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ID PMID Title PublicationDate abstract
32413739 Cinnamaldehyde suppresses NLRP3 derived IL-1β via activating succinate/HIF-1 in rheumatoi 2020 Jul Cinnamaldehyde (CA) is an essential component of cinnamon (Cinnamomum cassia Presland), which is often used as a flavoring condiment in beverages, pastries, perfumes, etc. Cinnamon is also used as herbal medicine in China and Southeast Asia to treat rheumatoid arthritis. However, the molecular mechanism is unclear. In this study, we aim to investigate its anti-inflammatory effects against Rheumatoid arthritis (RA) using activated macrophages (Raw246.7) in vitro and adjuvant arthritis rats (AA) in vivo. The results demonstrated that CA significantly reduced synovial inflammation in AA rats, possibly due to suppression of the expressions of pro-inflammatory cytokines, especially the IL-1β. Further investigation found that CA also suppressed the activity of HIF-1α by inhibiting the accumulation of succinate in cytoplasm. As we know, the reduction of HIF-1α nucleation slows down IL-1β production, because HIF-1α activates the expression of NLRP3, which is involved in the assembly of inflammasome and processing of IL-1β. In addition, CA also inhibited the expression of the succinate receptor GPR91, which in turn inhibited the activation of HIF-1α. In conclusions, our results suggested that CA might be a potential therapeutic compound to relieve rheumatoid arthritis progress by suppressing IL-1β through modulating succinate/HIF-1α axis and inhibition of NLRP3.
33350780 The association between age and adverse events due to biologic disease-modifying antirheum 2020 Dec 24 We examined whether the age of patients with rheumatoid arthritis was associated with adverse events (AEs) caused by biologic disease-modifying antirheumatic drugs (bDMARDs).Patients with rheumatoid arthritis using bDMARDs from Showa University Hospital, Showa University Northern Yokohama Hospital, and Showa University Koto Toyosu Hospital from January 2005 to December 2017 were eligible for this retrospective cohort study. The maximum observation period was determined to be 1 year. Outcomes in patients older and younger than 75 years were compared. The primary outcome was the rate of drug discontinuation because of AEs caused by bDMARDs. Univariate and multivariate analyses were performed using Pearson's chi-squared test and logistic regression analysis, respectively.A total of 416 patients were enrolled; median (interquartile range [IQR]): 60.0 (44.3 - 71.0) years and 84.6% women; patients ≥ 75 years were 67/416 (16.1%). The rates of drug discontinuation because of AEs caused by bDMARDs were 10.5% (7/67) in patients 75 years and older and 10.9% (38/349) in those younger than 75 years (relative risk 0.95, 95% confidential interval 0.45-2.24). In logistic regression analysis adjusted for covariates, the rate of drug discontinuation showed no significant difference between the patients ≥ 75 years and the those < 75 years (adjusted odds ratio 0.70, 95% confidential interval 0.29-1.75, P = .45).The rate of drug discontinuation because of AEs caused by bDMARDs was not significantly different between patients 75 years and older and patients younger than 75 years.
31498070 IL-34 modulates rheumatoid synovial fibroblasts proliferation and migration via ERK/AKT si 2020 May OBJECTIVES: The interface between pro-inflammatory cytokines and rheumatoid synovial fibroblast (sFLS) has central effects on rheumatoid arthritis (RA). The present study aimed to explore the role of IL-34 expression as one of major cytokine implicated in RA. METHODS: We examined the expression of IL-34 after RA sFLS stimulated by IL-1β and TGF-β1 separately by reverse transcription polymerase chain reaction (RT-PCR). Transwell and wound closure techniques were used to detect whether IL-34 is involved in promoting cell migration. Cellular viability was determined via CCK-8 and cultural morphology assays between IL-34 downregulated group and non-transfected counterpart. We also tested the expression of VEGF gene with RT-PCR analysis and activation of the major signalling pathways by western blot in IL-34 down-regulated group, IL-1β or TGF-β1 treated groups. Propidium iodide (PI) staining and fluoresceine isothiocyanate (FITC) Annexin V and propidium iodide apoptosis assay were used to analyse cell cycle arrest and apoptosis separately in IL-34 down-regulated cells. RESULTS: We found that IL-1β significantly enhanced IL-34 expression, while contrarily, TGF-β1 restrained IL-34 gene expression. Transwell and wound closure techniques showed that IL-34 was involved considerably in promoting cell migration. However, IL-34 knock-down restricted sFLS migration possibly through the diminishing of MMP2 and MMP9 expression. Interestingly, IL-34 down-regulated cells exhibited significantly low cellular viability compared with the non-transfected counterpart via CCK-8 and cultural morphology assays. We found that IL-34 down-regulated cells have low VEGF gene expression compared with treated cells. PI staining showed a G0/G1 cell cycle arrest in IL-34 down-regulated cells. FITC Annexin V and propidium iodide apoptosis assay verified that IL-34 down-regulated cells induced massive apoptosis through apoptotic signalling caspase3, while IL-1β treated cells presented termination of cellular apoptosis signalled by BCL-2. Furthermore, we observed IL-34 induced activation of ERK1/2 and AKT pathways while IL-34 down-regulation significantly decreased the activation of these pathways. CONCLUSIONS: Our data add novel insights into the pathogenesis of RA and we suggest that IL-34 plays a dominant role in controlling migration and proliferation of sFLS. Consequently, therapeutic strategies targeting IL-34 could be a potent therapy for RA.
32297585 Circadian Rhythms of Endothelial Nitric Oxide Synthase and Toll-like Receptors 2 Productio 2020 BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune polygenic disease characterized by rapid disability progression and high prevalence. Progression of RA is closely associated with chronobiological changes in the production of some hormones and inflammatory mediators, influencing the disease course and therapy efficacy. The main pathogenetic mechanism of RA is angiogenesis, which is controlled by biological clock-genes. Further investigation of circadian rhythms of angiogenic mediators production in RA patients may be considered as important and relevant. The aim of this study was to establish daily variability of serum endothelial Nitric Oxide Synthase (NOS3) and toll-like receptors 2 (sTLR2) levels in female RA patients depending on the NOS3 gene polymorphism. METHODS: We examined 173 RA patients (100% female) aged 43.7 ± 7.35 years and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). RA was diagnosed by ACR/EULAR 2010 criteria. Blood serum NOS3 and sTLR2 levels were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С (rs2070744) polymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kits. The SPSS22 software package was used for statistical processing of the results. RESULTS: Females with RA demonstrated oppositely directed serum NOS3 and sTLR2 daily changes: NOS3 level in the morning (08:00) was lower than in the evening (+ 45.5 ± 30.7%), and sTLR2 level in the evening (at 20:00) was lower than in the morning (-21.6 ± 13.1%). RA patients had differences in NOS3 and sTLR2 production depending on NOS3 T786C genotype. CC subjects had NOS3 level at 08:00, 20:00 and day average levels lower (16-25%), and sTLR2 level higher (24-27%) than those of TT subjects. RA patients, carriers of CC genotype, had higher chances of NOS3 and sTLR2 aberrant production compared to TT and TC genotype carriers (OR = 2.99 and 4.79, respectively). CONCLUSION: RA patients demonstrated oppositely directed circadian changes of serum NOS3 and sTLR2. CC genotype carriers had lower NOS3 and higher sTLR2 production rates than TT and TC genotype carriers.
32200425 Effectiveness of the use of an algorithm in the diagnostic approach of joint pain patients 2020 Nov There is a high percentage of error in the approach of patients with joint pain by primary care physicians. An algorithm can help improve this misdiagnosis problem. Our study seeks to determine the effectiveness of an algorithm when used by primary care physicians for the diagnosis of cases of joint pain patients. A randomized clinical experiment was carried out. Primary care physicians from five cities in Colombia developed a series of clinical cases, which were presented to them through a website on their personal cell phones. Half of the doctors developed the cases using the diagnostic algorithm, and the other half developed the cases without the use of the algorithm. Main measures were proportion of correct diagnosis, number, type of laboratory and diagnostic images requested for the diagnostic approach of clinical cases. Two hundred and twenty-four primary care physicians participated. The overall proportion of cases correctly diagnosed was 37.3% higher in the intervention group; we found a greater difference in cases of spondyloarthritis (60.8%), followed by systemic lupus erythematosus with joint involvement (32.2%), rheumatoid arthritis (30.3%) and osteoarthritis (25.9%). The average number of tests requested to develop clinical cases was lower in the intervention group than in the control group, both globally and for each of the four diseases, with statistically significant differences for each of the comparisons. The diagnostic algorithm proved to be an effective tool when used by primary care physicians; the proportion of correct diagnoses increased, and the number of tests requested in the development of the cases decreased.
33164400 [Editorial explanation for Clinical practice guideline for Tripterygium Glycosides/Tripter 2020 Sep Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the treatment of rheumatoid arthritis(T/CACM 1337-2020) was approved on June, 2020 by the Standardization Office of Chinese Association of Chinese Medicine. Our group developed this guideline for the clinical application of Tripterygium Glycosides/Tripterygium wilfordii Tablets according to the manual for the clinical experts consensus of Chinese patent medicine from January, 2018, when this project was approved by Chinese Association of Chinese Medicine. In this article, the detailed information on our compilation process was provided, in order to facilitate the understanding and the application of the guideline, as well as provide reference for the development of clinical practice guideline for other Chinese patent medicine.
32043949 Rheumatoid Arthritis and Tenosynovitis at the Metatarsophalangeal Joints: An Anatomic and 2020 Apr Background Although tenosynovitis in the hands is associated with rheumatoid arthritis (RA), it is unknown whether tenosynovitis of the forefoot is associated with RA. Purpose To determine the anatomy of tendon sheaths of the forefoot and the relationship between MRI-detected tenosynovitis at metatarsophalangeal (MTP) joints and RA. Materials and Methods Fourteen forefeet of donated bodies were examined at flexor tendons and extensor tendons for the presence and course of tendon sheaths. In the prospective study between June 2013 and March 2016, newly presenting patients with RA, patients with other early arthritides, and healthy control participants all underwent MRI of unilateral MTP joints 1-5. MRI studies were scored by two independent readers for tenosynovitis, synovitis, and bone marrow edema. The association between the presence of these features and RA was examined by using logistic regression. Results Macroscopically, all extensor and flexor tendons crossing MTP joints demonstrated sheaths surrounding tendons. Microscopically, a synovial sheath was present. MRI evaluation was performed in 634 participants: 157 newly presenting patients with RA (109 women; mean age, 59 years ± 11 [standard deviation]), 284 patients with other early arthritides (158 women; mean age, 56 years ± 17), and 193 healthy control participants (136 women; mean age, 50 years ± 16). MRI-detected tenosynovitis was associated with RA, both when compared with patients with other arthritides (odds ratio [OR], 2.5; 95% confidence interval [CI]: 1.7, 3.9; P < .001) and healthy control participants (OR, 46; 95% CI: 14, 151; P < .001). The association was OR of 2.4 (95% CI: 1.5, 3.8; P < .001) for flexor tendons and OR of 3.1 (95% CI: 1.9, 5.2; P < .001) for extensor tendons. The sensitivity of tenosynovitis in RA was 65 of 157 (41%; 95% CI: 35%, 50%). The specificity for RA was 63 of 284 (78%; 95% CI: 72%, 82%) compared with other arthritides, and three of 193 (98%; 95% CI: 96%, 99%) compared with healthy control participants. Conclusion Tendons at metatarsophalangeal joints are surrounded by tenosynovium. MRI-detected tenosynovitis at metatarsophalangeal joints was specific for rheumatoid arthritis when compared with findings in patients with other arthritides and findings in healthy control participants. © RSNA, 2020 Online supplemental material is available for this article.
32718130 Handheld dermatoscopy as an easy-to-use capillaroscopic instrument in rheumatoid arthritis 2020 Oct 22 BACKGROUND/AIM: Nailfold video capillaroscopy is considered as a reliable method for evaluating peripheral microangiopathy in rheumatologic diseases. In this study, we aimed to demonstrate the utility of handheld dermatoscopy as an easy-to-use nailfold capillaroscopic instrument in patients with rheumatoid arthritis. MATERIALS AND METHODS: This cross-sectional study included patients with rheumatoid arthritis and healthy subjects. A handheld dermatoscopic examination of proximal nail fold was performed in each subject. The possible correlation of capillaroscopic findings with disease activity was evaluated using the disease activity score 28 (DAS28). RESULTS: A total of 59 patients with rheumatoid arthritis and 60 healthy subjects were enrolled in the study. The presence of capillaryenlargement, avascular areas, capillary deformities, and capillary vascular anomalies in the group of patients showed a statistically significant difference when compared with the healthy subjects. No correlation was found between the nail fold capillaroscopic findings and DAS28 score. CONCLUSION: Hand-held dermatoscopy seems to be a useful technique in the evaluation of nail fold capillary changes. We suggest that in patients with rheumatoid arthritis, when capillaroscopic examination is needed, it can be evaluated using handheld dermatoscopy. Selected patients who showed findings using this method can be further examined with classical capillaroscopy to obtain more quantitative data.
32674900 [Biotherapies in elderly patients]. 2020 Sep The ageing of the population leads health professionals to question the tolerance and the effectiveness of the different biotherapies used in autoimmune diseases. Due to the exponential increase of biotherapies and their indications, several studies have been carried out to evaluate their impact on elderly patients suffering from autoimmune disease. However, these studies are still too few to take into account all the different specificities of elderly patients and their comorbidities; prescribers are therefore hesitant with their introduction after 75 years or even 65. More than the age of patients, it is necessary to evaluate the comorbidities before introducing this kind of treatments. Every biotherapy has different indications and contraindications, which must be known to adapt each treatment to each patient. This focus aims to remind of the adaptations and contraindications of the different biological disease-modifying anti-rheumatic drugs for geriatric population, and improve their uses since the treatments for these patients are sometimes not enough. Here we resume the methods allowing supervisors to identify errors of clinical reasoning in medical students and interns and we explain remediation techniques adapted to the types of error identified. Access to short illustrative videos of a MOOC (Massive Open On line Course) devoted to the supervision of clinical reasoning constitutes practical help for supervisors who are not expert in the complexity of medical pedagogy at the bedside.
31449733 Comprehensive Profiling of the Rheumatoid Arthritis Antibody Repertoire. 2020 Feb OBJECTIVE: Autoantibodies against citrullinated proteins are found in 64-89% of rheumatoid arthritis (RA) patients, with 88-99% specificity. This study was undertaken to create an unbiased, comprehensive profile of serum antibodies against the human proteome, including the citrullinome and the homocitrullinome, in RA patients, using a high-density peptide array. METHODS: Our high-density peptide array, consisting of >4.6 million peptides, contained the entire annotated human proteome. The 20,246 proteins were represented as overlapping 16-mer peptides. In addition to native peptides, citrullinated and homocitrullinated peptides were included, as substitutions for arginine and lysine, and provided a comprehensive screen against all possible epitopes. Twenty-six serum samples (from 8 controls and 18 RA patients) were profiled on the high-density peptide array. Using RA-specific epitopes, we constructed an 8-epitope diagnostic biomarker on a Gyrolab xPlore instrument with a cohort of 92 serum samples (from 29 controls and 63 RA patients). The diagnostic biomarker was further validated with an independent cohort of 181 serum samples (from 54 controls and 127 RA patients). RESULTS: In the initial cohort the diagnostic performance of the 8-epitope biomarker yielded 96.6% specificity and 92.1% sensitivity. The overall diagnostic performance in the validation cohort was 94.4% specificity and 85% sensitivity. In both cohorts, the performance of the 8-epitope diagnostic biomarker compared favorably against the Abnova cyclic citrullinated peptide 2 (CCP2) assay. Using data from the peptide array, we identified novel RA-specific epitopes and formed the basis of a new RA diagnostic assay. CONCLUSION: Comprehensive antibody profiling using a high-density peptide array not only identified novel RA-specific epitopes but also allowed us to construct a novel diagnostic biomarker that is as specific as and more sensitive than the Abnova CCP2 assay.
33295721 Tuberculosis risk in patients with rheumatologic disease treated with biologic drugs. 2020 Sep INTRODUCTION: The risk of tuberculosis is higher in cases who have used antiTNF treatments. However, it is not clearly known whether there is a relationship between other biologic agents and the risk of developing tuberculosis or not. We aimed to investigate the prevalence of active tuberculosis among patients with rheumatic disease treated with biologic drugs. MATERIALS AND METHODS: The study was performed at a tertiary referral center from January 2015 to December 2019. A total of 2000 patients with rheumatic diseases were screened and 461 patients were enrolled in the study due to regular records. They were underwent LTBI screening tests and were followedup at least 1 year after TNF inhibitor treatment initiation. RESULT: The median age of all patients was 48 (min-max: 19-80). 283 patients (61.3%) were female and 178 (38.7%) were male. The most common diseases were ankylosing spondylitis (67.2%), rheumatoid arthritis (26%) and psoriatic arthritis (5.2%). Anti-TNF treatments were given to 85.2% of all cases and other biologic treatments were given to 14.8%. Tuberculin skin test was applied to 429 patients and 70.4% positivity was found. Quantiferon-TB test was applied to 93 patients and 20.4% positivity was found. 320 patients were treated for LTBI due to positive tuberculin skin test and/or positive quantiferon-TB test. TB was developed in only one patient out of 393 patients who were treated with anti-TNF treatments and the the prevalence of TB development was found 255/100.000. CONCLUSIONS: The incidence of tuberculosis was quite low in our patients with rheumatic disease who were receiving anti-TNF treatment compared to previous studies. Also, in patients who were using other biological treatments, no TB cases were developed.
33333119 Rational design of metal-organic frameworks to deliver methotrexate for targeted rheumatoi 2021 Feb 10 Methotrexate (MTX) has been used as an anchor drug for the treatment of rheumatoid arthritis (RA), while the patients with chronic MTX administration suffer from severe side-effects. To this end, targeted delivery of MTX by nanomedicine has attracted great interest. In this work, we aimed to employ metal-organic frameworks (MOFs) as nanocarrier to deliver MTX by virtue of its facile and green preparation and exceptionally high drug loading. While MTX could be easily and effectively loaded via different MOF construction strategies, such as direct coordination, physical encapsulation, and covalent conjugation, we found that most of the MTX loading MOFs showed premature and burst drug release, attributable to the unstable coordination between MTX and metals. To address this issue, we rationally designed the MOFs by conjugating MTX with tannic acid (TA) at 2:1 M ratio and then coordinating with ferric ion (Fe(3+)), followed by surface modification of hyaluronic acid (HA). The resulting MOFs achieved ultra-high drug loading (45%) and sustained drug release, and could selectively recognize the diseased cells for anti-inflammatory effect. The in vivo therapeutic evaluation suggested that the MOFs could enhance the anti-rheumatic activity of MTX while minimizing its toxic effects by targeted drug delivery, resulting in improved therapeutic index. This work provides a biocompatible nano-platform to deliver MTX for RA treatment, and importantly, calls for special attention to the gap between MOFs design and their biological applications, and the gap needs to be filled by careful evaluation of in vivo stability and burst drug release.
32828146 Metformin repositioning in rheumatoid arthritis. 2021 Jul OBJECTIVES: Metformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autoimmune disease and malignancy conditions through the effect of metformin on the immune system. Although there have been reports on the therapeutic effects of metformin on mouse models of collagen-induced arthritis, simulating human rheumatoid arthritis (RA), the effect of metformin on human RA remains unknown. Therefore, we investigated the inhibitory effect of metformin on the pathogenesis of human RA in vitro. METHODS: Osteoclastogenesis was evaluated with or without metformin. through tartrate-resistant acid phosphatase staining, osteoclast-specific enzyme expression analysis, and a bone resorption assay. Human fibroblast-like synoviocyte MH7A cells were stimulated with TNF-α, and the expression of proinflammatory cytokines and protease and growth factor genes was evaluated with or without metformin. Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-α. Moreover, we examined angiogenesis by performing a tube formation assay using human umbilical vein endothelial cells (HUVECs) with or without metformin. RESULTS: Osteoclastogenesis was suppressed in the presence of metformin, and the expression of osteoclast-specific genes was reduced. The TNF-α-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin. Additionally, the induced formation of tubular networks in HUVECs was also disrupted following treatment with metformin. CONCLUSIONS: These results suggest that metformin might improve the pathogenesis of RA, including joint inflammation and destruction. Thus, metformin might be utilised as a potential therapeutic agent in the treatment of RA.
32164778 Identification of molecules associated with response to abatacept in patients with rheumat 2020 Mar 12 BACKGROUND: Abatacept (ABA) is a biological disease-modifying antirheumatic drug (bDMARD) for rheumatoid arthritis (RA). The aim of this study was to identify molecules that are associated with therapeutic responses to ABA in patients with RA. METHODS: Peripheral blood was collected using a PAX gene Blood RNA kit from 45 bDMARD-naïve patients with RA at baseline and at 6 months after the initiation of ABA treatment. Gene expression levels of responders (n = 27) and non-responders (n = 8) to ABA treatment among patients with RA at baseline were compared using a microarray. The gene expression levels were confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Gene expression analysis revealed that the expression levels of 218 genes were significantly higher and those of 392 genes were significantly lower in the responders compared to the non-responders. Gene ontology analysis of the 218 genes identified "response to type I interferon (IFN)" with 24 type I IFN-related genes. RT-qPCR confirmed that there was a strong correlation between the score calculated using the 24 genes and that using OAS3, MX1, and IFIT3 (type I IFN score) (rho with the type I IFN score 0.981); the type I IFN score was significantly decreased after treatment with ABA in the responders (p < 0.05), but not in the non-responders. The receiver operating characteristic curve analysis of the type I IFN score showed that sensitivity, specificity, and AUC (95% confidence interval) for the responders were 0.82, 1.00, and 0.92 (0.82-1.00), respectively. Further, RT-qPCR demonstrated higher expression levels of BATF2, LAMP3, CD83, CLEC4A, IDO1, IRF7, STAT1, STAT2, and TNFSF10 in the responders, all of which are dendritic cell-related genes or type I IFN-related genes with significant biological implications. CONCLUSION: Type I IFN score and expression levels of the nine genes may serve as novel biomarkers associated with a clinical response to ABA in patients with RA.
32056521 Oxidative Stress in Autoimmune Diseases: An Under Dealt Malice. 2020 Oxidative stress is the off-balance of antioxidants and free radicals. All kinds of diseases and disorders give rise to oxidative damage including autoimmune diseases. An autoimmune disorder is a pathological condition characterized by the breakdown of self-tolerance of the immune system in the body. Immunological processes against tissues and organs lead to enhanced oxidative stress and, in turn, misbalance of oxidative stress aggravates the pathobiology of the disease. Highly reactive nature of free radicals, for example hydroxyl and superoxide ions, alters DNA, protein, and lipids in the body which augment the pathologic processes of diseases. The damaged biomolecules are responsible for systemic complications and secondary disease co-morbidities. In this review, we discuss the role of oxidative stress in some incapacitating autoimmune diseases like Rheumatoid arthritis, Systemic Lupus Erythematosus, Type 1 Diabetes, and Multiple Sclerosis. Oxidative stress plays a central and course defining role in these diseases and it has become a necessity to study the pathological mechanism involved in oxidative stress to better understand and offer treatment holistically. Presently there are no clinically available parameters for measurement and treatment of pathological oxidative stress, therefore it requires intensive research. Probably, in the future, the discovery of easily detectable markers of oxidative stress can aid in the diagnosis, prognosis, and treatment of progressively destructive autoimmune diseases.
32151502 Linking ICF components to outcome measures for hand osteoarthritis and rheumatoid arthriti 2020 Oct STUDY DESIGN: Systematic review. INTRODUCTION: A patient with rheumatoid arthritis (RA) or osteoarthritis (OA) may have functional impairments, decreased quality of life, and productivity reductions. The International Classification of Functioning (ICF) provides a scientific basis for understanding health, outcomes, and determinants. PURPOSE OF THE STUDY: The purpose of this study was to critically appraise the current literature for outcome measures associated with the management of OA or RA to determine if they describe the components of the ICF that includes body functions and structures, activities, participation, environmental factors, as well as quality of life. The secondary purpose is to examine if patient satisfaction was addressed in the interventions associated with management of OA or RA. METHODS: A comprehensive literature search was conducted in the CINAHL and PubMed databases using the search terms joint protection, hand OA, hand RA, and assistive devices. RESULTS: Six of the outcome measures were linked to body structures and body functions, three were associated with activity limitations and participation restrictions, one was linked to environmental factors, and two outcome measures addressed quality of life. DISCUSSION: Practitioners should incorporate outcome measures that address environmental factors and quality of life as they relate to the ICF. CONCLUSION: Most of the outcome measures associated with hand OA or RA are related to body structures and body functions or activity limitations and participation restrictions.
31737959 Inhibition of Ctsk modulates periodontitis with arthritis via downregulation of TLR9 and a 2020 Jan OBJECTIVES: The mechanisms underlying the effects of Toll-like receptor 9 (TLR9) and autophagy on rheumatoid arthritis (RA)-aggravated periodontitis are unclear. We aimed to explore a novel target, cathepsin K (Ctsk)-mediated TLR9-related autophagy, during the progress of periodontitis with RA. MATERIALS AND METHODS: DBA/J1 mouse model of periodontitis with RA was created by local colonization of Porphyromonas gingivalis (Pg) and injection of collagen. The expression of Ctsk was inhibited by adeno-associated virus (AAV). Micro-CT, immunohistochemistry (IHC), Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of TLR9-related autophagy in periodontitis with RA. Small interfering RNA (siRNA) and CpG oligodeoxynucleotides (CpG ODN) were applied in macrophages. Western blot, immunofluorescence (IF) and qRT-PCR were used to verify the in vivo results. RESULTS: RA can promote periodontitis bone destruction in the lesion area, while inhibiting Ctsk could effectively alleviate this effect. The infiltration of macrophages, TLR9, autophagy proteins (TFEB and LC3) and inflammatory cytokines increased in the periodontitis-with-RA group and was reduced by the inhibition of Ctsk in the periodontal region. Macrophage stimulation confirmed the in vivo results. With the activation of TLR9 by CpG ODN, inhibition of Ctsk could suppress both TLR9 downstream signalling proteins and autophagy-related proteins. CONCLUSIONS: This study advanced a novel role for Ctsk in TLR9 and autophagy to explain the interaction between periodontitis and RA.
32416449 Chronotherapy targeting cytokine secretion attenuates collagen-induced arthritis in mice. 2020 Jul OBJECTIVE: Diurnal variation of symptoms are observed in rheumatoid arthritis, especially in productions of cytokines that show peak concentrations during mid night. In contrast, cytokines of collagen-induced arthritis (CIA) mice increase in daytimes under Mid-light condition. By using chronotherapy, differences in drug efficacies according to administration time of Baricitinib, a wide ranged cytokine blocker, were examined in CIA mice. METHODS: CIA mice were administered a dose of 3 mg/kg of Baricitinib once a day at zeitgeber time (ZT) 0 or ZT12 for 21 days. Arthritis scores, histopathology and factors related to joint destruction in sera were examined. Phosphorylation of STAT3 in liver, expressions of cytokines in spleen, and Interleukin (IL)-6 and tumor necrosis factor (TNF)-α in sera were measured. RESULTS: In CIA mice, diurnal variations were observed both in expressions of cytokines and phosphorylation of STAT3. Arthritis scores of ZT0/12 group decreased from day3 as compared to untreated mice, and those of ZT0 group significantly decreased as compared to ZT12 group from day12. Pathological findings, immunohistochemistry of cytokines and Receptor activator of nuclear factor kappa-Β ligand (RANKL)/osteoprotegerin ratio in sera well reflected results of arthritis scores. Diurnal variation of STAT3 phosphorylation was suppressed in ZT0 group. At ZT2, expressions of IL-6/Interferon-γ/TNF/granulocyte-macrophage colony-stimulating factor in ZT0 group were significantly decreased as compared to untreated mice, though not in ZT12 group. In ZT0 group, IL-6 and TNF-α in sera were decreased for longer time than that in ZT12 group. CONCLUSION: Chronotherapy using Baricitinib targeting cytokine secretions is effective in CIA mice. Clinical applications of chronotherapy can be expected to enhance the drug efficacy.
32896266 Biological and targeted-synthetic disease-modifying anti-rheumatic drugs with concomitant 2021 Jul OBJECTIVES: To determine the real-life efficacy, safety, and drug-retention rates of leflunomide (LEF) or methotrexate (MTX) as a synthetic DMARD used in combination with biological DMARDs for rheumatoid arthritis (RA). METHODS: The TReasure database is a web-based, prospective, observational cohort of RA and spondyloarthritis patients from 17 centres in different regions of Turkey and data entry was enabled since December 2017. Until May 2019, 2556 RA patients on biologic treatment were recorded. Demographic and RA-related data of 1526 patient either received LEF or MTX were compared, efficacy of both drugs compared by RA-disease activity composite indices. Reasons fordrug discontinuation also recorded. Drug retention rates were compared with Kaplan-Meier curves (log-rank test). RESULTS: Of 2556 RA patients 1526 (59.7%) were receiving concomitant LEF (n=646, 42.3%; median follow up 35 months) or concomitant MTX (n=880, 57.3%; median follow-up 32 months) at the time of initiation to their first bDMARDs. The LEF group were older and had longer disease duration, proportion of females and seropositive patients was higher in this group. In the LEF group, non-anti-TNF agents were used in higher rate. Remission rates, changes in composite indices and rate of comorbidities and adverse events were similar in both groups. The retention rate of LEF + non-anti-TNF b/tsDMARDs was higher compared to MTX + anti-TNF bDMARDs (p=0.002, log-rank). Rates of adverse events were similar in both groups. CONCLUSIONS: LEF in combination with either anti-TNF or non-anti-TNF drugs appears as an effective and safe therapeutic option at least as MTX.
32366246 Quality of life and influencing factors of patients with rheumatoid arthritis in Northeast 2020 May 4 PURPOSE: Rheumatoid arthritis (RA) is a disease with a high disability rate, resulting in severe family and social burden. The aim of treatment is to improve the health-related quality of life (QoL) of patients. The purpose of this study was to evaluate the QoL of patients with RA in Northeast China and analyze its influencing factors. METHODS: The study group consisted of 200 patients diagnosed with RA. The control group consisted of 200 healthy subjects. All subjects were residents in Northeast China. The investigation was conducted by questionnaire survey and electronic medical record. The WHOQOL-BREF, The Short-Form 36 Health Survey (SF-36) and Quality of Life Instruments for Chronic Diseases-RA (QLICD-RA) were used as questionnaires. RESULTS: The QoL scores acquired by SF-36, WHOQOL-BREF and QLICD-RA scales showed significant differences between RA and control groups (P < 0.001). Multiple regression analysis showed that sleep duration (P = 0.001), psychological counseling (P < 0.001) and C4 level (P = 0.001) influenced the SF-36 scale evaluation model. IgA levels (P < 0.001) and being overweight (P = 0.030) were included in the WHOQOL-BREF evaluation model. Adequate sleep (P = 0.001) and psychological counseling(P = 0.050) entered the QLICD-RA scale evaluation model (P = 0.050), in which psychological counseling, normal C4 levels and being overweight were protective factors for RA, insufficient sleep and IgA levels were risk factors for RA. CONCLUSIONS: The QoL of RA patients is generally lower than those of healthy subjects in the Northeast China, Northeast China. Sleep duration, BMI (Body mass index), psychological counseling, C4 and IgA levels are factors that influence the QoL scores of RA patients.