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ID PMID Title PublicationDate abstract
34151716 Early radiological progression remains associated with long-term joint damage in real-worl 2022 Mar OBJECTIVE: To evaluate radiological damage and to explore characteristics associated with radiological progression in rheumatoid arthritis (RA) treated to the target of remission in a real-world setting. METHODS: Baseline to 6 year follow-up data were used from an observational early RA cohort. Radiographs of hands and feet at baseline, 6 months, and 1, 3, and 6 years were scored using the modified Sharp/van der Heijde score (SHS). The threshold for rapid radiological progression (RRP) after 6 months was based on the calculated smallest detectable change of 3.95. Negative binomial generalized linear mixed model and logistic regression analyses were performed to examine which variables were associated with RRP and 6 year radiological progression. RESULTS: Most radiological damage occurred in the first year of treatment [median 2.0 interquartile range (IQR) 1.0-4.0 SHS points] compared to the subsequent 5 years of follow-up (median 3.0 IQR 1.0-5.0 SHS points). While low disease activity was achieved within 6 months on average, 18.8% of the patients developed RRP. Anti-cyclic citrullinated peptide (anti-CCP) positivity [incidence rate ratio (IRR) 1.42, p = 0.03], baseline erosive disease (IRR 1.60, p = 0.02), and RRP (IRR 3.28, p < 0.001) were associated with 6 year radiological progression. Erosive disease was the strongest predictor of RRP (odds ratio 8.8, p < 0.001). CONCLUSION: Long-term radiological outcome is limited in most real-world RA patients treated to the target of remission, but RRP still occurs. Anti-CCP positivity, baseline erosive disease, and RRP remain associated with long-term radiological outcome.
34462830 Circular RNA circ_0008360 Inhibits the Proliferation, Migration, and Inflammation and Prom 2022 Feb Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of many diseases, including rheumatoid arthritis (RA). However, the functions and molecular mechanism of circ_0008360 in RA remain unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ_0008360, microRNA-135b-5p (miR-135b-5p), and histone deacetylase 4 (HDAC4). Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to assess cell proliferation, migration, and apoptosis, respectively. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-135b-5p and circ_0008360 or HDAC4 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. Western blot assay was used to detect the protein expression of HDAC4 and proliferating cell nuclear antigen (PCNA). The expression of circ_0008360 was downregulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0008360 suppressed the proliferation, migration, and inflammation and promoted apoptosis of RA-FLSs, and circ_0008360 knockdown showed opposite effects. Moreover, miR-135b-5p was a direct target of circ_0008360, and miR-135b-5p could reverse the effects of circ_0008360 on proliferation, migration, inflammation, and apoptosis in RA-FLSs. Furthermore, HDAC4 was a downstream target of miR-135b-5p, and miR-135b-5p accelerated the proliferation, migration, and inflammation and suppressed apoptosis of RA-FLSs by targeting HDAC4. In addition, circ_0008360 positively regulated HDAC4 expression by sponging miR-135b-5p. Circ_0008360 inhibited the proliferation, migration, and inflammation and facilitated apoptosis of RA-FLSs by sponging miR-135b-5p and upregulating HDAC4, providing a potential target for prevention and treatment of RA.
35338383 The beneficial effect of csDMARDs co-medication on drug persistence of first-line TNF inhi 2022 May The study aimed to compare treatment retention for first-line TNF inhibitor (TNFi) in the ATTRA registry patients receiving either combination with conventional synthetic DMARDs or TNFi as monotherapy. A retrospective multicenter study analyzed data of all adult patients with rheumatoid arthritis (n = 3032) starting TNF inhibitor as the first-line biological therapy in combination with csDMARDs or in monotherapy from January 1st 2012 to December 31st 2020. Kaplan-Meier method was employed to calculate drug retentions. Survival curves of treatment retentions were compared through Log-rank test between the studied subgroups. The hazard ratio for drug discontinuation was assessed through univariate cox regression models. In patients who started the first line TNFi therapy, the median treatment retention was 47.7 (42.2; 53.1) months for combination therapy and 22.7 (14.9; 30.6) months for TNFi monotherapy (p < 0.001). Estimated one-year survival was higher in patients on TNFi combined with csDMARDs as compared with TNFi monotherapy (75.3% vs 65.7%); two-year survival rate was 63.2% vs 49.2%, three-year survival rate was 55.4% vs 42.4% and five-year survival 44.9% vs 26.4% of patients. The estimated survival on the first TNFi was higher in patients taking combination therapy with methotrexate than with other csDMARDs (p = 0.003). Use of csDMARDs co-medication was associated with significantly better first TNFi drug survival compared to monotherapy. The combination of TNFi with MTX is more effective than the combination with leflunomide, which did not demonstrate a significant effect.
34320607 Association between nuclear factor of activated T cells C2 polymorphisms and treatment res 2022 Jan 1 OBJECTIVES: Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors. METHODS: This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. RESULTS: This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283). CONCLUSION: This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.
35092909 Aconiti Lateralis Radix Praeparata lipid-soluble alkaloids alleviates IL-1β-induced infla 2022 Mar BACKGROUND: Fuzi lipid-soluble alkaloids (FLA) is the main bioactive components extracted from the traditional Chinese medicine Aconiti Lateralis Radix Praeparata ("Fuzi" in Chinese), which has promising analgesic and anti-inflammatory effects. However, the effects and the underlying mechanisms of FLA on rheumatoid arthritis (RA) have not been studied. The present study aimed to explore the anti-arthritic effects of FLA and its underlying mechanisms. METHODS: To standardize the FLA, UPLC-HR-MS was used for quantitative and qualitative analysis of the representative alkaloids. Cell viability was measured by MTT. The anti-inflammatory activity of FLA was examined by analyzing the expression levels of inflammatory mediators such as TNF-α, IL-6, MMP-1, MMP-3, PGE2, and COX-2 using ELISA and RT-PCR analysis. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of HFLS-RA and analyzed by flow cytometry. Western blot analysis was used to analyze the expression of NF-κB, MAPKs and mitochondrial apoptosis pathway related proteins. RESULTS: FLA had a significant inhibitory effect on the proliferation of HFLS-RA induced by IL-1β, which was accompanied by decreased expression levels of TNF-α, IL-6, MMP-1, MMP-3, COX-2 and PGE2. Remarkably, FLA inhibited the activation of NF-κB and MAPKs signaling pathways in IL-1β-induced HFLS-RA, as well as inducing HFLS-RA apoptosis through the mitochondrial apoptosis pathway. CONCLUSIONS: FLA inhibited the expression and synthesis of inflammatory mediators by inhibiting the activation of NF-κB and MAPKs signaling pathways in HFLS-RA, and induced apoptosis of HFLS-RA via the mitochondrial apoptosis pathway.
34657778 Estimated 10-year cardiovascular risk in a large Italian cohort of rheumatoid arthritis pa 2022 Feb BACKGROUND: Several cardiovascular (CV) risk algorithms are available to predict CV events in the general population. However, their performance in patients with rheumatoid arthritis (RA) might differ from the general population. This cross-sectional multicentre study aimed to estimate the 10-year CV risk using two different algorithms in a large RA cohort and in patients with osteoarthritis (OA). METHODS: In a consecutive series of RA patients and matched OA controls without prior CV events, clinical and serologic data and traditional CV risk factors were recorded. The 10-year CV risk was assessed with the Systematic COronary Risk Evaluation (SCORE) and the "Progetto Cuore" algorithms. RESULTS: 1,467 RA patients and 342 OA subjects were included. RA patients were more frequently diabetic (9.9% vs 6.4%; p=0.04) and smokers (20.4% vs 12.5%; p=0.002) but had lower prevalence of obesity (15% vs 21%; p=0.003). Dyslipidaemia was more prevalent in OA (32.5% vs 21.7%; p<0.0001). The 10-year estimated CV risk was 1.6% (95%CI 1.3-1.9) in RA and 1.4% (95%CI 1.3-1.6) in OA (p=0.002) according to SCORE and 6.5% (95%CI 6.1-6.9) in RA and 4.4% (95%CI 3.9-5.1) in OA (p<0.001) according to "Progetto Cuore". Regardless of the score used, RA patients had a 3- to-4-fold increased 10-year risk of CV events compared to OA subjects. CONCLUSION: RA patients have a significantly higher 10-year risk of CV events than OA subjects. In addition to effective disease control and joint damage prevention, specific protective measures targeting modifiable traditional CV risk factors should be implemented in RA.
35292498 Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs i 2022 Mar 15 OBJECTIVES: To identify differing patient characteristics at the time of stop and restart of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA), stratified by stop reason. DESIGN: Explorative descriptive cohort study. SETTING: Swiss Clinical Quality Management in Rheumatic Diseases (1999-2018). PARTICIPANTS: Patients with RA who stopped their first b/tsDMARD. OUTCOME MEASURES: We assessed patient characteristics at b/tsDMARD stop and restart, stratified by stop reason (non-response, adverse event, remission, other). RESULTS: Among 2526 eligible patients, most patients (38%) stopped their b/tsDMARD due to non-response. At treatment stop, most characteristics did not differ by stop reason, yet some differed significantly (p<0.0001, those stopping due to remission had lowest median Health Assessment Questionnaire measurements (0.1) and were least likely to use leflunomide combination therapy (3.9%) and to have fibromyalgia (6.7%)). The majority of patients restarted b/tsDMARDs without changes in patient characteristics at restart. However, among the 48% of patients who restarted a b/tsDMARD after having previously stopped due to remission or other reasons, disease activity measurements were significantly worse compared with treatment stop date (mean disease activity score-erythrocyte sedimentation rate score of 2.0 at b/tsDMARD restart vs 3.5 at treatment stop (p<0.0001)). Furthermore, we observed non-significant trends in several patient characteristics (eg, higher proportion of women (75% at b/tsDMARD restart vs 70% at treatment stop, p=0.38), patients with seropositivity (anti-citrullinated protein antibody positive 67% vs 58%, p=0.25), with family history of rheumatic diseases (24% vs 20%, p=0.15), osteoarthritis/arthroplasty (25% vs 20%, p=0.34) and the metabolic syndrome (11% vs 6%, p=0.15). CONCLUSION: Differences among patient characteristics across b/tsDMARD cessation strata were few. However, differences between stop and restart may have identified an RA phenotype that is challenging to treat. Further research on identifying the patient characteristics predictive of successful drug holidays and the optimal time to initiate and stop a drug holiday is warranted.
34788483 Blood MALT1, Th1, and Th17 cells are dysregulated, inter-correlated, and correlated with d 2022 Jan OBJECTIVE: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) participates in inflammatory and autoimmune diseases via activating various signaling pathways and promoting the differentiation of T-helper (Th) 1 and Th17 cells; however, it is rarely reported in rheumatoid arthritis (RA). This study aimed to assess the correlation of MALT1 with Th1 and Th17 cells and evaluate its potential as a biomarker for evaluating disease activity and treatment outcomes in RA patients. METHODS: This study enrolled 139 RA patients and 45 health controls (HCs); then, blood MALT1, Th1, and Th17 cells were determined. For RA patients only, blood MALT1 at week (W) 6 and W12 after treatment was also detected. Additionally, clinical response and remission of RA patients were assessed at W12. RESULTS: MALT1 (p < 0.001), Th1 (p = 0.011), and Th17 (p < 0.001) cells were all increased in RA patients than HCs; meanwhile, increased MALT1 was associated with elevated Th1 (p = 0.003) and Th17 (p < 0.001) cells in RA patients. Besides, MALT1, Th1, and Th17 cells were positively correlated with parts of disease activity indexes in RA patients (all p < 0.050). In addition, MALT1 was gradually declined from W0 to W12 (p < 0.001) in RA patients. Specifically, MALT1 at W6 and W12 was lower in response patients than no response patients (both p < 0.010), also in remission patients than no remission patients (both p < 0.050). CONCLUSION: MALT1, Th1, and Th17 cells are dysregulated, inter-correlated, and correlated with disease activity in RA patients; meanwhile, the decline of MALT1 expression can partly reflect RA treatment response and remission.
35045800 Long non-coding RNA cancer susceptibility candidate 2 regulates the function of human fibr 2022 Feb Rheumatoid arthritis (RA) is a perennial inflammatory condition. Preliminary research indicated that long non-coding (lnc)RNA cancer susceptibility candidate 2 (CASC2) was downregulated in the serum of RA patients. Our study was designed to reveal the roles of lncRNA CASC2 in RA and the latent mechanisms underlying its role. Bioinformatics method (Starbase) and dual-luciferase reporter assay revealed that microRNA (miR)-18a-5p directly interacted with lncRNA CASC2. Furthermore, lncRNA CASC2 and miR-18a-5p expression in the serum samples of RA patients and healthy controls were measured via reverse transcription-quantitative PCR. Compared with the healthy subjects, lncRNA CASC2 was downregulated, whereas miR-18a-5p was upregulated in patients with RA. Overexpression of lncRNA CASC2 decreased the viability of human fibroblast-like synoviocytes (HFLSs) and induced apoptosis, as revealed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry analyses. Furthermore, the Western blotting assay suggested that Bax was upregulated and Bcl-2 was downregulated in lncRNA CASC2 up-regulated HFLSs. Downregulation of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)1, and MMP3 levels by lncRNA CASC2 up-regulation was determined using enzyme-linked immunosorbent assays (ELISAs). However, HFLSs co-transfected with miR-18a-5p mimic exhibited opposite effects compared with the case for the overexpression of lncRNA CASC2. The aforementioned methods were used to verify that a binding site exists between B-cell translocation gene 3 (BTG3) and miR-18a-5p. The effects of miR-18a-5p inhibitor on HFLSs were reversed by BTG3 silencing. Overall, lncRNA CASC2 alleviated RA by adjusting the miR-18a-5p/BTG3 signaling axis and could serve as a novel therapeutic option for RA.
34128802 Central sensitisation features are associated with neuropathic pain-like symptoms in patie 2022 May OBJECTIVES: Several studies have indicated that arthralgia may be driven by central sensitisation. Central sensitivity syndrome (CSS) is a concept that unifies various symptoms due to central sensitisation. Recently, the central sensitisation inventory (CSI) was developed as a screening questionnaire to detect CSS. Using the CSI, we examined the prevalence, the clinical characteristics of CSS, and the association between CSS and neuropathic pain (NP)-like symptoms among rheumatoid arthritis (RA) patients. METHODS: The CSI was administered to 240 RA outpatients. We evaluated their disease activity and several potentially relevant patient-reported outcomes. We compared the clinical parameters depending on the severity of CSS and examined the effect of the CSI score on NP-like symptoms among the relevant clinical parameters using multivariate analyses. RESULTS: The mean disease duration was 9.58 ± 7.76 years. Eighteen (7.5 %) patients had CSS, which was associated with evaluator global assessment (EGA) (odds ratio (OR) 0.860); fibromyalgia symptom scale (OR 1.46); painDETECT questionnaire score (OR 1.24); hospital anxiety and depression scale-anxiety (OR 1.35); and physical (OR 0.898), mental (OR 0.828), and role-social (OR 0.946) component summary scores on the Short-Form 36-Item Health Survey. CSI score was the factor that contributed most to NP-like symptoms (p=0.000, β=0.266). CONCLUSIONS: NP-like symptoms might be one of the symptoms of CSS in longstanding RA patients. In longstanding RA patients who have disproportionately greater NP-like symptoms and/or widespread pain compared with degree of inflammation, detecting CSS using CSI might help to understand the pathogenesis of patients.
33902096 Efficacy of Atorvastatin Plus Conventional Disease-Modifying Antirheumatic Drugs on Diseas 2022 Jan 1 METHODS: We queried the PubMed, Embase, Web of Science, and the CENTRAL (Cochrane Central Register of Controlled Trials) databases for this study. The pooled efficacy was evaluated using standardized mean differences. The inverse of the variance model was used for data pooling. RESULTS: Based on the search, we identified 9 randomized controlled trials. The trials included 258 patients in the atorvastatin plus DMARD groups and 246 patients in the DMARD alone groups. The primary outcome was the change from baseline in the 2018 (209:228 Disease Activity Score in 28 Joints). Based on the Disease Activity Score in 28 Joints, disease activity in RA patients decreased significantly in patients given atorvastatin plus DMARD compared with patients given DMARD alone (standardized mean difference, -2.46; 95% confidence interval, -3.98 to -0.95; p = 0.0015; I2 = 97%; p < 0.01). Subgroup analysis did not identify any confounding factors, and no publication bias was detected in the meta-analysis. CONCLUSIONS: The result supports that atorvastatin could be added to DMARDs to treat patients with RA.
35316384 [Prescription frequency of physical therapy for inflammatory rheumatic diseases]. 2022 Jun OBJECTIVE: To investigate the frequency of outpatient physical therapy (PT) in persons with rheumatoid arthritis (RA), axial spondylarthritis (axSpA), psoriatic arthritis (PsA) or systemic lupus erythematosus (SLE) between 2005 and 2020. METHODS: Adult insured persons of the BARMER health insurance fund with a diagnosis of RA (ICD-10: M05, M06), axSpA (M45), PsA (M07.0-3) or SLE (M32.1,8,9) were included. The prescription of PT was identified via the national item number index for therapeutic products. The proportion of persons with at least 1 prescription in the years 2005 to 2020 is reported as well as PT prescriptions by age and gender groups. In addition, the number and duration of prescriptions were compared and it was analyzed whether persons in specialist care received PT more frequently. RESULTS: In 2020, 43% (SLE), 46% (RA, PsA) and 49% (axSpA) received at least 1 PT prescription. Physiotherapy was prescribed most frequently (37%), followed by manual therapy (14%) and thermotherapy (10%). Since 2005 the number of insured persons receiving PT has not changed. Manual therapy is increasingly prescribed (+7%), while massage (-10%), thermotherapy (-7%) and electrotherapy (3% in 2005, 2% in 2020) have been decreasing (data relating to RA). The number of prescriptions has not relevantly changed since 2010. Persons in orthopedic care received PT more frequently than persons in general or rheumatological care. Female patients 61-80 years old were most frequently treated with PT. CONCLUSION: Slightly less than half of all persons with an RA, axSpA, PsA or SLE diagnosis received outpatient PT. This proportion has hardly changed in the last 15 years.
34255815 Low-dose oral glucocorticoid therapy and risk of osteoporotic fractures in patients with r 2022 Apr 11 OBJECTIVES: Clinical trials have shown that low-dose glucocorticoid therapy in patients with RA reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA. METHODS: This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7-12 months) and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, adjusted for lifestyle parameters, comorbidities and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids. RESULTS: Among 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent dose/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98, 1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11, 2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids. CONCLUSION: Clinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.
35627636 Content, Structure and Delivery Characteristics of Yoga Interventions for Managing Rheumat 2022 May 17 The global burden of rheumatoid arthritis among adults is rising. Yoga might be a potential solution for managing rheumatoid arthritis. This systematic review aims to synthesise the content, structure and delivery characteristics of effective yoga interventions for managing rheumatoid arthritis. The JBI methodology for systematic reviews of effectiveness and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines will be followed. PRISMA for systematic review protocols (PRISMA-P) was used to write the protocol. Randomised controlled trials assessing the effectiveness of yoga interventions for managing rheumatoid arthritis in adults will be included in this review. We aim to search the following databases to find published and unpublished studies: ABIM, AMED, AYUSH Research Portal, CAM-QUEST, CINAHL, CENTRAL, EMBASE, MEDLINE, PeDro, PsycInfo, SPORTDiscus, TRIP, Web of Science, DART-Europe-e-theses portal, EthOS, OpenGrey and ProQuest Dissertations and Theses. No date or language restrictions will be applied. A narrative synthesis will be conducted. Meta-regression will be conducted to explore the statistical evidence for which components (content, structure and delivery characteristics) of yoga interventions are effective.
35078534 Statin indication according to the 2019 World Health Organization cardiovascular disease r 2022 Jan 25 BACKGROUND: We aimed to assess the concordance of recommendation for initiating statin therapy according to the 2019 World Health Organization (WHO) cardiovascular disease (CVD) risk charts and to the presence of carotid plaque (CP) identified with carotid ultrasound in Mexican mestizo rheumatoid arthritis (RA) patients, and to determine the proportion of patients reclassified to a high cardiovascular risk after the carotid ultrasound was performed. METHODS: This was a cross-sectional study nested of a RA patients' cohort. A total of 157 Mexican mestizo RA patients were included. The cardiovascular evaluation was performed using the 2019 WHO CVD risk charts (laboratory-based model) for the Central Latin America region. A carotid ultrasound was performed in all patients. The indication to start statin therapy was considered if the patient was classified as high risk, moderate risk if > 40 years with total cholesterol (TC) > 200 mg/dl or LDL-C > 120 mg/dl, and low risk if > 40 years with TC > 300 mg/dl, according to the WHO CVD risk chart or if the patient had carotid plaque (CP). Cohen's kappa (k) coefficient was used to evaluate the concordance between statin therapy initiation. RESULTS: Initiation of statin therapy was considered in 49 (31.2%) patients according to the 2019 WHO CVD risk charts and 49 (31.2%) patients by the presence of CP. Cardiovascular risk reclassification by the presence of CP was observed in 29 (18.9%) patients. A slight agreement (k = 0.140) was observed when comparing statin therapy recommendations between 2019 WHO CVD risk charts and the presence of CP. CONCLUSION: The WHO CVD risk charts failed to identify a large proportion of patients with subclinical atherosclerosis detected by the carotid ultrasound and the concordance between both methods was poor. Therefore, carotid ultrasound should be considered in the cardiovascular evaluation of RA patients.
35635065 MicroRNA-122-3p plays as the target of long non-coding RNA LINC00665 in repressing the pro 2022 May MicroRNAs (miRNAs) play important roles in many diseases, including rheumatoid arthritis (RA). However, the mechanisms underlying the effects of miR-122-3p-3p on RA are not distinct and require further investigation. Patients with RA and healthy controls were recruited to analyze the miR-122-3p levels. The MH7A cells were stimulated with interleukin (IL)-1β to mimic the local inflammation of RA. Cell Counting Kit-8 (CCK-8) and flow cytometry were performed to measure the viability and apoptosis of MH7A cells. Diana tools and TargetScan were used to predict the target relationships. Luciferase reporter assay was used to validate the target relationship. miR-122-3p is downregulated in RA patients and IL-1β-stimulated MH7A cells. miR-122-3p suppresses MH7A cell viability and promotes MH7A cell apoptosis. miR-122-3p targets LINC00665. LINC00665 eliminates the inhibitory effect of miR-122-3p on IL-1β-stimulated MH7A cells. Eukaryotic translation initiation factor 2 alpha kinase 1 (EIF2AK1) targets miR-122-3p. In addition, EIF2AK1 is highly expressed in patients with RA. In addition, EIF2AK1 activates the mTOR signaling pathway. miR-122-3p represses RA progression by reducing cell viability and increasing synoviocyte apoptosis.
35638484 Predictors and radiological characteristics of rheumatoid arthritis-associated interstitia 2022 May BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that is commonly associated with extra-articular manifestations. Pulmonary disease is frequently encountered, which causes serious morbidity and increases mortality. Among the pulmonary manifestations, interstitial lung disease (ILD) is the most common. We aimed to analyse the frequency and clinical characteristics of a cohort of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD); describe the radiological features of ILD; identify predictive factors for developing ILD; and evaluate the impact of ILD on patient survival. MATERIALS AND METHODS: This retrospective study included all patients with RA who attended the rheumatology clinic of Kuala Lumpur Hospital from 2018 to 2021. RA-ILD was identified from high-resolution computed tomography (HRCT) thorax images evaluated by two thoracic radiologists. Descriptive and logistic regression analyses were conducted using SPSS version 26.0. RESULTS: Of the 732 patients with RA, 7.4% (54) had ILD. Univariate analysis identified Indian ethnicity, rheumatoid factor (RF) positivity, anti-cyclic citrullinated peptide antibody titre, and diabetes mellitus as risk factors for developing ILD. Multivariable logistic regression showed that RA-ILD was positively associated with female gender [Adjusted odds ratio (aOR)=3.40 (95% confidence interval (CI): 1.04, 11.17)], Indian ethnicity [aOR=2.03 (95% CI: 1.16, 3.57)], and positive RF [aOR=2.39 (95% CI: 1.18, 4.87)]. Nonspecific interstitial pneumonia (NSIP) was the predominant HRCT pattern. Majority of patients had limited disease (<20% of lung involvement) and good functional exercise capacity. There was significant improvement (p<0.05) in mean forced vital capacity (FVC) following treatment with immunosuppressive agents. No mortality occurred throughout the median follow-up period of 3.2 years. CONCLUSION: RA patients of Indian ethnicity had an increased risk for developing ILD, suggesting that genetics play a crucial role. Other independent predictors were female gender and RF positivity. The pattern of HRCT thorax and extent of lung involvement influenced prognosis and survival of patients with RA-ILD.
35637840 High Efficacy Combined Microneedles Array with Methotrexate Nanocrystals for Effective Ant 2022 INTRODUCTION: Methotrexate (MTX) is the first-line drug for the treatment of rheumatoid arthritis (RA) in several countries. However, MTX has an extremely low solubility in water, and the side effects caused by its delivery mode restrict its curative effect. In this study, we designed a dissolving microneedles array (DMNA) containing MTX nanocrystals (MTX-NCs) (MTX-NC@DMNA) to improve the treatment of RA. DMNA-based drug delivery combines the advantages of patient compliance with the use of transdermal drug delivery systems and high-efficiency injection administration; thus, it can mitigate the side effects that result from current administration routes. Carrier-free and surfactant-free MTX-NCs were prepared to overcome bioavailability limitations and poor drug loading problems. METHODS: The MTX-NCs prepared by reverse solvent precipitation method was encapsulated in the DMNA. The morphology, mechanical properties, safety, stability and in vivo dissolution were evaluated, and its pharmacodynamic characteristics were assessed in a rat model of RA. RESULTS: The particle size of the MTX-NCs was 148.1 ± 10.1 nm. The MTX-NC@DMNA were found to be rigid enough to penetrate the skin and deliver the drug successfully. The results indicated effective skin recovery after removal of the DMNA. It was found that the MTX-NC@DMNA significantly reduced foot swelling in the rats and regulated the balance in the levels of related cytokines. It also reduced pathological damage to the synovium, joint, and cartilage, and effectively alleviated organ injury in the rats. CONCLUSION: Transdermal administration of MTX-NC@DMNA may be an effective approach for treating RA.
35614600 Translation and validation of Modified Health Assessment Questionnaire score in local lang 2022 Apr OBJECTIVE: To translate and validate the Modified Health Assessment Questionnaire from English to Urdu. METHODS: The validation study was conducted at the Rheumatology outpatient department of Fauji Foundation Hospital, Rawalpindi, Pakistan, from July 1 to September 30, 2019. Two translators were given the modified health assessment questionnaire for translation from English to Urdu. It was then back-translated by two independent translators. The translated version of the tool was applied to rheumatoid arthritis patients to check for reliability, test-retest and internal consistency. It was applied to another group of patients to check for criterion validity. Reliability analysis was checked by applying Cronbach alpha. Criterion validity was checked by assessing disease activity score-28 and its correlation with Modified Health Assessment Questionnaire. Data was analysed using SPSS 23. RESULTS: Of the 30 patients in the initial testing, 28(93%) were females and 2(6.6%) were males, with an overall mean age of 38±13.2 years. Of the 100 patients in the second group, 97(97%) were women and 3(3%) were men, with an overall mean age of 42±12.37 years. The mean disease duration of the cohort was 8.4±4.8 years. The Cronbach alpha value was 0.797 and interclass coefficient was 0.7, reflecting good reliability. A significantly high correlation between Modified Health Assessment Questionnaire and disease activity score-28 was noted along with pain, tenderness, swollen joints, patient global assessment, age and erythrocyte sedimentation rate (p<0.05), while poor correlation was found with gender, disease duration, rheumatoid arthritis factor and anti-cyclic citrullinated peptide antibody (p>0.05). CONCLUSIONS: The Urdu version of the Modified Health Assessment Questionnaire was found to be a reliable tool for the indigenous population.
35048212 Bone mineral density, vitamin D receptor (VDR) gene polymorphisms, fracture risk assessmen 2022 May PURPOSE: To assess vitamin D receptor (VDR) gene polymorphisms and bone mineral density and to investigate the possible risk factors of osteoporosis and fracture in rheumatoid arthritis (RA). METHODS: A total of 97 RA patients and 45 matched controls were enrolled. Serum vitamin D level, VDR genotyping, dual-energy X-ray absorptiometry (DEXA) scan, trabecular bone score (TBS), and fracture risk assessment (FRAX) in 10 years were assessed. Disease activity score (DAS28) and modified health assessment questionnaire (MHAQ) were measured. RESULTS: The mean age of the patients was 47.9 ± 8.9 years; 85 females, 12 males (F:M 7.1:1) and mean disease duration 9.4 ± 6.2 years. DAS28 was 4.52 ± 1.04 and MHAQ 0.6 ± 0.4. There was a significant difference between cases and controls as regards DEXA and FRAX (p < 0.0001) but the TBS and VDR genotyping were comparable (p = 0.29 and p = 0.12, respectively). The vitamin D level was comparable with the control (9.3 ± 6.5 vs 10.4 ± 7.5 ng/mL, p = 0.4). None of the patients was receiving anti-osteoporotic therapy or biologic therapy. There was a significant association between the presence of osteoporosis and age, disease duration, menopause, and rheumatoid factor (RF) positivity. The TBS was significantly lower and FRAX higher in patients with positive RF and anti-CCP. FRAX was significantly related and the TBS inversely with the age, disease duration, serum uric acid, alkaline phosphatase, and MHAQ. CONCLUSIONS: Reduced BMD and increased tendency to fractures are remarkable in RA patients. Vitamin D level was decreased in patients and control, and VDR gene polymorphisms were not linked to RA. TBS and FRAX are effective tools to assess osteoporotic fractures in RA. Key Points • Reduced bone mineral density (BMD) and increased tendency to fractures are remarkable in rheumatoid arthritis (RA) patients. • Vitamin D level was decreased in patients and control, and VDR gene polymorphisms were not linked to RA. • Trabecular bone score (TBS) and fracture risk assessment (FRAX) in 10 years are effective tools to assess osteoporotic fractures in RA.