Atherosclerosis, the leading cause of mortality in Western societies, affects large elastic arteries, causing focal deposition of proliferative inflammatory and lipid-laden cells within the artery. Several risk factors have been causally implicated in the ???reaction to injury??? hypothesis first described by Ross in 1969. The ???injury??? sustained by endothelial cells may be either mechanical or chemical. Environmental factors have a role in the production of chemical agents that are injurious to the endothelium. Mechanical stresses such as wall tensile stress are proportional to systemic blood pressure and pulse pressure. Essentially, these systemic pressures are fairly evenly distributed throughout the circulation. However, atherosclerotic lesions characteristically occur at focal sites within the human vasculature; at or near bifurcations, within the ostia of branch arteries and at regions of marked or complex curvature, where local haemodynamic abnormalities occur. The most discussed haemodynamic factor seems to be low or highly oscillating wall shear stress which exists on the outer wall of bifurcations and on the inner aspect of curving vessels. The magnitude of these haemodynamic forces may not be great but the subtleties of their variable spatial distribution may help to explain the multifocal distribution of atherosclerotic plaques. With the altered haemodynamics there is endothelial injury and phenotypic changes in the endothelium result, which in turn lead to endothelial cell dysfunction. These haemodynamic variables are difficult to measure directly in vivo. In this work a novel model is developed utilising human autologous vein bypass grafts as a surrogate vessel for the observation of pathological structural changes in response to altered haemodynamics. The influence of haemodynamic factors (such as wall shear stress) in the remodeling of the vein graft wall and the pathogenesis of Myointimal Hyperplasia (MIH) and resultant wall thickening in femoral bypass grafts is analysed. The haemodynamic determinants of MIH (which have been established in many animal models) are similar to those implicated in atherosclerosis. The accelerated responses of the vein (Intimal hyperplasia develops much more rapidly than atherosclerotic lesions in native vessels) make it an ideal model to expediently examine the hypothesised relationships prospectively in an in vivo setting. Furthermore, the utilisation of in vivo data acquired from non-invasive diagnostic methods (such as Magnetic Resonance Angiography (MRA) and Duplex ultrasound) combined with the application of state-of-the-art Computational Fluid Dynamic (CFD) techniques makes the model essentially non-invasive. The following hypotheses are examined: 1) regions of Low shear and High tensile stress should develop disproportionately greater wall thickening, 2) regions of greater oscillatory blood flow should develop greater wall thickening, and 3) regions of lower wall shear should undergo inward (or negative) remodelling and result in a reduction in vessel calibre. The conclusions reached are that abnormal haemodynamic forces, namely low Time-averaged Wall Shear Stress, are associated with subsequent wall thickening. These positive findings have great relevance to the understanding of vein graft MIH and atherosclerosis. It was also evident that with non-invasive data and CFD techniques, some of the important haemodynamic factors are realistically quantifiable (albeit indirectly). The detection of parameters known to be causal in the development of graft intimal hyperplasia or other vascular pathology may improve ability to predict clinical problems. From a surgical perspective this might be employed to facilitate selection of at-risk grafts for more focused postoperative surveillance and reintervention. On a broader stage the utilisation of such analyses may be useful in predicting individuals at greater risk of developing atherosclerotic deposits, disease progression, and the likelihood of clinical events such as heart attack, stroke and threat of limb loss.

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.

Abdominal aortic aneurysm (AAA) is a common disease that is life threatening when rupture occurs. The aims of this thesis were to study (I) the long-term survival after AAA repair, (II) the cost of repair with open (OR) and endovascular (EVAR) technique, (III) the effect of different statistical methods on interpretation of cost data, (IV) the prevalence of the disease among patients with suspected arterial disease referred to the vascular laboratory, and (V) the cost-effectiveness of selective high-risk screening. Analyses of data from the Swedish vascular registry (Swedvasc), local patient registries, patient records and hospital cost registries form the basis of this thesis. Short- and long-term survival after intact AAA repair improved over the past two decades, despite increasing patient age and rate of comorbidities over time. Compared to a general population adjusted for age, sex and calendar year, the relative 5-year survival was 90% among those surviving repair. While short-term survival improved over time after ruptured repair, relative long-term survival was stable. Despite differences in patient selection and cost structure, the total cost of AAA repair with EVAR and OR was similar in a population based setting (€28,193). There was lack of consistency in the methods used in cost-analysis in the current literature, and p-values were highly dependent on test method. The practice of selective (non-population-based) screening for AAA among patients referred to the vascular laboratory was studied. The prevalence of AAA was 4.2% among male and 1.5% among female patients. AAA was associated with high age and prevalence of arterial stenosis. Of AAAs detected through selective screening, 21.5% had undergone elective repair at 7.5 years follow-up. In a health-economic evaluation, the incremental cost-effectiveness ratio of selective screening was €11,084 per life year gained. In conclusion, survival after intact AAA repair has improved over time, despite changes in case-mix. Results of health economic reports on cost of AAA repair can be highly dependent on patient selection as well as presentation of data and the statistical methods used. Selective screening for AAA among patients referred to the vascular laboratory is cost-effective.

Syftet för denna studie var att studera förekomsten av postoperativa sårinfektioner hos patienter som genomgått kärloperation med inguinal incision under åren 2008 till och med mars månad 2013. Undersöka skillnader gällande riskfaktorer inom studerad patientgrupp för förekomst av postoperativ sårinfektion samt studera om patienter som utfört endovaskulär metod under samma vårdtillfälle oftare drabbades av postoperativ sårinfektion än de patienter som inte genomgått endovaskulär metod under samma vårdtillfälle. Metoden som användes var granskning av patientjournaler efter utifrån studien utvalda specifika operationskoder. Granskningen av de 54 patientjournalerna skedde med hjälp av egenmodifierad tidigare använd granskningsmall. Studieresultatet visar att förekomsten av postoperativa sårinfektioner hos den studerade patientgruppen uppgår till 22,2 %. Skillnader mellan infektion och utförd endovaskulär metod kunde ses men inte påvisas med statistisk signifikans. Studien visade också att kvinnor oftare än män drabbas av postoperativ sårinfektion. Slutsatsen är att ungefär var femte patient i studien, som genomgått denna typ av kirurgi, ådrog sig en postoperativ sårinfektion och att många av dessa ledde till en kostsam postoperativ sårbehandling med Vacuum assisted closure, (VAC). / The purpose of this study was to investigate the incidence of postoperative wound infections in patients undergoing vascular surgery with inguinal incision in the years 2008 until March 2013. Examining differences in the risk factors in the studied group of patients occurrence of postoperative wound infection and to study whether patients who performed endovascular method during the same hospitalization more often suffered postoperative wound infection than patients who did not undergo endovascular method during the same hospitalization. The method used was the examination of patient records for the study, based on selected specific audit template. Study results show that the incidence of postoperative wound infections in the studied patient population amounts to 22,2 %. Differences between infection and performed endovascular method could be seen but not detected with statistical significance. The study also showed that women more often than men suffer from postoperative wound infection. The conclusion is that approximately one in five patients in the study who have undergone this type of surgery, suffered a postoperative wound infection and that many of these led to a costly postoperative wound Vacuum Assisted Closure (VAC).

Atherosclerosis, the leading cause of mortality in Western societies, affects large elastic arteries, causing focal deposition of proliferative inflammatory and lipid-laden cells within the artery. Several risk factors have been causally implicated in the ???reaction to injury??? hypothesis first described by Ross in 1969. The ???injury??? sustained by endothelial cells may be either mechanical or chemical. Environmental factors have a role in the production of chemical agents that are injurious to the endothelium. Mechanical stresses such as wall tensile stress are proportional to systemic blood pressure and pulse pressure. Essentially, these systemic pressures are fairly evenly distributed throughout the circulation. However, atherosclerotic lesions characteristically occur at focal sites within the human vasculature; at or near bifurcations, within the ostia of branch arteries and at regions of marked or complex curvature, where local haemodynamic abnormalities occur. The most discussed haemodynamic factor seems to be low or highly oscillating wall shear stress which exists on the outer wall of bifurcations and on the inner aspect of curving vessels. The magnitude of these haemodynamic forces may not be great but the subtleties of their variable spatial distribution may help to explain the multifocal distribution of atherosclerotic plaques. With the altered haemodynamics there is endothelial injury and phenotypic changes in the endothelium result, which in turn lead to endothelial cell dysfunction. These haemodynamic variables are difficult to measure directly in vivo. In this work a novel model is developed utilising human autologous vein bypass grafts as a surrogate vessel for the observation of pathological structural changes in response to altered haemodynamics. The influence of haemodynamic factors (such as wall shear stress) in the remodeling of the vein graft wall and the pathogenesis of Myointimal Hyperplasia (MIH) and resultant wall thickening in femoral bypass grafts is analysed. The haemodynamic determinants of MIH (which have been established in many animal models) are similar to those implicated in atherosclerosis. The accelerated responses of the vein (Intimal hyperplasia develops much more rapidly than atherosclerotic lesions in native vessels) make it an ideal model to expediently examine the hypothesised relationships prospectively in an in vivo setting. Furthermore, the utilisation of in vivo data acquired from non-invasive diagnostic methods (such as Magnetic Resonance Angiography (MRA) and Duplex ultrasound) combined with the application of state-of-the-art Computational Fluid Dynamic (CFD) techniques makes the model essentially non-invasive. The following hypotheses are examined: 1) regions of Low shear and High tensile stress should develop disproportionately greater wall thickening, 2) regions of greater oscillatory blood flow should develop greater wall thickening, and 3) regions of lower wall shear should undergo inward (or negative) remodelling and result in a reduction in vessel calibre. The conclusions reached are that abnormal haemodynamic forces, namely low Time-averaged Wall Shear Stress, are associated with subsequent wall thickening. These positive findings have great relevance to the understanding of vein graft MIH and atherosclerosis. It was also evident that with non-invasive data and CFD techniques, some of the important haemodynamic factors are realistically quantifiable (albeit indirectly). The detection of parameters known to be causal in the development of graft intimal hyperplasia or other vascular pathology may improve ability to predict clinical problems. From a surgical perspective this might be employed to facilitate selection of at-risk grafts for more focused postoperative surveillance and reintervention. On a broader stage the utilisation of such analyses may be useful in predicting individuals at greater risk of developing atherosclerotic deposits, disease progression, and the likelihood of clinical events such as heart attack, stroke and threat of limb loss.

Peripheral vascular disease (PVD) is defined by insufficient blood flow to limbs and can result in pain, gangrene, and amputation. Minimally invasive angioplasty treatments for PVD are common but suffer from high failure rates. We conducted three studies: 1) a systematic review to describe methods of intraoperative blood flow assessment; 2) a retrospective cohort study to describe the correlation between outpatient blood flow assessment and clinical outcomes; and 3) a prospective observational study to describe the reliability and association between intraoperative blood flow assessment and clinical outcomes. While limb blood flow is routinely assessed before and after interventions, intraoperative assessment has not been well described. Postoperative blood flow assessments are strongly correlated with clinical outcomes. Intraoperative blood flow assessment is feasible and strongly correlated with clinical outcomes. Intraoperative blood flow assessment may be a useful tool to guide intraoperative decision making.

No description available.

La question du remplacement des chirurgiens vasculaires pour les années à venir est préoccupante du fait d’un grand nombre de départs en retraite. Mais la question du seul remplacement des effectifs ne suffit pas pour une spécialité qui s’adresse principalement à des patients âgés dans le contexte actuel d’augmentation et de vieillissement de la population française.Dans le but de répondre aux besoins en chirurgie vasculaire dans les années futures, nous avons dans un premier temps réalisé un état des lieux de la démographie des praticiens de la spécialité et estimé la cinétique des départs en retraite des prochaines années.Pour pouvoir tenir compte de l’évolution de la future activité, nous avons établi un modèle prédictif de cette activité concernant les actes de chirurgie carotidienne, de chirurgie des anévrysmes de l’aorte abdominale sous-rénale et de chirurgie des artères sous-inguinales, d’après le seul vieillissement de la population. Ce modèle applique les méthodes de l’INSEE aux actes recueillis dans le Programme Médicalisé des Systèmes d’Information. Nous l’avons ensuite affiné par l’intégration d’autres paramètres influençant l’évolution de l’activité grâce au calcul et à l’application d’un coefficient de pondération obtenu sur la période d’activité de 2000 à 2008. D’après le modèle, l’activité entre 2008 et 2030 augmentera de 38% sur les segments étudiés.Les projections pondérées permettent de prédire une augmentation de l’activité de 30% entre 2011 et 2025. D’un point de vue purement mathématique, les besoins de formation seraient de 120 chirurgiens pour le remplacement des départs en retraite, et de 59 chirurgiens supplémentaires du fait de l’augmentation de l’activité. / The question of replacement of vascular surgeons for the future is of concern because of a large number of retirements. But the question of replacement only is not sufficient for a specialty that is primarily for older patients in the current context of increasing and aging of the French population.In order to meet the need for vascular surgery in the coming years, we initially performed an overview of the demographics of practitioners of the specialty and estimated the retirements. To take into account the evolution of the future activity, we have established a predictive model for the acts of carotid surgery, surgery of infrarenal abdominal aortic aneurysms and surgery of peripheral arterial disease, according to the aging population. This model applies the methods of the INSEE for acts collected in the Medicalised Information System Program database.We then refined it by including other parameters modifying workload evolution. We have calculated and applied a weighting factor obtained during the period of activity from 2000 to 2008. According to the model, the activity between 2008 and 2030 will increase by 38% in the studied procedures.The weighted projections predict an acts’ increase 30% between 2011 and 2025.From a purely mathematical point of view, the training needs of 120 surgeons would be to replace retirements, and 59 more surgeons because of the increased workload.

Iatrogenic vascular injuries (IVIs) and injuries associated with vascular surgery can cause severe morbidity and death. The aims of this thesis were to study those injuries in the Swedish vascular registry (Swedvasc), the Swedish medical injury insurance where insurance claims are registered, the Population and Cause of death registries, and in patient records, in order to explore preventive strategies. Among 87 IVIs during varicose vein surgery 43 were venous, mostly causing bleeding in the groin. Among 44 arterial injuries, only 1/3 were detected intraoperatively. Accidental arterial stripping predominated, with poor outcome. Four patients died, all after venous injuries. IVIs increased over time, and constitute more than half of the vascular injuries registered in the Swedvasc. Lethal outcome was more common (4.9%) among patients suffering IVIs than among non-iatrogenic vascular injuries (2.5%). Risk factors for death were age, diabetes, renal insufficiency and obstructive lung-disease. Fifty-two patients died within 30 days after IVI. The most common lethal IVIs were puncture during endovascular procedures (n=24, 46%), penetrating trauma during open surgery (11) and occlusion after compression (6). Symptoms were peripheral ischemia (n=19), external bleeding (14), and hypovolemic chock without external bleeding (10). Most died within two weeks (n=36, 69%). After >2 weeks the IVI as a cause of death was uncertain. Among 193 insurance claims after vascular surgery during 2002-2007, nerve injuries (91) and wound infections (22) dominated. Most patients suffered permanent injuries, three died. Patients with insurance claims were correctly registered in the Swedvasc in 82%. In 32 cases of popliteal artery injury during knee arthroplasty symptoms were bleeding (n=14), ischaemia (n=7) and false aneurysm formation (n=11). Only twelve injuries (38%) were detected intraoperatively. Patency at 30 days was 97%, but only seven (22%) patients had complete recovery. Six of those had intraoperative diagnosis of popliteal injury and immediate vascular repair. In conclusion, registration of IVIs is increasing and outcome is often negatively affected by diagnostic and therapeutic delay. Not all fatalities after IVIs are attributable to the injury itself. The most common causes of insurance claims after vascular surgery were nerve injuries, and 82% were correctly registered in Swedvasc.

Objectives: Cardiovascular disease is the leading cause of mortality and morbidity in the developed world. Surgery can improve prognosis and relieve symptoms. Risk prediction models are increasingly being used to inform clinicians and patients about the risks of surgery, to facilitate clinical decision making and for the risk-adjustment of surgical outcome data. The importance of risk prediction models in cardiovascular surgery has been highlighted by the publication of cardiovascular surgery outcome data and the need for risk-adjustment. The overall objective of this thesis is to advance risk prediction modelling in cardiovascular surgery with a focus on the development of models for elective AAA repair and assessment of models for cardiac surgery. Methods: Three large clinical databases (two elective AAA repair and one cardiac surgery) were utilised. Each database was cleaned prior to analysis. Logistic regression was used to develop both regional and national risk prediction models for mortality following elective AAA repair. A regional model to identify the risk of developing renal failure following elective AAA repair was also developed. The performance of a widely used cardiac surgery risk prediction model (the logistic EuroSCORE) over time was evaluated using a national cardiac database. In addition an updated model version (EuroSCORE II) was validated and both models’ performance in emergency cardiac surgery was evaluated. Results: Regional risk models for mortality following elective AAA repair (VGNW model) and a model to predict post-operative renal failure were developed. Validation of the model for mortality using a national dataset demonstrated good performance compared to other available risk models. To improve generalisability a national model (the BAR score) with better discriminatory ability was developed. In a prospective validation of both models using regional data, the BAR score demonstrated excellent discrimination overall and good discrimination in procedural sub-groups. The EuroSCORE was found to have lost calibration over time due to a fall in observed mortality despite an increase in the predicted mortality of patients undergoing cardiac surgery. The EuroSCORE II demonstrated good performance for contemporary cardiac surgery. Both EuroSCORE models demonstrated inadequate performance for emergency cardiac surgery. Conclusions: Risk prediction models play an important role in cardiovascular surgery. Two accurate risk prediction models for mortality following elective AAA repair have been developed and can be used to risk-adjust surgical outcomes and facilitate clinical decision making. As surgical practice changes over time risk prediction models may lose accuracy which has implications for their application. Cardiac risk models may not be sufficiently accurate for high-risk patient groups such as those undergoing emergency surgery and specific emergency models may be required. Continuing research into new risk factors and model outcomes is needed and risk prediction models may play an increasing role in clinical decision making in the future.