Comparison of Outcomes After Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement Among Patients With Aortic Stenosis at Low Operative Risk

Importance:  Transcatheter aortic valve replacement (TAVR) has been shown to be a valid alternative to surgical aortic valve replacement (SAVR) in patients at high operative risk with severe aortic stenosis (AS). However, the evidence of the benefits and harms of TAVR in patients at low operative risk is still scarce.Objective:  To compare the short-term and midterm outcomes after TAVR and SAVR in low-risk patients with AS.Design, Setting, and Participants:  This retrospective comparative effectiveness cohort study used data from the Nationwide Finnish Registry of Transcatheter and Surgical Aortic Valve Replacement for Aortic Valve Stenosis of patients at low operative risk who underwent TAVR or SAVR with a bioprosthesis for severe AS from January 1, 2008, to November 30, 2017. Low operative risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality score less than 3% without other comorbidities of clinical relevance. One-to-one propensity score matching was performed to adjust for baseline covariates between the TAVR and SAVR cohorts.Exposures:  Primary TAVR or SAVR with a bioprosthesis for AS with or without associated coronary revascularization.Main Outcomes and Measures:  The primary outcomes were 30-day and 3-year survival.Results:  Overall, 2841 patients (mean [SD] age, 74.0 [6.2] years; 1560 [54.9%] men) fulfilled the inclusion criteria and were included in the analysis; TAVR was performed in 325 patients and SAVR in 2516 patients. Propensity score matching produced 304 pairs with similar baseline characteristics. Third-generation devices were used in 263 patients (86.5%) who underwent TAVR. Among these matched pairs, 30-day mortality was 1.3% after TAVR and 3.6% after SAVR (P = .12). Three-year survival was similar in the study cohorts (TAVR, 85.7%; SAVR, 87.7%; P = .45). Interaction tests found no differences in terms of 3-year survival between the study cohorts in patients younger than vs older than 80 years or in patients who received recent aortic valve prostheses vs those who did not.Conclusions and Relevance:  Transcatheter aortic valve replacement using mostly third-generation devices achieved similar short- and mid-term survival compared with SAVR in low-risk patients. Further studies are needed to assess the long-term durability of TAVR prostheses before extending their use to low-risk patients.</p

Blood Transfusion and Outcome After Transfemoral Transcatheter Aortic Valve Replacement

Objective: To investigate the prognostic impact of red blood cell (RBC) transfusion on the outcome after transfemoral transcatheter aortic valve replacement (TAVR).Design: Nationwide, retrospective multicenter study.Setting: Five University Hospitals.Participants: The nationwide FinnValve registry included data from 2,130 patients who underwent TAVR for aortic stenosis from 2008 to 2017. After excluding patients who underwent TAVR through nontransfemoral accesses, 1,818 patients were selected for this analysis.Intervention: TAVR with or without coronary revascularization.Measurements and Main Results: RBCs were transfused in 293 patients (16.1%). Time-trend analysis showed that the rates of RBC transfusion decreased significantly from 27.5% in 2012 to 10.0% in 2017 (p Conclusions: Patients who received blood transfusion after TAVR had an increased risk of early and late adverse events. These adverse effects were particularly evident with increasing amount of RBC transfusion and operations for excessive bleeding.</p

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Computerized Information Standards Enabling Innovation in Public Procurement of Buildings

Computerized and standardized information enables innovation in processes, products and services. Where early research on the impact of standards tended to focus on barriers, more recent research advocates standardisation as enabler of innovation albeit in a stakeholder-oriented, flexible manner. This paper asks whether computerized information standards enable or constrain innovation in public procurement of buildings. In architectural and engineering design of public buildings handling of information involves interoperability problems that hamper innovation. Moreover the project based product development tends be done in constellations of firms in interorganisational contracting, which do not provide stability or room for innovation. A large hospital project was investigated through interviews, documents and observations. The effects of implementing building information standards are both inter- and intraorganisational. The building client claims to have saved money, through better structured building component data that gave considerable positive effects during tendering. The IT-suppliers develop IT-tools, preparing for new markets