Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
35147770 Risk factors for nonunion following open reduction and internal fixation for proximal hume 2022 Feb 11 PURPOSE: The incidence of proximal humerus fractures (PHF) is rising and surgical intervention carries risk for fracture nonunion. The purpose was (1) to compare patient demographics of those that developed nonunion and (2) identify patient risk factors that predispose to nonunion following open reduction and internal fixation (ORIF) for PHF. METHODS: A retrospective review of the Medicare Claims Database from 2005 to 2014 for patients who underwent primary ORIF for PHFs. Patients who developed nonunion were identified as the study group (n = 1020) and compared to a control group (n = 51,209). Primary endpoints were to compare demographics of the study group and the comparison cohorts and to identify patient-related risk factors associated with nonunion within 6-months following the index procedure. A logistic regression model was constructed to determine the association of comorbid conditions on developing a nonunion. A p value of 0.001 was the significance threshold. RESULTS: Patients who developed nonunion were younger, more likely to be male, and had higher Elixhauser-Comorbidity Index scores (7 vs. 5; p < 0.0001) when compared with controls. Iron deficiency anemia (OR: 1.32; p = 0.0001), tobacco use (OR: 1.32; p = 0.0004), rheumatoid arthritis (OR: 1.29; p = 0.0001), depression (OR: 1.28; p = 0.0002), and BMI range from 30-39 kg/m(2) (OR: 1.21; p = 0.001) were significant risk factors for nonunion. CONCLUSIONS: Certain patient risk factors including tobacco use, iron deficiency anemia, rheumatoid arthritis, depression, and a BMI in the range of 30-39 were associated with nonunion within 6 months of ORIF for PHF. This study may help in the risk stratification of these patients.
35127697 A Preliminary Inquiry Into the Potential Mechanism of Huang-Lian-Jie-Du Decoction in Treat 2021 Huang-Lian-Jie-Du decoction (HLJDD) has been widely applied to treat inflammation-associated diseases for thousands of years in China. However, the concrete molecular mechanism of HLJDD in the treatment of rheumatoid arthritis (RA) remains unclear. In this work, network pharmacology and molecular docking were applied to preliminarily analyze the potential active ingredients, drug targets, and related pathways of HLJDD on treating RA. A total of 102 active compounds with corresponding 189 targets were identified from HLJDD, and 41 common targets were further identified by intersecting with RA-related targets. Functional enrichment analysis was performed to screen the biological pathways associated with RA. Ten hub targets were further identified through constructing the protein-protein interaction (PPI) network of common targets, which were mainly enriched in the interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway. Furthermore, a complex botanical drugs-ingredients-hub-targets-disease network was successfully constructed. The molecular docking results exhibited that these vital ingredients of HLJDD had a stable binding to the hub targets. Among these ingredients, quercetin (MOL000098) was the most common molecule with stable binding to all the targets, and PTGS2 was considered the most important target with multiple regulations by the most active ingredients. In vitro, we successfully validated the inhibitory role of quercetin in the cellular proliferation of human RA fibroblast-like synoviocyte cell line (MH7A cells). These findings indicated that the potential mechanisms of HLJDD for RA treatment might be attributed to inhibiting the immune-inflammatory response, reducing the release of chemokines, and alleviating the destruction of extracellular matrix (ECM) in the synovial compartment.
35071522 Acquired coagulation dysfunction resulting from vitamin K-dependent coagulation factor def 2022 Jan 7 BACKGROUND: Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease with the main clinical feature of progressive joint synovial inflammation, which can lead to joint deformities as well as disability. RA often causes damage to multiple organs and systems within the body, including the blood hemostasis system. Few reports have focused on acquired coagulation dysfunction resulting from vitamin K-dependent coagulation factor deficiency associated with RA. CASE SUMMARY: A 64-year-old woman with a history of RA presented to our hospital, complaining of painless gross hematuria for 2 wk. Blood coagulation function tests showed increased prothrombin time, international normalized ratio, and activated partial thromboplastin time. Abnormal blood coagulation factor (F) activity was detected (FII, 7.0%; FV, 122.0%; and FX, 6.0%), indicating vitamin K-dependent coagulation factor deficiency. Thromboelastography and an activated partial thromboplastin time mixed correction experiment also suggested decreased coagulation factor activity. Clinically, the patient was initially diagnosed with hematuria, RA, and vitamin K-dependent coagulation factor deficiency. The patient received daily intravenous administration of vitamin K1 20 mg, etamsylate 3 g, and vitamin C 3000 mg for 10 d. Concurrently, oral leflunomide tablets and prednisone were administered for treatment of RA. After the treatment, the patient's symptoms improved markedly and she was discharged on day 12. There were no hemorrhagic events during 18 mo of follow- up. CONCLUSION: RA can result in vitamin K-dependent coagulation factor deficiency, which leads to acquired coagulation dysfunction. Vitamin K1 supplementation has an obvious effect on coagulation dysfunction under these circumstances.
35623291 Efficacy of DMARDs and methylprednisolone treatment on the gene expression levels of HSPA5 2022 May 24 BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by joint damage and even extra-articular involvement. In this study, the gene expression levels of MALAT1, H19 and their possible downstream microRNAs, miR-199a-5p, miR-1-3p, and the predicted targets of these miRNAs, HSPA5 and MMD, were examined. METHODS: Twenty-five newly diagnosed RA patients and 25 healthy individuals were included. For six months, patients were treated with conventional disease-modifying antirheumatic drugs (DMARDs) and Methylprednisolone (mPRED). Blood samples were obtained from healthy controls and patients (before and after treatment). After RNA extraction, the RT-qPCR technique was used to evaluate the expression level of the studied genes. RESULTS: Data showed that the expression level of MALAT1, H19, miR-199a-5p, and miR-1-3p was significantly higher in the newly diagnosed patients with RA than the healthy subjects, but the increase in the expression level of HSPA5 and MMD genes in the new cases was not significant compared to healthy controls. After treatment, except for the expression level of lncRNAs, the expression level of miRNAs, HSPA5, and MMD significantly increased. Based on ROC curve analysis of MALAT1, H19, miR-199a-5p and miR-1-3p have a high ability to identify patients from healthy individuals (AUC = 0.986, AUC = 0.995, AUC = 0.855, AUC = 0.675, respectively). CONCLUSION: MALAT1 and H19 may be candidates as potential biomarkers for the discrimination between RA patients and controls. DMARDs plus mPRED therapy do not have a desirable effect on reducing inflammatory responses and ER stress.
35645965 Association Between Rheumatoid Arthritis and Risk of Parkinson's Disease: A Meta-Analysis 2022 BACKGROUND: Rheumatoid arthritis (RA) and Parkinson's disease (PD) are two common chronic diseases worldwide, and any potential link between the two would significantly impact public health practice. Considering the current inconsistent evidence, we conducted a meta-analysis and systematic review to examine the risk of PD in patients with RA. METHODS: Two investigators (DL and XH) conducted a comprehensive search of PubMed, Embase, and Web of Science using medical subject headings terms combined with free words to identify relevant papers published from inception through December 31, 2021. All studies that explored the relationship between RA and PD were included for quantitative analysis and qualitative review. Random- and fixed-effects models were used to pool the risk ratios (RRs) of PD in patients with RA. The Newcastle-Ottawa scale was used to assess the quality of included studies. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guideline. RESULTS: Four population-based studies involving 353,246 patients and one Mendelian randomized study were included in our study. The pooled result showed a significantly reduced risk of PD in patients with RA than in the general population (RR = 0.74, 95% CI: 0.56-0.98, P = 0.034). No apparent effects of gender, age, region, follow-up time, or study design on PD risk were observed. Sensitivity analysis showed that pooled results were relatively stable, and no publication bias was detected. The Mendelian randomization study indicated a significant inverse association between RA and PD (genetic correlation: -0.10, P = 0.0033) and that each one standard deviation increase in the risk of RA was significantly associated with a lower risk of PD. Of note, the current study is limited by the relatively small number of included studies and unmeasured confounding factors, especially for RA-related anti-inflammatory agents. CONCLUSIONS: This study supports that people with RA had a lower PD risk than those without RA. Further studies are needed to explore the underlying molecular mechanisms of the interaction between the two diseases.
35453643 Circulating miRNA Correlates with Lipid Profile and Disease Activity in Psoriatic Arthriti 2022 Apr 13 This study aimed to investigate the associations of microRNA (miRs) signatures with cytokines, serum lipids, and disease activity in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA). In total, 65 patients (PsA n = 25, AS n = 25, RA n = 15) and 25 healthy controls (HC) were enrolled into the study. The expression of miR-223-5p, miR-92b-3p, miR-485-3p, miR-10b-5p, let-7d-5p, miR-26a-2-3p, miR-146b-3p, and cytokines levels were measured in sera. DIANA-mirPath analysis was used to predict pathways targeted by the dysregulated miRs. Disease activity scores were calculated. Lipid profile, uric acid, glucose level, and C-reactive protein (CRP) concentrations were determined in the blood. Based on lipid profiles, the PsA group had hypertriglyceridaemia, and RA patients revealed mixed dyslipidaemia, while in AS, no specific changes were found. miR expression analysis revealed upregulation of miR-26a-2-3p and miR-10b-5p in PsA, miR-485-3p in AS, and let-7d-5p in RA. Several correlations between disease activity indexes, metabolites levels, and expression of miRs were observed in PsA, RA, and AS patients. Finally, in ROC analysis, miR-26a-2-3p/miR-485-3p, and let-7d-5p/miR-146b-3p tandems revealed high sensitivity and specificity in distinguishing between PsA, AS, and RA. Our study illustrates the superiority of miR expressions in distinguishing between RA, PsA, and AS. In PsA, a unique regulatory pathway exists through miR-26a-2-3p, miR-223-5p, miR-10b-5p, and miR-92b-3p that converges proatherogenic metabolism and disease activity.
35524837 Promising role of polymeric nanoparticles in the treatment of rheumatoid arthritis. 2022 May 7 Rheumatoid arthritis (RA) is a chronic inflammatory illness caused by an autoimmune disorder of synovial membrane resulting in synovial membrane dysfunction. The available treatment particularly focuses on inhibiting macrophage proliferation and reducing the generation of pro-inflammatory cytokines. However, therapeutic success of current treatment options at targeted site is limited; therefore, development of promising therapeutic strategy is the need of time that may provide better targeted delivery of drug with added safety. In development of precision medicine to manage RA, nanotechnology is a viable option to be considered. Recent research using nanoparticles for the treatment of RA, particularly polymeric nanoparticles, has been discussed in this article. Using polymeric nanoparticles as a therapeutic method has shown considerable promise of enhancing treatment success over standard medications used in routine. It is exclusively evident that the viability of using nanoparticles is mainly owed due to their biocompatibility, chemical stability, controlled drug release, and selective drug delivery to inflamed tissues in RA model animals. The current analysis focuses on the critical design characteristics of RA-targeted nanotechnology-based strategies in quest of better therapeutic strategies for RA, and to identify leading polymer as the most effective medications in RA therapy.
35586477 Is Pharmacogenetic Panel Testing Applicable to Low-Dose Methotrexate in Rheumatoid Arthrit 2022 PURPOSE: Pharmacogenetic (PGx) panel testing could help to determine the heritable component of a rheumatoid arthritis (RA) patient's susceptibility for therapy failure and/or adverse drug reactions (ADRs) from methotrexate (MTX). Considering the literature mentioning the potential applicability of PGx panel testing within MTX regimens, we discuss the case of a patient who was treated with MTX, suffered from ADRs, and obtained a reactive PGx panel testing. GENOTYPING: We used a commercial PGx panel test involving the ABC-transporters P-glycoprotein (P-gp; gene: ABCB1), and breast cancer resistance protein (BCRP; gene: ABCG2), the solute carriers reduced folate carrier 1 (RFC1; gene: SLC19A1), and organic anion transporting polypeptide 1B1 (OATP1B1; gene: SLCO1B1), and the enzymes inosine triphosphatase (ITPA), and glutathione transferase P1 (GSTP1). In addition, we genotyped the patient for the enzymes 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR)/inosine monophosphate (IMP) cyclohydrolase (gene name: ATIC), gamma-glutamyl hydrolase (gene name: GGH) and methylenetetrahydrofolate reductase (gene name: MTHFR). RESULTS: The PGx profile of the patient revealed genetic variants in SLC19A1, ABCB1, and MTHFR, which may explain the ADRs experienced during the treatment with MTX and a potentially lower efficacy of MTX. Based on our interpretation of the PGx profile, we recommended the patient to avoid MTX in the future. CONCLUSION: The MTX pathway is complex, which makes the interpretation of genetic variants affecting metabolism challenging. A reactive PGx panel test was applicable to explain ADRs experienced during MTX treatment for a patient with RA. However, the clinical utility of PGx-guided MTX treatment in a primary care setting is still limited. In order to base a recommendation for MTX on PGx data, we need genome-wide association studies, large prospective multicenter studies and PGx studies, which analyze different multi-gene haplotypes and gene-drug-drug interactions for MTX.
35437350 Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response 2022 PURPOSE: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR >0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1~4 and ABCG2, were genotyped. RESULTS: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR >0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CCC. CONCLUSION: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.
35433937 A narrative review of the role of the Notch signaling pathway in rheumatoid arthritis. 2022 Mar BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease affected by genetics and the environment factors. Its early diagnosis and treatment are difficult, and the infection risk is serious. The treatment effects for most patients were not significant, which has become a difficult challenge to overcome. Cell signals play an important role in regulating basic cellular activities such as immunity. Notch signaling is a near secretory signal that can affects many processes of cell normal morphogenesis, including the differentiation of pluripotent progenitor cells, apoptosis, cell proliferation and the formation of cell boundary. In addition, the expression and activation of Notch signaling are increased in the synovial cells and vascular endothelial cells of RA patients. The purpose of this review was to elucidate the related mechanisms of Notch signaling in RA progression, as well as the potential therapeutic value of Notch signaling in a variety of autoimmune diseases. METHODS: Literatures about Notch signaling and RA were extensively reviewed to analyze and discuss. KEY CONTENT AND FINDINGS: This article briefly reviews the role of Notch signaling in RA. It also summarizes the functional role of Notch signaling in the treatment of RA, with the goal to provide a new treatment option for RA patients. CONCLUSIONS: In this review, the approach we discussed focuses on Notch signaling as a potential therapeutic target against RA, enriching therapeutic strategies for inflammatory diseases including RA.
35415310 Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge 2022 Dec Excessive cell-free DNA (cfDNA) released by damaged or apoptotic cells can cause inflammation, impacting the progression of rheumatoid arthritis (RA). cfDNA scavengers, such as cationic nanoparticles (NPs), have been demonstrated as an efficient strategy for treating RA. However, most scavengers are limited by unfavorable biocompatibility and poor scavenging efficacy. Herein, by exploiting the favorable biocompatibility, biodegradability and bioadhesion of polydopamine (P), we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfDNA for RA therapy. Results showed that DPs endowed with superior binding affinity of cfDNA and little cytotoxicity, which effectively inhibited lipopolysaccharide (LPS) stimulated inflammation in vitro, resulting in the relief of joint swelling, synovial hyperplasia and cartilage destruction in RA rats. Significantly, DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfDNA binding affinity, leading to excellent RA therapeutic effect among all of the treated groups, which was even close to normal rats. These finding provides a novel strategy for the treatment of cfDNA-associated diseases.
35354508 A distinctive profile of family genetic risk scores in a Swedish national sample of cases 2022 Mar 31 BACKGROUND: Functional somatic disorders (FSD) feature medical symptoms of unclear etiology. Attempts to clarify their origin have been hampered by a lack of rigorous research designs. We sought to clarify the etiology of the FSD by examining the genetic risk patterns for FSD and other related disorders. METHODS: This study was performed in 5 829 186 individuals from Swedish national registers. We quantified familial genetic risk for FSD, internalizing disorders, and somatic disorders in cases of chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), using a novel method based on aggregate risk in first to fifth degree relatives, adjusting for cohabitation. We compared these profiles with those of a prototypic internalizing psychiatric - major depression (MD) - and a somatic/autoimmune disorder: rheumatoid arthritis (RA). RESULTS: Patients with FM carry substantial genetic risks not only for FM, but also for pain syndromes and internalizing, autoimmune and sleep disorders. The genetic risk profiles for IBS and CFS are also widely distributed although with lower average risks. By contrast, genetic risk profiles of MD and RA are much more restricted to related conditions. CONCLUSION: Patients with FM have a relatively unique family genetic risk score profile with elevated genetic risk across a range of disorders that differs markedly from the profiles of a classic autoimmune disorder (RA) and internalizing disorder (MD). A similar less marked pattern of genetic risks was seen for IBS and CFS. FSD arise from a distinctive pattern of genetic liability for a diversity of psychiatric, autoimmune, pain, sleep, and functional somatic disorders.
35366159 Risk factors for septic arthritis and multiple arthroscopic washouts: minimum 2-year follo 2022 Apr 2 BACKGROUND: Septic arthritis (SA) is a dangerous condition that requires emergency treatment. Managed by culture-specific antibiotics, irrigation, and debridement (I&D), some patients require repeat surgical treatment. The objectives were to determine the risk factors for SA and risk factors for repeat arthroscopic I&D in SA patients. We hypothesized that variables which directly or indirectly contributed to a larger infection burden would be associated with the development of SA and the need for repeat arthroscopic I&D. METHODS: All patients ≥ 18 years old presenting to the emergency department, orthopaedic and rheumatology clinics at our major trauma centre between January 2018 and January 2020 with a hot, swollen joint were retrospectively evaluated. Patients with previous trauma and metalwork in the affected joint, periprosthetic joint infection, previous joint arthroplasty surgery, soft tissue infection, missing data, transferred to another centre, diagnosis not concerning the joint, and < 24-month follow-up were excluded. Two hundred eleven patients were included (SA: 28; pseudogout: 32; gout: 50; others: 101). Variables of interest in the 3-month period preceding the diagnosis of SA were compared between SA and non-SA patients using univariable analysis. A multivariable logistic regression model was formed using covariates with corresponding univariable tests of p < 0.200. Similar analyses were performed to compare SA patients with multiple washouts/procedures with those with one washout/procedure. RESULTS: Multivariable analysis showed multiple risk factors for SA, namely rheumatoid arthritis (RA) (OR: 3.4; 95% CI: 1.2-10.0; p = 0.023); skin infection (OR: 3.3; 95% CI: 1.2-9.0; p = 0.017), liver disease (OR: 9.9; 95% CI: 2.2-43.9; p = 0.003), knee joint involvement (OR: 3.5; 95% CI: 1.3-9.4; p = 0.014), and use of immunosuppressive medication (OR: 3.5; 95% CI: 1.2-10.6; p = 0.027). Risk factors for multiple washouts included synovial WBC levels > 10.5 × 10(9) cells/L (OR: 3.0; 95% CI: 2.3-38.8; p = 0.009) and RA (OR: 3.5; 95% CI: 1.9-66.3; p = 0.017). CONCLUSIONS: These findings suggest that prophylactic actions against septic arthritis should be targeted at patients with liver disease, RA, or skin infection. Repeat arthroscopic I&D of septic joints may be needed, especially in patients with synovial WBC levels > 10.5 × 10(9) cells/L and RA. Key Points • The risk factors for septic arthritis determined in this study are rheumatoid arthritis, skin infection, liver disease, knee joint involvement, and immunosuppressant usage. • Some septic arthritis patients need multiple rounds of arthroscopic irrigation and debridement. The risk factors for this are a synovial WBC count > 10.5 × 10(9) cells/L and rheumatoid arthritis.
35604547 Diabetes-Related Complications and Costs in Medicare Beneficiaries with Comorbid Rheumatoi 2022 May 23 INTRODUCTION: Targeted DMARD (tDMARD) use in patients with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM) may increase whole-body insulin sensitivity. Evidence comparing the T2DM-related clinical and economic impact of abatacept versus other tDMARDs is limited. This study compared differences in T2DM-related healthcare resource utilization (HCRU) and costs in patients with RA and T2DM. METHODS: This retrospective study used 100% Medicare Fee-for-Service claims (parts A/B/D) to identify patients ≥ 65 age, diagnosed with RA and T2DM, and were either TNFi-experienced (switched from a TNFi to another tDMARD) or tDMARD-naïve, initiating their first tDMARD (abatacept, TNFi, or non-TNFi) between 2010 and 2017. Abatacept users were propensity-score (PS) matched to TNFi and other non-TNFi users separately on baseline demographics, comorbidities, medications, T2DM-related HCRU, and costs. Post-index follow-up: until discontinuation of index treatment, disenrollment, death, or end of study period, whichever occurred first. T2DM-related complications and HCRU were assessed. Costs were normalized to per-patient-per-month (PPPM) and inflated to 2019 US$. RESULTS: The TNFi-experienced group included 2169 abatacept/TNFi and 2118 abatacept/other non-TNFi PS-matched pairs; the tDMARD-naïve group included 2667 abatacept/TNFi and 2247 abatacept/other non-TNFi PS-matched pairs. For TNFi-experienced patients, T2DM-related complication rates for inpatient settings PPPM trended lower for abatacept than TNFi (21 vs. 24, p = 0.046) and other non-TNFi groups (21 vs. 26; p < 0.0001). T2DM-related total costs PPPM for TNFi-experienced patients demonstrated lower trends for abatacept than TNFi ($489 vs. $594, p = 0.016) and other non-TNFi users ($493 vs. $606, p = 0.012). CONCLUSIONS: Medicare beneficiaries with RA and T2DM who switch to/initiate abatacept as their first tDMARD have directionally lower rates and costs of T2DM-related complications compared with patients switching to/initiating other tDMARDs. Abatacept treatment may help reduce clinical and economic burdens associated with T2DM in patients with RA.
35535352 The Clinical Presentation and Factors Associated with Disease Severity of Rheumatoid Arthr 2022 BACKGROUND: Rheumatoid arthritis (RA) is a chronic, debilitating disease that leads to joint destruction and disability if left untreated. Few studies on RA have been conducted in Uganda, and there is limited information on disease severity and associated factors. This study sought to characterize the clinical presentation and to determine disease severity and the factors associated with disease severity among participants with RA in Uganda. METHODS: Between August 2018 and February 2019, patients presenting to the rheumatology outpatient clinic in Mulago National Referral Hospital were enrolled into the study using a cross-sectional design. Participants' demographics and clinical characteristics were collected using a study questionnaire, and laboratory results were extracted from their charts. The patients' functionality was assessed using the Modified Health Assessment Questionnaire and their disease severity was assessed using the RA Disease Activity Score based on 28-joint count (DAS28). RESULTS: A total of 170 participants were enrolled, of whom 81.2% were female. Nearly two-thirds (111/170) were classified as having severe disease. Having a functional status score of >0.5 (adjusted odds ratio 1.7, 95% confidence interval 1.4-2.2, p<0.001) was significantly associated with severe disease. CONCLUSION: In this population, the majority of the patients seen at the rheumatology outpatient clinic had severe disease, suggesting that patients may be presenting late, with limited early detection of the disease. Impaired functional status was associated with increased disease severity and may be used by clinicians to highlight disease severity when it is not possible to assess the RA DAS28.
35512175 Musculoskeletal ultrasound for treating rheumatoid arthritis to target-a systematic litera 2022 May 4 OBJECTIVE: We aimed to systematically review the literature to retrieve evidence on the diagnostic and prognostic value of musculoskeletal ultrasound for a treat to target (T2T) approach in rheumatoid arthritis (RA). METHODS: Eight research questions were developed addressing the role of ultrasound (including different ultrasound scores and elementary lesions) for diagnosis, monitoring and prognosis of RA. PubMed and Embase were searched (2005-2020). Articles on RA and reporting data on musculoskeletal ultrasound were included and extracted according to the underlying questions, and risk of bias assessed according to the study design. RESULTS: Out of 4,632 records, 60 articles were included. Due to clinical heterogeneity, meta-analysis was not possible. Ultrasound better predicted disease relapses with respect to clinical examination in patients in remission, while both methods performed similarly in predicting response to therapy, achievement of remission and radiographic progression. Ultrasound was superior to clinical examination in diagnosing joint involvement using another imaging modality, such as magnetic resonance imaging, as reference. Limited ultrasound scores performed like more extensive evaluations for the detection of joint inflammation and for outcome prediction. Higher ultrasound scores of synovitis were linked to poor outcomes at all disease stages, however, a specific cut-off distinguishing between low- and high-risk groups did not emerge. CONCLUSIONS: These data confirm the pivotal role of ultrasound when evaluating synovial inflammation and when identifying RA patients at higher risk of relapse. Further research is needed to better define the role of ultrasound in a T2T management strategy in moderately-to-highly active RA.
35472175 Immunosuppressants contribute to a reduced risk of Parkinson's disease in rheumatoid arthr 2022 Apr 26 BACKGROUND: Observational studies have suggested a decreased risk of Parkinson's disease (PD) in patients with rheumatoid arthritis (RA). However, the results are controversial and the biological mechanism underlying this effect remains largely unknown. METHODS: The effect sizes of five observational studies were summarized to determine the association between RA and PD. A two-step Mendelian randomization (TSMR) analysis was conducted using genome-wide association studies data sets of RA, PD and prescription of non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants (IS) and glucocorticoids (GC). A multivariable MR (MVMR) was also performed to verify the impact of prescription history on PD risk. RESULTS: Integrated data from observational studies showed that RA was associated with a decreased risk of PD in the European population (effect size = -0.38, P = 0.004). We found that genetically predicted RA was correlated with a decreased risk of PD [odds ratio (OR) = 0.91, P = 0.007]. In the TSMR, RA patients tended to have an increased prescription of GC (OR = 1.16, P = 2.96e - 07) and IS (OR = 1.77, P = 5.58e - 64), which reduced the risk of PD (GC: OR = 0.86, P = 0.0270; IS: OR = 0.82, P = 0.0277), respectively. Further MVMR analysis demonstrated that only IS was linked to a decreased risk of PD (OR = 0.86, P = 0.004). CONCLUSION: This work clarified that patients with RA had a decreased risk of PD, which was partially attributed to the use of IS in RA patients but not GC or NSAIDs.
35046715 Association Between Blood PLT and RBC Related Indices and Disease Activity in Patients wit 2022 BACKGROUND: Platelet (PLT) and red blood cell (RBC) have been demonstrated to play a critical role in inflammatory processes. This study aimed to evaluate the association of blood PLT and RBC related parameters with the disease activity in rheumatoid arthritis (RA) patients, and also to investigate the role of these indices in differentiating among RA patients with different disease activity. METHODS: Clinical data from RA patients were retrospectively analyzed. RA patients were divided into inactive group and active group according to DAS28-CRP. The relationship between blood PLT and RBC counts-related indices and DAS28-CRP was detected by Spearman correlation. ROC curve was used to assess the diagnostic value of these indices in differentiating active RA from inactive RA. RESULTS: Active RA patients exhibited higher level of PLT counts but significantly lower levels of RBC counts, hemoglobin (Hb), red blood cells-platelet ratio (RPR) and hemoglobin-platelet ratio (HPR) compared with inactive RA. PLT counts were positively but RBC counts, Hb, RPR and HPR were negatively related with DAS28-CRP. CONCLUSION: Blood PLT and RBC related indices were significantly associated with RA disease activity. These indices may be used to distinguish active RA from inactive RA.
35022672 Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rhe 2022 Jan 12 OBJECTIVES: The REDO trial showed that ultra-low dose rituximab (500 mg or 200 mg) was similarly effective in the majority of rheumatoid arthritis (RA) patients. This pre-planned secondary analysis investigates 1) associations between rituximab dosage, drug levels, anti-drug antibodies (ADA) and B cell counts and 2) the predictive value of pharmacokinetic and -dynamic parameters, patient, disease and treatment characteristics in relation to response to ultra-low dose rituximab. METHODS: For 140 RA patients from the REDO trial, differences in drug levels, ADA and B cell counts were examined at baseline, three and six months after dosing. Treatment response was defined as absence of flare and no extra rituximab or > 1 glucocorticoid injection received during follow-up. The association between potential predictors and response was investigated using logistic regression analyses. RESULTS: Lower doses of rituximab resulted in lower drug levels but did not significantly affect ADA levels and B cell counts. 3 (10.7%), 12 (20.7%) and 7 (13.0%) patients failed to meet response-criteria in respectively the 1000 mg, 500 mg and 200 mg group. Drug levels, ADA and B cell counts as well as patient, disease and treatment characteristics were not predictive for response to ultra-low dose rituximab. CONCLUSION: Results of this study further support that continued treatment with 500 or 200 mg rituximab is similarly effective as 1000 mg in RA patients doing well on rituximab. These results, combined with absence of clinical dose response relation in the original REDO study, suggest that 200 mg rituximab is not yet the lowest effective rituximab retreatment dose in RA.
35434407 Effects of Locomotion Training on the Physical Functions and Quality of Life in Patients w 2022 OBJECTIVES: This study investigated the effects of locomotion training on physical functions and quality of life in patients with rheumatoid arthritis (RA). METHODS: Thirty-five patients with RA underwent locomotion training for 6 months. Health data collected from the subjects at baseline and after 6 months were the Health Assessment Questionnaire Disability Index (HAQ-DI), pain Visual Analog Scale, 10-m walking test, Timed Up-and-Go (TUG) test, single-leg standing test, Short Form-8 score with physical and mental component summaries, and 25-question Geriatric Locomotive Function Scale. The primary endpoint was a change in HAQ-DI at 6 months. RESULTS: In terms of the primary outcome, the HAQ-DI significantly improved from 0.48 ± 0.69 at baseline to 0.27 ± 0.36 at 6 months (P=0.011). The significant secondary outcomes were a change in TUG test for comfortable walking from 9.8 ± 2.1 s at baseline to 8.9 ± 2.0 s at 6 months (P=0.002) and increased single-leg standing times for the right and left legs from 24.7 ± 23.5 s and 22.6 ± 22.8 s at baseline to 30.9 ± 22.1 s and 32.4 ± 24.1 s at 6 months (P=0.004, P <0.001), respectively. CONCLUSIONS: The findings suggest that locomotion training for 6 months may improve the HAQ-DI in patients with RA.