Early sac shrinkage predicts a low risk of late complications after endovascular aortic aneurysm repair

Background Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). Patients with early postoperative shrinkage may experience fewer subsequent complications, and consequently require less intensive surveillance. Methods Patients undergoing EVAR from 2000 to 2011 at three vascular centres (in 2 countries), who had two imaging examinations (postoperative and after 6-18 months), were included. Maximum diameter, complications and secondary interventions during follow-up were registered. Patients were categorized according to early sac dynamics. The primary endpoint was freedom from late complications. Secondary endpoints were freedom from secondary intervention, postimplant rupture and direct (type I/III) endoleaks. Results Some 597 EVARs (71·1 per cent of all EVARs) were included. No shrinkage was observed in 284 patients (47·6 per cent), moderate shrinkage (5-9 mm) in 142 (23·8 per cent) and major shrinkage (at least 10 mm) in 171 patients (28·6 per cent). Four years after the index imaging, the rate of freedom from complications was 84·3 (95 per cent confidence interval 78·7 to 89·8), 88·1 (80·6 to 95·5) and 94·4 (90·1 to 98·7) per cent respectively. No shrinkage was an independent risk factor for late complications compared with major shrinkage (hazard ratio (HR) 3·11; P < 0·001). Moderate compared with major shrinkage (HR 2·10; P = 0·022), early postoperative complications (HR 3·34; P < 0·001) and increasing abdominal aortic aneurysm baseline diameter (HR 1·02; P = 0·001) were also risk factors for late complications. Freedom from secondary interventions and direct endoleaks was greater for patients with major sac shrinkage. Conclusion Early change in aneurysm sac diameter is a strong predictor of late complications after EVAR. Patients with major sac shrinkage have a very low risk of complications for up to 5 years. This parameter may be used to tailor postoperative surveillance. Towards personalized surveillanc

Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Background and aims Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. Methods We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. Results We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. Conclusions We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT

Recurrent Sites for New Centromere Seeding

Using comparative FISH and genomics, we have studied and compared the evolution of chromosome 3 in primates and two human neocentromere cases on the long arm of this chromosome. Our results show that one of the human neocentromere cases maps to the same 3q26 chromosomal region where a new centromere emerged in a common ancestor of the Old World monkeys ∼25-40 million years ago. Similarly, the locus in which a new centromere was seeded in the great apes' ancestor was orthologous to the site in which a new centromere emerged in the New World monkeys' ancestor. These data suggest the recurrent use of longstanding latent centromeres and that there is an inherent potential of these regions to form centromeres. The second human neocentromere case (3q24) revealed unprecedented features. The neocentromere emergence was not accompanied by any chromosomal rearrangement that usually triggers these events. Instead, it involved the functional inactivation of the normal centromere, and was present in an otherwise phenotypically normal individual who transmitted this unusual chromosome to the next generation. We propose that the formation of neocentromeres in humans and the emergence of new centromeres during the course of evolution share a common mechanism

A cereal-based evening meal rich in indigestible carbohydrates increases plasma butyrate the next morning

Epidemiological studies have shown an inverse relation between a whole grain consumption and risk of type-2 diabetes and cardiovascular disease. One tentative mechanism relates to colonic metabolism of indigestible carbohydrates. In a previous study, we reported a positive relation between colonic fermentation and improved glucose tolerance. This work can be seen as an extension of that study, focusing on the tentative role of specific colonic metabolites, i.e. SCFA. Plasma concentrations of acetate, propionate, and butyrate were determined in the morning in healthy participants (5 women and 10 men, mean +/- SD: 25.9 +/- 3.2 y, BMI < 25) following 8 different cereal-based evening meals (50 g available starch) varying in content of indigestible carbohydrates. Each participant consumed all test meals in a random order on separate evenings. At a standardized breakfast following evening test meals, the postprandial glucose response (incremental area under the curve, 0-120 min) was inversely related to plasma butyrate (r = -0.26; P < 0.01) and acetate (r = -0.20; P < 0.05) concentrations. Evening meals composed of high-amylose barley kernels or high-beta-glucan barley kernels resulted in higher plasma butyrate concentrations the following morning compared with an evening meal with white wheat bread (P < 0.05). The results support the view that cereal products rich in indigestible carbohydrates may improve glucose tolerance through a mechanism involving colonic fermentation and generation of SCFA, where in particular butyric acid may be involved. This mechanism may be one explanation by which whole grain is protective against type 2 diabetes and cardiovascular disease

Long-term trajectories of non-native vegetation on islands globally

Human-mediated changes in island vegetation are, among others, largely caused by the introduction and establishment of non-native species. However, data on past changes in non-native plant species abundance that predate historical documentation and censuses are scarce. Islands are among the few places where we can track human arrival in natural systems allowing us to reveal changes in vegetation dynamics with the arrival of non-native species. We matched fossil pollen data with botanical status information (native, non-native), and quantified the timing, trajectories and magnitude of non-native plant vegetational change on 29 islands over the past 5000 years. We recorded a proportional increase in pollen of non-native plant taxa within the last 1000 years. Individual island trajectories are context-dependent and linked to island settlement histories. Our data show that non-native plant introductions have a longer and more dynamic history than is generally recognized, with critical implications for biodiversity baselines and invasion biology