578 research outputs found
Smoking and systemic sclerosis: influence on microangiopathy and expression of anti-topoisomerase I antibodies in a monocentric cohort
No full textObjectives: To investigate whether systemic sclerosis (SSc) patients exposed to active tobacco smoke exhibit a different autoantibody profile or are at higher risk for severe microangiopathy compared to never-smokers, and to assess differences between men and women. Methods: We performed an exploratory observational study in a cohort of SSc patients fulfilling the 2013 ACR/EULAR classification criteria. According to the smoking habit, patients were categorised as ever-smokers or never-smokers. Microvascular damage was assessed at baseline using nailfold videocapillaroscopy. The presence of SSc-specific autoantibodies was investigated. Results: The studied population was composed of 361 patients (279 women, 82 men). Of these, 208 (58%) were ever-smokers and 153 (42%) were never-smokers. Anti-centromere, anti-topoisomerase I (ATA) and anti-RNA polymerase III antibodies were found, respectively, in 90 (43%), 41 (20%), and 11 (5%) ever-smokers, and in 66 (43%), 40 (26%) and 5 (3%) never-smokers (all p>0.05). Scleroderma patterns early, active and late were present respectively in 12%, 44% and 21% of ever-smokers, and in 9%, 48%, and 29% of never-smokers (all p>0.05). In multivariable logistic regression, being a never-smoker was significantly associated with ATA positivity (OR 1.77, 95% CI 1.04-2.99, p= 0.034). In the gender-based sub-cohorts, 36 (27%) female patients who never smoked were ATA positive, compared to 16 (11%) ever-smoking women (p<0.001). Conclusions: We observed a significant association between smoking history and positivity of ATA and we outlined the idea of a different effect of smoking on autoantibody expression between men and women
Cumulative endogenous estrogen exposure is not associated with severity of peripheral microangiopathy in patients with systemic sclerosis
No full textPathophysiology and treatment of rheumatic disease
Contribution of Sex and Autoantibodies to Microangiopathy Assessed by Nailfold Videocapillaroscopy in Systemic Sclerosis: A Systematic Review of the Literature
No full textObjective Microangiopathy and dysregulation of the immune system play important roles in the pathogenesis of systemic sclerosis (SSc). Factors that trigger vascular injury in SSc have not been elucidated so far. We undertook this study to evaluate whether sex or expression of specific antinuclear autoantibodies might associate with the degree of microangiopathy through performance of a systematic review that summarizes what is known about these associations.Methods A standardized search of PubMed, Embase, Web of Science, and the Cochrane Library were performed to identify studies that described autoantibodies in SSc patients and microangiopathy and, for the second search, those that described sex and microangiopathy.Results We included 11 studies that described the relationship between SSc-specific autoantibodies and microangiopathy and 6 studies that reported on the association between sex and microangiopathy. Contradictory results were found on the association between SSc-specific autoantibodies and microangiopathy, and no association was found between sex and microangiopathy based on the current literature.Conclusion Based on this review of the literature, we can conclude that sex does not seem to influence degree of microangiopathy in SSc, while results on association between SSc-specific autoantibodies and degree of microangiopathy were inconclusive
Zasady gry w dziedzinie ekonomii
No full textArtykuł wskazuje rolę, jaką odgrywają elementy gry (zwłaszcza konkurencyjności, skrajnej wytrzymałości) w kulturze (J. Huizinga, R. Caillois, E. Fink) a szczególnie w sferze gospodarki. Przedstawiono tu podstawowe cechy elementu gry, takie jak zjawisko culture building (budowanie kultury).
Autor wskazuje na rolę, jaką odgrywają te elementy, które są wyraźnie odzwierciedlone w teorii ekonomii, koncentrując się na klasycznej teorii Adama Smitha neoklasycznej koncepcji Homo Oeconomicus, teorii gier i zachowań ekonomicznych, teoriach instytucjonalnych, jak również teorii wyboru publicznego.This article reflects the role of play elements (and especially competitive, agonal principle) in culture (J. Huizinga, R. Caillois, E. Fink), particularly in the sphere of economy. Basic characteristics of the play element as a culture-building phenomenon are summarized here. The author points at play elements, as they are explicitly reflected by the theory of economics, focusing on the classical theory of Adam Smith, neoclassical concept of Homo Oeconomicus, theory of games and economic behavior, institutional theories, as well as the public-choice theory
Health-related quality of life in patients with systemic sclerosis: evolution over time and main determinants
No full textObjectives. In SSc patients, disease specific determinants that influence health-related quality of life (HRQoL) over time have not been described. We aim to, in patients with SSc, (i) evaluate if and how HRQoL changes over time, and (ii) assess how different SSc domains and functional impairments contribute to changes in HRQoL over time.Methods. All SSc patients from the Leiden SSc cohort were included; patients with disease duration <24 months were classified as incident cases. HRQoL was assessed prospectively on an annual basis using the EQ-5D and the SF36. To assess baseline associations between clinical characteristics and HRQoL, linear regressions were performed. To identify possible associations between SSc characteristics and HRQoL change over time, linear mixed models were performed in both incident and prevalent cases.Results. In total, 492 SSc patients were included (n = 202 incident cases), with a median follow-up duration of 3.4 years. At baseline, presence of organ involvement was independently associated with a worse SF36 physical component score and lower EQ-5D score. Over time, gastrointestinal symptoms, Raynaud and digital ulcers were independently associated with deterioration of HRQoL in both incident and prevalent cases. In prevalent cases, pulmonary arterial hypertension (PAH) was associated with a decrease in HRQoL over time. Worse functioning as measured by six-min walking distance, mouth-opening, finger-to-palm distance and grip-strength contributed significantly to deterioration of HRQoL over time.Conclusion. In SSc, key clinical burdens that contribute to worsening of HRQoL over time include digital ulcers, Raynaud and gastrointestinal involvement. In addition, PAH is a significant burden in prevalent disease.Pathophysiology and treatment of rheumatic disease
Figure 1: Effect of TNF and IL-10 on the clearance of
No full textHospital Leiden, Netherlands; and Department of Psychonomics, Free University Amsterdam (D I Boomsma PhD) Correspondence to: Dr Rudi G J Westendorp, Department of Clinical Epidemiology, University Hospital Leiden, C0-P, 2300 RC Leiden, Netherlands Genetic influence on cytokine production and fatal meningococcal disease Rudi G J Westendorp, Jan A M Langermans, Tom W J Huizinga, Abdul H Elouali, Cornelis L Verweij, Dorret I Boomsma, Jan P Vandenbrouke Introduction There is a strong genetic component to fatal infectious disease. Adoptees have a fivefold increased risk of fatal infectious disease if a biological parent has died from infection. 1 By contrast, death from infection in an adoptive parent resulted in no excess relative risks of death. Our knowledge of the factors that contribute to this genetic susceptibility is limited. Tumour necrosis factor (TNF) is a decisive proinflammatory mediator in the host defence to infection. Treatment with recombinant human TNF can pr
One year in review 2020: novelties in the treatment of rheumatoid arthritis
No full textRheumatoid arthritis (RA) management is driven by evidence, and new 2019 EULAR recommendations help in refining the relevant place of different disease-modifying anti-rheumatic drugs (DMARDs) in treatment schedules. At present, new drugs are in phase of development, mainly Janus Kinase inhibitors (JAKis), however, specific treatment strategies seem to count more than individual DMARDs in terms of treatment responses, given the substantial lack of head-to-head comparisons between specific biological (b) and targeted synthetic (ts)DMARDs, and with the general perception of a similar efficacy profile across drugs. In this setting, when reliable biomarkers able to predict treatment responses are lacking, treatment decisions are mainly driven by specific clinical or individual factors, given the recognised role of comorbidities, treatment-specific side effects, patients' preferences, and costs on drug choice. In this narrative review, the authors give their specific point of view on the management of RA, based on a critical revision of the literature published in 2019, focusing on relevant novelties and future research directions.Pathophysiology and treatment of rheumatic disease
Sex hormones and sex hormone-targeting therapies in systemic sclerosis: A systematic literature review
No full textBackground: The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women, a contribution of sex hormones has been proposed.Objectives: We undertook this systematic literature review to investigate: (1) the role played by male and female sex hormones in the pathogenesis of SSc; (2) how sex hormone levels change in SSc patients and how hormonal variations modify the progression of SSc; (3) the effect of therapies targeting sex hormones on the disease course.Methods: A literature search was performed in Pubmed, Embase, Web of Science, and Cochrane library databases. Given the heterogeneity in study design, different quality assessment tools were applied where appropriate.Results: We retrieved 300 articles and 30 were included in the review. The available evidence points to a fibrogenic, but also a vasodilatory, role of estrogens in SSc. With the limitation of small sample sizes, women with SSc tend to have lower levels of androgens and non-significantly higher levels of estradiol compared to healthy controls, while in men we found increased levels of estradiol and discordant results for androgens. After menopause the skin score seems to decrease and prevalence of pulmonary artery hypertension seems to rise, which might be prevented by the use of hormone replacement therapy. No recent high-quality trial evaluated the efficacy of hormone-targeting therapies in SSc.Conclusions: Few translational studies of varying quality evaluated the role of sex hormones in SSc showing possible profibrotic and vasodilatatory effects of estrogens, but more research is needed to elucidate the extent of this contribution. Insights on the influence of sex hormones, along with the availability of new compounds acting on estrogen pathways, might provide ideas for additional studies on the application of sex hormone-targeting therapies in SSc. (C) 2019 Elsevier Inc. All rights reserved
Comment on: glucocorticoids prescribing practices in systemic sclerosis: an analysis of the EUSTAR database
No full textPathophysiology and treatment of rheumatic disease
Evolution of Systemic Sclerosis–Associated Interstitial Lung Disease One Year After Hematopoietic Stem Cell Transplantation or Cyclophosphamide
No full textObjective Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc-ILD). The aims of our retrospective observational study were to evaluate: 1) the evolution of SSc-ILD in SSc patients treated with HSCT (assessed by high-resolution computed tomography [HRCT]; a group of patients treated with CYC was included as frame of reference); 2) how results of pulmonary function tests (PFTs) are associated with HRCT findings; and 3) which factors predict ILD reduction. Methods We semiquantitatively scored total ILD extent, reticulations, and ground-glass opacities (GGO) scores at baseline and at the 1-year HRCTs of SSc patients treated with HSCT or CYC. Linear association between changes in HRCT scores and PFT results and predictors of ILD improvement were studied. Results We included 51 patients (those treated with HSCT [n = 20] and those treated with CYC [n = 31]). The mean change in total ILD score was -5.1% (95% confidence interval [95% CI] -10.2, 0.0) in the HSCT treatment group (P = 0.050), and -1.0% (95% CI -4.3, 2.3) in the CYC treatment group (P = 0.535). For all patients, the evolution of HRCT scores was weakly associated with relative changes in PFT results. In univariate logistic regression, higher ground-glass opacities, higher total ILD, and lower single-breath diffusing capacity for carbon monoxide scores at baseline predicted improvement of ILD extent after treatment, but a multivariable model could not be built to assess independency of predictors. Conclusion One year after treatment with HSCT, a nonsignificant but clear reduction of SSc-ILD extent was observed. Changes in PFT results were associated with changes in HRCT scores but the correlation was weak and cannot be considered conclusive.Pathophysiology and treatment of rheumatic disease
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