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Tegler, Gustaf
Publications (10 of 11) Show all publications
Holsti, M., Wanhainen, A., Lundin, C., Björck, M., Tegler, G., Svensson, J. & Sund, M. (2018). Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue. European Journal of Vascular and Endovascular Surgery, 56(1), 110-118
Open this publication in new window or tab >>Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue
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2018 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 56, no 1, p. 110-118Article in journal (Refereed) Published
Abstract [en]

Objective: Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised.

Methods: This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta <= 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA >= 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence.

Results: Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue.

Conclusion: Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall.

Place, publisher, year, edition, pages
W B SAUNDERS CO LTD, 2018
Keywords
Abdominal aortic aneurysm, Collagen, Basement membrane, Extracellular matrix, Circulation
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-365839 (URN)10.1016/j.ejvs.2018.03.002 (DOI)000444270700019 ()29656960 (PubMedID)
Funder
Swedish Research Council, K2013-64X-2040607-3Västerbotten County Council, VLL-582791Västerbotten County Council, VLL-680121Västerbotten County Council, VLL-764621Swedish Heart Lung Foundation, 2012-0353
Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2018-11-27Bibliographically approved
Burdess, A., Mani, K., Tegler, G. & Wanhainen, A. (2018). Early Experience With a Novel Thoracic Stent Design for the Prevention of Distal Stent Graft-Induced New Entry Tears (d-SINE). Paper presented at 45th Annual VEITH Symposium, NOV 14-15, 2018, New York, NY. Journal of Vascular Surgery, 68(5), E153-E153
Open this publication in new window or tab >>Early Experience With a Novel Thoracic Stent Design for the Prevention of Distal Stent Graft-Induced New Entry Tears (d-SINE)
2018 (English)In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 68, no 5, p. E153-E153Article in journal, Meeting abstract (Other academic) Published
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-373536 (URN)10.1016/j.jvs.2018.08.110 (DOI)000450594000100 ()
Conference
45th Annual VEITH Symposium, NOV 14-15, 2018, New York, NY
Note

Supplement

Meeting Abstract: AAN 2

Available from: 2019-01-21 Created: 2019-01-21 Last updated: 2019-01-21Bibliographically approved
Burdess, A., Wanhainen, A., Tegler, G. & Mani, K. (2018). Fenestrated and Branched Endovascular Repair of Aortic Arch Pathology. Paper presented at 45th Annual VEITHS ymposium, NOV 14-15, 2018, New York, NY. Journal of Vascular Surgery, 68(5), E154-E154
Open this publication in new window or tab >>Fenestrated and Branched Endovascular Repair of Aortic Arch Pathology
2018 (English)In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 68, no 5, p. E154-E154Article in journal, Meeting abstract (Other academic) Published
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-373535 (URN)10.1016/j.jvs.2018.08.111 (DOI)000450594000101 ()
Conference
45th Annual VEITHS ymposium, NOV 14-15, 2018, New York, NY
Note

Supplement

Meeting Abstract: AAN 3

Available from: 2019-01-21 Created: 2019-01-21 Last updated: 2019-01-21Bibliographically approved
Burdess, A., Mani, K., Tegler, G. & Wanhainen, A. (2018). Stent-graft induced new entry tears after type B aortic dissection: how to treat and how to prevent?. Journal of Cardiovascular Surgery, 59(6), 789-796
Open this publication in new window or tab >>Stent-graft induced new entry tears after type B aortic dissection: how to treat and how to prevent?
2018 (English)In: Journal of Cardiovascular Surgery, ISSN 0021-9509, E-ISSN 1827-191X, Vol. 59, no 6, p. 789-796Article, review/survey (Refereed) Published
Abstract [en]

Progress of aortic disease after stent-graft treatment of aortic dissection includes the risk of stent graft-induced new entry (SINE). In this paper we review the incidence and mechanisms thought to be responsible for retrograde ascending and distal SINE after thoracic endovascular aortic repair (TEVAR) for type B dissection, and examine potential techniques for treatment and prevention. Although the risk of proximal SINE is low, the fatality of this complication requires vigilance in patients who develop new onset symptoms in the early period after TEVAR treatment. Careful technique, minimal oversizing, and use of disease specific stent grafts may reduce the risk for proximal SINE. Distally, SINE is more frequently seen during follow-up in patients treated for chronic dissection. The most important risk factor is oversizing of the stent-graft compared to the true lumen distal landing zone. Development of new disease specific stent grafts with reduced distal radial force may reduce the risk for distal SINE.

Place, publisher, year, edition, pages
EDIZIONI MINERVA MEDICA, 2018
Keywords
Aneurysm, dissecting, Stents, Endovascular procedures
National Category
Cardiac and Cardiovascular Systems Surgery
Identifiers
urn:nbn:se:uu:diva-376314 (URN)10.23736/S0021-9509.18.10570-2 (DOI)000456108200006 ()29781592 (PubMedID)
Available from: 2019-02-05 Created: 2019-02-05 Last updated: 2019-02-05Bibliographically approved
Gavali, H., Mani, K., Tegler, G., Kawati, R., Covaciu, L. & Wanhainen, A. (2017). Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome. European Journal of Vascular and Endovascular Surgery, 54(2), 157-163
Open this publication in new window or tab >>Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome
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2017 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 54, no 2, p. 157-163Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of the study was to investigate the frequency and outcome of prolonged intensive care unit (ICU) length of stay (LOS) after abdominal aortic aneurysm (AAA) repair in the endovascular era.

Methods: All patients operated on for AAA between 1999 and 2013 at Uppsala University hospital were identified. Data were retrieved from the Swedish Vascular registry, the Swedish Intensive Care registry, the National Population registry, and case records. Prolonged ICU LOS was defined as >= 48 h during the primary hospital stay. Patients surviving >= 48 h after AAA surgery were included in the analysis.

Results: A total of 725 patients were identified, of whom 707 (97.5%) survived >= 48 h; 563 (79.6%) underwent intact AAA repair and 144 (20.4%) ruptured AAA repair. A total of 548 patients (77.5%) required < 48 h of intensive care, 115 (16.3%) 2-6 days and 44 (6.2%) >= 7 days. The rate of prolonged ICU LOS declined considerably over time, from 41.4% of all AAA repairs in 1999 to 7.3% in 2013 (p < .001) whereas the use of endovascular aortic repair (EVAR) increased from 6.9% in 1999 to 78.0% in 2013 (p < .001). The 30 day survival rate was 98.2% for those with < 48 h ICU stay versus 93.0% for 2-6 days versus 81.8% for >= 7 days (p < .001); the corresponding 90 day survival was 97.1% versus 86.1% versus 63.6% (p < .001) respectively. For patients surviving 90 days after repair, there was no difference in long-term survival between the groups.

Conclusion: During the period of progressively increasing use of EVAR, a simultaneous significant reduction in frequency of prolonged ICU LOS occurred. Although prolonged ICU LOS was associated with a high short-term mortality, long-term outcome among those surviving the initial 90 days was less affected.

Keywords
Abdominal aortic aneurysm, Critical care, Length of stay, Outcome, Time trends
National Category
Surgery Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-334093 (URN)10.1016/j.ejvs.2017.05.014 (DOI)000407536300005 ()28648757 (PubMedID)
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2017-11-21Bibliographically approved
Tegler, G., Estrada, S., Hall, H., Wanhainen, A., Björck, M., Sörensen, J. & Antoni, G. (2014). Autoradiography screening of potential positron emission tomography tracers for asymptomatic abdominal aortic aneurysms. Upsala Journal of Medical Sciences, 119(3), 229-235
Open this publication in new window or tab >>Autoradiography screening of potential positron emission tomography tracers for asymptomatic abdominal aortic aneurysms
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2014 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 229-235Article in journal (Refereed) Published
Abstract [en]

Objective. The aetiology and early pathophysiological mechanisms of aortic aneurysm formation are still unknown and challenging to study in vivo. Positron emission tomography (PET) is a potentially valuable instrument for non-invasive in vivo pathophysiological studies. No specific tracer to identify the pathophysiological process of aneurysmal dilatation is yet available, however. The aim of this study was to explore if different PET tracers could be useful to image aneurysmal disease. Methods and results. Human aneurysmal aortic tissue, collected during elective resection of abdominal aortic aneurysm (AAA) of asymptomatic patients, was investigated in vitro by means of autoradiography with [Ga-68]CRP-binder targeting C-reactive protein, [C-11]DAA1106 targeting translocator protein (18 kDa), [C-11]D-deprenyl with unknown target receptor, [C-11] deuterium-L-deprenyl targeting astrocytes, [F-18]fluciclatide targeting integrin alpha(V)beta(3), [Ga-68]IMP461 and bi-specific antibody TF2 052107 targeting carcinoembryonic antigen, [F-18]F-metomidate targeting mitochondrial cytochrome P-450 species in the adrenal cortex, and [F-18]vorozole targeting aromatase. Of the investigated tracers, only [F-18]fluciclatide exhibited specific binding, whereas the other PET tracers failed to show specific uptake in the investigated tissue and are probably not useful for the intended purpose. Conclusion. It seems likely that alpha(V)beta(3) integrin expression in AAA can be visualized with PET and that the alpha(V)beta(3) selective tracer, [F-18]fluciclatide, may be suitable for in vivo molecular imaging of asymptomatic AAA. Additional evaluation of [F-18]fluciclatide and alpha(V)beta(3) integrin expression in AAA will be performed in vitro as well as in vivo.

Keywords
AAA, PET tracers, pathophysiology
National Category
Surgery Physiology Other Medical Biotechnology
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-197428 (URN)10.3109/03009734.2014.894157 (DOI)000340110800003 ()
Funder
Swedish Research Council, K2013-64X-20406-07-3
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2018-01-11Bibliographically approved
Tegler, G., Wallgren, A., Estrada, S., Wanhainen, A., Björck, M., Sörensen, J. & Antoni, G. (2013). [18F]fluciclatide- Autoradiography study of angiogenesis in abdominal aortic aneurysm.
Open this publication in new window or tab >>[18F]fluciclatide- Autoradiography study of angiogenesis in abdominal aortic aneurysm
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2013 (English)Manuscript (preprint) (Other academic)
Keywords
AAA, PET, 18F-Fluciclatide, integrin alfaVbeta3, angiogenesis, pathophysiology
National Category
Surgery Physiology Other Medical Biotechnology
Identifiers
urn:nbn:se:uu:diva-197432 (URN)
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2018-01-11
Tegler, G., Sörensen, J., Ericson, K., Björck, M. & Wanhainen, A. (2013). 4D-PET/CT with [11C]-PK11195 and [11C]-D-deprenyl does not identify the chronic inflammation in asymptomatic abdominal aortic aneurysms. European Journal of Vascular and Endovascular Surgery, 45(4), 351-356
Open this publication in new window or tab >>4D-PET/CT with [11C]-PK11195 and [11C]-D-deprenyl does not identify the chronic inflammation in asymptomatic abdominal aortic aneurysms
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2013 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 45, no 4, p. 351-356Article in journal (Refereed) Published
Abstract [en]

Objectives

The aim of this study was to investigate the relevance of inflammation in the pathogenesis of abdominal aortic aneurysm (AAA) in vivo with two novel positron emission tomography (PET) tracers: [11C]-PK11195 which targets the translocator protein (18 kDa) expressed on macrophages and [11C]-d-deprenyl with a yet unknown target receptor expressed in chronic inflammation.

Design

Prospective clinical study.

Materials/methods

Five patients were examined with [11C]-PK11195-positron emission tomography/computed tomography (PET/CT) and 10 with [11C]-d-deprenyl-PET/CT. Nine large AAAs (54–66 mm) scheduled for repair and six small AAA (35–44 mm). All 15 patients were male and the AAAs were all asymptomatic. Regional activity was measured as standardised uptake values (SUVs) and retention index was calculated. Biopsies were taken from the aneurysm wall for histological examinations, in the nine patients operated on.

Results

No aortic uptake was recorded on the visual inspection, neither with [11C]-PK11195 nor with [11C]-d-deprenyl. For [11C]-PK11195 the median SUV of the AAA wall was 0.9 (range 0.8–1.0) and for [11C]-d-deprenyl, 0.7 (range 0.4–1.2). No increased uptake was seen in the aneurysmal infrarenal aorta compared with the non-aneurysmal suprarenal aorta. Histological examination of the aneurysm wall showed high inflammatory cell infiltration with lymphocytes and macrophages.

Conclusions

The chronic inflammation observed in the vessel wall was not detectable with [11C]-PK11195 and [11C]-d-deprenyl. In order to study the relevance of the inflammation in the pathogenesis of AAA in vivo other PET tracers need to be investigated.

Keywords
AAA, PET, 11C-PK1195, 11C-D-deprenyl, pathophysiology
National Category
Surgery Physiology Other Medical Biotechnology Clinical Laboratory Medicine
Research subject
Surgery; Pathology
Identifiers
urn:nbn:se:uu:diva-197429 (URN)10.1016/j.ejvs.2013.01.011 (DOI)000316924900007 ()23394769 (PubMedID)
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2019-01-04Bibliographically approved
Tegler, G. (2013). Abdominal Aortic Aneurysm: Molecular Imaging Studies of Pathophysiology. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Abdominal Aortic Aneurysm: Molecular Imaging Studies of Pathophysiology
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. p. 111
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 899
Keywords
Abdominal aortic aneurysm, AAA, Positron emission tomography, PET, Molecular Imaging, Pathophysiology, Autoradiography, Angiogenesis, integrin alphaVbeta3, FDG, 18F-FDG, 11C-PK11195, 11C-D-deprenyl, [18F]fluciclatide, Fluciclatide, Bukaortaaneurysm, Molekylär bilddiagnostik, Patofysiologi, PET, Autoradiografi, Angiogenes
National Category
Medical and Health Sciences Surgery Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Surgery; Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-194663 (URN)978-91-554-8656-3 (ISBN)
Public defence
2013-05-31, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2013-05-08 Created: 2013-02-18 Last updated: 2013-08-30Bibliographically approved
Tegler, G., Ericson, K., Sörensen, J., Björck, M. & Wanhainen, A. (2012). Inflammation in the walls of asymptomatic abdominal aortic aneurysms is not associated with increased metabolic activity detectable by 18-fluorodeoxglucose positron-emission tomography. Journal of Vascular Surgery, 56(3), 802-807
Open this publication in new window or tab >>Inflammation in the walls of asymptomatic abdominal aortic aneurysms is not associated with increased metabolic activity detectable by 18-fluorodeoxglucose positron-emission tomography
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2012 (English)In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 56, no 3, p. 802-807Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

We hypothesized that the general inflammation observed in the wall of large, asymptomatic abdominal aortic aneurysms (AAAs) could be detected in vivo by 18-fluorodeoxglucose (FDG) positron-emission tomography (PET) and, if so, that this method could be used to study if active inflammation is an early pathogenetic finding in small AAAs detected by screening.

METHODS:

In this prospective clinical study, 12 men were examined with FDG-PET computed tomography. Seven had large asymptomatic AAAs (range, 52-66 mm) that required surgery, and five had small AAAs (range, 34-40 mm) under surveillance. In the surgery group, biopsy specimens were taken from the aneurysm wall for histologic examinations.

RESULTS:

Compared with normal segments of the aorta, liver, and blood and compared with healthy controls matched for age and sex, no increased FDG uptake, measured as standardized uptake value, was detected in any of the large or small AAAs. The SUVmean difference between infrarenal aorta and blood was -0.3 for cases and -0.1 for controls (P = .06). The corresponding differences between the infrarenal aorta and liver was -0.8 and -0.8 (P = .91) and between infrarenal aorta and suprarenal aorta was -0.2 and -0.1 for cases and controls, respectively (P = .20). The histologic examination of the aneurysm walls showed high inflammatory cell infiltration with T lymphocytes, B lymphocytes, and macrophages.

CONCLUSIONS:

The chronic inflammation observed in the wall of asymptomatic AAAs was not sufficiently metabolically active to result in an increased glucose metabolism detectable by FDG-PET by means of this standard protocol. To study the importance of inflammation in the pathogenesis of AAAs in vivo, PET tracers other than FDG need to be developed.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-181755 (URN)10.1016/j.jvs.2012.02.024 (DOI)000308085500029 ()22854268 (PubMedID)
Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2017-12-07Bibliographically approved
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