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ID PMID Title PublicationDate abstract
29502236 A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases. 2018 Jun Tocilizumab (TCZ) is the first humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman's disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced cytokine release syndrome. The global clinical development program for TCZ provides a wealth of clinical data on intravenous TCZ, and more recent studies in patients with RA have provided evidence characterizing the role of intravenous TCZ as monotherapy in early disease and led to the introduction of a subcutaneous formulation of TCZ. In addition, recently published open-label extension and observational studies continue to support the long-term efficacy and safety of TCZ in both clinical trial and real-world settings. Given the involvement of IL-6-mediated signaling in inflammatory disorders, TCZ is also being investigated in other immunological diseases. In particular, a phase 2 trial on the safety and efficacy of subcutaneous TCZ in adults with systemic sclerosis shows clinically relevant improvements in skin sclerosis and lung function in these patients. Another anti-IL-6 receptor agent, sarilumab, targeting the IL6 receptor alpha subunit, was recently approved for the treatment of patients with RA, although long-term data for this biologic are not yet published. In this article we review the placement of TCZ in current treatment guidelines; recent clinical trial data, including quality of life in patients with RA; recent updates to the TCZ safety profile; recent investigations of TCZ in other immunological diseases; and the clinical development of other novel IL-6-targeted agents.
29361202 Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review. 2018 Oct OBJECTIVE: Chikungunya virus infection is a rapidly emerging global viral infection that can cause chronic, debilitating arthritis that in some ways mimics rheumatoid arthritis. The aim of this study was to evaluate the available evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya arthritis. METHODS: A systematic literature search was performed to identify all published trials that evaluated MTX as monotherapy or combination therapy in patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane Library databases were searched from study inception to August 2017. We also searched Google Scholar, the International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov. RESULTS: Among 131 possibly relevant studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a non-controlled prospective study, and 1 was an unblinded randomized clinical trial of combination MTX therapy. In the randomized clinical trial, triple therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to hydroxychloroquine monotherapy, as assessed by the mean ± SD Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (3.39 ± 0.87 versus 4.74 ± 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 ± 0.31 versus 1.88 ± 0.47; P < 0.0001). CONCLUSION: The number of available studies is limited, but taken together, these studies demonstrate that MTX is sufficiently efficacious to justify further study of MTX for the treatment of chronic chikungunya arthritis. The trials lacked rigorous study designs and used different treatment strategies and outcome measures. This systematic review underscores the need for randomized, prospective, placebo-controlled studies of MTX monotherapy for the treatment of chronic chikungunya arthritis.
30186023 Pharmaceutical Approval Update. 2018 Sep Baricitinib (Olumiant) tablets for rheumatoid arthritis; plazomicin (Zemdri) injection for complicated urinary tract infections; and cannabidiol (Epidiolex) oral solution for seizures with Lennox-Gastaut syndrome and Dravet syndrome.
29912956 Correction: Clinical management of seronegative and seropositive rheumatoid arthritis: A c 2018 [This corrects the article DOI: 10.1371/journal.pone.0195550.].
30160015 Morin Exerts Anti-Arthritic Effects by Attenuating Synovial Angiogenesis via Activation of 2018 Nov SCOPE: Morin, a flavonoid occurring in many dietary plants, can reduce the number of synovial blood vessels and ameliorate collagen-induced arthritis (CIA) in rats. Herein, its underlying mechanisms in view of the peroxisome proliferator activated receptor-γ (PPARγ) pathway are addressed. METHODS AND RESULTS: In vitro, wound-healing and transwell assays are conducted to explore the effect of morin on HUVECs migration. Morin inhibits HUVECs migration and tube formation induced by VEGF, which is reversed by PPARγ antagonist GW9662 or siPPARγ. Molecular docking and competitive binding assays show that morin could bind to PPARγ. Morin increases the expression of PDK4 and CD36 in a PPARγ-dependent manner and increases the luciferase activity in cells transfected with PPARγ plasmid, which indicates that morin could activate PPARγ after binding. In addition, morin increases the expression of PTEN, a target gene of PPARγ that suppresses angiogenesis and inhibits PI3K/Akt signaling. The effects of morin on the PTEN-PI3K/Akt pathway are diminished by GW9662 and siPPARγ. In vivo studies show that morin ameliorates rat CIA, reduces synovial angiogenesis, and upregulates the expression of PTEN in the synovium, which is almost completely abolished by GW9662. CONCLUSIONS: Morin is a potential agonist of PPARγ, which attenuates synovial angiogenesis and arthritis via the PPARγ-PTEN-PI3K/Akt pathway.
29622300 Measuring Patient Preferences: An Overview of Methods with a Focus on Discrete Choice Exp 2018 May There is increasing recognition of the importance of patient preferences and methodologies to measure them. In this article, methods to quantify patient preferences are reviewed, with a focus on discrete choice experiments. In a discrete choice experiment, patients are asked to choose between 2 or more treatments. The results can be used to quantify the relative importance of treatment outcomes and/or other considerations relevant to medical decision making. Conducting and interpreting a discrete choice experiment requires multiple steps and an understanding of the potential biases that can arise, which we review in this article with examples in rheumatic diseases.
29657832 Predictive value of serum calprotectin (S100A8/A9) for clinical response after starting or 2018 OBJECTIVES: Calprotectin (S100A8/A9) has been correlated with disease activity in rheumatoid arthritis (RA). The aim of this study was to investigate the predictive value of serum calprotectin for clinical response after starting and tapering anti-tumour necrosis factor treatment in RA. METHODS: Serum samples and clinical outcomes were derived from two longitudinal RA studies.At baseline (starting or tapering of adalimumab or etanercept), calprotectin levels were determined by ELISA. In the Biologic Individual Optimised Treatment Outcome Prediction (BIO-TOP) study, treatment effect was assessed after 6 months using the European League Against Rheumatism (EULAR) response criteria. In the Dose Reduction Strategies of Subcutaneous TNF Inhibitors (DRESS) study, patients were classified at 18 months as being successfully dose reduced, discontinued or not able to reduce the dose. Area under the receiver operating characteristic curves (AUC) were generated to evaluate the predictive value of calprotectin and logistic prediction models were created to assess its added value. RESULTS: In the BIO-TOP study, calprotectin levels were higher in responders (n=50: 985 ng/mL (p25-p75: 558-1417)) compared with non-responders (n=75: 645 ng/mL (p25-p75: 415-973), p=0.04).AUC for predicting EULAR good response was 0.61 (95% CI 0.50 to 0.71). The prediction model with calprotectin (AUC 0.77, 95% CI 0.68 to 0.85) performed similarly to the baseline model (AUC 0.74, 95% CI 0.65 to 0.82, p=0.29). In the DRESS study, calprotectin levels were similar between the three groups (n=47; n=19; n=36) and calprotectin was not predictive for clinical response after tapering. CONCLUSIONS: Serum calprotectin has some predictive value for clinical response after starting anti-TNF treatment, although it has no added value to other clinical factors. In patients with low disease activity, serum calprotectin is not predictive for clinical response after tapering anti-TNF treatment. TRIAL REGISTRATION NUMBER: NTR4647 (BIO-TOP study) and NTR3216 (DRESS study); Pre-results.
29204858 A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARD 2018 Jun INTRODUCTION: Understanding the effects of corticosteroid utilization prior to initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform decision-makers on the appropriate use of these medications. This study examined treatment patterns and associated burden of corticosteroid utilization before initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. METHODS: A retrospective analysis was conducted of adult RA patients in the US MarketScan Database (2011-2015). The following patterns of corticosteroid utilization were analyzed: whether corticosteroids were used; duration of use (short/long duration defined as < or ≥ 3 months); and dosage (low as < 2.5, medium as 2.5 to < 7.5 and high as ≥ 7.5 mg/day). Effects of corticosteroid use on time to biologic DMARD initiation were examined using Cox proportional hazards models. Likelihood and number of adverse events were examined using logistic and negative binomial regression models. Generalized linear models were used to examine healthcare costs. Independent variables in all models included patient demographics and health characteristics. RESULTS: A total of 25,542 patients were included (40.84% used corticosteroids). Lower hazard of biologic DMARD initiation was associated with corticosteroid use (hazard ratio = 0.89, 95% confidence interval = 0.83-0.96), long duration and lower dose. Corticosteroid users compared to non-users had higher incidence rates of various adverse events including cardiovascular events (P < 0.05). Higher likelihood of adverse events was associated with corticosteroid use and long duration of use, as was increased number of adverse events. Corticosteroid users had a greater annualized mean number of physician visits, hospitalizations, and emergency department (ED) visits than non-users in adjusted analysis. Corticosteroid users compared to non-users had higher mean costs for total healthcare, physician visits, hospitalizations, and ED visits. CONCLUSIONS: Among patients with RA, corticosteroid utilization is associated with delayed initiation of biologic DMARDS and higher burden of adverse events and healthcare utilization/costs before the initiation of biologic DMARDs. FUNDING: AbbVie Inc.
29875003 Current Status and Future Prospects of Small-molecule Protein-protein Interaction (PPI) In 2018 The overexpression of Tumor Necrosis Factor (TNF) is directly related to the development of several autoimmune diseases, such as rheumatoid and psoriatic arthritis, inflammatory bowel disease, Crohn's disease, refractory asthma, and multiple sclerosis. Receptor Activator of Nuclear Factor Kappa- B Ligand (RANKL) belongs to the TNF family and is the primary mediator of osteoclast-induced bone resorption through interaction with its receptor RANK. The function of RANKL is physiologically inhibited by the action of osteoprotegerin (OPG), which is a decoy receptor that binds to RANKL and prevents the process of osteoclastogenesis. Malfunction among RANK/RANKL/OPG can also result in bone loss diseases, including postmenopausal osteoporosis, rheumatoid arthritis, bone metastasis and multiple myeloma. To disrupt the unwanted functions of TNF and RANKL, current attempts focus on blocking TNF and RANKL binding to their receptors. In this review, we present the research efforts toward the development of low-molecular-weight pharmaceuticals that directly block the detrimental actions of TNF and RANKL.
30886957 Methotrexate therapy impacts on red cell distribution width and its predictive value for c 2018 BACKGROUND: Methotrexate (MTX) is well known to affect folic acid metabolism, so MTX treatment can result in alterations of mean corpuscular volume (MCV), which may impact on red cell distribution width (RDW), as MCV levels feed into RDW calculation. We thus questioned whether RDW levels and subsequently its diagnostic utility in RA subjects, as reported before, are influenced by ongoing MTX therapy.We assessed the impact of disease modifying drug (DMARD) treatment, especially MTX, on RDW and evaluated their influence on the predictive value of RDW for cardiovascular (CV) events in patients with rheumatoid arthritis (RA). As far as we know, this is the first study evaluating the influence of MTX on RDW. METHODS: Medical treatment, disease activity, laboratory parameters and history of CV events were retrospectively analysed in 385 RA patients at disease onset and at last follow up at our clinic. Additionally, in patients with CV event, data were recorded at last follow up prior the CV event. RESULTS: Disease parameters and laboratory findings associated with a serious vascular event were older age (p < 0,001), longer disease duration (p = 0,002) and a higher RDW at diagnosis (p = 0,025). No differences in RDW levels became evident with any other treatment regimen beside MTX. MTX treated patients had significantly higher RDW compared to subjects without this drug (p < 0,001). In RA patients without MTX treatment, we found RDW level significantly different between those with versus without a CV event, whereas this difference disappeared in subjects receiving MTX. CONCLUSION: MTX impacts on RDW and might therefor reduce its prognostic value for CV events in patients taking MTX, whereas an increased RDW at diagnosis remains an early risk predictor for myocardial infarction and stroke in RA patients.
29493823 Quantification of hand synovitis in rheumatoid arthritis: Arterial mask subtraction reinfo 2018 Mar 1 BACKGROUND: Synovitis, which is a hallmark of rheumatoid arthritis (RA), needs to be precisely quantified to determine the treatment plan. Time-intensity curve (TIC) shape analysis is an objective assessment method for characterizing the pixels as artery, inflamed synovium, or other tissues using dynamic contrast-enhanced MRI (DCE-MRI). PURPOSE/HYPOTHESIS: To assess the feasibility of our original arterial mask subtraction method (AMSM) with mutual information (MI) for quantification of synovitis in RA. STUDY TYPE: Prospective study. SUBJECTS: Ten RA patients (nine women and one man; mean age, 56.8 years; range, 38-67 years). FIELD STRENGTH/SEQUENCE: 3T/DCE-MRI. ASSESSMENT: After optimization of TIC shape analysis to the hand region, a combination of TIC shape analysis and AMSM was applied to synovial quantification. The MI between pre- and postcontrast images was utilized to determine the arterial mask phase objectively, which was compared with human subjective selection. The volume of objectively measured synovitis by software was compared with that of manual outlining by an experienced radiologist. Simple TIC shape analysis and TIC shape analysis combined with AMSM were compared in slices without synovitis according to subjective evaluation. STATISTICAL TESTS: Pearson's correlation coefficient, paired t-test and intraclass correlation coefficient (ICC). RESULTS: TIC shape analysis was successfully optimized in the hand region with a correlation coefficient of 0.725 (P < 0.01) with the results of manual assessment regarded as ground truth. Objective selection utilizing MI had substantial agreement (ICC = 0.734) with subjective selection. Correlation of synovial volumetry in combination with TIC shape analysis and AMSM with manual assessment was excellent (r = 0.922, P < 0.01). In addition, negative predictive ability in slices without synovitis pixels was significantly increased (P < 0.01). DATA CONCLUSIONS: The combination of TIC shape analysis and image subtraction reinforced with MI can accurately quantify synovitis of RA in the hand by eliminating arterial pixels. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
30886976 Vitamin D in individuals before onset of rheumatoid arthritis - relation to vitamin D bind 2018 BACKGROUND: Vitamin D has been implicated as being involved in the aetio-pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA). Previous studies present contradictory results. Vitamin D binding protein (DBP), the major transport protein, is also involved in various inflammatory processes. The aim of this study was to investigate the relationship between circulating levels of 25-hydroxyvitamin D [25(OH) D], DBP and polymorphisms in group-specific component (GC) in pre-symptomatic individuals and matched controls within prospective cohorts of the Northern Sweden. METHODS: Blood samples donated to the Medical Biobank prior to the onset of symptoms of RA (n = 515, mean [SD] time before the onset of symptoms 6.2 [9.3] years) and from matched (2:1) population-based controls (n = 267) were used. Plasma 25(OH) vitamin D levels were analyzed using liquid chromatography tandem-mass spectrometry and DBP levels were analyzed using enzyme-linked immunosorbent assay. GC polymorphisms (rs4588 and rs7041) were analyzed with TaqMan assays (Applied Biosystems). RESULTS: Levels of 25(OH) D or DBP were not statistically different between pre-symptomatic individuals and controls in a crude, or a multiple-adjusted logistic regression model. However, an increased risk for future RA was found in females of DBP (OR 1.014 [95%CI 1.001-1.028]) per 10 mg/L adjusted for carriage of the minor allele of rs4588, in a multiple-adjusted model (p < 0.05). CONCLUSIONS: This study indicated that vitamin D is not associated with the future risk of RA although increasing levels of DBP were however, associated with an increased risk of disease in females carrying the minor allele of a DBP encoding SNP.
30886956 Rheumatoid Arthritis Portrayal by UK National Newspapers 2011-2016: A Service User - Led T 2018 BACKGROUND: An important source of knowledge, beliefs, and attitudes about illness is the mass media. Research has established the often negative and emotive language utilised by journalists to report on physical and mental long-term illnesses. The limited amount of research on rheumatological conditions has largely focused on the extent of, and/or accuracy of media coverage. This is the first published study to examine systematically the language used by the United Kingdom (UK) popular press to specifically describe rheumatoid arthritis (RA). METHODS: A patient and public involvement (PPI) approach, involving academics and service users with RA, was used to conduct the research. LexisNexis online repository of print media was searched for articles within a defined five year time frame, which included RA in the headline and/or lead paragraph of 15 UK national non-specialist newspapers. Resultant articles were uploaded to NVivo, and a realist perspective aided a thematic analysis of the data set. RESULTS: A search of LexisNexis produced 413 newspaper articles, of which 147 met the inclusion criteria. Three themes emerged: (1) language used to describe RA; (2) language used to refer to those who live with RA and; (3) language used to report on potential new treatments for RA. Negative and emotive terms such as 'attack', 'painful', 'crippling', and 'agony' were the most frequently used to describe the experience of RA. People diagnosed with RA were often portrayed as 'sufferers' or 'victims', though neutral language was also deployed. 'Hope' and 'breakthrough' were the most reported terms for potential new treatments for RA. Across the three themes, tabloid and middle market newspaper articles applied more sensationalised language with attention grabbing headlines and news stories. By contrast, such emotive terminology was less apparent in broadsheets. CONCLUSIONS: The media is a source of information about RA for the general population, but the quality of newspaper journalism about the condition requires improvement. The findings may act as a stimulus for a national public awareness initiative and/or social marketing campaign. How the language currently constructed to describe RA in the press is received by people with RA would be an important area for future research.
30498453 An Updated Meta-Analysis of the Associations Between MicroRNA Polymorphisms and Susceptibi 2018 Aims: Rheumatoid arthritis (RA) is characterized by cartilage and bone damage leading to disability. Here, the association between microRNA (miRNA) polymorphisms and susceptibility to RA was evaluated by performing an updated meta-analysis and systematic review. Main methods: An electronic search of databases including PubMed and Embase was performed from inception to December 8, 2017 to retrieve studies investigating the association between miRNA polymorphisms and RA risk. Two reviewers independently screened literature according to the inclusion and exclusion criteria and extracted data. The meta-analysis was conducted using Stata 14.0 software. Key findings: Thirteen case-control studies with 2660 cases and 4098 controls were screened out after a systematic search. One study from the miR-146a rs2910164 G > C polymorphism group and two from the miR-499 rs3746444 T > C polymorphism group were excluded because of deviations from Hardy-Weinberg equilibrium. Pooled analysis demonstrated that miR-146a rs2910164 G > C polymorphism was not significantly associated with susceptibility to RA. However, a significant association was observed between miR-499 rs3746444 T > C polymorphism and RA risk (C vs. T: OR = 1.22, 95% CI = 1.05-1.42, P = 0.008; TC vs. TT: OR = 1.26, 95% CI = 1.05-1.50, P = 0.011; TC/CC vs. TT: OR = 1.26, 95% CI = 1.07-1.5, P = 0.007). Subgroup analysis based on ethnicity showed no significant association between miR-499 T > C polymorphism and susceptibility to RA in the Asian population (P > 0.05). However, in Caucasian population, the C allele in the miR-499 T > C polymorphism was a contributor to RA susceptibility in some genetic models (C vs. T: OR = 1.64, 95% CI = 1.28-2.11, P < 0.001; TC vs. TT: OR = 1.95, 95% CI = 1.40-2.71, P < 0.001; TC/CC vs. TT: OR = 1.96, 95% CI = 1.43-2.69, P < 0.001). Significance: The miR-146a rs2910164 G > C polymorphism was not associated with susceptibility to RA. In the Caucasian population, the C allele in the miR-499 T > C polymorphism contributed to RA susceptibility.
30464787 Treatment Persistence and Healthcare Costs Among Patients with Rheumatoid Arthritis After 2018 Jun BACKGROUND: Targeted disease-modifying antirheumatic drug (DMARD) options for rheumatoid arthritis (RA) include tumor necrosis factor (TNF) inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) or alternative mechanisms of action (MOAs), such as a T-cell co-stimulation modulator (abatacept), Janus kinase inhibitor (tofacitinib), or interleukin-6 inhibitor (tocilizumab). OBJECTIVE: To examine treatment persistence and healthcare costs in patients with RA who changed therapy by cycling therapy (ie, switching within the same drug class), or switching between, the TNF inhibitors and alternative MOA medication classes. METHODS: We analyzed medical and pharmacy claims for commercially insured patients who cycled or switched between targeted DMARD agents between January 1, 2010, and September 30, 2014 (ie, the index date), to determine treatment patterns (ie, treatment switching, discontinuation, restarting after a gap ≥60 days, or persistence) and costs (plan- and patient-paid) for 1 year postindex. The cost per persistent patient was the total healthcare cost divided by the number of treatment-persistent patients. RESULTS: The analysis included 6203 patients who cycled between TNF inhibitors, 2640 patients who switched from TNF inhibitors to alternative MOA agents, 699 patients who cycled between alternative MOA agents, and 687 patients who switched from alternative MOA agents to TNF inhibitors. The 1-year treatment persistence rates (with P values vs TNF inhibitor cyclers) were 45.2% for TNF inhibitor cyclers, 50.3% for TNF inhibitor-alternative MOA switchers (P <.001), 51.4% for alternative MOA agent cyclers (P = .002), and 46.1% for alternative MOA-TNF inhibitor switchers (P = .63). Compared with TNF inhibitor cyclers, the cost per persistent patient was lower for TNF inhibitor-alternative MOA switchers (-$16,853 RA-related; -$19,280 targeted DMARDs), alternative MOA agent cyclers (-$21,662 RA-related; -$25,153 targeted DMARDs), and alternative MOA-TNF inhibitor cyclers (-$7206 RA-related; -$7919 targeted DMARDs). CONCLUSION: Among patients with RA, patients who switched from a TNF inhibitor to an alternative MOA agent and those who cycled between alternative MOA agents had significantly higher treatment persistence rates and a substantially lower cost per persistent patient than those who cycled between TNF inhibitors. These findings support the evaluation of switching medication classes for patients with RA when a targeted therapy fails.
29236221 DPP-4 Inhibitor-Induced Rheumatoid Arthritis Among Diabetics: A Nested Case-Control Study. 2018 Feb INTRODUCTION: The risk of rheumatoid arthritis (RA) associated with dipeptidyl peptidase-4 inhibitor (DPP-4i) use is unclear. This study assesses the RA risk associated with DPP-4i use among a diabetic cohort initiating second-line therapy. METHODS: This was a nested case-control study, using the adult diabetic population starting second-line antidiabetic therapy from IMS LifeLink Plus(®) database (2006-2015). Cases were those with two or more RA diagnosis, at least one prescription, and 180 days enrollment prior to the event date (earliest of the two: first RA diagnosis, first RA prescription). Controls were drawn from the nest after matching (1:15) with cases on index date (± 90 days), age (± 5 years), sex, and event date (imputed to have the same time difference between cohort entry and event date as the matched case). Exposure and covariate information was gathered from the 180-day period prior to event date. Conditional logistic regression was used to assess exposure among cases and controls. Adjusted analysis was carried out after controlling for important medications and comorbidities. RESULTS: The final sample consists of 790 cases and 11,850 controls; of these, 151 cases (19.11%) and 2177 controls (18.37%) had DPP-4i claims during the exposure assessment period. DPP-4i therapy was not significantly associated with the development of RA after adjusting for covariates (OR = 1.156, 95% CI 0.936-1.429). Changing the exposure definition or exposure window to 1 year and subgroup analyses yielded similar results except for the non-insulin-using subgroup (OR = 1.299, 95% CI 1.001-1.985) which showed a significant positive association. CONCLUSION: DPP-4i were not significantly associated with the risk of RA compared with other second-line antidiabetic therapies.
30450276 Recurrent rheumatoid pleural effusions complicated by Mycobacterium heckeshornense infecti 2018 A 41-year-old man with rheumatoid arthritis (RA) presented with worsening dyspnea and deconditioning. He had recently been treated with adalimumab for rheumatoid pleural effusions but developed non-tuberculous mycobacterial pleurisy due to Mycobacterium heckeshornense. Despite therapy with appropriate anti-mycobacterial agents, he ultimately required video assisted thoracoscopy for decortication. While Mycobacterium heckeshornense has been reported to cause infection in multiple sites including the lung, this is the first case to our knowledge of infection confined to the pleural space. Rheumatoid pleural effusions can be complex and difficult to treat, especially when complicated by mycobacterial infection.
30441255 Towards the Establishment of a Biomedical Ontology for the Primary Sjögren's Syndrome. 2018 Jul Primary Sjögren's Syndrome (pSS) has been characterized as a hypersensitivity reaction type II systemic autoimmune chronic disease causing exocrine gland dysfunction mainly affecting women near the menopausal age. pSS patients exhibit dryness of the main mucosal surfaces and are highly prone to lymphoma development. This paper presents a first biomedical ontology for pSS based on a reference model which was determined by pSS clinical experts. The ensuing ontology constitutes the fundamental basis for mapping pSS-related ontologies from international cohorts to a common ontology. The ontology mapping (i.e., schematic interlinking) procedure is, in fact, a preliminary step to harmonize heterogeneous medical data obtained from various cohorts.
30632530 Sorafenib Reveals Anti-Arthritic Potentials in Collagen Induced Experimental Arthritis Mod 2018 Sep OBJECTIVES: This study aims to examine the effects of sorafenib on a collagen-induced arthritis model. MATERIALS AND METHODS: The study included 50 randomly selected female Wistar-albino rats (8-10-week-old, weighing between 200 g to 250 g). The rats were divided into five equal groups as control, arthritis, etanercept, sorafenib high-dose, and sorafenib low-dose groups, respectively. Arthritis was induced by injecting mixed intradermal chicken type II collagen and incomplete Freund's adjuvant. Twenty-four hours after the advent of arthritis; rats in group 3 were injected subcutaneous etanercept (6 mg/kg/week), while those in groups 4 and 5 were given sorafenib (10 or 30 mg/ kg/day) orally until they were sacrificed on the 34th day. The rat claws and trunk bloods were carefully examined to note perisynovial inflammation and cartilage/bone injury through histopathology. Tissue vascular endothelial growth factor (VEGF) and VEGF receptor levels were carefully checked using western blot analysis. RESULTS: Analysis of the experimental data showed that collagen-induced arthritis decreased in treatments groups after 12-13 days and 34th day in contrast with the arthritis group. Histopathological examination revealed broad perisynovial inflammation and cartilage/bone break down in the arthritis group. Compared to the control group, tissue VEGF and VEGF receptor levels increased in the arthritis group. Sorafenib and etanercept decreased tissue VEGF and VEGF receptor levels, perisynovial inflammation, damage of cartilage/bone. CONCLUSION: Our findings indicate that sorafenib treatment ameliorates collagen-induced arthritis with anti-VEGF effectiveness.
30109356 Quetiapine ameliorates collagen-induced arthritis in mice via the suppression of the AKT a 2018 Oct OBJECTIVE AND DESIGN: To investigate the amelioration effects of quetiapine on rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis (CIA) DBA/1J mouse model. SUBJECTS: RAW 264.7 macrophage and DBA/1J mice. TREATMENT: Lipopolysaccharide and collagen. METHODS: RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β were analyzed by ELISA. Proteins involved in signaling pathways related to the formation of rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of quetiapine in CIA mouse model was also assayed. (18)F-FDG/micro-PET was used to monitor the inflammation status in the joints, and the severity of bone erosion was evaluated with micro-CT and H&E staining. RESULTS: The inhibition of pro-inflammatory cytokines by quetiapine was found through the ERK and AKT phosphorylation and subsequent NF-κB and CREB signaling pathways. Pro-inflammatory cytokines such as IL-17, IL-6 and IL-1β were decreased, while immunosuppressive factors such as TGF-β and IL-10 were increased in CIA mice treated with quetiapine. Notably, no uptake of (18)F-FDG and bone erosion was found with micro-PET images on days 32 and 43 in the quetiapine-treated and normal control groups. However, significant uptake of (18)F-FDG could be observed in the CIA group during the same time course. Similar results were further verified with ex vivo autoradiography. CONCLUSION: Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.