Browse

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

ID PMID Title PublicationDate abstract
30564449 Investigating sirukumab for rheumatoid arthritis: 2-year results from the phase III SIRROU 2018 OBJECTIVES: The phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group SIRROUND-D study evaluated long-term efficacy and safety of the interleukin (IL)-6 inhibitor, sirukumab, in patients with active rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients were randomised 1:1:1 to sirukumab 100  mg every 2 weeks (q2w), 50  mg every 4 weeks or placebo q2w subcutaneously. Patients initially randomised to placebo were rerandomised at Weeks 18, 40 or 52 to one of the sirukumab groups until Week 104. RESULTS: Of 1670 randomised patients, 1402 were included in the full analysis set and 1269 in the radiographic analysis set at Week 104. American College of Rheumatology scores, Disease Activity Score based on C-reactive protein, Clinical Disease Activity Index and clinically meaningful improvements in patient-reported outcomes were sustained at Week 104 among patients initially randomised to sirukumab. Placebo patients subsequently rerandomised to sirukumab showed clinical improvements at Week 104 that were comparable to results among patients initially randomised to sirukumab. Radiographic progression from Week 52 to Week 104 was comparable between all groups whether initially randomised to sirukumab or subsequently rerandomised to sirukumab from placebo. No new safety signals were identified in the extended exposure period compared with the initial 52 weeks of treatment. CONCLUSIONS: Sirukumab treatment resulted in sustained reductions in clinical signs and symptoms and minimal progression in radiographic damage over 2 years among patients with RA refractory to DMARDs. The safety profile of sirukumab was as expected for an anti-IL-6 agent, with no new signals reported.
30519074 Genetic polymorphism of the methotrexate transporter ABCG2, blood pressure and markers of 2018 PURPOSE: Methotrexate (MTX) treatment is associated with lower blood pressure (BP) and arterial stiffness in rheumatoid arthritis (RA). We investigated associations between single-nucleotide polymorphism (SNP) of the ATP-binding cassette efflux transporter gene ABCG2 (rs2231142), BP, and arterial stiffness in RA patients treated with MTX. PATIENTS AND METHODS: Clinical and 24-hour peripheral and central BP, arterial wave reflection (Augmentation Index, AIx), arterial stiffness (Pulse Wave Velocity, PWV), and intracellular MTX polyglutamate (MTXPGs) concentrations were assessed in 56 RA patients on stable treatment with MTX using a repeated cross-sectional study design with measurements at baseline and after 8 months. RESULTS: Majority of the RA patients were homozygotes for the normal allele (CC, n=46) whereas 10 were rs2231142 heterozygotes (AC, n=10). MTXPGs concentrations were non-significantly higher in AC when compared to CC (144.3 vs 116.3 nmol/L packed RBCs, P=0.10). At baseline, the AC group had significantly lower age-adjusted clinical systolic BP (SBP) (P=0.01), 24-hour peripheral SBP (P=0.003), and central SBP (P=0.02) when compared to the CC group. However, AIx and PWV values were not significantly different between the two groups. When data from both visits were combined in a single analysis, and additionally adjusted for visit, gender, body mass index, and Disease Activity Score 28, the trend in SBP differences between-groups persisted but was no longer significant. CONCLUSION: Future studies are required to test the hypothesis that this genetic polymorphism is associated with lower BP, arterial stiffness, and possibly, cardiovascular risk, in RA patients treated with MTX.
30233362 The Bone-Protecting Efficiency of Chinese Medicines Compared With Western Medicines in Rhe 2018 Background: Rheumatoid Arthritis (RA) is a systemic autoimmune disease leading to joint destruction. The prevention of bone and cartilage destruction has received increased attention in recent years. Objective: To evaluate the current evidences regarding the bone-protecting efficacy of Chinese medicine or the combination of Chinese medicine and Western medicine for RA. Methods: We comprehensively searched PubMed, Embase, the Cochrane Library (www.thecochranelibrary.com), the China National Knowledge Infrastructure (CNKI), the Database for Chinese Technical Periodicals (VIP), and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the two therapy methods. Results: Sixteen studies including 1,171 patients were included in the final analysis. The results showed that Chinese medicine could significantly improve the bone mineral density (BMD) (mean difference [MD] = 0.05 /g·cm(-2), 95% CI [0.03, 0.08], P < 0.00001), and decrease the serum matrix metalloproteinase 3 (MMP-3) ([SMD] = -2.84, 95% CI [-4.22, -1.47], P < 0.0001). Conclusions: Chinese medicine may provide an efficiently alternative choice for the treatment of RA in terms of the bone-protecting efficiency. Given the inherent limitations of the included studies, future well-designed RCTs are required to confirm and update the findings of this analysis.
29342965 Lipid-Based Nanoparticles as a Potential Delivery Approach in the Treatment of Rheumatoid 2018 Jan 15 Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease, results in immune dysfunction and destruction of joints and cartilages. Small molecules and biological therapies have been applied in a wide variety of inflammatory disorders, but their utility as a therapeutic agent is limited by poor absorption, rapid metabolism, and serious side effects. To improve these limitations, nanoparticles, which are capable of encapsulating and protecting drugs from degradation before they reach the target site in vivo, may serve as drug delivery systems. The present research proposes a platform for different lipid nanoparticle approaches for RA therapy, taking advantage of the newly emerging field of lipid nanoparticles to develop a targeted theranostic system for application in the treatment of RA. This review aims to present the recent major application of lipid nanoparticles that provide a biocompatible and biodegradable delivery system to effectively improve RA targeting over free drugs via the presentation of tissue-specific targeting of ligand-controlled drug release by modulating nanoparticle composition.
29891264 Homologies and heterogeneity between Rheumatology Congresses: Mexican, American College of 2020 Mar BACKGROUND: Medical meetings are a tool to help physicians advance and update their medical knowledge. Their quality is the responsibility of colleges and institutions. OBJECTIVE: To assess and compare the academic level of four different annual rheumatology meetings. MATERIAL AND METHODS: As a source of information, we used the abstracts published in the supplements of the journal Reumatología Clínica, SE1 Vol. 12, issued in February 2016, SE 1 Vol. 13 issued in February 2017, the electronic application of the 2016 ACR/ARHP of the 2016 American Congress of Rheumatology, devoted to the works presented at the 44th Mexican Congress of Rheumatology (CMR 44), the 45th Mexican Congress of Rheumatology (CMR 45), and the 2016 ACR/ARHP Annual Meeting (ACR 2016), as well as the Web page on the files and abstracts of EULAR 2017, respectively; from each work we compiled information on the major disease being referred to, the type of information provided and the type of report. We should point out that some were combined conditions or designs, from which we selected that which we considered to be the most important. RESULTS: In all, 275, 340, 3275 and 4129 studies were submitted to the XLIV Mexican Congress of Rheumatology, XLV Mexican Congress of Rheumatology, the 2016 ACR/ARHP Annual Meeting and EULAR 2017, respectively. Rheumatoid arthritis was the most common disorder, dealt with in 23%, 26%, 21% and 27% in CMR 44, CMR 45, 2016 ACR and EULAR 2017, respectively, followed by systemic lupus erythematosus; in third place, Mexican congresses reported trials related to systemic vasculitis, whereas spondylitis was the main subject of international congresses. In the case of rheumatoid arthritis, clinical topics accounted for 30% in the Mexican congresses and ACR, and nearly 20% in EULAR. Observational studies accounted for 40% in the Mexican congresses vs. 33% in 2016 ACR and 55% in EULAR 2017. Studies on basic science were minimal in the Mexican congress, whereas in 2016 ACR, they represented 21% and 12% in EULAR 2017. CONCLUSION: Rheumatology meetings constitute a tool to obtain adequate evidence-based medical knowledge in this important branch of medicine. For our Mexican Congress, we should encourage collaborative efforts between institutions, which will result in a greater number of controlled studies, clinical trials and basic studies that support the quality of the congress. We wish to emphasize that a greater diffusion of other musculoskeletal diseases is needed, not only autoimmune diseases, since the former represent an important percentage of the daily practice.
30487998 Efficacy, safety and immunogenicity of GP2015, an etanercept biosimilar, compared with the 2018 OBJECTIVES: To demonstrate the equivalent efficacy and compare the safety and immunogenicity of an etanercept biosimilar, GP2015, with reference etanercept (ETN) in patients with moderate-to-severe, active rheumatoid arthritis (RA), characterised by an inadequate response to synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: In the EQUIRA study, eligible patients (n=376) were randomised 1: 1 to 50  mg GP2015 or ETN subcutaneously, once weekly, for 24 weeks (treatment period 1). Patients from both groups, with at least moderate European League Against Rheumatism response at week 24, received GP2015 up to week 48 (treatment period 2). All patients continued to receive concomitant methotrexate at a stable dose (10-25  mg/week) until end of the study. The 24-week results are presented here. RESULTS: Equivalent efficacy between GP2015 and ETN was demonstrated if the 95% CI for the difference in disease activity score 28-joint count C reactive protein (DAS28-CRP) change from baseline to week 24 between treatment arms was contained within the prespecified equivalence margin range of -0.6 to 0.6. The least squares mean difference (GP2015-ETN) in change from baseline in DAS28-CRP up to week 24 was -0.07 (95% CI -0.26 to 0.12 [primary endpoint)]. The incidence of treatment-emergent adverse events was comparable between GP2015 (43.5%) and ETN (49.5%). None of the GP2015-treated patients developed neutralising anti-drug antibodies (NAbs) whereas 1.6% and 0.6% of patients in ETN group were NAb positive at weeks 4 and 12, respectively. CONCLUSION: In patients with RA who had an inadequate response to DMARDs, GP2015 demonstrated a similar efficacy and a comparable safety and immunogenicity profile with ETN. TRIAL REGISTRATION: NCT02638259.
30230962 Treatment of active rheumatoid arthritis: comparison of patients younger vs older than 75 2018 Objectives: Little information is available on the characteristics of elderly patients starting TNFα antagonist treatment for rheumatoid arthritis (RA). The objective of this work was to compare prescription patterns in RA patients younger vs. older than 75 years. Methods: Biologic-naive patients with active RA (DAS28 > 3.2) despite first-line therapy were included between 2007 and 2009 in the prospective, multicentre, longitudinal, observational, population-based CORPUS-RA cohort. TNFα antagonist users were defined as having received at least one TNFα antagonist during the first study year. The groups < 75 years and ≥ 75 years were compared regarding comorbidities, inflammation (CRP and ESR), disease activity (DAS28), disability (HAQ-DI), number of physician visits, and treatment. To verify the impact of the cut off, we also compared patients aged 70 years or more to patients younger than 70 years. Results: Of 543 RA patients, 382 had complete one-year follow-up data, including 114 TNFα antagonist users, 3 (6%) among the 49 patients aged 75 years or over and 111 (32%) of the 333 patients younger than 75 years (p < 0.01). Disease activity in the two age groups was similar at inclusion and after one year. Comorbidities and a history of auto-immunity were more common in the older group. Compared to their younger counterparts, the older patients received glucocorticoids more often (p = 0.003) and synthetic disease-modifying anti-rheumatic drugs less often (p = 0.01). Conclusion: TNFα antagonists are used less often and glucocorticoids more often in elderly patients with active RA compared to their younger counterparts. The fact that this study was performed in 2007-9 is a limitation in terms of relevance to today's patients and further studies should be conducted in new cohorts of active RA.
29531640 Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conve 2018 Feb 15 AIM: To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS: Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs (DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics. RESULTS: Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events (-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events (+5.85 mg/dL, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events (-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β = -0.58, P = 0.01) and hydroxychloroquine (β = -5.78, P = 0.01) use as predictors of lower post-medication-initiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure (β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events. CONCLUSION: No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.
29749583 IL-35: a new immunomodulator in autoimmune rheumatic diseases. 2018 Jun IL-35 is a relatively new cytokine that emerges as an important immunomodulator. IL-35 belongs to IL-12 cytokine family that includes IL-12, IL-23, IL-27, and IL-35. These cytokines are heterodimers that share subunits and their receptors also share subunits. Whereas IL-12 and IL-23 are clearly proinflammatory cytokines, the role of IL-35 is less clear. In mice, IL-35 appears to be anti-inflammatory and to protect from autoimmune inflammatory diseases. IL-35 induces the expansion of a subset of regulatory T cells (Tregs) and Bregs and mediates their suppressive function and inhibits Th17 cells. It also upregulates osteoprotegerin and suppresses RANKL, thus inhibiting bone resorption. In autoimmune rheumatic diseases, findings are conflicting, although in systemic lupus erythematosus, there is reduced function of IL-35. In psoriatic arthritis, a disease characterized by bone erosion and bone formation in peripheral joints and bone formation in spinal joints, serum levels of IL-35 were found increased in one study. Further data are required to define the exact role of IL-35 in human autoimmune rheumatic diseases.
29264638 Suicidal behaviors in patients with rheumatic diseases: a narrative review. 2018 Apr Chronic rheumatic disorders are characterized by inflammation and chronic pain, and both anxiety and depression have been frequently observed in these patients. Depression and chronic pain are recognized as risk factors for the development of suicidal behaviors. Accordingly, the objective of the present review is to provide a comprehensive review of suicidal behaviors associated with rheumatic diseases. Medline and EMBASE were searched for English language publications using key words related with rheumatic diseases, suicide, suicide attempts, and suicidal ideation. 34 records (30 full-length published papers and 4 studies published in abstract form) that included data related to the frequency and/or potential determinants of suicidal behaviors in rheumatic diseases were included in the review. It was found that both suicidal ideation and completed suicide seem to be more frequent in patients experiencing systemic lupus erythematosus, fibromyalgia and arthritis. Major determinants were comorbid depression in fibromyalgia and arthritis, and neuropsychiatric disease in systemic lupus erythematosus. Based on these findings, suicide risk should be assessed in patients suffering from systemic lupus erythematosus, fibromyalgia and/or arthritis.
29904406 Systematic review and meta-analysis of the efficacy and safety of Biqi capsule in rheumato 2018 Jun Biqi capsule is a Traditional Chinese Medicine preparation for treating rheumatoid arthritis (RA), and clinical studies have indicatedthat its effect may be more beneficial than that of Western medicine. The present study aimed to estimate the efficacy and safety of Biqi capsule alone or combined with methotrexate (MTX) compared with MTX alone for treating RA by performing a meta-analysis of randomized controlled trials and controlled clinical trials. A systematic literature search of studies published until March 2017 was performed. References from relevant studies were screened to obtain additional articles. The results were independently evaluated for relevance, and full-text studies were assessed for eligibility. The risk of bias was assessed using the Cochrane collaboration tool for assessing risk of bias. Out of 558 citations that were initially retrieved, a total of 5 studies comprising 522 patients met the inclusion criteria. The risk of bias of these trials was generally unclear or high. Meta-analysis indicated that Biqi capsule had better effects on C-reactive protein [standardized mean difference (SMD), -7.05; 95% CI -(10.77-3.33)] and tender joint count [SMD, -3.02; 95% CI, -(3.81-2.22)] and fewer adverse effects (AEs) than MTX [relative risk (RR), 0.19; 95% CI, 0.08-0.43]. Biqi capsule plus MTX was superior to MTX in terms of the total effect (RR, 1.17; 95% CI, 1.06-1.28), rheumatoid factor [SMD, -12.54; 95% CI, -(16.87-8.20)], swollen joint count [SMD, -1.50; 95% CI, -(1.99-1.01)], score of joint swelling [SMD -2.07; 95% CI, -(2.76-1.38)], tender joint count [SMD, -2.16; 95% CI, -(2.86-1.47)] and score of joint tenderness [SMD, -4.69; 95% CI, -(5.92-3.47)]. There was no difference in AEs between Biqi capsule plus MTX and MTX (RR, 0.71; 95% CI, 0.34-1.50). In conclusion, the present study indicated that compared with MTX, Biqi capsule plus MTX appeared to have more benefits but that Biqi capsule alone was not better for RA patients than MTX. In the other words, Biqi capsule plus MTX is more effective and has fewer AEs compared to MTX. However, the trials selected in the present meta-analysis have various limitations, including the lack of blinding and the short duration of the treatment; therefore, the conclusions are not sufficiently definitive. More randomized controlled trials are necessary to evaluate the use of Biqi capsule for managing RA.
30194599 In Vivo Analysis of Alpha-1-Antitrypsin Functions in Autoimmune Disease Models. 2018 Alpha-1-antitrypsin (AAT) is a circulating protein, a serpin, with multiple protective functions. Beside the well-known proteinase inhibitory function, which protects the lungs from chronic obstructive pulmonary disease (COPD), many studies have shown that AAT inhibits pro-inflammatory cytokine gene expression and functions. These anti-inflammatory and immune-regulatory properties have led to studies testing the therapeutic effect of AAT in autoimmune disease models. Initially, a study using recombinant adeno-associated viral (rAAV) vector showed that AAT gene therapy prevented type 1 diabetes (T1D) development in a nonobese diabetic (NOD) mouse model. Consequently, several studies confirmed that AAT therapy prevented and reversed T1D. AAT therapy has also been tested and has demonstrated protective effects in a collagen-induced arthritis model and a systemic lupus erythematosus (SLE) mouse model. This chapter describes methods that evaluate AAT functions in autoimmune mouse models.
29799788 Ursolic acid facilitates apoptosis in rheumatoid arthritis synovial fibroblasts by inducin 2018 May 25 Rheumatoid arthritis (RA) is characterized by hyperplastic pannus formation mediated by activated synovial fibroblasts (RASFs) that cause joint destruction. We have shown earlier that RASFs exhibit resistance to apoptosis, primarily as a result of enhanced expression of myeloid cell leukemia-1 (Mcl-1). In this study, we discovered that ursolic acid (UA), a plant-derived pentacyclic triterpenoid, selectively induces B-cell lymphoma 2 homology 3-only protein Noxa in human RASFs. We observed that UA-induced Noxa expression was followed by a consequent decrease in Mcl-1 expression in a dose-dependent manner. Subsequent evaluation of the signaling pathways showed that UA-induced Noxa is primarily mediated by the JNK pathway in human RASFs. Chromatin immunoprecipitation (IP) studies into the promoter region of Noxa indicated the role of transcription factor specificity protein 1 in JNK-mediated Noxa expression. Furthermore, the results from IP studies and proximity ligation assays indicated that UA-induced Noxa colocalizes and associates with Mcl-1 to prime it for proteasomal degradation through K(48)-linked ubiquitination by the selective recruitment of Mcl-1 ubiquitin ligase E3, a homologous to E6-associated protein C terminus domain-containing E3 ubiquitin ligase. These findings unveil a novel mechanism of inducing apoptosis in RASFs and a potential adjunct therapeutic strategy of regulating synovial hyperplasia in RA.-Kim, E. Y., Sudini, K., Singh, A. K., Haque, M., Leaman, D., Khuder, S., Ahmed, S. Ursolic acid facilitates apoptosis in rheumatoid arthritis synovial fibroblasts by inducing SP1-mediated Noxa expression and proteasomal degradation of Mcl-1.
30244468 Evaluation of Autoreactive Responses. 2018 Loss of tolerance to self-antigens is considered to be one of the initial reasons for the onset of rheumatoid arthritis (RA). Identification of self-antigens and evaluation of autoreactive antibodies can foster understanding of the pathogenesis of the disease and the development of new therapeutics. By detection of responses to a particular self-antigen, such as α-enolase, keratin, fibrinogen, fibronectin, collagen, or vimentin, in patient- and animal model-derived samples, high-affinity T-cell receptor-dependent activation of autoreactive T cells to self-antigens can be elucidated. This chapter introduces a simple method to estimate T-cell autoreactive responses to CII in a murine CIA model. A limiting dilution system is established in order to assess CII-dependent T-cell responses, which are reflected by the level of cytokine release.
29272556 Characterization of adherence and persistence profile in a real-life population of patient 2018 Apr AIMS: Published data on long-term adherence and persistence with adalimumab (Humira(®) ) in clinical practice are scarce and often limited to selected patient populations. This study assessed adherence with adalimumab across different indications and identified correlates and outcomes of poor adherence. METHODS: We analysed data originating from the electronic database of Maccabi Healthcare Services (MHS) that includes 2.1 million enrolees. We randomly selected patients with at least one dispense of adalimumab since it was included in the local health basket in Israel in 2008 until the end of 2013. Patients with the following indications (n = 1339) were included: Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriatic arthritis (PSA), ankylosing spondylitis (AS) and psoriasis. Adherence with therapy was assessed by the medication possession ratio (MPR) during the follow-up period. RESULTS: Good adherence (MPR ≥ 80%) was observed among 80% of study patients and was associated with lower risk for ≥1 hospitalization per year of follow-up (adjusted-OR = 1.94, 95% CI:1.15-3.28). Patients with AS and CD persisted on adalimumab therapy the most, reaching median use of 27.0 and 26.7 months, respectively. Half (52.4%) of the patients discontinued treatment during a mean (SD) follow-up of 3.07 (1.71) years. High socioeconomic status was associated with lower risk for discontinuation (adjusted-HR = 0.74; 0.60-0.91). UC and concomitant prednisolone use were associated with increased risk for treatment discontinuation (HR = 1.31; 1.00-1.72, and HR = 1.40; 1.17-1.68, respectively). CONCLUSION: Our results indicate encouraging persistence and adherence with adalimumab of patients with inflammatory conditions.
30774509 LIFE QUALITY EVALUATION USING "TIME TRADE OFF" METHOD FOR RHEUMATOID HANDS. 2018 OBJECTIVE: Rheumatoid arthritis is a prevalent disease in the population (range 0.5% to 1%) and involves both orthopedic and rheumatologic treatment. The Time Trade-Off (TTO) technique, which determines the number of years the patient or the professional would be allowed before a successful procedure in terms of life expectancy and value of the procedure, has been gaining ground in clinical protocols. From this standpoint, we sought to compare evaluations provided by the patients, orthopedists, and rheumatologists in determining the TTO and to correlate their responses with the clinical repercussions using previously established scores such as the Brief Michigan Hand Questionnaire and the Disease Activity Score-28 (DAS-28). METHODS: A prospective study was conducted that involved 37 patients with rheumatoid arthritis, orthopedists, and rheumatologists. The TTO questionnaire was administered by an independent evaluator for evaluation using the DAS-28 and the Brief Michigan Hand Questionnaire. RESULTS: The descriptive analysis revealed similar medians between the orthopedists, rheumatologists, and patients for single assessments. However, there was a weak correlation between the results from the patient and rheumatologist, the patient and Brief Michigan Questionnaire, and those of the orthopedic surgeon and the DAS-28. CONCLUSION: Similar median values demonstrated equivalent TTO among the orthopedist, rheumatologist, and patient. However, given the weak correlations between the scores, it was not possible to substitute results using a single evaluation scale. Level of Evidence II, Prognostic Studies.
27271273 Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regula 2018 May BACKGROUND/AIMS: Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. RESULTS: GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IκBα synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-κB (NF-κB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. CONCLUSIONS: Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF-κB signaling pathway.
30148011 Prevalence of Rheumatic Diseases in a Tertiary Care Hospital of Karachi. 2018 Jun 22 BACKGROUND: Rheumatic diseases are referred to as conditions affecting joints, muscles, ligaments, tendons, and bones. According to a report by World Health Organization, rheumatic and musculoskeletal diseases were labeled as the second most reported cause of disability around the globe. The purpose of this study was to estimate the prevalence of rheumatic diseases in a tertiary care hospital of Karachi; additionally, associations with age groups, gender and comorbidities were obtained as well. METHODS: A cross-sectional study was conducted at the Orthopedic Out Patient Department (OPD) of Dr. Ruth KM Pfau Civil Hospital, Karachi over a span of three months in 2018 (February till May). All 346 patients were follow-up diagnosed cases in the age range of 11-90 years, divided into groups of adolescents, young adults, adults, and older adults. The subjects were questioned about their symptoms, duration of illness, presence of comorbidities, genetic background and the therapy they are undergoing along with compliance. Simple statistical analysis of frequency was done, whereas chi-square test was applied to study associations with gender, age groups, and comorbidities. RESULTS: During the study period, a total of 2000 patients visited the orthopedic OPD, 346 of which were diagnosed cases of rheumatic diseases, yielding a prevalence of 17.3%. The mean age of rheumatic patients who partook in the study was 46.15 ± 15.49 (Range: 12 - 84). Osteoarthritis was recorded as the most prevalent condition, followed by non-specific low back pain and rheumatoid arthritis. Osteoarthritis was statistically significant in young adults, adults, and older adults, while non-specific low back pain had significant associations with gender, young adults, and adults. Diabetes was significantly associated with osteoarthritis, non-specific low back pain, shoulder pain syndrome and psoriatic arthritis, while hypertension significantly co-existed with systemic lupus erthematosus. CONCLUSION: Rheumatic diseases constitute a major disease burden in almost all of the age groups, especially in young patients (18-40 years) within our setup.
30021183 The History, Symptoms, Causes, Risk Factors, Types, Diagnosis, Treatments, and Prevention 2018 Jul Gout, a common and complex form of inflammatory arthritis, is characterized by abnormally elevated levels of uric acid in the blood. It is estimated that 52.5 million people in the U.S. have arthritis or one of the rheumatic diseases, according to the Centers for Disease Control and Prevention. There are over 100 rheumatic diseases and conditions. In the U.S., the most common types of arthritis or rheumatic diseases are osteoarthritis, gout, fibromyalgia, and rheumatoid arthritis, in that order according to prevalence. This article focuses on gout. Although there is no cure for gout, the disease can be effectively treated and managed with a combination of medication (manufactured and/or compounded) and self-management strategies.
29470693 Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4-oxadiazo 2018 Aug Chronic inflammation is pathologically associated with various clinical conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic drugs currently available in market presents a wide range of problems. Therefore, the current study was aimed to evaluate anti-inflammatory and analgesic activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were developed for evaluation of anti-inflammatory and analgesic activity. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of inflammatory mediators. Pain behaviours were evaluated by performing Von Frey, Randall Selitto, cold acetone and hot plate test respectively. X-ray imaging and haematoxylin and eosin (H&E) staining were performed for examination of soft tissues of treated mice paw. Additionally, Kodzeila's screen test and weight test were performed for determination of any side effects on motor function and muscle strength. Acute pretreatment of animals with MOPBS (1, 10, 50 and 100 mg/kg, i.p.) produced a significant reduction of paw oedema against carrageenan-induced acute inflammation as well as notable inhibition of mechanical hyperalgesia, allodynia and thermal hyperalgesia. Similarly, in chronic inflammation model, administration of MOPBS (50 mg/kg, i.p.) produced a remarkable reduction of paw oedema. Additionally, MOPBS pretreatment showed a significant inhibition of thermal hyperalgesia, mechanical allodynia, and mechanical hyperalgesia in chronic arthritis model. Several pro-inflammatory mediators such as nitric oxide (NO), vascular endothelial growth factor (VEGF), interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were inhibited by MOPBS treatment in blood plasma and paw tissues, respectively. MOPBS also enhanced the mRNA expression levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), superoxide dismutase (SOD2) and heme oxygenase (HO-1) and in turn reduced arthritis severity and inflammation. Furthermore, anti-inflammatory data were confirmed by X-rays and histological analysis. MOPBS pretreatment did not produce any apparent toxic effect on gastric, kidney and liver function and on muscle strength and motor function. Hence, the present data suggest that MOPBS might be a candidate for several chronic inflammatory diseases such RA and other auto-immune diseases.