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ID PMID Title PublicationDate abstract
34670994 Effects of a Weight and Pain Management Program in Patients With Rheumatoid Arthritis With 2022 Jan 1 BACKGROUND: Obesity is associated with poor outcomes for patients with rheumatoid arthritis (RA). Effective weight management is imperative. Although traditional lifestyle behavioral weight loss programs have demonstrated efficacy for reducing weight, these interventions do not meet the pain-related weight loss challenges of RA patients with obesity. OBJECTIVE: A 12-session group program (90 minutes per session) was developed integrating pain coping skills training into a lifestyle behavioral weight loss intervention. In addition to the weekly group sessions, participants engaged in supervised exercise sessions 3 times per week. METHODS: Through a small, pilot randomized trial, 50 participants were randomized to receive the intervention (n = 29) or standard care of RA (n = 21). Feasibility data (i.e., accrual, attrition, adherence) was examined using descriptive statistics (e.g., percent). We examined patterns of change in study outcomes from baseline to follow-up separately for the intervention and standard care arms using descriptive statistics and paired t tests. Effect sizes are also presented. RESULTS: Of those randomized to the intervention group,79.3% initiated treatment, with participants attending 74.3% of group skills sessions and 64.2% of exercise sessions. Intervention participants evidenced reductions in weight (mean, -2.28 kg) and waist circumference (mean, -4.76 cm) and improvements in physical functioning, eating behaviors, pain, and self-efficacy for weight control. CONCLUSIONS: Findings suggest that incorporating a combined pain coping skills training and behavioral weight loss intervention into medical management of RA may improve outcomes. Study accrual and attrition, as well as intervention adherence, will inform future, larger randomized efficacy trials of the intervention.Retrospectively registered: January 29, 2020, NCT04246827.
35590341 Identification of biomarkers by machine learning classifiers to assist diagnose rheumatoid 2022 May 19 BACKGROUND: This study aimed to search for blood biomarkers among the profiles of patients with RA-ILD by using machine learning classifiers and probe correlations between the markers and the characteristics of RA-ILD. METHODS: A total of 153 RA patients were enrolled, including 75 RA-ILD and 78 RA-non-ILD. Routine laboratory data, the levels of tumor markers and autoantibodies, and clinical manifestations were recorded. Univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and partial least square (PLS) were performed, and the receiver operating characteristic (ROC) curves were plotted. RESULTS: Univariate analysis showed that, compared to RA-non-ILD, patients with RA-ILD were older (p < 0.001), had higher white blood cell (p = 0.003) and neutrophil counts (p = 0.017), had higher erythrocyte sedimentation rate (p = 0.003) and C-reactive protein (p = 0.003), had higher levels of KL-6 (p < 0.001), D-dimer (p < 0.001), fibrinogen (p < 0.001), fibrinogen degradation products (p < 0.001), lactate dehydrogenase (p < 0.001), hydroxybutyrate dehydrogenase (p < 0.001), carbohydrate antigen (CA) 19-9 (p < 0.001), carcinoembryonic antigen (p = 0.001), and CA242 (p < 0.001), but a significantly lower albumin level (p = 0.003). The areas under the curves (AUCs) of the LASSO, RF, and PLS models attained 0.95 in terms of differentiating patients with RA-ILD from those without. When data from the univariate analysis and the top 10 indicators of the three machine learning models were combined, the most discriminatory markers were age and the KL-6, D-dimer, and CA19-9, with AUCs of 0.814 [95% confidence interval (CI) 0.731-0.880], 0.749 (95% CI 0.660-0.824), 0.749 (95% CI 0.660-0.824), and 0.727 (95% CI 0.637-0.805), respectively. When all four markers were combined, the AUC reached 0.928 (95% CI 0.865-0.968). Notably, neither the KL-6 nor the CA19-9 level correlated with disease activity in RA-ILD group. CONCLUSIONS: The levels of KL-6, D-dimer, and tumor markers greatly aided RA-ILD identification. Machine learning algorithms combined with traditional biostatistical analysis can diagnose patients with RA-ILD and identify biomarkers potentially associated with the disease.
34902228 Toward Individualized Prediction of Response to Methotrexate in Early Rheumatoid Arthritis 2022 Jun OBJECTIVE: To test the ability of machine learning (ML) approaches with clinical and genomic biomarkers to predict methotrexate treatment response in patients with early rheumatoid arthritis (RA). METHODS: Demographic, clinical, and genomic data from 643 patients of European ancestry with early RA (mean age 54 years; 70% female) subdivided into a training (n = 336) and validation cohort (n = 307) were used. The genomic data comprised 160 single-nucleotide polymorphisms (SNPs) previously associated with RA or methotrexate metabolism. Response to methotrexate monotherapy was defined as good or moderate by the European Alliance of Associations for Rheumatology (EULAR) response criteria at the 3-month follow-up. Supervised ML methods were trained with 5 repeats and 10-fold cross-validation using the training cohort. Prediction performance was validated in the independent validation cohort. RESULTS: Supervised ML methods combining age, sex, smoking, rheumatoid factor, baseline Disease Activity Score in 28 joints (DAS28) scores and 160 SNPs predicted EULAR response at 3 months with the area under the receiver operating curve of 0.84 (P = 0.05) in the training cohort and achieved a prediction accuracy of 76% (P = 0.05) in the validation cohort (sensitivity 72%, specificity 77%). Intergenic SNPs rs12446816, rs13385025, rs113798271, and ATIC (rs2372536) had variable importance above 60.0 and along with baseline DAS28 scores were among the top predictors of methotrexate response. CONCLUSION: Pharmacogenomic biomarkers combined with baseline DAS28 scores can be useful in predicting response to methotrexate in patients with early RA. Applying ML to predict treatment response holds promise for guiding effective RA treatment choices, including timely escalation of RA therapies.
31994908 The expression of zinc finger 804a (ZNF804a) and cyclin-dependent kinase 1 (CDK1) genes is 2022 Jun CONTEXT: ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways. OBJECTIVE: This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients. METHODS: ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated. RESULTS: ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls (p < .001). ZNF804a down-regulation was negatively correlated with CRP, RF, disease activity score of 28 joints (DAS) using CRP (DAS-CRP) and TNF-α. CDK1 overexpression was correlated with IFN-1 and ACPA in RA patients. CONCLUSION: ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.
35264379 Lamotrigine-associated haemophagocytic lymphohistiocytosis (HLH) confounded with underlyin 2022 Mar 9 Haemophagocytic lymphohistiocytosis (HLH) is one of the rare haematological syndromes more commonly reported in infants/children than adults. This disease is known for its aggressive dysregulated immune response affecting the host rapidly, causing multiorgan dysfunction and thus carries a high mortality. The disease still remains cryptic in this current decade despite all the developments in the ever-evolving field of haematology. Due to its rare occurrence and being more frequent in infants and the paediatric population, the literature lacks enough data to standardise therapies. Such events in adults and the elderly are invariably related to an underlying insult such as infections, other autoimmune or rheumatological diseases or drugs. We describe an interesting case of a middle-aged Caucasian woman who presented with fever, pancytopenia and hepatitis, who was eventually diagnosed with HLH just in time to receive the life-saving specific treatment as per available guidelines.
35322865 Piceatannol suppresses inflammation and promotes apoptosis in rheumatoid arthritis‑fibro 2022 May Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly targets the synovial membrane, thus causing stiffness, deformity and dysfunction of joints. To date, no effective anti‑inflammatory treatments are available for RA. Piceatannol (PIC) is a natural derivative of resveratrol, which has been reported to attenuate the inflammatory response. To evaluate the effect of PIC on RA and to determine the underlying molecular target of PIC, both in vitro and in vivo experiments were performed in the present study. A CIA rat model was established to evaluate the therapeutic effects of PIC. TNF‑α, IL‑1β and IL‑6 levels in blood were measured by ELISA. Western blotting, immunofluorescence analysis and reverse transcription‑quantitative PCR (RT‑qPCR) were used to analyze the expression levels of protein and mRNA. In vitro, RA‑fibroblast‑like synoviocytes (FLSs) were pretreated with PIC and subsequently stimulated with TNF‑α. The results revealed that PIC significantly upregulated the expression levels of proapoptotic proteins such as Bax and cleaved caspase‑3. PIC also significantly reduced the production of proinflammatory cytokines, including PGE2, IL‑6 and IL‑1β, and significantly downregulated the expression of cyclooxygenase‑2 at both the mRNA and protein expression levels. Furthermore, PIC downregulated the expression of MMP‑3 and MMP‑13, which have been found to be highly expressed in the synovium of patients with RA. Mechanistically, PIC was capable of significantly downregulating the expression levels of proteins involved in the NF‑κB and MAPK signaling pathways. The results of the in vivo experiments using a rat collagen‑induced arthritis model demonstrated that PIC decreased the arthritis score and exerted beneficial effects in cartilage and significantly reduced the expression of MMP‑13. In conclusion, the findings of the present study revealed that PIC could suppress the inflammatory response, promote apoptosis, and exert a significant regulatory effect on the NF‑κB and MAPK signaling pathways in RA‑FLSs. Therefore, PIC may represent a potential drug for the future treatment of RA.
34373923 The impact of statins on coronary atherosclerosis progression and long-term cardiovascular 2022 May 5 OBJECTIVES: To evaluate whether statins lower cardiovascular disease (CVD) risk in RA and if tentative benefits are related to changes in coronary plaque burden or composition. METHODS: In an observational cohort study, 150 patients without CVD underwent coronary atherosclerosis evaluation (total, noncalcified, partially and fully calcified plaque) with CT angiography. Prespecified cardiovascular events including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication and heart failure were prospectively recorded. Change in plaque burden and composition was re-assessed in 102 patients within 6.9 (0.3) years. RESULTS: Time-varying statin therapy, modeled using inverse probability treatment and censoring weights, did not significantly attenuate CVD risk in RA overall [adjusted odds ratio (OR) = 0.39 (95% CI: 0.15, 1.07), P =0.067]. However, statins associated with lower CVD risk in patients with baseline CRP > 0.5 mg/dl [adjusted OR = 0.09 (95%CI: 0.03, 0.30), P <0.001] but not in those with CRP < 0.5 mg/dl (P-interaction = 0.023), after controlling for Framingham-CVD score and time-varying bDMARD use. In patients treated with statin >50% of follow-up time, CRP did not associate with new plaque formation [adjusted OR = 0.42 (95% CI: 0.09, 1.94)], in contrast to statin-naïve [adjusted OR = 1.89 (95% CI:1.41, 2.54)] and statin-treated <50% time [adjusted-OR = 1.41 (95% CI: 1.03, 1.95), P-interaction = 0.029]. Statin therapy >50% follow-up time predicted dissipation [adjusted-OR = 5.84 (95% CI: 1.29, 26.55)] and calcification of prevalent noncalcified lesions [adjusted-OR = 4.16 (95% CI: 1.11, 15.54)], as well as new calcified plaque formation in segments without baseline plaque [adjusted-OR = 2.84 (95% CI:1.09, 7.41)]. CONCLUSION: Statin therapy associated with lower long-term cardiovascular risk in RA patients with higher inflammation. Moreover, statin therapy modified the impact of inflammation on new coronary plaque formation and predicted both regression and calcification of prevalent noncalcified lesions.
34403275 No association between recent antibiotic use and risk of rheumatoid arthritis: results fro 2022 Jan BACKGROUND: Retrospective research partly characterizes the link between antibiotic use and rheumatoid arthritis (RA) development. This prospective cohort study may help reassess the association. RESEARCH DESIGN AND METHODS: We included 133,125 participants from the Nurses' Health Study (NHS) and NHS II databases. Three groups were established: nonuse, short-term use (1-14 days), and middle- to long-term use (≥15 days) to explore the link. Cox regression model was chosen to evaluate the hazard ratios (HRs) for RA. RESULTS: Short-term antibiotic use was not associated with the subsequent risk of RA (adjusted HR = 0.88, 95% Confidence Interval [CI] 0.38-1.38) compared to the no antibiotic use group in the multivariable adjusted model. The age-stratified model showed no sufficient evidence of increased risk in participants with middle- to long-term antibiotic use (HR = 1.32, 95% CI 0.89-1.98). The effect further attenuated to null after controlling for confounding factors (adjusted HR = 1.06, 95% CI 0.42-1.71). CONCLUSIONS: We found no evidence of an association between antibiotic use and RA risk. Our findings may reduce potential concerns about increased RA risk among antibiotic users.
35236687 Herpes zoster meningitis in a rheumatoid arthritis patient treated with tofacitinib. 2022 Mar 2 A man in his 70s with rheumatoid arthritis presented with seizures and coma and was transferred to our emergency department. Two months prior to admission, he started to take tofacitinib 10 mg/day. On admission, we noted a rash with a blister on the forehead, and herpes zoster was diagnosed. Cerebrospinal fluid examination suggested meningitis. An MRI of the brain showed no abnormality. Based on these findings, he was suspected with herpes zoster meningitis. We discontinued tofacitinib and treated the patient with intravenous acyclovir for 2 weeks. He regained complete consciousness, but right forehead skin lesion, severe vision loss in the right eye and right facial nerve paralysis remained as sequelae. Six weeks after admission, we restarted tofacitinib with oral valaciclovir as antiviral prophylaxis. Two years after admission, we administered Shingrix, an adjuvant recombinant vaccine for herpes zoster, and discontinued oral valaciclovir.
35197361 Passive smoking in childhood and adulthood and risk of rheumatoid arthritis in women: resu 2022 Feb OBJECTIVE: The association between passive smoking exposure in childhood or in adulthood, and the risk of rheumatoid arthritis (RA) has been incompletely investigated. We aimed to assess the relationship between exposure to passive smoking and the risk of incident RA in a French prospective cohort of healthy women. METHODS: The E3N Study (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l'Education Nationale) is a French prospective cohort of women included in 1990. Exposures to passive smoking were assessed using self-reported questionnaires. RA cases were self-reported and subsequently validated. Cox proportional hazards regression models adjusted for age and for potential confounders were used to estimate HRs and 95% CIs for incident RA. RESULTS: Among 79 806 women, 698 incident cases of RA were identified; 10 810 (13.5%) women were exposed to passive smoking in childhood, and 42 807 (53.6%) in adulthood. Median age at inclusion was 47.8 years. Passive smoking in childhood and in adulthood was associated with RA risk in all models (HRs (95% CIs) 1.24 (1.01 to 1.51) and 1.19 (1.02 to 1.40), respectively). The absolute risk of RA among never smokers with exposure to passive smoking in childhood and/or adulthood (47.6/100 000 person-years) was close to the risk of ever smokers with no passive smoking exposure (47.2/100 000 person-years), while it was highest in ever smokers also exposed to passive smoking (53.7/100 000 person-years). CONCLUSION: Exposure to passive smoking in childhood and/or adulthood increases the risk of RA by the same order than active smoking. Such exposure should be suppressed, especially in individuals at risk of RA.
34812532 iTRAQ-based proteomic analysis of differentially expressed proteins in sera of seronegativ 2022 Jan OBJECTIVE: The diagnosis of seronegative rheumatoid arthritis (SNRA) is often difficult due to the unavailability of reliable laboratory markers. The aim of this study was to identify differentially expressed proteins in sera of SNRA, seropositive RA (SPRA), and healthy donors (HD). METHODS: A total of 32 seropositive RA patients, 32 SNRA patients, and 35 HD were enrolled in our study. Differentially expressed proteins between 3 groups were identified via isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis, and an ELISA test was used for the validation test. Correlation analysis was conducted by GraphPad Prism. RESULTS: Using iTRAQ quantitative proteomics, we identified 14 proteins were significantly different between SPRA and SNRA, including 4 upregulated proteins and 10 downregulated proteins. Four differentially expressed proteins were validated by ELISA test, and the results showed that SAA1 protein was significantly higher in SPRA and SNRA patients compared with HD, and PSME1 was elevated in SPRA patients. What's more, SAA1 was increased in the anti-CCP or RF high-level group in RA patients, and PSME1 was increased in the RF high-level group. Alternatively, SAA1 was positively correlated with inflammation indicators in RA patients, while PSME1 showed no correlation with inflammation indicators. CONCLUSIONS: iTRAQ proteomic approaches revealed variations in serum protein composition among SPRA patients, SNRA patients, and HD and provided new idea for advanced diagnostic methods and precision treatment of RA.
35305721 A computational model revealing the immune-related hub genes and key pathways involved in 2022 Rheumatoid arthritis (RA) has one of the highest disability rates among inflammatory joint disorders. However, the reason and possible molecular events are still unclear. There are various treatment options available, but no complete cure. To obtain early diagnosis and successful medication in RA, it is necessary to explore gene susceptibility and pathogenic factors. The main intend of our work is to explore the immune-related hub genes with similar functions that are differentially expressed in RA patients. Three datasets such as GSE21959, GSE55457, and GSE77298, were taken to analyze the differently expressed genes (DEGs) among 55 RA and 33 control samples. We obtained 331 upregulated and 275 downregulated DEGs from three Gene Expression Omnibus (GEO) datasets using the R package. Furthermore, a protein-protein interaction network was built for upregulated and downregulated DEGs using Cytoscape. Subsequently, MCODE analysis was performed and obtained the top two modules in each DEG's upregulated and downregulated protein-protein interactions (PPIs) network. CytoNCA and cytoHubba were performed and identified overlapping DEGs. In addition, we narrowed down DEGs by filtering with immune-related genes and identified DE-IRGs. Gene ontology (GO) and KEGG pathway analysis in upregulated and downregulated DEGs were executed with the DAVID platform. Our study obtained the nine most significant DE-IRGs in RA such as CXCR4, CDK1, BUB1, BIRC5, AGTR1, EGFR, EDNRB, KALRN, and GHSR. Among them, CXCR4, CDK1, BUB1, and BIRC5 are overexpressed in RA and may contribute to the pathophysiology of the disease. Similarly, AGTR1, EGFR, EDNRB, KALRN, and GHSR are all low expressed in RA and may have a contribution to pathogenesis. GO, KEGG functional enrichment, and GeneMANIA showed that the dysregulated process of DE-IRGs causes RA development and progression. These findings may be helpful in future studies in RA diagnosis and therapy.
34687348 Belgian rheumatologists' preferences regarding measures of disease activity in patients wi 2022 May The reliability and clinical usefulness of the different composite disease activity scores and their individual components in Rheumatoid Arthritis (RA) are still debated. This study investigated which measures of disease activity were preferred by rheumatologists. A mixed-method study was performed. First, ten Belgian rheumatologists were invited for individual interviews on their current practice and preferences for measurement of RA disease activity. Results of this qualitative study and evidence from literature served as input for developing a survey. This survey asked rheumatologists to rate preferred standard disease activity score(s), their individual components, ultrasound and related patient-reported outcomes (PROs), by maximum difference scaling. The relative importance score (RIS) for each indicator was calculated using hierarchical Bayes modeling. The qualitative study included 6/10 invited rheumatologists. Composite scores and components were perceived as useful, while PROs were found subjective. Interestingly, ultrasound was used to mediate discrepancies between physician and patient. The survey based on this was sent to 244 Belgian rheumatologists, 83/244 (34%) responded, including 66/83 (80%) complete and 17/83 (20%) incomplete surveys (two missing essential information). Most rheumatologists (75/81, 93%) used a disease activity score and 68/81 (84%) preferred the DAS28-CRP. Swollen joint count obtained the highest mean ± SD RIS (22.54 ± 2.64), followed by DAS28 ESR/CRP (20.61 ± 4.06), ultrasound (16.47 ± 7.97), CRP (13.34 ± 6.11) and physician's global assessment (12.59 ± 7.83). PROs including fatigue, pain, and patient's global assessment, and Health Assessment Questionnaire, obtained the lowest mean RIS (0.34-2.54). Rheumatologists place more faith in self-assessed disease activity components or in laboratory tests. Trust in PROs to evaluate disease activity is low in clinical practice.
34936935 Methotrexate-loaded folic acid of solid-phase synthesis conjugated gold nanoparticles targ 2022 Mar 1 PURPOSE: Methotrexate (MTX) is a first-line drug for rheumatoid arthritis (RA). Targeting of MTX to inflamed joints is essential to the prevention of potential toxicity and improving therapeutic effects. Gold nanoparticles (GNPs) are characterized by controllable particle sizes and good biocompatibilities, therefore, they are promising drug delivery systems. We aimed at developing a GNPs drug delivery system incorporating MTX and folic acid (FA) with strong efficacies against RA. METHODS: MTX-Cys-FA was synthesized through solid-phase organic synthesis. Then, it was coupled with sulfhydryl groups in GNPs, thereby successfully preparing a GNPs/MTX-Cys-FA nanoconjugate with targeting properties. Physical and chemical techniques were used to characterize it. Moreover, we conducted its stability, release, pharmacokinetics, biodistribution and cell cytotoxicity, cell uptake, cell migration, as well as its therapeutic effect on CIA rats. The histopathology was conducted to investigate anti-RA effects of GNPs/MTX-Cys-FA nanoconjugates. RESULTS: The GNPs/MTX-Cys-FA nanoconjugate exhibited a spherical appearance, had a particle size of 103.06 nm, a zeta potential of -33.68 mV, drug loading capacity of 11.04 %, and an encapsulation efficiency of 73.61%. Cytotoxicity experiments revealed that GNPs had good biocompatibilities while GNPs/MTX-Cys-FA exhibited excellent drug-delivery abilities. Cell uptake and migration experiment showed that nanoconjugates containing FA by LPS activated mouse mononuclear macrophages (RAW264.7) was significantly increased, and they exerted significant inhibitory effects on human fibroblast-like synoviocytes (HFLS) of RA (p<0.01). In addition, the nanoconjugate prolonged blood circulation time of MTX in collagen-induced arthritis (CIA) rats (p<0.01), enhanced MTX accumulation in inflamed joints (p<0.01), enhanced their therapeutic effects (p<0.01), and reduced toxicity to major organs (p<0.01). CONCLUSION: GNPs/MTX-Cys-FA nanoconjugates provide effective approaches for RA targeted therapeutic strategies.
34542990 A Machine Learning Approach for Predicting Sustained Remission in Rheumatoid Arthritis Pat 2022 Mar 1 METHODS: In this longitudinal study, patients with RA who started a biological disease-modifying antirheumatic drug (bDMARD) in a tertiary care center were analyzed. Demographic and clinical characteristics were collected at treatment baseline, 12-month, and 24-month follow-up. A wrapper feature selection algorithm was used to determine an attribute core set. Four different ML algorithms, namely, LR, random forest, K-nearest neighbors, and extreme gradient boosting, were then trained and validated with 10-fold cross-validation to predict 24-month sustained DAS28 (Disease Activity Score on 28 joints) remission. The performances of the algorithms were then compared assessing accuracy, precision, and recall. RESULTS: Our analysis included 367 patients (female 323/367, 88%) with mean age ± SD of 53.7 ± 12.5 years at bDMARD baseline. Sustained DAS28 remission was achieved by 175 (47.2%) of 367 patients. The attribute core set used to train algorithms included acute phase reactant levels, Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, as well as several clinical characteristics. Extreme gradient boosting showed the best performance (accuracy, 72.7%; precision, 73.2%; recall, 68.1%), outperforming random forest (accuracy, 65.9%; precision, 65.6%; recall, 59.3%), LR (accuracy, 64.9%; precision, 62.6%; recall, 61.9%), and K-nearest neighbors (accuracy, 63%; precision, 61.5%; recall, 54.8%). CONCLUSIONS: We showed that ML models can be used to predict sustained remission in RA patients on bDMARDs. Furthermore, our method only relies on a few easy-to-collect patient attributes. Our results are promising but need to be tested on longitudinal cohort studies.
33905483 Clinical and biomechanical factors associated with falls and rheumatoid arthritis: baselin 2022 Feb 2 OBJECTIVE: To identify the clinical and biomechanical characteristics associated with falls in people with RA. METHODS: A total of 436 people ≥60 years of age with RA completed a 1 year prospective survey of falls in the UK. At baseline, questionnaires recorded data including personal and medical history, pain and fatigue scores, health-related quality of life (HRQoL), physical activity and medication history. The occurrence of falls wasmonitored prospectively over 12 months by monthly self-reporting. A nested sample of 30 fallers (defined as the report of one or more falls in 12 months) and 30 non-fallers was evaluated to assess joint range of motion (ROM), muscle strength and gait parameters. Multivariate regression analyses were undertaken to determine variables associated with falling. RESULTS: Compared with non-fallers (n = 236), fallers (n = 200) were older (P = 0.05), less likely to be married (P = 0.03), had higher pain scores (P < 0.01), experienced more frequent dizziness (P < 0.01), were frequently taking psychotropic medications (P = 0.02) and reported lower HRQoL (P = 0.02). Among those who underwent gait laboratory assessments, compared with non-fallers, fallers showed a greater anteroposterior (AP; P = 0.03) and medial-lateral (ML) sway range (P = 0.02) and reduced isokinetic peak torque and isometric strength at 60° knee flexion (P = 0.03). Fallers also showed shorter stride length (P = 0.04), shorter double support time (P = 0.04) and reduced percentage time in swing phase (P = 0.02) and in knee range of motion through the gait cycle (P < 0.01). CONCLUSION: People with RA have distinct clinical and biomechanical characteristics that place them at increased risk of falling. Assessment for these factors may be important to offer more targeted rehabilitation interventions.
34254354 LncRNA NEAT1_1 suppresses tumor-like biologic behaviors of fibroblast-like synoviocytes by 2022 Mar Fibroblast-like synoviocytes (FLSs) are the predominant effector cells in the pathological progression of rheumatoid arthritis (RA). Therefore, elucidating the underlying molecular mechanism of the biologic behaviors in RA-FLSs will be helpful in developing the potent targets for the treatment of RA. We have previously documented that the tumor-like biologic behaviors of RA-FLSs are exacerbated by urokinase-type plasminogen activator receptor (uPAR), a specifically up-regulated receptor in RA-FLSs. Here, we investigate the further mechanism of uPAR and clarify its function in RA-FLSs. We demonstrate that miR-221-3p positively correlates to uPAR and regulates uPAR level in RA-FLSs. Simultaneously, one long noncoding RNA, nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) is identified, which can predictively target miR-221-3p at three sites, indicating a strong possibility of being a competing endogenous RNA in RA-FLSs. Interestingly, NEAT1_1 and miR-221-3p can colocate in the nucleus and cytoplasm in RA-FLSs. Importantly, NEAT1_1 can act as a rheostat for the miR-221-3p/uPAR axis and the downstream JAK signaling. In line with the biologic function, NEAT1_1 negatively regulates the tumor-like characters, and cytokine secretions of RA-FLSs. Collectively, our data provide new insight into the mechanisms of NEAT1_1 in modulating RA-FLSs tumor-like behaviors. The targeting of NEAT1_1 and miR-221-3p/uPAR axis may have a promising therapeutic role in patients with RA.
35115042 Ultrasound-guided lymph node biopsy sampling to study the immunopathogenesis of rheumatoid 2022 Feb 3 BACKGROUND: Analyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA). Yet, invasive tissue collection methods are scarcely applied, because they are often considered burdensome, although patients do not always consider invasive methods as a high burden. We aimed to investigate the perspectives of study participants undergoing ultrasound-guided inguinal lymph node (LN) needle biopsy sampling and determine the molecular and cellular quantity and quality of LN biopsies. METHODS: Together with patient research partners, questionnaires were developed to evaluate the motives, expectations, and experiences of participants undergoing a LN biopsy. Healthy controls and RA(-risk) patients were asked to complete these questionnaires before and after the procedure. RNA and lymphocyte yields from obtained LN biopsies were also calculated. RESULTS: We included 50 individuals, of which 43 (86%) reported their pre- and post-procedure experiences. The median reported pain on a 5-point Likert scale (1 not to 5 very painful) was 1. Interestingly, almost all (n = 32; 74%) study participants would undergo a second procedure and more than half (n = 23; 54%) would encourage others to take part in the LN biopsy study. Motives for current and future participation were mostly altruistic. Inguinal hematoma occurred frequently, but no other significant or unexpected complications ensued. The LN biopsies yielded sufficient and high-quality RNA and lymphocyte numbers. CONCLUSIONS: Ultrasound-guided inguinal LN biopsy sampling is well-tolerated, safe, and provides sufficient material for further molecular and cellular analyses. Our participants' positive experiences endorse the application of this research tool to further elucidate the pathogenesis of RA and other inflammatory diseases.
34508557 SM03, an anti-human CD22 monoclonal antibody, for active rheumatoid arthritis: a phase II, 2022 May 5 OBJECTIVE: SM03, a novel chimaeric mAb specific to B cell-restricted antigen CD22, has been developed to treat RA and other B-cell-related diseases. This 24-week phase II randomized, double-blind, multi-dose, placebo-controlled study aimed to evaluate the efficacy and safety of SM03 in moderately-to-severely active RA patients in China. METHODS: One hundred and fifty-six patients on background MTX were randomized in a 1:1:1 ratio to receive a cumulative dose of 3600 mg (high dose, 600 mg × 6 infusions at weeks 0, 2, 4, 12, 14 and 16) or 2400 mg SM03 (low dose, 600 mg × 4 infusions at weeks 0, 2, 12 and 14) or the placebo. The primary outcome was the 24-week ACR 20% improvement criteria (ACR20) response rate. Safety was also assessed. RESULTS: The 24-week ACR20 response rate was significantly higher with high- (65.3%, P = 0.002) and low-dose SM03 (56.9%, P = 0.024) than with placebo (34.0%), but comparable between the high- and low-dose group. The rate of adverse events was not statistically different among the high-dose group (35.3%), the low-dose group (51.9%) and the placebo group (34.6%). Thirteen (12.6%) patients receiving SM03 reported treatment-emergent infections, including 3.9% patients in the high-dose group. No patients reported severe treatment-emergent infections or malignancies. CONCLUSIONS: In active RA Chinese patients receiving background MTX, SM03 at a cumulative dose of both 2400 mg and 3600 mg is efficacious and well-tolerated throughout the 24 weeks of treatment. Moreover, SM03 has demonstrated a good safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04192617.
34850085 Impact of denosumab discontinuation on changes in bone mineral density and bone erosion in 2022 Feb 28 OBJECTIVES: This study investigated changes in bone mineral density (BMD) and erosion after denosumab discontinuation in rheumatoid arthritis (RA) patients without osteoporosis who participated in the DESIRABLE study. METHODS: This multicentre observational study consisted of a prediscontinuation visit (date of final assessment in DESIRABLE) and a postdiscontinuation visit (2.5 years after the last administered dose of denosumab). Percentage change in lumbar spine (LS) BMD from baseline was assessed as the primary endpoint. RESULTS: Fifty-nine patients were enrolled. The percentage change in LS BMD decreased to baseline levels at the postdiscontinuation visit. Compared with baseline, C-telopeptide of type I collagen levels increased after denosumab discontinuation but most patients had levels within the reference range. Bone erosion scores were not significantly different between the on-treatment period and after denosumab discontinuation (p = .0666) but there was a numerical increase postdiscontinuation. The progression in bone erosion score was significantly reduced in patients whose disease activity was in remission versus those not in remission (p = .0195). CONCLUSIONS: In RA patients without osteoporosis, denosumab discontinuation can be explored while considering patient background factors (disease activity and risk of fracture) and accounting for progression of bone erosion and LS BMD decrease after withdrawal.