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- Benson, Tyler W, et al.
(författare)
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Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms.
- 2023
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Ingår i: bioRxiv : the preprint server for biology.
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (J) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.KEY POINTS: Soluble glycoprotein VI, which is a platelet-derived blood biomarker, predicts a diagnosis of AAA, with high sensitivity and specificity in distinguishing patients with fast from slow-growing AAA.Blockade of glycoprotein VI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential.
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- Beck, AW, et al.
(författare)
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Variations in abdominal aortic aneurysm care : a report from the International consortium of vascular registries
- 2016
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Ingår i: Circulation. - 0009-7322 .- 1524-4539.
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Tidskriftsartikel (refereegranskat)abstract
- Background: This project by the ICVR (International Consortium of Vascular Registries), a collaboration of 11 vascular surgical quality registries, was designed to evaluate international variation in the contemporary management of abdominal aortic aneurysm (AAA) with relation to recommended treatment guidelines from the Society for Vascular Surgery and the European Society for Vascular Surgery.Methods: Registry data for open and endovascular AAA repair (EVAR) during 2010 to 2013 were collected from 11 countries. Variations in patient selection and treatment were compared across countries and across centers within countries.Results: Among 51 153 patients, 86% were treated for intact AAA (iAAA) and 14% for ruptured AAA. Women constituted 18% of the entire cohort (range, 12% in Switzerland–21% in the United States; P<0.01). Intact AAAs were repaired at diameters smaller than recommended by guidelines in 31% of men (<5.5 cm; range, 6% in Iceland–41% in Germany; P<0.01) and 12% of women with iAAA (<5 cm; range, 0% in Iceland–16% in the United States; P<0.01). Overall, use of EVAR for iAAA varied from 28% in Hungary to 79% in the United States (P<0.01) and for ruptured AAA from 5% in Denmark to 52% in the United States (P<0.01). In addition to the between-country variations, significant variations were present between centers in each country in terms of EVAR use and rate of small AAA repair. Countries that more frequently treated small AAAs tended to use EVAR more frequently (trend: correlation coefficient, 0.51; P=0.14). Octogenarians made up 23% of all patients, ranging from 12% in Hungary to 29% in Australia (P<0.01). In countries with a fee-for-service reimbursement system (Australia, Germany, Switzerland, and the United States), the proportions of small AAA (33%) and octogenarians undergoing iAAA repair (25%) were higher compared with countries with a population-based reimbursement model (small AAA repair, 16%; octogenarians, 18%; P<0.01). In general, center-level variation within countries in the management of AAA was as important as variation between countries.Conclusions: Despite homogeneous guidelines from professional societies, significant variation exists in the management of AAA, most notably for iAAA diameter at repair, use of EVAR, and the treatment of elderly patients. ICVR provides an opportunity to study treatment variation across countries and to encourage optimal practice by sharing these results.
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- Behrendt, C. A., et al.
(författare)
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International Variations in Amputation Practice: A VASCUNET Report
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 56:3, s. 391-399
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study international differences in incidence and practice patterns as well as time trends in lower limb amputations related to peripheral arterial disease and/or diabetes mellitus. Methods: Data on lower limb amputations during 2010-2014 were collected from population based administrative data from countries in Europe and Australasia participating in the VASCUNET collaboration. Amputation rates, time trends, in hospital or 30 day mortality and reimbursement systems were analysed. Results: Data from 12 countries covering 259 million inhabitants in 2014 were included. Individuals aged >= 65 years ranged from 12.9% (Slovakia) to 20.7% (Germany) and diabetes prevalence among amputees from 25.7% (Finland) to 74.3% (Slovakia). The mean incidence of major amputation varied between 7.2/100,000 (New Zealand) and 41.4/100,000 (Hungary), with an overall declining time trend with the exception of Slovakia, while minor amputations increased over time. The older age group (>= 65 years) was up to 4.9 times more likely to be amputated compared with those younger than 65 years. Reported mortality rates were lowest in Finland (6.3%) and highest in Hungary (20.3%). Countries with a fee for service reimbursement system had a lower incidence of major amputation compared with countries with a population based reimbursement system (14.3/100,000 versus 18.4/100,000, respectively, p < .001). Conclusions: This international audit showed large geographical differences in major amputation rates, by a factor of almost six, and an overall declining time trend during the 4 year observation of this study. Diabetes prevalence, age distribution, and mortality rates were also found to vary between countries. Despite limitations attributable to registry data, these findings are important, and warrant further research on how to improve limb salvage in different demographic settings. (C) 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.
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- Berggren, A M, et al.
(författare)
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Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats
- 1996
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Ingår i: British Journal of Nutrition. - 0007-1145. ; 76:2, s. 94-287
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Tidskriftsartikel (refereegranskat)abstract
- It has increasingly been suggested that the short-chain fatty acids (SCFA) acetic, propionic and butyric acids, derived from colonic fermentation of dietary fibre and other indigestible carbohydrates, exert different physiological effects. Formation of propionic acid is discussed in terms of beneficial effects on glucose and cholesterol metabolism. The aim of the present study was to evaluate possible metabolic effects of propionic acid and to differentiate between effects mediated in the upper gastrointestinal tract and those mediated in the hind-gut. For this purpose, obese hyperinsulinaemic (fa/fa) rats were studied during a 19 d test period. Sodium propionate was either fed orally through the diet (1 g/d), or infused rectally (0.15 g/d) to animals given diets high in cholesterol (20 g/kg) and saturated fat (130 g/kg). At the end of the test period total liver cholesterol pools were 20% lower (P < 0.01) in rats given dietary or rectally infused propionate (481 and 484 mg respectively) compared with the control group (614 mg). This was due to lower liver weights (P < 0.05) in propionate-treated animals, 15.5 and 15.3 g, v. 18.2 g in the control group, and no differences were noted in hepatic cholesterol concentrations. The urinary glucose excretion was measured during days 15-19 and was found to be lower (P < 0.05) in rats fed with propionate (23 mg) compared with the control group or the group infused rectally (39 and 38 mg respectively). In addition, fasting plasma glucose concentrations decreased significantly (P < 0.05) over the test period. It is concluded that orally supplied propionate affects both glucose and cholesterol metabolism as judged from lowered urinary glucose excretion, fasting blood glucose and liver cholesterol pools. On the other hand, propionate administered to the hind-gut at a physiologically relevant level reduces the hepatic cholesterol pool.
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- Blaak, E E, et al.
(författare)
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Impact of postprandial glycaemia on health and prevention of disease.
- 2012
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Ingår i: Obesity Reviews. - 1467-7881. ; 13:10, s. 923-984
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Tidskriftsartikel (refereegranskat)abstract
- Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise perfomance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal-related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia.
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| 10. |
- Karthikesalingam, A., et al.
(författare)
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Comparative analysis of the outcomes of elective abdominal aortic aneurysm repair in England and Sweden
- 2018
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 105:5, s. 520-528
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere is substantial international variation in mortality after abdominal aortic aneurysm (AAA) repair; many non-operative factors influence risk-adjusted outcomes. This study compared 90-day and 5-year mortality for patients undergoing elective AAA repair in England and Sweden.MethodsPatients were identified from English Hospital Episode Statistics and the Swedish Vascular Registry between 2003 and 2012. Ninety-day mortality and 5-year survival were compared after adjustment for age and sex. Separate within-country analyses were performed to examine the impact of co-morbidity, hospital teaching status and hospital annual caseload.ResultsThe study included 36 249 patients who had AAA treatment in England, with a median age of 74 (i.q.r. 69–79) years, of whom 87·2 per cent were men. There were 7806 patients treated for AAA in Sweden, with a median of age 73 (68–78) years, of whom 82·9 per cent were men. Ninety‐day mortality rates were poorer in England than in Sweden (5·0 versus 3·9 per cent respectively; P < 0·001), but were not significantly different after 2007. Five‐year survival was poorer in England (70·5 versus 72·8 per cent; P < 0·001). Use of EVAR was initially lower in England, but surpassed that in Sweden after 2010. In both countries, poor outcome was associated with increased age. In England, institutions with higher operative annual volume had lower mortality rates.ConclusionMortality for elective AAA repair was initially poorer in England than Sweden, but improved over time alongside greater uptake of EVAR, and now there is no difference. Centres performing a greater proportion of EVAR procedures achieved better results in England. Improving in England
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