Browse

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

ID PMID Title PublicationDate abstract
34550600 The molecular structure and role of LECT2 or CHM-II in arthritis, cancer, and other diseas 2022 Jan Leukocyte cell-derived chemotaxin-2 (LECT2 or LECT-2), also called chondromodulin II (ChM-II or CHM2) plays a versatile role in various tissues. It was first identified as a chemotactic factor to promote the migration of neutrophils. It was also reported as a hepatokine to regulate glucose metabolism, obesity, and nonalcoholic fatty liver disease. As a secreted factor, LECT2 binds to several cell surface receptors CD209a, Tie1, and Met to regulate inflammatory reaction, fibrogenesis, vascular invasion, and tumor metastasis in various cell types. As an intracellular molecule, it is associated with LECT2-mediated amyloidosis, in which LECT2 misfolding results in insoluble fibrils in multiple tissues such as the kidney, liver, and lung. Recently, LECT2 was found to be associated with the development of rheumatoid arthritis and osteoarthritis, involving the dysregulation of osteoclasts, mesenchymal stem cells, osteoblasts, chondrocytes, and endothelial cells in the bone microenvironment. LECT2 is implicated in the development of cancers, such as hepatocellular carcinoma via MET-mediated PTP1B/Raf1/ERK signaling pathways and is proposed as a biomarker. The mechanisms by which LECT2 regulates diverse pathogenic conditions in various tissues remain to be fully elucidated. Further research to understand the role of LECT2 in a tissue tropism-dependent manner would facilitate the development of LECT2 as a biomarker for diagnosis and therapeutic target.
35325802 Aberrant functional connectivity between anterior cingulate cortex and left insula in asso 2022 Mar 15 BACKGROUND: Brain activity is reported to be associated with individual pain susceptibility and inflammatory status, possibly contributing to disease activity assessment in inflammatory arthritis (IA) including rheumatoid arthritis (RA) and spondyloarthritis (SpA). However, what alteration of brain function associated with disease activity and therapeutic effectiveness in IA remains unclear. We aimed to identify the alterations of brain functional connectivity (FC) shared in both RA and SpA, and evaluate its relationship to anti-rheumatic treatment response using functional magnetic resonance imaging (MRI). PATIENTS AND METHODS: Structural and resting-state functional MRI data were acquired from patients with IA, patients with osteoarthritis (OA) and heathy controls (HCs). Two datasets were adopted to derive (51 IA, 56 OA, and 17 HCs) and validate (31 IA) the observations. 33 IA patients in the derivation dataset and all the patients in validation dataset required biological treatment and were clinically evaluated before and after therapy. Via whole-brain pair-wise FC analyses, we analyzed IA-specific FC measures relevant to therapeutic response to biologics. RESULTS: The value of FC between left insular cortex (IC) and anterior cingulate cortex (ACC) was significantly low in IA patients compared with OA patients and HCs. We demonstrated that the FC between left anterior long insular gyrus as a subdivision of IC and ACC was significantly associated with therapeutic response to biologics regarding the improvement of patients' global assessment (PGA) in both derivation and validation datasets. CONCLUSION: Disease-specific resting-state FC provides a means to assess the therapeutic improvement of PGA and would be a clinical decision-making tool with predictability for treatment response in both RA and SpA.
35614946 Effects of Pereskia aculeate Miller Petroleum Ether Extract on Complete Freund's Adjuvant- 2022 Objective: To investigate the therapeutic effect of petroleum ether extract of P. aculeate Miller (PEEP) on rheumatoid arthritis (RA). Methods: In vitro: The Cell Counting Kit-8 (CCK-8) was used to detect cell activity and select the optimal concentration of the extract; the effective site was screened by nitric oxide (NO) colorimetric method and Q-PCR method; the expression of p38, p-p38, p-MK2, and Tristetraprolin (TTP) in RAW 264.7 cells were detected by Western blot. In vivo: The rat model was established by complete Freund's adjuvant (CFA). The different doses of PEEP on CFA rats were observed with life status, paw swelling, spleen index, X-ray, Hematoxylin eosin (HE) staining; the secretion of Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and Prostaglandin E2 (PGE(2)) were detected by Enzyme linked immunosorbent assay (ELISA); the expressions of p38, p-p38, p-MK2, and TTP in the ankle joints of CFA rats were detected by Western blot. Result: In vitro: PEEP, Ethyl Acetate Extract of P. aculeate Miller (EEEP), N-butanol Extract of P. aculeate Miller (BEEP) have no toxic effects on RAW264.7 macrophages. PEEP, EEEP, and BEEP reduce the secretion of NO in RAW264.7 cells induced by lipopolysaccharide (LPS), only PEEP significantly inhibited the mRNA expression levels of inflammatory factors TNF-α and IL-6; PEEP-dependently reduce the secretion of TNF-α and IL-6, decrease the expression of p-p38 and p-MK2, and the level of TTP phosphorylation in LPS-induced RAW264.7 cells. In vivo: PEEP improve the living conditions of CFA rats, reduce foot swelling, spleen index, bone surface erosion and joint space narrowing; reduce the formation of synovial cells, inflammatory cells and pannus in the foot and ankle joints. PEEP reduce the secretion of TNF-α, IL-6, PGE(2) in rat serum, downregulate the expression of p-p38 and p-MK2 in the ankle joint, and reduce the phosphorylation of TTP. Conclusion: PEEP improve the living conditions of CFA rats, reduce the degree of foot swelling, protect immune organs, reduce inflammatory cell infiltration, cartilage damage, pannus formation, reduce inflammation and RA damage. The mechanism through regulating the signal pathway of p38 mitogen-activated protein kinase (p38/MAPK), which reduces the release of TNF-α, IL-6, and PGE(2) in the serum.
35500150 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 in rheumatoid arthritis 2022 May 2 BACKGROUND: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) correlates with treatment outcomes in inflammatory bowel disease and rheumatoid arthritis (RA). This study aimed to further evaluate the MALT1 longitudinal change and its relationship with tumor necrosis factor inhibitors (TNFi) response in RA patients. METHODS: Seventy-one RA patients receiving TNFi [etanercept (n = 42) or adalimumab (n = 29)] were enrolled. MALT1 was detected by RT-qPCR in peripheral blood samples of RA patients before treatment (W0), at week (W)4, W12, and W24 after treatment. RA patients were divided into response/non-response, remission/non-remission patients according to their treatment outcome at W24. Meanwhile, MALT1 was also detected by RT-qPCR in 30 osteoarthritis patients and 30 healthy controls (HCs). RESULTS: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 was elevated in RA patients compared with HCs (Z=-6.392, p < 0.001) and osteoarthritis patients (Z = -5.020, p < 0.001). In RA patients, MALT1 was positively correlated with C-reactive protein (r(s)  = 0.347, p = 0.003), but not other clinical characteristics, treatment history, or current TNFi category. Meanwhile, MALT1 decreased from W0 to W12 in total RA patients (x(2)  = 86.455, p < 0.001), etanercept subgroup (x(2)  = 46.636, p < 0.001), and adalimumab subgroup (x(2)  = 41.291, p < 0.001). Moreover, MALT1 at W24 (p = 0.012) was decreased in response patients compared with non-response patients; MALT1 at W12 (p = 0.027) and W24 (p = 0.010) were reduced in remission patients than non-remission patients. In etanercept subgroup, MALT1 at W24 (p = 0.013) was decreased in response patients compared with non-response patients. In adalimumab subgroup, MALT1 at W24 (p = 0.015) was lower in remission patients than non-remission patients. CONCLUSION: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 reduction after treatment is associated with response and remission to TNFi in RA patients.
35211491 The Aftermath of Tapering Tocilizumab After Achieving Treatment Target in Patients With Rh 2022 BACKGROUND: Although recent guidelines recommend that tapering of biologic disease-modifying anti-rheumatic drugs (bDMARDs) can be considered in patients with rheumatoid arthritis (RA), there has been little evidence supporting the strategy during the non-tumor necrosis factor inhibitor treatment. This study aims to investigate the effectiveness and safety of tapering tocilizumab (TCZ) dose in patients with RA who attain low disease activity (LDA) after TCZ therapy in a nationwide cohort. METHODS: Data were collected from a nationwide cohort of patients with RA receiving biologic disease-modifying anti-rheumatic drugs in South Korea (KOBIO-RA). This study included 350 patients who were treated with TCZ and achieved Clinical Disease Activity Index-low disease activity (CDAI)-LDA (CDAI ≤ 10) after 1 year of treatment. We performed longitudinal analysis considering clinical data measured at all 1-year intervals for the included patients using the generalized estimating equation. A total of 575 intervals were classified into two groups according to their dose quotient (DQ) of TCZ (tapering group vs. standard-dose group). The main outcome was maintaining CDAI-LDA in the following 1-year interval. RESULTS: Tapering TCZ dose strategy was used in 282 (49.0%) intervals with a mean (SD) DQ of 66.0 (15.5) %. Loss of CDAI-LDA occurred in 91 (15.1%) intervals. Multivariable GEE showed that the tapering group was associated with more frequent failure to sustain CDAI-LDA (adjusted OR [95% CI]: 0.57 [0.33-0.99]), which subsequently led to impaired functional status. The likelihood of achieving DAS28-deep remission (DAS28-ESR <1.98) was also significantly lower in the tapering group (adjusted OR 0.68 [0.46-0.99]). CDAI remission was achieved in only 69 (12.0%) of the total intervals, with no significant difference in the proportion of intervals achieving the target between the two groups. Incidence of adverse events was comparable in both groups except for hypercholesterolemia, which was lower in the tapering group. CONCLUSIONS: Tapering TCZ dose after achieving LDA increases the risk of losing LDA without a significant merit in safety.
35142867 Toll-like receptor-7 activation in CD8+ T cells modulates inflammatory mediators in patien 2022 Feb 10 Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology with aberrant immunological responses leading to inflammation, swelling and pain of the joints. CD8(+) T cells have been known to be one of the major immune modulators in the progression of RA and the presence of toll-like receptors (TLRs) on these cells further accentuate their role in RA. Herein, we report an increased expression of TLR7 in the endosomes of CD8(+) T cells of RA patients correlating with disease severity. The stimulation of TLR7 with Imiquimod (IMQ) in these CD8(+) T cells drives the signalling cascade via NFkB and pERK activation and hence an increase in the mRNA transcripts of signature cytokines and cytolytic enzymes. However, a parallel synthesis of Tristetraprolin (TTP), an mRNA destabilizing protein prevents the translation of the mRNA transcripts, leading to a rapid degeneration of the target mRNA. We thus report that a direct TLR7 ligation by its agonist increases cytokine transcript signature but not an equivalent protein surge.
34917185 Influence of anti-TNF therapy and homocysteine level on carotid intima-media thickness in 2022 Jan It is a well-known fact that disruptions in the immune system and systemic inflammation are associated with accelerated atherosclerosis in rheumatoid arthritis (RA) patients. Elevated levels of tumor necrosis factor α (TNF-α), a major pro-inflammatory cytokine, are involved in endothelial cell activation of medium and large arteries, leading to increased endothelial permeability, generation of superoxide anion radical and hydrogen peroxide, and decreased availability of nitric oxide (NO). The present study aims to determine the influence of anti-TNF therapy and homocysteine (Hcy) levels on the carotid intima-media thickness (IMT) in patients with RA. Assessments were performed on 115 patients diagnosed with RA on biological treatment to determine the evolution of IMT and Hcy levels. Carotid ultrasonography was used to assess the IMT, as a fast and easy tool for the prediction of cardiovascular events in patients with RA. The first measurement of IMT was noted as IMT1, followed by a second measurement after 1 year, noted as IMT2. The group of patients was divided into approximately three equal groups, each being treated with a different biological product, respectively, etanercept, adalimumab, and infliximab. In the 3 groups, after 1 year of anti-TNF-α therapy, IMT2 progression was significantly reduced compared to baseline. No significant differences were found among the three groups of treatment. A strong association was observed between IMT1-IMT2 in the etanercept group (P<0.001, r=0.758), in the adalimumab group (P<0.001, r=0.761) and in the infliximab group (P<0.001, r=0.829). The low level of Hcy2 after 12 months of anti-TNF-α therapy was significantly correlated with a decrease in IMT2 (P<0.001) in patients who had a high level of Hcy and IMT >0.9 mm at baseline. The results from the present study showed that biological treatment and the low level of homocysteinemia reduced the cardiovascular risk in RA, regardless of the treatment chosen (infliximab, adalimumab, or etanercept).
34816388 Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patient 2022 Feb INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit-risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk-benefit of UPA versus adalimumab (ADA). METHODS: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria-PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles. RESULTS: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7-12), 48 weeks (NNTs: 9-16), and 156 weeks (NNTs: 9-15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA. CONCLUSION: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster).
35462548 Circulating CTRP5 in rheumatoid arthritis: an exploratory biomarker study. 2022 Apr 25 BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that is characterized by the overproduction of cytokines. Among the newly discovered cytokines are the adipokines which are primarily produced by and released from the adipose tissue and some immune cells, as well as synovial cells. they are involved in various immune responses and inflammatory processes. However, there are controversial data regarding the pro-inflammatory or anti-inflammatory effects of adipokines in different conditions. C1q/TNF-related protein 5 (CTRP5) is a newly identified adipokine and adiponectin paralogous protein, which has been shown to be correlated with inflammatory diseases. Accordingly, the present study was designed to investigate the serum levels of CTRP5 in RA patients and evaluate any possible alterations in comparison to healthy individuals. METHODS: Serum CTRP-5 levels were measured in 46 patients and 22 healthy controls by ELISA. The demographic, laboratory, and clinical features of the patients were also evaluated in order to find any correlations. RESULTS: Serum levels of CTRP-5 were significantly (p < 0.0001) higher in patients with RA (14.88 ± 25.55) compared to healthy controls (4.262 ± 2.374). There was a significant correlation between serum CTRP-5 levels and triglyceride (TG) (r: - 0.3010, p: 0.0498), as well as erythrocyte sedimentation rate (ESR) (r: 0.3139, p: 0.0457), C-reactive protein (CRP) (r: 0.5140, p: 0.0008), and the number of white blood cells (WBC) (r: 0.3380, p: 0.0307), which are considered as the markers indicating the extent of inflammation. Moreover, CTRP-5 was found to be correlated with interstitial lung disease (ILD) (r: 0.3416, p: 0.0385), a comorbidity associated with RA disease. CONCLUSION: This study demonstrated the increased level of circulating CTRP-5 in RA patients, which correlated with some inflammation-associated parameters and RA-associated comorbidities. Our observations suggest CTRP-5 as a putative inflammatory biomarker in RA, which may be useful besides the other disease-related markers.
35416949 COVID-19 infection and hospitalisation risk according to vaccination status and DMARD trea 2022 Apr 13 OBJECTIVES: To investigate the incidence of COVID-19 hospitalisation in unvaccinated and vaccinated patients with rheumatoid arthritis (RA) compared with matched controls, and in patients with RA according to DMARD treatment. METHODS: Danish nationwide matched cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalisation (Danish National Patient Register) and first-time positive SARS-CoV2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PY) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals. RESULTS: In total, 28 447 unvaccinated patients and 568 940 comparators had Irs for COVID-19 hospitalisation of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PY, respectively (aHR 1.88, 1.44-2.46). When fully vaccinated, corresponding Irs were 0.9 (0.5-1.6) and 0.5 (0.4-0.6) per 1000 PY (aHR 1.94, 1.03-3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09-1.57) for testing positive for SARS-CoV2 and 1.09 (0.92-1.14) among vaccinated. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalisation compared with conventional DMARD treated patients. CONCLUSION: The incidence of COVID-19 hospitalisation was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.
35432329 PAD4 Immunization Triggers Anti-Citrullinated Peptide Antibodies in Normal Mice: Analysis 2022 The critical immunological event in rheumatoid arthritis (RA) is the production of antibodies to citrullinated proteins (ACPAs), ie proteins on which arginines have been transformed into citrullines by peptidyl arginine deiminases (PAD). In C3H mice, immunization with PAD4 triggers the production of ACPAs. Here, we developed a peptide array to analyze the fine specificity of anti-citrullinated peptide antibodies and used it to characterize the ACPA response after hPAD4 immunization in mice expressing different H-2 haplotypes. Sera from C3H, DBA/2, BALB/c and C57BL/6 mice immunized with human PAD4 (hPAD4) or control-matched mice immunized with phosphate buffered saline (PBS) were used to screen peptide arrays containing 169 peptides from collagen, filaggrin, EBNA, proteoglycan, enolase, alpha and beta fibrinogen, histon and vimentin. Human PAD4 immunization induced antibodies directed against numerous citrullinated peptides from fibrinogen, histon 4 and vimentin. Most peptides were recognized under their arginine and citrullinated forms. DBA/2 and BALB/c mice (H-2d) had the lowest anti-citrullinated peptide IgG responses. C3H (H-2k) and BL6 mice (H-2b) had the highest anti-citrullinated peptide IgG responses. The newly developed peptide array allows us to characterize the ACPA production after hPAD4 immunization in mice on the H-2d, H-2k or H-2b backgrounds. This sensitive tool will be useful for further studies on mice for prevention of ACPA production by PAD tolerization.
35647047 Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Cardiovascula 2022 BACKGROUND: The nomenclature from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) is considered to identify more cardiovascular disease (CVD) risks in the general population. Patients with rheumatoid arthritis (RA) carry an excess risk for CVD. However, the prevalence of MAFLD and its relationship with CVD risks in RA have not been reported. METHODS: This cross-sectional study retrospectively analyzed clinical data from a Chinese RA cohort. MAFLD was diagnosed according to the criteria proposed by an international expert panel from 22 countries in 2020. CVD risk in patients with RA was estimated by the Prediction for Atherosclerotic Cardiovascular Disease Risk in China with a 1.5 multiplication factor. RESULTS: Among 513 included patients with RA, 78.4% were women and the mean ± SD age was 51.8 ± 12.6 years. The prevalence of MAFLD was 21.4%. There were 10.9% patients with RA concomitated with CVD events and 32.4% with a high-estimated 10-year CVD risk. Besides a higher liver fibrosis score and a higher ratio of advanced fibrosis, RA patients with MAFLD had a higher rate of CVD events (17.3 vs. 9.2%) and a higher proportion of high estimated 10-year CVD risk (55.5 vs. 26.1%) than those without. Multivariate logistic regression analysis showed that MAFLD was associated with an increase in CVD events [adjusted odds ratio (AOR) = 2.190, 95% CI 1.135-4.227] and high estimated 10-year CVD risk (AOR = 2.483, 95% CI 1.412-4.365, all p < 0.05). CONCLUSION: Metabolic dysfunction-associated fatty liver disease was associated with increased CVD risk in patients with RA, which implies the importance of early detection and management of MAFLD in patients with RA.
35460957 Complications of Scheker semiconstrained distal radioulnar joint arthroplasty in a low-vol 2022 Apr 20 Semiconstrained arthroplasty of the distal radioulnar joint (DRUJ) (Scheker prosthesis, Aptis Medical, Glenview, KY, USA) is a treatment option in case of irreparable destruction of the DRUJ. In our unit, a Scheker endoprosthesis was implanted in 5 wrists in 4 patients. 3/5 wrists (60%) in 3/4 patients (75%) underwent revision surgery. Reasons for revision surgery were implant loosening, periprosthetic fracture of the radius and suspicion of periprosthetic infection. Asymptomatic loosening of the screw of the radial head cover was detected in one wrist. Scheker arthroplasty is technically demanding. The prosthesis is prone to failure over the long term. Before implantation, all patients should be informed of the high risk of revision surgery.
35113363 Effectiveness of Etanercept in Rheumatoid Arthritis: Real-World Data from the German Non-i 2022 Apr BACKGROUND: For rheumatoid arthritis (RA), the treat-to-target concept suggests attaining remission or at least low disease activity (LDA) after 12 weeks. OBJECTIVES: This German, prospective, multicenter, non-interventional study aimed to determine the proportion of patients with RA who achieved their treat-to-target aim after 12 and 24 weeks of etanercept (ETN) treatment in a real-life setting, as opposed to patients achieving their therapeutic target at a later timepoint (week 36 or 52). METHODS: A total of 824 adults with a confirmed diagnosis of RA without prior ETN treatment were included. Remission and LDA were defined as DAS28 < 2.6 and DAS28 ≤ 3.2, respectively. RESULTS: The proportion of patients achieving remission was 24% at week 12 and 31% at week 24. The proportion of patients achieving LDA was 39% at week 12 and 45% at week 24. The proportion of patients achieving remission or LDA further increased beyond week 24 up to week 52. Improvement in pain and reduction in concomitant glucocorticoid treatment were observed. Improvements in patient-reported outcomes were also seen in patients who did not reach remission or LDA. No new safety signals were detected. CONCLUSIONS: A considerable proportion of patients with RA attained the target of remission or LDA after 12 weeks of ETN treatment. Even beyond that timepoint, the proportion of patients achieving treatment targets continued to increase up to week 52. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02486302.
35239551 Two-Staged Total Knee Arthroplasty in Juvenile Rheumatoid Arthritis with Severe Flexion De 2022 Mar 3 CASE: Juvenile rheumatoid arthritis (JRA) is associated with severe flexion contracture of the knees disabling a patient's ability to walk. Although various treatment modalities are available in the literature, we report a 2-stage procedure in a case of a 22-year-old female JRA patient with bilateral severe flexion deformity of the knee: stage 1-correction of the flexion contracture deformity by ring fixators and stage 2-total knee arthroplasty (TKA) for arthritis. To the best of our knowledge, no such approach has been reported previously. CONCLUSIONS: An Ilizarov ring fixator is a safe technique for gradual correction of a severe flexion deformity. Subsequent TKA can be performed as a standard procedure.
35325041 Elevations in Adipocytokines and Mortality in Rheumatoid Arthritis. 2022 Mar 23 OBJECTIVES: This study assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with rheumatoid arthritis (RA). METHODS: Participants were adults from the Veteran's Affairs RA Registry. Adipokines and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum at enrollment. Dates and causes of death were derived from the Corporate Data Warehouse and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox proportional hazard models evaluated associations between biomarkers and all-cause and cause-specific mortality. RESULTS: A total of 2,583 participants were included. Higher adiponectin levels were associated with older age, male sex, white race, lower body mass index (BMI), autoantibody seropositivity, radiographic damage, longer disease duration, prednisone use, and osteoporosis. Higher adiponectin concentrations were also associated with higher levels of inflammatory cytokines but not higher disease activity at enrollment. Leptin was primarily associated with greater BMI and comorbidity. The highest quartile of adiponectin (vs. lowest quartile) was associated with higher all-cause mortality [HR: 1.46 (95% CI: 1.11, 1.93) p = 0.009] and higher cardiovascular mortality [HR: 1.85 (95% CI: 1.24, 2.75) p = 0.003], after accounting for covariates. Higher leptin levels were also associated with greater all-cause and cancer mortality. CONCLUSIONS: Elevations in adipokines are associated with age, BMI, comorbidity, and severe disease features in RA and independently predict early death. Associations between adiponectin and inflammatory cytokines support the hypothesis that chronic subclinical inflammation promotes metabolic changes that drive elevations in adipokines and yield adverse health outcomes.
35253099 Synergy of sarcopenia and vitamin D deficiency in vertebral osteoporotic fractures in rheu 2022 Mar 6 OBJECTIVES: To explore the synergistic effect of vitamin D deficiency and sarcopenia on vertebral osteoporostic fracture (VF) in patients with rheumatoid arthritis (RA). METHODS: A total of 188 patients with RA and 158 control subjects were enrolled. Bone mineral density (BMD) at the total hip, neck of femur, lumbar vertebra 1-4, and skeletal muscle mass was measured by dual energy X-ray absorptiometry (DXA) and biological electrical impedance, respectively. Serum 25(OH)D was tested by electrochemiluminescence. The prevalence of VF and osteoporosis (OP) were compared between RA and controls. The synergism of sarcopenia and vitamin D deficiency on VF in patients with RA was tested by χ(2) test and logistic regression. RESULTS: The prevalence of OP at all measured sites and VF in RA patients were all higher than those in controls (P < 0.0001). The incidence of VF in RA either with sarcopenia or with vitamin D deficiency was higher than for those without sarcopenia or without vitamin D deficiency (χ(2) = 5.069, P = 0.027, χ(2) = 8.822, P = 0.001). Age, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28, health assessment questionnaire (HAQ), Sharp score, and body mass index (BMI) were significantly different between RA with sarcopenia or not (P < 0.05). Logistic regression analysis found that age (OR = 1.095, 95%, CI: 1.044-1.150, P < 0.0001) was a significant risk factor for VF in patients with RA, while high skeletal muscle mass (SMI) (OR = 0.513, 95% CI: 0.327-0.804, P = 0.004) was a protective factor for VF in RA patients. CONCLUSIONS: VF, sarcopenia, and vitamin D deficiency are common in patients with RA. Sarcopenia and vitamin D deficiency may be risk factors for the incidence of VF in RA patients. KEY POINTS: • RA patients had a higher incidence of OP and VF, also a high prevalence of sarcopenia and vitamin D deficiency. • Vitamin D deficiency and sarcopenia may might have a synergistic effect on VF in RA. • Aging and sarcopenia are risk factors for VF in RA patients, and sarcopenia were associated with disease activity and structural damage.
35198006 Genetically Determined Circulating Levels of Cytokines and the Risk of Rheumatoid Arthriti 2022 Background: Accumulation of inflammatory leukocytes in articular tissues is the hallmark feature of rheumatoid arthritis (RA). Increasing evidence from observational studies has suggested that several cytokines may be involved in the development of RA. However, traditional observational studies are susceptible to bias from confounding and reverse causation; therefore, the potential causal relationships of individual cytokines with the risk of RA remain elusive. Objective: In this study, we evaluated whether genetically determined circulating levels of cytokines were associated with the risk of RA by performing Mendelian randomization (MR). Methods: We identified single nucleotide polymorphisms (SNPs) associated with circulating levels of cytokines and growth factors from a genome-wide association study (GWAS) including 8,293 participants of Finnish ancestry as instrumental variables (IVs). The association estimates of these IVs with the risk of RA were obtained from a GWAS meta-analysis including 14,361 RA cases and 43,923 controls of European ancestry. We conducted a series of MR analyses to assess the relationship between genetically determined circulating cytokines and the risk of RA, including the random-effects inverse variance-weighted, weighted-median, MR-Egger regression, and MR pleiotropy residual sum and outlier tests. For potential cytokine-RA associations supported by MR evidence, sensitivity analyses were further performed using restricted IV sets of SNPs with colocalization evidence and that excluding pleiotropic SNPs. Results: In the primary MR analysis, there was a suggestive inverse association between genetically determined circulating level of macrophage inflammatory protein-1β (MIP-1b) and the risk of RA [odds ratio (OR): 0.95, 95% confidence interval (CI) = 0.92-0.99, p = 0.016]. The effect estimates were similar in alternative MR analyses. Among SNPs used as IVs for MIP-1b, we found 92 SNPs without documented pleiotropy and three SNPs with evidence of colocalization. The association of MIP-1b with RA from sensitivity analyses using these two sets of restricted IVs remained stable. Conclusion: Our study suggests that genetically determined elevated circulating level of MIP-1b may be associated with a lower risk of RA. Further studies are warranted to determine how MIP-1b and related pathways may contribute to the development of RA.
34995758 Management of bone fragility in patients with rheumatoid arthritis in France: An analysis 2022 Jan 4 OBJECTIVES: Rheumatoid arthritis (RA) is considered a major risk factor for fragility fractures. We examined the quality of management of bone fragility in RA patients in a real-life setting. METHODS: We performed a longitudinal case-control retrospective study in a 1/97th random sample of French health care claims database from 2014 to 2016 to determine the extent of bone fragility management in patients with RA compared with non-RA matched controls. RESULTS: Compared to their non-RA controls (n=4652), RA patients (n=1008; mean age: 61.1years; methotrexate: 69.7%; other conventional disease-modifying antirheumatic drugs (cDMARDs): 26.8%; biologic: 26.0%; corticosteroids: 36.9%) had more reimbursements for bone mineral density (BMD) measurements (21.6 vs. 9.2%; OR=2.7 [2.3; 3.3]; P<0.01) and for bisphosphonates (7.1 vs. 3.6%, OR=2.0 [1.5; 2.7]; P<0.05). In patients exposed to corticosteroids, RA patients underwent more BMD assessments than non-RA controls (28.0 vs. 18.8%; OR=1.7 [1.3; 2.2]; P<0.05). RA patients exposed to corticosteroids were more likely to sustain fracture than non-exposed RA patients (5.7 vs. 2.4%, P<0.01). In addition, only when comparing patients exposed to corticosteroids, was there statistical evidence of an association between RA and an increased fracture rate (6.2 vs. 3.5%, P<0.05). CONCLUSION: Patients with RA exposed to corticosteroids are at high risk of fracture. Patients with RA had more bone fragility management than controls.
35629898 A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Diseas 2022 Apr 27 Metabolomic analysis provides a wealth of information that can be predictive of distinctive phenotypes of pathogenic processes and has been applied to better understand disease development. Rheumatoid arthritis (RA) is an autoimmune disease with the establishment of chronic synovial inflammation that affects joints and peripheral tissues such as skeletal muscle and bone. There is a lack of useful disease biomarkers to track disease activity, drug response and follow-up in RA. In this review, we describe potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities. TMAO (choline and trimethylamine oxide) and TCA (tricarboxylic acid) cycle products have been suggested to modulate metabolic profiles during the early stages of RA and are present systemically, which is a relevant characteristic for biomarkers. Moreover, the analysis of lipids such as cholesterol, FFAs and PUFAs may provide important information before disease onset to predict disease activity and treatment response. Regarding therapeutics, TNF inhibitors may increase the levels of tryptophan, valine, lysine, creatinine and alanine, whereas JAK/STAT inhibitors may modulate exclusively fatty acids. These observations indicate that different disease modifying antirheumatic drugs have specific metabolic profiles and can reveal differences between responders and non-responders. In terms of comorbidities, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. In conclusion, synovial fluid, blood and urine samples from RA patients seem to provide critical information about the metabolic profile related to drug response, disease activity and comorbidities.