| 1. |
- Elhai, M, et al.
(författare)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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| 2. |
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| 3. |
- Bosson, J. K., et al.
(författare)
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Psychometric Properties and Correlates of Precarious Manhood Beliefs in 62 Nations
- 2021
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Ingår i: Journal of Cross-Cultural Psychology. - : SAGE Publications. - 0022-0221 .- 1552-5422. ; 52:3
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Tidskriftsartikel (refereegranskat)abstract
- Precarious manhood beliefs portray manhood, relative to womanhood, as a social status that is hard to earn, easy to lose, and proven via public action. Here, we present cross-cultural data on a brief measure of precarious manhood beliefs (the Precarious Manhood Beliefs scale [PMB]) that covaries meaningfully with other cross-culturally validated gender ideologies and with country-level indices of gender equality and human development. Using data from university samples in 62 countries across 13 world regions (N = 33,417), we demonstrate: (1) the psychometric isomorphism of the PMB (i.e., its comparability in meaning and statistical properties across the individual and country levels); (2) the PMB's distinctness from, and associations with, ambivalent sexism and ambivalence toward men; and (3) associations of the PMB with nation-level gender equality and human development. Findings are discussed in terms of their statistical and theoretical implications for understanding widely-held beliefs about the precariousness of the male gender role.
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| 4. |
- Rodriguez-Palmero, Agusti, et al.
(författare)
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DLG4-related synaptopathy : a new rare brain disorder
- 2021
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 23:5, s. 888-899
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Tidskriftsartikel (refereegranskat)abstract
- PurposePostsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.MethodsThe clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing.ResultsThe clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit–hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies.ConclusionThe present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.
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| 5. |
- Olsson, MIT, et al.
(författare)
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Gender Gap in Parental Leave Intentions : Evidence from 37 Countries
- 2023
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Ingår i: Political Psychology. - : Wiley-Blackwell Publishing Ltd. - 0162-895X .- 1467-9221. ; 44:6, s. 1163-1192
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Tidskriftsartikel (refereegranskat)abstract
- Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women's political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women's (rather than men's) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men's higher uptake in prior research) were not associated with leave intentions in men. Rather, men's leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed.
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| 6. |
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| 7. |
- Distler, J. H. W., et al.
(författare)
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Is there a role for TNF-alpha antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique
- 2011
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 29:2, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To obtain experiences and expert opinion on treatment of SSc patients with TNF-alpha antagonists. Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-alpha antagonists. Assessment forms on the frequency of TNF-alpha inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-alpha inhibitors in SSc. Results: Seventy-nine centres returned information on use of TNF-alpha antagonists in SSc patients. A total of 65 patients were treated with TNF-alpha inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-alpha inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-alpha antagonists in SSc. Arthritis was suggested as an indication for TNF alpha antagonists by 75% of the experts. However; after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-alpha antagonists decreased and 59% recommended that TNF-alpha antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-alpha antagonists for arthritis associated with SSc. Conclusions: Most of the experts do not recommend the routine use of TNF-alpha antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-alpha antagonists are needed before general recommendations can be given.
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| 8. |
- Spierings, Julia, et al.
(författare)
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A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis : The UPSIDE study protocol
- 2021
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure. Methods and analysis The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years. Ethics and dissemination The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels. Trial registration numbers NCT04464434; NL 8720.
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| 9. |
- Acosta-Herrera, M, et al.
(författare)
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Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.
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| 10. |
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| 11. |
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| 12. |
- Meisters, Rachelle, et al.
(författare)
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EULAR/eumusc.net standards of care for rheumatoid arthritis : cross-sectional analyses of importance, level of implementation and care gaps experienced by patients and rheumatologists across 35 European countries
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:11, s. 1423-1431
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Tidskriftsartikel (refereegranskat)abstract
- Objective As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. Methods Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. Results Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. Conclusions Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.
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| 13. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 14. |
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| 15. |
- Van Olden, C. C., et al.
(författare)
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A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 289:3, s. 340-354
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples. Methods The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years. Results Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra-individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. Conclusion The BARIA study can add more understanding in how gut-microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity-associated disease epidemic.
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| 16. |
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| 17. |
- Gorlova, Olga, et al.
(författare)
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Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (IcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and autoantibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
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| 18. |
- van Rijswijk, A., et al.
(författare)
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The effects of laparoscopic Roux-en-Y gastric bypass and one-anastomosis gastric bypass on glycemic control and remission of type 2 diabetes mellitus: study protocol for a multi-center randomized controlled trial (the DIABAR-trial)
- 2022
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolic surgery induces rapid remission of type 2 diabetes mellitus ( T2DM). There is a paucity of high level evidence comparing the efficacy of the laparoscopic Roux-en-Y gastric bypass (RYGB) and the laparoscopic one-anastomosis gastric bypass (OAGB) in glycemic control. Also, the mechanisms that drive the conversion of T2DM in severe obese subjects to euglycemia are poorly understood. Methods: The DIABAR-trial is an open, multi-center, randomized controlled clinical trial with 10 years follow-up which will be performed in 220 severely obese patients, diagnosed with T2DM and treated with glucose-lowering agents. Patients will be randomized in a 1:1 ratio to undergo RYGB or OAGB. The primary outcome is glycemic control at 12 months follow-up. Secondary outcome measures are diverse and include weight loss, surgical complications, psychologic status and quality of life, dietary behavior, gastrointestinal symptoms, repetitive bloodwork to identify changes over time, glucose tolerance and insulin sensitivity as measured by mixed meal tests, remission of T2DM, presence of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in liver biopsy, oral and fecal microbiome, cardiovascular performance, composition of bile acids, and the tendency to develop gallstones. Discussion: The DIABAR-trial is one of the few randomized controlled trials primarily aimed to evaluate the glycemic response after the RYGB and OAGB in severe obese patients diagnosed with T2DM. Secondary aims of the trial are to contribute to a deeper understanding of the mechanisms that drive the remission of T2DM in severe obese patients by identification of microbial, immunological, and metabolic markers for metabolic response and to compare complications and side effects of RYGB and OAGB.
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| 19. |
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| 20. |
- Bakker, G. J., et al.
(författare)
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Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity
- 2022
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Ingår i: Obesity Science & Practice. - : Wiley. - 2055-2238. ; 8:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. Material and Methods: Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m(2)) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. Results: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. Conclusions: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.
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| 21. |
- Furer, Victoria, et al.
(författare)
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2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:1, s. 39-52
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Tidskriftsartikel (refereegranskat)abstract
- To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.
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| 22. |
- Kowal-Bielecka, Otylia, et al.
(författare)
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Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
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| 23. |
- Radstake, Timothy R. D. J., et al.
(författare)
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Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 71-426
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Tidskriftsartikel (refereegranskat)abstract
- Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.
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| 24. |
- Bossini-Castillo, Lara, et al.
(författare)
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A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:4, s. 638-641
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. Methods A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. Results A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). Conclusions The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
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| 25. |
- Dures, E., et al.
(författare)
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2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - 0003-4967 .- 1468-2060.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs.Methods A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs.Results Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making.Conclusions These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.
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| 26. |
- Furer, Victoria, et al.
(författare)
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Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) : A systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD
- 2019
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives The aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available. Methods A literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate. Results Sixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively. Conclusion Current evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.
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| 27. |
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| 28. |
- Meijnikman, A. S., et al.
(författare)
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Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts
- 2022
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 71:9, s. 1929-1936
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Tidskriftsartikel (refereegranskat)abstract
- Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors and may contribute to development of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). In this article, we investigated whether chronically elevated insulin levels are associated with cellular senescence in the human liver. In 107 individuals undergoing bariatric surgery, hepatic senescence markers were assessed by immunohistochemistry as well as transcriptomics. A subset of 180 participants from the ongoing Finnish Kuopio OBesity Surgery (KOBS) study was used as validation cohort. We found plasma insulin to be highly associated with various markers of cellular senescence in liver tissue. The liver transcriptome of individuals with high insulin revealed significant upregulation of several genes associated with senescence: p21, TGFβ, PI3K, HLA-G, IL8, p38, Ras, and E2F. Insulin associated with hepatic senescence independently of NAFLD and plasma glucose. By using transcriptomic data from the KOBS study, we could validate the association of insulin with p21 in the liver. Our results support a potential role for hyperinsulinemia in induction of cellular senescence in the liver. These findings suggest possible benefits of lowering insulin levels in obese individuals with insulin resistance.
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| 29. |
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| 30. |
- Rondaan, Christien, et al.
(författare)
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Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases : A systematic literature review for the 2019 update of EULAR recommendations
- 2019
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 5:2
-
Forskningsöversikt (refereegranskat)abstract
- Aim To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations. Methods An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by efficacy, immunogenicity and safety of vaccination in adult patients with AIIRD, including those receiving immunomodulating therapy. Furthermore, a search was performed on the effect of vaccinating household members of patients with AIIRD on the occurrence of vaccine-preventable infections in patients and their household members (including newborns). The literature search was performed using Medline, Embase and the Cochrane Library (October 2009 to August 2018). Results While most investigated vaccines were efficacious and/or immunogenic in patients with AIIRD, some were less efficacious than in healthy control subjects, and/or in patients receiving immunosuppressive agents. Adverse events of vaccination were generally mild and the rates were comparable to those in healthy persons. Vaccination did not seem to lead to an increase in activity of the underlying AIIRD, but insufficient power of most studies precluded arriving at definite conclusions. The number of studies investigating clinical efficacy of vaccination is still limited. No studies on the effect of vaccinating household members of patients with AIIRD were retrieved. Conclusion Evidence on efficacy, immunogenicity and safety of vaccination in patients with AIIRD was systematically reviewed to provide a basis for updated recommendations.
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| 31. |
- Safy, M., et al.
(författare)
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Efficacy and safety of selective glucocorticoid receptor modulators in comparison to glucocorticoids in arthritis, a systematic review
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Background Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking. Objective To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis. Methods A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results. Results A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety. Conclusion Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance. © 2017 Safy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 32. |
- van de Laar, IMBH, et al.
(författare)
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European reference network for rare vascular diseases (VASCERN) consensus statement for the screening and management of patients with pathogenic ACTA2 variants
- 2019
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Ingår i: Orphanet journal of rare diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 14:1, s. 264-
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Tidskriftsartikel (refereegranskat)abstract
- The ACTA2 gene encodes for smooth muscle specific α-actin, a critical component of the contractile apparatus of the vascular smooth muscle cell. Pathogenic variants in the ACTA2 gene are the most frequently encountered genetic cause of non-syndromic hereditary thoracic aortic disease (HTAD). Although thoracic aortic aneurysm and/or dissection is the main clinical manifestation, a variety of occlusive vascular disease and extravascular manifestations occur in ACTA2-related vasculopathy. Current data suggest possible mutation-specific manifestations of vascular and extra-aortic traits.Despite its relatively high prevalence, comprehensive recommendations on the care of patients and families with pathogenic variants in ACTA2 have not yet been established. We aimed to develop a consensus document to provide medical guidance for health care professionals involved in the diagnosis and treatment of patients and relatives with pathogenic variants in ACTA2.The HTAD Working Group of the European Reference Network for Rare Vascular Diseases (VASCERN) convened to review current literature and discuss expert opinions on clinical management of ACTA2 related vasculopathy. This consensus statement summarizes our recommendations on diagnosis, monitoring, treatment, pregnancy, genetic counselling and testing in patients with ACTA2-related vasculopathy. However, there is a clear need for additional prospective multicenter studies to further define proper guidelines.
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| 33. |
- Chisholm, S. A., et al.
(författare)
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Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone
- 2013
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 18:3, s. 14-23
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of gonorrhoea is threatened by antimicrobial resistance, and decreased susceptibility and resistance to recommended therapies is emerging in Europe. Current associations between resistance and molecular type remain poorly understood. Gonococcal isolates (n=1,066) collected for the 2009 and 2010 European Gonococcal Antimicrobial Surveillance Programme were typed by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). A total of 406 sequence types (STs) were identified, 125 of which occurred in >= two isolates. Seven major genogroups of closely related STs (varying by <= 1% at just one of the two target loci) were defined. Genogroup 1407 (G1407), observed in 20/21 countries and predominant in 13/21 countries, accounted for 23% of all isolates and was associated with decreased susceptibility to cefixime and resistance to ciprofloxacin and raised minimum inhibitory concentrations for ceftriaxone and azithromycin. Genogroup 225 (G225), associated with ciprofloxacin resistance, was observed in 10% of isolates from 19/21 countries. None of the other genogroups were associated with antimicrobial resistance. The predominance of a multidrug-resistant clone (G1407) in Europe is worrying given the recent reports of recommended third generation cephalosporins failing to treat infections with this clone. Identifying associations between ST and antimicrobial resistance aids the understanding of the dissemination of resistant clones within a population and could facilitate development of targeted intervention strategies.
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| 34. |
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| 35. |
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| 36. |
- Crowson, Cynthia S., et al.
(författare)
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Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 77:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. Methods: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. Results: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). Conclusions: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.
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| 37. |
- Low, Nicola, et al.
(författare)
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Chlamydia control activities in Europe : cross-sectional survey
- 2012
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 22:4, s. 556-561
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe.METHODS: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire.RESULTS: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816).CONCLUSION: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes.
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| 38. |
- Mikkelsen, Randi Bonke, et al.
(författare)
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Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:12
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and diabetes are associated with inflammation and altered plasma levels of several metabolites, which may be involved in disease progression. Some metabolites can activate G protein-coupled receptors (GPCRs) expressed on immune cells where they can modulate metabolic inflammation. Here, we find that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes (T2D) compared with nondiabetic controls. Administration of 3-hydroxydecanoate to mice promotes immune cell recruitment to adipose tissue, which was associated with adipose inflammation and increased fasting insulin levels. Furthermore, we demonstrate that 3-hydroxydecanoate stimulates migration of primary human and mouse neutrophils, but not monocytes, through GPR84 and Gαi signaling in vitro. Our findings indicate that 3-hydroxydecanoate is a T2D-associated metabolite that increases inflammatory responses and may contribute to the chronic inflammation observed in diabetes.
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| 39. |
- Bossini-Castillo, Lara, et al.
(författare)
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Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.
- 2011
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 1976-1981
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.Methods. A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.Results. The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)].Conclusion. Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.
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| 40. |
- Cenit, MC, et al.
(författare)
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Influence of the IL6 gene in susceptibility to systemic sclerosis
- 2012
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:12, s. 2294-2302
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Tidskriftsartikel (refereegranskat)abstract
- Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc.Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology.Results.Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04–1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77–0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04–1.23).Conclusion.Our results suggest that the IL6 gene may influence the development of SSc and its progression.
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| 41. |
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| 42. |
- Louca, Panayiotis, et al.
(författare)
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The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery
- 2023
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Ingår i: Cell Reports Medicine. - 2666-3791. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
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| 43. |
- Mujcic, Ajla, et al.
(författare)
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The effectiveness of distance-based interventions for smoking cessation and alcohol moderation among cancer survivors : A meta-analysis
- 2020
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Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 29:1, s. 49-60
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Forskningsöversikt (refereegranskat)abstract
- Objective The objective of this study is to evaluate current evidence for the effectiveness of distance-based interventions to support smoking cessation (SC) or alcohol moderation (AM) among cancer survivors. Secondary, differences in effectiveness are explored regarding multibehaviour interventions versus single-behaviour interventions targeting SC or AM only. Methods A systematic search of PubMed, PsycINFO, Web of Science, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials was conducted. Intervention studies with and without control groups and randomized controlled trials were included. Random effects meta-analyses were conducted for the main outcomes: SC and AM rates at the follow-up closest to 6 months. Using subgroup analyses and meta-regression, effectiveness of single-behaviour versus multibehaviour interventions was evaluated. Results A total of 17 studies with 3796 participants; nine studies on SC only, eight studies on multibehaviour interventions including an SC or AM module, and no studies on AM only were included. All studies had at least some concerns regarding bias. Distance-based SC interventions led to higher cessation rates than control conditions (10 studies, odds ratio [OR] = 1.56; 95% CI, 1.13-2.15, P = .007). Single-behaviour SC interventions reduced smoking rates compared with baseline (risk difference [RD] = 0.29; 95% CI, 0.19-0.39, P < .0001), but multibehaviour interventions did not (RD = 0.13; 95% CI, -0.05 to 0.31, P = 0.15). There was insufficient evidence that distance-based multibehaviour interventions reduced alcohol use compared with controls (three studies, standardized mean difference [SMD] = 0.12; 95% CI, -0.08 to 0.31, P = .24). Conclusions Distance-based SC interventions are effective in supporting SC among cancer survivors. Single-behaviour SC interventions appear more effective than multibehaviour interventions. No evidence was found for the effectiveness of distance-based AM interventions for cancer survivors.
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| 44. |
- Smith, Vanessa, et al.
(författare)
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Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis
- 2020
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Ingår i: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 19:3
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Forskningsöversikt (refereegranskat)abstract
- Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a ‘mainstream’ investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.
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