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ID PMID Title PublicationDate abstract
30553912 Betulinic acid inhibits the migration and invasion of fibroblast-like synoviocytes from pa 2019 Feb The aggressive phenotype displayed by fibroblast-like synoviocytes (FLSs) contributes to cartilage and bone destruction in rheumatoid arthritis (RA). Betulinic acid has been demonstrated to have a positive therapeutic effect on tumor, inflammation and immune disorder, however, the effects of betulinic acid on RA FLSs have not been verified. Therefore, in the present study, we observed the effect of betulinic acid on the migration and invasion of RA FLSs and explored its underlying signal mechanisms. Our results showed that betulinic acid treatment suppressed the migration, invasion and reorganization of the actin cytoskeleton of RA FLSs. In addition, we found that the mRNA expression of IL-1β, IL-6, IL-8 and IL-17A were markedly down-regulated by treatment with betulinic acid in TNF-α-induced RA FLSs. To gain insight into the molecular mechanisms, we evaluated the effect of betulinic acid on NF-κB activation in RA FLSs. The results indicated that betulinic acid treatment reduced the TNF-α-induced activation of NF-κB signal pathway and the NF-κB nuclear accumulation. We also observed that treatment with betulinic acid attenuated synovial inflammation and joint destruction in mice with CIA. Taken together, these results suggest that betulinic acid inhibits the migration and invasion of RA FLSs by blocking NF-κB signal pathway activation.
30427250 IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review. 2019 Mar Tocilizumab (TCZ) is an interleukin-6 (IL-6) inhibitor used for the treatment of rheumatoid arthritis (RA). It was developed in 2008, and its effectiveness is supported by evidence from all over the world based on its first decade of use. Although the overall efficacy and safety profiles of TCZ are similar to those of tumor necrosis factor (TNF) inhibitors, TCZ displays certain differences. The most notable advantage of TCZ is its usefulness as a monotherapy. Additionally, TCZ is favorable in the improvement of systemic inflammatory symptoms such as anemia and fatigue. The low immunogenicity of TCZ contributes favorably to long-term drug retention. Due to frequent relapse after TCZ cessation, TCZ use should be tapered beyond remission. During TCZ therapy, C-reactive protein (CRP) is unable to recognize disease activity and the severity of infection. The most common adverse events (AEs) are infection and abnormalities in laboratory findings including dyslipidemia, neutropenia, thrombocytopenia, and abnormality of liver enzymes. TCZ obscures the symptoms of infection. Therefore, stealth infections without obvious CRP elevation can sometimes cause severe damage to patients. Lower intestinal perforation is an uncommon but serious AE in TCZ therapy. Further clinical investigations will continue to refine the IL-6 inhibitory strategy.
31233243 Site-specific absence of microfibrillar-associated protein 4 (MFAP4) from the internal ela 2019 Aug Microfibrillar-associated protein 4 (MFAP4) is a non-structural matrix protein with cell regulatory activities and a potential as seromarker for fibrosis. We aimed to study the occurrence of MFAP4 in the synovial membrane from patients with rheumatoid arthritis (RA) vs osteoarthritis (OA). Formaldehyde-fixed synovial tissue sections, from patients with RA (N = 6) and OA (N = 6) undergoing total hip arthroplasty, were deparaffinized and immunostained with monoclonal antibodies against MFAP4. Elastin was detected using ElastiKit. MFAP4 in serum (sMFAP4) and synovial fluid was measured by an immunoassay. MFAP4 was present in synovial biopsies from both RA and OA patients, particularly prominent in deep arterioles where it colocalized with elastin. Notably however, MFAP4 was absent from the internal elastic lamina in RA arterioles irrespective of disease duration and synovitis activity, while present although with irregular staining patterns in OA specimens. sMFAP4 was increased in RA and OA serum vs healthy controls: median (interquartile range) 29.8 (25.3-39.1) and 25.5 U/L (18.1-43.3) vs 17.7 U/L (13.7-21.2), p = 0.006 and p = 0.02, respectively The concentration of synovial fluid was lower than in serum in both RA and OA. These findings may suggest that MFAP4 is involved in adaptive vessel wall remodeling associated with chronic joint disease.
31378321 Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Patien 2019 Oct 1 Little is known on the outcomes of surgical aortic valve replacement (SAVR) versus transcatheter aortic valve implantation (TAVI) in patients with rheumatoid arthritis (RA). We queried the Nationwide Inpatient Sample Database (2012 to 2016). We performed a propensity-score-matched analysis based on 25 clinical and hospital variables to compare patients with RA who underwent SAVR versus TAVI. Our primary outcome was in-hospital mortality. Our final analysis included 5,640 hospitalizations with RA who underwent isolated AVR; of whom, 2,465 (43.7%) underwent TAVI. There was an increasing trend in TAVI procedures during the study years (p(trend)= 0.001). There was a trend toward reduced in-hospital mortality among TAVI compared with SAVR but did not reach statistical significance (0.8% vs 1.6%, odds ratio = 0.50; 95% confidence interval 0.23 to 1.06, p = 0.097). TAVI was associated with lower rates of postoperative bleeding (28.7% vs 43.9%, p <0.001), blood transfusion (12.3% vs 40.2%, p <0.001), acute kidney injury (9.8% vs 16.0%, p <0.001), cardiac tamponade (0.0% vs 1.6%, p <0.001), and discharges to skilled nursing facility (SNF) (20.1% vs 42.2%, p <0.001). However, TAVI was associated with a higher rate of complete heart block (14.3% vs 6.1%, p <0.001) and pacemaker implantations (14.8% vs 5.7%, p <0.001). There were no differences between both groups in cardiogenic shock, acute stroke, acute myocardial infarction, and vascular complications. In conclusion, real-word data showed no significant difference in in-hospital mortality between TAVI and SAVR in patients with RA. TAVI was associated with lower rates of acute kidney injury and bleeding complications at the expense of higher incidence of pacemaker implantations.
31310690 Earlier discontinuation of TNF-α inhibitor therapy in female patients with inflammatory b 2019 Aug BACKGROUND: In rheumatoid arthritis and psoriasis female sex has been shown to be associated with discontinuation of anti-tumour necrosis factor-α (TNF-α) therapy. AIM: To retrospectively assess the association between sex and TNF-α drug persistence in patients with inflammatory bowel disease (IBD). METHODS: All IBD patients on anti-TNF-α therapy with a minimum follow-up of 12 months in a single tertiary centre were identified. Patient and treatment characteristics and reasons for anti-TNF-α discontinuation were recorded. Overall and cause-specific drug persistence was analysed with Kaplan-Meier followed by Cox proportional hazards regression models. RESULTS: We included 529 patients (49.9% male) with 631 treatment episodes (2280 anti-TNF-α treatment years) and 289 discontinuations of therapy. Female sex (adjusted hazard ratio [aHR] 1.42, 95% confidence interval [CI] 1.16-1.74), greater age at start of therapy per decade (aHR 1.15, 95% CI 1.04-1.27] and dose escalation (aHR 3.74, 95% CI 2.78-5.02) were associated with TNF-α inhibitor discontinuation. Total cohort cause-specific analysis identified female sex to be associated with side effects (aHR 4.05, 95% CI 2.36-6.98) but not to other discontinuation reasons. Adalimumab (aHR 1.70, 95% CI 1.11-2.60) and golimumab (aHR 4.97, 95% CI 2.30-10.74) use and dose-escalation (aHR 7.71, 95% CI 5.28-11.26) were associated with secondary loss of response. CONCLUSION: Drug persistence of anti-TNF-α therapy is lower in females as compared to males, mainly because of higher rates of side effects in females. Understanding the sex specific differences in effectiveness and safety of anti-TNF-α compounds can aid physicians in clinical decision-making.
31019515 Development and Optimization of an ELISA to Quantitate C3(H (2) O) as a Marker of Human Di 2019 Discovery of a C3(H(2)O) uptake pathway has led to renewed interest in this alternative pathway triggering form of C3 in human biospecimens. Previously, a quantifiable method to measure C3(H(2)O), not confounded by other complement activation products, was unavailable. Herein, we describe a sensitive and specific ELISA for C3(H(2)O). We initially utilized this assay to determine baseline C3(H(2)O) levels in healthy human fluids and to define optimal sample storage and handling conditions. We detected ~500 ng/ml of C3(H(2)O) in fresh serum and plasma, a value substantially lower than what was predicted based on previous studies with purified C3 preparations. After a single freeze-thaw cycle, the C3(H(2)O) concentration increased 3- to 4-fold (~2,000 ng/ml). Subsequent freeze-thaw cycles had a lesser impact on C3(H(2)O) generation. Further, we found that storage of human sera or plasma samples at 4°C for up to 22 h did not generate additional C3(H(2)O). To determine the potential use of C3(H(2)O) as a biomarker, we evaluated specimens from patients with inflammatory-driven diseases. C3(H(2)O) concentrations were moderately increased (1.5- to 2-fold) at baseline in sera from active systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients compared to healthy controls. In addition, upon challenge with multiple freeze-thaw cycles or incubation at 22 or 37°C, C3(H(2)O) generation was significantly enhanced in SLE and RA patients' sera. In bronchoalveolar lavage fluid from lung-transplant recipients, we noted a substantial increase in C3(H(2)O) within 3 months of acute antibody-mediated rejection. In conclusion, we have established an ELISA for assessing C3(H(2)O) as a diagnostic and prognostic biomarker in human diseases.
31848494 [Significance of anti-carbamylated protein antibodies in patients with rheumatoid arthriti 2019 Dec 18 OBJECTIVE: To evaluate the value of anti-carbamylated protein (CarP) antibody in the diagnosis of rheumatoid arthritis-associated intersitial lung diseas (RA-ILD). METHODS: Clinical and laboratory data and serum samples of patients with RA between December 2017 and June 2019 in Department of Rheumatology, General Hospital of Ningxia Medical University were collected. The patients were subclassified as RA-ILD and RA-without ILD based on computed tomography scans of the chest, Enzyme 1inked immunosorbent assay (ELISA) was used to assess anti-CarP antibody in the serum of each group. The occurrence of ILD and other laboratory indexes were analyzed. Comparison of measurement data between the 2 groups was performed by two independent sample t-test or Mann-Whitney U nonparametric test, while the count data were compared by Chi square test; Receiver operating characteristic curve (ROC) was drawn to determine the cut-off value of anti-CarP antibody to RA-ILD diagnosis and to analyze its diagnostic efficacy. RESULTS: The anti-CarP antibody level in the RA-ILD group was 21.14 (12.29, 29.75), which was significantly higher than that in the RA-without ILD group 11.6 (6.66, 19.05) (P=0.000). The difference was statistically significant (P<0.05). The positive rate of anti-CarP antibody in RA-ILD group (53%) was significantly higher than that in RA-without ILD group (16%) (P<0.05); There was no significant differences in the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) between the two groups (P>0.05). The age and disease activity score (DAS28) in the RA-ILD group were significantly higher than those in the RA-withhout ILD group (P<0.05). The proportion of men and smoking in the RA-ILD group was higher than that in the RA-without ILD group, but the difference was not statistically significant. The ROC curve showed that the anti-CarP antibody had a cut off value of 20.56 U/mL, with the sensitivity of 53.50%, and specificity of 84.20%, the area under the ROC curve were 0.76. Spearman correlation analysis showed that rheumatoid factor (RF) and age were positively correlated with anti-CarP antibody (r=0.172, P=0.043; r=0.200, P=0.006). Anti-CarP antibody level was not associated with the DAS28 score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-CCP antibody, swollen joint count, and tender joint count (P>0.05). CONCLUSION: The anti-CarP antibody level in RA-ILD patients is higher than that in RA-without ILD, suggesting that anti-CarP antibody may have a role in the development of RA-ILD.
31485459 Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibrobla 2019 Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5 Gy has been demonstrated to have a positive impact on pain, inflammation, and bone in inflamed joints. We now examined for the first time how LD-RT influences FLS and bone marrow-derived macrophages in co-culture systems of an experimental model of RA to reveal further mechanisms of immune modulatory effects of low and intermediate dose of ionizing radiation. For this, the bone marrow of hTNF-α tg mice was differentiated either with cytokines to obtain key macrophage phenotypes (M0, M1, and M2) or with supernatants (SN) of untreated or irradiated FLS. Flow cytometry analyses were used to analyse the impact of radiation (0.1, 0.5, 1.0, and 2.0 Gy) on the phenotype of macrophages in the presence or absence of SN of FLS. LD-RT had no impact on cytokine-mediated macrophage polarization in M0, M1, or M2 macrophages. However, SN of irradiated FLS particularly reduced CD206 expression on macrophages. Macrophage phenotype was stable when being in contact with SN of nonirradiated FLS, but significantly increased surface expression of CD206 and slightly decreased CD80 and CD86 expression were observed when macrophage themselves were irradiated with 0.5 Gy under these microenvironmental conditions, again highlighting discontinuous dose dependencies in the low and intermediate dose range. One can conclude that FLS-dependent microenvironmental conditions have a slight influence on the modulation of macrophage phenotype under radiation exposure conditions. Future studies are needed to reveal the impact of radiation exposure on the functions of treated macrophages under such microenvironmental conditions.
30983166 A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Preven 2019 Sep OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. METHODS: A randomized, double-blind, placebo-controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. RESULTS: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI -14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. CONCLUSION: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations.
31309790  Role of µ-Opioid Receptor Polymorphism in Patients of Rheumatoid Arthritis and their Co 2019 Apr INTRODUCTION: With 1 billion tobacco users worldwide, nicotine dependence has a major impact on global health. Advances in medication development for nicotine dependence require an improved understanding of the neurobiology of this complex, relapsing brain disorder. AIMS: To study association of µ Opioid Receptor polymorphism in patients of rheumatoid arthritis and its correlation with severity of disease and prevalent alleles of the OPRM1 genes. MATERIAL AND METHODS: This is a case control study wherein all available patients and volunteers were recruited. 142 controls subjects with no known history of disease and 85 study group cases were included. RESULTS: Comparison of genotype frequencies showed a statistically significant difference between the studied groups (p<0.004). A statistically significant difference was found when the allelic frequencies between the two groups were compared (p<0.0001), with the 17T allele having a-1.7518 fold higher risk of having RA (risk ratio (RR)=1.7518, 95%CI of RR=1.2988-2.3627, OR =3.2914; 95%CI =1.9608-5.5251). Significant difference was also found when the allelic frequencies between the two groups were compared (p<0.0001), with the 118G allele having a 1.5-fold higher risk of developing RA (RR)=1.5801, 95%CI =1.3091-1.9071, OR=3.1357; 95%CI 2.1083-4.6638). CONCLUSION: The study definitely needs to be extended to larger cohort of patients and control samples and to a larger set of candidate µ opioid receptors. Extending the studies to a larger cohort will also allow genetic analyses of clinically defined endophenotypes observed in the patients of this chronic metabolic disease with attributes of autoimmune disorder and multiple symptoms in patients.
30520175 The voice of patients in system redesign: A case study of redesigning a centralized system 2019 Jun BACKGROUND: The published literature demands examples of health-care systems designed with the active engagement of patients to explore the application of this complex phenomenon in practice. METHODS: This case study explored how the voice of patients was incorporated into the process of redesigning an element of the health-care system, a centralized system for intake of referrals from primary care to rheumatologists for patients with suspected rheumatoid arthritis (RA)-centralized intake. The phenomenon of patient engagement using "patient and community engagement researchers" (PaCERs) in research and the process of redesigning centralized intake were selected as the case. In-depth evaluation of the case was undertaken through the triangulation of findings from the document review and participants' reflection on the case. RESULTS: In this case, patients and PaCERs participated in multiple activities including an initial meeting of key stakeholders to develop the project vision; a patient-to-patient PaCERs study to gather perspectives of patients with RA on the challenges they face in accessing and navigating the health-care system, and what they see as key elements of an effective system that would be responsive to their needs; the development of an evaluation framework for future centralized intake; and the choice of candidate centralized intake strategies to be evaluated. CONCLUSIONS: The described feasible multistep approach to active patient engagement in health-care system redesign contributes to an understanding of the application of this complex phenomenon in practice. Therefore, the manuscript serves as one more step towards a patient-centred health-care system that is redesigned with active patient engagement.
31118103 Distinct fatty acid signatures in infrapatellar fat pad and synovial fluid of patients wit 2019 May 22 BACKGROUND: Infrapatellar fat pad (IFP) has recently emerged as a potential source of inflammation in knee arthropathies. It has been proposed to be one source of adipocytokines, fatty acids (FA), and FA-derived lipid mediators that could contribute to the pathophysiological processes in the knee joint. Alterations in synovial fluid (SF) lipid composition have been linked to both osteoarthritis (OA) and rheumatoid arthritis (RA). The aim of the present study was to compare the FA signatures in the IFP and SF of RA and OA patients. METHODS: Pairs of IFP and SF samples were collected from the same knees of RA (n = 10) and OA patients (n = 10) undergoing total joint replacement surgery. Control SF samples (n = 6) were harvested during diagnostic or therapeutic arthroscopic knee surgery unrelated to RA or OA. The FA composition in the total lipids of IFP and SF was determined by gas chromatography with flame ionization and mass spectrometric detection. RESULTS: Arthropathies resulted in a significant reduction in the SF proportions of n-6 polyunsaturated FA (PUFA), more pronouncedly in OA than in RA. OA was also characterized with reduced percentages of 22:6n-3 and lower product/precursor ratios of n-3 PUFA. The proportions of total monounsaturated FA increased in both RA and OA SF. Regarding IFP, RA patients had lower proportions of 20:4n-6, total n-6 PUFA, and 22:6n-3, as well as lower product/precursor ratios of n-3 PUFA compared to OA patients. The average chain length of SF FA decreased in both diagnoses and the double bond index in OA. CONCLUSIONS: The observed complex alterations in the FA signatures could have both contributed to but also limited the inflammatory processes and cartilage destruction in the RA and OA knees.
30280370 Introduction of a uniform record keeping practice for rheumatology clinics in Sri Lanka-an 2019 Jan In Sri Lanka, record keeping in rheumatology clinics is purely paper-based. Clinic record books are given to patients, and the hospital does not retain clinical data. Different clinics and different rheumatology specialists practice different formats of record keeping in Sri Lanka. This project was aimed to develop a uniform record keeping system which can be used in all government rheumatology clinics in Sri Lanka. Project was carried out in two phases. First phase was carried out in seven rheumatology clinics to identify deficiencies in existing practice of record keeping in rheumatoid arthritis (RA), spondyloarthritis (SPA), and systemic lupus erythematosus (SLE). Second phase was to develop new clinic documents and a computer-based system, using the findings of the first phase. Recording of classification criteria at the time of diagnosis was 40.6% for RA and 90.3% for SLE. Initial clinical notes were not available in 18.3% of RA patients. Recording of individual classification criteria in SPA was ranged between 10% and70%, and it was 100% for arthritis. During second phase, new paper-based and computer-based record keeping systems were developed. Existing practice of record keeping is incomplete, especially in RA and SPA. The necessity of new, uniform record keeping system was recognized. Paper-based and computer-based record keeping systems acceptable to specialist rheumatologists, medical officers, and the Ministry of Health were developed and tested. The newly developed paper-based system is being used nationally while the electronic system is yet to introduced.
32254955 Targeted hexagonal Pd nanosheet combination therapy for rheumatoid arthritis via the photo 2019 Jan 7 Methotrexate (MTX) is a drug that is used for the clinical treatment of rheumatoid arthritis (RA), a stubborn disease caused by over-immunization. However, the toxicity that arises as a result of poor selectivity to inflammatory cells severely limits the application of MTX. Therefore, new therapeutic strategies are needed for treating RA. Here, we describe the design and synthesis of a nanotherapy agent, Pd-Cys@MTX@RGD, which can target inflammatory cells and control MTX release. The novel hexagonal palladium (Pd) nanosheets were used as a near-infrared (NIR) photothermal agent modified with arginine-glycineaspartic acid (RGD) peptides on the surface to enhance the ability of the nanosheet targeting of inflammatory cells. In subsequent experiments, the Pd-Cys@MTX@RGD nanosheets were observed to greatly reduce the toxicity of MTX, showing controlled MTX release under irradiation of 808 nm (0.3 W cm(-2)). Moreover, taking advantage of the fact that MTX can be combined with multiple therapeutic methods, the photothermal therapy (PTT) of Pd nanosheets provided a compensatory effect to enhance the therapeutic efficacy of MTX. Under combination therapy, Pd-Cys@MTX@RGD was shown to effectively inhibit the inflammatory response induced by vascular endothelial growth factor (VEGF) and IL-1β. And, in vivo, multifunctional Pd-Cys@MTX@RGD effectively inhibited the symptoms of RA by inhibiting the expression of pro-inflammatory cytokines (TNF-α,COX-2). We hope that the construction of nanomaterials can add potential value to the design of chemical drugs and therapeutic strategies for RA.
31678279 Ellagic acid attenuates testicular disruption in rheumatoid arthritis via targeting inflam 2019 Dec 15 BACKGROUND AND PURPOSE: Reduced male fertility has been regarded as a serious complication of rheumatoid arthritis. Phytochemicals have been described as protective agents against rheumatoid arthritis-linked testicular impairment. The current study aimed to investigate the potential protective effects of ellagic acid on rheumatoid arthritis-evoked testicular dysfunction vis-à-vis the reference anti-inflammatory celecoxib. EXPERIMENTAL APPROACH: Ellagic acid (50 mg/kg/day) and celecoxib (5 mg/kg/day) were administered orally for 20 days in adjuvant-induced arthritic rats. KEY FINDINGS: Current data revealed that ellagic acid counteracted rheumatoid arthritis-evoked testicular histopathologic changes, disrupted sperm characteristics and low gonadosomatic index with comparable efficacy to celecoxib. Ellagic acid also enhanced the testicular steroidogenesis via upregulating the gene expression of 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein with consequent boosting of serum testosterone. Notably, ellagic acid attenuated the testicular inflammatory responses through suppression of myeloperoxidase, tumor necrosis factor-α and cyclo-oxygenase-2 protein expression together with enhancing the anti-inflammatory signal interleukin 10. Ellagic acid also curbed the redox alterations via lowering the production of lipid peroxides and nitric oxide and elevation of the anti-oxidant reduced glutathione. In support of cell survival, ellagic acid combated testicular apoptosis through downregulating caspase-3 protein expression. SIGNIFICANCE: The present work accentuates the beneficial actions of ellagic acid in rheumatoid arthritis-incurred testicular impairment and disrupted spermatogenesis via combating the inflammatory, oxidative and apoptotic aberrations.
30612769 Clinical Outcomes After Hip Arthroscopy for Patients With Rheumatoid Arthritis: A Matched- 2019 Feb PURPOSE: This study analyzed minimum 2-year hip arthroscopy outcomes in rheumatoid arthritis (RA) patients and non-RA control patients. It also examined whether disease-modifying antirheumatic drugs (DMARDs) affected RA patient outcomes. We hypothesized that patients with RA undergoing hip arthroscopy would have lower reported outcome scores. METHODS: Data were prospectively collected on all hip arthroscopies performed from 2009-2013. The indications for surgery were patients with hip pain and with physical examination and imaging studies confirming intra-articular pathology in whom conservative management had failed. The exclusion criteria were previous ipsilateral hip conditions and Tönnis grade greater than 1. Patients with at least 2 years of follow-up and preoperative RA diagnoses were matched (1:2 ratio) to controls without RA (based on age ± 5 years, body mass index ± 5, and lateral center-edge angle [18°-25°, 26°-39°, or >39°]). RA cases were further analyzed based on DMARD use. Patient-reported outcome (PRO) scores were collected preoperatively and postoperatively at 3 months, as well as annually thereafter. The outcomes collected included the modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Sports Specific Subscale, visual analog scale (VAS) score for pain, satisfaction rating, future procedures, and complications. RESULTS: We matched 26 hips in 20 RA patients to a control group of 52 hips in 52 patients. At a minimum of 2 years of follow-up, RA patients reported no significant improvements except in the Non-Arthritic Hip Score, whereas the control group significantly improved in all PRO and VAS scores. Preoperative PRO and VAS scores between the RA and control groups were not significantly different, but postoperatively, all scores were lower in RA patients at a minimum of 2 years, whether they were taking DMARDs or not. Patients taking DMARDs showed slightly more improvement in PRO and VAS scores. There was a greater trend toward more secondary arthroscopy procedures for RA patients (19.2% vs 7.7%, P = .47), but total hip arthroplasty rates were similar. Complication rates were low in both groups. CONCLUSIONS: Patients undergoing hip arthroscopy who have a diagnosis of RA had less improvement in PRO and VAS scores and were less satisfied than a matched control group of patients without RA at a minimum 2-year follow-up. Patients who were taking DMARDs had slightly better improvement in their PRO and VAS scores than nonmedicated patients. With this early follow-up, we could not show a difference in the rate of conversion to total hip arthroplasty, although RA patients required more revision arthroscopies than controls. Patients with a diagnosis of RA who undergo hip arthroscopy should be counseled about the potential for lesser degrees of postoperative improvement and should have their expectations managed accordingly. LEVEL OF EVIDENCE: Level III, comparative trial.
30402903 PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ 2019 Mar BACKGROUND: CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40-CD154 interaction promotes pro-inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T- and B-cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN-γ secretion in RA patients. METHODS: PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR-RFLP method. Later, we selected only ten anti-CCP-positive RA patients, naïve to disease-modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly. RESULTS: The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN-γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032). CONCLUSION: The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro-inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.
31354242 Efficacy and safety of total glucosides of paeony combined with methotrexate and leflunomi 2019 Purpose: Total glucosides of paeony (TGP) have been confirmed to reduce hepatotoxicity caused by methotrexate (MTX) and leflunomide (LEF) in rheumatoid arthritis (RA). Nevertheless, high-quality evidence-based meta-analysis data on the issue are unavailable. This study aimed to evaluate the efficacy and safety of this combination treatment for RA. Materials and methods: PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials, Chinese Biomedical Literature database, China National Knowledge Internet, Wan Fang, and VIP were searched up to February 2019. Randomized controlled trials (RCTs) on the efficacy and safety of TGP combined MTX and LEF for RA were included. Results: Eight RCTs were included in the final meta-analysis. Pooled results showed better therapeutic effects against RA in the TGP-treated group (RR =1.10, 95% CI: 1.04 -1.16). The TGP+MTX+LEF group showed a reduced erythrocyte sedimentation rate (MD = -2.80 mm/h, 95% CI: -5.08 - -0.52), C-reactive protein level (MD = -4.17 mg/L, 95% CI: -7.84 - -0.51), and rheumatoid factor (MD = -12.09 IU/mL, 95% CI: -14.05 - -10.14). Besides, the combination treatment tended to benefit lipid profiles (total cholesterol: 95% CI: -1.27-0.06; triglycerides: 95% CI: -0.49 - -0.08; high-density lipoprotein cholesterol: 95% CI: 0.15-0.83; and low-density lipoprotein cholesterol: 95% CI: -0.54 - -0.02). Adverse events, hepatotoxicity in particular, significantly decreased (RR =0.55, 95% CI: 0.38-0.80) in the TGP group. Conclusion: Compared to MTX and LEF therapy, TGP combination treatment may be a more effective and safer strategy. It is advisable to apply TGP as an adjuvant given its hepatoprotective and possible lipid-regulating effect. However, further large-scale and high-quality clinical trials are warranted, and the efficacy of TGP in terms of its effect on lipid profiles should be further confirmed.
31622607 Rheumatoid arthritis induces enteric neurodegeneration and jejunal inflammation, and querc 2019 Dec 1 AIMS: The aim of our study was to study the pathological mechanisms induced by the rheumatoid arthritis (RA) on the Enteric Nervous System (ENS). MAIN METHODS: We evaluated the effect of the chronic arthritis and its treatment with 50 mg/kg quercetin alone (AQ) and combined with 17.5 mg/kg ibuprofen (AIQ) for 60 days on neurons, glial cells and intestinal wall. Other groups were used: control (C), arthritic (A) and arthritic treated with 17.5 mg/kg ibuprofen (AI). After 60 days, the jejunum was removed and processed for immunohistochemical techniques. Immunostainings were performed for HuC/D and S100 (myenteric and submucosal plexuses), and GFAP (only myenteric plexus), while immunolabeling for CD45 and CD20 lymphocytes was performed using cryosections. Western blot was performed for GDNF, S100 and GFAP. KEY FINDINGS: A group yielded a remarkable density decrease of the neurons and glial cells with morphometric changes in the myenteric and submucosal plexuses, reduction of the GDNF expression and GFAP-related parameters (GFAP expression, occupancy area and GFAP-expressing glial cells) and intestinal inflammation and atrophy of the mucosa and intestinal wall. AQ group substantially reversed most of these effects, except for intestinal atrophy of the jejunum. The AI and AIQ groups displayed lower beneficial results than AQ for parameters related to the neurons and glial cells, although AIQ did not prevent the inflammation of the mucosa. SIGNIFICANCE: The severe chronic rheumatoid arthritis induced severe effects on ENS and mucosa, and quercetin treatment continues to be an important antioxidant supplement preventing the progression of the RA severity.
31026415 Nonclassical Monocytes in Health and Disease. 2019 Apr 26 Monocytes are innate blood cells that maintain vascular homeostasis and are early responders to pathogens in acute infections. There are three well-characterized classes of monocytes: classical (CD14(+)CD16(-) in humans and Ly6C(hi) in mice), intermediate (CD14(+)CD16(+) in humans and Ly6C(+)Treml4(+) in mice), and nonclassical (CD14(-)CD16(+) in humans and Ly6C(lo) in mice). Classical monocytes are critical for the initial inflammatory response. Classical monocytes can differentiate into macrophages in tissue and can contribute to chronic disease. Nonclassical monocytes have been widely viewed as anti-inflammatory, as they maintain vascular homeostasis. They are a first line of defense in recognition and clearance of pathogens. However, their roles in chronic disease are less clear. They have been shown to be protective as well as positively associated with disease burden. This review focuses on the state of the monocyte biology field and the functions of monocytes, particularly nonclassical monocytes, in health and disease.