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35221674 Network Pharmacology and Molecular Docking Study of the Chinese Miao Medicine Sidaxue in t 2022 PURPOSE: This study aimed to investigate the molecular mechanisms of Compound Sidaxue (SX), a prescription of Chinese Miao medicine, in treating rheumatoid arthritis (RA) using network pharmacology and in vivo experimental approaches. METHODS: Network pharmacology was adopted to detect the active components of four Traditional Chinese herbal medicine (TCM) of SX, and the key targets and signaling pathways in the treatment of RA were predicted, and the key components and targets were screened for molecular docking. The predicted targets and pathways were validated in bovine type II collagen and incomplete Freund's adjuvant emulsifier-induced rat RA model. RESULTS: In this study, we identified 33 active components from SX, predicted to act on 44 RA-associated targets by network pharmacology. PPI network demonstrated that TNF-α, VEGF-A, IL-2, IL-6, AKT, PI3K, STAT1 may serve as the key targets of SX for the treatment of RA. The main functional pathways involving these key targets include PI3K-AKT signaling pathway, TNF signaling pathway, NF-κB signaling pathway. Molecular docking analysis found that the active components β-amyrin, cajanin, eleutheroside A have high affinity for TNF-α, VEGFA, IL-2, AKT, and PI3K, etc. SX can improve joint swelling in Collagen-induced arthritis (CIA) rats, reduce inflammatory cell infiltration and angiogenesis in joint synovial tissue, and down-regulate IL-2, IL-6, TNF-α, VEGF, PI3K, AKT, p-AKT, NF-κBp65, the expression of p-NF-κBp65, STAT1, and PTGS2 are used to control the exacerbation of inflammation and alleviate the proliferation of synovial pannus, and at the same time play the role of cartilage protection to achieve the effect of treating RA. CONCLUSION: Through a network pharmacology approach and animal study, we predicted and validated the active compounds of SX and their potential targets for RA treatment. The results suggest that SX can markedly alleviate CIA rat by modulating the VEGF/PI3K/AKT signaling pathway, TNF-α signaling pathway, IL/NF-κB signaling pathway.
35043586 The prevalence and correlates of depression in Korean adults with rheumatoid arthritis: Re 2022 Apr PURPOSE: This study aimed to investigate the prevalence and correlates of depression in Korean patients with rheumatoid arthritis (RA). METHODS: We analyzed the data of the Korean National Health and Nutrition Examination Survey (KNHANES). The sociodemographic, clinical, and psychiatric variables were compared between the RA group (n = 277) and the gender- and age-matched non-RA group (n = 1068). Participants in the RA group who had a Patient Health Questionnaire-9 (PHQ-9) score of 10 or more were sub-categorized as the depression group (n = 52), and the prevalence of depression with RA was determined. Complex samples logistic regression analysis was performed to clarify the associated factors for depression in patients with RA. RESULTS: The prevalence of depression in patients with RA was 17.4%. The RA group experienced more pain, restrictions on usual activities, and stress in their daily lives. RA patients with 3 or more comorbid diseases, extreme pain, problems in usual activities, and moderate to severe perceived stress were more likely to develop depression. Female gender and low income were also associated factors to consider. CONCLUSION: Depression is significantly prevalent in Korean RA patients. Along with managing pain and daily life functions, interventions to reduce perceived stress are needed for comprehensive RA management.
35353950 Isoginkgetin inhibits inflammatory response in the fibroblast-like synoviocytes of rheumat 2022 Jun Inflammatory and invasive fibroblast-like synoviocytes (FLS) contribute to the pathology of rheumatoid arthritis (RA). Isoginkgetin (IGKG) has been identified as having anti-inflammatory properties. This study investigated whether IGKG could be utilized to treat RA. Primary FLS were isolated from synovial tissues derived from six RA patients, which were over-expressed with matrix metallopeptidase 9 and cultured with or without tumor necrosis factor (TNF)-α and then further treated with IGKG. IGKG down-regulated the content of various interleukins (ILs), namely, IL-1β, IL-6, and IL-8, in RA-FLS supernatant with or without TNF-α stimulation, with diminished migration and invasion properties as assayed by the transwell system. Furthermore, down-regulated inflammatory cytokine secretion and down-regulated migration and invasion properties could be reversed through matrix metallopeptidase 9 overexpression. Dual-luciferase reporter gene assay indicated that IGKG could inhibit nuclear factor kappa B transcription activity. Western blot analysis also demonstrated that IGKG down-regulated the expression of p-IκBα, p-p65, and MMP9. IGKG displayed the ability to inhibit the inflammatory response of RA-FLS through the NF-κB/MMP9 pathway with diminished migration and invasion.
35162812 The Effect of Periodontal Treatment on Clinical and Biological Indicators, Quality of Life 2022 Feb 4 Non-surgical periodontal therapy (NSPT) has been shown to have systemic effects. It has been suggested that, similar to rheumatoid arthritis (RA), periodontitis (PD) has an impact on general health, in terms of psychological, physical, and social aspects. This study determines the effect of periodontal treatment in RA activity, health-related quality of life, and oral health self-perception before and after periodontal treatment in RA patients. A quasi-experimental, prospective, non-randomized study was conducted, and 52 patients were included in the study. Periodontal parameters and the instruments disease activity score-28 (DAS-28), SF-36, and OHIP-14 were measured at baseline and at 3 months after NSPT. All differences were statistically assessed. The study protocol was registered in Clinical Trials (NCT04658615). No statistically significant differences were found in the scores of DAS-28 before and after the intervention in the group with PD and reduced periodontium. When the effect of periodontal treatment was analyzed in the group of 29 patients who were followed up, it was found that there were statistically significant differences before and after in variables such as psychological distress, emotional role, and mental health, which indicates an improvement in the scores of these variables. NSPT influenced the health-related quality of life measured with SF-36 and OHIP-14 in patients with RA. In conclusion, NSPT has an effect on self-reported quality of life and health indicators more than the RA activity as measured with DAS-28. However, the clinical effect of periodontal treatment in RA patients provides important data to support periodontal care in patients.
35589354 Randomised controlled trial of cognitive behaviour therapy versus mindfulness for people w 2022 May 19 INTRODUCTION: Psychosocial treatments have been shown to benefit people with rheumatoid arthritis (RA) on various outcomes. Two evidence-based interventions are cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR). However, these interventions have been compared only once. Results showed that CBT outperformed MBSR on some outcomes, but MBSR was more effective for people with RA with a history of recurrent depression, with efficacy being moderated by history of depressive episodes. However, this was a post-hoc finding based on a small subsample. We aim to examine whether a history of recurrent depression will moderate the relative efficacy of these treatments when delivered online. METHODS AND ANALYSIS: This study is a randomised controlled trial comparing CBT and MBSR delivered online with a waitlist control condition. History of recurrent depressive episodes will be assessed at baseline. The primary outcome will be pain interference. Secondary outcomes will include pain intensity, RA symptoms, depressive symptoms and anxiety symptoms. Outcome measures will be administered at baseline, post-treatment and at 6 months follow-up. We aim to recruit 300 participants, and an intention-to-treat analysis will be used. Linear mixed models will be used, with baseline levels of treatment outcomes as the covariate, and group and depressive status as fixed factors. The results will demonstrate whether online CBT and MBSR effectively improve outcomes among people with RA. Importantly, this trial will determine whether one intervention is more efficacious, and whether prior history of depression moderates this effect. ETHICS AND DISSEMINATION: The trial has been approved by the Human Research Ethics Committee of the University of Sydney (2021/516). The findings will be subject to publication irrespective of the final results of the study, and based on the outcomes presented in this protocol. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000997853p).
35319841 [Effects of transcutaneous auricular vagus nerve stimulation on bone and cartilage destruc 2022 Mar 25 OBJECTIVE: To observe the alleviating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on articular cartilage and bone destruction in rats with collagen-induced arthritis (CIA), and explore the cellular and molecular mechanisms of taVNS against rheumatoid arthritis (RA). METHODS: The male SD rats were randomly divided into normal control group (n=12), model group (n=12), and taVNS group (n=12). The CIA rat model was established by multi-point injection of emulsion prepared from type Ⅱ bovine collagen and Freund's incomplete adjuvant into the root of rat tail. The rats in the taVNS group were treated with taVNS at bilateral auricular conchae, 30 min per time, once a day, for consecutive 28 d. The cartilage destruction of the ankle joint was observed by safranin O-fast green staining, the production of osteoclasts in the joint tissue by tartrate-resistant acid phosphatase (TRAP) staining, and the bone erosion by X-ray and Micro-CT imaging. The protein expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) in the synovial tissues were detected by Western blot. RESULTS: Compared with the normal control group, the CIA rats presented with typical RA symptoms and elevated arthritis index (AI,P<0.05). After intervention with taVNS, the AI remarkably declined in comparison with that in the model group (P<0.05). Compared with the control group, the model group displayed loss of cartilage matrix in the ankle joint, thinned cartilage layer, obvious cartilage damage, and increased number of osteo-clasts in the joint (P<0.01); the imaging results showed bone loss and three-dimensional structural destruction of ankle joint and aggravated bone erosion (P<0.01); the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio were significantly elevated in the synovial tissue of ankle joint (P<0.01, P<0.05), while the expression level of OPG was decreased (P<0.05). Compared with the model group, taVNS resulted in relatively intact cartilage layer of ankle joint, alleviated cartilage destruction, decreased number of osteoclasts (P<0.01), improved bone erosion, loss, and three-dimensional structural destruction (P<0.01), and diminished MMP-1, MMP-3, and MMP-13 expression and RANKL/OPG ratio in the synovial tissue of ankle joint (P<0.05, P<0.01), while the expression level of OPG was increased (P<0.05). CONCLUSION: taVNS effectively relieves bone and cartilage destruction in CIA rats, which might be related to its efficacy in reducing the production of osteoclasts in joint tissues and down-regulating the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio.
33666155 Increased interleukin-11 associated with disease activity and development of interstitial 2022 Jan OBJECTIVES: To investigate the association of serum interleukin-11 (IL-11) with disease activity and occurrence of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). METHODS: One hundred and six RA patients were included, including 31 with ILD. All patients were divided into two groups according to the 28-joint Disease Activity Score (DAS28), active-disease group (DAS28>3.2) and target-achieved group (DAS28≤3.2). Serum IL-11 was detected by ELISA. Serum autoantibodies [anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF)], inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)], and complete blood count were measured with routine methods. RESULTS: Serum IL-11 was upregulated in RA patients compared with healthy controls (HC), and increased more significantly in patients with ILD (RA-ILD) than patients without ILD (RA-nonILD). In both RA-ILD and RA-nonILD patients, serum level of IL-11 was higher in the active-disease group than that in the target-achieved group. Pearson correlation analysis confirmed that IL-11 was positively correlated with DAS28. No significant correlation was found between serum level of IL-11 and ACPA or RF. IL-11 was positively correlated with ESR and CRP levels and PLT count in RA patients. CONCLUSIONS: IL-11 was found to be involved in the development of arthritis and ILD in RA patients, and might constitute a potential target for the treatment of RA-ILD.
35534053 Positive impact on 10-year outcome of the window of opportunity for conventional synthetic 2022 May OBJECTIVE: This study aimed to assess the impact of disease-modifying antirheumatic drugs (DMARDs) on 10-year outcomes in rheumatoid arthritis (RA). METHODS: Patients with RA from the ESPOIR cohort with complete data on Disease Activity Score in 28 Joints (DAS28) and Health Assessment Questionnaire (HAQ) at 10 years (n=418) and complete radiographic data at baseline and 10 years (n=343) were included in this study. Outcomes were favourable outcome (FavOut) at 10 years, defined as DAS28 of <2.6 and HAQ score of <0.5 at 10 years, and absence of structural damage progression (AbsSDP) at 10 years, defined as change in Sharp-van der Heijde Score less than the smallest detectable change at 10 years (11.5 points). Three multivariate logistic regression models predicting 10-year outcome were built, considering (1) baseline variables only, (2) baseline variables and DMARD exposure (ever exposed, yes/no) and (3) baseline variables and DMARD exposure as weighted cumulative exposure (WCE) variables. RESULTS: Overall, 196/418 (46.9%) patients showed FavOut and 252/343 (73.5%) AbsSDP. WCE models had the best predictive performance, with area under the curve=0.80 (95% CI 0.74 to 0.87) for FavOut and 0.87 (95% CI 0.83 to 0.92) for AbsSDP. In the WCE model, the odds of FavOut and AbsSDP were reduced with conventional synthetic disease-modifying antirheumatic drug (csDMARD) initiation at 12 months versus at baseline (OR 0.78, 95% CI 0.65 to 0.94, and OR 0.89, 95% CI 0.76 to 0.98, respectively). Early biologics initiation was not significantly associated with either outcome. CONCLUSIONS: WCE models can identify and quantify the long-term benefit of early csDMARD initiation on 10-year functional and structural outcomes in patients with RA.
34743422 Development of type 1 diabetes in a patient treated with anti-interleukin-6 receptor ant 2022 Apr Interleukin-6 is a pleiotropic cytokine that plays a pathogenic role in type 1 diabetes. Therefore, anti-interleukin-6 receptor antibody, tocilizumab, used for the treatment of rheumatoid arthritis, is considered a candidate for immune intervention in type 1 diabetes. Here, we report the case of a 73-year-old woman (HLA-DR9-DQ3 homozygote) with well-controlled rheumatoid arthritis who developed type 1 diabetes while receiving tocilizumab treatment. At 57 years-of-age, the patient was diagnosed with rheumatoid arthritis, for which she underwent tocilizumab therapy that enabled complete suppression of her joint inflammation. A total of 17 months after starting tocilizumab therapy, she noticed polydipsia, polyuria, general fatigue and weight reduction (-2 kg/month), and was diagnosed with type 1 diabetes with diabetic ketoacidosis based on an arterial pH of 7.26, serum ketone body of 7,437 μmol/L, blood glucose level of 925 mg/dL, glycated hemoglobin of 13.2% and the presence of anti-islet autoantibodies. This case report shows valuable insight regarding the effect of anti-interleukin-6 receptor antibody therapy on type 1 diabetes prevention.
34910195 Effect of TNF inhibitors with bisphosphonates vs bisphosphonates alone on bone mineral den 2022 Apr 18 BACKGROUND: The present study aimed prospectively to investigate the effect of a combination of tumour necrosis factor inhibitors and bisphosphonates (TNFi with BP) on bone mineral density (BMD) and bone and cartilage biomarkers compared to that of BP alone at 1 year in patients with rheumatoid arthritis (RA). METHODS: Two groups of patients with RA and osteoporosis were enrolled. One group (37 patients) had already received BP, while the other group (37 patients) had already received TNFi with BP. The serum bone resorption and formation markers, cartilage markers, BMD in the lumbar spine, femoral neck, and distal radius were prospectively investigated at the beginning of the study and at 6 and 12 months. RESULTS: The percentages of change recorded for the various assessment categories were as follows in the TNFi with BP group: (1) tartrate-resistant acid phosphatase-5b had significantly decreased and osteocalcin had increased; (2) matrix metalloproteinase-3 and cartilage oligomeric matrix protein had significantly decreased; and (3) each BMD did not differ significantly between the groups. CONCLUSION: Our data suggested that TNFi with BP therapy not only suppressed cartilage degradation and bone resorption but also increased bone formation; however, this treatment did not affect the BMD at 1 year.
34263700 Pretreatment resistin levels are associated with erosive disease in early rheumatoid arthr 2022 May OBJECTIVE: Resistin is an adipocytokine related to insulin resistance and inflammation. We investigated whether resistin is associated with disease activity and inflammation in disease-modifying anti-rheumatic drug (DMARD)-naïve rheumatoid arthritis (RA) patients, whether it has predictive value for radiological disease progression, and whether tumour necrosis factor-α (TNF-α) is involved in these effects. METHOD: Ninety-nine patients with early, DMARD-naïve RA participated in the NEO-RACo study. Patients were treated for the first 4 weeks with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo treatment). Thereafter, they were randomized to receive either infliximab or placebo added to the combination for 6 months. Patients were followed for 5 years. Disease activity was evaluated using the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate, radiographs were scored with the modified Sharp-van der Heijde method, and plasma resistin concentrations were measured by immunoassay. Human THP-1 macrophages were used in the in vitro studies. RESULTS: A high resistin level at baseline was associated with active inflammatory disease and predicted more rapid radiological progression during 5 year follow-up. Adding infliximab to the DMARD combination delayed radiological progression and overcame the poor predictive value of resistin. Resistin increased TNF-α production in human macrophages, indicating a possible connection between resistin and TNF-α. CONCLUSION: The results suggest that high resistin concentration may be a useful marker to distinguish patients with an increased risk of erosive disease in early active RA, and that adding TNF-α antagonist to the traditional DMARD combination may delay radiological progression of the disease in these patients. The study has been registered at https://www.clinicaltrials.gov(NCT00908089).
35361268 Risk factor analysis of perioperative complications in patients with rheumatoid arthritis 2022 Mar 31 BACKGROUND: Rheumatoid arthritis (RA) often causes cervical spine lesions as the disease condition progresses, which induce occipital neuralgia or cervical myelopathy requiring surgical interventions. Meanwhile, patients with RA are susceptible to infection or other complications in the perioperative period because they frequently have comorbidities and use immunosuppressive medications. However, the risk factors or characteristics of patients with RA who experience perioperative complications after cervical spine surgery remain unknown. A risk factor analysis of perioperative complications in patients with RA who underwent primary cervical spine surgery was conducted in the present study. METHODS: A total of 139 patients with RA who underwent primary cervical spine surgery from January 2001 to March 2020 were retrospectively investigated. Age and height, weight, serum albumin, serum C-reactive protein, American Society of Anesthesiologists Physical Status (ASA-PS), Charlson comorbidity index, medications used, cervical spine lesion, surgery time, bleeding volume, and procedures were collected from medical records to compare the patients with complications to those without complications after surgery. The risk factors for perioperative complications were assessed by univariate and multivariate logistic regression analysis. RESULTS: Twenty-eight patients (20.1%) had perioperative complications. Perioperative complications were significantly associated with the following factors [data presented as odds ratio]: lower height [0.928, p=0.007], higher ASA-PS [2.296, p=0.048], longer operation time [1.013, p=0.003], more bleeding volume [1.004, p=0.04], higher rates of vertical subluxation [2.914, p=0.015] and subaxial subluxation (SAS) [2.507, p=0.036], occipito-cervical (OC) fusion [3.438, p=0.023], and occipito-cervical/thoracic (long) fusion [8.021, p=0.002] in univariate analyses. In multivariate analyses, lower height [0.915, p=0.005], higher ASA-PS [2.622, p=0.045] and long fusion [7.289, p=0.008] remained risk factors. High-dose prednisolone use [1.247, p=0.028], SAS [6.413, p=0.018], OC fusion [17.93, p=0.034], and long fusion [108.1, p<0.001] were associated with severe complications. CONCLUSIONS: ASA-PS and long fusion could be indicators predicting perioperative complications in patients with RA after cervical spine surgery. In addition, cervical spine lesions requiring OC fusion or long fusion and high-dose prednisolone use were suggested to be risk factors for increasing severe complications.
34511571 Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthr 2022 Apr 1 Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.
34902811 N6-methyladenosine modification of TGM2 mRNA contributes to the inhibitory activity of sar 2022 Jan BACKGROUND: Developing alternative targets and drugs for rheumatoid arthritis (RA) treatment is currently an urgent issue. The relationship between TGM2 and the abnormal immune microenvironment in synovium tissues, as well as the specific role of TGM2 in RA are yet to be elucidated. Sarsasapogenin (Sar) is a sapogenin extracted from the Chinese medical herb Anemarrhena asphodeloides Bunge. and served as a representative anti-inflammatory drug capable of ameliorating inflammatory responses in several human diseases. However, the therapeutic effect of Sar on RA remains unknown. PURPOSE: This investigation aims to elucidate the role of TGM2 in RA and investigate whether Sar is a candidate drug to target TGM2 of fibroblast-like synoviocytes (FLS). METHODS: Bioinformatics analyses were applied for elucidating the role of N(6)-methyladenine (m6A) RNA methylation in RA and identifying the specific target regulated by m6A methylation in RA-FLS. Methylated RNA immunoprecipitation, CCK8 assay, Edu assay, flow cytometry, RT-qPCR and Western blot were utilized to investigate the function of Sar and TGM2 in RA-FLS. RESULTS: Bioinformatics analyses emphasized the importance of m6A RNA methylation in RA and identified an m6A methylation-mediated gene TGM2. Interestingly, both m6A RNA methylation and TGM2 expression in RA synovium tissues correlated with activated immuno-inflammatory phenotype and associated with clinical characteristics and therapy response of RA patients. TGM2 served as a promoter of RA-FLS proliferation by inducing DNA replication and cell cycle transition and inhibiting apoptosis through activating NF-κB signaling. Intriguingly, Sar could impair m6A methylation of TGM2 mRNA and downregulate TGM2 expression. Downregulated TGM2 contributed to the suppressive role of Sar in DNA replication and the stimulatory role of Sar in cell cycle arrest and apoptosis of RA-FLS. Mechanically, Sar inhibited the expression of key regulators in DNA replication, cell cycle, and apoptosis by impairing NF-κB signaling, thus abolishing FLS proliferation to ameliorate RA progression. CONCLUSIONS: This cross-validated work based on three independent datasets is detailedly delineated using cell lines and clinical samples, recognizing that TGM2 can be an attractive target and Sar might be a novel anti-RA drug.
34583914 Prevalence and clinical characteristics of symptomatic diffuse interstitial lung disease i 2022 May BACKGROUND AND OBJECTIVES: In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. MATERIALS AND METHODS: In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. RESULTS: Of the 2729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26-2.29) with an age at diagnosis of RA of 57.3 ± 13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. CONCLUSIONS: We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.
35091461 Risk factors for herpes zoster in Korean patients with rheumatoid arthritis treated with J 2022 Jan OBJECTIVE: To determine the risk of herpes zoster (HZ) in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis). METHODS: We performed a nested case-control study with 1:10 matching for sex and age using single-centre prospective cohorts of patients with RA receiving targeted therapy in Korea. Then we performed conditional logistic regression analyses to determine the risk associated with JAKi use compared with biologic disease-modifying antirheumatic drug (bDMARD) use, with adjusting for various factors. We also used logistic regression analysis to identify other risk factors for the development of HZ in JAKi users. RESULTS: From a total of 1147 patients, 61 cases and 610 matched controls were selected. In conditional logistic regression analysis, JAKi use did not increase the risk of HZ development (OR 1.35, 95% CI 0.70 to 2.61) after adjusting for other factors. Rather, duration of RA less than 10 years (OR 0.54, 95% CI 0.30 to 0.97) and having had three or more previous targeted therapies (OR 5.29, 95% CI 1.45 to 19.31) were risk factors for HZ. Among JAKi users, higher disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) (OR 1.44, 95% CI 1.06 to 1.97) was identified as a risk factor in addition to three or more previous targeted therapies (OR 10.12, 95% CI 1.92 to 53.49). CONCLUSIONS: The number of previous targeted therapies, but not JAKi use, was identified as a risk factor for HZ development in Korean patients with RA in a real-world setting. High disease activity was an additional risk factor for JAKi users.
35295202 Association between the Platelet-Derived Growth Factor/Platelet-Derived Growth Factor Rece 2022 This research examines the association between the platelet-derived growth factor/platelet-derived growth factor receptor (PDGF/PDGFR) system and rheumatoid arthritis (RA) susceptibility through a comprehensive search of the PubMed database to study the expression of the PDGF/PDGFR system in RA. Review Manager software version 5.3 was used for statistical analysis. Six eligible studies published in the English language were included, including 108 rheumatoid arthritis cases and 85 controls with the corresponding 126 and 97 tests, respectively, relating the expression of the PDGF/PDGFR system to the risk of RA. The overall results indicated a significant association between the PDGF/PDGFR system expression and RA (OR = 5.25, 95% CI: 3.00-9.18, p < 00001), RA patients in Asian countries (OR = 4.13, 95% CI = 2.04-8.39, p < 0.0001) and in Western countries (OR = 9.18, 95% CI = 2.04-8.39, p = 0.03), and only PDGF expression in RA patients (OR = 5.28, 95% CI = 2.73-10.21, p < 0.00001). Thus, only the PDGFR expression was insignificantly associated with RA susceptibility (OR = 9.25, 95% CI = 0.63-136.30, p = 0.11). Hence, the PDGF/PDGFR system most likely contributes to susceptibility to RA.
35157164 Safety of JAK inhibitor use in patients with rheumatoid arthritis who developed herpes zos 2022 Jun INTRODUCTION: To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA). METHODS: Medical records of all patients who received JAKi at a tertiary referral center between August 2015 and June 2021 were retrospectively reviewed. Data from patients who developed HZ reactivation were collected, and the HZ-related safety of those who continued JAKis after reactivation was evaluated. RESULTS: Of the 416 patients who received JAKis, 33 (7.9%) developed HZ reactivation during treatment (tofacitinib, n = 22; baricitinib, n = 11). The mean age of the patients was 60.2 ± 11.8 years. Fourteen patients (42.4%) received glucocorticoids with a median dose of 3.75 mg of prednisone (IQR, 2.5-5.0). The median duration of JAKi administration before HZ reactivation was 11 months (IQR, 4-29). JAKi was continued in 24 (72.7%) patients during the HZ episode, while it was temporarily discontinued and then resumed after the HZ episode in 5 (15.2%) patients. Three (9.1%) patients had acute complications, such as encephalitis with HZ ophthalmicus. Four (12.1%) patients, including the 3 with complications, permanently discontinued JAKis. Of the 29 patients who were observed for a median of 12 months (IQR, 6-21) after the initial HZ reactivation episode, reactivation recurred in one (3.4%); this patient maintained JAKi treatment for a further 18 months without additional HZ recurrence. CONCLUSION: JAKis were commonly continued or re-administered in patients with HZ reactivation, and the majority of these patients did not experience significant complications or recurrence of HZ reactivation. Thus, the use of JAKi after HZ reactivation episode seems to be tolerated.
34801482 Integrative serum metabolomic analysis for preventive effects of Yaobitong capsule in adju 2022 Jan 15 Yaobitong capsule (YBTC) has been used for the prevention and treatment of inflammation-related lumbago and leg pain. However, its intervention mechanism still remains unclear. This study was aimed to evaluate the control efficiency of YBTC on adjuvant-induced rheumatoid arthritis (RA) rats by metabonomic method and to explore its possible anti-arthritis mechanism. Taking into account the complexity of endogenous metabolites in serum samples, an integrated metabolomics method based on RP/HILIC-UHPLC-Q-TOF MS was developed, to overcome the limitations of a single chromatographic in this study. The results showed that 32 potential biomarkers of arthritis were identified, primarily related to amino acid metabolism, glucose metabolism, lipid metabolism and nucleotide metabolism. Further receiver operating characteristic analysis revealed that the area under the curve of two down-regulated metabolites (3-Hydroxy-hexadecanoic acid, 2-Oxoarginine) and one up-regulated metabolite (l-Glutamic acid) among 32 biomarkers were 0.906, 0.969 and 1.000, respectively, indicating that high predictive ability of this method for RA. In this study, an integrated serum metabolomics method based on high-resolution mass spectrometry was successfully established for the first time to study the intervention mechanism of YBTC in RA, providing evidence regarding the clinical application of YBTC and a new insight for the prevention of RA in the future.
33890623 A novel fluorescence optical imaging scoring system for hand synovitis in rheumatoid arthr 2022 Feb 2 OBJECTIVES: To develop and validate a new semiquantitative fluorescence optical imaging (FOI) scoring system-the FOI Enhancement-Generated RA Score (FOIE-GRAS) for synovitis assessment in the hand. METHODS: The development of FOIE-GRAS was based on consensus of four experts in musculoskeletal imaging. Forty-six RA patients, eligible for treatment intensification and with ≥1 clinically swollen joints in the hands, and 11 healthy controls were included. FOI, ultrasound and clinical assessment of both hands were obtained at baseline and for RA patients after 3 and 6 months' follow-up. Twenty RA patients had an FOI rescan after 4 h. Synovitis was scored using FOIE-GRAS and the OMERACT ultrasound synovitis scoring system. All FOI images were scored by two readers. Inter-scan, inter- and intra-reader reliability were determined. Furthermore, FOIE-GRAS agreement with ultrasound and responsiveness was assessed. RESULTS: FOIE-GRAS synovitis was defined as early enhancement, and scores were based on the degree of coverage of the specific joint region after 3 s (0-3). Inter-scan, intra- and inter-reader intraclass correlations coefficients (ICC) were good to excellent for all baseline scores (0.76-0.98) and moderate to good for change (0.65-76).The FOIE-GRAS had moderate agreement with ultrasound (ICC 0.30-0.54) for total score, a good standardized response mean (>0.80), and moderate correlation with clinical joint assessment and DAS28-CRP. The median (interquartile range) reading time per FOI examination was 133 (109, 161) s. Scores were significantly lower in controls [1 (0, 4)] than RA patients [11 (6, 19)]. CONCLUSION: The FOIE-GRAS offers a feasible and reliable assessment of synovitis in RA, with a moderate correlation with ultrasound and DAS28-CRP, and good responsiveness.