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ID PMID Title PublicationDate abstract
31691863 Computer-aided diagnosis in rheumatic diseases using ultrasound: an overview. 2020 Apr Clinical evaluation of rheumatic and musculoskeletal diseases through images is a challenge for the beginner rheumatologist since image diagnosis is an expert task with a long learning curve. The aim of this work was to present a narrative review on the main ultrasound computer-aided diagnosis systems that may help clinicians thanks to the progress made in the application of artificial intelligence techniques. We performed a literature review searching for original articles in seven repositories, from 1970 to 2019, and identified 11 main methods currently used in ultrasound computer-aided diagnosis systems. Also, we found that rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies are the four musculoskeletal and rheumatic diseases most studied that use these innovative systems, with an overall accuracy of > 75%.
30649471 Activated protein C targets immune cells and rheumatoid synovial fibroblasts to prevent in 2019 Oct 1 OBJECTIVES: To investigate whether activated protein C (APC), a physiological anticoagulant can inhibit the inflammatory/invasive properties of immune cells and rheumatoid arthritis synovial fibroblasts (RASFs) in vitro and prevent inflammatory arthritis in murine antigen-induced arthritis (AIA) and CIA models. METHODS: RASFs isolated from synovial tissues of patients with RA, human peripheral blood mononuclear cells (PBMCs) and mouse thymus cells were treated with APC or TNF-α/IL-17 and the following assays were performed: RASF proliferation and invasion by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell invasion assays, respectively; cytokines and signalling molecules using ELISA or western blot; Th1 and Th17 phenotypes in human PBMCs or mouse thymus cells by flow cytometry. The in vivo effect of APC was evaluated in AIA and CIA models. RESULTS: In vitro, APC inhibited IL-1β, IL-17 and TNF-α production, IL-17-stimulated cell proliferation and invasion and p21 and nuclear factor κB activation in RASFs. In mouse thymus cells and human PBMCs, APC suppressed Th1 and Th17 phenotypes. In vivo, APC inhibited pannus formation, cartilage destruction and arthritis incidence/severity in both CIA and AIA models. In CIA, serum levels of IL-1β, IL-6, IL-17, TNF-α and soluble endothelial protein C receptor were significantly reduced by APC treatment. Blocking endothelial protein C receptor, the specific receptor for APC, abolished the early or preventative effect of APC in AIA. CONCLUSION: APC prevents the onset and development of arthritis in CIA and AIA models via suppressing inflammation, Th1/Th17 phenotypes and RASF invasion, which is likely mediated via endothelial protein C receptor.
31605388 Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthri 2020 Feb The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.
31754088 Efficacy, immunogenicity and cost analysis of a systematic switch from originator inflixim 2019 Oct Biosimilar drugs are intended to be as effective as the originator product but with a lower cost to healthcare systems. In our center we promoted a switch from originator infliximab (IFXor) to biosimilar infliximab (CT-P13). We analyzed efficacy, safety, immunogenicity and cost savings of switching. Eligible patients were adults with the diagnosis of rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) on therapy with IFXor for at least 6 months and with stable disease activity. Efficacy was measured considering change from baseline in Disease Activity Score in 28 joints (DAS28) for RA and PsA and in Ankylosing Spondylitis Disease Activity Score (ASDAS) for SpA. Disease worsening was considered when an increase of 1.2 from baseline in DAS28 or an increase of 1.1 in ASDAS occurred. Serum IFX levels (sIFX) were dichotomized as therapeutic (between 3-6 µg/mL), low (< 3 µg/mL), and high (> 6 µg/mL). Anti-drug antibody (ADA) levels were dichotomized into detectable (> 10 ng/ml) or non-detectable (< 10 ng/ml). A cost analysis was done based on the purchasing prices of the 2 drugs at our center. During a period of 1 year switch to CT-P13 was performed in 60 patients for non-medical reasons. We had a total of 36 patients with SpA, 16 with RA and 8 with PsA. Disease activity was stable over the observation period and similar to the values observed with IFXor. Median follow-up time was 15 months during which 5 patients stopped CT-P13. Forty two switchers had blood samples collected before and after switch. A total of 27 patients had unaltered sIFX levels and ADA status during follow up. Three patients had detectable ADA at baseline, with low sIFX levels. After switch, ADAs became negative in 2 of those patients, and the other patient kept detectable ADA levels. ADAs became positive in 5 patients after switch. The switch to CT-P13 represented a 26.4 % reduction of costs in the use of IFX therapy in these patients. The switch in routine care of a group of RA, SpA and PsA patients from IFXor to CT-P13 did not affect efficacy, safety, immunogenicity and reduced costs in 26.4%. The observed changes in blood samples were not associated with higher disease activity and did not lead to stopping IFX therapy.
31858962 Association between autoantibody level and disease activity in rheumatoid arthritis is dep 2020 Jul OBJECTIVES: It is still controversial whether autoantibody (AAb) serum levels have a value for response monitoring in rheumatoid arthritis (RA). Therefore, we retrospectively investigated a real-life outpatient RA cohort to determine which factors are associated with change in serum AAb levels and RA disease activity. The primary goal of the study was to determine predictors for changes in DAS28 and autoantibodies over time and identify traits of non-rituximab treated patients, which would define strong association of disease activity with changes in AAb-levels. METHODS: Seventy-eight patients with seropositive RA were monitored for DAS28, CRP, ESR, anti-cyclic citrullinated peptides (CCP), anti-mutated citrullinated vimentin (MCV), and rheumatoid factor (RF). Using linear mixed regression modelling, factors influencing DAS28 and serum AAb were determined. Patients showing above (good correlators) and below (bad correlators) average correlation of serum AAb with DAS28 were further characterised. RESULTS: In non-rituximab treated patients (88.5%), associations of changes in AAb and DAS28 were strengthened with more morning stiffness (p=0.002), DMARD use (p=0.02), tender joints (p=0.01), swollen joints (p<0.01), higher ESR (p<0.01) and VAS (p<0.001) at baseline. Decrease of anti-CCP was also predicted by longer disease duration (-4.4 U/ml per year disease duration, p=0.048) and/or no erosions (-2.0 U/ml/month, p<0.01) at baseline, whereas erosive disease predicted an increase (+1.4 U/ml/month, p=0.015) in anti-CCP. Conversely, patients with erosive disease showed a trend to decrease RF (-1.9 U/ml/month, p=0.06). CONCLUSIONS: In non-rituximab treated RA patients, the association between disease activity and change in autoantibody levels is not static, but strengthens with increase in signs of inflammation (ESR, VAS, swollen joints, tender joints, morning stiffness) at baseline. Therefore, studies of changes in AAb need to consider baseline inflammation as confounder.
30787006 Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syn 2019 May OBJECTIVES: To investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA. METHODS: By linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996-2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016. We used Cox regression to estimate the HR of ACS among patients with RA and the siblings of patients with RA versus the general population, overall and stratified by RA serostatus. We explored the impact of traditional cardiovascular (CV) risk factors on the observed associations. RESULTS: We identified 8109 patients with incident RA, and 11 562 full siblings of these. Compared with the general population, the HR of ACS in RA was 1.46 (95% CI 1.28 to 1.67) and 1.22 (95% CI 1.09 to 1.38) among their siblings. The increased risks seemed confined to seropositive RA (patients: 1.52 [1.30 to 1.79], their siblings: 1.27 [1.10 to 1.46]); no significant risk increase was observed among siblings of patients with seronegative RA (HR 1.13 [95% CI 0.92 to 1.39]). Adjustment for 19 traditional CV risk factors did not appreciably alter these associations. CONCLUSION: Siblings of patients with RA are at increased risk of ACS, suggesting shared susceptibility between RA and ACS, indicating the need and potential for additional cardio-preventive measures in RA (and their siblings).
30220237 Clinical effectiveness and long-term retention of abatacept in elderly rheumatoid arthriti 2019 Nov Objective: To study the clinical effectiveness and long-term retention rate of abatacept (ABA) in elderly rheumatoid arthritis (RA) patients in daily clinical practice.Methods: A retrospective cohort study was performed using data from a multicenter registry. Our study population comprised 500 consecutive RA patients treated with ABA. We compared clinical effectiveness and ABA retention rates between the Young (≤62 years), Middle (62 to 72 years), and Elderly (≥72 years) groups. We also performed separate examinations to identify predictive factors for ABA discontinuation in those with versus those without concomitant methotrexate (MTX) treatment.Results: Mean age was 52.7 years in the Young group, 67.7 years in the Middle group, and 78.1 years in the Elderly group. No significant group-dependent differences were found in mean DAS28 score, categorical distribution of DAS28, and EULAR response rate across the 52 weeks. The ABA retention rates at three years as determined by the Kaplan-Meier method were similar in all three groups. Patient age was not a significant predictor of ABA discontinuation due to adverse events in patients with concomitant MTX; however, it was found to be a significant predictor for those who did not use MTX (Cox hazard model).Conclusion: ABA would be a reasonable treatment option for elderly RA patients from the viewpoints of both clinical effectiveness and long-term retention. However, physicians should watch carefully for any serious adverse reactions in elderly RA patients with intolerance to MTX.
30321963 Total ankle arthroplasty and national registers: What is the impact on scientific producti 2019 Aug PURPOSE: The purpose of this systematic review was to analyze clinical studies on total ankle replacement (TAR) whose data were extracted from national registers. METHODS: A systematic review of the literature, to identify all studies reporting outcomes after TAR, was performed. Two independent investigators performed the research using MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase and Cochrane Databases (1950 to December 2017). The search terms used were "total ankle replacement" or "total ankle arthroplasty" AND "register" or "registers" or "registry" or "registries" or "national registry" or "national register". RESULTS: Analysis of the literature included 18 articles from 2007 to 2017. Of these 5 articles performed a comprehensive analysis of the national registers, 5 articles evaluated complications and reasons of failure after TAR, 6 articles made a specific outcome register analysis, one article compared TAR and ankle arthrodesis while the last one analyzed the role of TAR in patients with rheumatoid arthritis. CONCLUSIONS: Scientific publications extracted from national joint registers for total ankle replacement provide useful but heterogeneous information on implants survivorship, implant models and risk factors. There is still a discrepancy between the data reported by designers in clinical studies and the data reported by the registries. The centralization of registers in specialized hospitals with dedicated surgeons, the use of patient reported outcomes (PROMs) in association with surgeon assessments and periodical publications can improve the development of registries and consequently of the literature in this regard.
30427585 Evaluation of the Short-, Mid-, and Long-Term Effects of Tofacitinib on Lymphocytes in Pat 2019 May OBJECTIVE: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Altered lymphocyte cell counts and a potential association with increased infection rates have been reported in RA patients treated with JAK inhibitors. This analysis was undertaken to evaluate the short-, mid-, and long-term effects of tofacitinib on lymphocytes and infection rates in patients with RA. METHODS: In this post hoc analysis, absolute lymphocyte counts (ALCs) were obtained from phase III studies (12-24 months; n = 717-958) and phase I/II/III/long-term extension studies of tofacitinib (≤117 months) (All RA population; n = 7,061); lymphocyte subset counts (LSCs) were from phase II studies (1.5-6 months' exposure; n = 236-486), an ORAL Sequel vaccine substudy (~22 months; n = 198), and an ORAL Sequel lymphocyte substudy (~50 months; n = 55-1,035) of tofacitinib. The reversibility of ALC/LSC changes was evaluated. The relationship of ALC and LSC to infections was analyzed in the All RA population. The value of monitoring ALC alone was assessed by examining correlations between ALCs and LSCs. RESULTS: Tofacitinib treatment resulted in an initial increase in ALC versus pretreatment baseline, which gradually declined to steady state by ~48 months. CD4+ and CD8+ T cell counts decreased over long-term treatment, and ALC and LSC changes were reversible upon treatment cessation. Patients with ALCs of <500 cells/mm(3) had an increased risk of serious infections. There was no strong association between CD4+ T cell, CD8+ T cell, B cell, or natural killer cell counts and serious infection incidence rates. ALC and CD4+ or CD8+ T cell counts correlated well (R = 0.65-0.86). CONCLUSION: Our findings indicate that monitoring of ALC alone appears to be adequate to assess infection risk in tofacitinib-treated patients with RA.
30864110 Color Doppler imaging of ocular hemodynamic changes in patients with rheumatoid arthritis 2019 Jun We aimed to investigate how orbital blood flow rates in patients with rheumatoid arthritis (RA) are affected by the active and remission phase of the disease. This prospective study included a total of 56 patients with RA (study group) and 24 control individuals (control group). All RA patients were divided into two groups, as active (Group 1) and remission (Group 2) according to the disease activity index (DAS 28) score. For each eye, retrobulbar vascular structures were evaluated [central retinal artery (CRA), posterior ciliary artery (PCA), and ophthalmic artery (OA)], respectively. The peak systolic velocity (PSV) and end-diastolic velocity (EDV) values were obtained for each artery and the vascular resistance index (RI) measurement was calculated. The median RI of the OA was 0.70 (0.57; 0.79) in the control group, 0.77 (0.55; 0.87) in group 1, and 0.73 (0.47; 0.87) in group 2. The median RI in the PCA was 0.70 (0.56; 0.82) in the control group, 0.76 (0.52; 0.88) in the group 1, and 0.74 (0.52; 0.86) in the group 2. The median RI of CRA was 0.73 (0.48; 0.81) in the control group, 0.71 (0.64; 0.81) in group 1, and 0.68 (0.61; 0.85) in group 2. The RI value was a significant difference between control and group 1 (p < 0.05). Active and remission RA patients had different effects on the flow rate of eye blood vessels.
30634014 Effect of inositol -stabilized arginine silicate on arthritis in a rat model. 2019 Mar The purpose of this study was to test the effects of arginine-silicate-inositol complex (ASI), compared to a combination of the individual ingredients (A+S+I) of the ASI, on inflammatory markers and joint health in a collagen-induced arthritis (CIA) rat model. A total of 28 Wistar rats were divided into four groups: (i) Control; (ii) Arthritic group, rats subjected to CIA induction by injection of bovine collagen type II (A); (iii) Arthritic group treated with equivalent doses of the separate components of the ASI complex (arginine hydrochloride, silicon, and inositol) (A+S+I); (iv) Arthritic group treated with the ASI complex. The ASI complex treatment showed improved inflammation scores and markers over the arthritic control and the A+S+I group. ASI group had also greater levels of serum and joint-tissue arginine and silicon than the A+S+I group. Joint tissue IL-6, NF-κB, COX-2, TNF-α, p38 MAPK, WISP-1, and β-Catenin levels were lower in the ASI group compared to the other groups (P < 0.05 for all). In conclusion, these results demonstrate that the ASI complex may be effective in reducing markers of inflammation associated with joint health and that the ASI complex is more effective than a combination of the individual ingredients.
31875586 PRKCH polymorphism is associated with rheumatoid arthritis in a Chinese population. 2020 Jan 20 Genetic factors have been widely considered to have a substantial effect on the susceptibility to rheumatoid arthritis (RA). The purpose of this study was to determine whether the four newly discovered polymorphisms in a genome-wide association study (GWAS) meta-analysis confer susceptibility to RA in a Chinese Han population. We conducted a case-control study involving 359 RA cases and 873 age-and gender-matched controls and performed genotyping of four single nucleotide polymorphisms (SNPs), rs227163, rs726288, rs3783782 and rs2469434, using the dye terminator-based SNaPshot method. Consequently, we detected significant differences of genotype distribution of rs3783782 in PRKCH between RA and controls. The minor allele frequencies (MAFs) of rs3783782 were significantly higher in RA patients compared to control subjects. Moreover, the rs227163 in TNFRSF9 had higher MAFs in male RA compared with male controls. In addition, the polymorphism of rs3783782 in PRKCH was significantly associated with RA susceptibility (OR = 1.67, 95% CI = 1.32-2.11, p = 1.32 × 10(-5)). After stratification by gender, the minor (A) allele was strongly associated with increased risk for RA in males (OR = 1.87, 95% CI = 1.34-2.60; p = 1.62 × 10(-4)) and in females (OR = 1.51, 95% CI = 1.08-2.10; p = 0.014). For rs227163, the minor (C) allele was found to be associated with RA risk only in males (OR = 1.34, 95% CI = 1.02-1.75; p = 0.036). These findings for the first time confirmed that rs3783782 in PRKCH was associated with RA susceptibility in a Chinese population, and rs227163 in TNFRSF9 was associated with RA risk in Chinese males; these SNPs may serve as genetic markers for RA.
30418115 Utility of administrative and clinical data to predict major change in medical treatment i 2019 Jul OBJECTIVES: To examine factors associated with major therapeutic changes (MTC) among US Veterans with moderate/severe rheumatoid arthritis (RA) based on Disease Activity Score based on 28 joints (DAS28). METHODS: We used data from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry from 1/1/2006 through 12/31/2014. The index date was a clinic visit with DAS28 >3.2 (moderate/severe disease) following an 18-month pre-index period that included ≥2 DAS28 measurements ≥60 days apart. The patients were followed for MTC from 7 days pre-index through 90 days post-index. Poisson multivariable regression models were used to identify associations with MTC. Chart review of a subset of randomly selected patients explored factors that impacted therapeutic decisions. RESULTS: Among 941 patients, 396 (42.1%) had MTC. Of these, 369 (39.2%) patients had worsening DAS28 at index, 118 (12.5%) had DAS28 improvements, and 454 (48.2%) patients had no change in DAS28 versus pre-index DAS28. Of the patients with worsening DAS28, no change in DAS28, and improved DAS28, respectively, 50.5%, 62.6%, and 70.3% had no MTC. Regression analyses showed index DAS28, oral steroid or non-biologic disease-modifying anti-rheumatic drug (nbDMARD) use in the previous year were associated with an increased likelihood of MTC; use of nbDMARDs in the previous 90 days was associated with a decreased likelihood of MTC. The most common reason for not modifying therapy despite DAS28 >3.2 was a judgement of mild disease. CONCLUSIONS: Clinicians frequently do not institute major therapeutic changes despite DAS28 indicating moderate/severe disease activity; multiple factors are involved in real-world treatment decisions.
30648228 Interventions to improve vaccine acceptance among rheumatoid arthritis patients: a systema 2019 Jun INTRODUCTION/OBJECTIVE: National guidelines emphasize the importance of annual immunization for patients living with rheumatoid arthritis (RA), but vaccination rates remain suboptimal in this population. Evaluating the efficacy of patient and/or provider-targeted interventions to improve vaccination uptake among RA patients could inform practice. METHODS: We conducted a systematic review (SR) to examine the efficacy of interventions (exposure) aiming to improve vaccination uptake in patients with RA (outcome). English and French language, peer-reviewed interventional studies to improve vaccination rates in RA patients published between 2009 and 2018 were included. RESULTS: The search yielded a total of 450 records. Five articles met inclusion criteria. All interventions focused on changing provider behavior using some form of vaccination reminder as the primary intervention strategy, though only two studies reported provider prescribing behavior as an outcome (which was 4% and 58%). Overall, studies varied greatly regarding intervention delivery mode (e.g., educational sessions, e-mail reminders, best practice alerts), and behavior change techniques used to encourage providers to prescribe vaccination (e.g., feedback and monitoring, shaping knowledge, self-regulation). For influenza, pneumococcal and herpes zoster, post-intervention (mean 12-16 months follow-up) vaccination rates increased by a mean of 16.6% (± 15.4%). CONCLUSIONS: Interventions to enhance vaccine uptake in RA focused almost exclusively on improving provider prescription of vaccines using reminder-type interventions. Although effective in improving vaccination rates, those studies used heterogeneous interventions and behavior change techniques. Few studies measured provider prescribing behavior as an outcome. Future studies targeting providers should measure relevant provided-related outcomes and their impact on patient outcomes, to determine overall efficacy.
30630713 Clinical outcome of Niigata-Senami-Kyocera modular unconstrained total elbow arthroplasty 2019 May BACKGROUND: Total elbow arthroplasty (TEA) is a treatment option for destructive and painful unstable elbows in rheumatoid arthritis (RA). We evaluated the clinical outcomes of unconstrained TEA (Niigata-Senami-Kyocera modular system). METHODS: Seventy-five unconstrained TEAs were performed in patients with RA (mean age, 64 years; age range, 41-79 years; follow-up rate, 97%). Outcome measures included the Japanese Orthopaedic Association (JOA) functional evaluation score for the elbow joint (JOA score), range of motion, and arc. Bone ingrowth of the humeral component, the incidence of stress shielding around the humeral component, the incidence of loosening of the ulnar component, complications, and the survival rate were investigated. RESULTS: The mean follow-up period was 5.2 years (range, 2-11.3 years). The JOA elbow score improved from 42 points preoperatively to 87 points postoperatively (P < .0001). Each specified item improved (P < .0001). Flexion improved from 109° to 134°; the flexion-plus-extension arc improved from 70° to 108° (P < .0001). Bone ingrowth of the humeral implant was achieved in all elbows. Stress shielding of the humeral component was detected in 11 elbows (14%); it was significantly higher in 10- and 9-mm-diameter humeral stems than in 8-mm-diameter humeral stems (P = .008). The ulnar component showed no loosening except in 1 elbow owing to infection. Complications were detected in 9 patients (9 elbows, 12%): periprosthetic infection (3), fracture (4), and dislocation (2). The survival rates were 97% at 5 years and 93% at 10 years postoperatively. DISCUSSION: The Niigata-Senami-Kyocera modular system for patients with RA showed good outcomes. Stress shielding can be avoided by using an 8-mm-diameter humeral stem.
31745043 Efficacy of a mouthwash containing essential oils and curcumin as an adjunct to nonsurgica 2019 Jul PURPOSE: The purpose of this study was to assess the efficacy of mouthwash containing essential oils and curcumin (MEC) as an adjunct to nonsurgical periodontal therapy on the disease activity of rheumatoid arthritis (RA) among RA patients with chronic periodontitis (CP). MATERIALS AND METHODS: A triple-blinded controlled trial was conducted among 45 female RA patients with CP randomized into three treatment groups as follows: Group A: scaling and root planing (SRP) with 0.2% chlorhexidine mouthwash as an adjunct (n = 15), Group B: SRP with MEC as an adjunct (n = 15), and Group C: SRP alone (n = 15). RA disease activity was assessed using erythrocyte sedimentation rate, serum C-reactive protein, serum anti-citrullinated protein antibody, and serum rheumatoid factor. Periodontal disease activity was assessed using plaque index, clinical attachment level (CAL), and pocket depth (PD). All parameters were recorded at baseline and 6 weeks thereafter. Data were assessed using one-way ANOVA and paired t-test. RESULTS: A significant reduction in periodontal and RA disease activity parameters was observed from baseline to 6 weeks following intervention (P < 0.05). The highest percentage of mean reduction in plaque index and RA parameters from baseline to 6 weeks was observed in Group B followed by Groups A and C. The highest percentage of mean reduction in PD and CAL was observed in Group A followed by Groups B and C (P < 0.001). CONCLUSION: This study reveals that MEC as an adjunct to SRP is effective in reducing the disease activity of RA and CP, thereby warranting the use of the same.
31005957 Treatment of Type II Collagen-Induced Rat Rheumatoid Arthritis Model by Interleukin 10 (IL 2019 Apr 21 BACKGROUND Rheumatoid arthritis model (CIA) rats were treated by tail vein injection of IL-10-modified bone marrow mesenchymal stem cells (BMSCs) to investigate its feasibility and intrinsic molecular mechanism. MATERIAL AND METHODS The CIA rat model was established by induction type II collagen, and IL-10-modified BMSCs was established by transfecting BMSCs with adenovirus. IL-10-modified BMSCs were used to treat the CIA rats. The therapeutic effect was evaluated by measuring the changes in body weight, ankle swelling, and forced swimming time, as well as observation of synovial hyperplasia and cartilage tissue repair by HE staining. Western blot analysis and ELISA were used to detect gene expression. RESULTS After 4 weeks and 8 weeks of treatment with IL10-BMSCs, the body weight, swelling value, resting time, and forced swimming struggle time of CIA rats were significantly higher than those of BMSCs-treated and -untreated CIA rats (P<0.05). Compared to BMSCs-treated CIA model rats, after treatment with IL10-BMSCs, the repair rate of osteoarticular cartilage was higher and the inhibition of synovial proliferation was better, and serum IL-17, IL-1ß, and TNF-alpha levels were lower. We found that the protein level of SIRT1 in peripheral blood mononuclear cells was lower, the protein level in spleen was higher, and phosphorylation of p65 protein in peripheral blood mononuclear cells was reduced. CONCLUSIONS The efficacy of tail vein injection of IL-10-modified BMSCs in treatment of CIA rats was superior to that of BMSCs alone, which may be related to the more pronounced suppression of IL-10-modified BMSCs in peripheral blood inflammation and spleen immune response.
31006511 IMPACT: Genomic Annotation of Cell-State-Specific Regulatory Elements Inferred from the Ep 2019 May 2 Despite significant progress in annotating the genome with experimental methods, much of the regulatory noncoding genome remains poorly defined. Here we assert that regulatory elements may be characterized by leveraging local epigenomic signatures where specific transcription factors (TFs) are bound. To link these two features, we introduce IMPACT, a genome annotation strategy that identifies regulatory elements defined by cell-state-specific TF binding profiles, learned from 515 chromatin and sequence annotations. We validate IMPACT using multiple compelling applications. First, IMPACT distinguishes between bound and unbound TF motif sites with high accuracy (average AUPRC 0.81, SE 0.07; across 8 tested TFs) and outperforms state-of-the-art TF binding prediction methods, MocapG, MocapS, and Virtual ChIP-seq. Second, in eight tested cell types, RNA polymerase II IMPACT annotations capture more cis-eQTL variation than sequence-based annotations, such as promoters and TSS windows (25% average increase in enrichment). Third, integration with rheumatoid arthritis (RA) summary statistics from European (N = 38,242) and East Asian (N = 22,515) populations revealed that the top 5% of CD4(+) Treg IMPACT regulatory elements capture 85.7% of RA h2, the most comprehensive explanation for RA h2 to date. In comparison, the average RA h2 captured by compared CD4(+) T histone marks is 42.3% and by CD4(+) T specifically expressed gene sets is 36.4%. Lastly, we find that IMPACT may be used in many different cell types to identify complex trait associated regulatory elements.
31594926 HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in C 2019 Oct 8 Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive bone erosion. Leflunomide is originally developed to suppress inflammation via its metabolite A77 1726 to attenuate bone erosion. However, distinctive responsiveness to Leflunomide is observed among RA individuals. Here we show that Leflunomide exerts immunosuppression but limited efficacy in RA individuals distinguished by higher serum C-reactive protein (CRP(Higher), CRP(H)), whereas the others with satisfactory responsiveness to Leflunomide show lower CRP (CRP(Lower), CRP(L)). CRP inhibition decreases bone erosion in arthritic rats. Besides the immunomodulation via A77 1726, Leflunomide itself induces AHR-ARNT interaction to inhibit hepatic CRP production and attenuate bone erosion in CRP(L) arthritic rats. Nevertheless, high CRP in CRP(H) rats upregulates HIF1α, which competes with AHR for ARNT association and interferes Leflunomide-AHR-CRP signaling. Hepatocyte-specific HIF1α deletion or a HIF1α inhibitor Acriflavine re-activates Leflunomide-AHR-CRP signaling to inhibit bone erosion. This study presents a precision medicine-based therapeutic strategy for RA.
31474422 Methotrexate therapy is not associated with increased liver stiffness and significant live 2019 Nov OBJECTIVE: To explore the significance of the association between treatment with methotrexate (MTX) and liver stiffness in rheumatoid arthritis (RA) patients. METHODS: We enrolled 140 consecutive RA patients under MTX treatment (MTX-treated RA; mean treatment duration: 6.2 years; mean MTX cumulative dose: 4.67 g), 33 RA patients naive to MTX (MTX-naive RA) and 100 age and sex-matched healthy blood donors (HD). Liver stiffness was assessed by real time two-dimensional shear wave elastography, with values ≥7.1 Kilopascals (kPa) defining significant liver fibrosis. RESULTS: kPa values in HD (4.32 ± 0.7) were lower than that in MTX-naive RA (4.92 ± 0.8) and MTX-treated RA (4.85 ± 0.9, p < .0005 for trend). On the contrary, the difference in kPa between MTX-naive and MTX-treated RA was not significant (p = .89). Similarly, liver stiffness was not significantly different across strata of cumulative MTX dose (4.95 ± 0.7 kPa in MTX <1 g, 4.90 ± 1.1 kPa in MTX 1-3 g and 4.80 ± 0.9 in MTX >3 g, p = .610). Significant liver fibrosis was diagnosed in 4 patients in the MTX-treated RA (highest kPa value = 7.6; no liver function test abnormalities or clinical signs of hepatic failure) and in none in both the MTX-naive RA and HD groups (p = .145). CONCLUSION: Liver stiffness values, although within the normal range, are significantly higher in RA patients vs. controls, irrespective of MTX treatment. RA patients taking MTX do not have a higher prevalence of significant liver fibrosis when compared to MTX naive RA patients and the general population.