| 1. |
- Andréasson, Kristofer, et al.
(författare)
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Disease Features and Gastrointestinal Microbial Composition in Patients with Systemic Sclerosis from Two Independent Cohorts
- 2022
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Ingår i: ACR Open Rheumatology. - : Wiley. - 2578-5745. ; 4:5, s. 417-425
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The study objective was to examine alterations in gastrointestinal (GI) microbial composition in patients with systemic sclerosis (SSc) and to investigate the relationship between SSc features and GI microbiota using two independent, international cohorts. Methods: Prospective patients with SSc from Lund University (LU), Sweden, from the University of California, Los Angeles (UCLA), United States, and control subjects provided stool specimens for 16S ribosomal RNA sequencing. Alpha and beta diversity analyses were performed. Multivariate negative binomial models identified differentially abundant genera between groups. Results: Patients from LU with SSc (n = 106) with recent SSc diagnosis (median disease duration 2.0 years) had lower abundance of commensal genera (eg, Faecalibacterium) and higher abundance of pathobiont genera (eg, Desulfovibrio) than LU-controls (n = 85). Patients from UCLA with SSc (n = 71) had a similar prevalence of females, a similar body mass index, and similar age but an increased disease duration (median 7.1 years) compared with patients from LU with SSc. Factors associated with beta diversity in patients with SSc from both LU and UCLA included disease duration (P = 0.0016), interstitial lung disease (P = 0.003), small intestinal bacterial overgrowth (P = 0.002), and immunosuppression use (P = 0.014). In multivariable analysis, the UCLA-SSc cohort had higher abundance of specific pathobiont genera (eg, Streptococcus) compared with the LU-SSc cohort. Conclusion: Enrichments and depletions in certain microbial genera were observed in patients recently diagnosed with SSc, suggesting that dysbiosis is present in early SSc. Specific disease features were independently associated with fecal microbial composition in both cohorts. After controlling for these factors, the abundance of several pathobiont bacteria differed between the cohorts, suggesting that environmental factors, along with disease manifestations, should be considered in future SSc studies.
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| 2. |
- 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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| 3. |
- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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