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ID PMID Title PublicationDate abstract
33216287 Real-World 1-Year Retention Rate of Subcutaneous Tocilizumab Treatment in Patients with Mo 2021 Mar INTRODUCTION: Drug retention is particularly relevant to assess long-term treatments. This real-world study mainly aimed to describe 1-year retention rate (RR) of subcutaneously administered tocilizumab (TCZ-SC) in patients with moderate to severe active rheumatoid arthritis (RA). METHODS: This non-interventional, prospective, multicenter study (NCT02608112) was conducted in patients with RA initiating TCZ-SC treatment, with an 18-month follow-up. RR was estimated at month 12 in the overall population and baseline subgroups (combination with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or not, age, body mass index, methotrexate dose), using the Kaplan-Meier method. Patient compliance to TCZ-SC was described using the 5-item Compliance Questionnaire for Rheumatology (CQR5). RESULTS: At inclusion 75% of the 285 analyzed patients were women, mean RA duration was 9 ± 9 years, previous RA treatments included biological agents (63%) and/or csDMARDs (94%), mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 4.8 ± 1.2. TCZ-SC RR at month 12 was estimated to be 64% (95% CI 58%-69%) with no statistical differences between subgroups. Clinical results improved with TCZ-SC; the proportion of patients treated with combined glucocorticoids decreased from 49% to 22% at month 12. At each follow-up time, at least 80% of patients were high adherers to TCZ-SC (at least 80% of theoretical injections). Among the 286 patients with at least one TCZ-SC injection, 25 patients (9%) experienced serious adverse events related to TCZ-SC with no differences according to patient age. CONCLUSIONS: This real-world study corroborates the RR at month 12 previously shown in interventional studies on TCZ-SC. Our data suggest there are no differences according to patient's profile (age, BMI), methotrexate doses, and TCZ-SC use. TRIAL REGISTRATION: NCT02608112.
33060030 The Association Between Smoking and the Development of Rheumatoid Arthritis: A Population- 2020 Oct 12 INTRODUCTION: Smoking is one of the few modifiable risk factors associated with the development of rheumatoid arthritis (RA). Most published data are over 10 years old, and none included Mediterranean populations. We therefore took advantage of primary care routinely collected data to study the association between smoking and the development of RA in the general population of Catalonia, Spain. METHODS: We conducted a case-control study including all patients with a new diagnosis of RA registered in the SIDIAP database between 01/01/2008 and 31/12/2018; and matched them to up to 1:5 controls by age, gender and general practitioner. Smoking was classified by primary care staff into never, ex- or current smoking. Odds Ratios and 95% confidence intervals for the association between current and ex-smoking (compared to never smoking) and RA were estimated using conditional logistic regression adjusted for potential confounders. RESULTS: A total of 13,920 RA cases and 69,535 controls were included. Compared with never smokers, current and ex-smokers were at increased risk of RA, with adjusted OR of 1.28 [95% CI 1.20-1.37] and OR 1.19 [1.12-1.26] respectively. CONCLUSION: Our findings confirm an association between smoking and the risk of developing RA. The effect seems to prevail in the long-term and even in ex-smokers for 2 or more years after smoking cessation. More research is needed on the effects of smoking discontinuation on RA prevention and related outcomes.
33026193 Incidence of congestive heart failure in rheumatoid arthritis: a review of literature and 2020 Oct 7 AIMS: Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder that not only affects peripheral joints but also increases the risk for cardiovascular disease (CVD) and mortality. Heart failure (HF) appears to be one of the most important contributors to the excess mortality risk among patients with RA. We assessed the incidence of HF in patients with RA compared with age-matched and sex-matched non-RA subjects, after accounting for traditional cardiovascular risk factors and clinical ischemic heart disease. METHODS AND RESULTS: We performed an aggregate analysis on three studies of RA patients having listed manifestations of HF. We performed a meta-regression analysis to evaluate the incidence of HF in RA patients with increased age and noted for any gender correlation. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed-effects and random-effects models. In the cumulative analysis of 5, 220, 883 patients, the incidence of HF was noted to be almost two-fold higher in patients with RA compared with a matched control population (OR 1.78, 95% CI 1.22-2.60, P < 0.003), HTN (OR 1.66, 95% CI 1.24-2.23, P < 0.001), and diabetes (OR 1.57, 95% CI 1.36-1.81, P < 0.001). Women had three-fold higher incidence of HF with RA (OR 3.38, 95% CI 2.59-4.40, P < 0.001). On meta-regression, the incidence of HF increased further with older age (coefficient = 0.12, P = 0.0004). CONCLUSIONS: Our systematic review that included over 5 million subjects confirms the suspected increased incidence of HF in RA patients. Women have the greatest risk for HF. Our analysis advocates the need for updating the current guidelines to incorporate screening and preventive methods for HF in RA patients.
32528679 Synovial fluid CD69(+)CD8(+) T cells with tissue-resident phenotype mediate perforin-depen 2020 OBJECTIVES: Although the importance of tissue-resident memory T (T(RM)) cells in organ-specific chronic inflammation has been recognised, little is known about their role in rheumatoid arthritis (RA). Here, we examined the characteristics of synovial fluid CD8(+) T cells that express canonical T(RM) markers CD69 and CD103, and their role in the pathogenesis of RA. METHODS: Synovial fluid mononuclear cells (SFMCs) were obtained from patients with RA. Flow cytometric analysis of surface markers and cytotoxic molecules of CD8(+) T cells was performed. TCR repertoire of CD8(+) T cells was analysed by TCRVβ CDR3 sequencing. Citrullination with the formation of neutrophil extracellular trap (NET) was evaluated by immunofluorescence staining. RESULTS: The frequency of CD8(+) T cells was increased in SFMCs, and these CD8(+) T cells were primarily comprised of CD45RA(-) memory T cells expressing CD69 and/or CD103. CD69(+)CD8(+) T cells exhibited T(RM) phenotypes, including upregulation of CXCR6, CD49a and CD101, and downregulation of S1PR1 and KLF2. TCR repertoire analysis showed that these cells were an oligoclonally expanded population with increased expression of cytotoxic molecules. The treatment of neutrophils with supernatant from IL-15-stimulated CD69(+)CD8(+) T cells induced perforin-mediated histone citrullination and NET formation irrespective of their CD103 expression. The frequency of perforin-expressing cells among CD69(+)CD8(+) T cells in SFMCs was significantly higher in patients with anti-citrullinated protein antibody (ACPA) than in those without ACPA. CONCLUSION: CD69(+)CD8(+) T cells in the SFMCs of RA patients exhibit T(RM)-like features. These cells may participate in the pathogenesis of RA via perforin-mediated citrullination.
31741182 Retrospective Analysis of the Impact of Adalimumab Initiation on Corticosteroid Utilizatio 2020 Mar INTRODUCTION: Treatment guidelines recommend low-dose corticosteroids as short-term therapy among rheumatoid arthritis (RA) patients. However, it may be difficult to wean/eliminate steroids once initiated. Initiation of more effective therapies such as biologics may help to taper corticosteroid use. The objective was to examine the impact of adalimumab (ADA) initiation on steroid utilization and non-drug medical costs among patients with RA. METHODS: A retrospective analysis was conducted among adult RA patients initiating ADA as the initial biologic in the MarketScan Database (2012-2016). Study outcomes included whether oral/injectable steroids were used, daily dose, dosage categories (< 5 and ≥ 5 mg/day), number of steroid injections, and non-drug medical costs. Outcomes were compared 6 months pre- and post-ADA initiation. Mixed effects logistic, classical linear, multinomial logistic models, and linear model with a log link and gamma distribution were used to adjust for patient demographic and health characteristics. RESULTS: The sample included 7404 ADA initiators. Compared to pre-ADA initiation, in the post-initiation period there was a reduction in proportions of patients using oral steroids (from 71.80 to 62.56%) and injectable steroids (from 34.91 to 29.88%), average daily dose of oral steroids (from 3.30 to 2.62 mg/day), patients with dose ≥ 5 mg/day (from 21.76 to 16.34%), number of injections (from 0.64 to 0.53), and non-drug medical costs (from $5356.30 to $5146.84) (P < 0.01). The multivariate analysis produced similar patterns. For example, post-ADA initiation, patients were less likely to use oral steroids [odds ratio (OR) 0.51; 95% confidence interval (CI) 0.47-0.56]; coefficient estimate for daily dose reduction was - 0.68 (95% CI - 0.81 to - 0.56); ratio estimate for medical costs was 0.91 (95% CI 0.86-0.97). CONCLUSIONS: Among patients with RA, following ADA initiation, there is a reduction in steroid utilization and dosage, and non-drug medical costs. Prospective studies should be conducted to confirm this relationship in the future.
33043247 Physical activity in established rheumatoid arthritis and variables associated with mainte 2020 BACKGROUND: A large number of patients with RA do not adhere to the recommended levels of physical activity to enhance health. According to EULAR recommendations, physical activity should be part of standard care in people with rheumatic diseases. There have been few larger studies on maintenance of physical activity over longer periods of time. The aim was to study self-reported physical activity levels over 7 years in patients with established rheumatoid arthritis (RA). In addition, to determine variables associated with maintenance or change of physical activity behavior. METHODS: Questionnaires were sent to the BARFOT cohort in 2010 (n = 1525) and in 2017 (n = 1046), and 950 patients responded to both questionnaires. Patients were dichotomized according to meeting MVPA recommendations (physically active at a moderate level ≥ 150 min/week or at an intense level ≥ 75 min/week) or not. Body mass index, smoking habits, tender joint count (TJC), swollen joint count (SJC), Patient Global Assessment (PatGA), pain intensity and distribution, fatigue, physical function (HAQ), health-related quality of life (EQ. 5D), comorbidities, and medical treatment were assessed. We used logistic regression analysis to study variables associated with maintenance and/or change of MVPA behavior. RESULTS: Forty-one per cent (n = 389) of the patients met MVPA recommendations on both occasions. Patients who met MVPA recommendations over 7 years were younger and a higher proportion were never-smokers. There was a negative association with being overweight or obese, having cardiovascular or pulmonary diseases, pain, fatigue, and physical function, whereas there was a positive association between QoL and maintaining MVPA recommendations. Similar factors were positively associated with a deterioration in physical activity level over time. CONCLUSIONS: Maintenance of physical activity over a long period of time is challenging for patients with established RA. Reports of high quality of life supported maintenance of physical activity while disease related and unhealthy lifestyle factors had a negative effect. Health professionals should consider the patient's standpoint when encouraging maintenance of physical activity, preferably using coordinated lifestyle interventions.
33041228 Experts document on methotrexate use in combined therapy with biological or targeted synth 2020 Oct 8 OBJECTIVE: We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). METHODS: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted 'yes' (yes/no). RESULTS: The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients' risk management. CONCLUSIONS: This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.
33230683 Incidence of autoimmune diseases in people living with HIV compared to a matched populatio 2021 Jun The objective of this paper is to estimate incidence and relative risk of autoimmune conditions in patients living with HIV compared to an HIV-negative matched population. We conducted a retrospective study in the medico-administrative database of the province of Québec, Canada. All HIV-positive patients treated with antiretrovirals were matched to up to 4 HIV-negative controls for age, sex, and period of follow-up. The following autoimmune conditions were identified using medical billing codes: vasculitis, hematological (immune thrombocytopenic purpura and immune hemolytic anemia), ankylosing spondylitis, psoriasis and psoriatic arthritis, inflammatory bowel disease and associated arthritis, connectivitis, and systemic lupus erythematosus. Incidence rates and adjusted hazard ratios (aHR) were obtained using survival models. A total of 4245 HIV-positive patients were matched to 16493 HIV-negative patients. Autoimmune diseases were diagnosed in 407 (9.6%) HIV-positive and 508 (3%) HIV-negative patients. The aHR for autoimmune diseases associated to HIV was 2.40 95% CI [2.10-2.75]. The strongest associations were seen for hematological disorders (aHR 8.34 95% CI [6.13-11.36]), followed by ankylosing spondylitis (1.82 95% CI [1.03-3.21]), inflammatory bowel disease and associated arthritis (1.80 95% CI [1.37-2.35]), psoriasis and associated arthritis (1.69 95% CI [1.23-2.33]), and rheumatoid arthritis (1.51 95% CI [1.08-2.11]).We found no association between HIV and the incidence of vasculitis, connectivitis, and systemic lupus erythematosus, but the number of cases for these diseases were few. Autoimmune diseases are more frequent among people living with HIV than age and sex-matched population-based controls. Key Points • Strength: The major strength of this study is its large sample size of 4200 people treated as HIV infection, matched to 16000 HIV negative for sex and age. • Novelty: We found that people living with HIV were more than twice as likely to suffer from auto-immune diseases than their matched counterparts.
33385861 Statins and lower mortality in rheumatic diseases: An effect of immortal time bias? 2021 Feb OBJECTIVE: Randomized controlled trials of the effectiveness of statins on rheumatic disease outcomes have shown limited or no benefit. On the other hand, observational studies have reported remarkable effectiveness of statins at reducing mortality in patients with rheumatic diseases. We evaluated these observational studies for the presence of immortal time bias, which tends to exaggerate the effectiveness of drugs by creating a survival advantage for exposed patients. METHODS: We searched PubMed for observational studies investigating the impact of statins in patients with common rheumatic diseases, including rheumatoid arthritis, osteoarthritis, lupus, ankylosing spondylitis, gout and systemic autoimmune diseases. Studies were included if estimates for all-cause mortality among statin users compared to non-users were reported. We evaluated each study for the presence of immortal time bias and estimated the impact of the bias on the published results. RESULTS: We found eight observational studies investigating the impact of statins on mortality among patients with rheumatic diseases. Four studies were affected by the classical variant of immortal time bias, while the others introduced immortal time into the comparator via random-calendar date assignment. The studies with the classical form of immortal time bias, which tends to exaggerate drug effectiveness, reported protective effects of statins on mortality ranging from 13% to 57% reductions. In contrast, immortal time bias through random-calendar date assignment, which tends to play down the effectiveness by introducing immortal time in the comparator, reported 16% to 37% reductions in mortality. CONCLUSION: Bias in observational studies may explain the discrepancy in findings with randomized controlled trials on the effectiveness of statins in patients with rheumatic diseases. Future observational studies will need to rely on incident and prevalent new-user designs that emulate randomized trials and avoid immortal time bias.
31993228 Effects of Hyperbaric Oxygen on T helper 17/regulatory T Polarization in Antigen and Colla 2020 Jan OBJECTIVES: We sought to investigate and prove the effect of hyperbaric oxygen therapy (HBOT) on T helper 17 (Th17)/regulatory T (Treg) cell polarization through changes in the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in rheumatoid arthritis (RA) animal model. METHODS: We used antigen and collagen-induced arthritis (ACIA) as a RA animal model. Sixteen male BALB/c models of ACIA mice were divided into two groups, the non-HBOT group as the control group and the HBOT group as the treatment group. Expression of HIF-1α, Th17 anti-cluster differentiation 196 (CD196), and Treg anti-interleukine 2 receptor β-chain cells (IL-2Rβ) in tissue from the left knee joint tissue were determined histologically. Oxidative stress and systemic inflammation were assessed by levels of superoxide dismutase (SOD), interleukin 17a (IL-17a), C-reactive protein (CRP), and rheumatoid factor (RF) using the enzyme-linked immune-sorbent assay. The degree of arthritis was assessed by clinical scoring of paw swelling and the diameter of paw swelling. RESULTS: We found a significant decrease (p < 0.050) in the expression of HIF-1α, Th17 (CD196), IL-17a, RF levels, and the clinical scores and the diameter of paw swelling when comparing both groups. There was no significant decrease in the level of CRP in the treatment group compared to the control group. The expression of Treg (IL-2Rβ) increased significantly (p < 0.050) and the level of SOD increased but not significantly (p > 0.050) in the treatment group compared to the control group. CONCLUSIONS: HBOT has effects on the polarization of Th17 to Treg through a decrease in expression of HIF-1α in mice with ACIA. HBOT is recommended for use as a support therapy for RA in combination with drug therapy.
32884795 Multicentric reticulohistiocytosis: A case report with response to adalimumab. 2020 Aug Although MRH can mimic rheumatoid arthritis, its ability to rapidly progress to arthritis mutilans and association with malignancy in up to 25% of patients warrant prompt recognition and treatment along with age-appropriate malignancy work-up.
32713340 Exploration of Nanoethosomal Transgel of Naproxen Sodium for the Treatment of Arthritis. 2020 BACKGROUND: The present work aimed to develop an ethosomal gel of naproxen sodium for the amelioration of rheumatoid arthritis. OBJECTIVE: In the present work, we have explored the potential of ethosomes to deliver naproxen into deeper skin strata. Further, the anti-inflammatory efficacy of naproxen ethosomal formulation was assessed using the carrageenan-induced rat paw edema model. METHODS: Naproxen sodium nanoethosomes were prepared using different proportions of lipoid S100 (50mg-200mg), ethanol (20-50%) and water, and were further characterized on the basis of vesicle morphology, entrapment efficiency, zeta potential, in-vitro drug release and ex-vivo permeation studies. RESULTS: The optimized ethosomal formulation was found to have 129 ± 0.01 nm particle size, 0.295 Polydispersity Index (PDI), -3.29 mV zeta potential, 88% entrapment efficiency and 96.573% drug release in 24 hours. TEM and SEM analysis of the optimized formulation showed slightly smooth spherical structures. The Confocal laser scanning microscopy showed that ethosomes could easily infiltrate into deeper dermal layers (upto 104.9μm) whereas the hydroalcoholic solution of the drug could penetrate up to 74.9μm. Further, the optimized ethosomal formulation was incorporated into 1% carbopol 934 gel base and optimized wherein the transdermal flux was found to be approximately 10 times more than the hydroethanolic solution. Also, the in-vivo pharmacodynamic study of the optimized ethosomal gel exhibited a higher percentage inhibition of swelling paw edema than marketed diclofenac gel. CONCLUSION: The ethosomal gel was successfully developed and has shown the potential to be a good option for the replacement of conventional therapies of rheumatoid arthritis.
32872481 Twelve Weeks of Strengthening Exercise for Patients with Rheumatoid Arthritis: A Prospecti 2020 Aug 29 Rheumatoid arthritis (RA) patients may benefit from exercise for several reasons. However, whole-limb strengthening exercises for such patients remain poorly studied. We hypothesized that systemic strength training that includes the upper and lower extremities would improve strength per se and enhance the quality of life. Here, we investigated the effects of 12 weeks of upper- and lower-limb strengthening exercise on the strength and quality of life of RA patients using the International Classification of Functioning, Disability, and Health model. This was a prospective, interventional controlled trial. Forty female RA patients were recruited and assigned to two groups not based on willingness to exercise, with 20 patients in the exercise group and 20 in the control group. All patients in the exercise group received once-weekly training sessions of 60 min over 12 weeks. All participants were assessed before and after the 12-week intervention period. We measured the hand grip strength and isometric quadriceps contraction, the cross-sectional area of the rectus femoris (CSA-RF) (via ultrasonography), and performed the 30 s sit-to-stand test and the 6 min walk test (6MWT). We derived the Borg scale score after the 6MWT and assessed the extent of social participation and quality of life using a Korean version of the 36-Item Short Form Health Survey (SF-36). A total of 35 subjects completed the experiment (18 in the exercise group, 17 in the control group). After the 12-week intervention period, the lower-limb strength and the CSA-RF were significantly increased in the exercise group. The activity level did not change significantly in either group. The exercise group exhibited significant improvements in the SF-36 mental health domain scores. Thus, strengthening exercise is useful for patients with RA.
32637421 Whole-Body Magnetic Resonance Imaging Assessment of Joint Inflammation in Rheumatoid Arthr 2020 Objective: To compare joint inflammation seen by whole-body magnetic resonance imaging (WBMRI), with "whole-body" ultrasound and clinical assessments, in patients with active rheumatoid arthritis (RA) before and during tumor necrosis factor-inhibitor (TNF-I, adalimumab) treatment. Methods: In 18 patients with RA, clinical assessment for joint tenderness and swelling, WBMRI, and ultrasound were obtained at baseline and week 16. Wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP), elbow (except for WBMRI), shoulder, knee, ankle, and metatarsophalangeal joints were examined. Joint inflammation was defined by WBMRI as the presence of synovitis and/or osteitis and by ultrasound as gray-scale synovial hypertrophy grade >2 and/or color Doppler grade >1. On patient level, agreement was assessed by Spearman correlation coefficients (rho) for sum scores for 28 joints (i.e., wrists, MCPs, PIPs, elbows, shoulders, and knees) between clinical examination (DAS28CRP), ultrasound (US28), and WBMRI (WBMRI26; elbows not included). On joint level, agreement on inflammation between WBMRI, ultrasound, and clinical findings was calculated with Cohen's kappa (κ). Results: At patient level, WBMRI26 and US28 sum scores showed good correlation (rho = 0.72; p < 0.01) at baseline, but not at follow-up (rho = 0.25; p = 0.41). At joint level, moderate agreement was seen for hand joints (κ = 0.41-0.44); for other joints κ <0.40. No correlation with DAS28CRP was seen. No statistically significant correlations were observed between changes in WBMRI26, US28, and DAS28CRP during treatment. Conclusions: WBMRI and ultrasound joint inflammation sum scores at patient level showed good agreement in clinically active RA patients before TNF-I initiation, whereas agreement was poorer at joint level, and after treatment.
33086997 A case report, a case who developed limited cutaneous scleroderma and pulmonary hypertensi 2020 Jul A 52-year-old woman was diagnosed as having anti-centromere antibody (ACA)-positive primary Sjögren syndrome (pSS). Eight years later, she visited our hospital because she had developed dyspnoea. She was diagnosed as having pulmonary arterial hypertension (PAH) with pulmonary veno-occlusive disease on the basis of the results of right heart catheterisation, a severe decrease in diffusing capacity of the lung for carbon monoxide (D(LCO), 17%) and desaturation (69%) after a 6-minute walk test. She was also diagnosed as having limited cutaneous systemic sclerosis (lcSSc) because she had developed finger sclerosis. The six-minute walk distance had improved by 54 m 3 months after commencing treatment with tadalafil. Clinicians should be alert to the possibility of patients with ACA-positive SS developing lcSSc and PAH during their clinical course.
32895147 [Characteristics of intestinal flora in patients with primary Sjögren syndrome]. 2020 Jul 30 OBJECTIVE: To investigate changes in intestinal flora in patients with primary Sj?gren syndrome (pSS) and explore the relationship between pSS disease activity and intestinal flora structure. METHODS: Fecal samples were collected from 18 female pSS patients, including 9 patients with active disease (group A) and 9 with disease inactivity or low activity (group B), with 10 healthy subjects as the control group. The total bacterial DNA was extracted from the fecal samples for PCR amplification, and Illumina Hiseq 2500 high-throughput sequencing was performed for the v3-v4 region of 16Sr DNA gene to obtain the biological information of the intestinal flora. The intergroup OTU analysis, structural diversity analysis, significant difference analysis and LEFSE analysis were performed with information mining of the literature think tanks. RESULTS: The dilution curves generated based on the OTUshannon index for analysis of sample complexity showed that the measured data were relatively complete and could reflect the diversity of the microorganisms in the subjects. Analysis of the Alpha diversity index showed that the Shannon index differed significantly between group A and group B, and the Simpson index differed significantly between group A and group B and between group A and the control group (P < 0.05). Sequence analysis the 3 groups all consisted mainly of 4 phylum (Firmicutes, Bacteroidetes, Actinobacteria, showed that the intestinal flora in and proteobacteria) and 4 genera (finegoldia, Prevotella, Streptococcus, and Corynebacterium_1), all showing no significant differences among the 3 groups (P > 0.05) with the exception of Streptococcus genus, which differed significantly among the 3 groups (P < 0.05). The 16S v3-v4 region in the genus Alloscardovia, Bacteroides, Barnesiella, Butyricicoccus, Facklamia, Faecalibacterium, Lachnospiraceae_FCS020_group, Lachnospiraceae_ND3007_group, Lachnospiraceae_UCG-001, Lachnospirace, Lachnospirace, Ruminococcaceae_UCG-002, Streptococcus and Coprococcus_1 differed significantly among the 3 groups (P < 0.05). The high-dimensional biometrics and genomic characteristics of the intestinal microorganisms differed significantly among the 3 groups (P < 0.05). According to the size of LDA SCORE (effect size), the core flora in group A included the genera Barnesiellaccae, Aerococcaceae, Family-XIII, Bacteroidaceae, Lachnospiraceae_UCG-001, Barnesiella, Facklamia, Alloscardovia, Faecalibacterium and Bacteroides, as compared with the genera Streptococcaceae, Streptococcus, Coprococcus_1, Ruminococcaceae_ucg-002, Lachnospiraceae_FCS020_group, Lachnospiraceae_ucg-004, Lachnospiraceae_ND3007_group, Lachnospiraceae_ucg-008 and Butyricicoccus in the control group. CONCLUSIONS: Patients with pSS have significant changes in the diversity of intestinal flora, especially in some specific bacteria in Streptococcu genus and in 16S v3-v4 region of the bacteria. The differences in the core bacteria in the intestinal flora of pSS patients suggest the role of flora structure changes in the pathogenesis of pSS.
31995009 Primary Sjögren's Syndrome and Cardiovascular Disease. 2020 Sjögren's syndrome is a rheumatic autoimmune disease that primarily affects middle-aged women and runs a slowly progressing course with sicca symptoms being the prevalent manifestation. Premature atherosclerosis and increased cardiovascular (CV) morbidity and mortality are frequently encountered in rheumatic diseases characterized by significant systemic inflammation, such as the inflammatory arthritides, systemic vasculitides and systemic lupus erythematosus. In the same context, chronic inflammation and immune aberrations underlying Sjögren's syndrome are also reported to be associated with augmented risk of atherosclerosis. Increased CV disease (CVD) frequency has been found in recent meta-analyses. The involvement of the CV system is not a common feature of Sjögren's syndrome; however, specific manifestations, such as autoantibody-mediated heart block, pericarditis, pulmonary arterial hypertension and dysautonomia, have been described. This review focuses on studies addressing CV morbidity in Sjögren's syndrome and presents current data regarding distinct CV features of the disease.
33324204 Computational Prediction of Antiangiogenesis Synergistic Mechanisms of Total Saponins of P 2020 Objective: To investigate the anti-angiogenesis mechanisms and key targets of total saponins of Panax japonicus (TSPJ) in the treatment of rheumatoid arthritis (RA). Methods: RStudio3.6.1 software was used to obtain differentially expressed genes (DEGs) by analyzing the differences in gene expression in the synovial tissue of RA and to predict the potential targets of active compounds from TSPJ by the PharmMapper and SwissTargetPrediction databases. We evaluated the overlapping genes by intersectional analysis of DEGs and drug targets. Based on the overlapping genes, we used Cytoscape 3.7.2 software to construct a protein-protein interactions (PPI) network and applied Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to determine the mechanisms of the treatment. Finally, the correlations with angiogenesis-related genes were explored. Collagen-induced arthritis (CIA) model was established and treated with different doses of TSPJ. The manifestations of CIA were determined by evaluation of arthritis index and histology score. Serum levels of vascular endothelial growth factor (VEGF) and the hypoxia-inducible factor 1 (HIF-1) were tested by ELISA. The mRNA levels of IL-1β and IL-17A were detected by real time-quantitative PCR. Results: Altogether, 2670 DEGs were obtained by differential analysis, and 371 drug targets were predicted for four active components (Araloside A, Chikusetsusaponin IVa, Ginsenoside Rg2, and Ginsenoside Ro). A total of 52 overlapping genes were included in the PPI network and the KEGG analysis. However, only 41 genes in the PPI network had protein interactions. The results of the KEGG enrichment analysis were all related to angiogenesis, including VEGF and HIF-1 signaling pathways. Seven genes with negative correlations and 16 genes with positive correlations were obtained by correlational analysis of DEGs in the VEGF and HIF-1 signaling pathways. SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), and the signal transducer and activator of transcription 3 (STAT 3) had a higher value of degree and showed a significant correlation in the pathways; they were regarded as key targets. Compared with the model group, TSPJ significantly relieved the symptoms and decreased the expression of VEGFA, HIF-1α, IL-1β, and IL-17A in serum or spleens of CIA mice. Conclusion: In the current study, we found that antiangiogenesis is one of the effective strategies of TSPJ against RA; SRC and STAT 3 may be the key targets of TSPJ acting on the VEGF and HIF-1 signaling pathways, which will provide new insight into the treatment of RA by inhibiting inflammation and angiogenesis.
32328136 Wasp Venom Possesses Potential Therapeutic Effect in Experimental Models of Rheumatoid Art 2020 Rheumatoid arthritis (RA) is an autoimmune disease. Wasp venom (WV), which is considered as a traditional folk medicine in Jingpo nationality in Yunnan, China, relieves rheumatoid arthritis. The current study aimed to investigate the effect of wasp venom ameliorating rheumatoid arthritis symptoms in experimental rats. We established a model of type II collagen- (CII-) induced arthritis (CIA) in SD rats and examined the inhibition of inflammation and autoimmune response. The antiarthritic effects of WV were evaluated through the paw swelling, and histopathological score and histopathology changes of the affected paw were assessed. The anti-inflammation effects were assayed by the level of IL-6, TNF-α, IL-1β, and the number of inflammatory cells in peripheral blood. The alteration of the T cell subset ratio in the spleen of rats was detected by flow cytometry, and at the same time, the viscera index and immune serum globulin levels were evaluated. The results suggested that various doses of WV (0.125, 0.25, and 0.5 mg/kg) significantly alleviated paw swelling and arthritis score in CIA rats with the untreated control (P < 0.05). WV (0.25 and 0.5 mg/kg) relieved synovial tissue lesions of ankle joints and histopathology scores of synoviocyte hyperplasia and inflammatory cell infiltration with vehicle group (P < 0.05). Regarding immunological regulation, 0.5 mg/kg WV lowered the immune serum globulin levels (P < 0.05), and we further found that WV (0.5 mg/kg) suppressed the immune response of Th cells, while enhancing the functions of Tc cells and Treg cells in spleen cells markedly (P < 0.05). The immunosuppressive action of WV displayed was analogous to its inhibitory effect on IL-1β, TNF-α, IL-8, IL-6, COX-2, and PGE2 levels in rat serum. In conclusion, these findings demonstrated that WV exhibited antiarthritic activity, which might be associated with their inhibitory effects on immunoregulation and anti-inflammatory action.
32700877 Pronounced dys-autonomic symptoms announcing a primary Sjögren's syndrome. 2020 Jul 23 Sjögren's syndrome (SS) is an autoimmune disease that involves the nervous system in about 20% of cases. In 25-92% of patients affected by Sjögren's syndrome, neurological symptoms may precede the sicca syndrome. A 65-year-old male presented with a seven-month history of episodes of near-syncope, constipation, anhidrosis, disabling fatigue and asthenia. Physical examination was unremarkable, whilst the ECG revealed sinus bradycardia. Laboratory tests showed lymphopenia and normal inflammatory markers. In order to assess a potential autonomic neuropathy, "Deep Breathing Test" (E/I 1.02), "Lying to Standing Test" (R/R' 0.95), and "Orthostatic Hypotension Tests" (T 120s Systolic reduction >20 mmHg and Diastolic reduction >10 mmHg) were performed, all of which were abnormal. ECG Holter monitoring revealed sinus bradycardia, and right bundle branch block with 24-h blood pressure monitoring revealing a diurnal hypotensive profile. The patient reported a three-month history of worsening dry mouth. On physical examination, the patient had anisocoria in response to light stimulation. Auto-antibody testing was performed to evaluate the presence of any autoimmune disease. The results of these studies included an abnormal elevation of ANA (1:320 speckled pattern), Ro/SS-a (>240U/l), and La/SS-b (162 U/ml) antibodies. The patient was discharged with a diagnosis of "Autonomic Neuropathy Most Likely Due to Primary Sjögren's Syndrome (SS)" and started the immunotherapy. After one month, he reported a significant improvement in his symptoms with a concomitant normalization of his "Orthostatic Hypotension Tests." This case underlines the potential for dys-autonomic symptoms to precede the onset of sicca syndrome in patients with Sjogren's Syndrome.