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ID PMID Title PublicationDate abstract
34053968 The Effect of Teriparatide for the Treatment of Multiple Spontaneous Clinical Vertebral Fr 2021 May Discontinuation of denosumab is associated with the risk of rebound in bone turnover and rebound-associated spontaneous clinical vertebral fractures. This case report presents an 86-year-old woman with rheumatoid arthritis who experienced rebound-associated spontaneous clinical vertebral fractures at 9 months after denosumab discontinuation. Following 5-year bisphosphonate treatment, the patient had 9 injections of 60-mg denosumab every 6 months. Because of tooth extraction, denosumab treatment was discontinued, and raloxifene was administered. At 9 months after the last denosumab injection, the patient experienced severe low back pain. Magnetic resonance imaging (MRI) and radiograph demonstrated clinical fracture at the fourth lumbar vertebra. MRI performed at 3 months after first fracture showed two additional fractures at the second and third lumbar vertebrae. Teriparatide was administered for management of rebound-associated spontaneous clinical, multiple vertebral fractures. Teriparatide was effective for accelerating the fracture healing and suppressing the occurrence of new fractures. However, 2-year treatment of teriparatide did not have suppressive effect of rebound in bone turnover and general bone loss. This case suggested that teriparatide was effective for suppression of new rebound-associated spontaneous clinical vertebral fractures, but not effective in prevention of general bone loss after denosumab discontinuation.
34426413 Tumor Necrosis Factor Inhibitors and the Risk of Cancer among Older Americans with Rheumat 2021 Nov BACKGROUND: TNF inhibitors (TNFi) effectively treat rheumatoid arthritis but may increase patient risk of some malignancies, particularly lymphomas or skin cancers. METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to conduct a case-control study in patients with rheumatoid arthritis (2007-2015). Cases were individuals with a first cancer diagnosed in SEER registries (ages 66-99, 22 cancer sites, N = 10,263). Skin cancer cases [nonmelanoma skin cancer (NMSC, N = 501), basal cell carcinoma (BCC, N = 161), squamous cell carcinoma (SCC, N = 150)] and cancer-free controls (N = 30,475) were selected from Medicare beneficiaries residing in SEER areas. Cases and controls had prior Medicare claims-based evidence for rheumatoid arthritis, and TNFi exposure was ascertained from part B and part D claims. Logistic regression was used to estimate adjusted odds ratios (aOR). RESULTS: TNFi exposure was present in 16.2% of controls and 12.8% to 33.7% of cancer cases, varying by site. TNFi use was associated with increased risk of NMSC overall (aOR 1.32, 95% confidence interval 1.06-1.63), non-Hodgkin lymphoma (NHL) overall (1.28, 1.06-1.56) and, specifically, follicular lymphoma (2.63, 1.63-4.24). TNFi exposure was not associated with other SEER cancer sites, BCC or SCC specifically, or other common NHL subtypes. CONCLUSIONS: Among older adults with rheumatoid arthritis, TNFi exposure was associated with elevated risk of NMSC and NHL, driven specifically by follicular lymphoma. Exposure was not associated with increased risk for other cancer sites. IMPACT: Our results support a role for TNF in lymphomagenesis. Given the association with NMSC, patients initiating TNFi therapy may benefit from skin cancer screening and sun protection measures.
33634330 Investigating the relationship between the severity of periodontitis and rheumatoid arthri 2021 Aug OBJECTIVES: This paper evaluates the prevalence and severity of periodontitis (PD) in patients with rheumatoid arthritis (RA), focusing on the link between the severity of PD with RA disease activity/disability scores, the influence of RA treatment on PD, and levels of vitamin D. METHODS: A total of 93 RA patients were enrolled in the cross-sectional study and analyzed accordingly as RA-PD (N = 63, 67.8%) and RA-only (N = 30, 32.2%) groups. A number of associations between rheumatological clinical data, i.e., Disease Activity Score (DAS28 CRP), health assessment questionnaires, and PD severity (measured by periodontal outcome parameters) with regard to serum levels of vitamin D were assessed. The outcome variables were compared by parametric and non-parametric tests. RESULTS: A total of 29% of RA patients were diagnosed with severe PD. The RA-PD group presented a higher mean DAS28 CRP score in moderate-severe PD compared to periodontally healthy-initial stage PD subjects (4.49 ± 1.22 vs. 3.86 ± 1.58, p = 0.033). RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) were less likely to be diagnosed with PD (p = 0.022) and revealed significantly lower PD outcome parameters, i.e., bleeding on probing (%) and bone loss (%) (p < 0.05). Vitamin D concentration was significantly lower in RA-PD group with diagnosed advanced severe PD (IV stage) compared to moderate PD (II stage) (39.61 ± 17.12 vs. 52.07 ± 18.23 nmol/l, p = 0.031). CONCLUSIONS: The study revealed a high prevalence of severe PD in RA patients, being significantly associated with higher RA disease activity and lower vitamin D level in RA-PD group, while bDMARD treatment was related to lower PD outcome parameters. Key Points • Severe PD is prevalent amongst RA patients and is associated with RA disease activity. The higher RA DAS28 CRP score is associated with moderate-severe PD compared to periodontally healthy-initial stage PD in RA patients. • Biologic DMARDs treatment used for RA is linked to lower PD rates and PD outcome parameters. • Significantly lower vitamin D level is found in advanced severe PD compared to moderate PD stage in RA-PD subjects.
33359768 Incidence and risk of developing rheumatic diseases in 19,724 patients with palindromic rh 2021 May OBJECTIVES: The spectrum of progression of palindromic rheumatism (PR) to chronic diseases is quite variable. Hence, this study aimed to investigate the incidence and risk of developing rheumatic diseases in PR using nationwide, population-based medical claims data from Korea. METHODS: We assessed the incidence rate (IR) of PR in the population in the given year. After matching individuals with PR with those without PR (1:10) for age, gender, and the index year, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard model. RESULTS: A total of 19,724 newly diagnosed incident PR cases were identified from 2010 to 2016. The mean age was 50.2±14.9 years. The incidence of PR was 7.02 (95% CI 6.92-7.12) per 100,000 person-years (6.22 and 7.80 in men and women, respectively). During observation, 8.79% patients with PR and 0.30% individuals without PR developed various outcome diseases. Patients with PR had an increased risk of seropositive rheumatoid arthritis (HR 46.51, 95% CI [41.05-52.69]), psoriatic arthritis (44.79 [15.16-132.35]), systemic lupus erythematosus (24.53 [16.15-37.24]), mixed connective tissue disease (22.01 [7.65-63.34]), Behçet's disease (21.04 [13.81-32.06]), Sjögren's syndrome (12.36 [8.54-17.88]), ankylosing spondylitis (9.00 [6.67-12.15]), dermatomyositis/polymyositis (6.14 [2.55-14.82]), and systemic sclerosis (3.75 [1.47-9.58]) compared with individuals without PR. CONCLUSIONS: This nationwide, population-based cohort study demonstrated that about one-eleventh of patients with PR eventually develop systemic rheumatic diseases and that patients with PR have an increased risk of developing various rheumatic diseases including seropositive rheumatoid arthritis.
33576925 Four-year follow-up of atherogenicity in rheumatoid arthritis patients: from the nationwid 2021 Aug OBJECTIVE: This study aimed to evaluate the impact of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) on lipid profile and atherogenic index of plasma (AIP) in rheumatoid arthritis (RA) patients and to compare the occurrence of dyslipidemia between patients using bDMARDs, tsDMARDs, or conventional DMARDs (cDMARDs). METHODS: Data on lipid profile, AIP, and occurrence of dyslipidemia were collected from the Korean College of Rheumatology BIOlogics registry. A comparison was conducted between patients using bDMARDs (tumor necrosis factor (TNF)-α inhibitor, tocilizumab, abatacept), Janus kinase inhibitors (JAKis), and cDMARDs. The Kaplan-Meier method was used to compare the occurrence of dyslipidemia between groups, and hazard ratios (HR) were calculated using the cox proportional hazard method. RESULTS: The data of 917, 826, 789, 691, and 520 RA patients were eligible for analysis at the baseline, 1-year, 2-year, 3-year, and 4-year follow-ups, respectively. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were higher in the cDMARDs group, whereas AIP was comparable. During the 4-year follow-up, AIP was comparable between the groups. The occurrence of dyslipidemia did not show a significant difference when comparing the bDMARDs/tsDMARDs and cDMARDs groups (P=0.06) or the TNF-α inhibitor, tocilizumab, abatacept, JAKi, and cDMARD user groups (P=0.3). In the multivariate cox proportional hazard model, older age (HR=1.03, P=0.005) and concomitant hypertension (HR=2.21, P=0.013) were significantly associated with dyslipidemia occurrence. CONCLUSION: Long-term use of bDMARDs and tsDMARDs is relatively safe with regard to lipid profile, AIP, and the occurrence of dyslipidemia in RA patients. Key Points • The use of bDMARDs and tsDMARDs did not increase the risk of dyslipidemia than cDMARDs use in patients with RA. • AIP was comparable between bDMARDs user, tsDMARDs user, and cDMARDs user group in 4-year follow-up data. • Based on the present study, the long-term use of bDMARDs or tsDMARDs did not significantly deteriorate atherogenic lipid profile nor an increased risk of dyslipidemia in patients with RA.
33741804 Impact of rheumatoid arthritis and biologic and targeted synthetic disease modifying antir 2021 May 1 PURPOSE OF REVIEW: Several new therapeutic drugs are now available for the management of rheumatoid arthritis (RA). Given that RA has been associated with an increased risk of certain cancers like lymphoma and lung cancer, concern remains about the safety of (newer) immunosuppressants used in RA management as it relates to the risk of cancer. RECENT FINDINGS: Most meta-analyses of randomized clinical trials of tumor necrosis factor inhibitors (TNFi) have not observed an association between TNFi and risk of incident cancer. Studies of non-TNFi biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs and cancer are also reassuring but limited and of short-term follow-up. Regarding the use of DMARDs in patients with RA and a prior malignancy, retrospective studies have shown that TNFi use is not associated with recurrence. SUMMARY: There is a need for ongoing studies on the safety of non-TNFi bDMARDs and targeted synthetic disease modifying anti-rheumatic drugs and recurrent cancer. Further research is also needed to guide the patients, rheumatologists, and oncologists regarding the safest DMARDs to choose for patients with RA and a recent diagnosis of cancer.
33548531 Rheumatoid Arthritis Increases Risk of Medical Complications Following Posterior Lumbar Fu 2021 May BACKGROUND: Rheumatoid arthritis (RA) is a systemic disease with prominent musculoskeletal manifestations that is associated with increased morbidity and mortality in patients undergoing cervical spine surgery; however, few studies have specifically examined postoperative outcomes in patients with RA following lumbar surgery. The aim of this study was to evaluate whether patients with RA who underwent posterior lumbar fusion experienced increased postoperative complications and economic burden compared with patients without RA. METHODS: Patients <85 years old who underwent elective 1- or 2-level instrumented posterior lumbar fusion for degenerative lumbar pathology between 2006 and 2012 were identified in the Medicare insurance claims database. Same-day revisions and cases for spinal infection, malignancy, and trauma were excluded. The resulting cohort was divided into patients with RA before fusion and patients without RA (controls). All outcomes of interest were compared using multivariate regression. Reoperation-free survival at 1- and 2-year follow-up was analyzed used log-rank test. Significance was defined as P < 0.05. RESULTS: RA patients had significantly higher risk of 90-day readmission (odds ratio [OR] = 1.27, P < 0.001), thromboembolic events (OR = 1.39, P = 0.010), sepsis (OR = 2.32, P < 0.001), pneumonia (OR = 1.57, P = 0.001), and wound complications (OR = 1.41, P < 0.001). Reoperation-free survival was significantly lower in RA patients at 2-year follow-up (90.4% vs. 92.4%, P < 0.001). Following adjusted regression, RA independently contributed to a $1491 increase in additional 90-day costs (P < 0.001). CONCLUSIONS: Preexisting RA may increase risk for short-term postoperative medical complications following posterior lumbar fusion, specifically infectious events. In addition, patients with RA have higher rates of subsequent reoperation following index surgery. Patients with RA be should counseled regarding these risks.
34620675 Association between previous rheumatoid arthritis and COVID-19 and its severity: a nationw 2021 Oct 7 OBJECTIVES: The prevalence of rheumatoid arthritis (RA) among patients with COVID-19 and the association between RA and the outcome of COVID-19 remain unclear. We aimed to compare the prevalence of RA between participants with and without COVID-19; we then analysed the association between the presence of RA and the severity of COVID-19. DESIGN: A cross-sectional study. SETTING: Data from a nationwide COVID-19 cohort database by the Korea National Health Insurance Corporation were used. PARTICIPANTS AND INTERVENTIONS: A total of 8070 patients with COVID-19 (1 January 2020 through 4 June 2020) were matched with 32 280 control participants with regard to age, sex and income. Patients with COVID-19 were confirmed by SARS-CoV-2 PCR and controls were collected from the database. RA was confirmed using the diagnostic code (International Classification of Disease, Tenth Revision) and medication claim codes. Conditional/unconditional logistic regression was applied to analyse the association between RA and COVID-19. PRIMARY OUTCOME AND SECONDARY OUTCOME: Laboratory confirmation of SARS-CoV-2 infection was defined as the primary outcome. The secondary outcome was severe COVID-19 defined as a history of intensive care unit admission, invasive ventilation or death. RESULTS: The prevalence of RA in the COVID-19 (0.4%, 35/8070) and control (0.4%, 121/32,280) groups did not differ (p=0.446). After adjusting for underlying diseases, no association between RA and COVID-19 was observed (adjusted OR=1.14, 95% CI: 0.78 to 1.67) and COVID-19 severity was not associated with RA (adjusted OR=0.62, 95% CI: 0.14 to 7.29). The overall mortality rate was 2.9% (237/8070) and RA was not significantly associated with mortality (adjusted OR=1.64, 95% CI: 0.33 to 8.15). CONCLUSION: We did not find an association between the presence of RA and COVID-19. In addition, RA was not associated with the severity of COVID-19.
34783974 The Effect of α7nAChR Signaling on T Cells and Macrophages and Their Clinical Implication 2022 Mar Rheumatoid arthritis (RA) is one of the most common autoimmune disease and until now, the etiology and pathogenesis of RA is not fully understood, although dysregulation of immune cells is one of the leading cause of RA-related pathological changes. Based on current understanding, the priority of anti-rheumatic treatments is to restore immune homeostasis. There are several anti-rheumatic drugs with immunomodulatory effects available nowadays, but most of them have obvious safety or efficacy shortcomings. Therefore, the development of novel anti-rheumatic drugs is still in urgently needed. Cholinergic anti-inflammatory pathway (CAP) has been identified as an important aspect of the so-called neuro-immune regulation feedback, and the interaction between acetylcholine and alpha 7 nicotinic acetylcholine receptor (α7nAChR) serves as the foundation for this signaling. Consistent to its immunomodulatory functions, α7nAChR is extensively expressed by immune cells. Accordingly, CAP activation greatly affects the differentiation and function of α7nAChR-expressing immune cells. As a result, targeting α7nAChR will bring profound therapeutic impacts on the treatment of inflammatory diseases like RA. RA is widely recognized as a CD4(+) T cells-driven disease. As a major component of innate immunity, macrophages also significantly contribute to RA-related immune abnormalities. Theoretically, manipulation of CAP in immune cells is a feasible way to treat RA. In this review, we summarized the roles of different T cells and macrophages subsets in the occurrence and progression of RA, and highlighted the immune consequences of CAP activation in these cells under RA circumstances. The in-depth discussion is supposed to inspire the development of novel cell-specific CAP-targeting anti-rheumatic regimens.
34036753 Prevalence of chronic obstructive pulmonary disease in patients with rheumatoid arthritis: 2021 Jun OBJECTIVE: Rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) are both chronic inflammatory diseases; the prevalence of COPD in RA patients is known to be high. However, the prevalence of both RA and COPD differs according to sex; the relationship between RA and COPD may also vary according to sex. Therefore, we investigated the prevalence of COPD and its association in patients with RA in Korea by sex. METHODS: We conducted a nationwide cross-sectional study using data from the Korea National Health and Nutrition Examination Survey. A total of 12 417 men and 15 878 women were included. In this study, RA was defined as physician diagnosed or currently under RA treatment. COPD was defined based on spirometry results, chronic symptoms, and smoking history. Multivariable logistic regression models were employed and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for COPD prevalence in patients with RA. RESULTS: The prevalence of COPD was 15.5% in men with RA, 3.5% in women with RA, 7.8% in men without RA, and 2.2% in women without RA. After adjustment for potential confounding variables, including smoking status, RA was significantly associated with COPD in men (OR 2.16, 95% CI 1.06-4.40), but not in women (OR 1.58, 95% CI 0.81-3.10). CONCLUSIONS: In Korea, the prevalence of COPD was high in patients with RA of both sexes; RA and COPD was significantly likely to be associated in men, but not in women.
33827788 Efficacy and safety of tofacitinib versus baricitinib in patients with rheumatoid arthriti 2021 Sep OBJECTIVES: The differences of efficacy between each Janus kinase (JAK) inhibitors have not been clarified in the patients with rheumatoid arthritis (RA) in clinical practice. Here, we compared the efficacy between tofacitinib (TOFA) and baricitinib (BARI) in clinical practice. METHODS: The efficacy of TOFA (n=156) in patients with RA was compared with BARI (n=138). Selection bias was reduced to a minimum using propensity score-based inverse probability of treatment weighting (IPTW). The Clinical Disease Activity Index (CDAI) trajectory for patients who started TOFA or BARI was analysed using growth mixture modelling (GMM). RESULTS: No significant difference was observed in patient characteristics between the TOFA and BARI groups in after adjustment by propensity score-based IPTW. The BARI group had a significantly higher rate of CDAI remission at week 24 after the introduction of JAK inhibitors than the TOFA group. The treatment-resistant group defined by GMM, comprising patients who did not achieve low disease activity at week 24, was more likely to include those who had received many biological disease-modifying antirheumatic drugs (bDMARDs) before the introduction of JAK inhibitors and those who received TOFA. Among patients with RA who received TOFA, those who had received ≥4 bDMARDs before the introduction of TOFA were more likely to be classified into the treatment-resistant group. CONCLUSIONS: BARI showed a similar safety profile and better clinical outcome when compared with TOFA after reduction to a minimum of selection bias. However, these were observed in a small population. Accordingly, further investigation is required in an accurately powered head-to-head trial.
33407587 Three hematologic/immune system-specific expressed genes are considered as the potential b 2021 Jan 6 BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic autoimmune connective tissue disease. However, early RA is difficult to diagnose due to the lack of effective biomarkers. This study aimed to identify new biomarkers and mechanisms for RA disease progression at the transcriptome level through a combination of microarray and bioinformatics analyses. METHODS: Microarray datasets for synovial tissue in RA or osteoarthritis (OA) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by R software. Tissue/organ-specific genes were recognized by BioGPS. Enrichment analyses were performed and protein-protein interaction (PPI) networks were constructed to understand the functions and enriched pathways of DEGs and to identify hub genes. Cytoscape was used to construct the co-expressed network and competitive endogenous RNA (ceRNA) networks. Biomarkers with high diagnostic value for the early diagnosis of RA were validated by GEO datasets. The ggpubr package was used to perform statistical analyses with Student's t-test. RESULTS: A total of 275 DEGs were identified between 16 RA samples and 10 OA samples from the datasets GSE77298 and GSE82107. Among these DEGs, 71 tissue/organ-specific expressed genes were recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs are mostly enriched in immune response, immune-related biological process, immune system, and cytokine signal pathways. Fifteen hub genes and gene cluster modules were identified by Cytoscape. Eight haematologic/immune system-specific expressed hub genes were verified by GEO datasets. GZMA, PRC1, and TTK may be potential biomarkers for diagnosis of early RA. NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158- miR-212-3p/miR-132-3p/miR-129-5p-TTK might be potential RNA regulatory pathways to regulate the disease progression of early RA. CONCLUSIONS: This work identified three haematologic/immune system-specific expressed genes, namely, GZMA, PRC1, and TTK, as potential biomarkers for the early diagnosis and treatment of RA and provided insight into the mechanisms of disease development in RA at the transcriptome level. In addition, we proposed that NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158-miR-212-3p/miR-132-3p/miR-129-5p-TTK are potential RNA regulatory pathways that control disease progression in early RA.
33523968 Critical role of synovial tissue-resident macrophage niche in joint homeostasis and suppre 2021 Jan Little is known about the mechanisms regulating the transition of circulating monocytes into pro- or anti-inflammatory macrophages in chronic inflammation. Here, we took advantage of our novel mouse model of rheumatoid arthritis, in which Flip is deleted under the control of a CD11c promoter (HUPO mice). During synovial tissue homeostasis, both monocyte-derived F4/80(int) and self-renewing F4/80(hi) tissue-resident, macrophage populations were identified. However, in HUPO mice, decreased synovial tissue-resident macrophages preceded chronic arthritis, opened a niche permitting the influx of activated monocytes, with impaired ability to differentiate into F4/80(hi) tissue-resident macrophages. In contrast, Flip-replete monocytes entered the vacated niche and differentiated into tissue-resident macrophages, which suppressed arthritis. Genes important in macrophage tissue residency were reduced in HUPO F4/80(hi) macrophages and in leukocyte-rich rheumatoid arthritis synovial tissue monocytes. Our observations demonstrate that the macrophage tissue-resident niche is necessary for suppression of chronic inflammation and may contribute to the pathogenesis of rheumatoid arthritis.
33537769 Phenotype and treatment of elderly onset compared with younger onset rheumatoid arthriti 2021 Oct 2 OBJECTIVE: To identify possible differences in baseline characteristics, initial treatment and treatment response between RA patient subgroups based on age at disease onset. METHODS: Daily practice data from the worldwide METEOR registry were used. Patients (7912) were stratified into three age-groups (age at disease diagnosis <45 years, 45-65 years, >65 years). Initial treatment was compared between the different age-groups. With Cox regression analyses the effect of age-group on time-to-switch from first to second treatment was investigated, and with linear mixed models differences in response to treatment (DAS and HAQ) between the age-groups were assessed, after correction for potential confounders. RESULTS: The >65 years age-group included more men, and more seronegative RA with somewhat higher inflammatory markers. Initial treatment choices differed only slightly between the age-groups, and the time-to-switch from initial treatment to the next was similar. DAS and HAQ improvement were dependent on the age-group, reflected by a significant interaction between age-group and outcome. The stratified analysis showed a difference of -0.02 and -0.05 DAS points and, -0.01 and 0.02 HAQ points per month in the <45 and 45-65 years age-groups as compared with the >65 year age group, a difference that did not seem clinically relevant. CONCLUSION: In this international study on worldwide clinical practice, patients with RA onset >65 years include more men and seronegative arthritis, and were initially treated slightly differently than younger patients. We observed no clinically relevant differences in timing of a next treatment step, or response to treatment measured by DAS and HAQ.
33969680 Encephalomyelitis associated with rheumatoid arthritis: a case report. 2021 Encephalitis/encephalomyelitis in the course of rheumatoid arthritis (RA) remains a matter of debate. We present a case of a patient with encephalomyelitis associated with RA confirmed with post-mortem neuropathological examination. A 68-year-old woman with a long-standing, seropositive history of RA presented progressive disturbances of consciousness. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed an increase of signal intensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images with corresponding restricted diffusion involving cerebral peduncles, pons, medulla oblongata, and cervical spinal cord and mild contrast-enhancement of the right cerebral peduncle. Extensive radiological and laboratory testing, including autoantibodies to paraneoplastic anti-neuronal and neuronal cell surface antigens, were all negative except for elevated rheumatoid factor. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with mononuclear cell predominance, mildly increased protein level, and negative viral PCRs, bacterial cultures, flow cytometry, and neuronal surface antibodies. Despite intensive treatment with corticosteroids, antibiotics, antiviral drugs, and intravenous immunoglobulin the patient died after 3 months of hospitalization. Post-mortem neuropathological examination revealed numerous, disseminated, heterochronous ischaemic lesions, rarely with haemorrhagic transformation, predominantly in the brainstem, and widespread, diffuse microglia and T-cell infiltrations with neuronal loss and astrogliosis, most severe in the frontal and temporal lobes. Mild, perivascular lymphocyte T infiltrations involved particularly small and medium-sized vessels and were associated with brainstem ischaemic lesions. The neuropathological picture confirmed diagnosis of encephalomyelitis, which together with the clinical course suggested association with RA. Concluding, encepha-lomyelitis due to RA remains a challenging, controversial entity that needs further research and the establishment of effective diagnostic and treatment guidelines.
33962594 Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rhe 2021 May 7 BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).
34698449 Pain catastrophizing hinders Disease Activity Score 28 - erythrocyte sedimentation rate re 2021 Dec AIM: This study aimed to assess the relationship between pain catastrophizing and achievement of 28-joint Disease Activity Score-defined remission of rheumatoid arthritis (RA), considering the presence or absence of systemic inflammation, and to evaluate associated factors for pain catastrophizing. METHOD: This cross-sectional study included 421 RA outpatients. The relationship between pain catastrophizing and remission was analyzed by adjusting several confounding factors. Univariable and multivariable analyses were performed to determine the relationship between pain catastrophizing and RA-related factors, comorbidities, and lifestyle habits. RESULTS: The prevalence of pain catastrophizing was 26%. Pain catastrophizing was negatively associated with remission (odds ratio 0.62, 95% confidence interval 0.38-1.00, P = .048). A multinomial logistic analysis showed that the presence of pain catastrophizing was an independent factor that was negatively correlated with the achievement of remission in the absence of systemic inflammation (odds ratio 0.51, 95% confidence interval 0.28-0.93, P = .029). Factors associated with elevated ratings on the Pain Catastrophizing Scale were a history of falls within the past year, a Health Assessment Questionnaire score >0.5, and smoking habit. Further, patients' subjective symptoms, including patient global assessment minus evaluator global assessment values ≥20 and high tender joint count minus swollen joint counts, were associated with elevated pain catastrophizing. CONCLUSION: Pain catastrophizing is a major obstacle to achieving remission in RA patients with normal C-reactive protein levels. Advanced physical disability, smoking habit, and history of falls were associated with pain catastrophizing, in addition to patients' subjective symptoms.
34426116 Mechanistic insights into the role of B cells in rheumatoid arthritis. 2021 Oct Rheumatoid arthritis (RA) is an autoimmune disease epitomized by severe inflammation that induces tendon, cartilage, and bone damage over time. Although different types of cells undertake pathogenic functions in RA, the B cell's significant involvement has increasingly been known following the development of rheumatoid factor and it has been re-emphasized in recent years. Therefore, the rheumatoid factors and anti-cyclic citrullinated peptide antibodies are well-known indications of infection and clinical manifestations, and that they can precede the development of illness by several years. The emergence of rituximab a B cell reducing chimeric antidote in 1997 and 1998 transformed B-cell-targeted therapy for inflammatory disorder from a research hypothesis to a functional fact. Ever since, several autoantibody-related conditions were addressed, including the more intriguing indications of effectiveness seen in rheumatoid arthritis patients. Numerous types of B-cell-targeted compounds are currently being researched. From the beginning, one of the primary goals of B-cell therapy was to reinstate some kind of immune tolerance. While B cells have long been recognized as essential autoantibody producers, certain antibody-independent functions and usefulness as a key targeted therapy were not recognized until recently. The knowledge of B cells' diverse physical and pathogenic roles in autoimmune diseases is growing. As a result, the number of successful agents targeting the B cell complex is becoming more ubiquitous. Therefore, in this article, we explore fresh perspectives upon the roles of B cells in arthritis treatment, as well as new evidence regarding the effectiveness of B lymphocytes reduction and the therapeutic outcome of biological markers.
34444236 Potential Short-Term Air Pollution Effects on Rheumatoid Arthritis Activity in Metropolita 2021 Aug 11 Rheumatoid arthritis (RA) flare is related to increased joint damage, disability, and healthcare use. The impact of short-term air pollution exposure on RA disease activity is still a matter of debate. In this cross-sectional study, we investigated whether short-term exposure to particulate matter (PM)(10), PM(2.5), nitrogen dioxide (NO(2)), and ozone (O(3)) affected RA disease activity (DAS28 and SDAI) in 422 consecutive RA residents in Lombardy, North of Italy. Air pollutant concentrations, estimated by Regional Environmental Protection Agency (Lombardy-Italy) at the municipality level, were used to assign short-term exposure from the day of enrolment, back to seven days. Some significant negative associations emerged between RA disease activity, PM(10), and NO(2), whereas some positive associations were observed for O(3). Patients were also stratified according to their ongoing Disease-Modifying anti-Rheumatic Drugs (DMARDs) treatment: no DMARDs (n = 25), conventional synthetic DMARDs (n = 108), and biological or targeted synthetic DMARDs (n = 289). Therapy interaction seemed partially able to influence the relationship between short-term air pollution exposure and RA disease activity (PM(2.5) levels and DAS28 at the day of the visit-O(3) levels and disease activity scores for the seven days before the evaluation). According to our results, the impact of short-term air pollution exposure (seven days) minimally impacts disease activity. Moreover, our study suggests therapy could alter the response to environmental factors. Further evidence is needed to elucidate determinants of RA flare and its management.
32980634 Targeted silver nanoparticles for rheumatoid arthritis therapy via macrophage apoptosis an 2021 Jan Infiltration of inflammatory cells, especially the M1 macrophages that secrete various types of inflammation cytokines, play crucial roles in the pathogenesis of rheumatoid arthritis (RA). To relief synovial inflammation, M1 macrophages must be eliminated or switched to anti-inflammatory M2 phenotype. We herein developed folic acid modified silver nanoparticles (FA-AgNPs) that can actively deliver into M1 macrophages to synergistically induce M1 macrophages reduction and M2 macrophages polarization for effective RA treatment. The AgNPs was facilely prepared, PEGylated and modified with FA to realize M1 macrophages targeting delivery via folate receptor overexpressed on M1 macrophages surface. After entering cells, FA-AgNPs dissolved and released Ag(+) in response to intracellular glutathione (GSH), which is the key element to exert a series of anti-inflammatory functions, such as M1 macrophages apoptosis and reactive oxygen species (ROS) scavenging to facilitate M2 macrophages polarization, both of which contributed to RA treatment. This nano-system could passively accumulate into inflamed joints, permit potent anti-inflammatory activity, and impose strong therapeutic efficacy in mice RA models with high biosafety. After treatment, FA-AgNPs could be gradually cleared from the body mainly via feces without tissue accumulation, and did not show any appreciable long-term toxicity. This work declares the first example of using bio-active nanoparticles for RA treatment without loading any drugs, and highlights the potential of FA-AgNPs for targeted RA therapy via simultaneous M1 macrophage apoptosis and M1-to-M2 macrophages re-polarization.