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ID PMID Title PublicationDate abstract
34830057 Epigenetic Regulation (Including Micro-RNAs, DNA Methylation and Histone Modifications) of 2021 Nov 10 The inflammatory reaction in rheumatoid arthritis (RA) is controlled by major epigenetic modifications that modulate the phenotype of synovial and immune cells. The aim of this work was to perform a systematic review focusing on miR expression, DNA methylation and histone modifications in RA. We demonstrated that, in human samples, the expressions of miR-155, miR-146a and miR-150 were significantly decreased while the expression of miR-410-3p was significantly increased in the RA group. Moreover, miR-146a significantly decreased pro-autoimmune IL-17 cytokine expression in RA. In a murine model, miR-34a inhibition can ameliorate the arthritis score. However, this evidence remain critically insufficient to support current therapeutic applications in RA patients.
33642418 Systematic review and meta-analysis: dipeptidyl peptidase-4 inhibitors and rheumatoid arth 2021 Jun 28 This review evaluated the risk of rheumatoid arthritis in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors (Dpp-4i). The MEDLINE (via PubMed), Embase, the Cochrane Library databases and web of science were used to search the effects of Dpp-4i on rheumatoid arthritis in patients with type 2 diabetes from inception to 7 September, 2020. We included studies that met the following criteria:(i) A randomized controlled trial (RCT), prospective or retrospective cohort study examining the relationship between Dpp-4i and rheumatoid arthritis. Exclusion criteria included the following: Reviews and researches related to other diseases or subjects; and studies without data on the prevalence of rheumatoid arthritis were excluded. Risk of Bias table contained in Review Manager 5.3 and Newcastle-Ottawa scale (NOS) were used for quality assessment of included RCT and observational studies separately. Meta-analysis was used to estimate the risk of disease. We conducted a subgroup analysis of duration of follow-up, adjusted (adjusted RR or unadjusted RR), sample size and study design. A total of 10 independent studies assessing 1,420,414 patients were included in this analysis. In this meta-analysis, we found that there was nonsignificant increase of rheumatoid arthritis with Dpp-4 inhibitor exposure (RR 0.96, 95%CI (0.69-1.32)). Our results revealed that Dpp-4 inhibitors do not seem to increase the risk of rheumatoid arthritis. Long-term follow-up monitoring is necessary.
33450018 The oral and gut microbiome in rheumatoid arthritis patients: a systematic review. 2021 Mar 2 BACKGROUND: Recently, researchers have proposed a possible relationship between RA and the microbiome of the oral cavity and gut. However, this relation has not been systematically established. Herein, we conducted a comprehensive review of the pertinent literature to describe this possible association. METHODS: We systematically performed searches in databases, namely EMBASE, the Cochrane Library, and PubMed, from inception to 7 June 2020 to identify case-control studies that compared the oral and gut microbiome in adult RA patients with those of controls. The primary outcome was specific bacterial changes between RA and controls. The secondary outcome was microbial diversity changes between RA and controls. RESULTS: In total, 26 articles were considered eligible for inclusion and reported some differences. Therein, ≥3 articles reported decreased Faecalibacterium in the gut of early-RA (ERA)/RA patients compared with healthy controls (HCs). Also, ≥3 articles reported decreased Streptococcus and Haemophilus and increased Prevotella in the oral cavity of ERA/RA patients compared with HCs. In addition, some Prevotella species, including P. histicola and P. oulorum, showed increased trends in RA patients' oral cavity, compared with HCs. The α-diversity of the microbiome was either increased or not changed in the oral cavity of RA patients, but it was more commonly either decreased or not changed in the gut of RA patients. CONCLUSIONS: In this systematic review, we identified the microbiome associated with RA patients in comparison with controls. More research is needed in the future to find the deep relationship between RA and the microbiome.
34134454 Plasma Levels of MicroRNA-146a-5p, MicroRNA-24-3p, and MicroRNA-125a-5p as Potential Diagn 2021 Jun 6 Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the articular tissue. This study aims to evaluate the expression of microRNA (miR)-146a-5p, miR-24-3p, and miR-125a-5p in the plasma of RA patients and compare them with those of healthy controls to obtain a specific expression profile for earlier diagnosis and assistance in treating patients. This study was performed on 50 RA patients and 50 healthy controls. Five microliters of blood were taken from each patient/control. Plasma RNA was extracted using the Trisol solution. cDNAs were synthesized; using moloney murine leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Real-time PCR was performed using SYBR green kit. The mean expression of miR-146a-5p, miR-24-3p, and miR-125a-5p in the RA group were 8.1±1.9, 6.5±1.2, and 6.8±2.2 and in the healthy group were 4.8±1.6, 3.6±2.2, and 3.4±1.7, respectively. Significant differences were also observed in the mean expression of these three miRNAs in four subgroups of RA patients with different disease activity based on disease activity score 28 (DAS28) (p<0.05). ROC curve analysis showed that miR-146a-5p (AUC=0.8, sensitivity= 96%, specificity=86%), miR-24-3p (AUC=0.7, Sensitivity=95%, Specificity=75%) and miR-125a-5p (AUC=0.71, sensitivity=93%, specificity=84%) could be used as suitable biomarkers for RA diagnosis. Increased expressions of miR-146a-5p, miR-24-3p, and miR-125a-5p in RA patients indicate that the miRNAs are involved in disease incidence and progression, and the measurement of their expression can play an essential role in the diagnosis and treatment of the disease.
33379028 Microdevice immunoassay with conjugated magnetic nanoparticles for rapid anti-cyclic citru 2021 Mar 1 Anti-cyclic citrullinated peptide IgG antibodies (anti-CCP) are produced as an immune response in the presence of post-translational modified peptides known as cyclic citrullinated peptides (CCP). Anti-CCP have been considered as specific biomarkers for the diagnosis of rheumatoid arthritis (RA), and due to their high specificity, it is possible to make a differential diagnosis of other rheumatic diseases. These autoantibodies can be detected in the early stages of RA and even up to 10 years before presenting the first symptoms of the disease opening a window of opportunity for timely treatment. In this work, a simple straight channel microdevice and CCP conjugated magnetic nanoparticles (MNPs-CCP) as solid support was developed for quantifying anti-CCP. An additional microdevice with an optical flow Z cell design coupled with optical fibers was used to perform the spectrophotometric detection. The dynamic range of concentrations was determined between 0.70 and 2000 U mL(-1) with a limit of detection of 0.70 U mL(-1). The developed microdevice immunoassay was probed using a positive control and a negative control of plasma employing only 6 μL of both samples and reagents. The results showed that the proposed microdevice was almost nine times faster than using a commercial anti-CCP ELISA kit obtaining equivalent results and being 16 times more sensitive. The microdevice immunoassay, with conjugated MNPs-CCP is a simple method for anti-CCP quantification being cheaper, faster, and more sensitive than the ELISA kit.
33576455 Grap2 cyclin D interacting protein negatively regulates CREB‑binding protein, inhibiting 2021 Apr Rheumatoid arthritis (RA) is one of the most critical articular diseases, which is characterized by synovial hyperplasia and impaired quality of life. The clinical features of RA include chronic inflammation of the joints associated with synovial cell overgrowth. However, the mechanism regulating the outgrowth of fibroblast‑like synoviocytes (FLS) is not fully understood. The present study reported that grap2 cyclin D interacting protein (GCIP), an inhibitor of DNA binding/differentiation (ID)‑like helix‑loop‑helix protein, interacted with cAMP‑response element‑binding protein (CREB)‑binding protein (CBP). Furthermore, GCIP repressed CREB‑ and NF‑κB‑dependent gene expression by inhibiting CBP binding to RNA polymerase II complexes. GCIP depletion via small interfering RNA enhanced FLS growth, whereas stable GCIP expression suppressed the growth of 293 cells. In addition, GCIP depletion in FLS induced the expression of cyclin D1, a CREB target gene. The present study identified a novel inhibitory mechanism in which an ID protein may functionally target the transcriptional coactivator CBP. These results suggested that GCIP downregulation may be pivotal in FLS outgrowth.
34464824 A multifunctional nano-therapeutic platform based on octahedral yolk-shell Au NR@CuS: Phot 2021 Oct Rheumatoid arthritis (RA) is a common chronic autoimmune disease that results from synovial hyperplasia. The hyperplasia of synovium directly degrades cartilage by secreting matrix-degrading enzymes and inducing cartilage degradation and even loss of joint function. In this study, a metal/semiconductor composite, octahedral copper sulfide shell, and gold nanorod core (Au NR@CuS) is designed for, photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT) combination therapy for RA to remove hyperplasia of the synovium. Upon laser irradiation, the coupling of the local surface electromagnetic field improves the electromagnetic field of the Au NR core and the absorption of light of the CuS shell, whereby the photothermal effect is enhanced. Due to the Fenton-like reactions and the integration of Au NR and CuS semiconductor photocatalyst inhibits hole recombination and provides a reaction site for photocatalysis, which introduces additional •OH to photodynamics therapy. In addition, the large octahedral void space in Au NR@CuS NPs can be used for loading a high quantity of drugs for chemotherapy, and modified with vasoactive intestinal peptide and hyaluronic acid (HA) formation VIP-HA-Au NR@CuS NPs to target synovial cells in RA. Under combination therapy, VIP-HA-Au NR@CuS NPs were shown to effectively inhibit the synovial cells and the edema degree of the CIA mouse was alleviated apparently. Both in vitro and in vivo studies indicate that the VIP-HA-Au NR@CuS NPs can provide a potential possibility for the treatment of RA.
32576051 The Association between the Plasma Sugar and Lipid Profile with the Gene Expression of the 2021 Aug BACKGROUND: Rheumatoid arthritis (RA) is an autoinflammatory and self-perpetuating disease with both articular and extra-articular manifestations, such as cardiovascular complications, which are the leading cause of mortality and morbidity in RA patients. Impaired sugar and lipid metabolism are considered as the critical risk factors for cardiovascular disease (CVD). Regarding the regulatory function of Raptor in the immunometabolism, in this study, we evaluated the association between plasma sugar and lipid profiles with the gene expression of Raptor and the cytokine tumor necrosis factor-α (TNF-α), as an inflammatory mediator, in peripheral blood leukocyte of RA patients. MATERIAL AND METHODS: Thirty-five RA patients who received combinational disease modified anti-rheumatoid drugs (DMARD) regimen and thirty healthy subjects enrolled in this study. The gene expression of Raptor was assessed by the real-time PCR method, and the Plasma levels of glucose and lipids, as well as TNF-α, were obtained using Hitachi device and enzyme-linked immunosorbent assay (ELISA) technique, respectively. RESULTS: The gene expression of Raptor was reduced significantly in RA patients compared to the healthy subjects (p = .001). The plasma level of HDL was significantly higher in RA patients than the control group (p = .001), while the plasma level of LDL was reduced significantly in these patients (p = .001). CONCLUSION: In our study, the reduced gene expression of Raptor may contribute to the impaired immunometabolism in RA patients, which is independent of plasma sugar and lipid profile.
33516754 Polyketal Nanoparticles Co-Loaded With miR-124 and Ketoprofen for Treatment of Rheumatoid 2021 May Ketoprofen, a non-steroidal anti-inflammatory drug, can effectively relieve pain associated with arthritis, and microRNA-124 (miR-124) can inhibit the progression of the disease. In this study, poly (cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) nanoparticles (NPs) co-loaded with ketoprofen and miR-124 were successfully prepared using an emulsified solvent evaporation method. The co-loaded NPs exhibited a mean particle diameter of 160 nm. The acid sensitivity of the NPs was determined through in vitro release experiments. An adjuvant-induced arthritis rat model of arthritis was established for evaluating the pharmacodynamics of the NPs through clinical scoring and degree of swelling. The PCADK NPs exhibited more potent pharmacodynamic effects owing to the acid-sensitive properties of the carrier materials, compared with Poly (lactic-co-glycolic acid) (PLGA) NPs. Furthermore, PCADK co-loaded NPs exhibited superior anti-inflammatory effects compared to NPs loaded with either miR-124 or ketoprofen alone. In conclusion, co-delivery of ketoprofen and miR-124 through NPs is a promising strategy for the treatment of arthritis.
34402295 [Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19~+B cells regul 2021 Jul To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.
33763076 Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of 2021 Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.
34184082 circPTPN22 as a novel biomarker and ceRNA in peripheral blood mononuclear cells of rheumat 2021 Aug The role of circular RNAs (circRNAs) in rheumatoid arthritis (RA) remains to be elucidated. To determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) and to identify novel biomarkers for RA and explore their potential effects in RA, the present study conducted high‑throughput RNA sequencing to analyze circRNA expression profiles in PBMCs from 4 RA patients and 3 healthy controls (HCs). Reverse transcription‑quantitative PCR was used to verify the expression of circPTPN22 in 42 RA patients, 44 HCs and 45 systemic lupus erythematosus (SLE) patients. In addition, bioinformatics analysis and Pearson's correlation test were conducted to assess the correlation of the relationships between circPTPN22 and RA progression. A receiver operating characteristic curve was calculated to evaluate the diagnostic value. Multilevel integrated analysis identified 41 upregulated and 30 downregulated circRNAs in RA patients compared with HCs. circPTPN22 was confirmed to be a common differentially expressed gene in RA and SLE compared with HCs. Area under the curve analysis suggested the diagnostic value of circPTPN22 expression to distinguish RA patients from both HCs and SLE patients. In addition, circPTPN22 levels in RA PBMCs were correlated with RA‑IgG, RA‑IgM, RA‑IgA, anti‑cyclic citrullinated peptide (anti‑CCP), rheumatoid factor and C reactive protein levels. A total of four putative microRNAs (miRNAs or miRs), namely, hsa‑miR‑3074‑5p, hsa‑miR‑373‑3p, hsa‑miR‑766‑3p and hsa‑miR‑34c‑5p, were screened to be sponged by circPTPN22 via bioinformatics analysis and then experimentally verified to be upregulated in RA PBMCs compared with controls. The data suggested that circPTPN22 might be a novel biomarker for the diagnosis of RA and participate in RA pathogenesis through a sponge mechanism.
34921093 Cardiovascular risk management in antiphospholipid syndrome: trends over time and comparis 2021 Dec OBJECTIVE: Antiphospholipid syndrome (APS) is characterised by increased cardiovascular morbidity and mortality, related to thrombo-inflammatory and atherogenic mechanisms. We examined the achievement of traditional cardiovascular risk factor (CVRF) therapeutic goals in APS versus other high cardiovascular risk disorders such as rheumatoid arthritis (RA) and diabetes mellitus (DM), and trends over time. METHODS: 122 patients with APS (74 primary APS, female 68%, mean age 44.5±11.3) were classified according to their first visit (2011-2015 and 2016-2020 APS subgroups, 61 patients in each subgroup) and matched 1:1 for age/sex with patients with RA and DM. Cardiovascular risk was estimated by the Systemic Coronary Risk Evaluation, and the CVRF therapeutic targets were defined according to the European Society of Cardiology (ESC) guidelines. Individual and multiple CVRF control was compared between APS subgroups, and in APS versus RA and DM. RESULTS: We found a comparable or higher prevalence of CVRFs between APS and age-matched/sex-matched patients with RA and DM but low CVRF target attainment in APS according to the ESC guidelines. Despite improving trends between 2011-2015 and 2016-2020, CVRF control in high/very high-risk patients with APS was 12%, 18%, 24% and 35% for low-density lipoprotein, waist circumference, exercise and body mass index, respectively, and 59%-65% for triglycerides, high-density lipoprotein (HDL) and blood pressure, in 2016-2020 subgroup. CVRF control was worse in APS versus RA for smoking (p=0.014), HDL (p<0.001), waist circumference (p=0.042) and five CVRFs (p=0.030), and versus DM for exercise (p=0.077). Similar results were found in the sensitivity analysis. CONCLUSIONS: Comparable prevalence of modifiable CVRFs to RA and DM but suboptimal CVRF target achievement was observed in APS, especially in high/very high-risk patients, highlighting the need for CVRF management strategies.
33123735 Dendritic cell integrin expression patterns regulate inflammation in the rheumatoid arthri 2021 Mar 2 OBJECTIVES: Immune dysregulation contributes to the development of RA. Altered surface expression patterns of integrin adhesion receptors by immune cells is one mechanism by which this may occur. We investigated the role of β2 integrin subunits CD11a and CD11b in dendritic cell (DC) subsets of RA patients. METHODS: Total β2 integrin subunit expression and its conformation ('active' vs 'inactive' state) were quantified in DC subsets from peripheral blood (PB) and SF of RA patients as well as PB from healthy controls. Ex vivo stimulation of PB DC subsets and in vitro-generated mature and tolerogenic monocyte-derived DCs (moDCs) were utilized to model the clinical findings. Integrin subunit contribution to DC function was tested by analysing clustering and adhesion, and in co-cultures to assess T cell activation. RESULTS: A significant reduction in total and active CD11a expression in DCs in RA SF compared with PB and, conversely, a significant increase in CD11b expression was found. These findings were modelled in vitro using moDCs: tolerogenic moDCs showed higher expression of active CD11a and reduced levels of active CD11b compared with mature moDCs. Finally, blockade of CD11b impaired T cell activation in DC-T cell co-cultures. CONCLUSION: For the first time in RA, we show opposing expression of CD11a and CD11b in DCs in environments of inflammation (CD11alow/CD11bhigh) and steady state/tolerance (CD11ahigh/CD11blow), as well as a T cell stimulatory role for CD11b. These findings highlight DC integrins as potential novel targets for intervention in RA.
34002814 Impact of biologic disease-modifying antirheumatic drugs on fracture risk in patients with 2021 May OBJECTIVE: This systematic review aimed to assess the impact of biologic disease-modifying antirheumatic drugs (bDMARDs) use on the risk of fracture in rheumatoid arthritis (RA) by conducting a pooled analysis of adjusted outcomes from individual studies. MATERIALS AND METHODS: PubMed, Embase, and BioMed Central were searched up to 20th January 2021. Multivariable-adjusted odds ratios (OR) or matched estimates on the impact of bDMARDs on fracture risk were pooled. RESULTS: Nine studies were included. We found no statistically significant difference in the risk of fractures in RA patients using bDMARDs vs. non-users. On sensitivity analysis, we found no change in the significance of the effect size on exclusion of any study. There was no statistically significant difference in fracture risk in studies only on tumor necrosis factor (TNF) inhibitors, as well as those including any bDMARDs. Pooled analysis of only three studies indicated a statistically significant reduction in vertebral fractures in bDMARD users vs. non-users. CONCLUSIONS: Within the ambit of several limitations of our review, there seems to be no impact of bDMARDs on the fracture risk in RA patients. Further studies evaluating the type and duration of bDMARD therapy with meticulous adjustment of confounding factors are required to strengthen current evidence.
34325277 The effects of miR-26b-5p on fibroblast-like synovial cells in rheumatoid arthritis (RA-FL 2021 Oct OBJECTIVE: To study the possible effects of miR-26b-5p on fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) through targeting enhancer of zeste homolog 2 (EZH2). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-26b-5p and EZH2 expressions in synovial tissues of RA patients and healthy controls. Dual luciferase reporter assay was adopted to verify the targeting relationship between miR-26b-5p and EZH2. RA-FLS was divided into Blank, mimics NC, mimics, NC siRNA, EZH2 siRNA and inhibitors + EZH2 siRNA groups, followed by the assessment of proliferation, apoptosis, migration and invasion. The expression of genes and proteins in RA-FLS was tested by qRT-PCR and western blotting, respectively. RESULTS: MiR-26b-5p expression was lower, while EZH2 expression was higher in synovial tissue of RA patients than healthy controls; and miR-26b-5p was negatively correlated with the EZH2 in synovial tissue of RA patients, which were both related with disease activities. MiR-26b-5p can target EZH2 in RA-FLS. In vitro, miR-26b-5p mimics down-regulated EZH2 expression in RA-FLS. Compared with EZH2 siRNA group, the miR-26b-5p expression in inhibitors + EZH2 siRNA group was reduced, but EZH2 expression was increased. EZH2 siRNA inhibited the proliferation, invasion and migration of RA-FLS, promoted cell apoptosis, and inhibited the expression of TNF-α, IL-1β, IL-6, IL-17, MMP-2, MMP-9, which were reversed by miR-26b-5p inhibitor. CONCLUSION: MiR-26b-5p may affect the biological characteristics of RA-FLS via targeting EZH2, including proliferation, apoptosis, invasion and migration, as well as the secretion of cytokines, thus playing a potential therapeutic role in RA.
33465281 miR-34a in extracellular vesicles from bone marrow mesenchymal stem cells reduces rheumato 2021 Feb Extracellular vesicles (Evs) participate in the development of rheumatoid arthritis (RA), but the mechanisms remain unclear. This study aimed to determine the mechanism by which microRNA-34a (miR-34a) contained in bone marrow mesenchymal stem cell (BM-MSC)-derived Evs functions in RA fibroblast-like synoviocytes (RA-FLSs). BM-MSC-derived Evs and an Evs inhibitor were extracted. A rat model of RA was established. miR-34a gain- and loss-of-function experiments were performed, and the inflammation in rat synovial fluid and tissues was detected. The role of miR-34a in RA-FLSs was also measured in vitro. The target gene of miR-34a was predicted using the online software TargetScan and identified using a dual-luciferase reporter gene assay, and the activation of the ATM/ATR/p53 signalling pathway was assessed. BM-MSC-derived Evs mainly elevated miR-34a expression, which reduced RA inflammation in vivo and inhibited RA-FLS proliferation and resistance to apoptosis in vitro, while inhibited miR-34a expression enhanced RA development. In addition, miR-34a could target cyclin I to activate the ATM/ATR/p53 signalling pathway, thus inhibiting abnormal RA-FLS growth and RA inflammation. Our study showed that miR-34a contained in BM-MSC-derived Evs could reduce RA inflammation by inhibiting the cyclin I/ATM/ATR/p53 signalling pathway.
33308005 Bail-out extracorporeal membrane oxygenation for hydroxychloroquine intoxication: a warnin 2021 Apr This case report describes an intentional intoxication with 18 g of hydroxychloroquine (HCQ) presenting with unconsciousness, ventricular dysrhythmias, cardiogenic shock and pulmonary oedema. Initial treatment consisted of sodium bicarbonate, lipid emulsion, diazepam and norepinephrine. Because of persistent cardiogenic shock veno-arterial extracorporeal membrane oxygenation (V-A ECMO) was successfully used as a bridge to recovery. This case underscores the possible side effects of HCQ and the importance of considering ECMO in cardiogenic shock caused by HCQ intoxication which may occur also in patients with coronavirus disease 2019 (COVID-19) based on the currently frequent use of such a compound.
34403509 IL-23/IL-17 axis and soluble receptors isoforms sIL-23R and sIL-17RA in patients with rheu 2021 Sep BACKGROUND: Rheumatoid arthritis (RA) and periodontitis (P) are chronic inflammatory diseases characterized by joint and radiographic bone loss, respectively. IL-23 and IL-17 have an essential role in the immunopathogenesis of RA, and P. IL-23 stimulates Th17 cells through which produces IL-17, IL-21, and RANKL. IL-17 stimulates fibroblasts to produce RANKL, which initiates bone loss in the joints in RA and the periodontal tissue in periodontitis. The aim of this study was to determine the expression pattern of IL-23/IL-17 axis and soluble receptors isoforms sIL-23R and sIL-17RA of patients with RA presenting P (RAP). MATERIAL AND METHODS: Healthy subjects (HS) (n = 42), patients with P (n = 40), RA (n = 20), and patients with RAP (n = 40) were included. Plasma samples were obtained to evaluate the IL-23, IL-17A, sIL-23R, and sIL-17RA by ELISA technique. A nonparametric Mann-Whitney U test was used to compare the differences between groups. A Chi-square was used to compare gender, grade and stage of periodontitis, and DAS28-ESR between the groups. Spearman's rank correlation coefficient was used to study the association between the molecules and clinical parameters. RESULTS: IL-23 levels were increased in the RAP group, and lower sIL-23R levels were found in the RAP groups. However, IL-17A was lower in the P and RAP group but not in RA patients. RAP group showed a decrease IL-17A levels in advanced stages of the periodontal disease. CONCLUSION: These results suggest that IL-23 and IL-17A tend to downregulate their expression patterns when patients present both rheumatoid arthritis and periodontitis.
32662409 BENEFIT: real-world effectiveness of SB4 after transition from reference etanercept in rhe 2021 Mar OBJECTIVES: The objective of this non-interventional study was to evaluate the effectiveness and safety of the etanercept biosimilar SB4 (BenepaliTM) following transition from reference etanercept in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). METHODS: Data were collected from clinical records of adult patients with stable RA or axSpA, in France, Germany, Italy and Spain. Key outcomes included the change from transition to 3 and 6 months in Disease Activity Score 28 (DAS28) for RA or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA. RESULTS: In total, 358 patients with RA and 199 patients with axSpA were enrolled. The mean individual change in disease score from transition was -0.02 (95% confidence interval [CI] -0.11, 0.08) at 3 months and 0.01 (95% CI -0.09, 0.11) at 6 months for DAS28, and -0.01 (95% CI -0.24, 0.21) at 3 months and -0.11 (95% CI -0.31, 0.10) at 6 months for BASDAI. In the RA cohort, 19 (5.3%) and 5 patients (1.4%) reported adverse events and serious adverse events (SAEs), respectively. In the axSpA cohort, 12 (6.0%) and 2 patients (1.0%) reported adverse events and SAEs, respectively. One SAE of pneumonia (RA cohort) was considered to be related to SB4 administration. At 6 months post-transition, the SB4 retention rate was 90.8% (95% CI 87.2%, 93.4%) in the RA cohort and 92.4% (95% CI 87.5%, 95.4%) in the axSpA cohort. CONCLUSIONS: Transition from reference etanercept to SB4 is effective and safe in patients with stable RA and axSpA.