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ID PMID Title PublicationDate abstract
31372115 Impaired renal functions in Pakistani cohort of rheumatoid arthritis. 2019 Jul OBJECTIVE: To determine the frequency of impaired renal functions and hypertension in rheumatoid arthritis. METHODS: This study was conducted between May 1(st) 2018 to February 1(st) 2019 at Rheumatology Division, Department of Medicine Central Park Medical College Lahore, total 260 study participants were selected, demographic detail were asked in detail, disease duration of RA and hypertension, DMARD's, self-use NSAID's,/hakeem medications, smoking were asked in detail, BMI and blood pressure were measured,5 ml of blood was taken by trained phlebotomist, and sent for the estimation of serum urea and creatinine on (COBAS-III) machine, after availability of results each individuals eGFR (creatinine clearance) was calculated by Cockroft Gualt((CG)) and Modification in diet in renal disease method (MDRD). RESULTS: In this study the mean age of study participants was 42.4 (± 9.5) years with disease duration of 7.7(±4.8) years, prevalence of Impaired renal functions of 14.6% (n=38) and hypertension in 53.5% (n=139).Regression analysis shows there is significant association between hypertension, smoking and self/hakeem medications with impaired renal functions (p-0.5). Kappa analysis shows both (MDRD & CG methods) had uniformity in picking up cases of impaired renal functions 75.6% (p-0.05). CONCLUSION: In RA decline in renal functions is seen with self-use NSAID's/hakeem medications along with other modifiable factors like smoking and hypertension, while conventional DMARD's don't show association with decline. There is very high prevalence of hypertension in rheumatoid arthritis.
33093874 Indications and outcome in total elbow arthroplasty: A systematic review. 2020 Oct BACKGROUND: Total elbow arthroplasty (TEA) is the established treatment for end-stage rheumatoid arthritis but improved surgical techniques have resulted in expanded indications. The aim of this study is to review the literature to evaluate the evolution of surgical indications for TEA. METHODS: A systematic review of PubMed and EMBASE databases was conducted. Case series and comparative studies reporting results after three types of primary TEA were eligible for inclusion. RESULTS: Forty-nine eligible studies were identified (n = 1995). The number of TEA cases published annually increased from 6 cases in 1980 to 135 cases in 2008. The commonest indication for TEA throughout the review period was rheumatoid arthritis but its annual proportion reduced from 77% to 50%. The mean Mayo Elbow Performance Score significantly improved for all indications. Three comparative studies reported statistically improved functional outcomes in rheumatoid arthritis over the trauma sequelae group. Complication and revision rates varied; rheumatoid arthritis 5.2-30.9% and 11-13%, acute fracture 0-50% and 10-11%, trauma sequelae 14.2-50% and 0-30%, osteoarthritis 50% and 11%, respectively. DISCUSSION: TEA can provide functional improvements in inflammatory arthritis, acute fractures, trauma sequelae and miscellaneous indications. Long-term TEA survivorship appears satisfactory in rheumatoid arthritis and fracture cases; however, further research into alternative surgical indications is still required.
30858630 The rheumatoid hand in the light of fluorescence: a diagnostic technique of the future? 2019 Fluorescence spectroscopy is usually applied in physics, chemistry and related sciences. However, in recent years we can observe a growing interest in fluorescence spectroscopy for medical diagnostics. Currently, it is beginning to be used in the monitoring of rheumatoid arthritis (RA) activity. As the knowledge on RA increases, growing importance is being placed on the evaluation of synovitis. Today, it is difficult to imagine contemporary rheumatology without ultrasound (US) and magnetic resonance imaging (MRI). However, it turns out that these are not the only methods allowing one to visualise subclinical lesions, particularly synovitis. Fluorescence optical imaging (FOI) is also useful for the evaluation of inflammatory lesions in the joints. In the future, FOI may become competitive with "traditional" imaging studies. It is characterised by low cost, short duration and similar sensitivity to US.
32010893 Association of Signal Transducer and Activator of Transcription 4 rs10181656 Polymorphism 2019 Dec OBJECTIVES: This study aims to investigate the association of polymorphism rs10181656 (C>G) of signal transducer and activator of transcription 4 (STAT4) gene with rheumatoid arthritis (RA) and systemic sclerosis (SSc) in the southwest of Iran as well as the probable relationship between the polymorphism with clinical features and disease activity parameters in both diseases. PATIENTS AND METHODS: A total of 200 patients (120 with RA [21 males, 99 females; mean age 44.83 years; range, 16 to 75 years] and 80 with SSc [13 males, 67 females; mean age 44.3 years; range, 30 to 75 years]) and 120 healthy controls (25 males, 95 females; mean age 46.93 years; range, 30 to 75 years) were recruited in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. A set of genotypes was confirmed by sequencing. RESULTS: A statistically significant association was detected between STAT4 rs10181656 polymorphism and RA (p=0.007). No significant correlation was detected between STAT4 rs10181656 polymorphism and SSc (p=0.357). None of the clinical features (anti-cyclic citrullinated peptide, rheumatoid factor) or disease activity parameters (limited cutaneous SSc, diffuse cutaneous SSc) showed any correlation with the genotype distribution of the STAT4 rs10181656 polymorphism in RA or SSc patients. CONCLUSION: Our findings suggest an association between RA susceptibility and STAT4 rs10181656 polymorphism. However, no significant association was found between the mentioned polymorphism and SSc. Clinical features and disease activity parameters did not show any association with the polymorphism.
30871014 Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases. 2019 Mar 12 In 2018, Baricitinib was approved by the Food and Drig Administration (FDA) for the treatment of rheumatoid arthritis. Baricitinib exerts its action by targeting Janus kinases (JAK). In this study, we describe the necessary steps for preparing the drug using two alternative routes.
30593897 Fatty acids uptake and oxidation are increased in the liver of rats with adjuvant-induced 2019 Mar 1 Severe rheumatoid cachexia is associated with pronounced loss of muscle and fat mass in patients with advanced rheumatoid arthritis. This condition is associated with dyslipidemia and predisposition to cardiovascular diseases. Circulating levels of triglycerides (TG) and free fatty acids (FFA) have not yet been consistently defined in severe arthritis. Similarly, the metabolism of these lipids in the arthritic liver has not yet been clarified. Aiming at filling these gaps this study presents a characterization of the circulating lipid profile and of the fatty acids uptake and metabolism in perfused livers of rats with adjuvant-induced arthritis. The levels of TG and total cholesterol were reduced in both serum (10-20%) and liver (20-35%) of arthritic rats. The levels of circulating FFA were 40% higher in arthritic rats, possibly in consequence of cytokine-induced adipose tissue lipolysis. Hepatic uptake and oxidation of palmitic and oleic acids was higher in arthritic livers. The phenomenon results possibly from a more oxidized state of the arthritic liver. Indeed, NADPH/NADP(+) and NADH/NAD(+) ratios were 30% lower in arthritic livers, which additionally presented higher activities of the citric acid cycle driven by both endogenous and exogenous FFA. The lower levels of circulating and hepatic TG possibly are caused by an increased oxidation associated to a reduced synthesis of fatty acids in arthritic livers. These results reveal that the lipid hepatic metabolism in arthritic rats presents a strong catabolic tendency, a condition that should contribute to the marked cachexia described for arthritic rats and possibly for the severe rheumatoid arthritis.
31126875 Interleukin-34 as a promising clinical biomarker and therapeutic target for inflammatory a 2019 Jun Interleukin-34 (IL-34), recently identified as a novel inflammatory cytokine and the second ligand for colony-stimulating factor-1 receptor, is known to play regulatory roles in the development, maintenance, and function of mononuclear phagocyte lineage cells - especially osteoclasts. Regarding its primary effect on osteoclasts, IL-34 has been shown to stimulate formation and activation of osteoclasts, which in turn magnifies osteoclasts-resorbing activity. In addition to its role in osteoclastogenesis, IL-34 has been implicated in inflammation of synovium via augmenting production of inflammatory mediators, in which altered IL-34 expression is regulated by pro-inflammatory cytokines responsible for cartilage degradation. Indeed, IL-34 has been documented to be highly expressed in inflamed synovium of rheumatoid arthritis (RA) and knee osteoarthritis (OA) patients, which are recognized as inflammatory arthritis. Furthermore, a number of clinical studies demonstrated that IL-34 levels were significantly increased in the circulation and synovial fluid of patients with RA and knee OA. Its levels were also found to be positively associated with disease severity - especially radiographic severity of both RA and knee OA patients. Interestingly, emerging evidence has accumulated that functional blockage of IL-34 with specific antibody can alleviate the severity of inflammatory arthritis. It is therefore reasonable to speculate that IL-34 may be developed as a potential biomarker and a new therapeutic candidate for inflammatory arthritis. To date, there are numerous studies showing IL-34 involvement and association with many aspects of inflammatory arthritis. Herein, this review aimed to summarize the recent findings regarding regulatory role of IL-34 in synovial inflammation-mediated cartilage destruction and update the current comprehensive knowledge on usefulness of IL-34-based treatment in inflammatory arthritis - particularly RA and knee OA.
30687331 Treatment Effects of the Second-Generation Tyrosine Kinase Inhibitor Dasatinib on Autoimmu 2018 Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that primarily manifests as persistent synovitis and progressive joint destruction. Imatinib exhibited a therapeutic effect in murine collagen-induced arthritis (CIA) via selective inhibition tyrosine kinases. The second-generation tyrosine kinase inhibitor dasatinib exhibits more durable hematological and cytogenetic effects and more potency compared to imatinib. However, the effect of dasatinib on CIA is poorly understood. The present study investigated the treatment effect of dasatinib on autoimmune arthritis. We demonstrated that dasatinib alleviated arthritis symptoms and histopathological destruction in CIA mice. Dasatinib treatment inhibited the production of proinflammatory cytokines including IL-1β, TNF-α, and IL-6, and promoted the production of the anti-inflammatory cytokine IL-10. Dasatinib treatment also suppressed the expression of anti-mouse CII antibodies including total IgG, IgG1, IgG2, and IgG2b, in CIA mice. We further demonstrated that dasatinib inhibited the migration and proliferation of fibroblast-like synoviocytes (FLS) from RA patients and promoted FLS apoptosis. The mRNA expression of MMP13, VEGF, FGF, and DKK1 was down-regulated in FLS treated with dasatinib. Our findings suggest that dasatinib exhibited treatment effects on CIA mice and that FLS are an important target cell of dasatinib treatment in autoimmune arthritis.
31548752 Acute coronary syndrome leading to revision of a co-morbid condition in a young man with a 2019 Although patients with rheumatoid arthritis (RA) may have an increased incidence of cardiovascular events, the development of coronary artery disease and of myocardial infarction at young age is rather uncommon. Herein, we report a case of a 26-year-old man without classical cardiovascular risk factors, but with a 2-year history of RA, who experienced recurrent episodes of angina-like chest pain. His electrocardiogram showed ST-elevation and T-wave inversion in anterior chest leads, and the patient was sent for coronary angiography, which revealed multivessel coronary artery disease. Subsequently, the patient underwent coronary artery bypass grafting. Closer analysis of the patient's history and of the laboratory findings led to revision of the diagnosis of RA: the patient was found to meet the classification criteria for systemic lupus erythematosus. Pitfalls of the classification criteria and the impact of the revised diagnosis on the patient's care are discussed.
31172817 Effect of mandarin peel extract on experimentally induced arthritis in male rats. 2021 Apr BACKGROUND: Rheumatoid arthritis (RA) is associated with joint damage. For treatment, non-steroidal anti-inflammatory drugs (NSAIDs), steroidal agents, and immune-suppressants are used. Their side-effects require a safe and effective natural alternative. ANIMALS AND METHODS: Thirty-six male albino rats, half kept under observation for 1 week (group I) and others for 2 weeks (group II) were used. Each group was subdivided into: normal (A), RA (B), and oral mandarin-peel extract (MPE) treated (C). Ankle diameter, serum levels of RF, interleukin (IL)-1β, TNFα, IL-4, IL-10, liver homogenates malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) were measured together with the histopathological examination. RESULTS: MPE treatment was associated with increased serum IL-4, IL-10, liver homogenates GSH, and SOD, and decreased ankle diameter, serum RF, IL-1β, TNFα, liver homogenates MDA, NO, inflammatory cell infiltrate, and necrosis. Two weeks' treatment was better. CONCLUSIONS: MPE has useful effects in alleviating the disturbed ankle diameter, serum pro- and anti-inflammatory mediators, oxidative stress, and ankle joint histopathology in rheumatic rats.
30679969 Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases. 2019 Feb The cardiovascular effects of disease-modifying antirheumatic drugs and particularly of methotrexate (MTX) are complex and frequently incorrectly understood, which might lead to the unjustified discontinuation of this treatment. MTX, 'the gold standard' and first line treatment in rheumatoid arthritis, psoriatic arthritis, and other immune-mediated inflammatory diseases, has been proven to decrease inflammation, improve cardiovascular risk factors, and reduce mortality. This is supported by both the mechanism of action, as well as a body of clinical data evidence. MTX's cardiovascular effects, although incompletely understood, are explained by its antiproliferative, immunosuppressive, anti-inflammatory, and antiatherogenic effects. Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, decreased risk of major cardiovascular adverse events, and benefits on survival. Given its systemic cardiovascular effects, MTX could be regarded as an important therapeutic agent not only to control disease activity in rheumatic diseases, but also to reduce cardiovascular risk and mortality.
30205019 Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfat 2019 Jan Heparan sulfate (HS) proteoglycans on immune cells have the ability to bind to and regulate the bioactivity more than 400 bioactive protein ligands, including many chemokines, cytokines, and growth factors. This makes them important regulators of the phenotype and behavior of immune cells. Here we review how HS biosynthesis in macrophages is regulated during polarization and in chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, asthma, chronic obstructive pulmonary disease and obesity, by analyzing published micro-array data and mechanistic studies in this area. We describe that macrophage expression of many HS biosynthesis and core proteins is strongly regulated by macrophage polarization, and that these expression patterns are recapitulated in chronic inflammation. Such changes in HS biosynthetic enzyme expression are likely to have a significant impact on the phenotype of macrophages in chronic inflammatory diseases by altering their interactions with chemokines, cytokines, and growth factors.
31520803 JAK inhibitors for the treatment of autoimmune and inflammatory diseases. 2019 Nov Cytokines play a central role in the pathophysiology of autoimmune and inflammatory diseases. Several cytokines signal through the JAK-STAT pathway, which is now recognized as a major target to inhibit the effect of a wide array of cytokines. JAK inhibitors are increasingly used in the setting of inflammatory and autoimmune diseases. While the currently approved drugs are panJAK inhibitors, more selective small molecules are being developed and tested in various rheumatic disorders. In this extensive review, we present evidence- or hypothesis-based perspectives for these drugs in various rheumatologic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, giant cell arteritis, and autoinflammatory diseases.
30910433 Antigen-induced arthritis of the temporomandibular joint via repeated injections of bovine 2019 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease and the temporomandibular joint (TMJ) is affected in up to 50%, resulting in pain, limited mouth opening and dental malocclusion. The outcome of conservative and surgical therapies is unsatisfying in many cases. The purpose of this study was to establish a large animal model of antigen-induced arthritis (AIA) of the TMJ that enables the investigation of the pathogenesis of RA and the evaluation of new therapies. In five domestic pigs, systemic immunization was performed via consecutive intramuscular injections of bovine serum albumin (BSA). Then, AIA was induced via the application of BSA into the TMJ. Injection with saline served as the control. After ten weeks, the joints and adjacent tissues were harvested for histological analysis and cytokine quantification. The changes observed in the AIA specimens included severe synovial inflammation, cartilage-specific glycosaminoglycan content loss, and cartilage surface and discus alterations as well as the formation of chondrocyte clusters. Protein analyses of the synovia showed enhanced levels of IL-1β, IL-6, TNFα and VEGF. A porcine model of immunologic arthritis of the TMJ was successfully established. This model may be used in future studies to investigate the underlying pathogenesis of RA and new therapeutic strategies.
31709258 Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Cu 2019 Rheumatoid arthritis (RA) is a type of inflammatory arthritis that affects ~1% of the general population. Although arthritis is the cardinal symptom, many extra-articular manifestations can occur. Lung involvement and particularly interstitial lung disease (ILD) is among the most common. Although ILD can occur as part of the natural history of RA (RA-ILD), pulmonary fibrosis has been also linked with methotrexate (MTX); a condition also known as MTX-pneumonitis (M-pneu). This review aims to discuss epidemiological, diagnostic, imaging and histopathological features, risk factors, and treatment options in RA-ILD and M-pneu. M-pneu, usually has an acute/subacute course characterized by cough, dyspnea and fever. Several risk factors, including genetic and environmental factors have been suggested, but none have been validated. The diagnosis is based on clinical and radiologic findings which are mostly consistent with non-specific interstitial pneumonia (NSIP), more so than bronchiolitis obliterans organizing pneumonia (BOOP). Histological findings include interstitial infiltrates by lymphocytes, histiocytes, and eosinophils with or without non-caseating granulomas. Treatment requires immediate cessation of MTX and commencement of glucocorticoids. RA-ILD shares the same symptomatology with M-pneu. However, it usually has a more chronic course. RA-ILD occurs in about 3-5% of RA patients, although this percentage is significantly increased when radiologic criteria are used. Usual interstitial pneumonia (UIP) and NSIP are the most common radiologic patterns. Several risk factors have been identified for RA-ILD including smoking, male gender, and positivity for anti-citrullinated peptide antibodies and rheumatoid factor. Diagnosis is based on clinical and radiologic findings while pulmonary function tests may demonstrate a restrictive pattern. Although no clear guidelines exist for RA-ILD treatment, glucocorticoids and conventional disease modifying antirheumatic drugs (DMARDs) like MTX or leflunomide, as well as treatment with biologic DMARDs can be effective. There is limited evidence that rituximab, abatacept, and tocilizumab are better options compared to TNF-inhibitors.
31118842 Achieving comprehensive remission or low disease activity in rheumatoid patients and its i 2019 PURPOSE: Ability to work is an important endpoint in rheumatoid arthritis (RA). It is not clear what outcome measures should be used to guide treatment in order to maximize workability. This study addressed the impact of RA on workability in a Saudi population and examined the correlation between objective measures of disease activity and reduced workability. This will allow better understanding of treatment targets that will translate into improved workability. PATIENTS AND METHODS: Data were collected through a digital patient record keeper: The Rheumatoid Arthritis Saudi Database. Male and female patients, ≥18 years of age, that met the American College for Rheumatology criteria for diagnosis of RA, were recruited, regardless of treatment. Demographic and disease-specific data were collected. Disease Activity Score-28 (DAS-28) was used to define patients as low (DAS-28 ≤3.2) vs high (DAS-28 >3.2) disease activity. Health assessment questionnaire (HAQ) score, visual analog scale (VAS) score, and musculoskeletal ultrasound 7 joint score were documented also. The work productivity and activity impairment (WPAI) score was used to measure absenteeism, presenteeism, overall work impairment, and activity impairment. DAS-28 score was correlated with WPAI score and linear regression used to identify the demographic and measures of treatment response that predict improvement in WPAI score. RESULTS: Higher absenteeism and more activity impairment were seen for patients with persistent DAS-28 >3.2 (non-achievers). HAQ and VAS scores correlated with presenteeism, overall work impairment, and activity impairment. CONCLUSION: Disease activity, as defined by DAS-28 score, correlates with absenteeism and work impairment in a Saudi population. However, on linear regression analysis, HAQ and VAS scores were the only measures predictive of work impairment. These scores should be used to monitor response to treatment regimens that aim to maximize work potential for Saudi individuals.
31766745 Exercise Exacerbates the Transcriptional Profile of Hypoxia, Oxidative Stress and Inflamma 2019 Nov 22 Physical exercise (PE) is recommended for Rheumatoid Arthritis (RA), but the molecular and biological mechanisms that impact the inflammatory process and joint destruction in RA remain unknown. The objective of this study was to evaluate the effect of PE on the histological and transcriptional changes in the joints of adjuvant-induced arthritis (AIA) rat model. AIA rats were subjected to PE on a treadmill for eight weeks. The joints were subjected to histological and microarray analysis. The differentially expressed genes (DEGs) by PE in the arthritic rats were obtained from the microarray. The bioinformatic analysis allowed the association of these genes in biological processes and signaling pathways. PE induced the differential expression of 719 genes. The DEGs were significantly associated with pathogenic mechanisms in RA, including HIF-1, VEGF, PI3-Akt, and Jak-STAT signaling pathways, as well as response to oxidative stress and inflammatory response. At a histological level, PE exacerbated joint inflammatory infiltrate and tissue destruction. The PE exacerbated the stressed joint environment aggravating the inflammatory process, the hypoxia, and the oxidative stress, conditions described as detrimental in the RA joints. Research on the effect of PE on the pathogenesis process of RA is still necessary for animal models and human.
30533376 A successful treatment of rheumatoid arthritis-related interstitial pneumonia with ninteda 2019 Rheumatoid arthritis-related interstitial pneumonia with a usual interstitial pneumonia (RA-UIP) has a poor prognosis and a new treatment strategy is required. The antifibrotic agent nintedanib reduces the annual rate of decline in forced vital capacity (FVC) in idiopathic pulmonary fibrosis (IPF) patients. Recently, the potential efficacy of antifibrotic agents against chronic progressive fibrotic diseases including RA-UIP has been attracting attention. A 74-year-old man diagnosed with IPF on high-resolution computed tomography (HRCT). His FVC was decreasing over time, and his exertional dyspnea and cough had progressed with progression of reticulation on imaging. He was treated with nintedanib, which resulted in decreased coughing together with a reduction in FVC decline, from -11.6%/year to -5.2%/year. A swollen joint appeared eight months after this intervention, and he was diagnosed with rheumatoid arthritis. In this patient, nintedanib was effective against RA-UIP. This is the first case in which nintedanib was shown to be effective for RA-UIP.
30937478 [Adult-onset Still's disease : Rare adult-onset autoinflammatory syndrome]. 2019 Jul Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by high spiking fever, arthritis, salmon-pink maculopapular rash and multiple organ involvement. We report a case of an adult-onset Still's disease that meets Yamaguchi's criteria and presented with typical clinical manifestations. AOSD is treated with anti-inflammatory medications. Standard therapy includes corticosteroids. Other medications like azathioprine, methotrexate or interleukin-1 or -6 blockers can be used when standard steroid treatment is not adequate.
31853784 Autoimmunity and Inflammation Link to Cardiovascular Disease Risk in Rheumatoid Arthritis. 2020 Mar Rheumatoid arthritis (RA) patients have a 50% increased risk of cardiovascular (CV)-related morbidity and mortality. This excess CV risk is closely linked to RA disease severity and chronic inflammation, hence is largely underestimated by traditional risk calculators such as the Framingham Risk Score. Epidemiological studies have shown that patients with RA are more likely to have silent ischemic heart disease, develop heart failure, and experience sudden death compared with controls. Elevations in pro-inflammatory cytokines, circulating autoantibodies, and specific T cell subsets, are believed to drive these findings by promoting atherosclerotic plaque formation and cardiac remodeling. Current European League Against Rheumatism (EULAR) guidelines state that rheumatologists are responsible for the assessment and coordination of CV disease (CVD) risk management in patients with RA, yet the optimal means to do so remain unclear. While these guidelines focus on disease activity control to mitigate excess CV risk, rather than providing a precise algorithm for choice of therapy, studies suggest a differential impact on CV risk of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), biologic DMARDs, and small molecule-based therapy. In this review, we explore the mechanisms linking the pathophysiologic intrinsic features of RA with the increased CVD risk in this population, and the impact of different RA therapies on CV outcomes.