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ID PMID Title PublicationDate abstract
30886614 Targeting Mesenchymal Stromal Cells/Pericytes (MSCs) With Pulsed Electromagnetic Field (PE 2019 Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium (synovitis), with inflammatory/immune cells and resident fibroblast-like synoviocytes (FLS) acting as major players in the pathogenesis of this disease. The resulting inflammatory response poses considerable risks as loss of bone and cartilage progresses, destroying the joint surface, causing joint damage, joint failure, articular dysfunction, and pre-mature death if left untreated. At the cellular level, early changes in RA synovium include inflammatory cell infiltration, synovial hyperplasia, and stimulation of angiogenesis to the site of injury. Different angiogenic factors promote this disease, making the role of anti-angiogenic therapy a focus of RA treatment. To control angiogenesis, mesenchymal stromal cells/pericytes (MSCs) in synovial tissue play a vital role in tissue repair. While recent evidence reports that MSCs found in joint tissues can differentiate to repair damaged tissue, this repair function can be repressed by the inflammatory milieu. Extremely-low frequency pulsed electromagnetic field (PEMF), a biophysical form of stimulation, has an anti-inflammatory effect by causing differentiation of MSCs. PEMF has also been reported to increase the functional activity of MSCs to improve differentiation to chondrocytes and osteocytes. Moreover, PEMF has been demonstrated to accelerate cell differentiation, increase deposition of collagen, and potentially return vascular dysfunction back to homeostasis. The aim of this report is to review the effects of PEMF on MSC modulation of cytokines, growth factors, and angiogenesis, and describe its effect on MSC regeneration of synovial tissue to further understand its potential role in the treatment of RA.
31858340 What do Australian patients with inflammatory arthritis value in treatment? A discrete cho 2020 Apr BACKGROUND AND OBJECTIVES: The purpose of this study was to develop an understanding of treatment preferences in patients with inflammatory arthritis (IA) [rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA)] focussing on treatment attributes that patients' value, their relative importance, and the risk-benefit trade-offs that characterise patients' choices around treatment. METHODS: A discrete choice experiment (DCE) approach was used. Attributes of interest were clinical efficacy; slowing of disease progression; risk of mild-moderate side effects; risk of severe side effects; frequency of administration; real-world product evidence; management of related conditions; and availability of a patient support programme. Using data from the DCE component, a restricted latent class model (LCM) was estimated to determine discrete 'classes' of treatment preferences. RESULTS: In this analysis, 206 participants were included (AS n = 59; PsA n = 62; RA n = 85). Two classes were identified. For 'class 1' (59.9%), the most important attributes (across all treatment modalities) were preventing disease progression, clinical efficacy and risk of mild-to-moderate side effects. For 'class 2' (40.1%), clinical and non-clinical attributes were important, and attribute importance depended on treatment modality. Patient demographic and treatment characteristics did not predict class membership. CONCLUSION: For most patients with IA, clinical efficacy, stopping disease progression and risks of mild-to-moderate side effects are important treatment attributes. Patients with prior biologic DMARD experience had greater preference for injection treatments. For a subset of patients, patient support programmes and the frequency of administration were important. Clinicians should be mindful of preferences when prescribing treatment to patients with IA.Key Points• Most patients consider clinical efficacy, stopping disease progression and the risk of mild-to-moderate side effects as important treatment attributes• Patients with prior biologic DMARD experience have greater preference for injection treatments.• For a subset of patients, patient support programmes, and the frequency of administration were important.• Clinicians should be mindful of preferences when prescribing treatment to patients with IA.
31249576 CTHRC1: A New Candidate Biomarker for Improved Rheumatoid Arthritis Diagnosis. 2019 Background: The purpose of this study was to determine whether plasma levels of the collagen triple helix repeat containing 1 (CTHRC1) protein can serve as a blood-based biomarker for improved diagnosis of rheumatoid arthritis (RA) patients and monitoring of RA disease activity. Methods: We measured levels of CTHRC1 in the plasma of patients diagnosed with RA, osteoarthritis (OA), reactive arthritis (ReA), as well as in healthy individuals. We then assessed the correlation between CTHRC1 protein and a range of indices including the 28-joint disease activity score (DAS28), rheumatoid factor (RF), C-reactive protein (CRP), anti-citrullinated protein antibodies (ACPA), erythrocyte sedimentation rate (ESR), as well as a panel of cytokines, including interleukin 1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon gamma (IFNγ). Receiver operating characteristic (ROC) analysis was further performed to assess the diagnostic value of CTHRC1. Results: CTHRC1 plasma levels were significantly elevated in RA patients compared to healthy individuals, OA and ReA patients. ROC curve and risk score analysis suggested that plasma CTHRC1 can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. CTHRC1 levels were positively associated with RF, ACPA, CRP, and disease activity based on the combined index of DAS28 with CRP (DAS28-CRP), and also strongly correlated with IL-1β, IL-6, IL-8, and IFNγ. Conclusion: Our studies show that CTHRC1 is a sensitive and easy-to-measure plasma marker that differentiates between RA and healthy status and also distinguishes between RA and other forms of arthritis, such as OA and ReA. At the current level of understanding, plasma CTHRC1 levels may improve the diagnosis of RA and these findings warrant confirmation in a larger, more comprehensive patient population.
31396542 Cross-Disease Innate Gene Signature: Emerging Diversity and Abundance in RA Comparing to S 2019 Overactivation of the innate immune system together with the impaired downstream pathway of type I interferon-responding genes is a hallmark of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To date, limited data on the cross-disease innate gene signature exists among those diseases. We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood mononuclear cells from well-defined patients with active stages of RA (n = 36, DAS28 ≥ 3.2), SLE (n = 28, SLEDAI > 6), and SSc (n = 22, revised EUSTAR index > 2.25). Emerging diversity and abundance of the innate signature in RA patients were detected: RA was characterized by the upregulation of TLR3, TLR5, IL1RAP/IL1R3, IL18R1, and SIGIRR/IL1R8 when compared to SSc (P (corr) < 0.02) and of TLR2, TLR5, and SIGIRR/IL1R8 when compared to SLE (P (corr) < 0.02). Applying the association rule analysis, six rules (combinations and expression of genes describing disease) were identified for RA (most frequently included high TLR3 and/or IL1RAP/IL1R3) and three rules for SLE (low IL1RN and IL18R1) and SSc (low TLR5 and IL18R1). This first cross-disease study identified emerging heterogeneity in the innate signature of RA patients with many upregulated innate genes compared to that of SLE and SSc.
31452427 Use and outcome of 1,220 primary total elbow arthroplasties from the Australian Orthopaedi 2019 Dec Background and purpose - The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was analyzed to determine trends in use of primary total elbow arthroplasty (TEA), the types of prostheses used, primary diagnoses, reasons for and types of revision, and whether the primary diagnosis or prosthesis design influenced the revision rate.Patients and methods - During 2008-2018, 1,220 primary TEA procedures were reported of which 140 TEAs were revised. Kaplan-Meier estimates of survivorship were used to describe the time to first revision and hazard ratios (HR) from Cox proportional hazard models, adjusted for age and sex, were used to compare revision rates.Results - The annual number of TEAs performed remained constant. The 3 most common diagnoses for primary TEA were fracture/dislocation (trauma) (36%), osteoarthritis (OA) (34%), and rheumatoid arthritis (RA) (26%). The cumulative percentage revision for all TEAs undertaken for any reason was 10%, 15%, and 19% at 3, 6, and 9 years. TEAs undertaken for OA had a higher revision rate compared with TEAs for trauma (HR = 1.8, 95% CI 1.1-3.0) and RA (HR = 2.0, CI 1.3-3.1). The Coonrad-Morrey (50%), Latitude (30%), Nexel (10%), and Discovery (9%) were the most used prosthesis designs. There was no difference in revision rates when these 4 designs were compared. The most common reasons for revision were infection (35%) and aseptic loosening (34%).Interpretation - The indications for primary and revision TEA in Australia are similar to those reported for other registries. Revision for trauma is lower than previously reported.
31663467 Treatment Patterns with Disease-Modifying Antirheumatic Drugs in U.S. Veterans with Newly 2019 Nov BACKGROUND: Delays in treatment for inflammatory arthritis (IA) are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability. OBJECTIVE: To characterize treatment initiation patterns in veterans with newly diagnosed rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). METHODS: ICD-9/10-CM codes and natural language processing were used to identify incident cases of RA, PsA, or AS between January 1, 2007, and December 31, 2015, in patients enrolled in the Veterans Health Administration. Patterns of treatment initiation and nontreatment with disease-modifying antirheumatic drugs (DMARDs) were assessed in the 12-month follow-up period after the incident diagnosis. Outcomes included the percentage of veterans treated with a DMARD, the mean time to the initial DMARD after diagnosis, and the percentage of veterans who accessed rheumatology care before DMARD initiation. To assess outcomes over time, veterans were grouped by year of initial IA diagnosis. Additionally, outcomes were compared between nonbiologic and biologic DMARDs and among IA subtypes (RA, PsA, and AS). Groups were statistically compared with 95% confidence intervals. RESULTS: The population consisted of 12,118 IA veterans (9,711 RA, 1,472 PsA, and 935 AS), with 91.3% males and a mean age of 63.7 years. The percentage of veterans treated with ≥ 1 DMARD (nonbiologic or biologic) during the 12-month follow-up period increased from 48.8% in 2007 to 66.4% in 2015. In veterans diagnosed with IA in 2015, DMARD treatment was more common for PsA patients (72.9%) and RA patients (68.6%) than for AS patients (28.9%). In the subset treated with a DMARD within 12 months after diagnosis, the mean time to the initial DMARD after diagnosis did not change throughout the observation period (35.5 days for RA, 43.9 days for PsA, and 59.5 days for AS). Rheumatology specialty care was accessed by 87.4% of veterans treated with a nonbiologic DMARD and 92.2% of veterans treated with a biologic DMARD, in patients diagnosed in 2015. CONCLUSIONS: DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in veterans with AS. The time to treatment after diagnosis was stable over time; it was shortest for RA, intermediate for PsA, and longest for AS. DMARD treatment was uncommon in veterans who did not access rheumatology specialty care. DISCLOSURES: AbbVie Pharmaceuticals and Marriott Daughters Foundation funded this study via investigator-initiated grants. Data analyses were completed by investigators independent of AbbVie and Marriott Daughters Foundation. Walker, Clewell, and Douglas are employed by, and stockholders in, Abbvie. Halwani reports grants from BMS, Kyowa Hakko Kirin, Seattle Genetics, Roche-Genentech, Miragen, Immunedesign, Takeda, Amgen, Pharmacyclics, and Abbvie. The other authors have nothing to disclose.
31764493 Efficacy and Safety of Hepatitis B Vaccination in Rheumatoid Arthritis Patients Receiving 2019 Dec OBJECTIVES: The aims of this study were to assess efficacy and safety of the hepatitis B vaccination in rheumatoid arthritis (RA) patients receiving conventional and/or biological disease-modifying antirheumatic drugs (DMARDs). METHODS: A longitudinal open-label study was conducted. Of 46 RA patients, 33 received only conventional synthetic DMARDs, and 13 received both conventional synthetic DMARDs and biological DMARDs, and 9 healthy age- and sex-matched control subjects were vaccinated with 20 μg recombinant hepatitis B vaccine (EuVax B) at weeks 0, 4, and 24. Hepatitis B surface antibody levels were measured 8 weeks after the last dose of vaccination. Seroprotection was defined as hepatitis B surface antibody level of 10 mIU/mL or greater. Disease Activity Score in 28 Joints scores were recorded at weeks 0, 4, and 32 in 46 RA patients who received hepatitis B vaccination and 47 treatment-matched RA patients who did not receive it. Adverse events were recorded at each visit.Statistical analyses were performed using SPSS version 16.0. RESULTS: Seroprotection was lower in the RA patients than in the control subjects (64% vs. 100%, p = 0.045). Patients receiving biological DMARDs and conventional DMARDs had a lower proportion of seroprotection compared with the control group (50% vs. 100% [p = 0.02] and 69.7% vs. 100% [p = 0.09], respectively). Among RA patients, responders were younger than nonresponders with a mean age of 57.5 (SD, 9.0) years and 64.9 (SD, 10.9) years (p = 0.04) and less likely to be treated with rituximab (6.9% vs. 37.5%, p = 0.01). Overall, hepatitis B vaccination was well tolerated. The rate of RA flare was not increased after hepatitis B vaccination. CONCLUSIONS: Patients with RA receiving DMARDs had less humoral response to hepatitis B vaccination as compared with control subjects. Aging and rituximab use were associated with impaired response to hepatitis B vaccination. Hepatitis B vaccination is safe and well tolerated in RA patients.
31602920 [Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheu 2019 Aug The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.
31602903 [Identification of biomarkers to response of Tripterygium Glycosides Tablets acting on rhe 2019 Aug Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.
31596875 Genetic associations with radiological damage in rheumatoid arthritis: Meta-analysis of se 2019 BACKGROUND: Previous studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants. METHODS: Seven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases. RESULTS: In the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10-8). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10-6). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P<5x10-6; in the European primary and secondary analyses 13 and 10 regions contained SNPs reaching P<5x10-6, respectively. Of the previously validated SNPs for radiological progression, only rs660895 (tagging HLA-DRB1*04:01) attained significance (P = 1.6x10-5) and had a consistent direction of effect across GWAS. CONCLUSIONS: Our meta-analysis confirms the known association between the HLA-DRB1 shared epitope and RA radiological damage. The lack of replication of previously validated non-HLA markers highlights a requirement for further research to deliver clinically-useful prognostic genetic markers.
30185379 Efficacy and safety of biological agents in the older rheumatoid arthritis patients compar 2019 Apr OBJECTIVE: Biologic anti-rheumatic drugs are used with less frequency among older patients compared to young patients. This population is less represented in studies performed to evaluate the efficacy and safety of this drugs. We aimed to assess the efficacy and safety of biological agents between the older RA patients compared to young. METHODS: A comprehensive, systematic search was conducted in major indexing databases using key terms for RA and each biological agent. The review process was completed by 2 investigators. Both randomized controlled trials and observational studies of at least 6-month duration conducted in adult RA patients were included. Outcomes of interest were clinical efficacy and safety. Effect-estimates were pooled using random-effects modeling if 4 or more studies used the same scale and time-frame for measuring outcomes. RESULTS: 24 studies (16 focusing on anti-TNF agents) representing 63,705 patients (24% were older) were included. Older RA patients had worse baseline RA disease activity, longer disease duration at the time of enrollment in the trial (14.4 ± 3.6 vs. 10.9 ± 3.6 years; p < 0.001) and higher steroid use (73.2 vs. 64.7%, p < 0.001) than younger. 5 out of 6 studies assessing anti-TNF agents showed worse efficacy outcomes in older patients. The pooled OR of infection and ADRs with anti-TNF agents in older compared to young RA patients was OR 1.59 (95% CI: 1.45-1.76) and 1.40 (95% CI: 1.23-1.61) respectively. CONCLUSIONS: Older patients had worse safety and efficacy with biological agents but also had worse baseline disease activity. There was significant heterogeneity in reporting outcomes and very limited studies in biological agents other than anti-TNF drugs.
31307535 Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a 2019 Jul 15 TRIAL DESIGN: We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. METHODS: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study. CONCLUSIONS: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN46017566 . Registered on 4 July 2014.
30990432 Automatic Hand Skeletal Shape Estimation From Radiographs. 2019 Jul Rheumatoid arthritis (RA) is an autoimmune disease whose common manifestation involves the slow destruction of joint tissue, a damage that is visible in a radiograph. Over time, this damage causes pain and loss of functioning, which depends, to some extent, on the spatial deformation induced by the joint damage. Building an accurate model of the current deformation and predicting potential future deformations are the important components of treatment planning. Unfortunately, this is currently a time-consuming and labor-intensive manual process. To address this problem, we propose a fully automated approach for fitting a shape model to the long bones of the hand from a single radiograph. Critically, our shape model allows sufficient flexibility to be useful for patients in various stages of RA. Our approach uses a deep convolutional neural network to extract low-level features and a conditional random field (CRF) to support shape inference. Our approach is significantly more accurate than previous work that used hand-engineered features. We provide a comprehensive evaluation for various choices of network hyperparameters, as current best practices lack significantly in this domain. We evaluate the accuracy of our pipeline on two large datasets of hand radiographs and highlight the importance of the low-level features, the relative contribution of different potential functions in the CRF, and the accuracy of the final shape estimates. Our approach is nearly as accurate as a trained radiologist and, because it only requires a few seconds per radiograph, can be applied to large datasets to enable better modeling of disease progression.
29158080 Risk-stratified management strategies for HBV reactivation in RA patients receiving biolog 2019 Feb It is estimated that more than two billion people around the world have been infected by Hepatitis B virus (HBV). Reactivation of HBV (rHBV) is a potentially fatal complication after biological therapy. With the increasing use of biologics and targeted therapy in rheumatoid arthritis (RA) patients who are refractory to conventional synthetic disease-modifying anti-rheumatic drugs, rHBV in those with past infection has become increasingly problematic, especially in HBV-endemic regions. Among those receiving biological therapy, the risk of rHBV varies according to the status of HBV infection and the degree of biologic-related immunosuppression. As rHBV is largely preventable, it is imperative that the risk status of rHBV in RA patients receiving biological and targeted therapy be stratified. Therefore, the aim of this review was to summarize the reported data on rHBV, and propose management strategies for RA patients with different risks of rHBV based on evidence presented in the current literature.
31076925 Neutrophil-Mediated Delivery of Dexamethasone Palmitate-Loaded Liposomes Decorated with a 2019 May 10 PURPOSE: The aim of this research was to design dexamethasone palmitate (DP) loaded sialic acid modified liposomes, with the eventual goal of using peripheral blood neutrophils (PBNs) that carried drug-loaded liposomes to improve the therapeutic capacity for rheumatoid arthritis (RA). METHODS: A sialic acid - cholesterol conjugate (SA-CH) was synthesized and anchored on the surface of liposomal dexamethasone palmitate (DP-SAL). The physicochemical characteristics and in vitro cytotoxicity of liposomes were evaluated. Flow cytometry and confocal laser scanning microscopy were utilized to investigate the accumulation of liposomes in PBNs. The adjuvant-induced arthritis was adopted to investigate the targeting ability and anti-inflammatory effect of DP loaded liposomes. RESULTS: Both DP-CL and DP-SAL existed an average size less than 200 nm with remarkably high encapsulation efficiencies more than 90%. In vitro and in vivo experiments manifested SA-modified liposomes provided a reinforced accumulation of DP in PBNs. As well, DP-SAL displayed a greater degree of accumulation in the joints and a stronger anti-inflammatory effect in terms of RA suppression. CONCLUSIONS: SA-modified liposomal DP was a promising candidate for RA-targeting treatment through the neutrophil-mediated drug delivery system.
31852669 Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of k 2020 Mar OBJECTIVE: In these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the IL1RN gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA). METHODS: Over 1000 subjects who met American College of Rheumatology criteria for tibiofemoral OA were selected from three independent, National Institute of Health (NIH)-funded cohorts. CTA and TTG haplotypes formed from three SNPs of the IL1RN gene (rs419598, rs315952, rs9005) were assessed for association with radiographic severity, and risk for incident radiographic OA (rOA) in a nested case-control cohort. These IL1RN haplotypes were also assessed for association with disease activity (DAS28) and plasma inflammatory markers in patients with RA. RESULTS: Carriage of the IL1RN TTG haplotype was associated with increased odds of more severe rOA compared with age-matched, sex-matched and body mass index-matched individuals. Examination of the osteoarthritis initiative Incidence Subcohort demonstrated that carriage of the TTG haplotype was associated with 4.1-fold (p=0.001) increased odds of incident rOA. Plasma IL-1Ra levels were lower in TTG carriers, while chondrocytes from TTG carriers exhibited decreased secretion of IL-1Ra. In patients with RA, the TTG haplotype was associated with increased DAS28, decreased plasma IL-1Ra and elevations of plasma inflammatory markers (hsCRP, interleukin 6 (IL-6)). CONCLUSION: Carriage of the IL1RN TTG haplotype is associated with more severe rOA, increased risk for incident OA, and increased evidence of inflammation in RA. These data suggest that the IL1RN TTG risk haplotype, associated with decreased IL-1Ra plasma levels, impairs endogenous 'anti-inflammatory' mechanisms.
31523786 Rheumatoid arthritis and neurodegenerative dementia: a nested case-control study and a fol 2020 Jan OBJECTIVES: The present study evaluated the associations between rheumatoid arthritis (RA) and neurodegenerative dementia using a Korean national sample cohort. METHODS: We designed two studies using the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. Study I included participants with dementia matched 1:4 with controls and analyzed the participants' history of RA. Study II included participants with RA matched 1:4 with controls and analyzed the occurrence of dementia. RA was defined by the presence of relevant ICD-10 codes (M05 or M06) and medication histories. Neurodegenerative dementia was defined using ICD-10 codes (G30 or F00). Crude and adjusted odds ratios (ORs) were analyzed using conditional logistic regression analyses. Crude and adjusted hazard ratios (HRs) were analyzed using the stratified Cox proportional hazard model. Subgroup analyses were performed on groups stratified by age and sex. RESULTS: The adjusted ORs for RA were 0.96 (95% CI = 0.78-1.16, P = 0.644) in the dementia group in study I. The adjusted HRs for dementia were 0.91 (95% CI = 0.76-1.10, P = 0.319) in the RA group in study II. No subgroup analysis reached the statistical significance level. CONCLUSION: We could not identify any significant relationship between RA and dementia.Key Points• Two studies were conducted to identify the relationship between rheumatoid arthritis and dementia using national cohort data.• Neither study showed any association between rheumatoid arthritis and dementia.
31918224 Reactive oxygen species-responsive dexamethasone-loaded nanoparticles for targeted treatme 2020 Feb Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that results in synovitis, cartilage destruction, and even loss of joint function. The frequent and long-term administration of anti-rheumatic drugs often leads to obvious adverse effects and patient non-compliance. Therefore, to specifically deliver dexamethasone (Dex) to inflamed joints and reduce the administration frequency of Dex, we developed Dex-loaded reactive oxygen species (ROS)-responsive nanoparticles (Dex/Oxi-αCD NPs) and folic acid (FA) modified Dex/Oxi-αCD NPs (Dex/FA-Oxi-αCD NPs) and validated their anti-inflammatory effect in vitro and in vivo. In vitro study demonstrated that these NPs can be effectively internalized by activated macrophages and the released Dex from NPs significantly downregulated the expression of iRhom2, TNF-α, and BAFF in activated Raw264.7. In vivo experiments revealed that Dex/Oxi-αCD NPs, especially Dex/FA-Oxi-αCD NPs significantly accumulated at inflamed joints in collagen-induced arthritis (CIA) mice and alleviated the joint swelling and cartilage destruction. Importantly, the expression of iRhom2, TNF-α, and BAFF in the joint was inhibited by intravenous injection of Dex/Oxi-αCD NPs and Dex/FA-Oxi-αCD NPs. Collectively, our data revealed that Dex-loaded ROS-responsive NPs can target inflamed joints and attenuate arthritis, and the 'iRhom2-TNF-α-BAFF' pathway plays an important role in the treatment of RA with the NPs, suggesting that this pathway may be a novel target for RA therapy.
31314620 Picture superiority effect as one of the potential advantages of musculoskeletal ultrasoun 2020 Jul Objective: We conducted a questionnaire survey within a standard clinical setting to clarify that picture superiority effect (PSE) could be obtained by musculoskeletal ultrasound (MSKUS) examination.Methods: One hundred patients with rheumatoid arthritis or arthralgia, who visited the Rheumatology Unit, Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine, and received first-time MSKUS from June 2017 to August 2017, were sequentially requested to complete an anonymous questionnaire based on their experiences of the explanation with or without MSKUS. MSKUS was implemented as point-of-care ultrasonography (POCUS) or on the other reserved examination day. Results: We obtained answers from all patients (n = 100); 80% or more subjects strongly agreed that the explanation complemented with MSKUS contributed to 'easier understanding,' 'better communication,' and 'preference for MSKUS-available hospital' (p < .001). This agreement was also observed in elderly patients and when MSKUS was implemented as POCUS. There was no correlation between the number of examined joints (r = 0.18, p = .15), time required for MSKUS (r = -0.17, p = .09), the severity of the MSKUS results (r = -0.06, p = .52), and degree of agreement.Conclusion: MSKUS addition has shown to offer PSE, which contributes to patients' understanding and experience of improved communication. We should acknowledge the effects of PSE by MSKUS and utilize it for informed consent and shared decision-making in musculoskeletal symptomatic patients.
31430413 Therapeutic effects of Crocin in autoimmune diseases: A review. 2019 Nov The immune system when acts against selfmolecules results in an imbalance in immunologic tolerance leading to the development of several autoimmune diseases (ADs) such as rheumatoid arthritis, asthma, ulcerative colitis, type 1 diabetes, and multiple sclerosis. Improved recognition of the mechanisms of ADs has led to the advancement of the management of these diseases. The principal mediators of ADs are inflammatory molecules. The herbal medicines due to their antioxidant and antiinflammatory properties have an important role in the management of ADs. Crocin is the principal chemical component extracted from saffron, which is a medicinal plant. This review focuses on the therapeutic effects of Crocin in various ADs.