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

ID PMID Title PublicationDate abstract
35368750 Effects and Safety of the Tripterygium Glycoside Adjuvant Methotrexate Therapy in Rheumato 2022 OBJECTIVE: This study aimed to systematically review the efficacy and clinical safety of different courses and doses of tripterygium glycoside (TG) adjuvant methotrexate (MTX) therapy in the treatment of rheumatoid arthritis (RA). METHODS: Randomized controlled trials (RCTs) of TG adjuvant MTX therapy in patients with RA were retrieved from SinoMed, China Network Knowledge Infrastructure, WanFang Data, PubMed, Cochrane Library, and Embase from inception to September 30, 2021. The effects and clinical safety evaluations were conducted using RevMan 5.3 software. RESULTS: A total of 9 RCTs and 892 patients with RA were included in this study. In the meta-analysis, a total of 463 and 429 patients were enrolled into the TG adjuvant MTX therapy group and MTX monotherapy group, respectively. In comparison with MTX monotherapy, the results of the analyzed effects showed that the TG adjuvant MTX therapy can achieve 20%, 50%, and 70% improvements in American College of Rheumatology (ACR) criteria ACR20, ACR50, and ACR70 at P = 0.005, P = 0.0001, and P = 0.004, respectively. Simultaneously, the efficacy of the TG adjuvant MTX therapy was improved at either 30 or 60 mg/day over a six-month course compared to MTX monotherapy (P < 0.0001). There was no statistical difference in the effects between the doses of 30 and 60 mg/day after three months (P = 0.82). TG adjuvant MTX also reduced the expression rate of the swollen joint count, tender joint count, erythrocyte sedimentation rate, rheumatoid factor, and C-reactive protein in subgroup analyses with different courses and doses. In terms of hepatic adverse effects (P = 0.28), leukopenia (P = 0.78), gastrointestinal adverse effects (P = 0.17), cutaneous adverse effects (P = 0.94), and irregular menstruation adverse effects (P = 0.29), there was no statistically significant difference with TG adjuvant MTX therapy and MTX monotherapy with different courses and doses. CONCLUSIONS: TG adjuvant MTX therapy is more effective than MTX monotherapy and is a safe strategy for RA treatment in doses of 30 or 60 mg/day over a treatment course of six months. However, high-quality multicenter RCT studies with large sample sizes are still needed to confirm the effects and clinical safety of different courses and doses of TG adjuvant MTX therapy.
35486976 Seroprevalence of SARS-CoV-2-specific antibodies and vaccination-related adverse events in 2022 Jun BACKGROUND: This study aimed to investigate the seroreactivity of Coronavirus disease 2019 (COVID-19) vaccination and its adverse events among systemic lupus erythematosus (SLE) patients, rheumatoid arthritis (RA) patients, and healthy controls (HCs). METHODS: A total of 60 SLE patients, 70 RA patients and 35 HCs, who received a complete inactivated COVID-19 vaccine (Vero cells) regimen, were recruited in the current study. Serum IgG and IgM antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2, and the self-reported vaccination-related adverse events among SLE patients, RA patients and HCs. The inactivated COVID-19 vaccines appeared to be well-tolerated and moderately immunogenic. In addition, case-only analysis indicated that in SLE patients, the disease manifestation of rash and anti-SSA autoantibody were associated with seroprevalence of IgG antibody against SARS-CoV-2, whereas the uses of ciclosporin and leflunomide had influence on the seroprevalence of IgM antibody against SARS-CoV-2. In RA patients, rheumatoid factor (RF) appeared to be associated with the seroprevalence of IgG antibody against SARS-CoV-2. CONCLUSION: Our study reveals that the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar among SLE, RA and HCs, suggesting that COVID-19 vaccine is safe and effective for SLE and RA patients to prevent from the pandemic of COVID-19.
35006578 Digital Additional Risk Minimization Measures: An Exploratory Study Using Qualitative Feed 2022 Feb BACKGROUND: Additional risk minimization measures (aRMMs) are required for some pharmaceutical products when routine risk minimization measures (i.e., product labeling) are deemed insufficient. Measures often include educational materials, such as paper brochures, leaflets, and/or alert cards that provide information to healthcare professionals and patients on the key risks associated with a product and risk minimization actions to take should particular signs or symptoms arise. Paper-based educational aRMMs have several limitations. They do not present information in an interactive manner, and their update and distribution can be costly and often complex. Measuring how effective they are in achieving their aims can also be difficult. Digital methods offer design and delivery flexibility, easier updating processes, opportunities to increase engagement with important information, as well possibilities for tracking distribution, receipt, and potentially understanding of the materials. Pharmaceutical companies have started to look to digital methods as an option for educational aRMMs, alongside paper materials. OBJECTIVES: Research into healthcare professionals and patient needs and preferences, as well as the general acceptability of digital educational options is needed to establish a baseline. This was an exploratory study intended to provide initial insights on the acceptability of digital aRMMs and to inform future research directions. METHODS: Digital concepts for educational aRMMs, one for healthcare professionals and one for patients, were evaluated with 30 healthcare professionals and 20 patients in six countries through 1:1 Zoom calls, with responses recorded in a structured Qualtrics-based survey. Criteria for selecting the six countries included local familiarity with aRMMs as well as interest in and capability to deliver a potential digital aRMM program by the sponsoring company's affiliate teams. Of the healthcare professionals, 19 were rheumatologists and 11 were dermatologists. 16 patients had rheumatologic (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) conditions and four had atopic dermatitis. These conditions were chosen as they aligned to potential therapeutic areas where the sponsoring company may have the opportunity to use a digital aRMM. Participants were given an overview of the concept as well as the opportunity to interact with it directly via the "control screen" function in Zoom before questions were posed. RESULTS: The results demonstrated that the majority of healthcare professionals (87%) and all patients interviewed would prefer website-based or app-based delivery, respectively, of aRMM information instead of, or alongside traditional paper-based approaches, with only 13% of healthcare professionals and no patients expressing a preference for paper-only communication. CONCLUSIONS: Given new options offered by digital technology, its widespread use in many fields, and the importance of patient safety as a topic, there is an imperative for pharmaceutical companies and regulators to work together to establish a way forward for the use of digital options for aRMMs. This study is limited in its generalizability but offers some ideas for future research directions.
35313088 Circulating Adipokines and Associations with Incident Cardiovascular Disease in Rheumatoid 2022 Mar 21 OBJECTIVE: To assess whether circulating levels of adiponectin, leptin, and FGF-21 are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA). METHODS: Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism [VTE], CVD-related deaths) were identified using administrative data and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox models were generated to quantify associations between adipokine concentrations and CVD incidence. Five-year incidence rates were predicted. RESULTS: Among 2,598 participants, 639 (25%) had at least one CVD event over 19,585 patient-years of follow-up. High adiponectin levels were independently associated with HF hospitalization (HR: 1.39 [1.07-1.79], p=0.01) and CVD-related death (HR: 1.49 [1.16-1.92], p=0.002) but not other CVD events. High leptin was independently associated with CVD-related death (HR: 1.44 [1.05-1.97], p=0.02). High FGF-21 levels were independently associated with lower rates of CAD (HR: 0.75 [0.58-0.97], p=0.03). In subgroup analyses, associations between high adiponectin and leptin levels with CVD-related death were driven by strong associations in non-obese patients. CONCLUSIONS: Adipokines are associated with HF hospitalization and CVD-related death in patients with RA, with stronger associations in non-obese participants. These findings suggest that adipokines effectively predict clinically important outcomes in RA perhaps through an association with body composition and metabolic health. Further study is needed to determine whether adipokine measures might augment existing tools to identify RA patients at increased risk of CVD.
35594658 Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observati 2022 May 17 BACKGROUND: Emerging evidence suggests that dysbiosis in gut microbiota may contribute to the occurrence or development of several rheumatic diseases. Since gut microbiota dysbiosis is potentially modifiable, it has been postulated to be a promising preventive or therapeutic target for rheumatic diseases. However, the current understanding on the potential associations between gut microbiota and rheumatic diseases is still inadequate. Therefore, we aimed to synthesise the accumulating evidence for the relation of gut microbiota to rheumatic diseases. METHODS: The PubMed, Embase and Cochrane Library were searched from inception to March 11, 2022 to include observational studies evaluating the associations between gut microbiota and rheumatic diseases. Standardised mean difference (SMD) of α-diversity indices between rheumatic diseases and controls were estimated using random-effects model. β-diversity indices and relative abundance of gut microbes were summarised qualitatively. FINDINGS: Of the included 92 studies (11,998 participants), 68 provided data for α-diversity. Taken together as a whole, decreases in α-diversity indices were consistently found in rheumatic diseases (observed species: SMD = -0.36, [95%CI = -0.63, -0.09]; Chao1: SMD = -0.57, [95%CI = -0.88, -0.26]; Shannon index: SMD = -0.33, [95%CI = -0.48, -0.17]; Simpson index: SMD = -0.32, [95%CI = -0.49, -0.14]). However, when specific rheumatic diseases were examined, decreases were only observed in rheumatoid arthritis (observed species: SMD = -0.51, [95%CI = -0.78, -0.24]; Shannon index: SMD = -0.31, [95%CI = -0.49, -0.13]; Simpson index: SMD = -0.31, [95%CI = -0.54, -0.08]), systemic lupus erythematosus (Chao1: SMD = -1.60, [95%CI = -2.54, -0.66]; Shannon index: SMD = -0.63, [95%CI = -1.08, -0.18]), gout (Simpson index: SMD = -0.64, [95%CI = -1.07, -0.22]) and fibromyalgia (Simpson index: SMD = -0.28, [95%CI = -0.44, -0.11]), whereas an increase was observed in systemic sclerosis (Shannon index: SMD = 1.25, [95%CI = 0.09, 2.41]). Differences with statistical significance in β-diversity were consistently reported in ankylosing spondylitis and IgG4-related diseases. Although little evidence of disease specificity of gut microbes was found, shared alterations of the depletion of anti-inflammatory butyrate-producing microbe (i.e., Faecalibacterium) and the enrichment of pro-inflammatory microbe (i.e., Streptococcus) were observed in rheumatoid arthritis, Sjögren's syndrome and systemic lupus erythematosus. INTERPRETATION: Gut microbiota dysbiosis was associated with rheumatic diseases, principally with potentially non-specific, shared alterations of microbes. FUNDING: National Natural Science Foundation of China (81930071, 81902265, 82072502 and U21A20352).
35393660 Short-chain fatty acids regulate B cells differentiation via the FFA2 receptor to alleviat 2022 Apr 7 BACKGROUND AND PURPOSE: Short-chain fatty acids (SCFAs) are metabolites from gut microbes involved in the host's inflammatory response and immunity. The aim of this study was to investigate the role of SCFAs in rheumatoid arthritis (RA) and possible mechanisms. EXPERIMENTAL APPROACH: Gut microbiota diversity in mice was analysed by 16S rDNA sequencing. SCFAs levels were analysed by gas chromatography mass spectrometry. T and B cells were analysed by flow cytometry. Bone damage was analysed by micro-CT and X-ray. Histopathological status was analysed by HE staining. Proteins in tissues were analysed by immunohistochemistry and PCR. Mice with CD19(+) B cells deficient in FFA2 receptors were used to explore the molecular mechanisms involved. KEY RESULTS: Levels of acetate, propionate, butyrate, and valerate were decreased in RA patients, and the first three correlated positively with the frequency of Bregs but not Tregs in peripheral blood. Administration of the three SCFAs prior to the onset of collagen-induced arthritis in mice improved arthritic symptoms, increased the Bregs frequency, and decreased transitional B and follicular B cell frequency. However, the preceding phenomena could not be observed in mice with CD19(+) B cells deficient in FFA2 receptors. The effects of the three SCFAs in RA were dependent on FFA2 receptors but were independent of the other five B cell receptors (FFA3 receptor, HCA(2) receptor, PPARγ, Olfr-78, and AhR). CONCLUSIONS AND IMPLICATIONS: SCFAs regulate B cells differentiation via FFA2 receptors to alleviate RA. This provides new insights into the treatment of RA from an immunological and microbiological perspective.
35509625 Xiaoyao-Qingluoyin Cure Adjuvant-Induced Arthritis by Easing LPS Response-Related Pathway- 2022 Qingluoyin (QLY) is a representative herbal formula prescribed for hot symptom-related rheumatoid arthritis treatment. Among its derivatives, Xiaoyao-Qingluoyin (XYQLY) attracts increasing attention due to the notable clinical efficacy. In this study, we compared its effects with QLY on adjuvant-induced arthritis (AIA) in rats and partially elucidated the antirheumatic mechanism using a network pharmacology-based strategy. After continuous oral treatments, clinical outcomes were systematically evaluated by radiographic, histological, immunohistochemical, and serological analyses. Possibly altered pathways were predicted based on reported interactions between the related chemicals and proteins/genes. The obtained conclusion was further validated by experiments in vitro. QLY and XYQLY eased polyarthritis in AIA rats after repeated doses, which reflected in reduced inflammation and bone degradation and downregulated p-p65, MMP3, and TLR4 expressions in joints. Meanwhile, they restored oxidative stress (MDA, SOD, GSH, T-AOC, and NO) and inflammatory indicators (TNF-α and CO) in serum. Synovium-based immunoblotting assay revealed that QLY and XYQLY were similarly effective in downregulating MMP3 and COX-2, but XYQLY treatment exhibited notable merit in suppressing p-p65 expression. Network pharmacology analysis hinted that XYQLY should exert greater impacts on LPS signaling and the downstream. Based on results from LC-MS analysis, we treated AIA rat-derived peripheral blood mononuclear cells with either QLY or XYQLY-based chemical combinations and confirmed that XYQLY had the better potential in inhibiting TLR4/NF-κB-controlled IL-6 production. Consequently, it led to a more profound decrease in Th17 cells counts. Overall evidence demonstrated that XYQLY was especially effective in regulating innate immunity and, therefore, improved immune environment in AIA rats as a whole.
35573706 Crosstalk between CD4 T cells and synovial fibroblasts from human arthritic joints promote 2022 Jun The content and organization of hyaluronan (HA) in the extracellular matrix (ECM) have been identified as strong indicators of inflammation in joint disease, although the source and role of HA as an effector of inflammation is not clear. In this study, we established co-cultures of activated human CD4 T cells with fibroblast-like synoviocytes (FLS) from osteoarthritis (OA) and rheumatoid arthritis (RA) subjects and examined the role of HA in promoting inflammatory events. Co-cultures of RA FLS with activated CD4 T cells generated an HA-enriched ECM that promoted enhanced monocyte adhesion compared to co-cultures of OA FLS with activated CD4 T cells. In addition, both OA FLS and RA FLS co-cultures with activated CD4 T cells elicited significant increases in the expression of IL1β, TNF, and IL6, with the increase in IL6 expression most prominent in RA co-cultures. Blocking HA synthesis and accumulation with 4-methylumbelliferone reduced expression of IL6, IL1β, and TNF in both OA FLS and RA FLS co-cultures. The increase in HA synthesis in the co-cultures was mimicked by IL6 trans-signaling of FLS in the absence of CD4 T cells. Inhibition of HA synthesis blocked the increase in IL6 by RA FLS mediated by IL6 trans-signaling, suggesting that the HA synthetic pathway may be a key mediator in IL6 expression by FLS. Overall, our study indicates that HA-enriched ECM generated by co-cultures of activated CD4 T cells with FLS from human joints creates a pathogenic microenvironment by promoting adhesion of leukocytes and expression of inflammatory cytokines including IL6.
35477534 Pseudoaneurysm with a fistula to the right ventricle late after surgical repair of type A 2022 Apr 27 BACKGROUND: Pseudoaneurysm with a shunt to the right ventricle after aortic repair for acute aortic dissection is an extremely rare and life-threatening condition. Surgical treatment is unavoidable, but surgery is complicated, and there are some pitfalls. This study describes the reoperation performed in a patient at a high surgical risk by clarifying the shunt site using multimodality imaging before surgery. CASE PRESENTATION: A 69-year-old woman with a history of systemic lupus erythematosus (SLE) and Sjogren's syndrome presented with a pseudoaneurysm 1 year after emergency surgery for acute type A aortic dissection. Eight years after the first surgery, she experienced sudden chest pain and presented to the emergency department. Her dyspnea worsened; therefore, echocardiography and three-dimensional computed tomography (3DCT) were performed, and a pseudoaneurysm and shunt to the right ventricle were identified. The medical team attempted to close the shunt with a percutaneous catheter but was unsuccessful, and she was referred to our department for surgical treatment. The pseudoaneurysm originating from the proximal side of the aorta was large (diameter = 55 mm), and echocardiography-gated 3DCT identified the shunt from the pseudoaneurysm to the right ventricle. First, extracorporeal circulation was initiated, and resternotomy was performed. We could not insert the left ventricular venting tube from the right side because of the pseudoaneurysm size. Instead, the tube was inserted from the left atrial appendage. We found a half-circumferential disengaged anastomosis around the proximal anastomosis, which formed the large pseudoaneurysm leading to a fistula in the right ventricle. We closed the fistula and performed a Bentall operation. The patient had a good postoperative course and was discharged on postoperative day 21. She continued treatment for SLE and Sjogren's syndrome, and her inflammatory reaction improved. CONCLUSIONS: We performed a Bentall operation and fistula closure with resternotomy in a patient with type A aortic dissection with SLE and Sjogren's syndrome. Multimodal imaging is essential in defining the pseudoaneurysm and the fistula surrounding the anatomy while ensuring their resolution and guiding the approach for operation.
35045743 HCV Infection Alters Salivary Gland Histology and Saliva Composition. 2022 May Hepatitis C virus (HCV) infection is the most common blood-borne chronic infection in the United States. Chronic lymphocytic sialadenitis and sicca syndrome have been reported in chronic HCV infection. Up to 55% of these patients may have xerostomia; the mechanisms of the xerostomia and salivary gland (SG) hypofunction remain controversial. The objectives of this project are to establish if xerostomia associates with SG and HCV infection and to characterize the structural changes in SG and saliva composition. Eighteen HCV-infected patients with xerostomia were evaluated for SG dysfunction; 6 of these patients (patients 1-6) were further evaluated for SG histopathological changes and changes in saliva composition. The techniques used include clinical and laboratory assessment, SG ultrasonography, histological evaluation, sialochemical and proteomics analysis, and RNA in situ hybridization. All the HCV patients had low saliva flow, chronic sialadenitis, and SG fibrosis and lacked Sjögren syndrome (SS) characteristic autoantibodies. Further evaluation of a subgroup of 6 HCV patients (patients 1-6) demonstrated diffuse lymphocytic infiltrates that are predominantly CD8(+) T cells with a significant increase in the number of inflammatory cells. Alcian Blue/periodic acid-Schiff staining showed significant changes in the ratio and intensity of the acinar secretory units of the HCV patients' minor SG. The submandibular glands showed significant ultrasonographic abnormalities in the parenchyma relative to the parotid glands. Significant changes were also observed in the concentration of sodium and mucin 5b. Although no significant correlation was observed between the lymphocytic infiltrates and the years of HCV chronic infection, a positive correlation was observed between HCV RNA-positive epithelial cells and the years of HCV infection. Consistent with the low saliva flow and xerostomia, patients showed changes in several markers of SG acinar and ductal function. Changes in the composition of the saliva suggest that HCV infection can cause xerostomia by mechanisms distinct from SS.
35560180 The hyper-expression of NLRP4 characterizes the occurrence of macrophage activation syndro 2022 May 13 To assess stimulator of interferon genes (STING) pathway in patients with adult-onset Still's disease (AOSD) who were complicated or not by macrophage activation syndrome (MAS), evaluating peripheral blood mononuclear cells (PBMCs), and synovial tissues. The relative mRNA expression of key molecules of the STING pathway (i.e. CGAS, NLRP4, PKDC, STING1, XRCC5, and XRCC6) and interferon (IFN)-γ was assessed in PBMCs obtained from patients with AOSD, who were complicated or not by MAS, and healthy controls (HCs). A bulky RNA sequencing was performed in synovial tissues from two patients with AOSD. Finally, the ability of heavy ferritin subunit (FeH) to induce the expression of NLRP4 was evaluated in cultured macrophages. Twenty patients with AOSD were analysed. Out of them, seven patients were complicated by MAS. Assessing mRNA relative expression in PBMCs, STING1, NLRP4, XRCC6, and IFN-γ were significantly expressed in AOSD than HCs. The mRNA relative expression of CGAS, PKDC, and XRCC5 did not differ between patients and HCs. Furthermore, NLRP4 and IFN-γ resulted to be significantly increased in patients with AOSD complicated by MAS than others. By RNA-sequencing analysis, we observed that Nlrp4 gene was significantly up-regulated in patients with AOSD. Following the stimulation with FeH, an increased expression of NLRP4 was observed in cultured macrophages. In conclusion, an increased expression of some key molecules of STING pathway characterized patients with AOSD. In addition, our results suggested that a hyper-activity of NLRP4 may be observed in patients with MAS. Furthermore, FeH increased the expression of NLRP4 in cultured macrophages.
35482248 Early Real-World Experience of Tofacitinib for Psoriatic Arthritis: Data from a United Sta 2022 Jun INTRODUCTION: This study characterized real-world demographic and baseline clinical characteristics, as well as treatment persistence and adherence, in patients with psoriatic arthritis (PsA) who had newly initiated tofacitinib treatment. METHODS: This retrospective cohort study included patients aged 18 years or older in the IBM MarketScan™ US database with at least one tofacitinib claim (first = index) between December 14, 2017 and April 30, 2019; PsA diagnoses on/within 12 months pre-index; and no diagnoses of rheumatoid arthritis any time pre-index. Patients were continuously enrolled for 12 months pre-index and 6 months post-index, with no pre-index claims for tofacitinib. Patient demographic and clinical characteristics on the day of index, and history of advanced treatments (including tofacitinib monotherapy or combination therapy), were recorded. Outcomes at 6 months post-index included tofacitinib persistence (less than 60-day gap without tofacitinib treatment) and adherence (proportion of days covered [PDC] and medication possession ratio 80% or higher). RESULTS: Of the 10,354 patients with tofacitinib claims within the study period, 318 patients with PsA met the inclusion criteria. More than 60% of patients received tofacitinib monotherapy post-index, with a mean duration of PsA of 760.5 days at index. For patients who received tofacitinib combination therapy post-index, methotrexate was the most common concomitant conventional synthetic disease-modifying antirheumatic drug. At 6 months post-index, persistence was similar in patients receiving tofacitinib monotherapy (69.8%) versus combination therapy (73.1%); adherence (as measured by PDC ≥ 0.8) was numerically lower in patients receiving tofacitinib monotherapy (56.8%) versus combination therapy (65.5%). CONCLUSIONS: This analysis of US-based claims data described patients who had newly initiated tofacitinib treatment an average of 2 years after PsA diagnosis, with approximately two-thirds of patients receiving tofacitinib monotherapy. Observed rates of tofacitinib persistence were similar across patients who received tofacitinib monotherapy and combination therapy 6 months after initiation; adherence rates were numerically lower in patients receiving monotherapy.
34559214 Adult-onset Still's disease or systemic-onset juvenile idiopathic arthritis and spondyloar 2022 May 30 OBJECTIVES: Systemic-onset JIA (SJIA) and adult-onset Still's disease (AOSD) are the same sporadic systemic auto-inflammatory disease. SpA is a group of inflammatory non-autoimmune disorders. We report the observations of eight patients with SJIA/AOSD who also presented features of SpA during their disease evolution and estimate the prevalence of SpA in SJIA/AOSD. METHODS: This was a retrospective national survey of departments of paediatric and adult rheumatology and internal medicine. To be included, SJIA patients had to fulfil the ILAR criteria, AOSD patients the Yamaguchi or Fautrel criteria, and all patients the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial or peripheral SpA, ESSG criteria for SpA or Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA. The data were collected with a standardized form. RESULTS: Eight patients (five adults) were identified in one paediatric and two adult departments. In all but one patient, SpA manifestations occurred several years after SJIA/AOSD onset [mean (s.d.) delay 6.2 (3.8) years]. Two patients had peripheral and three axial SpA, and four later exhibited PsA and one SAPHO syndrome. The prevalence of SpA in an adult cohort of 76 patients with AOSD was 6.58% (95% CI 2.17, 14.69), greater than the prevalence of SpA in the French general population (0.3%; 95% CI 0.17, 0.46). The prevalence of SpA in an SJIA cohort of 30 patients was 10% (95% CI 2.11, 26.53), more than that reported in the general population of industrialized countries, estimated at 0.016-0.15%. CONCLUSION: While the temporal disassociation between SpA and AOSD in most cases might suggest a coincidental finding, our work raises the possibility of an SpA/AOSD spectrum overlap that needs further study.
35412605 The value of ultrasound-defined tenosynovitis and synovitis in the prediction of persisten 2022 Apr 12 OBJECTIVES: The value of ultrasound-defined tenosynovitis in predicting the persistence of inflammatory arthritis is not well described. In particular, the predictive utility of ultrasound-defined tenosynovitis of larger tendons is yet to be reported. We assessed the value of ultrasound-defined tenosynovitis alongside ultrasound-defined synovitis and clinical and serological variables in predicting persistent arthritis in an inception cohort of disease-modifying antirheumatic drug (DMARD)-naïve patients with early arthritis. METHODS: One hundred and fifty DMARD-naïve patients with clinically apparent synovitis of one or more joints and a symptom duration ⩽3 months underwent baseline clinical, laboratory and ultrasound (of 19 bilateral joints and 16 bilateral tendon compartments) assessments. Outcomes were classified as persistent or resolving arthritis after 18 months follow-up. The predictive value of ultrasound-defined tenosynovitis for persistent arthritis was compared with those of ultrasound-defined synovitis, clinical and serological variables. RESULTS: At 18 months, 99 patients (66%) had developed persistent arthritis and 51 patients (34%) had resolving disease. Multivariate logistic regression analysis showed that ultrasound-detected digit flexor tenosynovitis (OR: 6.6, 95% CI: 2.0 - 22.1, p = 0.002) provided independent predictive data for persistence over and above the presence of ultrasound-detected joint synovitis and rheumatoid factor antibodies. In the RF/ACPA-negative sub-cohort, ultrasound-defined digit flexor tenosynovitis remained a significant predictive variable (OR: 4.7, 95% CI: 1.4 - 15.8, p = 0.012), even after adjusting for ultrasound-defined joint synovitis. CONCLUSION: Ultrasound-defined tenosynovitis provided independent predictive data for the development of persistent arthritis. The predictive role of ultrasound-defined digit flexor tenosynovitis should be further assessed; investigators should consider including this tendon site as a candidate variable when designing imaging-based predictive algorithms for persistent inflammatory arthritis development.
35648328 Novel anti-arthritic mechanisms of trans-cinnamaldehyde against complete Freund's adjuvant 2022 Jun 1 Trans-cinnamaldehyde (TCA), a natural cinnamaldehyde derivative of cinnamon oil, is known for anti-inflammatory, anti-bacterial, anti-fungal, anti-diabetic, and anti-cancer activities. However, no study has examined the protective mechanisms of TCA on complete Freund's adjuvant (CFA)-induced arthritis. Chronic arthritis was induced in mice by triple dose injection of 0.1 ml CFA in the first two days, then a treatment with TCA (100 mg/kg, i.p.) and the anti-arthritic drug; methotrexate (MTX, 0.75 mg/kg, i.p., 3 times/week) started from day 10 after CFA and continued till day 35.TCA ameliorated the CFA-induced arthritis features, indicated by the decrease in serum rheumatoid factor, paw swelling, arthritis index and the arthritis changes in limb histology. Additionally, TCA treatment showed anti-inflammatory actions through downregulation of TNF-α, NF-κB and COX-2 expressions and marked reduction in IL-1β, IL-6, IL-23 and IL-17 levels in inflamed paw tissues.Consequently, TCA can decrease arthritis progression and inhibit the immune/inflammatory responses initiated by TNF-α/IL-1β/IL-6/IL-23/IL-17 signals, via NF-κB modulation, almost to the same extent accomplished by MTX. Therefore, TCA could be a promising anti-arthritic drug.
35612561 Satisfaction With a Virtual Learning Collaborative Aimed at Implementing Treat-to-Target i 2022 May 25 OBJECTIVE: Limited information is available concerning experiences of participants in a virtual learning collaborative (LC), and little qualitative data or participant feedback on how this format can be improved. One prior in-person LC in rheumatology successfully improved adherence with treat-to-target (TTT) for RA. We conducted a virtual LC on TTT and herein report on participant satisfaction. METHODS: We conducted a virtual LC with 18 rheumatology practices from across the United States during 2020 to 2021. The LC included a virtual kickoff meeting and monthly videoconferences, accompanied by data submission and feedback. At the conclusion of the LC, we surveyed the 45 LC participants concerning individual experience and satisfaction. RESULTS: All sites and 78% of participants responded to the surveys. The LC included small and large practices, 14 academic and 4 nonacademic, and respondents ranged in their roles: 24 physicians, 5 nurses or nurse practitioners, 3 administrators, and 3 other roles. Overall, 94% of respondents indicated they were either somewhat or very satisfied with the LC, and 94% said they would recommend a similar LC to a colleague. Aspects of the LC described as "very useful" included a kickoff meeting, intersite discussion, and monthly speakers; however, digital tools such as the Web site and meeting recordings were not found useful. CONCLUSIONS: Virtual LCs are feasible, and participants reported strong satisfaction. Virtual LCs were highly valued by rheumatologists, trainees, and their practice staffs. Potential topics were identified for future LCs that could improve the quality of care delivered to rheumatology patients.
32965906 Electrodiagnostic Evaluation Of Carpal Tunnel Syndrome. 2022 Jan Carpal tunnel syndrome (CTS) accounts for approximately 90% of all focal entrapment neuropathy, making it a frequent electrodiagnostic consultation. It is present in about 3.8% of the general population. It is more common in women than in men, and while it occurs in all age groups, incidence generally reaches a peak within the age of 40 to 60 years. Hypothyroidism, diabetes mellitus, rheumatoid arthritis, gout, peripheral edema, acromegaly, tumors, trauma, and pregnancy are risk factors that predispose patients to develop CTS. Furthermore, patients whose occupations rely on the hands' repetitive movements and those with forceful hand movements are also prone to developing CTS. The clinical presentation typically reveals numbness, weakness, and paresthesias within the thumb, index, middle, and radial side of the ring finger. The thenar area has normal sensation as the palmar cutaneous sensory branch innervates it, which does not pass through the carpal tunnel. However, the recurrent thenar motor branch does pass through the carpal tunnel and gives innervation to the opponens pollicis, abductor pollicis brevis, and superficial head of the flexor pollicis brevis. Patients' symptoms tend to worsen at night or during the hand's repetitive movements, especially those requiring prolonged wrist flexion. Depending on the severity of the patient's symptoms, they can categorize into three stages. Stage 1 presents with frequent awakenings at night due to tingling in their hands and fingers, which may last through the morning with associated stiffness. Stage 2 shows symptoms that are also present during the day. Motor deficits may also be apparent with patients reporting dropping objects from their hands. Stage 3, the final stage, demonstrates atrophy of the thenar muscles and may respond poorly to surgical decompression.
35442847 Changes in orthopaedic operating theatre practice, monitored using settle plates. 2022 Apr 20 INTRODUCTION: The importance of ultraclean air in reducing deep infection was studied by Charnley who showed that the rate decreased as the airborne bacterial load was reduced. The effectiveness was shown in a large Medical Research Council (MRC) trial, but registry data have not shown a consistent benefit. Because we treat patients with rheumatoid arthritis, we decided to look at our theatre air quality. METHODS: In phase 1 we monitored air quality using settle plates, exposed for one hour after the incision, on the instrument trolleys in a joint replacement theatre. In phase 1 the scrub person did not wear a body exhaust system. In phase 2 all three staff used a body exhaust system, and we played close attention to the orientation and position of the surgical lights and trolleys. RESULTS: In phase 1 we grew 0.24 colonies/plate/hour in the ultraclean zone, which is comparable to the Charnley trial findings. In the second phase we grew 0.03 colonies/plate/hour (p<0.001). When plates were placed on the trolleys in controlled positions there was a tendency for the colonies to appear on the corners of the trolleys at the edge of the clean zone (NS). DISCUSSION: The study showed that in phase 1 colony counts comparable to the original Charnley studies were achieved. Colony counts of 0.03 colonies/plate/hour can be achieved in contemporary practice, with all team members using body exhausts.
35411968 Comparison of percutaneous permeation profiles of flurbiprofen enantiomers. 2022 Jun Flurbiprofen is clinically effective for the treatment of acute or long-term rheumatoid arthritis and osteoarthritis. Studies showed that S-flurbiprofen had better anti-inflammatory effect than R-flurbiprofen. As flurbiprofen racemates are usually used in the form of transdermal preparations, such as Flurbiprofen Cataplasms (Zepolas), it is of great significance to investigate the percutaneous permeation profiles of flurbiprofen enantiomers for considering whether it is necessary to develop the transdermal preparation with single optical enantiomer. Taking the economy into consideration, the flurbiprofen enantiomers as the mode drug and the CHIRALPAKAAGP column we had as instrument were used to perform the following experiments. On the basis of experiences provided by predecessors, we made some improvements to the analytical conditions, and method validation was developed to verify the feasibility of the method. The results showed that the established method could be used to analyze the percutaneous permeation profiles of flurbiprofen enantiomers in the flurbiprofen cataplasms accurately and effectively, and the percutaneous permeation profiles of flurbiprofen enantiomers had no significantly difference no matter under what conditions (P > 0.05).
35642781 Relapsing Polychondritis as a Cause of Sudden and Unexpected Death With Central Nervous Sy 2022 May 30 Relapsing polychondritis (RP) is a rare inflammatory disease process that affects cartilaginous tissues throughout the body. Although the pathogenesis remains unknown, RP is thought to be an autoimmune disorder in which host immune cells are conditioned to attack the body's cartilage, such as the ears, nose, eyes, joints, and airways, resulting in inflammation and destruction of otherwise healthy tissues. In rare and unusual cases, neurological involvement has been described.We report a case of a 36-year-old man with a medical history of asthma and suspected seronegative rheumatoid arthritis/RP and panuveitis who was found deceased in his residence. Postmortem examination revealed cartilaginous destruction of the external ear and large airways and meningoencephalitis involving the left medial temporal lobe without an underlying infectious cause.Progressive destruction of airway tissue and increased susceptibility to pulmonary infection is the most common cause of death in RP. Central nervous system involvement is exceedingly rare, presenting with highly variable clinical and pathological manifestations. A review of RP and systemic manifestations will follow. Accurate recognition of this multisystem autoimmune disease as a cause of sudden and unexpected death is critical for proper death certification and to broaden our understanding of this disease.