| 1. |
- Lundberg, Christina, 1972-
(författare)
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Screening for Atherosclerosis with Magnetic Resonance Imaging and Ultrasound
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a major cause of death and disability worldwide. Although traditional risk factors can identify the healthy or severely affected individuals, sudden lethal outcome is still frequent in those suggested as intermediate in risk for cardiovascular events (CVE). Adding imaging to the traditional scoring systems might improve risk stratification.This thesis investigates whether the addition of magnetic resonance imaging (MRI) and ultrasound (US) to traditional risk factors might render atherosclerosis suitable for mass screening, selective screening or screening in research settings.In paper I the carotid arteries were assessed in six different manners (carotid intima media thickness (CIMT) in two different locations, presence of plaque, number of plaques, plaque size and plaque composition) using US. More than 800 Caucasian subjects were assessed at ages 70 and 75, and outcome examined at 80 years of age. Plaques with an area exceeding 10mm2 in the bulb were found to be most closely related to CVE.Paper II established that carotid plaque volume measured with MRI did not correlate with carotid plaque area assessed with US. MRI reached the highest levels of reproducibility of the two methods.Paper III used the previously created total atherosclerotic score (TAS), a scoring system based on whole body magnetic resonance angiography (WBMRA) that assesses global atherosclerosis. TAS was found to predict CVE in 305 PIVUS-subjects at age 70 years during 5 years of follow-up. The risk for CVE was found to be eightfold with TAS>0.In paper IV CIMT was assessed with US at ages 70 and 75 years. CIMT at baseline, but not the change in CIMT over five years, was significantly related to TAS, thus suggesting carotid changes to correlate with atherosclerosis throughout the body.In conclusion, in research settings WBMRA and MRI, as well as US, can be used for screening and following up of atherosclerotic changes, as their predictive values and reproducibility are good. US might be feasible in selective screening but none of these methods are as of now suitable for mass screening.
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| 2. |
- Mani, Kevin, 1975-
(författare)
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Abdominal Aortic Aneurysm : Epidemiological and Health Economic Aspects
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 3. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 4. |
- Ersryd, Samuel
(författare)
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Abdominal compartment syndrome and colonic ischaemia after abdominal aortic aneurysm repair in the endovascular era
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal Compartment Syndrome (ACS) and colonic ischaemia (CI) are serious and potentially lethal complications after open (OSR) and endovascular repair (EVAR) of ruptured (rAAA) and intact (iAAA) abdominal aortic aneurysms. The aims of this thesis were to investigate the incidence, outcome, and risk factors associated with ACS (Papers I-III) and to evaluate extraluminal colonic tonometry for postoperative surveillance of colonic perfusion (Paper IV).Papers I-III combined data from the nationwide Swedish vascular registry (Swedvasc) (2008-2015) with case records and radiologic imaging. Paper I investigated incidence and outcome of ACS. The incidence was approximately 7% for both EVAR and OSR after rAAA and 1.6% after OSR and 0.5% after EVAR for iAAA. ACS was associated with a more than two-fold (59% vs 27%) 90-day mortality after rAAA and six-fold (19% vs 3%) after iAAA. Paper II investigated risk factors and outcome among subgroups. Risk of death could not be attributed to a specific main pathology of ACS: CI, postoperative bleeding and general oedema, nor to timing of decompressive laparotomy in relation to AAA surgery. However, the duration of intra-abdominal hypertension (IAH) predicted the need for renal replacement therapy. Paper III investigated risk factors after EVAR for rAAA. ACS was rare without pronounced pre- or intraoperative physiologic derangement associated with circulatory instability. Aortic morphology did not impact ACS development, nor did presence of a patent inferior mesenteric and lumbar arteries, known risk factors for type II endoleak. Paper IV studied patients operated on for iAAA/rAAA (n=27), and demonstrated extraluminal colonic tonometry safe, reliable and indicative of CI among all affected patients (n=4).In conclusion, ACS was common after rAAA repair, with poor outcome irrespective of AAA repair technique and indication for repair. Outcome did not differ depending on the main pathophysiological finding associated with ACS development, while a longer duration of IAH increased the risk of renal replacement therapy. ACS after EVAR for rAAA was largely associated with pre- and intraoperative physiologic factors. These findings highlight the importance of vigilant intra-abdominal pressure measurement after rAAA repair and in case of haemodynamic instability, as well as timely interventions to treat IAH. Extraluminal colonic tonometry appears promising for surveillance of postoperative colonic perfusion.
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| 5. |
- Hager, Jakob, 1967-
(författare)
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Abdominal Aortic Aneurysm : Aspects on how to affect mortality from rupture
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal Aortic Aneurysm (AAA) is a disease that mainly affects elderly men, and ruptured AAA (rAAA) is associated with a mortality of > 80%. AAA seldom gives any symptoms prior to rupture.The aims of this thesis were to investigate different aspects of how to affect mortality from rAAA.In Study I, we identified 849 patients treated for rAAA during 1987-2004, and studied the 30-day survival after surgery, depending on whether they came directly to the treating hospital (one-stop) or were transferred via another hospital (two-stop). A two-stop referral pattern resulted in a 27% lower population-based survival rate for patients 65-74 years of age. However, the consequences would be small even if a one-stop referral pattern could be generally accomplished, due to the huge over-all mortality related to rAAA, hence an argument to find and treat AAA before rupture, e.g. by screening.In Study II, we examined the AAA-prevalence and the risk factors for AAA among 70-year-old men. The screening-detected AAA-prevalence was 2.3%, thus less than half the predicted. The most important risk factor was smoking.In Study III, we compared the screening-detected AAA-prevalence, the attendance rate, and the rate of opportunistic detection of AAA, between almost 8000 65- and 6000 70-year-old men. There was no difference in the screening-detected prevalence; probably due to the fact that almost 40% of the AAAs among the 70-year-old were already known prior to screening, compared to roughly 25% in the 65-year-old. The attendance rate was higher among the 65-year-old men, 85.7% compared 84.0% in the 70-year-old. Thus, there is no benefit of screening for AAA among 70- instead of 65-year-old men.In Study IV, a cost-effectiveness analysis, we found that screening for AAA still appears to be cost-effective, despite profound changes in disease pattern and AAA-management.In conclusion, we found that mortality from rAAA is not affected in any substantial way by different referral patterns and hence centralisation of services for AAA/rAAA is not a solution. A better alternative is to prevent rupture through early detection by screening. Screening 65-year-old men for AAA still appears to be cost-effective, despite profound changes in disease pattern and AAA-management during the last decade. Screening 70- instead of 65-year-old men will not increase the efficacy of screening.
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| 6. |
- Holsti, Mari, 1963-
(författare)
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Vascular remodelling and circulating basement membrane fragments in abdominal aortic aneurysm
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An abdominal aortic aneurysm (AAA) is a degenerative disease, characterized by advanced inflammation and extracellular matrix (ECM) remodelling. Enhanced protease activity mediated by cytokines results in the degradation of ECM proteins, leading to the generation of different bioactive fragments. Some of these generated fragments are released from the vascular basement membrane (VBM), a highly specialized ECM. VBM provides mechanical and structural stability and regulates many important cellular functions of the vascular system. Type IV and XVIII collagens are two structural proteins in VBM, with crucial roles in maintaining of the VBM integrity and vascular architecture. Circulating levels of type IV and XVIII collagen fragments are found physiologically, but have also been associated with many diseases. Remodelling of VBM and expression of its components has not been as well studied in AAA as that of the interstitial ECM.Here we investigate these VBM collagens, their expression and possible association with aortic diameter and expansion rate in individuals with an AAA in comparison with different control groups. Further we study whether there is a link between the circulating VBM collagen fragments and several inflammatory markers, all highly involved in AAA pathogenesis. Lastly, we study the impact of surgical intervention on plasma levels of VBM collagens in patients treated by either open surgical repair (OSR) or endovascular aortic aneurysm repair (EVAR).Methods: Circulating levels of type IV and XVIII collagen fragments were analysed in individuals with an AAA and compared with healthy controls and patients with peripheral artery disease (paper I). A possible association between VBM collagen fragments and the aortic diameter and expansion was studied in a large population-based cohort of 615 men stratified into three aortic diameter groups based on initial maximum aortic diameter (paper II). Furthermore, 159 individuals were followed up over time with repeated measurements of aortic diameter and blood samples. The follow up cohort were divided into two subgroups based on expansion rate of AAA. Moreover, the location of VBM collagens in tissue from aortic wall in individuals with an AAA was characterized and the expression pattern was compared with normal aorta (paper II). In paper III, the association between the plasma levels of VBM collagens and inflammatory markers; IL-1 (IL-1α and IL-1β), IL-6, IL-8, TNF-α INF-γ and hs-CRP were studied in same cohort as paper II. Finally, the effect of surgical intervention on circulating levels of VBM collagen fragments was investigated in AAA patients who had undegone either OSR or EVAR by comparison of plasma levels before and after AAA repair.Ultrasound technique was used for measurements of aortic diameter (paper I, II, III and IV). Analysis of circulating VBM collagens and inflammatory markers were performed by ELISA-assay (Paper I, II, III and IV) and Multiplex-assays, respectively (paper III). Aortic wall tissues were analysed by haematoxylin and eosin (H&E) and immunofluorescence staining (Paper II).Results: There were significantly increased plasma levels of VBM collagen fragments in individuals with an AAA, compared with healthy controls and individulas with a peripheral artery disease (PAD), (Paper I). The levels of type IV collagen in AAA patients did not differ from the group with PAD, and there were no significant differences between the control groups regarding plasma levels of both VBM collagen fragments (Paper I). The increased levels of VBM collagen fragments were significantly associated with aortic diameter with highest levels in the group with an AAA (Paper II). Altered expression of the VBM collagens and fragmentation of elastic fibres were observed in tissue from AAA patients (Paper II). A significant association between the levels of pro-inflammatory cytokines IL-6 and IL-8, and VBM collagens was found. Additionally, there were a significant association between the plasma levels of IL-8, TNF-α and hs-CRP and an AAA (Paper III). Aneurysms with faster expansion rate had significantly higher levels of IL-6, IL-1β, and type XVIII/endostatin collagen. Additionally, IL-6, type XVIII/endostatin collagen and baseline-aortic diameter were significantly associated with expansion rate (Paper III). AAA repair was associated with changes in plasma levels of VBM collagens (Paper IV).Conclusion: Circulating levels of VBM collagens were increased in patients with an AAA, and significantly associated with aortic diameter and expansion rate. The expression of VBM collagens was altered in AAA tissue compared with normal aorta. In addition, plasma levels of several inflammatory markers were associated as with VBM collagens, aortic diameter and expansion rate. The levels of both VBM collagens were altered at short and long time after AAA repair.
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| 7. |
- Högberg, Dominika
(författare)
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Screening for asymptomatic carotid atherosclerosis
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 8. |
- Lyttkens, Linda
(författare)
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Health Related Quality of Life in patients with screening detected Sub-Aneurysmal aorta and Abdominal Aortic Aneurysm
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective Paper I: Most screening and opportunistically detected abdominal aortic aneurysms (AAA) are small and kept under surveillance for several years before preventive surgery. Living with the diagnosis of an AAA may have an influence on the patient’s life. The aim was to review systematically review the current knowledge of the effect on health related quality of life (HRQoL) and patients’ experiences of living with an AAA while under surveillance.Paper II: To investigate HRQoL and comorbidity in men with screening detected AAA, Sub-Aneurysmal aorta (SAA) and Controls at baseline screening and after long-term follow-up.Methods Paper I: A systematic literature review of quantitative and qualitative studies, which were quality assessed according to the GRADE system, was carried out. PubMed, Cochrane, Embase, CINAHL, PsycINFO, and MEDLINE were searched. Narrative synthesis and meta-analysis were performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Paper II: Between 2006 and 2015, 16 689 sixty-five-year old men participated in the aortic screening program in the county of Uppsala in Sweden. All 539 men diagnosed with an SAA or AAA were invited to participate in the study UpAAA and 324 accepted. Baseline questionnaires was distributed after screening, and at 5-year follow-up. For each year a control group of approx. 50 men, participating in the screening program with normal aorta, were included. ResultsPaper I: Synthesis and meta-analyses of studies based on the Short Form-36 demonstrated that patients with an AAA consistently rated their general health lower than controls and conveyed no significant negative impact for patients with an AAA when assessed at follow up and compared with pre-screening. Analysis of HRQoL estimates of mental health, anxiety, and depression demonstrated no significant differences for patients with AAA compared with controls, or within the AAA group. Qualitative studies revealed that patients with an AAA felt safe being under surveillance and receiving a diagnosis of AAA set thoughts and feelings in motion regarding health, ageing, and mortality. Patients’ lack of knowledge about the disease, its progression, and future planning can cause insecurity and worries.Paper II: AAA and SAA group both has impairment in the physical dimensions of HRQOL and a higher prevalence of co-morbidity at baseline, compared to controls. At 5-year follow-up, the similarities between AAA and SAA group remained with no difference in HRQOL but a higher prevalence of CVD, hypertension and diabetes in men with AAA. Compared with controls both AAA and SAA had significantly higher impairment in HRQoL, and prevalence of co-morbidity and the AAA group was most affected.
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| 9. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Rationale for a Swedish cohort consortium
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 124:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.
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| 10. |
- Sörelius, Karl, 1981-
(författare)
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Aortic infections : The Nadir of Vascular Surgery
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aortic infections are rare, life-threatening and constitute a major challenge in surgical management. This thesis aims to evaluate short – and long-term outcome of endovascular aortic repair (EVAR) for mycotic aortic aneurysms (MAA) and the subsequent risk of recurrent infections, changes in surgical practice over time for abdominal MAAs in Sweden and outcome for different treatment modalities, as well as the risk of secondary vascular infection after treatment with Open abdomen after aortic surgery.Paper I, a retrospective single centre study of patients with MAA treated with EVAR, demonstrated a good short-term outcome, 91% survival at 30-days, and acceptable mid-term survival, 73% at 1-year.Paper II, a retrospective international multicentre study of patients treated with EVAR for MAA, confirmed the results in paper I, and showed that EVAR is feasible and for most MAA patients a durable treatment option, 5-year survival was 55% and 10-year 41%. A total of 19% died from an infection-related complication, mostly during the first postoperative year. Non-Salmonella-positive culture was a predictor for late infection–related death.Paper III, a population-based cohort study on all abdominal MAAs operated on between 1994-2014 in Sweden. Overall survival was 86% at 3-months, 79% at 1-year and 59% at 5-years. The survival was significantly better after endovascular compared to open repair up to 1-year without increasing recurrence of infection or reoperation, thereafter there was no difference. After 2001 EVAR constituted 60 % of all repairs, thus indicating a paradigm shift in treatment for abdominal MAAs in Sweden.Paper IV, a prospective multicentre study of patients treated with open abdomen after aortic surgery. Infectious complications, such as graft infections, occurred after intestinal ischaemia and prolonged OA-treatment, and were often fatal.
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| 11. |
- Tegler, Gustaf
(författare)
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Abdominal Aortic Aneurysm : Molecular Imaging Studies of Pathophysiology
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The pathological process behind abdominal aortic aneurysm (AAA) formation is poorly understood and difficult to study. The aim of the thesis was to study the pathophysiology of AAA formation with positron emission tomography (PET) technology, a molecular imaging technique, allowing in vivo studies of pathophysiological changes.In study I 18F-FDG, a glucose analogue, was tested. It had previously been reported as a useful tracer studying inflammation in AAAs. These studies included, however, foremost large, symptomatic, and inflammatory AAAs. In the present study on five small and seven large asymptomatic AAAs, no increase in 18F-FDG uptake could be revealed in vivo.In study II 11C-PK11195, a macrophage tracer, and 11C-D-deprenyl, an unspecific inflammatory tracer, previously never tested on asymptomatic AAAs, were tested in vivo on five and 10 AAA-patients respectively, without signs of increased levels of inflammatory activity in the aorta.In study III several tracers were screened in vitro through autoradiography on AAA tissue. [18F]fluciclatide, targeting the integrin αVβ3 receptor upregulated in angiogenesis, was the only tracer with an increased uptake.In study IV [18F]fluciclatide-autoradiography was performed on AAA tissue from five patients and non-aneurysmal aortic tissue obtained from five age and sex matched organ donors. The study showed a 56% increased specific uptake in AAA, although not significant (P=0.136). Immunohistochemical revealed inflammatory cell foci in close relation to the vessels.In conclusion, PET has potential to elucidate the pathophysiology of AAA formation. For the large group of small asymptomatic AAAs, 18F-FDG is not suitable, as the chronic inflammation in asymptomatic AAA is not sufficiently metabolically active. Furthermore, 11C-PK11195 and 11C-D-deprenyl were unable to show the chronic inflammation seen in asymptomatic AAA.The interesting finding with uptake of [18F]fluciclatide showed that angiogenesis may be imaged in large asymptomatic AAAs in vitro, through the integrin αVβ3 receptor. Thus, it is likely that future studies of the role of angiogenesis in AAA formation in vivo, in small AAAs, could use this target site. The development of an integrin αVβ3 receptor tracer, preferably with higher affinity, is in progress for further in vitro and in vivo studies.
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| 12. |
- Thorbjørnsen, Knut
(författare)
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Aspects of subaneurysmal aortas in a screening setting
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With the introduction of screening programmes for abdominal aortic aneurysm (AAA) more individuals are being identified with a subaneurymal aorta (SAA; diameter 25-29mm). More recent data indicate that these aortas may not be as harmless as previously thought, but there is, however, no general agreement on how SAA should be managed.The aims of this thesis were to study men with screening detected SAA, regarding: (I) prevalence, risk factors and comorbidities; (II), the long-term natural course regarding development to AAA ≥30mm, in particular the progression to AAA ≥55mm, to assess the AAA repair rate, turn down, and mortality rates; (III) the association between aortic morphological baseline factors; (SAA diameter, aortic index related to height and body surface area as well as relative aortic diameter to proximal aorta) and the risk for later progression to AAA ≥55mm; and (IV) describe health utility (HU) values and compare them in men with screened AAA, SAA and in men with normal aortic diameters.There was a marked similarity in the risk factor profile between men with SAA representing 2% of the screening population and men with AAA with smoking as the most important risk factor, with an incremental association between smoking and disease severity. Most SAAs eventually progress to an AAA ≥30mm, of which 30% eventually reach the threshold for AAA-repair within 10 years. A follow-up policy with an ultrasound scan after five years can safe and effectively identify those at risk of developing clinically relevant AAAs, and should be considered for anyone with reasonably good life expectancy. Baseline SAA diameter, aortic size index, and aortic height index were all independently associated with progression to AAA ≥55mm, with aortic size index as the strongest predictor, whereas relative aortic diameter was not. These morphological factors may be considered for stratification of follow-up at initial screening. At baseline screening, HUs were similar between men with AAA, SAA, and normal aortas. Compared to SAAs and controls, lower health utility scores were observed in men with AAA after five years, most likely associated with higher frequency of smoking and comorbidities.
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| 13. |
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| 14. |
- Bengts, Sophy, et al.
(författare)
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Altered IL-32 Signaling in Abdominal Aortic Aneurysm
- 2020
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Ingår i: Journal of Vascular Research. - : KARGER. - 1018-1172 .- 1423-0135. ; 57:4, s. 236-244
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Tidskriftsartikel (refereegranskat)abstract
- Introduction and Objective:Interleukin (IL)-32 is a pro-inflammatory cytokine not previously studied in relation to abdominal aortic aneurysm (AAA). The aim of this study was to elucidate the expression and localization of IL-32 in AAA.Methods:Expression and localization of IL-32 in human aortic tissue was studied with immunohistochemical analysis and Western blot (AAA:n= 5; controls:n= 4). ELISA was used to measure IL-32 in human plasma samples (AAA:n= 140; controls:n= 37) and in media from cultured peripheral blood mononuclear cells (PBMCs) from 3 healthy donors. IL-32 mRNA in PBMCs, endothelial cells, aortic smooth muscle cells (SMCs), and aortic tissue samples of AAA (n= 16) and control aortas (n= 9) was measured with qPCR.Results:IL-32 was predominantly expressed in SMCs and T-cell-rich areas. Highest mRNA expression was observed in the intima/media layer of the AAA. A weaker protein expression was detected in non-aneurysmal aortas. Expression of IL-32 was confirmed in isolated T cells, macrophages, endothelial cells, and SMCs, where expression was also inducible by cytokines such as interferon-gamma. There was no difference in IL-32 expression in plasma between patients and controls.Conclusion:IL-32 signaling is altered locally in AAA and could potentially play an important role in aneurysm development. Further studies using animal models would be helpful to study its potential role in AAA disease.
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| 15. |
- Djavani Gidlund, Khatereh
(författare)
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Intra-abdominal Hypertension and Colonic Hypoperfusion after Abdominal Aortic Aneurysm Repair
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colonic ischaemia (CI), Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are devastating complications after abdominal aortic aneurysm (AAA) surgery. The aims of this thesis were to study the incidence and clinical consequences of IAH/ACS and the association between CI and intra-abdominal pressure (IAP) among patients undergoing OR for ruptured AAA (rAAA), to compare extraluminal pHi monitoring, with standard intra-luminal monitoring among patients operated on for AAA, and to study the frequency and clinical consequences of IAH/ACS after endovascular repair (EVAR) for rAAA. The incidence of ACS was 26% in a retrospective study of 27 patients undergoing OR for rAAA. Consensus definitions on IAH/ACS were appropriate for patients after OR for rAAA: 78% (7/9) of patients with IAH grade III or IV developed organ failure and all patients who developed CI had some degree of IAH. Active fluid resuscitation treating hypovolaemia to avoid CI may partly cause IAH. The association between CI and IAP was investigated in a prospective study on 29 patients operated on for rAAA, 86% (25/29) were treated for hypovolaemia and ten (34%) had both IAH and CI. Since monitoring colonic perfusion is very important and there is no ideal method, a new technique, extraluminal colonic tonometry to detect colonic perfusion was compared with standard intraluminal tonometry. Although, this new method was not able to determine the severity of ischaemia it may serve as a screening test. EVAR of rAAA is feasible and patients may benefit from this less invasive procedure. Of 29 patients treated with this technique, 10% developed ACS, and all patients except one with preoperative shock developed some degree of IAH. In conclusion, IAP/ACS is common after both OR and EVAR for rAAA, and is associated with adverse outcome. Monitoring IAP and colonic perfusion with timely intervention may improve outcome.
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| 16. |
- Estrada, Sergio, et al.
(författare)
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Preclinical evaluation of [C-11]GW457427 as a tracer for neutrophil elastase
- 2022
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Ingår i: Nuclear Medicine and Biology. - : Elsevier. - 0969-8051 .- 1872-9614. ; 106-107, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Neutrophils are part of the innate immune system and function as a first line of defense against invading microorganisms. Overactivity of the immune system may result in a devastating immuno-inflammation with extensive damage to tissue leading to organ damage and/or failure. The literature suggests several human diseases in which neutrophil elastase (NE) is postulated to be important in the pathophysiology including inflammatory bowel disease (IBD), chronic obstructive pulmonary disorder (COPD), abdominal aortic aneurysms (AAA), breast and lung cancer, and recently also in Sars-cov-2 virus infection (Covid-19). In particular, the lungs are affected by the destructive power of the protease neutrophil elastase (NE). In this paper, we report the pre-clinical development of a selective and specific positron emission tomography (PET) tracer, [C-11] GW457427, as an in vivo biomarker for the study of NE, now available for human studies.Methods: [C-11]GW457427 was produced by methylation of GW447631 using [C-11]methyl triflate and GMP validated production and quality control methods were developed. Chemical purity was high with no traces of the precursor GW611437 or other uv-absorbing compounds. A method for the determination of intact [C-11] GW457427 in plasma was developed and the binding characteristics were evaluated in vitro and in vivo. An animal model for lung inflammation was used to investigate the specificity and sensitivity of the [C-11]GW457427 tracer for neutrophil elastase (NE) in pulmonary inflammation, verified by blockade using two structurally different elastase inhibitors.Results: [C-11]GW457427 was obtained in approximately 45% radiochemical yield and with a radiochemical purity higher than 98%. Molar activity was in the range 130-360 GBq/mu mol. Binding to NE was shown to be highly specific both in vitro and in vivo and a significantly higher uptake of tracer was found in a lipopolysaccharide mouse model of pulmonary inflammation compared with control animals. The uptake in lung tissue measured as standardized uptake value (SUV) strongly correlated with tissue NE content as measured by ELISA. In vitro studies also showed specific tracer binding in aortic tissue of patients with abdominal aorta aneurysm (AAA). The rate of metabolism in rats was appropriate considering the critical balance between available tracer for binding and requirement for blood clearance with about 40% and 20% intact [C-11]GW457427 in plasma at 5 and 40 min, respectively. Radioactivity was cleared from blood and organs in control animals with mainly hepatobiliary excretion with distribution in the intestines and the urinary bladder; but without retention of the tracer in healthy organs of interests such as the lung, liver, kidneys or in the cardiovascular system. A dosimetry study in rat indicated that the whole-body effective dose was 2.2 mu Sv/MBq with bone marrow as the limiting organ. It is estimated that up to five PET-CT investigations could be performed in humans without exceeding a total dose of 10 mSv.Conclusion: [C-11]GW457427 is a promising in vivo PET-biomarker for NE with high specific binding demonstrated both in vitro and in vivo. A GMP validated production method including quality control has been developed and a microdosing toxicity study performed with no adverse signs. [C-11]GW457427 is currently being evaluated in a First-In-Man PET study.
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| 17. |
- Gabel, Gabor, et al.
(författare)
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Parallel Murine and Human Aortic Wall Genomics Reveals Metabolic Reprogramming as Key Driver of Abdominal Aortic Aneurysm Progression
- 2021
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:17
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Tidskriftsartikel (refereegranskat)abstract
- Background: While numerous interventions effectively interfered with abdominal aortic aneurysm (AAA) formation/progression in preclinical models, none of the successes translated into clinical success. Hence, a systematic exploration of parallel and divergent processes in clinical AAA disease and its 2 primary models (the porcine pancreatic elastase and angiotensin-II infusion [AngII] murine model) was performed to identify mechanisms relevant for aneurysm disease.Methods and Results: This study combines Movat staining and pathway analysis for histological and genomic comparisons between clinical disease and its models. The impact of a notable genomic signal for metabolic reprogramming was tested in a rescue trial (AngII model) evaluating the impact of 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15)-mediated interference with main glycolytic switch PFKFB3. Histological evaluation characterized the AngII model as a dissection model that is accompanied by adventitial fibrosis. The porcine pancreatic elastase model showed a transient inflammatory response and aortic dilatation, followed by stabilization and fibrosis. Normalization of the genomic responses at day 14 confirmed the self-limiting nature of the porcine pancreatic elastase model. Clear parallel genomic responses with activated adaptive immune responses, and particularly strong signals for metabolic switching were observed in human AAA and the AngII model. Rescue intervention with the glycolysis inhibitor PFK15 in the AngII model showed that interference with the glycolytic switching quenches aneurysm formation.Conclusions: Despite clear morphological contrasts, remarkable genomic parallels exist for clinical AAA disease and the AngII model. The metabolic response appears causatively involved in AAA progression and provides a novel therapeutic target. The clear transient genomic response classifies the porcine pancreatic elastase model as a disease initiation model.
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| 18. |
- Holmberg, Lina
(författare)
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Trauma Care - Implementation, Evaluation and Validation
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trauma is a major cause of death and morbidity in all ages, which makes continuous improvement of trauma care a high priority. During the last decades, Sweden’s trauma system has evolved with initiation of a national trauma registry (SweTrau) in 2011 and the Swedish National Trauma Triage criteria (SNTTC) in 2017. However, the Swedish trauma panorama has evolved as well, something this thesis aimed to explore, alongside with evaluating the safety and accuracy of the SNTTC and performing the first validation of SweTrau. Paper I is a prospective stepped-wedge cohort study, showing unchanged 30-day mortality, over- and undertriage after the implementation of the SNTTC, as well as a reduction of the lowest level of trauma call by almost 50%, proving that the SNTTC are safe to use. In Paper II, a retrospective multicentre cohort study, the SNTTC are further investigated, displaying a sensitivity of almost 85% while also assessing specificity, positive predictive value (PPV) and positive likelihood ratio (LR+). With no additional enhancing criteria found, the SNTTC are concluded to efficiently identify severely injured patients. Paper III reports the first validation of SweTrau; an on-site re-registration compared with the original registration in SweTrau. It demonstrates that the data in SweTrau is reliable, with high accuracy (85.8%), correctness (89.7%), data completeness (88.5%) and correlation (87.5%), while being comparable to international trauma registries using the Utstein template of trauma. Case completeness and timeliness are identified as areas of improvement. In Paper IV, nine-year trauma trends in two major trauma centres are analysed in a retrospective cohort study. A sharp reduction in intensive care unit admissions is seen, as well as a worrying increase in penetrating trauma (>50%) and mortality for patients with a low injury severity score (1.3%-2.7%, p=0.005), all of which require further investigation. In conclusion; this thesis has confirmed that the SNTTC are safe and efficient, as well as pin-pointed important trauma areas to focus on in the future. Finally, it has established the validity of the data in SweTrau - a major source of Swedish trauma research.
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| 19. |
- Kunath, Anne, et al.
(författare)
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Inhibition of angiotensin-induced aortic aneurysm by metformin in apolipoprotein E-deficient mice
- 2021
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Ingår i: JVS-Vascular Science. - Philadelphia, PA, United States : Elsevier. - 2666-3503. ; 2, s. 33-42
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Metformin is associated with a reduced incidence and growth of abdominal aortic aneurysms (AAAs). The aim of the present study was to investigate the inhibitory effects of metformin on AAA development and possible underlying mechanisms in experimentally induced AAAs in mice, along with the possible synergistic effects of metformin and imatinib.Methods: Angiotensin II was used to induce AAAs in apolipoprotein E knockout (ApoE -/- ) mice for 28 days. The mice were treated with metformin (n = 11), metformin combined with imatinib (n = 7), or vehicle (n = 12), starting 3 days before angiotensin II infusion. Ultrasound examination was used to analyze aneurysm formation. Cholesterol and blood pressure levels were measured at the start and end of the study. Gene array and quantitative polymerase chain reaction were used to analyze the changes in gene expression in the aorta. Wire myography was used to study vascular function.Results: Metformin (n = 11) suppressed the formation and progression of AAAs by 50% compared with the vehicle controls (n = 12), with no further effects from imatinib (n = 7). Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a. Furthermore, metformin inhibited blood pressure increases and reduced vascular contractions, as determined by wire myography, and restored the anticontractile function of perivascular adipose tissue.Conclusion: Metformin inhibited aneurysm formation and progression and normalized vascular function in ApoE -/- mice with no additional effect of imatinib. This might be mediated by the protective effects on vascular endothelial function and perivascular adipose tissue via reduced expression of genes promoting inflammation, including SPP1, MMP12, Gpnmb, and Clec7a.Clinical relevance: Retrospective studies of the effects of metformin in patients with aneurysm have so far only been performed of those with type 2 diabetes. The present study shows that metformin has effects on nondiabetic mice and revealed the mechanistic effects mediated by the drug that could also be important to study as outcomes in humans. Future clinical trials using metformin are warranted in patients without diabetes with abdominal aortic aneurysms.
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| 20. |
- Kuzniar, Marek
(författare)
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On Pathophysiology and Treatment of Aortic Disease
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pathophysiological processes underlying abdominal aortic aneurysm (AAA) formation and aortic dissections (AD) are largely unknown. Molecular imaging of the inflammatory component may improve our understanding of AAA and AD pathophysiology. The aims of this thesis were to evaluate the feasibility of positron emission tomography/magnetic resonance imaging (PET/MRI) to study in vivo pathophysiological changes of these aortic pathologies, and to study the outcomes after complex contemporary endovascular treatment thereof.In Paper I, we evaluated the feasibility of 18-F-fluorodeoxyglucose (FDG) PET/MRI to identify markers for inflammation in asymptomatic medium-large AAA. We identified FDG uptake and gadolinium enhancement (GE) in the aneurysmal wall, however FDG uptake corresponded rarely with mural inflammatory changes on MRI. In Paper II, we investigated whether inflammatory activity by means of FDG-PET/MRI can be detected in small to medium sized AAA, confirming the presence of inflammatory markers in the majority of patients. In Paper III, FDG-PET/MRI was used to characterize the inflammation and its transformation from acute to chronic phase in acute Stanford type B dissections. Highly increased FDG-activity was present in the dissected descending aorta in the acute phase, which markedly decreased over the course of a few months. MRI inflammatory changes were present in 60% of patients.In Paper IV, we evaluated the outcome and aortic remodelling after thoracic endovascular aortic repair (TEVAR) for chronic dissections. High rate of false lumen thrombosis occurred for dissections localized to the thoracic aorta covered by the stent-graft, but was more uncommon for extensive dissections distally. Aortic remodelling and sac shrinkage occurred in the thoracic aorta, but not distally. Reintervention rates were substantial (one third of cases). Paper V evaluated outcome of complex endovascular repair of post-dissection aneurysms of the arch and thoraco-abdominal aorta. Results were comparable to other recent reports using this new approach, however occurrence of retrograde Stanford type A dissection following arch fenestrated repair warrants caution.In conclusion, FDG-PET/MRI is a promising technique for studying inflammation in AAAs and ADs in vivo. For chronic aortic dissections, endovascular treatment results in good short-term outcome, but in the long-term re-interventions were common and adequate follow-up is thus of importance
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| 21. |
- Ravn, Hans, 1958-
(författare)
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Popliteal Artery Aneurysm : Epidemiology, Surgical Management and Outcome
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Even if popliteal artery aneurysm (PAA) is the most common peripheral aneurysm, no single surgeon or institution has enough patients to study this disease with appropriate scientific methods, and no population-based investigation exists. PAA epidemiology, treatment, management, and outcome were studied in a population-based study of 571 patients (717 legs) primarily operated on for PAAs and 100 episodes of preoperative thrombolysis in Sweden between 1987 and 2002. Patients were identified in the Swedish Vascular Registry and case-records were reviewed. Information on amputation and survival was obtained for all patients, and 190 patients were re-examined with ultrasound, after mean 7.2 years (range 2-18)Median age was 71 years; 5.8% were women. Patients with unilateral PAA had AAA in 28%, increasing to 38% when PAAs were bilateral. Crude survival was 91.4% at one and 70% at five years, significantly lower than among age and sex matched controls. The cumulative incidence for operation of PAA in Sweden was estimated to 8.3/million person year. One-year amputation-rate was 8.8 %, increasing to 11% after follow-up (7.2 years). Independent risk factors for amputation within one year were poor run-off, age, emergency procedure, and prosthetic graft. Run-off was improved by preoperative thrombolysis among 87% of legs, when acute ischemia. After surgical repair with a medial approach the risk of late expansion of the aneurysm was 33%, with a posterior approach 8% , p=0.014. Among 190 re-examined patients, 108 (57%) had at least one additional aneurysm at index-operation, increasing to 131 (68%) at re-examination, the total number of aneurysms increasing by 42% (from 244 to 346).Conclusions: Multiple aneurysms are common among patients operated on for PAA. Preoperative thrombolysis improves run-off and decreases the amputation-rate in PAAs with acute ischemia. Vein grafts do better than prosthetic grafts, especially when a long bypass is needed. Posterior approach, when possible, reduces the risk of late expansion. A complete examination of the aorto-iliac and femoro-popliteal arteries is warranted at the time of surgery. All patients should be kept under life-long surveillance in order to detect and treat newly developed aneurysms timely. Normal arterial segments should be re-examined after three years.
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| 22. |
- Rossignoli, Aranzazu, et al.
(författare)
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Plasma cholesterol lowering in an AngII-infused atherosclerotic mouse model with moderate hypercholesterolemia
- 2018
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 42:1, s. 471-478
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is the main underlying causes of cardiovascular disease. There is a well‑established association between high blood cholesterol levels and the extent of atherosclerosis. Furthermore, atherosclerosis has been proposed to augment abdominal aortic aneurysm (AAA) formation. As patients with AAA often have parallel atherosclerotic disease and are therefore often on cholesterol‑lowering therapy, it is not possible to fully address the independent effects of plasma cholesterol lowering (PCL) treatment on AAA. The present study investigated the effect of angiotensin II (AngII)‑infusion in modestly hypercholesterolemic Ldlr‑/‑Apob100/100Mttpflox/floxMx1‑Cre mice with or without PCL treatment on a morphological and molecular level, in terms of atherosclerosis and AAA development. AngII infusion in the study mice resulted in an increased atherosclerotic lesion area and increased infiltration of inflammatory leukocytes, which was not observed in mice with PCL induced prior to AngII infusion. This suggested that AngII infusion in this mouse model induced atherosclerosis development, and that plasma cholesterol levels represent a controlling factor. Furthermore, AngII infusion in Ldlr‑/‑Apob100/100Mttpflox/floxMx1‑Cre mice caused a modest aneurysmal phenotype, and no differences in AAA development were observed between the different study groups. However, the fact that modest hypercholesterolemic mice did not develop AAA in a classical aneurysmal model indicated that plasma cholesterol levels are important for disease development.
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| 23. |
- Wanhainen, Anders, 1966-
(författare)
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Abdominal Aortic Aneurysm : Experience from a Screening Study in Northern Sweden
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal aortic aneurysm (AAA) is a common problem with life-threatening consequences and was suspected to be a serious health problem in Norsjö, a municipality in northern Sweden. A screening study was undertaken to investigate the prevalence, risk factors associated with AAA and the effect of screening on quality of life (QoL). All men and women, aged 65-75 years, were invited to an ultrasonography (US) examination, 91% attended and 92 subjects were also evaluated with computed tomography (CT).Depending on diagnostic criteria, the AAA prevalence was 3.6-16.9% in men and 0.8-9.4% in women. Seventy-five percent of the differences between US- and CT anteroposterior measurements were less than 5 mm. A decrease in mental health was observed among AAA patients with low baseline SF-36 scale scores. Elevated cholesterol at age 60 years were associated with screening detected AAA after 12 years of follow-up. Smoking, atherosclerosis and having a first degree relative with AAA were associated with AAA at screening. Compared to blood samples obtained 12 years prior to screening an elevation of hsCRP over time was observed among AAA patients. Based on a systematic review of the literature, different screening strategies were analysed in a Markov cohort model. The cost per life year gained ranged from $8 309 to $14 084 and was estimated to $10 474 when 65 year old men were screened once.Conclusions: The highest prevalence of AAA ever reported, in a population-based screening program, was found in Norsjö. The risk of having an AAA at screening showed a strong but complex association with atherosclerosis and its risk factors, genetic and inflammatory mechanisms may also be important. Screening 65-year-old men for AAA may be cost-effective, but QoL aspects on the cost-effectiveness of AAA screening merits further investigation.
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| 24. |
- Wågsäter, Dick, Professor, et al.
(författare)
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Circulating microRNA in patients with popliteal and multiple artery aneurysms
- 2021
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Ingår i: JVS-vascular science. - : Elsevier. - 2666-3503. ; 2, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with popliteal artery aneurysm (PA) often have multiple aneurysms, such as bilateral disease or a concomitant abdominal aortic aneurysm (AAA). microRNAs (miRs) are regulators of biological processes and have been investigated as biomarkers for AAA. The aim of this study was to explore if the presence of multiple aneurysms and/or location correlated with miR levels in blood.Methods: Using quantitative polymerase chain reaction, 23 miRs were analyzed in plasma from 183 patients with PA.Results: Fifteen of the miRs were associated with the number and/or location of aneurysms (1.3- to 2.1-fold changes). Levels of miR-93 (1.4-fold) and miR-215 (1.6- to 1.9-fold) were changed in all compared groups. MiR-24 and miR-23a were altered in those with AAA (1.4- and 1.5-fold, respectively) or bilateral PA (1.5- and 1.4-fold, respectively), compared with in those without. MiR-145 were significantly altered (1.7-fold) in those with isolated PA and AAA, whereas miR-326 were altered in those with bilateral (2.3-fold) and isolated PA (1.9-fold).Conclusions: Different miRs seem to be important or to be markers for different subgroups of patients with PA. The identified miRs target vascular smooth muscle cell proliferation and vascular inflammation. Further studies are needed to increase the understanding of the pathogenesis of aneurysmal disease.
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| 25. |
- Wågsäter, Dick, Professor, et al.
(författare)
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miR-10b promotes aortic aneurysm formation and aortic rupture in angiotensin II-induced ApoE-deficient mice
- 2021
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Ingår i: Vascular pharmacology. - : Elsevier. - 1537-1891 .- 1879-3649. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal aortic aneurysm (AAA) is associated with increased plasma levels of microRNA (miR) -10b. 5 nmols of miR-10b or miR control was administrated to Apolipoprotein E-deficient mice three days prior implantation of osmotic mini-pumps containing angiotensin II, and for three additional times once a week, which increased expression of miR-10b in plasma. Animals receiving miR-10b had a mortality rate due to aortic rupture of 61% compared to 11% in the miR controls (p < 0.05). Further, miR- 10b resulted in an increased aneurysm formation and growth (p < 0.05), which was accompanied by increased elastin degradation, neutrophil and mast cell markers (p < 0.05). In conclusion, miR-10b is functionally affecting aneurysm development and rupture and not only a marker of AAA. More mechanistic studies are required to better understand miR-10b's role in AAA formation.
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| 26. |
- Yoon, William J., 1984-
(författare)
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Advancing Endovascular Management of Thoracic Aortic Disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite technological advances and new endograft designs, endovascular treatment of the thoracic aorta still has important limitations. The aims of this thesis were to obtain further understanding on specific limitations in treating complex thoracic aortic pathologies with current technologies, to gain more insights into the hemodynamic consequences of thoracic endografting, and to explores the potential of deep learning algorithm-based automatic assessment of follow-up CTA imaging.Limitations imposed by the aortic arch branches on the proximal landing zone (PLZ) remain the biggest challenge for thoracic endovascular aortic repair (TEVAR). When left subclavian artery (LSA) preservation is required to obtain an adequate PLZ, single-branched endografts, such as the thoracic branch endoprosthesis (TBE), offer a complete endovascular solution, but still are limited by the lack of understanding of the hemodynamic effects and long-term data on clinical performance. Paper I explored the impact of TBE implantation on the LSA hemodynamics using computational fluid dynamic (CFD) analysis. It was shown TBE implantation produces modest hemodynamic disturbances which are unlikely to result in clinically relevant changes.Paper II evaluated the anatomic feasibility of TBE in blunt traumatic aortic injury patients who would require LSA revascularization. Only 32% of these patients had met all the anatomic requirements, justifying the need for additional designs. It was also shown that significant morphologic differences in arch anatomy exist between thoracic aortic pathologies.A major challenge in treating aortic dissection is unsatisfactory compliance of the distal portion of stent-grafts in a dissected aorta. Paper III evaluated the hemodynamic effect of a novel dissection-specific stent-graft (DSSG) with the aim to prevent distal stent graft-induced new entry (dSINE). The CFD analysis showed changes in shear-stress distribution different from that with standard thoracic stent-graft, transitioning high wall shear stress gradient zones into the stent-covered aorta. This transition may help prevent intimal injury and consequent dSINE development.Despite close surveillance imaging, early signs of endograft component separation resulting in type IIIa endoleak and sac repressurization are easily missed. Paper IV developed an AI-assisted fully automated CT image assessment method for early detection of endograft component separation and explored its potential.In depth understanding of the limitations of TEVAR helps continue progress in providing optimal patient- and pathology-specific endovascular solutions. CFD-based hemodynamic analysis and AI-driven automated image assessment have the potential to aid in TEVAR optimization.
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