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ID PMID Title PublicationDate abstract
31490947 Comparison of oral versus parenteral methotrexate in the treatment of rheumatoid arthritis 2019 OBJECTIVE: Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA. METHODS: PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy). RESULTS: The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events. CONCLUSION: Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents.
31787605 Reasons for Biologic and Targeted Synthetic Disease-modifying Antirheumatic Drug Cessation 2020 Aug 1 OBJECTIVE: To provide real-world evidence about the reasons why Australian rheumatologists cease biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) when treating patients with rheumatoid arthritis (RA), and to assess (1) the primary failure rate for first-line treatment, and (2) the persistence on second-line treatments in patients who stopped first-line tumor necrosis factor inhibitors (TNFi). METHODS: This is a multicenter retrospective, noninterventional study of patients with RA enrolled in the Australian Optimising Patient outcome in Australian RheumatoLogy (OPAL) dataset with a start date of b/tsDMARD between August 1, 2010, and June 30, 2017. Primary failure was defined as stopping treatment within 6 months of treatment initiation. RESULTS: Data from 7740 patients were analyzed; 6914 patients received first-line b/tsDMARD. First-line treatment was stopped in 3383 (49%) patients; 1263 (37%) were classified as primary failures. The most common reason was "lack of efficacy" (947/2656, 36%). Of the patients who stopped first-line TNFi, 43% (1111/2560) received second-line TNFi, which resulted in the shortest median time to stopping second-line treatment (11 months, 95% CI 9-12) compared with non-TNFi. The longest second-line median treatment duration after first-line TNFi was for patients receiving rituximab (39 months, 95% CI 27-74). CONCLUSION: A large proportion of patients who stopped first-line TNFi therapy received another TNFi despite evidence for longer treatment persistence on second-line b/tsDMARD with a different mode of action. Lack of efficacy was recorded as the most common reason for making a switch in first-line treatment of patients with RA.
31292313 Validating an Empirical Mathematical Model for Dynamic Contrast-enhanced MR Imaging of Han 2020 Aug 3 PURPOSE: To evaluate the feasibility of an empirical mathematical model (EMM) to fit dynamic contrast-enhanced MRI (DCE-MRI) data of hand and wrist synovitis and whether parameters of EMM are significantly correlated with clinical disease activity in patients with rheumatoid arthritis (RA). METHODS: Thirty-one consecutive patients with RA prospectively underwent Institutional Review Board (IRB)-approved DCE-MRI scans with temporal resolution of 20 s using a 1.5T system. ROIs were placed where the highest signal increase was observed and the kinetic curves were analyzed using an EMM: ΔS(t) = A(1 - e(-α t)) e(-βt), where ΔS is relative enhancement, t is time from when the signal increase was first observed, starting from baseline (ΔS = 0), A is the upper limit of signal intensity, α (s(-1)) is the rate of signal increase, and β (s(-1)) is the rate of signal decrease during washout. The initial slope of the kinetic curve (Aα), the initial area under the curve (AUC30), the time at which the kinetic curve reached its peak (T(peak)) and the signal enhancement ratio (SER) defined as the change in signal intensity between the initial and delayed time points (t = 60 and 300 s, respectively) were calculated. RA magnetic resonance imaging scores (RAMRIS) with and without contrast media were evaluated. These parameters or scores were compared with the Disease Activity Score (DAS) 28-erythrocyte sedimentation rate (ESR). RESULTS: A showed a significant correlation with DAS28-ESR (r = 0.58; P = 0.0005). β, AUC30 and T(peak) were also significantly correlated with DAS28-ESR with a lesser degree (r = 0.49; P = 0.0051, r = 0.50; P = 0.0038 and r = -0.51; P = 0.0028, respectively), whereas α, Aα, SER and RAMRIS were not. CONCLUSION: EMM could fit the DCE-MRI data of hand and wrist synovitis. AUC30 obtained from the uptake phase of the kinetic curve as well as A, β and T(peak) obtained throughout the kinetic curve might be effective to predict the clinical disease activity.
30836033 Patients with rheumatic diseases share similar patterns of healthcare resource utilization 2019 Jul Objectives: Healthcare service needs have changed with the use of effective treatment strategies. Using data from the modern era, we aimed to explore and compare health service-related direct costs in juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and axial spondyloarthritis (AxSpA). Methods: We linked a longitudinal, population-based clinical data set from Finland's largest non-university hospital's rheumatology clinic with an administrative database on health service-related direct costs in 2014. We compared all-cause costs and costs of comorbidities between adult patients with JIA, PsA, RA, and AxSpA (including ankylosing spondylitis). We also characterized patients with high healthcare resource utilization. Results: Cost distributions were similar between rheumatic diseases (p = 0.88). In adulthood, patients with JIA displayed a similar economic burden to much older patients with other inflammatory rheumatic diseases. A minority were high utilizers: among 119 patients with JIA, 15% utilized as much as the remaining 85%. For PsA (213 patients), RA (1086), and AxSpA (277), the high-utilization proportion was 10%. Both low and high utilizers showed rather low disease activity, but in high utilizers, the patient-reported outcomes were slightly worse, with the most distinct differences in pain levels. Of health service-related direct costs, index rheumatic diseases comprised only one-third (43.6% in JIA) and the majority were comorbidity costs. Conclusions: Patients with JIA, PsA, RA, and AxSpA share similar patterns of healthcare resource utilization, with substantial comorbidity costs and a minority being high utilizers. Innovations in meeting these patients' needs are warranted.
30718913 N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial 2019 Mar N-myristoyltransferase (NMT) attaches the fatty acid myristate to the N-terminal glycine of proteins to sort them into soluble and membrane-bound fractions. Function of the energy-sensing AMP-activated protein kinase, AMPK, is myristoylation dependent. In rheumatoid arthritis (RA), pathogenic T cells shift glucose away from adenosine tri-phosphate production toward synthetic and proliferative programs, promoting proliferation, cytokine production, and tissue invasion. We found that RA T cells had a defect in NMT1 function, which prevented AMPK activation and enabled unopposed mTORC1 signaling. Lack of the myristate lipid tail disrupted the lysosomal translocation and activation of AMPK. Instead, myristoylation-incompetent RA T cells hyperactivated the mTORC1 pathway and differentiated into pro-inflammatory T(H)1 and T(H)17 helper T cells. In vivo, NMT1 loss caused robust synovial tissue inflammation, whereas forced NMT1 overexpression rescued AMPK activation and suppressed synovitis. Thus, NMT1 has tissue-protective functions by facilitating lysosomal recruitment of AMPK and dampening mTORC1 signaling.
31894253 Humulus japonicus extract ameliorates collagen‑induced arthritis in mice through regulat 2020 Feb Humulus japonicus (HJ) is a widely used herbal medicine in Asia with anti‑oxidative, anti‑microbial, and anti‑inflammatory effects. We investigated the potential therapeutic effects of HJ in rheumatoid arthritis (RA) using a mouse model of collagen‑induced arthritis (CIA) and a lipopolysaccharide‑stimulated murine macrophage cell line (RAW 264.7). The CIA mice were administered 300 mg/kg HJ orally starting 3 days prior to second immunization. The clinical and histopathological findings were assessed in the paw of CIA mice. The levels of autoantibodies and inflammatory markers were determined in the plasma and cell culture supernatant, respectively. The expression at mRNA and protein levels was analyzed by reverse transcription quantitative‑PCR and western blot analysis, respectively. HJ significantly decreased the gross arthritic scores and paw swelling in CIA mice. Furthermore, synovial inflammation, cartilage destruction, and bone erosion were markedly reduced by HJ. It also decreased the expression of inflammatory enzymes in both the paw of mice and RAW 264.7 cells. Moreover, the expression of genes related to all macrophages and pro‑inflammatory M1 macrophage were significantly decreased, whereas the expression of anti‑inflammatory M2 macrophage marker was markedly increased in the paw of HJ‑treated CIA mice. In addition, HJ suppressed the levels of plasma anti‑type II collagen antibody following the decreased expression of T helper type 1 (Th1) and Th2 cell‑associated surface markers and cytokines in the paw. HJ also significantly inhibited the expression of IL‑6 both in vitro and in vivo, followed by reduced STAT3 phosphorylation and expression in the paw of CIA mice. Finally, the expression of osteoclast‑related genes was decreased in the paw of HJ‑treated CIA mice. These findings suggest that HJ can play a role in suppressing the development of CIA by overall regulation of articular inflammation. This study should provide new insights into the use of HJ as a therapeutically effective natural product against RA.
31703717 Comparative risk of malignancies and infections in patients with rheumatoid arthritis init 2019 Nov 8 BACKGROUND: Patients with rheumatoid arthritis (RA) are at an increased risk of developing certain cancers and infections compared with the general population. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are effective treatment options for RA, but limited evidence is available on the comparative risks among b/tsDMARDs. We assessed the risk of malignancies and infections in patients with RA who initiated abatacept versus other b/tsDMARDs in a real-world setting. METHODS: This retrospective, observational study used administrative data from three large US healthcare databases (MarketScan, PharMetrics, and Optum) to identify patients treated with abatacept or other b/tsDMARDs. In both groups, age-stratified incidence rates (IRs) with 95% confidence intervals (CIs) were calculated for total malignancy and hospitalized infections; propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs for total malignancy, lung cancer, lymphoma, breast cancer, non-melanoma skin cancer (NMSC), hospitalized infections, opportunistic infections, and tuberculosis (TB), both within individual databases and in meta-analyses across the three databases. RESULTS: A rounded total of 19.2, 13.6, and 4.2 thousand patients initiating abatacept and 55.3, 40.8, and 13.8 thousand initiating other b/tsDMARDs were identified in the MarketScan, PharMetrics, and Optum databases, respectively. The IRs for total malignancy and hospitalized infections were similar between the two groups in each age stratum. In meta-analyses, total malignancy risk (HR [95% CI] 1.09 [1.02-1.16]) of abatacept versus other b/tsDMARDs was slightly but statistically significantly increased; small, but not statistically significant, increases were seen for lung cancer (1.10 [0.62-1.96]), lymphoma (1.27 [0.94-1.72]), breast cancer (1.15 [0.92-1.45]), and NMSC (1.10 [0.93-1.30]). No significant increase in hospitalized infections (0.96 [0.84-1.09]) or opportunistic infections (1.06 [0.96-1.17]) was seen. For TB, low event counts precluded meta-analysis. CONCLUSIONS: In this real-world multi-database study, the risks for specific cancers and infections did not differ significantly between patients in the abatacept and other b/tsDMARDs groups. The slight increase in total malignancy risk associated with abatacept needs further investigation. These results are consistent with the established safety profile of abatacept.
30414353 Screening of Hyperlipidemia Among Patients With Rheumatoid Arthritis in the United States. 2019 Dec OBJECTIVE: To determine the proportion of primary lipid screening among patients with rheumatoid arthritis (RA) and compare it with those among patients with diabetes mellitus (DM) and patients with neither RA nor DM, and to assess whether primary lipid screening varied according to the health care provider (rheumatologist versus non-rheumatologist). METHODS: We analyzed claims data from US private and public health plans from 2006-2010. Eligibility requirements included continuous medical and pharmacy coverage for ≥12 months (baseline period) and >2 physician diagnoses and relevant medications to define RA, DM, RA and DM, or neither condition. Among the 330,695 eligible participants, we calculated the proportion with a lipid profile ordered during the 2 years following baseline. Time-varying Cox proportional hazard models were used to determine the probability of hyperlipidemia screening in participants with RA according to provider specialty. RESULTS: More than half of the patients were ages 41-71 years. Among patients with RA (n = 12,182), DM (n = 62,834), RA and DM (n = 1,082), and those who did not have either condition (n = 167,811), the proportion screened for hyperlipidemia was 37%, 60%, 55%, and 41%, respectively. Patients with RA who visited a rheumatologist and a non-rheumatology clinician during follow-up had a 55% (95% confidence interval 1.36-1.78) higher screening probability than those who only visited a rheumatologist. CONCLUSION: Primary lipid screening was suboptimal among patients with RA. It was also lower for patients with DM and minimally different from the general population. Screening was higher for RA patients who received care from both a rheumatologist and a non-rheumatologist (e.g., primary care physician).
31430609 Low serum levels of insulin-like growth factor-1 are associated with an increased risk of 2019 Sep Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are not only involved in individual growth and metabolism, but they are also associated with inflammation and homeostasis of articular cartilage and bone. Recent studies have identified the involvement of IGF-1 and IGFBP-3 in the development of rheumatoid arthritis (RA). Nevertheless, the results were inconsistent, and the relevant data were not synthetically assessed. Therefore, this review aimed to systematically evaluate the associations of serum IGF-1 and IGFBP-3 levels with the development of RA. Several databases were used to retrieve relevant publications (up to January 2018). Pooled standard mean difference (SMD) and 95% confidence interval (CI) were demonstrated using a forest plot. A total of 27 studies from 19 publications were included. Meta-analysis results showed that RA patients had lower serum IGF-1 levels when compared to controls (SMD = -0.650, 95% CI = -1.184 to -0.115, P = .017). However, there was no significant association between serum IGFBP-3 levels and RA (SMD = 0.590, 95% CI = -1.323 to 2.504, P = .545). Subgroup analyses further showed that serum IGF-1 levels in RA patients are discrepant in terms of race, age, and measurement type (all P < .05). In conclusion, the decreased levels of serum IGF-1 were closely associated with the development of RA. Future longitudinal studies are needed to validate the link between serum IGF-1 levels with RA pathogenesis as well as the effects of IGF-1 on RA treatment.
31017736 Osteogenic circulating endothelial progenitor cells are linked to electrocardiographic con 2019 Sep BACKGROUND: Osteogenic circulating endothelial progenitor cells (EPC) play a pathogenic role in cardiovascular system degeneration through promulgating vasculature calcification, but its role in conduction disorders as part of the cardiovascular degenerative continuum remained unknown. AIM: To investigate the role of osteocalcin (OCN)-expressing circulating EPCs in cardiac conduction disorders in the unique clinical sample of rheumatoid arthritis (RA) susceptible to both abnormal bone metabolism and cardiac conduction disorders. METHODS: We performed flow cytometry studies in 134 consecutive asymptomatic patients with rheumatoid arthritis to derive osteogenic circulating OCN-positive (OCN+) CD34+KDR+ vs. CD34+CD133+KDR+ conventional EPC. Study endpoint was the prespecified combined endpoint of electrocardiographic conduction abnormalities. RESULTS: Total prevalence of cardiac conduction abnormality was 9% (n = 12). All patients except one had normal sinus rhythm. One patient had atrial fibrillation. No patient had advanced atrioventricular (AV) block. Prevalence of first-degree heart block (>200 ms), widened QRS duration (>120 ms) and right bundle branch block were 6.7%, 2.1%, and 2.2% respectively. Circulating osteogenic OCN(+) CD34(+) KDR(+) EPCs were significantly higher among patients with cardiac conduction abnormalities (p = 0.039). Elevated OCN(+) CD34(+) KDR(+) EPCs> 75th percentile was associated with higher prevalence of cardiac conduction abnormalities (58.3% vs. 20.02%, p = 0.003). Adjusted for potential confounders, elevated OCN(+) CD34(+) KDR(+) EPCs> 75th percentile remained independently associated with increased risk of cardiac conduction abnormalities (OR = 4.4 [95%CI 1.2-16.4], p = 0.028). No significant relation was found between conventional EPCs CD34+CD133+KDR+ and conduction abnormalities (p = 0.36). CONCLUSIONS: Elevated osteogenic OCN(+) CD34(+) KDR(+) EPCs are independently associated with the presence of electrocardiographic conduction abnormalities in patients with rheumatoid arthritis, unveiling a potential novel pathophysiological mechanism.
30982700 Gender differences in information needs and preferences regarding depression among individ 2019 Sep OBJECTIVE: We assessed the information needs of persons with any of three immune-mediated inflammatory diseases (multiple sclerosis [MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) regarding depression, as a first step toward developing patient-relevant information resources, ultimately to facilitate self-management and appropriate care. We also compared information needs across genders. METHODS: We surveyed participants with MS, IBD and RA regarding depression-related information needs including types of treatments, effectiveness, risks, benefits, and perceived helpfulness of treatments. We compared responses between groups using multivariate regression. RESULTS: 328 participants provided complete responses (MS: 141, IBD: 114, RA: 73). Most of the topics queried were perceived as very important, and similarly important for all groups. Women placed higher importance than men on most topics. The most popular formats for receiving information were discussion with a counselor (very preferred: 67.4%) and written information (very preferred: 65.5%); this did not differ between groups. CONCLUSIONS: Persons affected by MS, IBD and RA are interested in receiving information about multiple topics related to depression treatment, from multiple sources. Women desire more information than men. PRACTICE IMPLICATIONS: These findings can be used to design information resources to meet information needs regarding depression in MS, IBD and RA.
31921150 Meta-Analysis of in vitro-Differentiated Macrophages Identifies Transcriptomic Signatures 2019 Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage models to perform a meta-analysis. Specifically, we obtained gene expression data from unstimulated macrophages (M0) and macrophages stimulated with lipopolysaccharides (LPS) for 2-4 h (M-LPS(early)), LPS for 24 h (M-LPS(late)), LPS and interferon-γ (M-LPS+IFNγ), IFNγ (M-IFNγ), interleukin-4 (M-IL4), interleukin-10 (M-IL10), and dexamethasone (M-dex). Our meta-analysis identified consistently differentially expressed genes that have been implicated in inflammatory and metabolic processes. In addition, we built macIDR, a robust classifier capable of distinguishing macrophage activation states with high accuracy (>0.95). We classified in vivo macrophages with macIDR to define their tissue- and disease-specific characteristics. We demonstrate that alveolar macrophages display high resemblance to IL10 activation, but show a drop in IFNγ signature in chronic obstructive pulmonary disease patients. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but acquired LPS-activation features in diabetic-obese patients. Rheumatoid arthritis synovial macrophages exhibit characteristics of IL10- or IFNγ-stimulation. Altogether, we defined consensus transcriptional profiles for the eight in vitro macrophage activation states, built a classification model, and demonstrated the utility of the latter for in vivo macrophages.
31621569 Osteoarthritis is as severe as rheumatoid arthritis: evidence over 40 years according to t 2019 Sep Osteoarthritis (OA) may be associated with substantial work disability, morbidity, costs, and increased mortality rates, often similar to rheumatoid arthritis (RA), documented in many published reports over the last 4 decades. However, OA generally has been viewed as less severe than RA. This discrepancy may be explained in part by:a) RA may have been considerably more severe in the past, prior to effective therapies.b) most older individuals have radiographic joint damage, which often is not associated with clinical symptoms.c) RA is associated with abnormal laboratory tests, which are regarded as conveying greater significance than symptoms of pain and disability according to a "biomedical model," the dominant paradigm of modern medicine.d) Most reports of OA and RA have emphasised differences between the 2 diseases even beyond laboratory abnormalities in pathogenesis, physical findings, and imaging.e) Even pain and functional disability seen in both diseases are assessed using different patient self-report questionnaires, a WOMAC (Western Ontario McMaster Universities osteoarthritis index) in OA, and HAQ (health assessment questionnaire) in RA.An identical measure is required for optimal direct comparisons, which has been used in 8 studies performed between 1979 and 2019 at 8 sites in North America, Europe, and Australia. These studies were primarily based on retrospective analyses at sites which collected a patient questionnaire in routine clinical care by all patients at all visits to inform clinical decisions. A pain visual analogue scale (VAS) was higher in OA compared to RA in 11/12 patient groups, while physical function on a HAQ (health assessment questionnaire) or derivative MDHAQ (multidimensional HAQ) and RAPID3 (routine assessment of patient index data) were slightly higher in RA before 2013 and higher in OA in later reports. Furthermore, a study of population-based data from the 1978 US Health Interview Survey indicated similar levels of disability and earnings losses according to surrogate variables for OA and RA. Therefore, at least over the last 40 years, pain and functional disability in OA have appeared to be severe and similar to RA. These observations also-illustrate the potential value of using an identical patient questionnaire in all patients at all visits in routine care settings, analogous to using the same laboratory tests such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) in all rheumatic diseases, and maintaining a database of the results for later analyses.
31019537 MiR-613 inhibits proliferation and invasion and induces apoptosis of rheumatoid arthritis 2019 BACKGROUND: This study aimed to investigate the effects of miR-613 on the proliferation, invasion and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Synovial tissue samples were collected from 20 rheumatoid arthritis (RA) patients and 10 patients with joint trauma undergoing joint replacement surgery. The RASFs were isolated and cultured. MiR-613 and DKK1 expression in both synovial tissues and cells was detected using quantitative real-time PCR (qRT-PCR). Dual luciferase reporter gene assay was employed to evaluate the effect of miR-613 on the luciferase activity of DKK1. Then RASFs were transfected with miR-613 mimics, si-DKK1 and pcDNA-DKK1. Changes in cellular proliferation, invasion and apoptosis were detected through BrdU assay, Transwell invasion assay and flow cytometry analysis, respectively. RESULTS: MiR-613 was significantly down-regulated in RA tissues and RASFs compared to normal tissues and cells, whereas DKK1 was up-regulated in RA tissues and RASFs. Dual luciferase reporter gene assay showed that miR-613 could specifically bind to the 3'UTR of DKK1 and significantly inhibit the luciferase activity. Moreover, miR-613 significantly reduced the expression of DKK1. Overexpression of miR-613 or knockdown of DKK1 suppressed proliferation and invasion of RASFs, and induced RASF apoptosis. The reverse results were observed when DKK1 was up-regulated in miR-613-overexpressing RASFs. CONCLUSIONS: MiR-613 can inhibit proliferation and invasion and induce apoptosis of RASFs by directly targeting DKK1 expression.
30539581 Histone Protein Epitope Mapping for Autoantibody Recognition in Rheumatoid Arthritis. 2019 Deiminated proteins are the target of diagnostic anti-citrullinated peptide/protein autoantibodies (ACPA) in rheumatoid arthritis (RA). Deiminated histone H4 contained in the neutrophil extracellular traps reacts with ACPA, becoming an interesting diagnostic antigen for RA. The identification of the ACPA binding site in histone H4 was performed experimentally by mapping the complete sequence. The method describes the synthesis of an overlapping peptide library covering the entire deiminated sequence of H4 and its further evaluation in ELISA. A detailed description of an ELISA protocol to test RA patients' sera against the synthesized peptides and ACPA is provided.
28778575 High prevalence of gallstone disease in rheumatoid arthritis: A new comorbidity related to 2019 Mar OBJECTIVE: To assess the prevalence of gallstone disease and identify associated risk factors in rheumatoid arthritis (RA) patients compared to the general population. METHODS: Eighty-four women with rheumatoid arthritis were included in the study. Each patient was assessed via a structured interview, physical examination, abdominal ultrasound and blood test including lipid profile. The prevalence of gallstone disease in rheumatoid arthritis was compared with data from a study of the Spanish population matched by age groups. RESULTS: Twenty-eight of the 84 women had gallstone disease (33.3%). RA women with and without gallstone disease were similar in most of the variables assessed, except for older age and menopausal status in the former. A greater prevalence of gallstone disease was seen in rheumatoid arthritis patients compared to the general population of the same age; however, the differences were significant only in women aged 60 or older (45.5% versus 23.1% respectively, P-value .008). The age-adjusted OR of developing gallstone disease in RA women compared with general population women was 2,3 (95% CI: 1.3-4.1). A significantly higher HDL3-c subfraction and higher apoA-I/HDL and HDL3-c/TC ratios were observed in patients with gallstone disease. CONCLUSION: Women with rheumatoid arthritis may have a predisposition to gallstones that can manifest in middle or older age compared with women in the general population. This situation could be related to chronic inflammation and HDL metabolism.
30557838 A smart nanosensor for the detection of human immunodeficiency virus and associated cardio 2019 Feb 1 Human immunodeficiency virus (HIV), which isa worldwide public health issue, is commonly associated with cardiovascular disorders (CVDs) and rheumatoid arthritis (RA). A smart nanosensor was developed for the detection of HIV and its related diseases (CVDs and RA) using graphene-based field-effect transistors (FETs). In this study, amine-functionalized graphene (afG) was conjugated with antibodies [anti-p24 for HIV, anti-cardiac troponin 1 (anti-cTn1) for CVDs, and anti-cyclic citrullinated peptide (anti-CCP) for RA] to detect various biomarkers. The antibodies were covalently conjugated to afG via carbodiimide activation. The bioconjugate (graphene-antibody) was characterized by various biophysical techniques such as UV-Vis, Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). The electrochemical performance of the sensor was evaluated with respect to changes in the resistance of the electrode surface due to the interaction of the antigen with its specific antibody. The developed sensor was highly sensitive and showed a linear response to p24, cTn1, and, CCP from 1 fg/mL to 1 μg/mL. The limit of detection (LOD) was 100 fg/mL for p24 and 10 fg/mL for cTn1 and CCP under standard optimized conditions. The graphene-based smart nanodevice demonstrated excellent performance; thus, it could be used for the on-site detection of HIV, CVD, and RA biomarkers in real samples.
31715307 Anti-inflammatory effect of nano-encapsulated nerolidol on zymosan-induced arthritis in mi 2020 Jan Nerolidol is naturally occurring sesquiterpene has wide range of biological properties including anti-inflammatory activity. However, it has high volatility with low solubility in nature. The present study aimed to develop and characterized nano-encapsulated nerolidol and evaluated its activity on zymosan-induced arthritis model. Nano-capsules were produced by interfacial deposition of preformed polymer method and characterized by particle size, pH, polydispersity index (PDI), zeta potential, drug content and transmission electron microscopy (TEM). In vitro cytotoxicity of formulations was evaluated by alamar blue and MTT assays. In vivo neutrophils migration assay was performed on intra-articular zymosan-induced arthritis model in mice. Nano-encapsulated nerolidol suspensions presented adequate properties: mean diameter of particles 219.5 ± 8.4 nm, pH: 6.84 ± 0.5, PDI≤0.2, the zeta potential was -20.3 ± 3.6 mV and drug content 71,2 ± 1.3%. The formulations did not demonstrated cytotoxicity under the conditions assessed. Nerolidol 300 mg/kg inhibited neutrophils migration into joint cavity by 18.8% remains compared with control group, and nano-encapsulated nerolidol 3 mg/kg inhibited (26.7% remains) similar to free nerolidol 10 mg/kg (27.4% remains). Histological, quantification of pro-inflammatory and anti-inflammatory cytokines proves the same results. In conclusion the data suggests that nanoencapsulation of nerolidol improved its anti-inflammatory effect on arthritis in mice.
31136632 New insights into the prevalence of depressive symptoms and depression in rheumatoid arthr 2019 OBJECTIVES: To investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease. METHODS: In this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation. RESULTS: In 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age <60 years (OR = 1.78), RAID score >2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy. CONCLUSIONS: Mild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms. CLINICAL TRIAL REGISTRATION NUMBER: This study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483).
31637609 Assessing disease severity in bio-naïve patients with RA on treatment with csDMARDs: insi 2020 Feb INTRODUCTION: This study aimed to characterize disease burden among patients with rheumatoid arthritis (RA) with moderate-to-high disease activity who had received conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy for ≥ 6 months but had not advanced to a biologic therapy. METHODS: Patients enrolled in the US Corrona RA Registry between June 1, 2014, and January 30, 2018, with 6 months of continuous csDMARD monotherapy, with moderate-to-high disease activity, who remained biologic naive, and who had ≥ 1 follow-up visit were identified. Disease activity was assessed among patients with a 6-month follow-up visit (± 3 months). Descriptive statistics were used to compare demographics and disease characteristics between patients with or without treatment advancement. RESULTS: The study included 409 patients with a disease activity assessment at 6 months (mean (SD) age 65.9 (12.6) years; mean duration of csDMARD therapy 407 (221) days). Of those patients, more than half (54%, n = 219) remained in moderate-to-high disease activity. Patients remaining in moderate-to-high vs. remission-to-low disease activity had higher baseline swollen (6.1) and tender joint counts (6.8). Over the 6-month period, treatment advancement occurred in 29% of patients. Those who advanced treatment (n = 118) vs. did not advance treatment (n = 291) were younger, had a shorter duration of RA, had higher disease activity, and reported higher levels of pain and fatigue. CONCLUSIONS: The substantial number of patients with persistent moderate-to-high disease on csDMARDs over a 6-month period and who did not advance treatment indicates that there is considerable need for a treat-to-target approach to care for patients with RA.Key Points•For patients with RA and an inadequate response to treatment with initial csDMARD monotherapy, guidelines recommend treatment advancement; however, this may not be occurring in real-world clinical settings.•In the current study, a substantial proportion of patients (54%) on csDMARDs had persistent moderate-to-severe disease activity at the 6-month (± 3 months) follow-up visit; however, only 29% of patients had their medication treatment advanced, indicating that there is considerable need for a treat-to-target approach to care for patients with RA.•Patients with younger age, shorter RA duration, and higher disease activity were more likely to have their medication treatment advanced, which suggests that potentially more aggressive treatment of disease activity is needed across the whole RA population.