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ID PMID Title PublicationDate abstract
30836801 Radiographic and clinical outcomes following etanercept monotherapy in Japanese methotrexa 2020 Mar Objectives: Compare outcomes with methotrexate (MTX) or etanercept (ETN) monotherapy in Japanese patients with active rheumatoid arthritis (RA) who were MTX-naïve or with intolerance or inadequate response to prior MTX (MTX-IR).Methods: Post hoc analysis of a phase 3 study comparing MTX, ETN 10 mg twice weekly, and ETN 25 mg twice weekly in Japanese patients with RA. Disease activity was evaluated using American College of Rheumatology (ACR) scores and 28-joint Disease Activity Score (DAS28), radiographic progression evaluated using van der Heijde's modified Total Sharp Score (mTSS), and functional status evaluated using Health Assessment Questionnaire Disability Index (HAQ-DI).Results: Among MTX-naïve and MTX-IR patients, greater proportions of those randomized to either ETN group achieved ACR20, ACR50, ACR70, DAS28 ≤3.2 or <2.6, clinically relevant inhibition of mTSS changes, and reductions in HAQ-DI compared with MTX at the majority of time points. There were very few clinically meaningful differences between ETN groups for any of the variables evaluated.Conclusion: ETN monotherapy was more effective than MTX in both MTX-naïve and MTX-IR patients, with very few clinically meaningful differences between ETN 10 mg and ETN 25 mg when given twice weekly. The relative benefits of ETN were greater in MTX-naïve patients than MTX-IR patients.ClinicalTrials.gov identifierNCT00445770.
33377396 Differential synovial tissue expression of TLRs in seropositive and seronegative rheumatoi 2021 Feb Toll-like receptors (TLRs) are known to have an important role in triggering the innate immune response and in priming antigen-specific adaptive immunity and inflammation. The differences in synovial tissue expression of the TLRs between seronegative and seropositive rheumatoid arthritis (RA) were examined from 9 seropositive RA, 5 seronegative RA and 4 osteoarthritis (OA) patients. Synovitis status was assessed using Krenn's scoring and TLR 1-9 expression by immunohistochemistry. Tissue citrulline content was analysed by HPLC method. In RA TLR expression was generally higher than in OA. TLR2 expression was higher in both seronegative and seropositive RA compared to OA. TLR 1, 4 and 8 expressions were higher in seropositive RA than in seronegative RA or in OA. For TLRs 3, 5, 6, 7 and 9 local differences of expression were found between groups. TLR 1-9 expression correlated with the synovitis grade. No statistical difference was found in synovial tissue citrulline content between the groups. In seropositive RA, the TLR repertoire in the synovial tissue differs from seronegative RA and could explain differences in disease outcomes. The high expression of protein sensing (TLR1, TLR2 and TLR4) and nucleic acid sensing TLRs (TLR7, TLR8 and TLR9) in the seropositive RA could make the synovium primed for reacting to citrullinated proteins and nucleic acids that could be released to extracellular space in formation of neutrophil extracellular traps. This reactivity could be augmented by Fc receptor activation by anti-citrullinated protein antibody immunocomplexes associated with seropositive RA.
32216502 Quercetin suppresses migration and invasion by targeting miR-146a/GATA6 axis in fibroblast 2020 Jun Background: Rheumatoid arthritis (RA) is a systematic autoimmune disease which may lead to joint dysfunction and disability. Aberrant migration and invasion of fibroblast-like synoviocytes (FLSs) is one of the most predominant etiopathogenesis of RA. Quercetin is a bioflavonoid which is implicated in the development of RA, yet its role in regulating the migration and invasion of FLSs is still elusive. The aim of this study is to investigate the impact of quercetin treatment on migration and invasion of FLSs and the underlying mechanism.Methods: Capacity of migration and invasion of FLSs were assessed using transwell assay. Immunofluorescence assay was used to determine the expression of F-actin. The RNA levels of miR-146a and GATA transcription factor 6 (GATA6) were measured using quantitative real-time PCR. Western blot was used to examine the protein level of GATA6. The correlation between miR-146a and GATA6 was validated using luciferase reporter assay.Results: Transwell assay revealed that the migration and invasion of FLSs were significantly inhibited after quercetin treatment, which was also proved by decreased expression of F-actin. The RNA level of miR-146a was decreased in RA tissues and was negatively related to the expression of GATA transcription factor 6 (GATA6). Quercetin treatment elevated the RNA level of miR-146a, but suppressed the expression of GATA6 in FLSs. Further luciferase reporter assay validated that GATA6 is a downstream target of miR-146a. Besides, miR-146a inhibited the migration and invasion of FLSs, and further GATA6 over-expression abrogated the miR-146a-induced inhibition. In addition, specific anti-miR-146a inhibitor abolished quercetin-mediated suppression of migration and invasion of FLSs.Conclusion: Our study suggested that quercetin suppresses the migration and invasion of FLSs via regulating the miR-146a/GATA6 axis.
30935255 Patients opinion and adherence to antimalarials in lupus erythematosus and rheumatoid arth 2020 May Objective: To obtain the opinion of patients with rheumatoid arthritis or lupus erythematosus about the use of antimalarials through questionnaires and to evaluate their adherence to medication.Methods: A cross-sectional study of patients treated with antimalarial medication for a period equal to or longer than 1 year attended between November 2012 and October 2014. A structured questionnaire with 12 questions was filled out.Results: Among 300 patients examined, 92% (275) used medication regularly. Hydroxychloroquine was used by 55% (166) of patients, chloroquine by 25% (75), and 20% (59) reported using both medications at different moments. Most of the patients (221 or 74%) were using medication seven days a week and had taken it for a period longer than 5 years; 61% (182) considered the treatment good and said, 21% (63) said, 'It is good, but I'm afraid of taking it'. Most of the patients (70% or 211) did not report any adverse symptoms. Their main claim was related to blurred vision, which was solved by a refraction examination.Conclusions: Fear has been a factor that makes adherence to treatment difficult. Making patients aware of the importance of the treatment is strongly relevant because antimalarials are well tolerated.
33276814 Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk 2020 Dec 4 BACKGROUND: Rheumatoid arthritis (RA) patients have increased risk for cardiovascular disease (CVD). Accurate CVD risk prediction could improve care for RA patients. Our goal is to develop and validate a biomarker-based model for predicting CVD risk in RA patients. METHODS: Medicare claims data were linked to multi-biomarker disease activity (MBDA) test results to create an RA patient cohort with age ≥ 40 years that was split 2:1 for training and internal validation. Clinical and RA-related variables, MBDA score, and its 12 biomarkers were evaluated as predictors of a composite CVD outcome: myocardial infarction (MI), stroke, or fatal CVD within 3 years. Model building used Cox proportional hazard regression with backward elimination. The final MBDA-based CVD risk score was internally validated and compared to four clinical CVD risk prediction models. RESULTS: 30,751 RA patients (904 CVD events) were analyzed. Covariates in the final MBDA-based CVD risk score were age, diabetes, hypertension, tobacco use, history of CVD (excluding MI/stroke), MBDA score, leptin, MMP-3 and TNF-R1. In internal validation, the MBDA-based CVD risk score was a strong predictor of 3-year risk for a CVD event, with hazard ratio (95% CI) of 2.89 (2.46-3.41). The predicted 3-year CVD risk was low for 9.4% of patients, borderline for 10.2%, intermediate for 52.2%, and high for 28.2%. Model fit was good, with mean predicted versus observed 3-year CVD risks of 4.5% versus 4.4%. The MBDA-based CVD risk score significantly improved risk discrimination by the likelihood ratio test, compared to four clinical models. The risk score also improved prediction, reclassifying 42% of patients versus the simplest clinical model (age + sex), with a net reclassification index (NRI) (95% CI) of 0.19 (0.10-0.27); and 28% of patients versus the most comprehensive clinical model (age + sex + diabetes + hypertension + tobacco use + history of CVD + CRP), with an NRI of 0.07 (0.001-0.13). C-index was 0.715 versus 0.661 to 0.696 for the four clinical models. CONCLUSION: A prognostic score has been developed to predict 3-year CVD risk for RA patients by using clinical data, three serum biomarkers and the MBDA score. In internal validation, it had good accuracy and outperformed clinical models with and without CRP. The MBDA-based CVD risk prediction score may improve RA patient care by offering a risk stratification tool that incorporates the effect of RA inflammation.
33337994 Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic s 2021 Sep OBJECTIVES: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. METHODS: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. RESULTS: In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. CONCLUSIONS: An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.
32568738 Inhibition of BMP3 increases the inflammatory response of fibroblast-like synoviocytes in 2020 Jun 22 Rheumatoid arthritis (RA) is a persistent autoimmune disease. Fibroblast-like synoviocytes (FLS) are a key component of invasive pannus and a pathogenetic mechanism in RA. Expression of bone morphogenetic protein 3 (BMP3) mRNA is reportedly decreased in the arthritic synovium. We previously showed that BMP3 expression is significantly downregulated in the synovial tissues of RA patients and models of adjuvant-induced arthritis (AIA). In the present study, we explored the association between BMP3 and FLS migration and secretion of proinflammatory factors in RA. We found that inhibition of BMP3 expression using BMP3 siRNA increased the proinflammatory chemokines and migration of FLS stimulated with TNF-α. Inhibition of BMP3 expression also increased expression of IL-6, IL-1β, IL-17A, CCL-2, CCL-3, VCAM-1, MMP-3, and MMP-9, but not TIMP-1, in AIA and RA FLS. Correspondingly, induction of BMP3 overexpression through intra-articular injection of ad-BMP3 diminished arthritis severity in AIA rats. We also found that BMP3 may inhibit activation of TGF-β1/Smad signaling. These data indicate that BMP3 may suppress the proliferation and migration of FLS via the TGF-β1/Smad signaling pathway.
33399728 [Change of diagnosis and diagnostic category in patients with juvenile idiopathic arthriti 2020 Aug INTRODUCTION: At least 50% of pediatric patients with Juvenile Idiopathic Arthritis (JIA) will require continued fo llow-up in adult rheumatology. The present International League of Associations for Rheumatology (ILAR) classification, currently under revision, differs from its classification of inflammatory arthritis in adults. Category changes have been reported in 10.8% of patients during follow-up. OBJECTIVE: To analyze JIA patients in follow-up for at least 7 years to detect diagnosis changes during transition to adult care, identifying factors of poor functional prognosis. PATIENTS AND METHOD: Retrospective study based on medical records of JIA patients seen at the pediatric polyclinic of the Puerto Montt Hospital between 2005 and 2017, who were monitored for at least 7 years. Descriptive analysis was performed according to clinical variables: diagnostic category, evolution before diagnosis, clinical and serological activity, and evolution before starting drug therapy. RESULTS: We evaluated 18 pa tients, corresponding to 3 patients with persistent oligoarticular arthritis (OA), 1 with extended OA, 4 with polyarticular arthritis (PA) rheumatoid factor (RF) negative, 4 with PA RF positive, 5 with syste mic JIA, and 1 with psoriatic arthritis, all have had follow-up more than 7 years. 11 out of 18 patients transitioned to adult care. Three out of 11 patients changed diagnosis to Rheumatoid Arthritis (RA) plus another autoimmune disease such as Sjögren's Syndrome + Systemic Lupus Erythematosus, Immune thrombocytopenia, or unclassified autoimmune disease, and 5 out of 11 children changed ILAR category from OA to Juvenile Rheumatoid Arthritis, extended OA to PA RF negative, and 3 from Systemic arthritis to PA RF negative. Age of onset, polyarticular forms, delay in diagnosis, and the start of therapy were associated with sequelae and persistent inflammation. CONCLUSIONS: Eight of the eleven JIA patients who transitioned to adult care changed their diagnosis or presented other autoimmune diseases. Some factors of poor prognosis must improve.
32573416 Severely destructive unilateral wrist arthritis as a rare variant of rheumatoid arthritis: 2021 Mar OBJECTIVES: Rheumatoid arthritis (RA) is a common autoimmune disease typically affecting joints symmetrically. A small number of patients develop unilateral and severely destructive wrist arthritis (DWA). The objective of our study was to characterise patients with this type of affection. METHODS: This was a retrospective cohort study of RA patients with positive RF/anti-CCP antibodies. Clinical characteristics, including, age, gender, disease duration, dexterity, occupational history, smoking status, and the number of prescribed DMARDs were recorded. Conventional radiographs were evaluated using the modified Sharp/van der Heijde scoring (mSS) method. RESULTS: We analysed our laboratory database of 1247 patients and identified 559 patients with a clinical diagnosis of RA. For 395 of the patients, radiographs of the hands were available for evaluation. 25 patients had extensive unilateral DWA, corresponding to a prevalence of 6.3% (25 of 395 patients). 11 patients were excluded due to incomplete data. Of the remaining 14 patients, 13 were female with a median age of 61 (33-83) years, and median disease duration of 18 (1-33) years. 8 of 11 (72.7%) patients were smokers; in three, smoking status was not known. 80% with known dexterity developed unilateral DWA in the dominant hand. Total mSS was significantly higher on the affected side (39, interquartile range 35.25-46.25) versus non-affected (13, IQR 3-23). MSS were not different if the carpal bones were excluded from scoring. Side of involvement (left vs. right), or dominant versus non-dominant hand, did not result in a different mSS. CONCLUSIONS: Unilateral DWA is a rare variant of RA which predominantly affects women who smoke.
32403006 Upregulation of circulating inflammatory biomarkers under the influence of periodontal dis 2020 Jul OBJECTIVES: Periodontal disease (PD) and rheumatoid arthritis (RA) are chronic immuno-inflammatory conditions with osteolysis being a hallmark feature. The influence of PD on RA's systemic inflammatory status and disease activity remains unclear. The objective of this study was to assess the systemic inflammation and disease activity of RA under the influence of PD. METHODS: In this case-control study, 38 RA patients (19 with PD and 19 without PD) were compared to 38 non-RA patients and 12 healthy controls. Periodontal parameters (bleeding on probing (BOP), probing pocket depth (PPD), PPD Total, PPD Disease and marginal bone loss (MBL) were determined. Serological analyses included quantification of 92 inflammatory biomarkers using a multiplex proximity extension assay, anti-citrullinated protein antibodies (ACPA), rheumatoid factor (IgM-RF) and erythrocyte sedimentation rate (ESR). RA disease activity was determined using Disease Activity Score for 28 joints (DAS28). All RA patients were on medication. RESULTS: IgM-RF was higher in RA patients with PD. PD conditions were more severe in the non-RA group. Inflammatory biomarkers (IL-10RB, IL-18, CSF-1, NT-3, TRAIL, PD-L1, LIF-R, SLAMF1, FGF-19, TRANCE, CST5, STAMPB, SIRT2, TWEAK, CX3CL1, CXCL5, MCP-1) were significantly higher in RA patients with PD than RA without PD. DAS28 associated with twice as many inflammatory biomarkers in RA patients with PD whereas IgM-RF and ACPA associated more frequently with biomarkers in the RA without PD group. IgM-RF correlated inversely with BOP. CONCLUSION: Periodontal disease augments systemic inflammation in RA. A profound influence exists independent of autoimmune status.
33269836 [Involvement of NF-κB signal pathway in acupuncture treatment of patients with rheumatoid 2020 Nov 25 OBJECTIVE: To observe the effect of acupuncture on nuclear factor kappa-B(NF-κB)signaling pathway in patients with rheumatoid arthritis (RA), so as to explore the mechanism of acupuncture in the treatment of RA. METHODS: A total of 120 RA patients admitted to the Xinyu Hospital of Traditional Chinese Medicine in Jiangxi Province from June 2018 to June 2019 were selected and randomly divided into a control group and a treatment group, with 60 cases in each group. The patients in the control group received oral administration of Methotrexate, (10-15) mg/time, once a week, for a total of 10 weeks. On the basis of oral administration of Methotrexate, patients in the treatment group were treated with acupuncture at Quchi(LI11), Zusanli(ST36), Taichong(LR3), Hegu(LI4), Shenshu(BL23), Geshu(BL17) and Dazhui(GV14) once daily. The treatment was conducted 6 consecutive times as a course for 10 courses. The serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), pain visual analog scale (VAS) score, number of swollen joints, and morning stiffness time before and after treatment were compared between the two groups. The expression levels of inflammatory related factors and NF-κB p65 protein in the synovial fluid were detected by enzyme-linked immunosorbent assay and Western blot separately. RESULTS: After treatment, both groups had significant decrease in CRP, ESR, VAS score, number of swollen joints and morning stiffness time, levels of NF-κB p65 protein, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 (P<0.05) in the joint fluid, and increase in transforming growth factor-β (TGF-β) and IL-10 (P<0.05). After treatment, compared with the control group, CRP, ESR, VAS score and morning stiffness time, and the levels of NF-κB p65, TNF-α, IL-1β and IL-6 in the treatment group were down-regulated (P<0.05), while the level of TGF-β was up-regulated (P<0.05). The treatment group had a higher total effective rate than the control group［85.0%(51/60) vs 75.0%(45/60), P<0.05］. CONCLUSION: Acupuncture can inhibit the expression of NF-κB signaling pathway in RA patients, regulate the levels of related inflammatory factors, and thus improve the symptoms of RA patients.
31612736 Association among anti-citrullinated protein antibody status, erosive disease and healthca 2020 Feb Objective: To characterize the rate of healthcare resource utilization (HCRU) between anti-cyclic citrullinated peptide (CCP; a surrogate for anti-citrullinated protein antibodies [ACPAs]) positive (+) patients with rheumatoid arthritis (RA), either with or without erosions, who initiated biologic disease-modifying antirheumatic drug (bDMARD) treatment.Methods: Data from the Corrona RA registry, a prospective registry of adult patients with RA from 177 sites across 42 states in the US, were analyzed. Annual rates of HCRU (measured based on rates of all-cause hospitalization, joint surgery, imaging procedures and use of assistive devices) were estimated in anti-CCP + patients with and without erosions following bDMARD initiation using a Poisson regression model.Results: Among the 3333 patients with known anti-CCP and erosion status and 12-month post-bDMARD follow-up information in the Corrona registry, 2047 were anti-CCP + and included in this analysis; 868 with and 1179 without erosions. Baseline characteristics were generally well balanced between patients with and without erosions; however, those with erosions had a longer mean RA duration and a higher prior DMARD use. Over 12 months, among anti-CCP + patients, those with erosions had significantly higher rates of all HCRU, except joint surgery, than those without erosions. Age-adjusted risk ratios (95% confidence interval) were as follows: all-cause hospitalization, 1.47 (1.14, 1.90); all-cause imaging, 1.25 (1.03, 1.53); and assistive device use 1.12 (1.00, 1.25). The rate of joint surgery visits was also numerically higher in patients with versus without erosion.Conclusions: ACPA seropositivity with erosive disease was associated with higher rates of HCRU compared with seropositivity without erosions. These findings suggest that providers may want to manage anti-CCP + patients aggressively to achieve better disease control to prevent the development of erosions and the associated increase in HCRU.
33087158 Galuteolin suppresses proliferation and inflammation in TNF-α-induced RA-FLS cells by act 2020 Oct 21 OBJECTIVE: Galuteolin (Galu) is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the effects of Galu on the TNF-α-induced RA-FLS cells (synoviocytes) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis and anti-inflammation. METHODS: After TNF-α stimulation, cell proliferation of RA-FLS was assessed by CCK-8 assay. TUNEL staining was used to detect the apoptosis. Western blot was used to detect the expressions of Iκκβ, p-p65, p65, p-IκB, IκB, Cleaved-caspase3, Caspase-3, Bcl-2, and Bax. HO-1 were determined by RT-PCR. The contents of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MMP-1 were determined by ELISA. RESULTS: Galu significantly suppressed cell proliferation in a dose-dependent manner. Additionally, Galu obviously promotes cell apoptosis rate of RA-FLS cells and elevated the expression levels of HO-1, caspase-3, and Bax, while reducing the expression level of Bcl-2. Furthermore, Galu apparently inhibited the levels of Iκκβ, p-p65, and p-IκB. Moreover, Galu also significantly reduced the levels of pro-inflammatory factors IL-1β, IL-6, IL-8, and MMP-1 in RA-FLS cells. CONCLUSION: Galuteolin exerts protective effects against TNF-α-induced RA-FLS cells by inhibiting apoptosis and inflammation, which can guide the clinical use of rheumatoid arthritis.
30499364 Disease activity, treatment and long-term prognosis of adult juvenile idiopathic arthritis 2020 Jan Objective: To evaluate the difference between adult juvenile idiopathic arthritis (JIA, starting at <16 years) and rheumatoid arthritis (RA).Methods: Data on 128 adult JIA patients were from the National Database of Rheumatic Diseases in Japan (NinJa), 2014, divided into 4 groups by period of disease onset (Group 1: 2000-2013, n = 32; Group 2: 1981-1999, n = 32; Group 3: 1966-1980, n = 31; Group 4: ∼1965, n = 33). Disease activity, treatment and long-term prognosis of adult JIA patients were compared with RA patients matched for sex- and disease duration in each era.Results: In Groups 1 and 2, adult JIA patients had significantly lower clinical disease activity indices (CDAI) (Group 1: adult JIA 1.5 [0.4-6.9]-vs-RA 5.3 [2.5-10.3], p = .001, Group 2: 2.6 [0.6-9.0]-vs-6.9 [3.5-11.0], p = .001, shown as median [quartile range], p-value, respectively), and had higher CDAI remission rates than RA patients (Group 1: 54.8%-vs-28.2%, p = .002, Group 2: 51.7%-vs-17.0%, p < .001). More adult JIA than RA patients in Group 1 used biologics (62.5%-vs-24.7%, p < .001). However, there were no adult JIA-vs-RA differences in joint destruction and physical function in any group.Conclusions: Adult rheumatologists must recognize that adult JIA patients are different from RA patients even when disease duration is the same.
30821928 Systematic Review of Recommendations on the Use of Disease-Modifying Antirheumatic Drugs i 2020 Mar OBJECTIVE: To evaluate consensus recommendations regarding management of rheumatoid arthritis (RA) in patients with cancer. METHODS: We searched electronic databases, guideline registries, and relevant web sites for cancer-specific recommendations on RA management. Reviewers independently selected and appraised the recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. We identified similarities and discrepancies among recommendations. RESULTS: Of 4,077 unique citations, 39 recommendations were identified, of which half described their consensus process. Average scores for the AGREE II domains ranged from 33% to 87%. Cancer risk in RA was addressed in 79% of recommendations, with acknowledgement of increased overall cancer risk. Recommendations did not agree on the safety of using disease-modifying antirheumatic drugs (DMARDs) in RA patients with cancer, except for the contraindication of tumor necrosis factor inhibitors in patients at risk for lymphoma. Most recommendations agreed that RA treatment should be stopped and re-evaluated with a new diagnosis of cancer. Recommendations for patients with a history of cancer differed depending on the drug, cancer type, and time since cancer diagnosis. Few recommendations addressed all issues. CONCLUSION: Recommendations for the treatment of RA in patients with cancer often fail to meet expected methodologic criteria. There was agreement on the need for caution when prescribing DMARDs to these patients. However, several areas continue to lack consensus, and given the paucity of evidence, there is an urgent need for research and expert opinion to guide and standardize the management of RA in patients with cancer.
32928474 Extensive evaluation of sample preparation workflow for gas chromatography-mass spectromet 2020 Sep 22 GC-MS platform has been proved to be an important analytical technique for plasma metabolomics, but lack of efficient sample preparation strategies prior to sample injection has limited its wide application. In the present work, twenty two extraction protocols including protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE) and ultrafiltration were simultaneously evaluated using non-spiked and metabolite standards spiked human plasma. Sample-to-extraction solvent ratio and metabolites derivatization conditions were also investigated and optimised. The results demonstrated that stepwise LLE protocol (MeOH-H(2)O/CHCl(3)/CHCl(3)-MeOH) was the most efficient extraction strategy for the combination of untargeted and targeted metabolomics. Sample-to-extraction solvent ratio of 1:3 (v:v) was found to perform better than higher solvent ratios. Also, the maximum derivatization performance was obtained when using 30 μL N-methyl-N-tri-methylsilyltrifluoroacetamide (MSTFA) and 1% trimethyl-chlorosilane (TMCS) incubated at 60 °C for 120 min. In the end, the optimised sample preparation method was applied successfully to plasma untargeted metabolomics of rheumatoid arthritis (RA) and four metabolites (gamma-butyrolactone, MG (0:0/18:0/0:0), tocopherol and oxalic acid) were found to be potential biomarkers for the diagnosis of RA.
32483659 Tertiary Lymphoid Organs in Rheumatoid Arthritis. 2020 Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects the joints, with inflammation of the synovial membrane, characterized by hyperplasia, neo-angiogenesis, and immune cell infiltration that drives local inflammation and, if untreated, can lead to joint destruction and disability. In parallel to the well-known clinical heterogeneity, the underlying synovitis can also be significantly heterogeneous. In particular, in about 40% of patients with RA, synovitis is characterized by a dense lymphocytic infiltrate that can acquire the features of fully functional tertiary lymphoid organs (TLO). These structures amplify autoimmunity and inflammation locally associated with worse prognosis and potential implications for treatment response. Here, we will review the current knowledge on TLO in RA, with a focus on their pathogenetic and clinical relevance.
32256192 Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis. 2020 Rheumatoid arthritis is a chronic autoimmune syndrome associated with several genetic, epigenetic, and environmental factors affecting the articular joints contributing to cartilage and bone damage. Although etiology of this disease is not clear, several immune pathways, involving immune (T cells, B cells, dendritic cells, macrophages, and neutrophils) and nonimmune (fibroblasts and chondrocytes) cells, participate in the secretion of many proinflammatory cytokines, chemokines, proteases (MMPs, ADAMTS), and other matrix lysing enzymes that could disturb the immune balance leading to cartilage and bone damage. The presence of autoantibodies preceding the clinical onset of arthritis and the induction of bone erosion early in the disease course clearly suggest that initiation events damaging the cartilage and bone start very early during the autoimmune phase of the arthritis development. During this process, several signaling molecules (RANKL-RANK, NF-κB, MAPK, NFATc1, and Src kinase) are activated in the osteoclasts, cells responsible for bone resorption. Hence, comprehensive knowledge on pathogenesis is a prerequisite for prevention and development of targeted clinical treatment for RA patients that can restore the immune balance improving clinical therapy.
31285112 Changes to Body Composition in Women With Long-Standing Established Rheumatoid Arthritis: 2020 Oct INTRODUCTION: Few studies on rheumatoid arthritis have investigated disease activity and body composition by dual-energy X-ray absorptiometry including evaluation of visceral adipose tissue. Thus, we sought to verify the association between body composition by dual-energy X-ray absorptiometry, including visceral adipose tissue, and inflammatory activity in long-standing established rheumatoid arthritis. METHODS: Seventy-eight postmenopausal women with rheumatoid arthritis (American College of Rheumatology 2010) were studied. Disease activity was assessed by composite indexes (DAS28, CDAI, SDAI) and C-reactive protein. Potential association between body composition and disease activity was analysed by Pearson correlation and Tukey´s test (p < 0.05). RESULTS: There was significant negative correlation between C-reactive protein and appendicular lean mass index (r = -0.234, p = 0.039). After adjusting for confounding variables, women with C-reactive protein >10 mg/L had a lower appendicular lean mass index than those with C-reactive protein 5-10 mg/L and <5 mg/L (6.3 ± 0.8 kg/m(2) vs 7.2 ± 1.2 kg/m(2) vs 6.8 ± 1.0 kg/m(2), respectively; p = 0.013). Women with moderate inflammation (C-reactive protein 5-10 mg/L) had more fat than those with C-reactive protein >10 mg/L and C-reactive protein <5 mg/L (12.4 ± 3.5 kg/m(2) vs 9.9 ± 3.6 kg/m(2) vs 10.5 ± 2.8 kg/m(2), respectively; p = 0.040), as well as more visceral adipose tissue than women with higher and lower C-reactive protein (812.5 ± 266.4 cm(3) vs 604.3 ± 236.3cm(3) vs 658.9 ± 255.6 cm(3); p = 0.009). CONCLUSIONS: High inflammatory activity that persists after a long disease duration was associated with both lower muscle and fat mass (including visceral adipose tissue), which is suggestive of more exuberant rheumatoid cachexia. Conversely, moderate activity was associated with greater visceral adipose tissue, which is associated with increased cardiovascular risk. These results point to the existence of different body composition profiles according to inflammatory status and the importance of individualized approaches to muscle mass and adiposity according to disease activity level in long-standing rheumatoid arthritis.
32036584 Benefits of exercise in patients with rheumatoid arthritis: a randomized controlled trial 2020 Jun BACKGROUND: Patients with rheumatoid arthritis (RA) tend to be more overweight, take less physical exercise, exhibit decreased cardiorespiratory fitness and demonstrate reduced muscle strength compared with age- and sex-matched controls. Impaired cognitive function in RA is an important associated factor, although it has been less well-recognized. The aim of this study was to investigate the effects of a specifically designed exercise programme on body composition, aerobic capacity, muscle strength and cognition in RA. METHODS: Sixty-six patients with RA were randomized to a specifically designed, personalized exercise programme or standard care. Assessments included body composition, fitness, grip strength and cognitive testing, in addition to disease related measures. RESULTS: Significant improvements in C-reactive protein (p = 0.025), fatigue scores (p = 0.047) and truncal fat (p = 0.004) were observed in the exercise group compared with controls. Median waist circumference was significantly reduced (94.0 to 91.4 cm, p < 0.0001). Improvements were also seen in aerobic capacity (23.2 to 27.6 ml/kg/min, p = 0.002) and in median right (12.0 to 13.0 kg, p = 0.025) and left grip strength (8.0 to 10 kg, p = 0.005). Cognitive function improved in the exercise group, with median Montreal Cognitive Assessment score 25.5 at 0 months compared to 28.0 at 3 months (p = 0.001). CONCLUSION: This study demonstrates that exercise has a significant and positive impact on cognitive function in RA. Furthermore, physical activity is safe and effective in chronic inflammatory joint disease and is recommended as a vital component in the holistic management of these patients.Key Points• A dedicated physical exercise programme is feasible and safe in patients with rheumatoid arthritis (RA).• Physical exercise helps reduce fatigue scores and improves cardiovascular fitness in stable RA patients.• Physical exercise has a positive impact on cognition in patients with RA.• A structured exercise programme should be an integral part of chronic disease management protocols for patients with RA.