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- Asbun, H.J., et al.
(författare)
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The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection
- 2020
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Ingår i: Annals of Surgery. - : Lippincott Williams and Wilkins. - 0003-4932 .- 1528-1140. ; 271:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019).Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety.Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery. © 2019 Wolters Kluwer Health, Inc. All rights reserved.
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- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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