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  • 301. Hull, Russell D.
    et al.
    Liang, Jane
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Yusen, Roger D.
    Benefit-to-harm ratio of thromboprophylaxis for patients undergoing major orthopaedic surgery2014In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 111, no 2, p. 199-212Article in journal (Refereed)
    Abstract [en]

    Surgeons consider the benefit-to-harm ratio when making decisions regarding the use of anticoagulant venous thromboembolism (VIE) prophylaxis. We evaluated the benefit-to-harm ratio of the use of newer anticoagulants as thromboprophylaxis in patients undergoing major orthopaedic surgery using the likelihood of being helped or harmed (LHH), and assessed the effects of variation in the definition of major bleeding on the results. A systematic literature search was performed to identify phase II and phase III studies that compared regulatory authority-approved newer anticoagulants to the low-molecular-weight heparin enoxaparin in patients undergoing major orthopaedic surgery. Analysis of outcomes data estimated the clinical benefit (number-needed-to-treat [NNT] to prevent one symptomatic VIE) and clinical harm (number-needed-to-harm [NNH] or the NNT to cause one major bleeding event) of therapies. We estimated each trial's benefit, to-harm ratio from NNT and NNH values, and expressed this as LHH = (1/NNT)/(1/NNH) = NNH/NNT, Based on reporting of efficacy and safety outcomes, most studies favoured enoxaparin over fondaparinux, and rivaroxaban over enoxaparin. However, when using the LHH metric, most trials favoured enoxaparin over both fondaparinux and rivaroxaban when they included surgical-site bleeding that did not require reoperation in the definition of major bleeding. The exclusion of bleeding at surgical site which did not require reoperation shifted the benefit-to-harm ratio in favour of the newer agents. Variations in the definitions of major bleeding may change the benefit-to-harm ratio and subsequently affect its interpretation. Clinical trials should attempt to improve the consistency of major bleeding reporting.

  • 302. Hull, Russell D.
    et al.
    Yusen, Roger D.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    State-of-the-art review: Assessing the safety profiles of new anticoagulants for major orthopedic surgery thromboprophylaxis2009In: Clinical and applied thrombosis/hemostasis, ISSN 1076-0296, E-ISSN 1938-2723, Vol. 15, no 4, p. 377-388Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: The safety and efficacy of new anticoagulants are often initially tested for venous thromboembolism (VTE) prevention in patients undergoing major orthopedic surgery. Concern among surgeons about the risks for bleeding may result in suboptimal use of thrombophylaxis. OBJECTIVE: To evaluate the definitions used to define bleeding outcomes in studies of new anticoagulants and to examine the influence the definition has on the perceived bleeding risk of thromboprophylaxis. METHODS: The MedLine database was searched for phase III studies of new anticoagulants versus the standard comparator, enoxaparin, in patients undergoing major orthopedic surgery. RESULTS: The definitions for major bleeding outcomes varied widely both across and within clinical trial programs of new anticoagulants. Studies which did not include surgical site bleeding in their definition for major bleeding showed lower major bleeding rates in comparison to those that did include this outcome. Other factors that influenced the rate of major bleeding included the timing of prophylaxis initiation in relation to surgery and the dose of anticoagulant therapy. The wide range of definitions used for major bleeding made it difficult to compare bleeding risk among studies of new anticoagulants. CONCLUSIONS: The definitions of bleeding events that clinical trials of thromboprophylaxis use in their assessment of new anticoagulants strongly influences each drug's perceived safety profile and may underestimate bleeding risks. Clinical studies of new anticoagulants urgently need standardization of bleeding definitions to allow intertrial comparability and to ensure consistent reporting of clinically relevant outcomes.

  • 303.
    Hultgren, R.
    et al.
    Karolinska Inst, Dept Mol Med, Stockholm, Sweden; Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden.
    Linne, A.
    Karolinska Inst, Sect Vasc Surg, Dept Surg, Dept Clin Sci & Educ, Södersjukhuset, Stockholm, Sweden.
    Svensjö, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Falun Cty Hosp, Dept Vasc Surg, Falun, Sweden.
    Cost-effectiveness of targeted screening for abdominal aortic aneurysm in siblings2019In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, no 3, p. 206-216Article in journal (Refereed)
    Abstract [en]

    Background: Population screening for abdominal aortic aneurysm (AAA) in 65‐year‐old men has been shown to be cost‐effective. A risk group with higher prevalence is siblings of patients with an AAA. This health economic model‐based study evaluated the potential cost‐effectiveness of targeted AAA screening of siblings.

    Methods: A Markov model validated against other screening programmes was used. Two methods of identifying siblings were analysed: direct questioning of patients with an AAA (method A), and employing a national multigeneration register (method B). The prevalence was based on observed ultrasound data on AAAs in siblings. Additional parameters were extracted from RCTs, vascular registers, literature and ongoing screening. The outcome was cost‐effectiveness, probability of cost‐effectiveness at different willingness‐to‐pay (WTP) thresholds, reduction in AAA death, quality‐adjusted life‐years (QALYs) gained and total costs on a national scale.

    Results_ Methods A and B were estimated to reduce mortality from AAA, at incremental cost‐effectiveness ratios of €7800 (95 per cent c.i. 4627 to 12 982) and €7666 (5000 to 13 373) per QALY respectively. The probability of cost‐effectiveness was 99 per cent at a WTP of €23 000. The absolute risk reduction in AAA deaths was five per 1000 invited. QALYs gained were 27 per 1000 invited. In a population of ten million, methods A and B were estimated to prevent 12 and 17 AAA deaths, among 2418 and 3572 siblings identified annually, at total costs of €499 500 and €728 700 respectively.

    Conclusion: The analysis indicates that aneurysm‐related mortality could be decreased cost‐effectively by applying a targeted screening method for siblings of patients with an AAA.

  • 304. Hytonen, Jarkko
    et al.
    Leppanen, Olli
    Taavitsainen, Jouni
    Korpisalo, Petra
    Laidinen, Svetlana
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Alitalo, Kari
    Rissanen, Tuomas
    Yla-Herttuala, Seppo
    Stimulation of transmural capillary endothelialization of small-diameter synthetic vascular grafts through local overexpression of a novel recombinant VEGFR2-ligand VEGF-A1092012In: Human Gene Therapy, ISSN 1043-0342, E-ISSN 1557-7422, Vol. 23, no 10, p. A44-A44Article in journal (Other academic)
  • 305. Håkansson, A
    et al.
    Rantatalo, M
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Patient specific biomodel of the whole aorta: the importance of calcified plaque removal2011In: VASA, ISSN 0301-1526, E-ISSN 1664-2872, Vol. 40, no 6, p. 453-459Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The use of anatomical models produced by 3D printing technique (rapid prototyping, RP) is gaining increased acceptance as a complementary tool for planning complex surgical interventions. This paper describes a method for creating a patient specific replica of the whole aorta.

    METHODS: Computed tomography angiography (CTA) DICOM-data was converted to a three-dimensional computer aided design-model (CAD) of the inner wall of the aorta representing the lumen where the calcified plaque contribution was removed in a multi-step editing-manoeuvre. The edited CAD-model was used for creating a physical plaster model of the true lumen in a 3D-printer. Elastic and transparent silicon was applied onto the plaster model, which was then removed leaving a silicon replica of the aorta.

    RESULTS: The median (interquartile range) difference between diameters obtained from CTA- and RP plaster-model at 19 predefined locations was 0.5 mm (1 mm) which corresponds to a relative median difference of 4.6% (7.0%). The average wall thickness of the silicone model was 3.5 mm. The elasticity property and performance during intervention was good with an acceptable transparency.

    CONCLUSIONS: The integration of RP-techniques with CAD based reconstruction of 3D-medical imaging data provides the needed tools for making a truly patient specific replica of the whole aorta with high accuracy. Plaque removal postprocessing is necessary to obtain a true inner wall configuration.

  • 306.
    Högberg, Dominika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Screening for asymptomatic carotid atherosclerosis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ischemic stroke is the most common cause of handicap in adults and the third most common cause of death in Sweden. Internal carotid artery atherosclerosis is an important cause and accounts for 20% of ischemic strokes. Screening for carotid atherosclerosis has been debated over the past two decades.

    The aims of this thesis were (I) to study the prevalence of and risk factors associated with carotid artery atherosclerosis among 65 year old men, (II) to evaluate a simplified ultrasound protocol (the grayscale/mosaic method) for the exclusion of significant carotid artery stenosis for screening purpose, (III) to evaluate the required effect of primary preventive therapy in reducing risk of stroke among patients with asymptomatic carotid disease in order for screening to be cost-effective and (IV) to study natural history of carotid atherosclerosis and outcome five years after screening in 65-year old men.

    The prevalence of atherosclerotic plaques was high (25%), while the prevalence of >50% stenosis was relatively low (2.0%). Smoking, hypertension, diabetes mellitus and coronary artery disease were independent risk factors and individuals with several risk factors had a higher prevalence of stenosis. Most of those at risk were not on any preventive medication. A simplified grayscale/mosaic method was found to have a high negative predictive value for significant carotid stenosis. The minimum stroke risk reduction effect required for preventive intervention to be cost effective was 22%. Carotid atherosclerotic plaque and stenosis 50-79% has a relatively benign development during five years if treated with BMT and risk factor adjustment. Very few progressed to symptomatic disease. More severe stenosis (80-99%) had higher rate of neurological events, and may benefit from additional intervention.

    In conclusion, prevalence of silent atherosclerotic disease in carotid arteries was common among 65-year-old men. Most of those at risk had no secondary prevention. There is a simple DUS method that could be used for screening purpose. Screening for carotid disease is only cost-effective if the preventive strategy lowers the risk of stroke by 22%. Men with plaques and moderate stenosis have a good prognosis, but among those with severe stenosis there is a need for further intervention.

    List of papers
    1. Carotid Artery Atherosclerosis Among 65-year-old Swedish Men: A Population-based Screening Study
    Open this publication in new window or tab >>Carotid Artery Atherosclerosis Among 65-year-old Swedish Men: A Population-based Screening Study
    Show others...
    2014 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 48, no 1, p. 5-10Article in journal (Refereed) Published
    Abstract [en]

    Objective: There are limited contemporary epidemiological data on the prevalence of carotid atherosclerosis in the general population. The aim was to determine the prevalence of and risk factors associated with carotid artery atherosclerosis among 65-year-old men. Methods: This was a population-based screening study. All 65-year-old men in the County of Uppsala, Sweden, who attended screehing for abdominal aortic aneurysm (AAA) 2007-2009, were invited for duplex scanning of the carotid arteries. Results: Of 4801 men invited, 4657 (97%) accepted. Carotid plaques (>2 x 6 mm) were observed in 1169 (25%) men, 94 (2.0%) had carotid stenoses (50-99%), and 15 (0.3%) had occluded carotid arteries. In a multivariate logistic regression model, smoking (OR 1.7, 95% CI 1.5-1.9), hypertension (1.5, 95% CI 1.3-1.7), diabetes mellitus (1.2, 95% CI 1.0-1.5), and coronary artery disease (1.5, 95% CI 1.3-1.8) were associated with prevalence of carotid atherosclerosis (plaque and/or stenosis). The use of antiplatelet agents and statins in participants with a carotid plaque was 20% and 29%, respectively. The corresponding figures in participants with a stenosis were 42% and 41%. Conclusions: This study offers contemporary data on the prevalence of carotid atherosclerosis in a population-based cohort of 65-year-old men. Most of those at risk had no other clinical manifestation of atherosclerosis, and therefore had no secondary prevention.

    Keywords
    Carotid stenosis, Atherosclerotic plaque, Prevalence, Screening
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-229726 (URN)10.1016/j.ejvs.2014.02.004 (DOI)000338820900003 ()24631197 (PubMedID)
    Available from: 2014-08-16 Created: 2014-08-12 Last updated: 2017-12-05Bibliographically approved
    2. Simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis
    Open this publication in new window or tab >>Simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis
    Show others...
    2016 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 3, p. 165-169Article in journal (Refereed) Published
    Abstract [en]

    Objectives: To evaluate a simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis for screening purposes. Material and methods: A total of 9,493 carotid arteries in 4,748 persons underwent carotid ultrasound examination. Most subjects were 65-year-old men attending screening for abdominal aortic aneurysm. The presence of a stenosis on B-mode and/or a mosaic pattern in post-stenotic areas on colour Doppler and maximum peak systolic velocity (PSV) in the internal carotid artery (ICA) were recorded. A carotid stenosis was defined as The North American Symptomatic Carotid Endarterectomy Trial (NASCET) >20% and a significant stenosis as NASCET >50%. The kappa (kappa) statistic was used to assess agreement between methods. Sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values were calculated for the greyscale/mosaic method compared to conventional assessment by means of PSV measurement. Results: An ICA stenosis was found in 121 (1.3%) arteries; 82 (0.9%) were graded 20%-49%, 16 (0.2%) were 50%-69%, and 23 (0.2%) were 70%-99%. Eighteen (0.2%) arteries were occluded. Overall, the greyscale/mosaic protocol showed a moderate agreement with ICA PSV measurements for the detection of carotid artery stenosis, x=0.455. The sensitivity, specificity, PPV, and NPV for detection of >20% ICA stenosis were 91% (95% CI 0.84-0.95), 97% (0.97-0.98), 31% (0.26-0.36), and 97% (0.97-0.97), respectively. The corresponding figures for >50% stenosis were 90% (0.83-0.95), 97% (0.97-0.98), 11% (0.08-0.15), and 100% (0.99-1.00). Conclusion: Compared with PSV measurements, the simplified greyscale/mosaic protocol had a high negative predictive value for detection of >50% carotid stenosis, suggesting that it may be suitable as a screening method to exclude significant disease.

    Keywords
    Carotid stenosis, screening, ultrasound
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-304440 (URN)10.1080/03009734.2016.1201177 (DOI)000381958400002 ()27379448 (PubMedID)
    Funder
    Swedish Research Council, K2013-64X-20406-07-3
    Available from: 2016-10-05 Created: 2016-10-05 Last updated: 2017-11-30Bibliographically approved
    3. Clinical effect and cost effectiveness of screening for asymptomatic carotid stenosis: A Markov model
    Open this publication in new window or tab >>Clinical effect and cost effectiveness of screening for asymptomatic carotid stenosis: A Markov model
    2018 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 55, no 6, p. 819-827Article in journal (Refereed) Published
    Abstract [en]

    Objectives:   Screening for asymptomatic carotid artery stenosis (ACAS) is controversial. The cost-effectiveness of screening depends on screening cost, ACAS prevalence, and the potential stroke reducing effect of best medical treatment (BMT). The aim of the study was to determine the threshold values for these parameters in order for screening for ACAS to be cost-effective.

    Material and methods: The clinical effect and cost-effectiveness of ultrasound-screening for ACAS with subsequent initiation of BMT versus not screening, was assessed in a Markov model with a life-time perspective. Key parameters; including stroke risk, all-cause mortality, and costs were based on contemporary published data, population statistics and ongoing screening programs. Prevalence of ACAS and rate of ongoing BMT was based on data from a population recently screened for ACAS. Minimum required stroke-risk reduction from BMT, incremental cost-efficiency ratio (ICER), absolute risk reduction for stroke (ARR), number needed to screen (NNS) were calculated. 

    Results: Screening was cost-effective at an ICER of €5744 per incremental quality adjusted life-year (QALY) gained. ARR was 135 per 100000 screened, NNS was 741 and QALYs gained were 6700 per 100000 invited. At a willingness-to-pay (WTP) threshold of €50,000 per QALY the minimum required stroke risk reduction from BMT was 22%. The assumed degree of stroke risk reduction was the most important determinant of cost-efficiency.  

    Conclusion: A moderate (22%) reduction in the risk of stroke from BMT was required for an ACAS screening strategy to be cost-effective at WTP of €50,000/QALY. Targeting populations with higher prevalence of ACAS could improve cost-efficiency.

    Keywords
    cost-eefectiveness, carotid stenosis, screening, preventive treatment
    National Category
    Health Care Service and Management, Health Policy and Services and Health Economy
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-328785 (URN)10.1016/j.ejvs.2018.02.029 (DOI)000434259600005 ()
    Projects
    Screening for asymptomatic carotid atherosclerosis
    Funder
    Swedish Research Council, K2013-64X-20406-07-3
    Available from: 2017-08-31 Created: 2017-08-31 Last updated: 2018-08-30Bibliographically approved
    4. Five-year outcomes in men screened for carotid artery stenosis at 65 years of age - a population-based cohort study.
    Open this publication in new window or tab >>Five-year outcomes in men screened for carotid artery stenosis at 65 years of age - a population-based cohort study.
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: The aim was to determine the prognosis of 65-year old men five years after carotid ultrasound screening, as well as risk factors for disease progression.

    Material and methods: All 65-year-old men living in the county of Uppsala 2007-2009 were invited to an ultrasound examination of both carotid arteries and re-invited at age 70. The cohort was grouped into: normal carotids, plaque without significant stenosis, moderate stenosis (50-79%), and severe stenosis (80-99%). The rates of disease progression to death, significant stenosis, and neurological events were assessed, as well as risk factors and medication.

    Results: Among men participating in carotid screening at age 65, 3057 were re-screened at age 70. In those with normal carotids (n=2318), 23 (1.0%) progressed to a moderate, and four (0.2%) developed a symptomatic severe stenosis. Among those with plaque (n=696), 25 (3.6%) progressed to moderate, and eight (1.1%) to severe stenosis, of whom four (0.6%) had symptoms. Of 31 with 50-79% stenosis, four (12.9%) had progressed to a severe stenosis, of whom two (6.5%) developed symptoms. Five of twelve subjects (42%) with 80-99% stenosis developed symptoms. Disease regression was present among 306 (41.4%) men. In multivariable analysis, smoking, coronary artery disease and hypercholesterolemia were associated with disease progression. The proportions of antiplatelet, statin and antihypertensive treatment in the population at age 70 were 22%, 29% and 55% respectively.

    Conclusion: Men with plaques and moderate stenosis have a good prognosis, but in those with severe stenosis there was a high risk of neurological events.

    Keywords
    carotid stenosis, atherosclerotic plaque, natural history, mortality, stroke rate
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-328800 (URN)
    Projects
    Screening for carotid atherosclerosis
    Available from: 2017-08-31 Created: 2017-08-31 Last updated: 2017-08-31
  • 307.
    Högberg, Dominika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Sahlgrens Univ Hosp, Dept Hybrid & Intervent Surg, Gothenburg, Sweden.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Response to "Re. Five Year Outcomes in Men Screened for Carotid Artery Stenosis at 65 Years of Age: A Population Based Cohort Study"2020In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 59, no 1, p. 152-152Article in journal (Other academic)
  • 308.
    Högberg, Dominika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Sahlgrens Univ Hosp, Dept Hybrid & Intervent Surg, S-41345 Gothenburg, Sweden.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Svensjö, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Falun Cty Hosp, Dept Surg, Falun, Sweden.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Five Year Outcomes in Men Screened for Carotid Artery Stenosis at 65 Years of Age: A Population Based Cohort Study2019In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 57, no 6, p. 759-766Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to determine the outcome of 65 year old men five years after carotid ultrasound screening, as well as risk factors for disease progression. Methods: All 65 year old men living in the county of Uppsala 2007-2009 were invited to an ultrasound examination of both carotid arteries and re-invited at age 70. The cohort was grouped into normal carotids, plaque without significant stenosis, moderate stenosis (50-79%), and severe stenosis (80-99%). The rate of disease progression was assessed from ultrasound data. Data on mortality, ipsilateral neurological events, risk factors, and medication were obtained from patient records and population registries. Results: Among men participating in carotid screening at age 65, 3,057 were re-screened at age 70. In those with normal carotids (n = 2,318), 23 (1.0%) progressed to a moderate stenosis, and four (0.2%) to a symptomatic severe stenosis. Among those with plaque (n = 696), 25 (3.6%) progressed to moderate stenosis, and eight (1.1%) to severe stenosis, of whom four (0.6%) had symptoms. Of 31 men with 50-79% stenosis, four (12.9%) had progressed to a severe stenosis, of whom two (6.5%) developed symptoms. Five of twelve subjects (42%) with 80-99% stenosis developed symptoms. Disease regression was present among 289/692 plaque (41.7%) and 16/33 stenosis (48.4%). In multivariable analysis, smoking, coronary artery disease and hypercholesterolemia were associated with disease progression. The proportions of antiplatelet, statin, and antihypertensive treatment in the population at age 70 were 22%, 29%, and 55%, respectively. Conclusion: Men with plaques and moderate stenosis have a good prognosis, but in those with severe stenosis there is a high risk of neurological events.

  • 309.
    Högberg, Dominika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. NU Hosp Org, Dept Surg, Trollhattan, Sweden..
    Dellagrammaticas, Demosthenes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 3, p. 165-169Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate a simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis for screening purposes. Material and methods: A total of 9,493 carotid arteries in 4,748 persons underwent carotid ultrasound examination. Most subjects were 65-year-old men attending screening for abdominal aortic aneurysm. The presence of a stenosis on B-mode and/or a mosaic pattern in post-stenotic areas on colour Doppler and maximum peak systolic velocity (PSV) in the internal carotid artery (ICA) were recorded. A carotid stenosis was defined as The North American Symptomatic Carotid Endarterectomy Trial (NASCET) >20% and a significant stenosis as NASCET >50%. The kappa (kappa) statistic was used to assess agreement between methods. Sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values were calculated for the greyscale/mosaic method compared to conventional assessment by means of PSV measurement. Results: An ICA stenosis was found in 121 (1.3%) arteries; 82 (0.9%) were graded 20%-49%, 16 (0.2%) were 50%-69%, and 23 (0.2%) were 70%-99%. Eighteen (0.2%) arteries were occluded. Overall, the greyscale/mosaic protocol showed a moderate agreement with ICA PSV measurements for the detection of carotid artery stenosis, x=0.455. The sensitivity, specificity, PPV, and NPV for detection of >20% ICA stenosis were 91% (95% CI 0.84-0.95), 97% (0.97-0.98), 31% (0.26-0.36), and 97% (0.97-0.97), respectively. The corresponding figures for >50% stenosis were 90% (0.83-0.95), 97% (0.97-0.98), 11% (0.08-0.15), and 100% (0.99-1.00). Conclusion: Compared with PSV measurements, the simplified greyscale/mosaic protocol had a high negative predictive value for detection of >50% carotid stenosis, suggesting that it may be suitable as a screening method to exclude significant disease.

  • 310.
    Högberg, Dominika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tjärnström, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Carotid Artery Atherosclerosis Among 65-year-old Swedish Men: A Population-based Screening Study2014In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 48, no 1, p. 5-10Article in journal (Refereed)
    Abstract [en]

    Objective: There are limited contemporary epidemiological data on the prevalence of carotid atherosclerosis in the general population. The aim was to determine the prevalence of and risk factors associated with carotid artery atherosclerosis among 65-year-old men. Methods: This was a population-based screening study. All 65-year-old men in the County of Uppsala, Sweden, who attended screehing for abdominal aortic aneurysm (AAA) 2007-2009, were invited for duplex scanning of the carotid arteries. Results: Of 4801 men invited, 4657 (97%) accepted. Carotid plaques (>2 x 6 mm) were observed in 1169 (25%) men, 94 (2.0%) had carotid stenoses (50-99%), and 15 (0.3%) had occluded carotid arteries. In a multivariate logistic regression model, smoking (OR 1.7, 95% CI 1.5-1.9), hypertension (1.5, 95% CI 1.3-1.7), diabetes mellitus (1.2, 95% CI 1.0-1.5), and coronary artery disease (1.5, 95% CI 1.3-1.8) were associated with prevalence of carotid atherosclerosis (plaque and/or stenosis). The use of antiplatelet agents and statins in participants with a carotid plaque was 20% and 29%, respectively. The corresponding figures in participants with a stenosis were 42% and 41%. Conclusions: This study offers contemporary data on the prevalence of carotid atherosclerosis in a population-based cohort of 65-year-old men. Most of those at risk had no other clinical manifestation of atherosclerosis, and therefore had no secondary prevention.

  • 311.
    Högberg, Dominika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Department Hybrid and Interventional Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Svensjö, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Department of Surgery, Falun County Hospital, Falun, Sweden.
    Clinical effect and cost effectiveness of screening for asymptomatic carotid stenosis: A Markov model2018In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 55, no 6, p. 819-827Article in journal (Refereed)
    Abstract [en]

    Objectives:   Screening for asymptomatic carotid artery stenosis (ACAS) is controversial. The cost-effectiveness of screening depends on screening cost, ACAS prevalence, and the potential stroke reducing effect of best medical treatment (BMT). The aim of the study was to determine the threshold values for these parameters in order for screening for ACAS to be cost-effective.

    Material and methods: The clinical effect and cost-effectiveness of ultrasound-screening for ACAS with subsequent initiation of BMT versus not screening, was assessed in a Markov model with a life-time perspective. Key parameters; including stroke risk, all-cause mortality, and costs were based on contemporary published data, population statistics and ongoing screening programs. Prevalence of ACAS and rate of ongoing BMT was based on data from a population recently screened for ACAS. Minimum required stroke-risk reduction from BMT, incremental cost-efficiency ratio (ICER), absolute risk reduction for stroke (ARR), number needed to screen (NNS) were calculated. 

    Results: Screening was cost-effective at an ICER of €5744 per incremental quality adjusted life-year (QALY) gained. ARR was 135 per 100000 screened, NNS was 741 and QALYs gained were 6700 per 100000 invited. At a willingness-to-pay (WTP) threshold of €50,000 per QALY the minimum required stroke risk reduction from BMT was 22%. The assumed degree of stroke risk reduction was the most important determinant of cost-efficiency.  

    Conclusion: A moderate (22%) reduction in the risk of stroke from BMT was required for an ACAS screening strategy to be cost-effective at WTP of €50,000/QALY. Targeting populations with higher prevalence of ACAS could improve cost-efficiency.

  • 312. Jonsson, M.
    et al.
    Gillgren, P.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Acosta, S.
    Lindstrom, D.
    Peri-procedural Risk with Urgent Carotid Artery Stenting: A Population based Swedvasc Study2015In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 49, no 5, p. 506-512Article in journal (Refereed)
    Abstract [en]

    Objectives: Current European Society for Vascular Surgery guidelines recommend that patients with a symptomatic carotid stenosis should be operated on within 14 days of onset of symptoms. Recent reports indicate that carotid endarterectomy (CEA) within 2 days of a neurological event may be associated with a higher. pen-procedural risk of stroke. Whether urgent carotid artery stenting (CAS) carries a similar high risk is unclear. The aim of this study was to analyze if urgent CAS increases the pen-procedural risks. Methods: Retrospective analysis of all CAS registered in Swedvasc, a validated nationwide registry, between January 1, 2005, and March 20, 2014. Only symptomatic patients treated for a stenosis of the internal carotid artery were included. Patients were categorized according to time from index event to surgery; 0-2 days, 3-7 days, 8-14 days, and 15-180 days. Primary outcome was 30 day combined stroke and death rate. Results: 323 patients underwent CAS for symptomatic carotid artery stenosis. The demographic and clinical data were similar in the groups. No procedure related complications or deaths were observed in the urgent CAS group. The 30 day combined stroke and death rate did not differ significantly between the groups; zero of 13 (0%; 95% Cl 0-26.6) in the group treated 0-2 days versus four of 85 (4.7%; 95% Cl 1.5-11.9), at 3-7 days, five of 80 (6.3%; 95% Cl 2.4-14.1) at 8-14 days, and six of 145 (4.1%; 95% Cl 1.7-8.9) for the patients treated at 15-180 days (p = .757). Stroke and death were not more frequent for patients treated within 1 week compared with after 1 week: 4 out of 98 (4.1%; 95% Cl 1.3-9.0) versus 11/225 (4.9%; 95% Cl 2.7-8.6) (p = .751). Conclusions: In this national registry study, CAS performed within 1 week of the onset of a neurologic event Was not associated with an additional risk of a pen-operative complication compared with those treated subsequently.

  • 313.
    Jonsson, M.
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Sect Vasc Surg, Dept Surg, S-11883 Stockholm, Sweden..
    Lindstrom, D.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Djavani Gidlund, Khatereh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Gävle Hospital, Sweden..
    Gillgren, P.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Sect Vasc Surg, Dept Surg, S-11883 Stockholm, Sweden..
    Near Infrared Spectroscopy as a Predictor for Shunt Requirement During Carotid Endarterectomy2017In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 53, no 6, p. 783-791Article in journal (Refereed)
    Abstract [en]

    Objective/Background: Near infrared speCtroscopy (NIRS) continuously monitors regional cerebral oxygenation (rSO2) in the frontal lobes. This method may be used in patients during carotid endarterectomy to indicate the need for shunting. The aim of the study was to evaluate the value of NIRS in determining the need for selective shunting during CEA. A secondary aim was to compare NIRS with stump pressure.

    Methods: Between January 2013 and October 2016, 185 patients from two vascular units, undergoing CEA under local anaesthesia were prospectively included. All patients gave informed consent to participate; there were no exclusion criteria. A Foresight® oximeter was used for rSO2 measurement, which was compared with stump pressure. Receiver operating characteristic curve analysis was used to identify optimal cutoff points, and sensitivity, specificity, and positive and negative predictive values were calculated.

    Results: Twenty patients (10.8%) developed neurological symptoms during clamping. Mean stump pressure was lower in the group that developed neurological symptoms than in the group who did not (34 +/- 19 mmHg vs. 55 +/- 17 mmHg [p < . 01]). Corresponding NIRS results for the decrease in rSO2 on the ipsilateral side was 15 +/- 7% versus 4 +/- 6% (p < .01). Using stump pressure <= 50 mmHg as cutoff value for predicting symptoms, the sensitivity was 85% (95% confidence interval [CI] 64-95) and specificity 54% (95% CI 46-61). With a relative decrease in NIRS saturation (triangle rSO2) of 9%, sensitivity was 95% (95% CI 76-99), and specificity 81% (95% CI 74-86) to predict ischaemic symptoms during carotid clamping. Neurological deterioration during carotid clamping was detected in one patient with a relative decrease in rSO2 of <9% compared with three patients with a stump pressure >50 mmHg.

    Conclusion: NIRS allows continuous non-invasive monitoring of cerebral oxygenation during CEA, with high sensitivity and acceptable specificity in predicting cerebral ischaemia and the need for shupting, which makes it an attractive alternative to stump pressure.

  • 314.
    Jonsson, Magnus
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Dept Surg, Stockholm, Sweden..
    Lindström, David
    Karolinska Inst, Inst Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden..
    Gillgren, Peter
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Dept Surg, Stockholm, Sweden..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Malmstedt, Jonas
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Dept Surg, Stockholm, Sweden..
    Long-Term Outcome After Carotid Artery Stenting: A Population-Based Matched Cohort Study2016In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 47, no 8, p. 2083-2089Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-Long-term outcome after carotid artery stenting (CAS), a less invasive technique than carotid endarterectomy (CEA), for prevention of stroke, is unclear. The aim was to assess long-term outcomes after CAS, compared with CEA, in a nationwide cohort study.

    Methods-All patients registered in the national Swedish Vascular Registry (Swedvasc) treated with primary CAS between 2005 and 2012 were identified. For every CAS, 2 CEA controls, matched for sex, age, procedure year, and indication (symtomatic/asymtomatic), were chosen. Postoperative stroke was identified by cross-matching the cohort with the InPatient Registry and charts review. Primary end point was ipsilateral stroke or death >30 days postoperatively.

    Results-A total of 1157 patients were included, 409 CAS and 748 CEA; 73% men with mean age 70 years and 69% were symptomatic. Risk factor profile was similar between the 2 groups. Median follow-up time was 4.1 years. Ipsilateral stroke or death of >30 days postoperatively occurred in 95 of 394 in the CAS group versus 120 of 724 in the CEA group (adjusted hazard ratio, 1.59; 95% confidence interval, 1.15-2.18). The corresponding adjusted rates for death, ipsilateral stroke of >30 days, and any stroke or death of >30 days were 25.7% versus 18.6% (hazard ratio, 1.20; 95% confidence interval, 0.84-1.72), 9.4% versus 2.9% (hazard ratio, 3.40; 95% confidence interval, 1.53-7.53), 34.2% versus 23.6% (hazard ratio, 1.49; 95% confidence interval, 1.10-2.00) for the CAS group versus CEA group, respectively.

    Conclusions-In this nationwide cohort study, CAS was associated with an increased long-term risk of ipsilateral stroke and death during after the perioperative phase when compared with CEA.

  • 315.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ankle brachial index most important to identify polyvascular disease in patients with non-ST elevation or ST-elevation myocardial infarction2016In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 30, p. 55-60Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atherosclerosis is a systemic disease. In patients with acute myocardial infarction (MI) the extent of polyvascular disease (PvD) is largely unknown. In this study we investigate the prevalence and clinical characteristics predictive of PvD in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) MI.

    METHOD: 375 patients with acute MI included in the REBUS (Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, carotid ultrasound and ankle brachial index (ABI). Results compared findings of atherosclerosis in three arterial beds to fewer than 3 beds. PvD was defined as atherosclerosis in all three arterial beds.

    RESULTS: A medical history of MI, peripheral artery disease (PAD) or stroke was reported at admission in 17.9%, 2.1% and 3.7% of the patients, respectively. After evaluation, abnormal ABI was found in 20.3% and carotid artery atherosclerosis in 54.9% of the patients. In the total population, PvD was found in 13.8% of patients with no significant differences observed between NSTEMI and STEMI patients. Age (p<0.001), diabetes (p=0.039), previous PAD (p=0.009) and female gender (p=0.016) were associated with PvD. ABI was the most important predictor of PvD with a positive predictive value of 68.4% (95% CI 57.7-79.2%) and specificity of 92.4% (95% CI 89.5-95.4%).

    CONCLUSIONS: PvD is underdiagnosed in patients suffering from MI, both NSTEMI and STEMI. ABI is a useful and simple measurement that appears predictive of widespread atherosclerosis in these patients.

  • 316.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Low Walking Impairment Questionnaire score after a recent myocardial infarction identifies patients with polyvascular disease2019In: JRSM Cardiovascular Disease, ISSN 2048-0040, Vol. 8, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate whether the Walking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during two-year follow-up.

    Design: A prospective observational study.

    Setting: Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital.

    Participants: Patients admitted with acute Non-STEMI- or STEMI-elevation myocardial infarction.

    Main outcome measures: The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance, speed, and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle-brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile.

    Results: The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance, odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8-16.1); speed, OR 7.4 (95% CI 1.5-36.5); stair climbing, OR 8.4 (95% CI 1.0-73.6). In stair climbing score, patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5-19.0). The adherence to medical treatment was high (between 81.7% and 99.2%).

    Conclusions: The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events.

  • 317. Kakkar, A.
    et al.
    Kessler, C.
    Goldhaber, S. Z.
    Kovacs, M. J.
    Spyropoulos, A. C.
    Ortel, T. L.
    Pabinger, I
    Huisman, M. , V
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Monreal, M.
    Turpie, A. G.
    Francis, C. W.
    Dalteparin sodium for the long-term management of venous thromboembolism in cancer patients. The DALTECAN Study2013In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 11, no S2, p. 18-19Article in journal (Other academic)
  • 318.
    Kakkos, S. K.
    et al.
    Univ Hosp Patras, Dept Vasc Surg, Patras 26504, Greece.;Imperial Coll London, St Marys Hosp, Dept Surg & Canc, London, England..
    Bicknell, C. D.
    Imperial Coll London, St Marys Hosp, Dept Surg & Canc, London, England..
    Tsolakis, I. A.
    Univ Hosp Patras, Dept Vasc Surg, Patras 26504, Greece..
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Editor's Choice - Management of Secondary Aorto-enteric and Other Abdominal Arterio-enteric Fistulas: A Review and Pooled Data Analysis2016In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 52, no 6, p. 770-786Article, review/survey (Refereed)
    Abstract [en]

    Objectives: To compare management strategies for secondary abdominal arterio-enteric fistulas (AEFs). Methods: This study is a review and pooled data analysis. Medline and Scopus databases were searched for studies published between 1999 and 2015. Particular emphasis was given to short- and long-term outcomes in relation to AEF repair type. Results: Two hundred and sixteen publications were retrieved, reporting on 823 patients. In-hospital mortality was 30.7%. Open surgery had higher in-hospital mortality (246/725, 33.9%), than endovascular methods (7/98, 7.1%, p<.001, OR 6.7, 95% CI 3-14.7, including staged endovascular to open surgery, 0/13, 0%). In-hospital mortality after graft removal/extra-anatomical bypass grafting was 31.2% (66/226), graft removal/in situ repair 34% (137/403), primary closure of the arterial defect 62.5% (10/16), and for miscellaneous open procedures 41.3% (33/80), p=.019. Among the subgroups of in situ repair, homografts were associated with a higher mortality than impregnated prosthetic grafts (p=.047). There was no difference in recurrent AEF-free rates between open and endovascular procedures. Extra-anatomical bypass/graft removal and in situ repair had a lower AEF recurrence rate than primary closure and homografts. Late sepsis occurred more often after endovascular surgery (2-year rates 42% vs. 19% for open, p=.001). The early survival benefit of endovascular surgery was blunted during follow-up, although it remained significant (p<.001). Within the in situ repair group, impregnated prosthetic grafts were associated with the worst overall and AEF related mortality free rates and vein grafts with the best. No recurrence, sepsis, or mortality was reported following staged endograft placement to open repair after a mean follow-up of 16.8 months (p=.18, p=.22, and p=.006, respectively, compared with patients in other groups). Conclusions: Endovascular surgery, where appropriate, is associated with better early survival than open surgery for secondary AEFs. Most of this benefit is lost during long-term follow-up, implying that a staged approach with early conversion to in situ vein grafting may achieve the best results in selected patients.

  • 319.
    Kaluza, Joanna
    et al.
    Warsaw Univ Life Sci SGGW, Dept Human Nutr, Nutr Res Lab, Warsaw, Poland;Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.
    Stackelberg, Otto
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Harris, Holly Ruth
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.
    Anti-inflammatory diet and risk of abdominal aortic aneurysm in two Swedish cohorts2019In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 105, no 24, p. 1876-1883Article in journal (Refereed)
    Abstract [en]

    Objective The relationship between dietary patterns and development of abdominal aortic aneurysm (AAA) is not well understood. Thus, we prospectively evaluated the association between the anti-inflammatory potential of diet and risk of AAA. Methods The study population included the Cohort of Swedish Men (45 072 men) and the Swedish Mammography Cohort (36 633 women), aged 45-83 years at baseline. The anti-inflammatory potential of diet was estimated using Anti-inflammatory Diet Index (AIDI) based on 11 foods with anti-inflammatory potential and 5 with proinflammatory potential (maximum 16 points) that was validated againsthigh sensitivity C reactive protein (hsCRP). Cox proportional hazard regression models were used to estimate HRs and 95% CIs. During the 14.9 years of follow-up (1 217 263 person-years), 1528 AAA cases (277 (18%) ruptured, 1251 non-ruptured) were ascertained via the Swedish Inpatient Register, the National Cause of Death Register and the Register for Vascular Surgery (Swedvasc). Results We observed an inverse association between the AIDI and AAA risk in women and men; HRs between extreme quartiles of the AIDI (>= 8 vs <= 5 points) were 0.55 (95% CI 0.36 to 0.83) in women and 0.81 (95% CI 0.68 to 0.98) in men. The AIDI was inversely associated with both ruptured and non-ruptured AAA incidence; the HR of participants in the highest quartile of AIDI compared with those in the lowest quartile was 0.61 (95% CI 0.41 to 0.90) for ruptured AAA and 0.79 (95% CI 0.65 to 0.95) for non-ruptured AAA. Conclusion Adherence to diet with a high anti-inflammatory potential was associated with a reduced AAA risk, an association that was even more pronounced for AAA rupture.

  • 320. Kappert, Kai
    et al.
    Leppänen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Paulsson, Janna
    Furuhashi, Masao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Carlsson, Mari-Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Heldin, Carl-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Fätkenheuer, Gerd
    Rosenkranz, Stephan
    Östman, Arne
    Highly Active Antiretroviral Therapy Attenuates Re-Endothelialization and Alters Neointima Formation in the Rat Carotid Artery After Balloon Injury2006In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 43, no 4, p. 383-392Article in journal (Refereed)
    Abstract [en]

    Highly active antiretroviral therapy (HAART) has led to a sustained decline of HIV-associated morbidity and mortality. HAART exhibits significant side effects, however, such as hyperlipidemia and hyperglycemia, which possibly contribute to accelerated atherosclerosis in HAART-treated patients. In addition, direct effects of HAART on vascular cells have been described, which may promote atherosclerotic lesion formation. The effects of HAART on balloon-induced neointima formation have not been studied previously. The rat carotid artery balloon model was used to evaluate the effects of HAART (lopinavir, ritonavir, lamivudine, and zidovudine) on neointima formation and endothelial recovery. Furthermore, the effects of concomitant administration of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor rosuvastatin were investigated. HAART-treated animals displayed an increase in lesion size (neointima/media ratio: 1.14 +/- 0.32 vs. 1.31 +/- 0.20 in control vs. HAART; P < 0.05) and an impaired regenerative capacity of the endothelium, as indicated by reduction in endothelial regrowth from an adjacent undilated vessel segment 14 days after injury (re-endothelialization area: 8.29 +/- 1.45 mm vs. 5.09 +/- 0.53 mm in control vs. HAART; P < 0.05). When rosuvastatin was given in addition to HAART, these effects were not observed. In conclusion, HAART inhibited endothelial cell-mediated healing and promoted neointima formation after angioplasty in rats. These deleterious effects were attenuated by cotreatment with rosuvastatin, however. Our studies suggest that currently used drug regimens against HIV infection may lead to an increased risk for restenosis after percutaneous vascular interventions. Moreover, the findings indicate that the additional treatment with statins might counteract these adverse effects by HAART.

  • 321. Kappert, Kai
    et al.
    Paulsson, Janna
    Sparwel, Jan
    Leppänen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Hellberg, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Östman, Arne
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Dynamic changes in the expression of DEP-1 and other PDGF receptor-antagonizing PTPs during onset and termination of neointima formation2007In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 21, no 2, p. 523-534Article in journal (Refereed)
    Abstract [en]

    Growth factor-dependent tissue remodeling, such as restenosis, is believed to be predominantly regulated by changes in expression of receptor-tyrosine-kinases (RTKs) and their ligands. As endogenous antagonists of RTKs, protein-tyrosine-phosphatases (PTPs) are additional candidate regulators of these processes. Using laser-capture-microdissection and quantitative RT-polymerase chain reaction (qRT-PCR), we investigated the layer-specific expression of the four platelet-derived growth factor (PDGF) isoforms, the PDGF-alpha and beta receptors, and five PTPs implied in control of PDGF-receptor signaling 8 and 14 days after balloon injury of the rat carotid. Results were correlated with analyses of PDGF-beta receptor phosphorylation and vascular smooth muscle cell (VSMC) proliferation in vivo. The expression levels of all components, as well as receptor activation and VSMC proliferation, showed specific changes, which varied between media and neointima. Interestingly, PTP expression--particularly, DEP-1 levels--appeared to be the dominating factor determining receptor-phosphorylation and VSMC proliferation. In support of these findings, cultured DEP-1(-/-) cells displayed increased PDGF-dependent cell signaling. Hyperactivation of PDGF-induced signaling was also observed after siRNA-down-regulation of DEP-1 in VSMCs. The results indicate a previously unrecognized role of PDGF-receptor-targeting PTPs in controlling neointima formation. In more general terms, the observations indicate transcriptional regulation of PTPs as an important mechanism for controlling onset and termination of RTK-dependent tissue remodeling.

  • 322. Kappert, Kai
    et al.
    Sparwel, Jan
    Sandin, Åsa
    Seiler, Alexander
    Siebolts, Udo
    Leppänen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Rosenkranz, Stephan
    Östman, Arne
    Antioxidants relieve phosphatase inhibition and reduce PDGF signaling in cultured VSMCs and in restenosis2006In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 26, no 12, p. 2644-2651Article in journal (Refereed)
    Abstract [en]

    Objective - Growth factor- and reactive oxygen species (ROS)-induced activation of VSMCs is involved in vascular disease. This study investigates whether inhibitory oxidation of protein tyrosine phosphatases (PTPs) contributes to signaling in VSMCs in vitro and in vivo, and analyzes whether ROS- and growth factor-dependent vascular smooth muscle cell (VSMC) signaling is blunted by antioxidants that are able to activate oxidized PTPs. Methods and Results - Signaling induced by H2O2 and platelet-derived growth factor (PDGF) was analyzed in VSMCs with or without the antioxidants N-acetyl-cysteine (NAC) and tempol. Effects of antioxidants on PDGF-stimulated chemotaxis and proliferation were determined. In vivo effects of antioxidants were analyzed in the rat carotid balloon-injury model, by analyzing neointima formation, cell proliferation, PDGF beta-receptor status, and PTP expression and activity. NAC treatment prevented H2O2-induced PTP inhibition, and reduced H2O2-and ligand-induced PDGF beta-receptor phosphorylation, PDGF-induced proliferation, and chemotaxis of VSMCs. Antioxidants inhibited neointima formation and reduced PDGF receptor phosphorylation in the neointima and also increased PTP activity. Conclusion - PTP-inhibition was identified as an intrinsic component of H2O2-and PDGF-induced signaling in cultured VSMCs. The reduction in PDGF beta-receptor phosphorylation in vivo, and the increase in PTP activity, by antioxidants indicate activation of oxidized PTPs as a previously unrecognized mechanism for the antirestenotic effects of antioxidants. The findings thus suggest, in general terms, reactivation of oxidized PTPs as a novel antirestenotic strategy.

  • 323.
    Karkamanis, Achilleas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Venermo, M
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Abdominal Aortic Aneurysm: Threshold for elective intervention2015In: Vascular and Endovascular Controversies Update / [ed] Greenhalgh R, London: BIBA Publishing , 2015, p. 185-192Chapter in book (Other academic)
  • 324.
    Karlsson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindbäck, Johan
    Uppsala University, Units outside the University.
    Pärsson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Expansion of small-diameter abdominal aortic aneurysms is not reflected by the release of inflammatory mediators IL-6, MMP-9 and CRP in plasma2009In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 37, no 4, p. 420-424Article in journal (Refereed)
    Abstract [en]

    Abdominal aortic aneurysm (AAA) is a common disease that develops gradually over several years and is characterised by weakening and dilatation of the aortic wall. AAAs also demonstrates a marked inflammatory infiltrate throughout the aortic wall. Chlamydophila pneumoniae (C. pneumoniae), is a common bacterium. About 50% of the population has been infected in adolescence. Thirteen studies report the presence of either C. pneumoniae or its antigens in 35-100% of AAA specimens.

    The overall aim of this thesis was to evaluate the possible role of C. pneumoniae in inflammatory response and expansion of AAA from a clinical point of view.

    In paper I, viable C. pneumoniae was detected in a majority of 26 patients with AAA having open surgery. Patients operated for AAA had higher C. pneumoniae antibodies titers than controls. In paper II, 247 patients were randomised in a double-blind trial, to evaluate the effect of azithromycin on the expansion of small AAAs. No such effect was seen and there was no correlation between C. pneumoniae antibody titers and AAA expansion. In paper III, 42 patients with AAA were compared to 100 age- and sex matched controls with normal aortas. C. pneumoniae antibodies were analysed in plasma samples obtained at screening, and in samples from a study conducted 5-15 (mean 12) years previously on the same population. There was no significant difference between the groups. In paper IV, were 211 patients were analysed, we could not find an association between levels in plasma of three markers of inflammation (IL-6, MMP-9 and CRP) and AAA expansion. A significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins.

    In conclusion, viable C. pneumoniae is found at the scene of the crime, but we were unable to reverse or halt expansion of AAA with antibiotic treatment. C. pneumoniae antibody titers cannot be used, to detect small AAA, or to evaluate AAA expansion. From a clinical point of view, based on the methods and analyses used in this thesis, the role of C. pneumoniae in the inflammatory response and expansion of abdominal aortic aneurysms is limited.

  • 325.
    Karlsson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Pärsson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    The association between serological markers for chlamydophila pneumoniae and the development of abdominal aortic aneurysm2011In: Annals of Vascular Surgery, ISSN 0890-5096, E-ISSN 1615-5947, Vol. 25, no 3, p. 322-326Article in journal (Refereed)
    Abstract [en]

    Background: To investigate the association between serological markers for Chlamydophila pneumoniae (Cpn) and the development of abdominal aortic aneurysm (AAA) in a population-based case-control study. Methods: A screening for AAA among 65-75-year-old men and women was performed in a population with high prevalence of disease. Most of the subjects had undergone previous testing at the age of 60, including blood sampling. A total of 42 patients with AAA were compared with 100 age- and gender-matched controls with normal aortas. Cpn immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies present in plasma samples obtained at the time of screening (current) and in the past 5-15 (mean, 12) years (historical) were analyzed. Cpn antibody titers (<1/64, 1/64, 1/264, and 1/1024) were analyzed using the microimmunofluorescence technique. Results: No differences in current Cpn immunoglobulin A and IgG antibodies titers (p = 0.111 and 0.659), historical titers (p = 0.449 and 0.228), or titer change (delta) (p = 0.794 and 0.172) were observed between patients with AAA and controls. In all, 82% of the patients with AAA had a current Cpn IgG titer of 1/1024 as compared with the 70% of the control group. All 11 patients who had an aortic diameter of >40 mm reported having high current Cpn IgG titers. The fact that such a large proportion of the healthy population demonstrated an immune response against Cpn made it difficult to demonstrate possible effects of Cpn infection on AAA formation in a case-control study. Conclusion: No significant associations were found between AAA detected by screening and Cpn antibody titer levels at the time of screening or during past screening at the age of 60.

  • 326.
    Karlsson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Gnarpe, Judy
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindbäck, Johan
    Uppsala University, Units outside the University.
    Pärsson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    The effect of azithromycin and Chlamydophila pneumoniae infection on expansion of small abdominal aortic aneurysms: a prospective randomised double-blind trial2009In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 50, no 1, p. 23-29Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of the study was to evaluate the effect of azithromycin on the expansion rate of small abdominal aortic aneurysms (AAAs), and to determine whether or not a correlation exists between serological markers for Chlamydophilia pneumonia (Cpn) infection and AAA expansion. METHODS: Nine vascular centers were included and 259 patients were invited to participate. Ten patients declined and 2 patients had chronic kidney failure, leaving a total of 247 patients. Inclusion criteria were: AAA 35-49 mm and age <80 years. Patients were randomized to receive either azithromycin (Azithromax, Pfizer Inc, New York, NY) 600 mg once daily for 3 days and then 600 mg once weekly for 15 weeks, or placebo in identical tablets. The ultrasound scans were performed in a standardized way within a month before inclusion and every 6 months for a minimum follow-up time of 18 months. Cpn serology was analyzed in blood samples taken at inclusion and 6 months later. Serum was analyzed for Cpn IgA and IgG antibodies by microimmunofluorescence (MIF). Computed tomography (CT) scans were done in 66 patients at inclusion and at 1 year for volume calculations. RESULTS: Thirty-four patients were excluded, ie, could not be followed for 18 months, 20 in the placebo group and 16 in the active treatment group. A total of 211 patients had at least two measurements and all were analyzed in an intention-to-treat analysis. Detectable IgA against Cpn was found in 115 patients and detectable IgG against Cpn in 160 patients. No statistically significant differences were found between the groups regarding median expansion rate measured by ultrasound scan (0.22 cm/year, interquartile range [IQR]: 0.09 to 0.34 in the placebo group vs 0.22, IQR: 0.12 to 0.36 in the treatment group, P = .85). Volume calculation did not change that outcome (10.4 cm(3)/year in the placebo group vs 15.9 cm(3)/year in the treatment group, P = .61). No correlation was found between serological markers for Cpn infection and the expansion rate. Patients taking statins in combination with acetylsalicylic acid (ASA) had significantly reduced expansion rate compared to patients who did not take statins or ASA, 0.14 cm/year vs 0.27 cm/year, P < .001. CONCLUSION: Azithromycin did not have any effect on AAA expansion. No correlation was found between serological markers for Cpn and AAA expansion, indicating no clinical relevance for Cpn testing in AAA surveillance. However, a significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins.

  • 327.
    Karthikesalingam, A.
    et al.
    St Georges Vasc Inst, London, England..
    Brownrigg, J.
    St Georges Vasc Inst, London, England..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Holt, P.
    St Georges Vasc Inst, London, England..
    Lessons from Comparing Elective AAA Repair in England and Sweden2016In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, p. 11-11Article in journal (Other academic)
  • 328.
    Karthikesalingam, A.
    et al.
    St Georges Univ London, St Georges Vasc Inst, London, England;St Georges Univ London, Mol & Clin Sci Res Inst, London, England.
    Grima, M. J.
    St Georges Univ London, St Georges Vasc Inst, London, England;St Georges Univ London, Mol & Clin Sci Res Inst, London, England.
    Holt, P. J.
    St Georges Univ London, St Georges Vasc Inst, London, England;St Georges Univ London, Mol & Clin Sci Res Inst, London, England.
    Vidal-Diez, A.
    St Georges Univ London, St Georges Vasc Inst, London, England;St Georges Univ London, Populat Hlth Res Inst, London, England.
    Thompson, M. M.
    St Georges Univ London, St Georges Vasc Inst, London, England.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Comparative analysis of the outcomes of elective abdominal aortic aneurysm repair in England and Sweden2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 5, p. 520-528Article in journal (Refereed)
    Abstract [en]

    Background

    There 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.

    Methods

    Patients 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.

    Results

    The 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.

    Conclusion

    Mortality 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

  • 329.
    Karthikesalingam, A.
    et al.
    St Georges Univ London, St Georges Vasc Inst, Room 0-231, London SW17 0RE, England.;St Georges Univ Hosp NHS Fdn Bust, London, England..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Holt, P. J.
    St Georges Univ London, St Georges Vasc Inst, Room 0-231, London SW17 0RE, England.;St Georges Univ Hosp NHS Fdn Bust, London, England..
    Vidal-Diez, A.
    St Georges Univ London, St Georges Vasc Inst, Room 0-231, London SW17 0RE, England.;St Georges Univ Hosp NHS Fdn Bust, London, England..
    Brownrigg, J. R. W.
    St Georges Univ London, St Georges Vasc Inst, Room 0-231, London SW17 0RE, England.;St Georges Univ Hosp NHS Fdn Bust, London, England..
    Shpitser, I.
    Univ Southampton, Dept Math Sci, Southampton, Hants, England..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Thompson, M. M.
    St Georges Univ London, St Georges Vasc Inst, Room 0-231, London SW17 0RE, England.;St Georges Univ Hosp NHS Fdn Bust, London, England..
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Comparison of long-term mortality after ruptured abdominal aortic aneurysm in England and Sweden2016In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, no 3, p. 199-206Article in journal (Refereed)
    Abstract [en]

    Background: Concern has been raised regarding international discrepancies in perioperative mortality after repair of ruptured abdominal aortic aneurysm (rAAA). The variation in in-hospital mortality is difficult to interpret, owing to international differences in discharge strategies. This study compared 90-day and 5-year mortality in patients who had a rAAA in England and Sweden. Methods: Patients undergoing rAAA repair were identified from English Hospital Episode Statistics and the Swedish Vascular Registry (Swedvasc) between 2003 and 2012. Ninety-day and 5-year mortality were compared after matching for age and sex. Within-country analyses examined the impact of co-morbidity, teaching hospital status or hospital annual caseload, adjusted with causal inference techniques. Results: Some 12 467 patients underwent rAAA repair in England, of whom 83.2 per cent were men; the median (i.q.r.) age was 75 (70-80) years. A total of 2829 Swedish patients underwent rAAA repair, of whom 81.3 per cent were men; their median (i.q.r.) age was 75 (69-80) years. The 90-day mortality rate was worse in England (44.0 per cent versus 33.4 per cent in Sweden; P < 0.001), as was 5-year mortality (freedom from mortality 38.6 versus 46.3 per cent respectively; P < 0.001). In England, lower mortality was seen in teaching hospitals with larger bed capacity, higher annual caseloads and greater use of endovascular aneurysm repair (EVAR). In Sweden, lower mortality was associated with EVAR, high annual caseload, or surgery on weekdays compared with weekends. Conclusion: Short-and long-term mortality after rAAA repair was higher in England. In both countries, mortality was lowest in centres performing greater numbers of AAA repairs per annum, and more EVAR procedures.

  • 330. Kirkpatrick, Andrew W
    et al.
    De Waele, Jan J
    De Laet, Inneke
    De Keulenaer, Bart L
    D'Amours, Scott
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Balogh, Zsolt J
    Leppäniemi, Ari
    Kaplan, Mark
    Chiaka Ejike, Janeth
    Reintam Blaser, Annika
    Sugrue, Michael
    Ivatury, Rao R
    Malbrain, Manu L N G
    WSACS--The Abdominal Compartment Society. A Society dedicated to the study of the physiology and pathophysiology of the abdominal compartment and its interactions with all organ systems.2015In: Anaesthesiology intensive therapy, ISSN 1731-2515, Vol. 47, no 3, p. 191-194Article in journal (Refereed)
  • 331.
    Kirkpatrick, Andrew W.
    et al.
    Foothills Med Ctr, Reg Trauma Serv, EG 23, Calgary, AB T2N 2T9, Canada..
    Roberts, Derek J.
    Univ Calgary, Dept Surg, Calgary, AB, Canada..
    De Waele, Jan
    Ghent Univ Hosp, Dept Crit Care Med, Ghent, Belgium.;Ghent Med Sch, Ghent, Belgium..
    Blaser, Annika Reintam
    Univ Tartu, Clin Anaesthesiol & Intens Care, Ulikooli 18, EE-50090 Tartu, Estonia..
    Malbrain, Manu L. N. G.
    ZNA Stuivenberg, ICU & High Care Burn Unit, Antwerp, Belgium..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Balogh, Zsolt J.
    Univ Newcastle, John Hunter Hosp, Newcastle, NSW 2300, Australia..
    Permissive Intraabdominal Hypertension following Complex Abdominal Wall Reconstruction2016In: Plastic and reconstructive surgery (1963), ISSN 0032-1052, E-ISSN 1529-4242, Vol. 137, no 4, p. 762E-764EArticle in journal (Refereed)
  • 332. Kirkpatrick, Andrew W
    et al.
    Roberts, Derek J
    De Waele, Jan
    Jaeschke, Roman
    Malbrain, Manu L N G
    De Keulenaer, Bart
    Duchesne, Juan
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Leppaniemi, Ari
    Ejike, Janeth C
    Sugrue, Michael
    Cheatham, Michael
    Ivatury, Rao
    Ball, Chad G
    Reintam Blaser, Annika
    Regli, Adrian
    Balogh, Zsolt J
    D'Amours, Scott
    Debergh, Dieter
    Kaplan, Mark
    Kimball, Edward
    Olvera, Claudia
    Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome2013In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, no 7, p. 1190-1206Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To update the World Society of the Abdominal Compartment Syndrome (WSACS) consensus definitions and management statements relating to intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS).

    METHODS:

    We conducted systematic or structured reviews to identify relevant studies relating to IAH or ACS. Updated consensus definitions and management statements were then derived using a modified Delphi method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, respectively. Quality of evidence was graded from high (A) to very low (D) and management statements from strong RECOMMENDATIONS (desirable effects clearly outweigh potential undesirable ones) to weaker SUGGESTIONS (potential risks and benefits of the intervention are less clear).

    RESULTS:

    In addition to reviewing the consensus definitions proposed in 2006, the WSACS defined the open abdomen, lateralization of the abdominal musculature, polycompartment syndrome, and abdominal compliance, and proposed an open abdomen classification system. RECOMMENDATIONS included intra-abdominal pressure (IAP) measurement, avoidance of sustained IAH, protocolized IAP monitoring and management, decompressive laparotomy for overt ACS, and negative pressure wound therapy and efforts to achieve same-hospital-stay fascial closure among patients with an open abdomen. SUGGESTIONS included use of medical therapies and percutaneous catheter drainage for treatment of IAH/ACS, considering the association between body position and IAP, attempts to avoid a positive fluid balance after initial patient resuscitation, use of enhanced ratios of plasma to red blood cells and prophylactic open abdominal strategies, and avoidance of routine early biologic mesh use among patients with open abdominal wounds. NO RECOMMENDATIONS were possible regarding monitoring of abdominal perfusion pressure or the use of diuretics, renal replacement therapies, albumin, or acute component-parts separation.

    CONCLUSION:

    Although IAH and ACS are common and frequently associated with poor outcomes, the overall quality of evidence available to guide development of RECOMMENDATIONS was generally low. Appropriately designed intervention trials are urgently needed for patients with IAH and ACS.

  • 333.
    Kirkpatrick, Andrew W.
    et al.
    EG 23 Foothills Med Ctr, Reg Trauma Serv, Calgary, AB T2N 2T9, Canada..
    Roberts, Derek J.
    Univ Calgary, Dept Surg, Calgary, AB, Canada.;Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada..
    Jaeschke, Roman
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada..
    De Waele, Jan
    Ghent Univ Hosp, Dept Crit Care Med, Ghent, Belgium.;Ghent Med Sch, Ghent, Belgium..
    De Keulenaer, Bart
    Fremantle Hosp, Intens Care Unit, Fremantle, WA, Australia..
    Duchesne, Juan
    Anesthesia & Emergency Med, Div Surg, Sect Trauma & Crit Care Surg, Tulane Surg Intens Care Unit, New Orleans, LA USA..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Leppaniemi, Ari
    Univ Helsinki, Meilahti Hosp, Dept Abdominal Surg, Haartmaninkatu, Hus, Finland..
    Ejike, Janeth C.
    Loma Linda Univ, Childrens Hosp, Loma Linda, CA 92350 USA..
    Sugrue, Michael
    Letterkenny Hosp, Dept Surg, Donegal, Ireland.;Univ Coll Hosp, Galway, Ireland..
    Cheatham, Michael
    Dept Surg Educ, Orlando, FL USA..
    Ivatury, Rao
    Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA..
    Ball, Chad G.
    EG 23 Foothills Med Ctr, Reg Trauma Serv, Calgary, AB T2N 2T9, Canada..
    Blaser, Annika Reintam
    Univ Tartu, Clin Anaesthesiol & Intens Care, EE-50090 Tartu, Estonia..
    Regli, Adrian
    Fremantle Hosp, Intens Care Unit, Fremantle, WA, Australia.;Sch Med & Pharmacol, Crawley, WA, Australia.;Univ Notre Dame, Fremantle, WA, Australia..
    Balogh, Zsolt J.
    Univ Newcastle, John Hunter Hosp, Newcastle, NSW 2300, Australia..
    D'Amours, Scott
    Liverpool Hosp, Trauma Dept, Liverpool, NSW, Australia..
    De Iaet, Inneke
    ZNA Stuivenberg, Ziekenhuis Netwerk Antwerpen, Intens Care Unit, Antwerp, Belgium.;ZNA Stuivenberg, Ziekenhuis Netwerk Antwerpen, High Care Burn Unit, Antwerp, Belgium..
    Malbrain, Manu L. N. G.
    ZNA Stuivenberg, Ziekenhuis Netwerk Antwerpen, Intens Care Unit, Antwerp, Belgium.;ZNA Stuivenberg, Ziekenhuis Netwerk Antwerpen, High Care Burn Unit, Antwerp, Belgium..
    Methodological background and strategy for the 2012-2013 updated consensus definitions and clinical practice guidelines from the abdominal compartment society2015In: ANAESTHESIOLOGY INTENSIVE THERAPY, ISSN 1642-5758, Vol. 47, p. S63-S77Article, review/survey (Refereed)
    Abstract [en]

    The Abdominal Compartment Society (www.wsacs.org) previously created highly cited Consensus Definitions/Management Guidelines related to intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Implicit in this previous work, was a commitment to regularly reassess and update in relation to evolving research. Two years preceding the Fifth World Congress on Abdominal Compartment Syndrome, an International Guidelines committee began preparation. An oversight/steering committee formulated key clinical questions regarding IAH//ACS based on polling of the Executive to redundancy, structured according to the Patient, Intervention, Comparator, and Outcome (PICO) format. Scientific consultations were obtained from Methodological GRADE experts and a series of educational teleconferences were conducted to educate scientific review teams from among the wscacs. org membership. Each team conducted systematic or structured reviews to identify relevant studies and prepared evidence summaries and draft Grades of Recommendation Assessment, Development and Evaluation (GRADE) recommendations. The evidence and draft recommendations were presented and debated in person over four days. Updated consensus definitions and management statements were derived using a modified Delphi method. A writing committee subsequently compiled the results utilizing frequent Internet discussion and Delphi voting methods to compile a robust online Master Report and a concise peer-reviewed summarizing publication. A dedicated Paediatric Guidelines Subcommittee reviewed all recommendations and either accepted or revised them for appropriateness in children. Of the original 12 IAH/ACS definitions proposed in 2006, three (25%) were accepted unanimously, with four (33%) accepted by >80%, and four (33%) accepted by >50%, but required discussion to produce revised definitions. One (8%) was rejected by >50%. In addition to previous 2006 definitions, the panel also defined the open abdomen, lateralization of the abdominal musculature, polycompartment syndrome, abdominal compliance, and suggested a refined open abdomen classification system. Recommendations were possible regarding intra-abdominal pressure (IAP) measurement, approach to sustained IAH, philosophy of protocolized IAP management and same-hospital-stay fascial closure, use of decompressive laparotomy, and negative pressure wound therapy. Consensus suggestions included use of non-invasive therapies for treating IAH/ACS, considering body position and IAP, damage control resuscitation, prophylactic open abdomen usage, and prudence in early biological mesh usage. No recommendations were made for the use of diuretics, albumin, renal replacement therapies, and utilizing abdominal perfusion pressure as a resuscitation-endpoint. Collaborating Methodological Guideline Development and Clinical Experts produced Consensus Definitions/Clinical Management statements encompassing the most contemporary evidence. Data summaries now exist for clinically relevant IAH/ACS questions, which will facilitate future scientific reanalysis.

  • 334.
    Koelbel, Tilo
    et al.
    Univ Heart Ctr, Dept Vasc Med, German Aort Ctr Hamburg, Martinistr 52, D-20246 Hamburg, Germany.
    Tsilimparis, Nikolaos
    Univ Heart Ctr, Dept Vasc Med, German Aort Ctr Hamburg, Martinistr 52, D-20246 Hamburg, Germany.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Rohlffs, Fiona
    Univ Heart Ctr, Dept Vasc Med, German Aort Ctr Hamburg, Martinistr 52, D-20246 Hamburg, Germany.
    Wipper, Sabine
    Univ Heart Ctr, Dept Vasc Med, German Aort Ctr Hamburg, Martinistr 52, D-20246 Hamburg, Germany.
    Debus, E. Sebastian
    Univ Heart Ctr, Dept Vasc Med, German Aort Ctr Hamburg, Martinistr 52, D-20246 Hamburg, Germany.
    von Kodolitsch, Yskert
    Univ Heart Ctr, Dept Cardiology, German Aort Ctr Hamburg, Hamburg, Germany.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Physician-Modified Thoracic Stent-Graft With Low Distal Radial Force to Prevent Distal Stent-Graft-Induced New Entry Tears in Patients With Genetic Aortic Syndromes and Aortic Dissection2018In: Journal of Endovascular Therapy, ISSN 1526-6028, E-ISSN 1545-1550, Vol. 25, no 4, p. 456-463Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe a novel modification technique to lower the distal radial force of a thoracic stent-graft so as to avert stent-graft-induced new entry tears (SINE) in the fragile aorta of patients with genetic aortic disease and aortic dissection. Technique: A commercially available thoracic stent-graft is partially deployed on a back table. The most distal Z-stent is removed, the distal fabric is marked by vascular clips, and the modified stent-graft is reloaded and deployed in the true lumen of an aortic dissection. The technique is demonstrated in 3 patients with aortic dissection related to genetic aortic diseases. Conclusion: Creating a low distal radial force stent-graft is easy and can be done in a short time. Endovascular implantation appears feasible and safe.

  • 335. Koraen-Smith, Linn
    et al.
    Troëng, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wahlgren, Carl-Magnus
    Urgent Carotid Surgery and Stenting May Be Safe After Systemic Thrombolysis for Stroke2014In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 45, no 3, p. 776-780Article in journal (Refereed)
    Abstract [en]

    Background and Purpose Early carotid surgery or stenting after thrombolytic treatment for stroke has become more common during recent years. It is unclear whether this carries an increased risk of postoperative complications and death. The aim of this nationwide population-based study was, therefore, to investigate the safety of urgently performed carotid procedures in patients treated with thrombolysis for stroke. Methods Using the national Vascular and Stroke registries, we identified 3998 patients who had undergone carotid endarterectomy or carotid artery stenting for symptomatic carotid stenosis between May 2008 and December 2012. Among these, 2% (79 of 3998) had undergone previous thrombolysis for stroke. We conducted a retrospective review of registry data and individual case records with regard to postoperative complications, including surgical-site bleeding, stroke, and death. The outcome was compared with the results for the remaining patient cohort (3919 of 3998) undergoing carotid surgery and stenting during the study period. Results The median time between thrombolysis and the carotid procedure was 10 days. Seventy-one patients underwent carotid endarterectomy, and 6 patients underwent carotid artery stenting. The 30-day death and stroke rate for the thrombolysis cohort was 2.5% (2 of 79), and for the whole cohort, it was 3.8% (139 of 3626; P=0.55). The postoperative bleeding rates requiring reoperation were not significantly different between the groups (3.8% [3 of 79] in the thrombolysis group versus 3.3% [119 of 3626] in the whole cohort; P=0.79). There was no correlation between time from lysis to surgery or stenting and complications at 30 days postoperatively. Conclusions Urgent carotid endarterectomy or carotid artery stenting after thrombolysis for stroke may be safe without increased risk of serious complications.

  • 336.
    Kragsterman, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Pärsson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Carotid Endarterectomy Induces the Release of Inflammatory Markers and the Activation of Coagulation as Measured in the Jugular Bulb2017In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 26, no 10, p. 2320-2328Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: Transient cerebral hypoxia may induce neuronal injury through an ischemia-reperfusion (I/R) response, with a subsequent activation of inflammation and coagulation-fibrinolysis. During carotid endarterectomy (CEA), the artery is clamped, which might impair the regional cerebral perfusion and initiate a local I/R response. Data suggest that the CD40-CD40 ligand dyad acts as a modulator in the induced activation. The aim of this study was to locally measure soluble CD40 ligand (sCD40L), in conjunction with inflammation and coagulation activation markers, during CEA.

    Subjects and Methods: This is a prospective study of 18 patients undergoing CEA. Blood samples from the venous jugular bulb (JB) and the radial artery (RA) were drawn at baseline and during the procedure. Measurements of sCD40L, interleukin-6 (IL-6), fragment 1 + 2 (F1 + 2), plasminogen activator inhibitor-1 (PAI-1), and D-dimer were analyzed. Comparisons during CEA were made between levels: baselines versus JB, JB versus RA, and sequential JB measurements. Fifty cardiovascular healthy patients were the reference group for the sCD40L baseline comparison.

    Results: Increased cerebral IL-6 levels were demonstrated throughout the procedure, as well as the temporal influence in F1 + 2, PAI-1, and D-dimer values. sCD40L remained unchanged throughout the procedure. This indicates a local cerebral inflammatory reaction together with an activation of coagulation-fibrinolysis, but it does not appear to primarily involve the CD40-CD40 ligand dyad.

    Conclusions: Signs of a local inflammatory reaction and activation of coagulation were observed during CEA, but levels of sCD40L remained stable, unaffected by carotid artery clamping and reperfusion.

  • 337.
    Kragsterman, Björn