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ID PMID Title PublicationDate abstract
33095149 Primary Sjögren's syndrome: central and peripheral nervous system involvements. 2020 Jul Primary Sjögren's syndrome (pSS) is a common systemic autoimmune disease characterised by exocrinopathy resulting in dryness of the mouth and eyes, unexplained fatigue and diffuse pain. Neurological involvement is uncommon in pSS, involving the central nervous system in 2-5% of cases and more frequently the peripheral nervous system in 5-15% of cases. The diagnosis of pSS is to be considered when confronted with symptoms such as mouth and eye dryness, fatigue and pain, the most frequent of pSS symptoms. Objective measures of oral and eye dryness may help assert the diagnosis of pSS, as well as ACR/EULAR criteria. Differential diagnoses have to be excluded in patients exhibiting neurological symptoms, such as cryoglobulinaemic vasculitis or multiple sclerosis, before considering a neurological involvement specific to pSS. The treatment of these neurological manifestations takes into account different parameters, such as the presence of cryoglobulinaemic vasculitis, the severity of the symptoms, a rapidly progressing evolution and the failure of previous symptomatic treatments.
32085884 Disease modifying drugs for rheumatological diseases: a brief history of everything. 2020 The rheumatological diseases are a group of chronic, painful, degenerative and debilitating conditions with an increasing prevalence across the globe. The pathogenesis of these disorders is complex, overlapping and not fully understood. As such, it is difficult and time consuming to achieve correct diagnosis and complete remission for an individual patient. In this review we describe the most common forms of inflammatory arthritis and discuss how the management and treatment options for these rheumatic diseases have developed over time. We outline the successes and the limitations of current treatment regimens and discuss the economic burden of the current options. With advancements in understanding of disease mechanisms, we discuss the importance of the biologics revolution in the context of rheumatological disease and how the development of biosimilars and small molecule inhibitors will impact current treatment options in order to alleviate some of the cost burden of biological therapies. The ideal treatment strategy for the future would involve personalized and predictive medicine where by treatments can be tailored to an individual patient's needs in order to achieve fast and successful remission with no adverse events.
32718263 Effects of betulinic acid on synovial inflammation in rats with collagen-induced arthritis 2020 Jan Betulinic acid (BA) inhibits the migration, invasion, and cytoskeletal reorganization of fibroblast-like synoviocytes (RA-FLS) in patients with rheumatoid arthritis. Here, to further explore the mechanism of action of BA in collagen-induced arthritis (CIA) rats, we investigated the pharmacodynamic effects of BA on synovial inflammation in a rat model of type II CIA. After inducing hind paw swelling, the rats were divided into four groups: healthy controls (normal), and rats that underwent CIA and received methotrexate treatment (MTX), BA treatment (BA), or no treatment (CIA). Body weight and hind paw swelling were determined regularly, and arthritis scores were calculated weekly. On day 35, rats were sacrificed and their hind ankle joints sectioned and stained with hematoxylin and eosin for histopathological evaluation. BA significantly reduced CIA-induced hind paw swelling, synovial tissue proliferation, cartilage destruction, and vasospasm. BA treatment also decreased serum interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in rats with CIA. The CCK-8 assay was used to detect the proliferation of isolated vimentin(+)CD68(-) RA-FLS; RA-FLS were stimulated with TNF-α in vitro. BA significantly inhibited TNF-α-stimulated RA-FLS proliferation, as well as IL-1β and IL-6 secretion. BA also downregulated the transcription of vascular endothelial growth factor (VEGF) and transforming growth factor β (TGF-β) and decreased the expression of the NF-кB pathway proteins (NF-kB-P65, IkBα, and IKKα/β) in the TNF-α-stimulated RA-FLS. These results indicate that BA alleviated the symptoms of CIA by inhibiting synoviocyte proliferation, modifying TNF-α- and NF-кB-related inflammatory pathways, and downregulating inflammatory mediators and growth factors including IL-1β, IL-6, VEGF, and TGF-β.
33343960 Complicated Rheumatoid Nodules in Lung. 2020 A 65-year-old nonsmoker lady carrying a diagnosis of seropositive erosive rheumatoid arthritis for nine years presented with acute shortness of breath, following a spontaneous pneumothorax while on combination therapy with methotrexate, leflunomide, and tocilizumab. Imaging studies revealed multiple cavitory lung nodules, and a transbronchial lung biopsy favoured a diagnosis of rheumatoid lung nodules. Her initial pathological samples were negative for any infectious cause. A follow-up computerized tomography scan (CT scan) confirmed enlargement of lung nodules with a positive antibody test for aspergillosis which needed antifungal therapy, and currently, her arthritis is managed well with rituximab therapy, sulfasalazine, and hydroxychloroquine.
33116749 Overexpression of Aquaporin 1 in Synovium Aggravates Rat Collagen-Induced Arthritis Throug 2020 INTRODUCTION: Previous studies have confirmed that aquaporin 1 (AQP1) is up-regulated in synovium of rheumatoid arthritis (RA), but its exact pathogenic mechanisms in RA are unclear. This study revealed the pathogenic role of AQP1 in rat collagen-induced arthritis (CIA) and the underlying mechanisms related to β-catenin signaling. MATERIALS AND METHODS: Secondary paw swelling and pathological changes of ankle joints were used to evaluate the severity of rat CIA. Synovial AQP1 and β-catenin expression were measured by immunohistochemistry (IHC) and Western blot assay. AQP1 siRNA was applied to knockdown AQP1 in cultured CIA fibroblast-like synoviocyte (FLS). Assays of MTT, PCNA immunofluorescence and transwell were performed to detect cell proliferation, migration and invasion. The protein levels of β-catenin pathway members and ratio of TOP/FOP luciferase activity were also measured. RESULTS: In vivo, we revealed that synovial AQP1 and β-catenin expressions in CIA rats were higher than normal rats, and synovial AQP1 expression of CIA rats increased in parallel with secondary paw swelling and total pathological score on joint damage. Correlation analysis of IHC results indicated that synovial AQP1 expression positively correlated with β-catenin expression in CIA rat. In vitro, AQP1 siRNA apparently reduced the proliferation, migration and invasion of CIA FLS by inhibiting β-catenin signaling pathway. As an activator of β-catenin signaling, lithium chloride (an inhibitor of GSK-3β) reversed the inhibitory effects of AQP1 siRNA on the cultured CIA FLS. CONCLUSION: We concluded that the overexpression of synovial AQP1 aggravated rat CIA by promoting the activation of FLS through β-catenin signaling pathway.
32011708 The role of biochemical markers of joint tissue remodelling to predict progression and tre 2020 Jun 1 Structural damage is a hallmark in RA, spondyloarthropy (SpA) and psoriatric arthritis (PsA). Its progression is difficult to predict and current radiological or inflammatory biological markers lack sensitivity. Biochemical markers of bone, cartilage and synovial tissues provide a dynamic indication of the anabolism and catabolism of joint tissues and can be easily measured by immunoassays. Novel biochemical markers including post-translational modifications of matrix proteins and enzyme-generated neoepitopes with increased tissue and/or biological pathway specificity have been developed. Their evaluation in clinical trials of novel biologic therapies and epidemiological studies indicated that their measurements could be useful to predict progression of structural damage and treatment efficacy, independently of current clinical, radiological and biological indices of disease activity. In this paper we briefly describe the latest developments in biochemical markers and critically analyse the clinical data assessing the utility of established and novel biochemical markers in RA, SpA and PsA.
32381074 Bone marrow mesenchymal stem cells improve bone erosion in collagen-induced arthritis by i 2020 May 7 BACKGROUND: Rheumatoid arthritis (RA) is characterized by joint inflammation and damage to the cartilage and bone in collagen-induced arthritis (CIA). Mesenchymal stem cells (MSCs) can improve articular symptoms and reduce bone erosion in CIA rats; however, the underlying mechanism remains unknown. This study aimed to investigate the mechanism underlying MSC-induced improvement of bone destruction in CIA. METHODS: Wistar rats were divided into a normal group, CIA control group, MTX intervention group, and BMSC intervention group, each comprising 8 rats. Serum RANKL, OPG, and CXCL10 levels of all groups were determined via flow cytometry after 42 days of interventions. RANKL, OPG, TRAF6, CXCL10, and CXCR3 were detected on the synovial membrane via immunohistochemistry, and their relative mRNA levels were determined via RT-PCR analysis. BMSCs were labeled with GFP and administered to CIA rats via the tail vein. At different time points, the distribution of implanted GFP-MSCs in synovial tissues was observed using a fluorescence microscope, and the potential of GFP-MSCs to differentiate into chondrocytes was assessed via immunofluorescence analysis. RESULTS: BMSC transplantation improved joint inflammation and inhibited bone destruction in CIA rats. BMSCs inhibited the expression of serum CXCL10 and CXCL10 and CXCR3 expression at the synovial membrane. Moreover, protein and mRNA expression analyses revealed that BMSCs potentially regulated RANKL/OPG expression levels in the serum and synovial tissue. Upon implantation into CIA rats, GFP-MSCs were traced in the joints. GFP-positive cells were observed in the cartilage tissue from day 11 and until 42 days after transplantation. Anti-type II collagen/GFP double-positive cells were observed in the articular cartilage (especially damaged cartilage) upon immunofluorescence staining of anti-type II collagen. CONCLUSIONS: BMSCs improve bone destruction in CIA by inhibiting the CXCL10/CXCR3 chemotactic axis, regulating the RANKL/OPG ratio, and directly differentiating into chondrocytes.
32252574 (64)Cu-ATSM and (99m)Tc(CO)(3)-DCM20 potential in the early detection of rheumatoid arthri 2021 Mar OBJECTIVES: Molecular imaging constitutes a promising technique for the early detection of rheumatoid arthritis (RA). Macrophages and hypoxia play significant roles in inflamed synovium. In the present study, we evaluated the efficacy of radiopharmaceuticals that target macrophage mannose receptors ((99m)Tc-labeled mannosylated dextran or (99m)Tc(CO)(3)-DCM20) and hypoxia (copper(II) diacetyl-di(N(4)-methylthiosemicarbazone) or Cu-ATSM) for the early detection of RA in collagen-induced arthritis (CIA) mice models. METHODS: CIA model was developed in DBA/1 mice, and the clinical score for arthritis was visually assessed on a regular basis. Two biodistribution studies were performed in a paired-labeled format using 2-deoxy-2-(18)F-fluoro-D-glucose ((18)F-FDG) as a reference: (1) (99m)Tc(CO)(3)-DCM20 with (18)F-FDG and (2) (67)Cu-ATSM with (18)F-FDG. RESULTS: The accumulation levels of (99m)Tc(CO)(3)-DCM20 and (67)Cu-ATSM in forepaws, hindpaws, and knee joints of CIA mice were significantly higher than that of control mice. In contrast, (18)F-FDG uptake in hindpaws and knee joints showed no significant difference between CIA and control mice. The radioactivity levels of (99m)Tc(CO)(3)-DCM20 and (67)Cu-ATSM were significantly correlated with the clinical scores for the paws. CONCLUSION: These results suggest the potential usefulness of (99m)Tc(CO)(3)-DCM20 and radiolabeled Cu-ATSM for the imaging and early detection of RA.
33437764 Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats 2020 Dec BACKGROUND: Metformin (MF) is a widely used biguanide oral hypoglycemic agent, which has obvious anti-inflammatory and immunomodulatory effects. However, the mechanism of MF on rheumatoid arthritis (RA) remains uncertain. In this study, we investigated the therapeutic effects of MF on collagen-induced arthritis (CIA). METHODS: CIA was induced in rats by intradermal injection of a mixture of bovine type II collagen and incomplete Freund's adjuvant (IFA) on day 0 and day 7 through the base of the tail. Intraperitoneal injection of MF (100 mg/kg) was given every 3 days, from day 14 for 3 weeks. The effects of MF on arthritis-induced systemic inflammation and synovitis were studied by pathological analysis of the knee joint and serological examination of peripheral blood in CIA rats. The bone protection effect of MF was studied by microscopic computed tomography (micro-CT) and histological analysis of the knee joint. The effects of MF on chondrocytes in CIA rats were studied by detecting the relevant pro-apoptotic mediators in the chondrocytes. RESULTS: After administration of MF in CIA rats, systemic inflammation and synovitis caused by arthritis were significantly suppressed. Histomorphometry and micro-CT analysis of the knee joint revealed that MF can protect bone by inhibiting the changes of trabecular bone in CIA rats. Histological analysis of the knee joint found that MF can inhibit osteoclast formation and degradation of the cartilage layer matrix. Detection of the relevant pro-apoptotic mediators in chondrocytes revealed that MF can significantly inhibit the apoptosis of chondrocytes in CIA rats. CONCLUSIONS: Our study showed that MF can inhibit systemic inflammation and synovitis and plays a role in bone protection by inhibiting cartilage layer matrix degradation, osteoclast formation, and chondrocyte apoptosis.
32270926 Fenebrutinib versus Placebo or Adalimumab in Rheumatoid Arthritis: A Randomized, Double-Bl 2020 Apr 9 OBJECTIVE: To evaluate fenebrutinib, an oral and highly selective non-covalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). METHODS: Patients with RA and inadequate response to methotrexate (cohort 1, n=480) were randomized to fenebrutinib (50 mg once daily, 150 mg once daily, 200 mg twice daily), 40 mg adalimumab every other week, or placebo. Patients with RA and inadequate response to tumor necrosis factor inhibitors (cohort 2, n=98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued methotrexate therapy. RESULTS: In cohort 1, American College of Rheumatology scores (ACR50) at week 12 were similar for fenebrutinib 50 mg once daily and placebo, and higher for fenebrutinib 150 mg once daily (28%) and 200 mg twice daily (35%) than placebo (15%) (p=0.017; p=0.0003). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (p=0.81). In cohort 2, more patients achieved ACR50 with fenebrutinib 200 mg twice daily (25%) than placebo (12%) (p=0.072). The most common adverse events for fenebrutinib included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. CONCLUSION: Fenebrutinib demonstrated efficacy comparable to adalimumab in patients with an inadequate response to methotrexate, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.
32448385 Cartilage-binding antibodies initiate joint inflammation and promote chronic erosive arthr 2020 May 24 BACKGROUND: Antibodies binding to cartilage proteins are present in the blood and synovial fluid of early rheumatoid arthritis patients. In order to develop animal models mimicking the human disease, we have characterized the arthritogenic capacity of monoclonal antibodies directed towards different joint proteins in the cartilage. METHODS: Purified antibodies specific to unmodified or citrullinated collagen type II (CII), collagen type XI (CXI), and cartilage oligomeric matrix protein (COMP) were produced as culture supernatant, affinity purified, pooled as antibody cocktails (Cab3 and Cab4), and injected intravenously into mice to induce arthritis. An adjuvant (lipopolysaccharide or mannan) was subsequently injected intraperitoneally on either day 5 or day 60 to enhance arthritis. Antibody binding and complement activation on the cartilage surface were analyzed by immunohistochemical methods. Bone erosions and joint deformations were analyzed by histological assessments, enzyme-linked immunosorbent assays, and micro-CT. Luminex was used to detect CII-triple helical epitope-specific antibody responses. RESULTS: The new cartilage antibody cocktails induced an earlier and more severe disease than anti-CII antibody cocktail. Many of the mouse strains used developed severe arthritis with 3 antibodies, binding to collagen II, collagen XI, and cartilage oligomeric matrix protein (the Cab3 cocktail). Two new models of arthritis including Cab3-induced LPS-enhanced arthritis (lpsCAIA) and Cab3-induced mannan-enhanced arthritis (mCAIA) were established, causing severe bone erosions and bone loss, as well as epitope spreading of the B cell response. Cab4, with addition of an antibody to citrullinated collagen II, induced arthritis more efficiently in moderately susceptible C57BL/6 J mice. CONCLUSIONS: The new mouse model for RA induced with cartilage antibodies allows studies of chronic development of arthritis and epitope spreading of the autoimmune response and bone erosion.
33117382 Inflammatory Joint Disease Is a Risk Factor for Streptococcal Sepsis and Septic Arthritis 2020 Septic arthritis is a medical emergency associated with high morbidity and mortality, yet hardly any novel advances exist for its clinical management. Despite septic arthritis being a global health burden, experimental data uncovering its etiopathogenesis remain scarce. In particular, any interplay between septic arthritis and preceding joint diseases are unknown as is the contribution of the synovial membrane to the onset of inflammation. Using C57BL/6 mice as a model to study sepsis, we discovered that Group A Streptococcus (GAS) - an important pathogen causing septic arthritis - was able to invade the articular microenvironment. Bacterial invasion resulted in the infiltration of immune cells and detrimental inflammation. In vitro infected fibroblast-like synoviocytes induced the expression of chemokines (Ccl2, Cxcl2), inflammatory cytokines (Tnf, Il6), and integrin ligands (ICAM-1, VCAM-1). Apart from orchestrating immune cell attraction and retention, synoviocytes also upregulated mediators impacting on bone remodeling (Rankl) and cartilage integrity (Mmp13). Using collagen-induced arthritis in DBA/1 × B10.Q F1 mice, we could show that an inflammatory joint disease exacerbated subsequent septic arthritis which was associated with an excessive release of cytokines and eicosanoids. Importantly, the severity of joint inflammation controlled the extent of bone erosions during septic arthritis. In order to ameliorate septic arthritis, our results suggest that targeting synoviocytes might be a promising approach when treating patients with inflammatory joint disease for sepsis.
32963579 The relationship between dietary patterns and rheumatoid arthritis: a case-control study. 2020 BACKGROUND AND AIM: A number of studies have investigated the effects of individual foods and/or nutrients on rheumatoid arthritis (RA), but research focusing on whole dietary patterns remains limited. The association of dietary patterns and rheumatoid arthritis is therefore not well elucidated. This study aims to determine existing relationships between major identified dietary patterns and RA. METHODS: This matched case-control study was conducted on 297 individuals in Isfahan, Iran. The presence of RA was determined by an expert rheumatologist, based on the American College of Rheumatology definitions, 2010. A 168-item questionnaire was used to collect dietary data. Major dietary patterns were identified using the factor analysis method. RESULTS: Two major dietary patterns, namely, healthy and western dietary patterns, were identified. Lower adherence to the healthy dietary pattern was associated with increased risk of RA (OR = 2.80; 95% CI 1.74-4.67; P < 0.001). The association remained significant even after taking other confounders into account (OR = 2.85; 95% CI 1.12-7.45; P = 0.03). A positively significant association was also observed between adherence to western dietary pattern and RA in the fully-adjusted final model (OR = 2.22; 95% CI 1.04-4.72; P = 0.03). CONCLUSIONS: The study suggests that there is an inverse association between adherence to a healthy dietary pattern and the odds of RA, and a positive significant relationship was found between western dietary pattern and RA. Further studies are required to confirm these findings.
32754034 Uncovering the Complexity Mechanism of Different Formulas Treatment for Rheumatoid Arthrit 2020 Traditional Chinese medicine (TCM) with the characteristics of "multi-component-multi-target-multi-pathway" has obvious advantages in the prevention and treatment of complex diseases, especially in the aspects of "treating the same disease with different treatments". However, there are still some problems such as unclear substance basis and molecular mechanism of the effectiveness of formula. Network pharmacology is a new strategy based on system biology and poly-pharmacology, which could observe the intervention of drugs on disease networks at systematical and comprehensive level, and especially suitable for study of complex TCM systems. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, causing articular and extra articular dysfunctions among patients, it could lead to irreversible joint damage or disability if left untreated. TCM formulas, Danggui-Sini-decoction (DSD), Guizhi-Fuzi-decoction (GFD), and Huangqi-Guizhi-Wuwu-Decoction (HGWD), et al., have been found successful in controlling RA in clinical applications. Here, a network pharmacology-based approach was established. With this model, key gene network motif with significant (KNMS) of three formulas were predicted, and the molecular mechanism of different formula in the treatment of rheumatoid arthritis (RA) was inferred based on these KNMSs. The results show that the KNMSs predicted by the model kept a high consistency with the corresponding C-T network in coverage of RA pathogenic genes, coverage of functional pathways and cumulative contribution of key nodes, which confirmed the reliability and accuracy of our proposed KNMS prediction strategy. All validated KNMSs of each RA therapy-related formula were employed to decode the mechanisms of different formulas treat the same disease. Finally, the key components in KNMSs of each formula were evaluated by in vitro experiments. Our proposed KNMS prediction and validation strategy provides methodological reference for interpreting the optimization of core components group and inference of molecular mechanism of formula in the treatment of complex diseases in TCM.
33344167 Hepatocyte growth factor overexpression promotes osteoclastogenesis and exacerbates bone l 2021 Mar BACKGROUND: Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes various biological processes. However, the effect of HGF on bone metabolism in rheumatoid arthritis (RA) remains unknown. Here, we investigated the role of HGF in regulating osteoclastogenesis and bone resorption in RA. METHODS: The expression of HGF in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of HGF on osteoclastogenesis was analysed by osteoclastogenesis and bone resorption assays. The effect of HGF inhibition was evaluated in a CIA mice model. The mechanism of HGF in regulating osteoclastogenesis and bone resorption was explored by a series of in vitro studies. RESULTS: HGF was overexpressed in CIA and RA. HGF stimulated osteoclastogenesis in vitro. SU11274, a selective small molecule blocker of c-Met, impeded the effect of HGF on osteoclastogenesis and bone resorption. HGF regulated osteoclastogenesis by JNK and AKT-GSK-3β-NFATc1 signallings. SU11274 protected CIA mice from pathological bone loss. CONCLUSIONS: These data strongly suggest that the highly expressed HGF in the joint tissues contributes to bone loss in RA. Inhibition of HGF/c-Met could effectively alleviate pathological bone loss and inflammatory symptoms in CIA mice. HGF/c-Met may be used as a new target for the treatment of bone loss in RA.
32346301 Cost-Effectiveness of a JAK1/JAK2 Inhibitor vs a Biologic Disease-Modifying Antirheumatic 2020 BACKGROUND: Baricitinib is a janus kinase (JAK1/JAK2) inhibitor developed for the treatment of patients suffering from rheumatoid arthritis (RA). Treating RA to the target of remission is current common practice. Cost-effectiveness of different treat-to-target (T2T) strategies, especially ones including new treatments is important for development and preference policy for treatment centers. European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) guidelines are currently unclear about preference between a JAK1/JAK2 versus a biological disease-modifying antirheumatic drug (bDMARD). OBJECTIVE: The main goal of this paper was to evaluate the cost-effectiveness of baricitinib versus first biological for methotrexate inadequate responders in a T2T strategy using a Markov model that incorporates hospital costs as well as societal costs. Costs and utilities over five years were compared between the two strategies. METHODS: A Monte Carlo simulation model was developed to conduct cost-utility analysis from the societal perspective over 5 years. Health states were based on the DAS28-erythrocyte sedimentation rate (ESR) categories. Effectiveness of baricitinib was retrieved from randomized controlled trials. Effectiveness of all other treatments, health state utilities, medical costs, and productivity loss were retrieved from the Dutch RhEumatoid Arthritis Monitoring (DREAM) cohorts. Annual discount rates of 1.5% for utility and 4% for costs were used. Probabilistic sensitivity analysis was employed to incorporate uncertainty and assess robustness of the results. RESULTS: Probabilistic sensitivity analysis results showed the baricitinib strategy yielded lower costs and higher utility over a 5-year period. Scenario analyses showed the baricitinib strategy to be cost-effective in both the moderate and severe RA populations. CONCLUSION: Results suggest that the use of a JAK1/JAK2 inhibitor instead of a bDMARD in a T2T approach is cost-effective in csDMARD refractory RA patients.
32611650 Relationship of pain and fatigue with health-related quality of life and work in patients 2020 Jun BACKGROUND/OBJECTIVE: The incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi). METHODS: Data from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire. RESULTS: 640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all p<0.0001), with HRQoL and WPAI measures considerably worse in patients with moderate to severe pain or fatigue than those with low pain or fatigue. CONCLUSIONS: Despite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies.
32704274 Musculoskeletal ultrasound in the Differential Diagnosis of Gouty Arthritis and Rheumatoid 2020 Jul OBJECTIVE: To explore the role of musculoskeletal ultrasound (MSUS) in the differential diagnosis of gouty arthritis (GA) and rheumatoid arthritis (RA) and to analyze the ultrasound imaging features of the two diseases. METHODS: A retrospective study was carried out. A total of 66 patients who had been admitted to The First Medical Center of Chinese PLA General Hospital from May 2018 to March 2019 were enrolled. Among them, 34 patients were diagnosed with RA and were included in the RA group; 32 patients were diagnosed with gouty arthritis and were included in the GA group. The imaging features of musculoskeletal ultrasound were compared between the two groups of patients. RESULTS: A total of 34 patients were included in the RA group, including 17 males and 17 females. A total of 32 patients were included in the GA group, including 14 males and 18 females. There were no significant differences in gender composition, age, and duration of disease between the two groups (P>0.05). In the RA group, there were joint bone erosions with a clear boundary in seven cases and with a blurred boundary in 27 cases; synovial hyperplasia was observed in 27 cases, and point-like hyperechoic masses were observed in four cases. In the GA group, there were joint bone erosions with a clear boundary in 27 cases and with a blurred boundary in five cases; synovial hyperplasia was observed in four cases, tophus was observed in 23 cases, point-like hyperechoic masses were observed in 27 cases, and the tram-track sign was observed in 23 cases. The differences in bone erosion boundaries (c2=26.854, P<0.01), synovial hyperplasia (c2=29.631, P<0.01), tophus (P<0.01), point-like hyperechoic mass (c2=33.095, P<0.01), and tram-track sign (P<0.01) were statistically significant between the two groups of patients. In the RA group, blood flow signaling was Grade 0 in one case, Grade-I in five cases, Grade-II in 14 cases, and Grade-III in 14 cases. In the GA group, blood flow signaling was Grade 0 in 26 cases, Grade-I in three cases, Grade-II in three cases, and Grade-III in zero cases. The difference in the synovial blood flow signaling between the two groups of patients was statistically significant (c2=34.323, P<0.01). CONCLUSIONS: MSUS has certain diagnostic value in the differentiation of GA and RA. Moreover, the two conditions have their own ultrasound imaging features.
33564725 Human umbilical cord-derived mesenchymal stem cells induce tissue repair and regeneration 2020 Dec 11 The immunosuppressive and anti-inflammatory properties of mesenchymal stem/stromal cells (MSCs) have prompted their therapeutic application in several autoimmune diseases, including rheumatoid arthritis (RA). MSCs derived from bone marrow and adipose tissue has earlier been tried with limited success. However, Wharton's jelly present in human umbilical cord is discarded after delivery which makes a rich source of MSCs with least ethical issues. The immunomodulatory properties of human umbilical cord-derived MSCs (UC-MSCs) were evaluated in-vitro on the mononuclear cells from synovial fluid (SF) and peripheral blood of RA patients. The therapeutic potential of UC-MSCs was checked by transplanting the cells in rats with collagen-induced arthritis (CIA). MSCs isolated from Wharton's Jelly significantly suppressed the proliferation and activation of lymphocytes from both peripheral blood as well as SF of RA patients, down-modulated the functions of activated CD4+, CD8+ T-cells, suppressed the secretion of pro-inflammatory cytokines, and induced the expansion of T-regulatory cells. Xenotransplantation of UC-MSCs in CIA rats clearly indicated a sustained impact in terms of slowing down the progression of disease activity and reversal of arthritic processes along with triggering of joint tissue repair mechanisms, which could be observed till 6 weeks post-transplantation. The results from the current study suggest that human umbilical cord is a rich source of MSCs for allotransplantation. The UC-MSCs may be used successfully as a cell-based therapeutic option either in isolation or in conjunction with existing therapeutic drugs not only to relieve the joint inflammation but also regenerate the damaged bone and cartilage tissues in arthritis. RELEVANCE TO PATIENTS: The current study highlights the potential use of MSCs as a cell-based therapeutic option for the treatment of inflammatory RA.
32116720 Alleviation of Synovial Inflammation of Juanbi-Tang on Collagen-Induced Arthritis and TNF- 2020 Rheumatoid arthritis (RA) is a chronic autoimmune disease that is primarily characterized by synovial inflammation. In this study, we found that a traditional Chinese decoction, Juanbi-Tang (JBT), JBT attenuated the symptoms of collagen-induced arthritis (CIA) mice and in tumor necrosis factor transgenic (TNF-Tg) mice by attenuating the arthritis index and hind paw thickness. According to histopathological staining of ankle sections, JBT significantly decreased the area of inflammation and reduced bone destruction of ankle joints in both these two types of mice. Moreover, decreased tartaric acid phosphatase-positive osteoclasts were observed in the JBT group compared with those found in the control group. We also revealed that JBT suppressed monocytes and T cells as well as the production of CCL2, CCR6, and CXCR3 ligands. We next used high-performance liquid chromatography to investigate the components and pharmacological properties of this classical herbal medicine in traditional Chinese medicine. Based on network pharmacology, we performed computational prediction simulation of the potential targets of JBT, which indicated the NF-kappa B pathway as its target, which was confirmed in vitro. JBT suppressed the production of pro-inflammatory cytokines including interleukin-6 (IL-6) and IL-8, and inhibited the expression of matrix metalloproteinase 1 in fibroblast-like synoviocytes derived from RA patients (MH7A cells). Furthermore, JBT also suppressed the phosphorylation of p38, JNK, and p65 in TNF-α-treated MH7A cells. In summary, this study proved that JBT could inhibit synovial inflammation and bone destruction, possibly by blocking the phosphorylation of NF-kappa B pathway-mediated production of proinflammatory effectors.