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ID PMID Title PublicationDate abstract
32106881 Rheumatoid artrhitis treatment in Brazil: data from a large real-life multicenter study. 2020 Feb 27 BACKGROUND: Last decades witnessed great technological advances in rheumatoid arthritis (RA) management, but their implementation in clinical practice might prove difficult. Despite the efficacy demonstrated in controlled trials this information needs to be confirmed by real life data. This study assessed real-life treatment among RA patients. METHODS: REAL study included Brazilian RA patients from eleven centers. Interview and medical records were performed. Continuous variables were compared using Student's t or Mann-Whitney and categorical variables were assessed with chi-square or Fisher's exact tests. RESULTS: 1115 patients were included, women 89.5%. Median age 56.6 years, disease duration 152.5 months; 78.7% were rheumatoid fator positive; 55.2% had erosive disease; DAS28 (disease activity index-28 joints) = 3.5, HAQ (health assessment questionnaire) =0.875. The median duration of symptoms until the start of first DMARD was 12 months. A total of 529 (47.2%) patients used corticosteroids; 1022 (90.8%) were on conventional synthetic (cs) DMARDs and 406 (36.1%) on biological (b) DMARDs. Methotrexate (MTX) was the most frequent csDMARD: 748 (66.5%) patients, followed by leflunomide (LFN), used by 381 (33.9%) of patients. MTX was associated to LFN in 142 (12.6%) patients. Only five (0.4%) patients used triple therapy (MTX + hydroxychloroquine + sulfasalazine) or sulfasalazine in monotherapy. CONCLUSIONS: Despite advances in therapeutic resources, roughly half RA patients failed achieve T2T goals and 55.2% developed erosive disease. The frequent use of corticosteroids and delay in initiating DMARDs were demonstrated. Issues concerning timely access to medical care are crucial for effective management.
31605388 Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthri 2020 Feb The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.
32612083 Factors Associated with Nutrition of Japanese Patients with Rheumatoid Arthritis Who Under 2020 The aim of this study is to identify the factors associated with nutrition in Japanese patients with rheumatoid arthritis (RA). Overall, 409 patients with RA who underwent the Mini Nutritional Assessment (MNA), bone mineral density determination, and body composition assessment by bioelectrical impedance analysis were enrolled. The analysis of factors associated with malnutrition was performed by comparing groups categorized by MNA score (≥24, 17-23.5, and <17). Moreover, correlation analysis for MNA score and variables was performed. The factors associated with malnutrition were the Health Assessment Questionnaire Disability Index (HAQ-DI) (p=0.005; odds ratio, 1.98), fat-free mass index (FFMI) (p=0.002; odds ratio, 0.59), and fat mass index (FMI) (p=0.022; odds ratio, 0.75). Statistical correlations of the MNA score with the following variables were observed: HAQ-DI (correlation coefficient [R], -0.261; p<0.001), FFMI (R, 0.371; p<0.001), and FMI (R, 0.272; p<0.001). This study identified nutrition-associated factors in Japanese patients with RA. The nutrition-associated factors were HAQ-DI, FFMI, and FMI. Therefore, physicians should evaluate nutrition of patients with RA.
32854412 Wearable Activity Trackers in the Management of Rheumatic Diseases: Where Are We in 2020? 2020 Aug 25 In healthcare, physical activity can be monitored in two ways: self-monitoring by the patient himself or external monitoring by health professionals. Regarding self-monitoring, wearable activity trackers allow automated passive data collection that educate and motivate patients. Wearing an activity tracker can improve walking time by around 1500 steps per day. However, there are concerns about measurement accuracy (e.g., lack of a common validation protocol or measurement discrepancies between different devices). For external monitoring, many innovative electronic tools are currently used in rheumatology to help support physician time management, to reduce the burden on clinic time, and to prioritize patients who may need further attention. In inflammatory arthritis, such as rheumatoid arthritis, regular monitoring of patients to detect disease flares improves outcomes. In a pilot study applying machine learning to activity tracker steps, we showed that physical activity was strongly linked to disease flares and that patterns of physical activity could be used to predict flares with great accuracy, with a sensitivity and specificity above 95%. Thus, automatic monitoring of steps may lead to improved disease control through potential early identification of disease flares. However, activity trackers have some limitations when applied to rheumatic patients, such as tracker adherence, lack of clarity on long-term effectiveness, or the potential multiplicity of trackers.
31858962 Association between autoantibody level and disease activity in rheumatoid arthritis is dep 2020 Jul OBJECTIVES: It is still controversial whether autoantibody (AAb) serum levels have a value for response monitoring in rheumatoid arthritis (RA). Therefore, we retrospectively investigated a real-life outpatient RA cohort to determine which factors are associated with change in serum AAb levels and RA disease activity. The primary goal of the study was to determine predictors for changes in DAS28 and autoantibodies over time and identify traits of non-rituximab treated patients, which would define strong association of disease activity with changes in AAb-levels. METHODS: Seventy-eight patients with seropositive RA were monitored for DAS28, CRP, ESR, anti-cyclic citrullinated peptides (CCP), anti-mutated citrullinated vimentin (MCV), and rheumatoid factor (RF). Using linear mixed regression modelling, factors influencing DAS28 and serum AAb were determined. Patients showing above (good correlators) and below (bad correlators) average correlation of serum AAb with DAS28 were further characterised. RESULTS: In non-rituximab treated patients (88.5%), associations of changes in AAb and DAS28 were strengthened with more morning stiffness (p=0.002), DMARD use (p=0.02), tender joints (p=0.01), swollen joints (p<0.01), higher ESR (p<0.01) and VAS (p<0.001) at baseline. Decrease of anti-CCP was also predicted by longer disease duration (-4.4 U/ml per year disease duration, p=0.048) and/or no erosions (-2.0 U/ml/month, p<0.01) at baseline, whereas erosive disease predicted an increase (+1.4 U/ml/month, p=0.015) in anti-CCP. Conversely, patients with erosive disease showed a trend to decrease RF (-1.9 U/ml/month, p=0.06). CONCLUSIONS: In non-rituximab treated RA patients, the association between disease activity and change in autoantibody levels is not static, but strengthens with increase in signs of inflammation (ESR, VAS, swollen joints, tender joints, morning stiffness) at baseline. Therefore, studies of changes in AAb need to consider baseline inflammation as confounder.
32389943 Systemic Sarcoidosis Associated with Certolizumab Pegol Treatment for Rheumatoid Arthritis 2020 Aug 15 A 69-year-old woman presented with appetite loss, fatigue, and a low-grade fever. She had been receiving certolizumab pegol for rheumatoid arthritis for six years. Computed tomography of the chest showed multiple micronodules in both lungs and bilateral hilar and mediastinal lymphadenopathy. An ophthalmic examination showed the findings of uveitis. Lymphocytosis with an increased CD4/CD8 ratio was seen in the bronchoalveolar lavage fluid. Video-assisted thoracoscopic biopsy specimens obtained from the right lung and a right hilar lymph node showed noncaseous epithelioid cell granulomas. Anti-tumor necrosis factor-α-induced sarcoidosis was diagnosed, and she was successfully treated with cessation of certolizumab pegol and systemic corticosteroid therapy.
32046611 How do people with rheumatoid arthritis experience participation in a smoking cessation tr 2020 Dec Purpose: The aim of this study was to gain more knowledge on how people with rheumatoid arthritis (RA) experienced participation in a randomized controlled trial (RCT) testing the effect of a smoking cessation intervention since this intervention have not been tested on an RA population beforeMethods: We conducted a qualitative study with semi-structured individual interviews with 12 participants from the intervention group in the RCT.Results: Through thematic analysis we identified four themes: Instilling hope for smoking cessation, referring to the initial invitation to participate in the RCT; Various components of importance in the intervention, referring to cooperation with the smoking cessation counsellor, improved carbon monoxide levels, fear of becoming addicted to nicotine replacement therapy, and suggestions for additional components in the intervention which could promote motivation; Breaking habits, referring to ongoing reflection on quitting smoking; and Increased awareness of health, arthritis and smoking, referring to the lack of information on smoking and RA from health professionals, and the impact of smoking on RA symptoms and overall health.Conclusion: The results reflect the participants' perspective on what is meaningful to them when trying to quit smoking and adds important knowledge to future smoking cessation studies in this patient group.
32223608 Incidence of Serious Infections and Design of Utilization and Safety Studies for Biologic 2020 Apr BACKGROUND: There is a need for postmarketing evidence generation for novel biologics and biosimilars. OBJECTIVE: To assess the feasibility, strengths, and limitations of the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Distributed Research Network (DRN) to examine the utilization and comparative safety of immune-modulating agents among patients with autoimmune diseases. METHODS: We conducted a retrospective cohort study among patients enrolled in health insurance plans participating in the BBCIC DRN between January 1, 2006, and September 30, 2015. Eligible patients were adult (≥18 years) new users of a disease-modifying nonbiologic and/or biologic agent with a prior diagnosis of rheumatoid arthritis (RA), other inflammatory conditions (psoriasis, psoriatic arthritis, ankylosing spondylitis), or inflammatory bowel disease (IBD). Follow-up started at treatment initiation and ended at the earliest of outcome occurrence (serious infection); treatment discontinuation; or switching, death, disenrollment, or end of study period. The study leveraged the FDA Sentinel System infrastructure for data management and analysis; descriptive statistics of patient characteristics and unadjusted incidence rates of study outcomes during follow-up were calculated. RESULTS: Eligible patient drug episodes included 111,611 with RA (75% female), 61,050 with other inflammatory conditions (51% female), and 30,628 with IBD (52% female). Across all 3 cohorts, approximately half of the patient drug episodes initiated a biologic (50% in RA; 60% in psoriasis, psoriatic arthritis, ankylosing spondylitis; and 55% in IBD). The crude incidence rate of serious infection was 9.8 (9.5-10.0) cases per 100 person-years in RA, 7.1 (6.8-7.5) in other inflammatory conditions, and 14.2 (13.6-14.8) in IBD patients. CONCLUSIONS: This study successfully identified large numbers of new users of biologics and produced results that were consistent with those from earlier published studies. The BBCIC DRN is a potential resource for surveillance of biologics. DISCLOSURES: This study was funded by the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC). HealthCore conducted this study in collaboration with Harvard Pilgrim Health Care. Zhang and Sridhar were employed by HealthCore at the time of this study. Haynes is employed by HealthCore funded by PCORI, the NIH, and the FDA. Barr and Eichelberger were employed by AMCP at the time of this study. Lockhart is employed by the BBCIC. Holmes and Clewell are employed by AbbVie. Accrott is an employee of and shareholder in Amgen. Marshall and Brown are employed by Harvard Pilgrim Health Care. Barr is a shareholder in Roche/Genentech. Curtis has received research grants from and consults with the following: Amgen, AbbVie, BMS, CORRONA, Lilly, Janssen, Myriad, Pfizer, Roche, Regeneron, and UCB. Brown has received research grants from GSK and Pfizer and consulting fees from Bayer, Roche, and Jazz Pharmaceuticals, along with funding from the Reagan-Udall Foundation for the FDA to conduct studies for medical product manufacturers, including Eli Lilly, Novartis, Abbvie, and Merck. Brown is also funded by PCORI, the NIH, and the FDA. McMahill-Walraven subcontracts with Harvard Pilgrim Health Care Institute for public health and safety surveillance distributed data network activtities and with the FDA, GSK, and Pfizer. She also reports fees from Reagan Udall Foundation for the FDA and the Patient Centered Outcomes Research Institute.
31875586 PRKCH polymorphism is associated with rheumatoid arthritis in a Chinese population. 2020 Jan 20 Genetic factors have been widely considered to have a substantial effect on the susceptibility to rheumatoid arthritis (RA). The purpose of this study was to determine whether the four newly discovered polymorphisms in a genome-wide association study (GWAS) meta-analysis confer susceptibility to RA in a Chinese Han population. We conducted a case-control study involving 359 RA cases and 873 age-and gender-matched controls and performed genotyping of four single nucleotide polymorphisms (SNPs), rs227163, rs726288, rs3783782 and rs2469434, using the dye terminator-based SNaPshot method. Consequently, we detected significant differences of genotype distribution of rs3783782 in PRKCH between RA and controls. The minor allele frequencies (MAFs) of rs3783782 were significantly higher in RA patients compared to control subjects. Moreover, the rs227163 in TNFRSF9 had higher MAFs in male RA compared with male controls. In addition, the polymorphism of rs3783782 in PRKCH was significantly associated with RA susceptibility (OR = 1.67, 95% CI = 1.32-2.11, p = 1.32 × 10(-5)). After stratification by gender, the minor (A) allele was strongly associated with increased risk for RA in males (OR = 1.87, 95% CI = 1.34-2.60; p = 1.62 × 10(-4)) and in females (OR = 1.51, 95% CI = 1.08-2.10; p = 0.014). For rs227163, the minor (C) allele was found to be associated with RA risk only in males (OR = 1.34, 95% CI = 1.02-1.75; p = 0.036). These findings for the first time confirmed that rs3783782 in PRKCH was associated with RA susceptibility in a Chinese population, and rs227163 in TNFRSF9 was associated with RA risk in Chinese males; these SNPs may serve as genetic markers for RA.
32277824 Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECT 2020 Nov 1 OBJECTIVE: To evaluate upadacitinib efficacy and safety dose response in Japanese patients with active RA and an inadequate response to conventional synthetic DMARDs (csDMARDs). METHODS: This was a multicentre, phase IIb/III, dose-ranging study conducted in Japan, in which patients on previously stable csDMARDs were randomized to receive upadacitinib 7.5, 15 or 30 mg once daily or matching placebo for a 12-week double-blind period. The primary endpoint was a 20% improvement in ACR criteria (ACR20) response at week 12 using non-responder imputation. Key secondary endpoints included ACR50, ACR70 and 28-joint DAS with CRP (DAS28-CRP) remission and low disease activity. Adverse events were also assessed. RESULTS: Of 197 patients treated, 187 completed the double-blind period. At week 12, more patients receiving upadacitinib 7.5, 15 or 30 mg vs placebo met the ACR20 response (75.5%, 83.7%, 80.0% vs 42.9%; P < 0.001), with significant differences observed as early as week 1. Stringent responses, including ACR50, ACR70 and DAS28-CRP <2.6, were achieved by significantly higher proportions of patients on upadacitinib than placebo and by numerically higher proportions on upadacitinib 15 or 30 mg vs upadacitinib 7.5 mg. Adverse events and infections (serious infections, opportunistic infections and herpes zoster) were more common with upadacitinib vs placebo and numerically highest with upadacitinib 30 mg. There were no venous thromboembolic events reported. CONCLUSION: Efficacy of upadacitinib was demonstrated in this population of Japanese patients with RA and an inadequate response to csDMARDs. Safety and tolerability were consistent with other upadacitinib RA studies. The 15 mg dose of upadacitinib showed the most favourable benefit-risk profile. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02720523.
32444035 Effects of hydroalcoholic extract of Berberis Integerrima on the anthropometric indices an 2020 May OBJECTIVES: Since, the main cause of death in Rheumatoid arthritis (RA) patients is the presence of type 2 diabetes, abnormal increase in blood lipids, blood pressure and obesity, the aim of this study was to assess the effects of Barberry on the anthropometric indices and metabolic profile in patients with RA. DESIGN: present study was a double-blinded, placebo-controlled randomized clinical trial. SETTING: 70 active RA patients were randomly allocated into intervention or placebo group INTERVENTION: Participants received 6 capsules of 500 mg barberry extract or placebo for 3 months. MAIN OUTCOME MEASURES: Serum levels of fasting blood sugar (FBS), triglyceride (TG), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), systolic and diastolic blood pressure and anthropometric factors were assessed at baseline and at the end of the trial. RESULTS: The results of intervention on 62 patients showed that weight, BMI, and conicity index increased in both groups, but this was significant only in the placebo group (p < 0.001). Waist and hip circumference were decreased in the intervention group and increased significantly in the placebo group (p < 0.001). Body fat percent (p = 0.04), LDL-C (p = 0.05) and SBP (p = 0.02) significantly were decreased in the intervention group. The results showed a significant decrease in body fat percent (p = 0.05), hip circumference (p < 0.001), FBS (p = 0.03) and HDL-C (p = 0.03) in the intervention group compared to the placebo. CONCLUSIONS: Overall, the results of this study demonstrated that the extract of Berberis Integerrima had beneficial effects on metabolic profile and anthropometric indices in RA patients.
33235261 Genetic risk score associations for myocardial infarction are comparable in persons with a 2020 Nov 24 Persons with rheumatoid arthritis (RA) have increased risk of myocardial infarction (MI). Overlapping associations with MI of weighted genetic risk scores (wGRS) for coronary artery disease (CAD) and RA is unknown in a population-based setting. Data from the prospective Nord-Trøndelag Health Study (HUNT2: 1995-1997 and HUNT3: 2006-2008) were used. wGRS added each participant's carriage of all risk variants weighted by the coefficient from published association studies. Published wGRS for CAD and RA were analysed in Cox regression with MI as outcome, age as analysis time, and censoring at the first MI, death, or 31.12.2017. 2609 of 61,465 participants developed MI during follow-up (mean 17.7 years). The best-fitting wGRS for CAD and RA included 157 and 27 single-nucleotide polymorphisms, respectively. In multivariable analysis including traditional CAD risk factors, the CAD wGRS was associated with MI [hazard ratio = 1.23 (95% CI 1.18-1.27) for each SD increase, p < 0.0001] in RA patients (n = 433) and controls. The RA wGRS was not significant (p = 0.06). Independently from traditional risk factors, a CAD wGRS was significantly associated with the risk for MI in RA patients and controls, whereas an RA wGRS was not. The captured genetic risk for RA contributed little to the risk of MI.
30980507 Systematic Review and Appraisal of the Cross-Cultural Validity of Functional Status Assess 2020 Jun OBJECTIVE: We conducted a systematic review and appraisal of the cross-cultural adaptation and cross-cultural validity of the Health Assessment Questionnaire (HAQ) and its derivatives, and of the more recent Patient-Reported Outcomes Measurement Information System (PROMIS) functional status assessment measures (FSAMs) in rheumatoid arthritis. METHODS: Four electronic medical databases were searched from inception until April 4, 2018 according to the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) group search strategy. Included studies were evaluated using the COSMIN tool for cross-cultural validity and were scored as excellent, good, fair, or poor. RESULTS: Of 58 articles identified by our search strategy and 3 by manual search, 39 were included: 29 described the translation, cultural adaptation, or cross-cultural validity of the HAQ disability index, 8 other HAQ derivatives, and 2 PROMIS measures, representing 22 languages. Of the 39 articles reviewed, 3 examined the cross-cultural validity of translated versions. These studies were rated as follows: 2 as excellent, 3 good, 13 fair, and 21 poor. Two studies examining cross-cultural validity noted differential item functioning (DIF) between Dutch and US populations for the HAQ-II and PROMIS measures, and a third study found DIF between Turkish and UK populations on the HAQ, indicating cultural differences in questionnaire response. CONCLUSION: This review highlights a paucity of data on the cross-cultural validity of FSAMs and the mostly poor- or fair-quality methods by which they were translated and adapted, which needs to be considered when using these measures for multinational clinical trials and for day-to-day use in clinical practice.
33419308 Implication of the Association of Fibrinogen Citrullination and Osteoclastogenesis in Bone 2020 Dec 20 Immune complexes containing citrullinated fibrinogen are present in the sera and synovium of rheumatoid arthritis patients and potentially contribute to synovitis. However, fibrinogen can inhibit the osteoclastogenesis of precursor cells. We investigated the direct effect of citrullinated fibrinogen on osteoclastogenesis to understand the role of citrullination on bone erosion of rheumatoid arthritis patients. We evaluated the fibrinogen citrullination sites using mass spectrometry and quantified osteoclast-related protein and gene expression levels by Western blotting, microarray, and real-time polymerase chain reaction. Differences in spectral peaks were noted between fibrinogen and citrullinated fibrinogen at five sites in α-chains, two sites in β-chains, and one site in a γ-chain. Transcriptome changes induced by fibrinogen and citrullinated fibrinogen were identified and differentially expressed genes grouped into three distinctive modules. Fibrinogen was then citrullinated in vitro using peptidylarginine deiminase. When increasing doses of soluble fibrinogen and citrullinated fibrinogen were applied to human CD14+ monocytes, citrullination restored osteoclastogenesis-associated changes, including NF-ATc1 and ß3-integrin. Finally, citrullination rescued the number of osteoclasts by restoring fibrinogen-induced suppression of osteoclastogenesis. Taken together, the results indicate that the inhibitory function of fibrinogen on osteoclastogenesis is reversed by citrullination and suggest that citrullinated fibrinogen may contribute to erosive bone destruction in rheumatoid arthritis.
32917272 Effects of disease activity on lipoprotein levels in patients with early arthritis: can ox 2020 Sep 11 BACKGROUND: An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease. METHODS: We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44-67] years and disease duration at study entry 5 [3-8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C. RESULTS: After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios. CONCLUSIONS: High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.
32113868 Candida bloodstream infection in patients with systemic autoimmune diseases. 2020 Jun OBJECTIVES: To describe the epidemiological, clinical and microbiological characteristics and mortality of patients with Candida bloodstream infection and systemic autoimmune diseases. METHODS: We performed a retrospective multicenter study of candidemia in adults with systemic autoimmune diseases between 2010 and 2016. RESULTS: Among 1040 patients with candidemia, 36 (3.5%) had a systemic autoimmune disease. The most common systemic autoimmune disease was rheumatoid arthritis (27.8%). The most common species was Candida albicans (66.7%). Twenty-two (61.1%) patients received a corticosteroid therapy and nine (25%) received an immunosuppressive therapy at the time of candidemia. The mortality rate was 27.8%. CONCLUSIONS: Systemic autoimmune diseases are not common in patients with candidemia. The unadjusted mortality rate was comparable to other candidemia studies in the general population.
32133566 Differentially expressed lncRNAs in peripheral blood mononuclear cells from middle-aged fe 2020 Aug OBJECTIVES: Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA) and has a large impact on the prognosis of RA, particularly among females, with an increased prevalence and severity compared with that of males. Here, we aimed to investigate the lncRNA profiles in peripheral blood mononuclear cells (PBMCs) from middle-aged female patients with RA-ILD to determine whether they could help diagnose RA-ILD. METHOD: We collected PBMCs from middle-aged female healthy controls, and RA and RA-ILD patients, excluding those with known risk factors of RA-ILD, such as being elderly or male, smoking, and having a history of other diseases. Then, a microarray analysis was applied to profile the lncRNA and mRNA levels in 3 pairs of samples. qPCR was performed to evaluate the candidate lncRNAs from 20 participants of each group. RESULTS: The expression levels of NR_002819, NR_038935, and ENST00000603415 were significantly increased in the RA-ILD group, while the expression level of ENST00000560199 was significantly decreased. As risk factors for RA-ILD, the area under the curve (AUC) values of NR_002819, NR_038935, and ENST00000603415 were 0.858, 0.704 (medium diagnostic accuracy), and 0.976 (high diagnostic accuracy), respectively. As a protective factor for RA-ILD, the AUC of ENST00000560199 was 0.853(medium diagnostic accuracy). CONCLUSIONS: To the best of our knowledge, this is the first study of lncRNA profiles in RA-ILD. The expression levels of NR_002819 (MALAT1), NR_038935, ENST00000603415, and ENST00000560199 were significantly different in the RA-ILD group and could be potential biomarkers for the assessment and diagnosis of middle-aged female RA-ILD patients. Key Points • The expression profile of lncRNAs in PBMCs from RA-ILD patients was evaluated. • NR_002819, NR_038935, and ENST00000603415 increased in RA-ILD patients. •ENST00000560199 decreased in RA-ILD patients. • The 4 lncRNAs might be potential biomarkers for diagnosis of RA-ILD.
32808204 Development of piperidinyl dipyrrrolopyridine-based dual inhibitors of Janus kinase and Br 2020 Aug 17 Rheumatoid arthritis is an autoimmune disorder causing joint deformity and work disability. Several drugs are available to deal with the disease including conventional drugs; biological drugs such as TNFα inhibitors, B cell-targeted drugs, T cell co-stimulation inhibitors, interleukin-6 inhibitors, and interleukin-1 inhibitors; and kinase inhibitory drugs. In spite of the broad spectrum of drugs available, the disease remains uncontrolled in a number of patients and there is a need for new drugs with better efficacy and universal response rate. The failure of the available drugs to control the disease can be owed to the complex pathogenesis with complementary pathways of disease progression. The blockade of one pathway cannot supersede pathogenesis through other complementary pathways. Janus kinase (JAK) and Bruton's tyrosine kinase (BTK) are the two important mediators of disease which control a number of signaling pathways involved in rheumatoid arthritis pathogenesis. In this study, using the computer-aided drug designing techniques (virtual screening, molecular docking, and molecular dynamics studies), we have designed piperidinyl dipyrrolopyridine-based dual inhibitors of Janus kinase and Bruton's tyrosine kinase. Dual JAK and BTK inhibitors seem promising to fight the complex pathogenesis of the disease at multiple fronts and can be the future drug for patients unresponsive to current remedies.
32510872 Fcγ Receptor I-Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat M 2020 Oct OBJECTIVE: Rheumatoid arthritis (RA) is often accompanied by joint pain and inflammation. Previous studies have demonstrated that functional Fcγ receptor I (FcγRI) is expressed in dorsal root ganglion (DRG) neurons and might contribute to pain in rodent models of antigen-induced arthritis (AIA). This study was undertaken to elucidate the roles of nociceptive neuronal FcγRI-coupled signaling in the development of joint pain in AIA. METHODS: RNA sequencing was used to investigate the transcriptome profile changes in the DRG in a rat model of AIA. A primary sensory neuron-specific Fcgr1a conditional-knockout (CKO) rat was established by crossing rats carrying a loxP-flanked Fcgr1a with a Pirt-specific Cre line. Behavioral, morphologic, and molecular studies were conducted to evaluate the differences between wild-type (WT) and CKO rats after AIA. RESULTS: We first showed that AIA induced a transcriptome profile change in the DRG, involving a number of key proteins downstream of the FcγRI-related signaling pathway. Compared to the WT rats, both the IgG immune complex-induced acute pain and AIA-induced pain were alleviated in CKO rats. Moreover, the AIA-induced activation of FcγRI-related signaling in DRGs was significantly reduced in CKO rats. In addition, CKO rats showed attenuated joint swelling after AIA. CONCLUSION: These results indicate that activation of FcγRI-coupled signaling in DRG neurons plays an important role in the development of joint pain in AIA. Our findings may provide novel insights into the interactions between the peripheral nervous system and the immune system in pathologic conditions and might suggest potential biotargets for the treatment of pain in RA.
32589073 Comparison of the efficacy and safety of CELBESTA® versus CELEBREX® in patients with rhe 2020 Jun OBJECTIVES: Celecoxib is a selective cyclooxygenase (COX)-2 inhibitor that is commonly used to reduce the incidence of gastrointestinal (GI) complications in patients with rheumatoid arthritis (RA). CELBESTA® is a generic equivalent to CELEBREX®, a celecoxib preparation. This study compared the efficacy and safety of CELBESTA® and CELEBREX® in patients with RA. METHODS: This was a multicenter, double-blind, double-dummy, active-controlled, randomized, parallel-group, non-inferiority clinical trial. The primary endpoint was a change from baseline in self-assessed pain intensity determined using a 100-mm visual analog scale after 6 weeks of treatment. RESULTS: After a washout period, 119 eligible subjects were randomized to one of two groups (CELBESTA® group, n = 61; CELEBREX® group, n = 58). CELBESTA® was not inferior to CELEBREX® because the upper limit of two-sided 95% confidence interval (CI) for the difference between the two groups (difference in the least square [LS] mean, -8.68 mm; two-sided 95% CI -16.59 mm to -0.77 mm) was less than the non-inferiority margin (10 mm). There were no significant differences in GI complications and renal toxicity. CONCLUSIONS: CELBESTA® was not inferior to CELEBREX® with regard to the pain relief efficacy in RA patients, and the tolerability and safety profiles were excellent and at similar levels for both preparations.