflammation and metabolic disorders, IL-1β has been implicated in both RA and T2D pathogenic mechanisms. Intriguingly, the potential role of anti-IL-1 drugs has been proposed in RA patients affected by T2D.
29228799 Calprotectin in patients with chronic rheumatoid arthritis correlates with disease activit 2018 Feb OBJECTIVE: Calprotectin (myeloid-related protein 8/14) is elevated in inflammatory diseases and a correlation of serum calprotectin and disease activity in rheumatoid arthritis (RA) has been shown. In this study, we investigated plasma calprotectin as a disease marker in patients with chronic RA treated with methotrexate (MTX) monotherapy and compared plasma calprotectin with C-reactive protein (CRP) in this matter. METHODS: Seventy-six patients with chronic RA were included in this open prospective study and of these 40 were included prior to initiation of MTX therapy. The patients were followed with laboratory and clinical parameters for 52-56 weeks. Plasma calprotectin was analyzed at the start of study and at various intervals. Radiographic evaluation was performed at baseline and after 17.2 months and progression in joint destruction was measured with Larsen score. The response to MTX was evaluated according to the American College of Rheumatology criteria. RESULTS: Patients starting MTX treatment had significantly higher levels of plasma calprotectin compared to patients well established on MTX therapy (p = .008). Among the 40 patients naive to MTX, 25 responded to MTX therapy and serum calprotectin decreased significantly in these patients (p = .0007). The radiographic damage showed no relation to calprotectin. CONCLUSIONS: Plasma calprotectin is associated with disease activity in patients with chronic RA and is more strongly correlated to MTX response compared to CRP. The role of calprotectin as a disease marker is promising and the advantages compared to CRP needs to be further investigated.
30076156 Predictors of disease activity and structural progression after treatment with adalimumab 2018 Nov OBJECTIVES: Methotrexate is considered to be first-line therapy for rheumatoid arthritis (RA). However, a substantial proportion of treated patients do not achieve the desired goals of therapy. This analysis aimed to identify predictors of insufficient response to methotrexate in patients with early RA. METHODS: The Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab (OPTIMA) and PREMIER studies in patients with RA for <1 and <3 years, respectively, examined the efficacy of methotrexate and adalimumab in methotrexate-naive patients. This post hoc analysis included patients for whom initial methotrexate monotherapy was not successful after 6 months. Candidate predictors of insufficient response and clinically relevant radiographic progression (CRRP) included demographics, baseline disease characteristics and time-averaged disease variables over a 12-week interval. In OPTIMA, adalimumab was added to therapy after insufficient treatment response; in PREMIER, initial methotrexate therapy was continued; clinical, functional and radiologic outcomes were assessed after 1 year. RESULTS: Baseline 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) and time-averaged DAS28(CRP) over 4, 8 and 12 weeks were the strongest predictors of insufficient response to methotrexate and CRRP. Addition of adalimumab to methotrexate therapy was associated with better clinical, functional and radiographic outcomes after 1 year compared with continuing on methotrexate monotherapy. CONCLUSIONS: In patients with early RA, baseline disease characteristics and early disease activity can predict response to methotrexate treatment and radiographic progression at 6 months. The addition of adalimumab at 6 months after methotrexate failure is associated with improved outcomes. These results support treatment-to-target strategies and timely adaptation of therapy in patients with early RA. TRIAL REGISTRATION NUMBER: NCT00420927, NCT00195663; Post-results.
28971583 Novel joint selection methods can reduce sample size for rheumatoid arthritis clinical tri 2018 Mar OBJECTIVES: To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. METHODS: Cohen's effect size (ES) was estimated (ES^) and a 95% CI (ES^L, ES^U) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL(ES^U), nU(ES^L)] were obtained on a post hoc sample size reflecting the uncertainty in ES^. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H(0) : ES = 0 versus alternative hypotheses H(1) : ES = ES^, ES = ES^L and ES = ES^U. We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study ES^S. RESULTS: Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10-245). Corresponding sample sizes using ICUS and IUS were 11 (7-40) and 11 (6-38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6-24) and 11 (6-35), respectively. CONCLUSIONS: Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations.
30260261 Smoking and response to rituximab in rheumatoid arthritis: results from an international E 2019 Jan OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.
29319370 Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relatio 2018 Apr OBJECTIVE: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals. METHODS: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls. RESULTS: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04-2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades. CONCLUSION: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.
30168781 Methotrexate-related lymphoproliferative disorder of the lumbar spine origin presenting wi 2018 Nov 1 The use of methotrexate (MTX) to treat rheumatoid arthritis (RA) is increasing. Recently, MTX-associated lymphoproliferative disorder (MTX-LPD) has been frequently reported as lymphoma occurring during MTX therapy. The authors report their experience with a relatively rare case of MTX-LPD presenting in the lumbar spine. The patient, a 73-year-old woman who experienced low-back pain while receiving MTX therapy for RA, was suspected of having developed MTX-LPD based on her medical history, images of the L1 vertebra, and transpedicular biopsy results. One week after discontinuing MTX, the patient's low-back pain reportedly improved. The woman was diagnosed with MTX-LPD based on histopathological findings. MTX discontinuation alone coincided with spontaneous tumor regression. Because MTX-LPD can occur in tissues other than lymph nodes, such as in bones and joints, it is a disease that should be considered when diagnosing spinal tumors in patients receiving MTX therapy.
28388816 Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease-Related Indicators 2018 Feb OBJECTIVE: Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. METHODS: Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown-like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. RESULTS: The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non-RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown-like structures was more than 1.5-fold higher in the RA group than in controls (0.58 versus 0.23 crown-like structure/high-power field, respectively; P = 0.001). ATMs were significantly more abundant in early RA and in those with anti-cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown-like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C-reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. CONCLUSIONS: ATMs and crown-like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown-like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.
29481721 Intramuscular Fat Accumulation and Associations With Body Composition, Strength, and Physi 2018 Dec OBJECTIVE: Rheumatoid arthritis (RA) is associated with adverse body composition profiles and low muscle density due to the accumulation of intramuscular fat. Linear regression was used to assess differences between RA patients and controls and to determine associations between muscle density, strength, and physical functioning. METHODS: Patients with RA, ages 18-70 years, and healthy control subjects underwent whole-body dual x-ray absorptiometry and peripheral quantitative computed tomography, in order to quantify the appendicular lean mass index (ALMI) and the fat mass index (FMI), visceral fat area, and muscle density. Dynamometry was used to measure hand grip strength and muscle strength at the knee and lower leg. Disability and physical functioning were measured using the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Linear regression analyses were performed to assess differences related to RA and associations between muscle density, strength, and function. RESULTS: The study group included 103 patients with RA (51 men) and 428 healthy control subjects. Among patients with RA, low muscle density was associated with higher disease activity, C-reactive protein and interleukin-6 levels, greater total and visceral fat area, lower ALMI Z scores, physical inactivity, and long-term use of glucocorticoids (>1 year). Patients with low ALMI Z scores had lower muscle density Z scores compared with reference participants with similarly low ALMI scores. Low muscle density was independently associated with lower muscle strength, higher HAQ scores, and lower SPPB scores, after adjustment for ALMI and FMI Z scores. CONCLUSION: The low muscle density observed in patients with RA was associated with low muscle mass, excess adiposity, poor strength, and greater disability. Interventions to address poor muscle quality could potentially affect important functional outcomes.
28758585 From A Formal Training Program In Musculoskeletal Ultrasound (MSUS) To A High Reproducibil 2018 OBJECTIVE: To assess the intra- and inter-observer reliability of Ultrasound (US) in scoring B-mode, Doppler synovitis and combined B-mode and Doppler synovitis scores in different peripheral joints of Rheumatoid Arthritis (RA) patients. METHODS: Four rheumatologists with a formal training in Musculoskeletal US (MSKUS) particularly focus on definitions and scoring synovitis on B-mode and Doppler mode participated in a patient- based reliability exercise on 16 active RA patients. The four rheumatologists independently and consecutively performed a B-mode and Power Doppler (PD) US assessment of 7 joints of each patient in two rounds in a blinded fashion. Each joint was semi quantitatively scored from 0 to 3 for B-mode Synovitis (BS), Doppler Synovitis (DS), and combined B-mode/Doppler synovitis (CS). Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by unweight Light's κ. RESULTS: The mean prevalence of synovitis on B-mode was 83% of joints; scores ranging from grade 1 in 18% of joints, to grade 3 in 33%. In 55% of joints synovial PD signal was detected and the distribution of scores range from 14% of joints for grade 3, to 26% for grade 2. After a total of 448 joints scanned with 896 adquired images our intraobserver and interobserver reliability was good to excellent for most of the joints. CONCLUSION: Formal, structured and continuous training in musculoskeletal ultrasound would bring a good to excellent reproducibility in rheumatological hands with a high reliability in real time acquisition BS, DS and CS modalities for scoring synovitis in patients with active rheumatoid arthritis.
28766392 Vagal influences in rheumatoid arthritis. 2018 Jan Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease with a prevalence of 0.5-1% in Western populations. Conventionally, it is treated with therapeutic interventions that include corticosteroids, disease-modifying anti-rheumatic drugs, and biological agents. RA exerts a significant socio-economic burden and despite the use of existing treatments some patients end up with disabling symptoms. The autonomic nervous system (ANS) is a brain-body interface that serves to regulate homeostasis by integrating the external environment with the internal milieu. The main neural substrate of the parasympathetic branch of the ANS is the vagus nerve (VN). The discovery of the role of the ANS and the VN in mediating and dampening the inflammatory response has led to the proposal that modulation of neural circuits may serve as a valuable therapeutic tool. Recent studies have explored the role of the VN in this inflammatory reflex and have provided evidence that stimulation may represent a novel new therapeutic intervention. Accumulating evidence suggests that modulation of the parasympathetic tone results in a broad physiological multi-level response, including decreased pro-inflammatory cytokine response in terms of tumour necrosis factor-α, interleukin-1 (IL-1), and IL-6, and may result in an enhanced macrophage switch from M1 to M2 cells and potentially an increased level of the anti-inflammatory cytokine IL-10. Therefore, therapeutic electrical modulation of the VN may serve as an alternative, non-pharmacological, neuroimmunomodulatory intervention in RA in the future. This review gives a focused introduction to the mechanistic link between the ANS and the immune system.
30213690 The Mediterranean diet, fish oil supplements and Rheumatoid arthritis outcomes: evidence f 2018 Nov The impact of dietary interventions such as specific types of diet or nutritional supplements in rheumatoid arthritis (RA) has been subject to increased attention in recent years. The recognition of the unmet need to better understand the effects of specific dietary interventions on disease outcomes in RA, along with the growing patient interest on lifestyle interventions beyond pharmacotherapy, have informed the undertaking of this narrative literature review. The benefits of the Mediterranean Diet (MD) have been shown in various studies, although only a limited number of trials focus specifically on RA. Based on the studies reviewed, the MD may provide benefits in reducing pain and swollen and tender joints in RA patients. There is more and better evidence that n-3 polyunsaturated fat (PUFA) supplementation has the potential to reduce inflammation and provide clinical benefit, possibly slowing progression to pharmacotherapy. Yet, many of these studies to date are limited in their methodology; this being partly a reflection of the complexity of the research questions being addressed. Consequently, the conclusions that can be robustly drawn from their results are restricted. With a focus on clinical trials on the MD and fish oil supplementation, this review critically appraises the evidence, discussing the findings of studies in the wider context of impact on RA outcomes, methodological challenges, and practical points to consider as part of the routine care of RA patients.
29903680 [Non-infective endocarditis]. 2018 Oct Non-infective endocarditis, also referred to as non-bacterial thrombotic endocarditis, represent a wide range of rare pathologies, often severe. This review gathered the data available in the literature, to decipher the major information collected on the pathophysiology, the diagnosis and the treatment of these heterogeneous diseases, often misdiagnosed. Characteristics of non-infective endocarditis are similar to infective endocarditis in terms of valvular lesions (mostly left-sided, with regurgitations and vegetations), and their complications (embolism). The diagnosis of non-infective endocarditis is usually considered in patients with blood culture-negative endocarditis. Beyond the usual suspects - marastic endocarditis and systemic lupus erythematosus - which represent more than 75% of the cases, Behçet disease and hypereosinophilic syndrome are the main causes of non-infective endocarditis. More seldomly, rheumatoid arthritis, adult-onset Still disease, allergy to pork in patients with valvular procine bioprosthesis, systemic scleroderma, Cogan or Sneddon syndrome should be suspected. Diagnostic approach is based on history and physical examination, with a special focus on extra-cardiac manifestations, as well as echocardiography, and computed tomography. Treatment relies on intensive management of the underlying disease. Curative anticoagulation is often necessary. Although indications for cardiac surgery are poorly defined, as compared to infective endocarditis, data currently available suggest that an optimal control of the underlying disease before cardiac surgery is of utmost importance, as it dramatically reduces the risk of postoperative complications.