Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 34262002 | Preliminary Screening Questionnaire for Sjögren's Syndrome in the Rheumatology Setting. | 2022 Mar 1 | OBJECTIVE: Sjögren's syndrome (SS) is frequently undetected or misdiagnosed as other rheumatologic diseases. We aimed to develop an SS screening questionnaire for the rheumatology practice. METHODS: We developed the Sjögren's Syndrome Screening Questionnaire (SSSQ) via secondary analysis of data from 974 participants referred by rheumatologists to the Sjögren's International Collaborative Clinical Alliance (SICCA) study. Participants answered 88 questions regarding symptoms, medical history, and demographics. They underwent ocular, dental, and serologic tests and were classified as SS or non-SS using the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria. We conducted univariate and multivariate logistic regression to identify questions most discriminative of SS, from which we derived an individual's likelihood of SS ("SSSQ score"). RESULTS: Five questions were significantly discriminative of SS in the multivariate analysis (p < 0.05): (1) Can you eat a cracker without drinking a fluid/liquid? (no: odds ratio [OR], 1.39; 95% confidence interval [CI], 1.06-1.82]); (2) How would you describe your dental and oral health in general? (fair/poor: OR, 1.68; 95% CI, 1.04-2.75); (3) During the last week, have you experienced tearing? (none of the time: OR, 2.26; 95% CI, 1.23-4.34); (4) Are you able to produce tears? (no: OR, 1.62; 95% CI, 1.12-2.37); and (5) Do you currently smoke cigarettes? (no: OR, 2.83; 95% CI, 1.69-4.91). SSSQ score ≥7 (possible range, 0-11) distinguishes SS from non-SS patients with 64% sensitivity and 58% specificity (area under receiver operating characteristic curve, 0.65). CONCLUSIONS: The SSSQ is a simple 5-item questionnaire designed to screen for SS in clinical practice, with a potential impact to reduce delays in diagnosis. | |
| 35323194 | Reactivity of Rheumatoid Arthritis-Associated Citrulline-Dependent Antibodies to Epstein-B | 2022 Mar 11 | Rheumatoid arthritis (RA) is a chronic disease which causes joint inflammation and, ultimately, erosion of the underlying bone. Diagnosis of RA is based on the presence of biomarkers, such as anti-citrullinated protein antibodies (ACPA) and rheumatoid factors, along with clinical symptoms. Much evidence points to a link between the Epstein-Barr virus and RA. In this study, we analyzed ACPA reactivity to citrullinated peptides originating from Epstein-Barr nuclear antigens (EBNA1, EBNA2, and EBNA3) in order to elaborate the diagnostic potential of citrullinated EBNA peptides. Moreover, ACPA cross-reactivity to citrullinated peptides from myelin basic protein (MBP) was analyzed, as citrullinated MBP recently was described to be associated with multiple sclerosis, and some degree of sequence homology between MBP and citrullinated EBNA exists. A peptide from EBNA2, (EBNA2-A, GQGRGRWRG-Cit-GSKGRGRMH) reacted with approximately 70% of all RA sera, whereas only limited reactivity was detected to EBNA1 and EBNA3 peptides. Moreover, screening of ACPA reactivity to hybrid peptides of EBNA3-A (EPDSRDQQS-Cit-GQRRGDENRG) and EBNA2-A and peptides containing citrulline close to the N-terminal confirmed that ACPA sera contain different populations of ACPAs. No notable ACPA reactivity to MBP peptides was found, confirming that ACPAs are specific for RA, and that other factors than the presence of a central Cit-Gly motif are crucial for antibody binding. Collectively, these findings illustrate that citrullinated EBNA2 is an optimal candidate for ACPA detection, supporting current evidence that EBV is linked to RA onset. | |
| 35136972 | Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid art | 2022 Feb 8 | OBJECTIVE: Over proliferation of synovium is a key event of invasive pannus formation and cartilage damage in the progression of rheumatoid arthritis (RA) disease. At the same time, ferroptosis may play a pivotal role in maintaining the balance of proliferation and death of synovium. In this study, we firstly evaluated the ferroptosis level in RA fibroblast-like synoviocytes (FLS) and then explored the role of glycine in ferroptosis. METHODS: Ferroptosis was evaluated in RA synovium and FLS. The therapeutic effect of glycine on RA was evaluated by clinical and histopathological score and cytokine level in a collagen-induced arthritis (CIA) mouse model. The influence of glycine on ferroptosis was evaluated by mitochondrial morphology observation and membrane potential assay in RA FLS. Methylase expression was detected to explore the mechanism behind the effect of glycine on glutathione peroxidase 4 (GPX4) methylation. RESULTS: Compared with healthy controls (HC), ferroptosis decreased in the RA synovium and FLS, with a decrease in Acyl Coenzyme A Synthetase Long Chain 4 (ACSL4) and an increase in Ferritin heavy chain 1(FTH1), GPX4, and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation and antioxidation levels of lipids were higher in RA FLS than in HC, the increase in antioxidation was slightly higher than oxidation. RNA-Seq and verification showed that glycine regulated the ferroptosis pathway through increase S-adenosylmethionine (SAM) concentration and decrease the expression of GPX4 and FTH1 by promoting SAM-mediated GPX4 promoter methylation and reducing FTH1 expression in RA FLS. CONCLUSIONS: In summary, we confirmed a decline in ferroptosis in RA and explored that glycine enhanced ferroptosis via SAM-mediated GPX4 promoter methylation and ferritin decrease. | |
| 34962619 | Comparison of Clinical Manifestations in Rheumatoid Arthritis vs. Spondyloarthritis: A Sys | 2022 Apr | INTRODUCTION: Misclassification of spondyloarthritis (SpA) as rheumatoid arthritis (RA) may lead to delayed SpA diagnosis and suboptimal therapeutic outcomes. Here, we evaluate the literature on clinical manifestations in patients with SpA and RA, particularly seronegative RA, to understand the potential overlap, distinctions, and most reliable approaches to accurate diagnosis. METHODS: In this systematic literature review, conducted according to PRISMA guidelines, we searched key biomedical databases for English-language publications of original research articles (up to July 23, 2020) and rheumatology conference abstracts (January 1, 2018-July 31, 2020) reporting key SpA clinical presentations in patients with SpA or RA. Publications were assessed for eligibility by two independent reviewers; discrepancies were resolved by a third. Studies were evaluated for publication quality using the Downs and Black checklist. RESULTS: Of 4712 records retrieved, 79 met the inclusion criteria and were included in the analysis. Of these, 54 included study populations with SpA and RA, and 25 with seropositive and/or seronegative RA. Entheseal abnormalities were more frequently reported among patients with SpA than RA and with seronegative vs. seropositive RA. Psoriasis, nail psoriasis, and dactylitis were exclusively seen in SpA vs. RA. In most publications (70 of 79), advanced imaging techniques allowed for more accurate distinction between SpA and RA. Overlapping clinical characteristics occur in SpA and RA, including inflammation and destruction of joints, pain, diminished functional ability, and increased risk for comorbidities. However, of 54 studies comparing SpA and RA populations, only seven concluded that no distinction can be made based on the SpA manifestations and outcomes examined. CONCLUSIONS: Typical SpA-related clinical symptoms and signs were observed in patients with RA, suggesting that misclassification could occur. Availability of advanced imaging modalities may allow for more prompt and comprehensive evaluation of peripheral manifestations in SpA and RA, reducing misclassification and delayed diagnosis. | |
| 35095899 | Cytohesin-2/ARNO: A Novel Bridge Between Cell Migration and Immunoregulation in Synovial F | 2021 | The guanine nucleotide exchange factor cytohesin-2 (ARNO) is a major activator of the small GTPase ARF6 that has been shown to play an important role(s) in cell adhesion, migration and cytoskeleton reorganization in various cell types and models of disease. Interestingly, dysregulated cell migration, in tandem with hyper-inflammatory responses, is one of the hallmarks associated with activated synovial fibroblasts (SFs) during chronic inflammatory joint diseases, like rheumatoid arthritis. The role of ARNO in this process has previously been unexplored but we hypothesized that the pro-inflammatory milieu of inflamed joints locally induces activation of ARNO-mediated pathways in SFs, promoting an invasive cell phenotype that ultimately leads to bone and cartilage damage. Thus, we used small interference RNA to investigate the impact of ARNO on the pathological migration and inflammatory responses of murine SFs, revealing a fully functional ARNO-ARF6 pathway which can be rapidly activated by IL-1β. Such signalling promotes cell migration and formation of focal adhesions. Unexpectedly, ARNO was also shown to modulate SF-inflammatory responses, dictating their precise cytokine and chemokine expression profile. Our results uncover a novel role for ARNO in SF-dependent inflammation, that potentially links pathogenic migration with initiation of local joint inflammation, offering new approaches for targeting the fibroblast compartment in chronic arthritis and joint disease. | |
| 35450218 | The Causal Relationship Between Rheumatoid Arthritis and Mechanical Complications of Prost | 2022 | The causal effects of rheumatoid arthritis (RA) on complications of arthroplasty are yet to be established. This study was the first to explore the causal effect of RA on mechanical complications of prosthesis through two-sample Mendelian randomization (MR). In the MR analysis, RA was selected as the exposure in this study while single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) were selected as the instrumental variables (IVs). Summary statistics data on mechanical complications of prosthesis was extracted from publicly available GWAS data, including 463,010 European descent individuals. MR analysis was performed using the standard inverse variance weighted method (IVW). Furthermore, other methods (MR Egger, weighted median, simple mode, and weighted mode) were also done to verify the results. Finally, the sensitivity analysis was executed. Results of the standard IVW showed that RA possibly increases the risk of mechanical complications of prosthesis [OR = 1.000255; 95% CI = (1.0001035, 1.000406); p = 9.69 × 10 (-4) ]. This outcome was also verified by other methods including weighted median [OR = 1.000285; 95% CI = (1.0001032, 1.000466); p = 1.41 × 10(-3)], simple mode [OR = 1.000446; 95% CI = (1.0001116, 1.000781); p = 1.04 × 10(-2)], and weighted mode [OR = 1.000285; 95% CI = (1.0001032, 1.000466); p = 2.29 × 10(-3)]. No heterogeneity and directional pleiotropy was observed upon sensitivity analysis, indicating the stability and reliability of the result. In summary, the present study showed that RA potentially increases the risks of complications of prosthesis, which might provide guidance in arthroplasty on RA patients. | |
| 35128973 | Patient Goals for Living with Rheumatoid Arthritis: A Qualitative Study. | 2022 Feb 7 | Rheumatoid arthritis is highly individualized in terms of its flare ups and periods of remission. Each patient's unique experience requires a high level of personalization in terms of treatment making it necessary to understand what their goals for living are. This study explores patient perceptions on how the burden of RA shapes patients' goals for living and their preferences for symptom and side-effect management within the United States. Fifteen patients diagnosed with RA with varying lengths of diagnosis were interviewed. A thematic analysis was conducted to construct a conceptual framework. Emerging themes identified disease burdens as: (1) inability to perform essential needs, (2) negative feelings about disease, and (3) its influence on relationships. These burdens shaped desired goals for living which guided the symptom and side-effect priorities the patient wanted managed. Practitioners should consider patient goals and preferences in conjunction with disease progression when engaging in treatment decisions. | |
| 35033680 | Frailty in rheumatoid arthritis: A systematic review and meta-analysis. | 2022 Jan 13 | OBJECTIVE: Rheumatoid arthritis (RA) may cause damage to multiple organs and may further restrict the patient's physical, psychological and social functions. This meta-analysis aimed to explore the prevalence of frailty and prefrailty and the influential factors in RA patients. METHODS: PubMed, Web of Science, Cochrane, Embase, and CNKI were searched to identify related articles. Articles published before July 23rd, 2021 that assessed frailty in patients with RA qualified for the systematic review and meta-analysis. A quality appraisal of the studies was performed using the Agency for Healthcare Research and Quality and Newcastle-Ottawa Scales. The pooled results were displayed as odds ratios or standardized mean differences (ORs/SMDs) and 95% confidence intervals (CIs). RESULTS: The article search generated 2273 articles, of which 16 satisfied the inclusion criteria and were merged in the final review. A total of 8556 RA patients were finally included. The pooled prevalence of frailty in the patients with RA was 33.5% (95% CI: 25.2-41.7%), and the pooled prevalence of prefrailty was 39.9% (95% CI: 29.4-50.3%). Subgroup analyses showed that frailty was more prevalent in females (24.7%) than in males (19.1%). The prevalence of prefrailty in females was similar to that in males among the RA patients. Frailty in RA was associated with the female sex (OR: 1.47, 95% CI: 1.04-2.07) and disease activity (OR: 1.47, 95% CI: 1.03-2.09). CONCLUSION: Frailty is prevalent in RA patients. Female gender and disease activity are associated with the prevalence of frailty in RA patients. | |
| 35634355 | Cell-based therapies for rheumatoid arthritis: opportunities and challenges. | 2022 | Rheumatoid arthritis (RA) is the most common immune-mediated inflammatory disease characterized by chronic synovitis that hardly resolves spontaneously. The current treatment of RA consists of nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic and targeted synthetic DMARDs. Although the treat-to-target strategy has been intensively applied in the past decade, clinical unmet needs still exist since a substantial proportion of patients are refractory or even develop severe adverse effects to current therapies. In recent years, with the deeper understanding of immunopathogenesis of the disease, cell-based therapies have exhibited effective and promising interventions to RA. Several cell-based therapies, such as mesenchymal stem cells (MSC), adoptive transfer of regulatory T cells (Treg), and chimeric antigen receptor (CAR)-T cell therapy as well as their beneficial effects have been documented and verified so far. In this review, we summarize the current evidence and discuss the prospect as well as challenges for these three types of cellular therapies in RA. | |
| 35330353 | Comparison of Adalimumab to Other Targeted Therapies in Rheumatoid Arthritis: Results from | 2022 Feb 25 | Few studies compared adalimumab to other targeted therapies in head-to-head randomized clinical trials (RCTs) for rheumatoid arthritis (RA), but multiple comparisons are not available. This Bayesian Network Meta-Analysis evaluated which targeted therapy is more likely to achieve ACR50 response with good safety at 24 weeks of treatment in RA. A systematic literature review was conducted for head-to-head phase 3 RCTs that compared adalimumab to other targeted therapies in combination with methotrexate (MTX) or as monotherapy to treat RA patients, and searched through MEDLINE, EMBASE, Cochrane Library and Clinicaltrial.gov. The outcomes of interest were ACR50 response and withdrawals due to adverse events at 24 weeks. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses, using a random effect model. Sixteen studies were included in the analysis. The most favorable SUCRA for the ACR50 response rate at 24 weeks of treatment in combination with MTX was ranked by upadacitinib, followed by baricitinib, tofacitinib and filgotinib. As monotherapy, the highest probability was ranked by tocilizumab followed by sarilumab. No significant differences in safety profile among treatment options were found. Jak-inhibitors in combination with MTX and interleukin-6 antagonism as monotherapy showed the highest probability to achieve ACR50 response after 24 weeks of treatment. None of assessed targeted therapies were associated to risk of withdrawal due to adverse events. Key messages: Direct and indirect comparison between adalimumab and other targeted therapies demonstrated some differences in terms of efficacy that may help to drive RA treatment. Jak-inhibitors and interleukine-6 antagonists ranked as first in the probability to achieve ACR50 response after 24 weeks of treatment in combination with methotrexate or monotherapy, respectively. | |
| 35141743 | Number Needed to Treat and Cost Per Responder of Janus Kinase Inhibitors Approved for the | 2022 Feb 10 | OBJECTIVE: This study evaluated the effectiveness and cost-effectiveness of baricitinib, tofacitinib and upadacitinib regimens, compared to conventional synthetic disease-modifying antirheumatic drug (csDMARD) alone, among Japanese patients with moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to csDMARD, measured in terms of number needed to treat (NNT) and cost per responder (CPR). METHODS: Efficacy data were derived from two recent network meta-analyses among global and Japanese population. The cost perspective was that of the Japanese Health Service. Both NNT and CPR were based on disease activity score for 28 joints with C-reactive protein (DAS28-CRP) remission and American College of Rheumatology (ACR)20/50/70 at 12 and 24 weeks. RESULTS: Over 12 weeks, the median NNT and the median CPR to achieve DAS28-CRP remission were 4.3 and JPY 1,799,696 [USD 16,361], respectively, for upadacitinib 15mg + csDMARD. The equivalent results were 6.0 and JPY 2,691,684 [USD 24,470] for baricitinib 4mg + csDMARD and 5.6 and JPY 2,507,152 [USD 22,792] for tofacitinib 5mg + csDMARD. Similar rankings were observed at 24 weeks and for other outcomes. CONCLUSIONS: Upadacitinib 15mg was associated with the lowest NNT and CPR among the three JAK inhibitors used in treatment regimens for Japanese patients with moderate-to-severe RA inadequately responsive to csDMARD. | |
| 35303379 | Ethical issues experienced by persons with rheumatoid arthritis in a wearable-enabled phys | 2022 Mar 18 | INTRODUCTION: Using wearables to self-monitor physical activity is a promising approach to support arthritis self-management. Little is known, however, about the context in which ethical issues may be experienced when using a wearable in self-management. We used a relational ethics lens to better understand how persons with rheumatoid arthritis (RA) experience their use of a wearable as part of a physical activity counselling intervention study involving a physiotherapist (PT). METHODS: Constructivist grounded theory and a relational ethics lens guided the study design. This conceptual framework drew attention to benefits, downsides and tensions experienced in a context of relational settings (micro and macro) in which participants live. Fourteen initial and eleven follow-up interviews took place with persons with RA in British Columbia, Canada, following participation in a wearable-enabled intervention study. RESULTS: We created three main categories, exploring how experiences of benefits, downsides and tensions when using the intervention intertwined with shared moral values placed on self-control, trustworthiness, independence and productivity: (1) For some, using a wearable helped to 'do something right' by taking more control over reaching physical activity goals. Some, however, felt ambivalent, believing both there was nothing more they could do and that they had not done enough to reach their goal; (2) Some participants described how sharing wearable data supported and challenged mutual trustworthiness in their relationship with the PT; (3) For some, using a wearable affirmed or challenged their sense of self-respect as an independent and productive person. CONCLUSION: Participants in this study reported that using a wearable could support and challenge their arthritis self-management. Constructing moral identity, with qualities of self-control, trustworthiness, independence and productivity, within the relational settings in which participants live, was integral to ethical issues encountered. This study is a key step to advance understanding of ethical issues of using a wearable as an adjunct for engaging in physical activity from a patient's perspective. PATIENT OR PUBLIC CONTRIBUTION: Perspectives of persons with arthritis (mostly members of Arthritis Research Canada's Arthritis Patient Advisory Board) were sought to shape the research question and interpretations throughout data analysis. | |
| 35505588 | Comorbidities in Black South Africans with established rheumatoid arthritis. | 2022 May 3 | OBJECTIVE: Comorbidities contribute both to morbidity and mortality in rheumatoid arthritis (RA). The aim of the current study was to investigate the prevalence and spectrum of comorbidities in South Africans with established RA. METHODS: A retrospective, consecutive case record review of 500 Black South African patients with established disease of ≥5 years attending a tertiary rheumatology service was performed. Common comorbidities including those listed in the Charlson Comorbidity Score (CCS) were documented. RESULTS: Most patients, 463 known alive (AG) and 37 known deceased (DG), were female (87%). Mean (SD) age and disease duration were 60 (11.1) and 10.7 (5.0) years respectively, and 98% had ≥1 comorbidities. Median CCS was 2, significantly higher in DG than AG (4 vs 2, P < .0001). Despite hypertension (70%) and hypercholesterolemia (47%) being the commonest comorbidities overall and type 2 diabetes (T2D) occurring in 15.4%, clinical cardiovascular events were rare (0.6%). Peptic ulcer disease (odds ratio [OR] = 8.67), congestive cardiac failure (OR = 7.09), serious infections (OR = 7.02) and tuberculosis (OR = 2.56) were significantly more common in DG than AG. Multivariate analysis showed that American College of Rheumatology functional class 3/4 was associated with increased risk for serious infections (OR = 3.84) and tuberculosis (OR = 2.10). CONCLUSION: Despite the high burden of cardiometabolic comorbidities in South Africans with established RA, cardiovascular events were rare. Serious infections and tuberculosis, both associated with severe functional disability, are a major cause of morbidity and mortality. | |
| 35444834 | Mitochondria Transfer to CD4(+) T Cells May Alleviate Rheumatoid Arthritis by Suppressing | 2022 | CD4(+) T cells contribute to the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). These cells infiltrate the joints of RA patients and produce cytokines, including Tumor necrosis factor (TNF)-α, that drive joint inflammation and bone destruction. Although biologic therapeutics targeting T cells and TNF-α have benefited patients suffering from RA, some patients are refractory to these therapies, develop antibodies that neutralize these biologics, or develop undesirable side effects. Recent studies indicate that CD4(+) T cell cytokine production is regulated in part by specific metabolic modules, suggesting that immunometabolic pathways could represent a novel therapeutic strategy for T cell-mediated diseases such as RA. Wu et al. (2021) demonstrate that mitochondrial function is impaired in CD4(+) T cells from RA patients, leading to reduced levels of various citric acid cycle metabolites (e.g., aspartate) that regulate TNF-α production. Treatment of RA-associated T cells with purified mitochondria was sufficient to restore these metabolic defects, limit production of numerous pro-inflammatory cytokines such as TNF-α and IL-17A, and reduce the development of RA-like disease in a humanized mouse model. These data suggest that T cells can be metabolically "re-engineered" ex vivo with exogenous mitochondria and that this mitochondria transfer approach confers anti-inflammatory properties that may reduce disease severity in RA and possibly other rheumatologic diseases. Increasing our understanding of how intercellular mitochondria transfer occurs may identify novel biological pathways that can be targeted therapeutically or harnessed to support cell engineering. | |
| 35387158 | Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheum | 2022 Dec | Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis and destruction of cartilage, promoted by sustained inflammation. However, current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint. Inspired by neutrophil chemotaxis for inflammatory region, we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles (uPB-Exo) via click chemistry, inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties. uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes, subsequently neutralizing pro-inflammatory factors, scavenging reactive oxygen species, and alleviating inflammatory stress. In addition, uPB-Exo effectively targeted to inflammatory synovitis, penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system, leading to precise diagnosis of RA in vivo with high sensitivity and specificity. Particularly, uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation, thereby significantly ameliorating joint damage. Therefore, nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic. | |
| 35134981 | Potential of the Prognostic Nutritional Index to Determine the Risk Factor for Severe Infe | 2022 Feb 4 | OBJECTIVE: To investigate the influence of nutritional status on severe infection complications in patients with rheumatoid arthritis (RA). METHODS: This retrospective cohort study on 2,108 Japanese patients with RA treated at our hospital in April 2016 evaluated the prognostic nutritional index (PNI) as an index of nutritional status. Patients were classified into the high or low PNI group according to the cutoff PNI value (45.0). Based on propensity score matching analysis, 360 patients in each group were selected for comparing the incidence of serious infection, clinical findings, and PNI scores. RESULTS: The incidence of infection was significantly higher in the low PNI group than in the high PNI group (p < 0.001). The occurrence rate of infectious complication at 104 weeks was significantly higher in the low PNI (<45.0) group than in the high PNI group (p < 0.001), but Cox hazards regression analysis showed that low PNI was not a risk factor of severe infections (hazard ratio 1.080, 95% confidence interval 0.933-1.250, p = 0.300). The incidence of infection was particularly high in elderly patients (≥65 years) with a low PNI, but the incidence in elderly patients with a high PNI was similar to that in nonelderly patients with a high PNI. CONCLUSIONS: Patients with RA and malnutrition had a higher incidence of severe infection; thus, evaluating and managing nutritional status is necessary for the appropriate and safe treatment of elderly patients with RA. | |
| 35464950 | The Potential of Gut Microbiota Metabolic Capability to Detect Drug Response in Rheumatoid | 2022 | Gut microbiota plays an essential role in the development of rheumatoid arthritis (RA) and affects drug responses. However, the underlying mechanism remains elusive and urgent to elucidate to explore the pathology and clinical treatment of RA. Therefore, we selected methotrexate (MTX) as an example of RA drugs to explore the interactions between the gut microbiota and drug responses and obtain an in-depth understanding of their correlation from the perspective of the metabolic capability of gut microbiota on drug metabolism. We identified 2,654 proteins and the corresponding genes involved in MTX metabolism and then profiled their abundances in the gut microbiome datasets of four cohorts. We found that the gut microbiota harbored various genes involved in MTX metabolism in healthy individuals and RA patients. Interestingly, the number of genes involved in MTX metabolism was not significantly different between response (R) and non-response (NR) groups to MTX, but the gene composition in the microbial communities significantly differed between these two groups. Particularly, several models were built based on clinical information, as well as data on the gene, taxonomical, and functional biomarkers by using the random forest algorithm and then validated. Our findings provide bases for clinical management not only of RA but also other gut microbiome-related diseases. First, it suggests that the potential metabolic capability of gut microbiota on drug metabolism is important because they affect drug efficiency; as such, clinical treatment strategies should incorporate the gene compositions of gut microbial communities, in particular genes involved in drug metabolism. Second, a suitable model can be developed to determine hosts' responses to drugs before clinical treatment. | |
| 35043719 | Outcomes of Pyrocarbon Arthroplasty in Metacarpophalangeal Joints Affected by Rheumatoid A | 2022 Jan 19 | BACKGROUND: Rheumatoid arthritis (RA) affecting the metacarpophalangeal (MCP) joint may warrant arthroplasty. The purpose of this study was to investigate implant survivorship, complications, radiographic outcomes, and clinical outcomes in patients undergoing MCP arthroplasty with a pyrocarbon implant to treat RA. METHODS: In all, 124 MCP joint pyrocarbon arthroplasties in 40 patients performed to treat RA were reviewed. Operations were at the index (n = 43, 35%), middle (n = 33, 27%), ring (n = 27, 22%), and small (n = 21, 17%) fingers from 1998 to 2009 in 105 (85%) female and 19 (15%) male joints with a mean age of 54 ± 11 years. Mean postoperative follow-up was 6 ± 3 years. All patients achieved at least 2 years of follow-up. RESULTS: Rates of implant survivorship at 1, 2, 5, and 10 years were 98%, 98%, 90%, and 81%, respectively. Fifteen percent (n = 18) of arthroplasties underwent revision at a mean 5 ± 3 years postoperatively. The overall reoperation rate was 29% (n = 36). Rates of survival from reoperation at 1, 2, 5, and 10 years were 85%, 84%, 76%, and 68%, respectively. Complications occurred in 32% (n = 40). Pain ratings improved postoperatively (P < .01). Arc of motion improved from 37 ± 21 to 43 ± 19 (P = .03). Both appositional and oppositional strength improved after surgery; however, there was no improvement in grip strength (P < .01). CONCLUSIONS: Metacarpophalangeal arthroplasty with a pyrocarbon implant demonstrated reliable improvement in pain and arc of motion in patients with RA. Complication and overall reoperation rates were high, while 1 in 10 undergo revision within 5 years postoperatively. | |
| 34921355 | Frequency and Duration of Early Non-serious Adverse Events in Patients with Rheumatoid Art | 2022 Apr | INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This post hoc analysis assessed frequency or duration of early select non-serious adverse events (AEs; excluding infections), and their impact on treatment discontinuation, in patients with RA or PsA treated with tofacitinib 5 or 10 mg twice daily, or placebo. METHODS: Data were pooled from five phase 3 and one phase 3b/4 studies in patients with moderate-to-severe RA, and two phase 3 studies in patients with active PsA. Select all-causality, non-serious AEs, reported to month 3 (placebo-controlled period), were headache, diarrhea, nausea, vomiting, and gastric discomfort (including dyspepsia, gastritis, epigastric discomfort, and abdominal discomfort or pain); incidence rates (unique patients with events per 100 patient-years of follow-up), duration of, and discontinuations due to these non-serious AEs were reported. RESULTS: We analyzed 3871 and 710 patients with RA and PsA, respectively. Incidence of non-serious AEs to month 3 was generally similar with tofacitinib and placebo. The most frequent non-serious AEs were headache and diarrhea with tofacitinib, and dyspepsia, nausea, and headache with placebo. Most events were mild or moderate in severity, lasting ≤ 4 weeks. Permanent discontinuations due to non-serious AEs were not observed in patients with PsA, and were < 1.0% in patients with RA across treatment groups. The most frequent cause of temporary discontinuation across all groups was gastric discomfort (0.3-0.8%). CONCLUSIONS: Non-serious AE incidence was generally similar in patients with RA or PsA receiving tofacitinib or placebo. Most events were mild or moderate and generally resolved within 4 weeks. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01877668; NCT01882439; NCT02187055. | |
| 35645419 | Assessment of quality of life in patients with Lyme arthritis and rheumatoid arthritis. | 2022 | OBJECTIVES: Patients' quality of life is one of the key concepts of modern medicine, which characterizes the role of physical and mental functioning in the course of the disease. This article presents a stratification of factors influencing the quality of life in patients with rheumatoid arthritis (RA) and Lyme arthritis (LA). MATERIAL AND METHODS: Ninety patients with RA were included in this study among them n = 44 (48.89%) also with LA diagnosis and n = 46 (51.11%) with RA. All studied patients were examined and questioned according to the Health Assessment Questionnaire-Disability Index and the 36-Item Short Form Survey (SF-36) to assess their quality of life. The disease activity score with examination of 28 joints was used to assess the activity of the disease. Multiple regression analysis was used to determine the most significant factors influencing patients' quality of life. RESULTS: Patients who agreed to participate in the study had high and moderate disease activity; however, patients with LA showed significantly higher baseline data on the intensity of the inflammatory process. According to the analysis of the questionnaire responses, a significantly reduced physical activity of both groups was revealed, but patients with LA had significantly worse BP (p = 0.002), GH (p = 0.006), and Mental Component Summary scales (p = 0.001). The greatest relationship between disease activity and quality of life by Physical Component Summary according to SF-36 (r = -0.80) was found in patients with LA and (r = -0.72) - with RA. CONCLUSIONS: The presence of Borrelia burgdorferi in patients with arthritis not only significantly reduced the motor activity of patients, but also complicated the mental adaptation to their own disease. Factors that affect the quality of life - the activity and duration of the disease in patients of both cohorts, and age and total number of affected joints - for patients with RA. |