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  • 1.
    Burdess, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Freeman Rd Hosp, Northern Vasc Unit, Newcastle, NSW, Australia..
    D'Oria, Mario
    Univ Hosp Cattinara ASUIGI, Cardiovasc Dept, Div Vasc & Endovasc Surg, Trieste, Italy..
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mogensen, John
    Cook Med, Bjaeverskov, Denmark..
    Koelbel, Tilo
    Univ Heart & Vasc Ctr, German Aort Ctr, Dept Vasc Med, Hamburg, Germany..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Umeå Univ, Dept Surg & Perioperat Sci, Surg, Umeå, Sweden..
    Early Experience With a Novel Dissection-Specific Stent-Graft to Prevent Distal Stent-Graft-Induced New Entry Tears After Thoracic Endovascular Repair of Chronic Type B Aortic Dissections2022In: Annals of Vascular Surgery, ISSN 0890-5096, E-ISSN 1615-5947, Vol. 81, p. 36-47Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to report short and mid-term outcomes of a novel, investigational, dissection-specific stent-graft (DSSG), specifically designed to address the features of chronic type B aortic dissection (CTBAD) and reduce the risk of distal stent-graft-induced new entry tears (dSINE).

    Materials and Methods: A retrospective single center cohort study of all patients undergoing TEVAR with the DSSG for CTBAD from January 1, 2017 to January 31, 2020. The DSSG, which is a modified stent-graft based on the Cook Zenith Alpha Thoracic platform, has no proximal barbs, and a customized longer body length with substantial taper. The second and third distal Z-stents are sited internally to avoid any contact of the metal skeleton with the dissection membrane and have reduced radial force, while the most distal stent was removed creating a distal 30 mm unsupported Dacron graft.

    Results: Sixteen patients (13 males, 3 females) with a median age of 66 years (range 31-79 years) underwent elective TEVAR of CTBAD using the DSSG. Six patients (38%) had an underlying connective tissue disorder. The median tapering was 10 mm (range 4 mm-21 mm) and median length 270 mm (range 210-380 mm). Technical success was achieved in all but one case (96%). One patient died within 30 days, due to retrograde type A dissection with cardiac tamponade. The 30-day rate of stroke, spinal cord ischemia, and re-interventions was 0%. After median imaging follow-up time of 17 months (range 1-31 months), one patient developed a dSINE 4 months after the index procedure. After median survival follow-up of 23 months (range 2-35 months), one late death occurred due to traumatic brain injury, while no aortic-related death occurred during follow-up. Complete false lumen (FL) thrombosis was achieved in 9 patients while the remaining 6 showed partial FL thrombosis. No instances of diameter increase at the level of treated aortic segment were noted with serial measurements showing either stable (n = 7) or decreased (n = 8) maximal transverse diameter.

    Conclusions: Use of a novel DSSG with low radial force for TEVAR in the setting of CTBAD is safe and feasible. This early real-world experience shows promising mid-term effectiveness with low rates of dSINE or unplanned re-interventions and satisfactory aortic remodeling during follow-up. Longer follow-up is needed, however, before any firm conclusions can be drawn.

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  • 2.
    Burdess, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Early Experience With a Novel Thoracic Stent Design for the Prevention of Distal Stent Graft-Induced New Entry Tears (d-SINE)2018In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 68, no 5, p. E153-E153Article in journal (Other academic)
  • 3.
    Burdess, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Stent-graft induced new entry tears after type B aortic dissection: how to treat and how to prevent?2018In: Journal of Cardiovascular Surgery, ISSN 0021-9509, E-ISSN 1827-191X, Vol. 59, no 6, p. 789-796Article, review/survey (Refereed)
    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.

  • 4.
    Burdess, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Fenestrated and Branched Endovascular Repair of Aortic Arch Pathology2018In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 68, no 5, p. E154-E154Article in journal (Other academic)
  • 5.
    D'Oria, Mario
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Budtz-Lilly, Jacob
    Aarhus Univ Hosp, Div Vasc Surg, Aarhus, Denmark..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Short-term and Mid-term Outcomes after Use of the Native Infrarenal Aorta as Distal Landing Zone for Fenestrated-Branched Endovascular Aortic Repair2021In: Annals of Vascular Surgery, ISSN 0890-5096, E-ISSN 1615-5947, Vol. 72, p. 114-123Article in journal (Refereed)
    Abstract [en]

    Background: This study aimed to examine outcomes after use of the native infrarenal aorta as distal landing zone for fenestrated-branched endovascular aortic repair (F-BEVAR) of pararenal-thoracoabdominal aortic aneurysms (PRAA-TAAA). Methods: All F-BEVAR procedures for treatment of PRAA-TAAA (2011-2019) at 2 aortic centers were examined. The outcomes of interest were as follows: i) technical success, ii) perioperative morbidity, iii) preservation of lumbar arteries and the inferior mesenteric artery, iv) type IB endoleaks, v) reinterventions, vi) survival, vii) aneurysm sac behavior, and viii) infrarenal aortic changes. Results: Twenty consecutive patients with distal landing in the native infrarenal aorta were included (median age 71 years; 25% men). The median number of visible lumbar arteries at baseline was 7, and a patent inferior mesenteric artery (IMA) before the operation was present in 19 (95%) of the cases. There were no deaths within 30 days. One patient (5%), operated on with a 4-BEVAR for a type 2 TAAA, experienced spinal cord ischemia (permanent paraplegia). The median decrease in the number of visible lumbar arteries at the first postoperative scan was 3 from the baseline value, whereas a patent IMA was preserved in 12 out of 19 patients. Only in one case (5%), a type IB endoleak was noted for an overall technical success rate of 95%, which required a standard EVAR 20 months after the initial operation. The median follow-up duration for the study cohort was 491 days; all patients were alive at the longest available individual follow-up, and no instances of new-onset type IB endoleaks were observed. Another 3 late reinterventions (in addition to the one mentioned previously) were performed during midterm follow-up, all because of target vessel instability. In patients with >= 12 months of follow-up after the index procedure (n = 12, 60% of the entire cohort), no instances of aneurysm sac increase >5 mm were noted; the median largest aortic diameter was 51 mm with a median difference from baseline of -6 mm. The median distal landing zone diameter increase was 4 mm from baseline but never beyond the nominal stent-graft diameter, whereas the median aortic bifurcation diameter differed 1 mm from baseline. Conclusions: This preliminary experience shows that the use of the native infrarenal aorta as a distal landing zone for F-BEVAR is safe in the short term and midterm in patients with suitable anatomy, allowing the sparing of collateral vessels. Longer follow-up is warranted to assess durability.

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  • 6.
    D'Oria, Mario
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Pre-Operative Moderate to Severe Chronic Kidney Disease is Associated with Worse Short-Term and Mid-Term Outcomes in Patients Undergoing Fenestrated-Branched Endovascular Aortic Repair2021In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 62, no 6, p. 859-868Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To review experience of fenestrated-branched endovascular aortic repair (F-BEVAR) for pararenal/thoraco-abdominal aortic aneurysms (PRAA/TAAA) and to assess the association between pre-operative moderate to severe chronic kidney disease (CKD) and post-operative outcomes.

    METHODS: All consecutive patients undergoing (elective and non-elective) F-BEVAR at a single centre (1 January 2011 - 1 July 2019) were identified. Renal function was calculated as the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. Accordingly, presence of moderate to severe CKD was defined as eGFR < 60 mL/min/1.73m2.

    RESULTS: Overall, 202 consecutive patients (mean age 72 ± 8 years; 25% women) underwent F-BEVAR for the treatment of PRAA/TAAA during the study period. Of these, 51 had a history of moderate to severe CKD (none on chronic haemodialysis). No statistically significant differences were found in demographics and major comorbidities between patients with or without a history of CKD. The overall peri-operative mortality rate was 2%, without statistically significant differences between study groups (p = .26). Patients with prior CKD had statistically significantly higher rates of acute kidney injury (AKI) (37% vs. 12%, p < .001). At three years, overall survival was statistically significantly lower in patients with history of CKD compared with those without pre-operative CKD (57% vs. 82%, p = .010). Similarly, freedom from renal function decline at three years was statistically significantly poorer in patients with prior history of CKD compared with those without pre-operative CKD (43% vs. 80%, p = .020). In a multivariable analysis CKD was independently associated with higher odds of peri-operative AKI (OR 2.8, 95% CI 1.9 - 5.8, p = .030), renal function decline (OR 4.9, 95% CI 1.7 - 9.2, p = .003), and all cause mortality (HR 3.2, 95% CI 1.2 - 8.6, p = .020).

    CONCLUSION: Despite low peri-operative mortality rates that are comparable to patients with unimpaired renal function, occurrence of AKI was statistically significantly higher in subjects with pre-existing moderate to severe CKD. History of CKD was independently associated to renal function decline and poorer midterm survival.

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  • 7.
    Estrada, Sergio
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Elgland, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala Univ Hosp, PET Ctr, Ctr Med Imaging, Uppsala, Sweden..
    Selvaraju, Ram Kumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bergström, Mats
    GlaxoSmithKline, Clin Imaging, Brentford, England..
    Jimenez-Royo, Pilar
    GlaxoSmithKline, Clin Imaging, Brentford, England..
    Jahan, Mahabuba
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala Univ Hosp, PET Ctr, Ctr Med Imaging, Uppsala, Sweden..
    Nordeman, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala Univ Hosp, PET Ctr, Ctr Med Imaging, Uppsala, Sweden..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala Univ Hosp, PET Ctr, Ctr Med Imaging, Uppsala, Sweden.;Uppsala Univ Hosp, PET Ctr, SE-75185 Uppsala, Sweden..
    Preclinical evaluation of [C-11]GW457427 as a tracer for neutrophil elastase2022In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 106-107, p. 62-71Article in journal (Refereed)
    Abstract [en]

    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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  • 8.
    Fernandez Prendes, Carlota
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    A systematic review of experimental and clinical studies reporting on in situ laser fenestration of aortic endografts.2022In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 75, no 2, p. 740-752.e1, article id S0741-5214(21)02190-XArticle in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To summarize available in-situ laser fenestration (ISLF) literature, including experimental studies with their subsequent recommendations regarding optimal fenestration technique and fabric; as well as the short and mid-term results of clinical studies.

    METHODS: A systematic review of English articles was performed in MEDLINE, the Cochrane Database and EMBASE, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines by two researchers. The search period was without starting date until the 31st August 2020, and search terms included were in situ, laser, fenestration, and endograft. Quality assessment of the studies was performed using the Newcastle-Ottawa scale by two other independent researchers.

    RESULTS: A total of 19 clinical studies were included, with a total of 428 patients (390 supra-aortic trunk ISLF, 38 visceral vessel ISLF). The technical success was 96.9% and 95.6% supra-aortic and visceral vessel ISLF, respectively. Most studies have less than 12-month follow-up, and the longest available follow-up (in one study) was 5-years for left-subclavian fenestration and 17-months for visceral vessel ISLF. Overall, the quality of the evaluated clinical studies was low. Six experimental studies were included, with the highest level of evidence suggesting fenestration of multifilament polyethylene terephthalate grafts, followed by dilation with either a 6- or 8-mm non-compliant balloon.

    CONCLUSION: Experimental studies favour the use of multifilament polyethylene terephthalate , followed by dilation with non-compliant balloons as the most durable "in-vitro" technique for ISLF. Short-term outcomes for arch and visceral vessel revascularization are promising, with low rates of in-hospital mortality, stroke, and end-organ ischemia. Nonetheless, the long-term durability of ISLF is yet to be determined and they should be limited to selected symptomatic or urgent cases.

  • 9.
    Gavali, Hamid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Kawati, Rafael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Covaciu, Lucian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome2017In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 54, no 2, p. 157-163Article in journal (Refereed)
    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.

  • 10.
    Holsti, Mari
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, Surg, Umea, Sweden.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lundin, Christina
    Umea Univ, Dept Surg & Perioperat Sci, Surg, Umea, Sweden.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Svensson, Johan
    Umea Univ, Dept Surg & Perioperat Sci, Surg, Umea, Sweden;Umea Univ, Umea Sch Business & Econ, Dept Stat, Umea, Sweden.
    Sund, Malin
    Umea Univ, Dept Surg & Perioperat Sci, Surg, Umea, Sweden.
    Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue2018In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 56, no 1, p. 110-118Article in journal (Refereed)
    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.

  • 11.
    Kuzniar, Marek K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Endovascular treatment of chronic aortic dissection with fenestrated and branched stent grafts2021In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 73, no 5, p. 1573-1582.e1Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Chronic aortic dissection with aneurysm development that includes the aortic arch and/or thoracoabdominal aorta (TAAA) is traditionally treated with open or hybrid surgery. Total endovascular treatment with fenestrated and branched aortic repair (F/B-EVAR) has recently been introduced as a less invasive alternative. The aim was to report the short- and midterm outcomes from a single tertiary vascular center.

    METHODS: All patients with chronic aortic dissection treated with F/B-EVAR from 2010 to 2019 at Uppsala University Hospital were identified. Perioperative and postoperative parameters were analyzed, with focus on short- (<30 days) and midterm survival, complication, and reintervention rates.

    RESULTS: F/B-EVAR was performed on 26 patients (median age, 63 years; range, 33-87 years; 18 men; median aortic diameter, 70 mm; range, 50-98 mm); with a median follow-up of 23 months (range, 0.5-118.0 months). One patient underwent both arch and TAAA repair. Overall, 13 arch repairs (arch group) after type A (n = 8) and type B (n = 5) dissection (all elective) were performed, and 14 TAAA repairs (TAAA group) after type A (n = 5) and type B (n = 9) dissection (one rupture). A total of 72 aortic branches were targeted (22 arch, 50 TAAA). Short-term technical success was achieved in 24 of 27 procedures (89%). Failures were related to one intraoperative retrograde type A dissection (RTAD) requiring open conversion (arch group), one persistent type IC endoleak on completion angiography (arch group), and one persistent type III endoleak (TAAA group). Mortality was 4% (n = 1) at 30 days and related to a second RTAD that occurred after discharge and was found on autopsy. Both RTADs occurred in patients with chronic type B dissection undergoing fenestrated arch repair. Paraplegia occurred in three cases (two arch, one TAAA) (11%), none permanent, and stroke in three cases (one arch, one TAAA) (11%); one was permanent. In the midterm, endoleaks were detected in 12 patients (44%); persistent false lumen flow (n = 3), type IB (n = 1), type IC (n = 3), type II (n = 7), and type IIIC (n = 2). The 3-year survival (Kaplan-Meier) of the arch repair was 75% and for the TAAA, 93%. Freedom from reintervention at 3 years were 100% for arch repairs and 48% for TAAA. In patients with a follow-up of more than 6 months (n = 23), all had stable or decreased aortic diameters and complete false lumen thrombosis at the level of stent graft was present in 65% (n = 15).

    CONCLUSIONS: Endovascular treatment of postdissection aneurysms is feasible, with acceptable short-term and midterm outcomes. RTAD after fenestrated and branched endovascular arch repair warrants caution when performed on patients with native ascending aortas, and reinterventions are frequent in TAAA repair.

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  • 12.
    Kuzniar, Marek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Feasibility of Assessing Inflammation in Asymptomatic Abdominal Aortic Aneurysms With Integrated 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging2020In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 59, no 3, p. 464-471Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study aimed to evaluate the feasibility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with contrast enhanced magnetic resonance imaging (MRI) to identify inflammation in asymptomatic abdominal aortic aneurysms (AAA).

    METHODS: FDG PET/MRI was performed on 15 patients with asymptomatic infrarenal AAAs >45 mm diameter. Prevalence of FDG uptake and MRI findings of inflammatory changes (oedema, wall thickening, and late gadolinium enhancement [LGE]) in the aortic wall were investigated at three levels: suprarenal aorta; non-aneurysmal aortic neck; and AAA.

    RESULTS: The median diameter of the AAAs was 54 mm (range 47-65 mm) and the median expansion rate in the last 12 months was 3 mm (range 1-13 mm). The standard uptake value (SUV) of FDG in the aneurysmal wall (SUVmax 2.5) was higher than the blood pool (SUVmax 1.0; p < .001). The maximum target to background ratio was higher in the suprarenal aorta (mean ± SD; 3.1 ± 0.6) and aortic neck (2.7 ± 0.5) than in the aneurysmal aorta (2.5 ± 0.5; p < .001). Thirty-six FDG hotspots were observed in the aneurysmal wall of 13 patients. Wall thickening and LGE were identified in eight patients. The number of FDG hotspots correlated with recent AAA growth (r = 0.62, p = .01). The recent aneurysm expansion rate was higher in aneurysms with LGE than in those without (7 mm vs. 2 mm; p = .03). MRI inflammatory changes were observed in nine of 36 hot spots (25%) and in three of 13 patients with focal FDG uptake.

    CONCLUSION: Fully integrated FDG PET/MRI can be used to study inflammation in asymptomatic AAAs. Heterogenous uptake of FDG in the aneurysmal wall indicates increased glucose metabolism, suggesting an ongoing inflammation. However, these FDG hotspots rarely correspond to MRI findings of inflammation, raising the question of which type of cellular activity is present in these areas. The presence of LGE and FDG hotspots both correlated to recent aneurysm growth, and their usefulness as clinical markers of aneurysm growth warrant additional investigation.

  • 13.
    Marek, Kuzniar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Assessing Inflammation in Small and Medium sized Asymptomatic Abdominal Aortic Aneurysms with Integrated 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance ImagingManuscript (preprint) (Other academic)
  • 14.
    Marek, Kuzniar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Umeå Univ, Dept Surg Sci & Perioperat Sci, Surg, Umeå, Sweden..
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Longitudinal Assessment of Inflammatory Activity in Acute Type B Aortic Dissection with Integrated Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging2023In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 66, no 3, p. 323-331Article in journal (Refereed)
    Abstract [en]

    Objective: The significance of the inflammatory response in the natural course of acute type B aortic dissection (ATBAD) is unknown. The aim was to characterise inflammation and its transformation over time in ATBAD using F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) with contrast enhanced magnetic resonance imaging (MRI).

    Methods: Ten patients underwent FDG-PET/MRI within two weeks of ATBAD (acute phase), three to four months (subacute phase), nine to 12 months (early chronic phase), and 21 to 24 months (late chronic phase) after ATBAD. Target background ratios (TBRs) were measured in the ascending aorta, aortic arch, and descending aorta. MRI inflammatory markers were assessed in the descending aorta.

    Results: Ten patients were included: median age 69 years, median clinical follow up 32 months. In the acute phase there was increased FDG uptake in the descending aorta (maximum TBR 5.8, SD [standard deviation] 1.3) compared with the ascending aorta (TBR 3.3, SD 0.8, p < .010) and arch (TBR 4.2, SD 0.6, p = .010). The maximum TBR of the descending aorta decreased from the acute to subacute phase (TBR 3.5, SD 0.6, p = .010) and further to the early chronic phase (TBR 2.9, SD 0.4, p = .030) but was stable thereafter. The acute phase maximum TBR in the ascending aorta (TBR 3.3) and arch (TBR 4.2) decreased to the subacute phase (ascending: TBR 2.8, SD 0.6, p = .020; arch: TBR 2.7, SD 0.4, p = .010) and was stable thereafter. Four patients underwent surgical aortic repair (three for aortic dilatation at one, five, and 28 months and one for visceral ischaemia at three weeks). MRI signs of inflammation were present in all surgically treated patients vs. two of six of medically treated patients (p= .048).

    Conclusion: ATBAD is associated with increased FDG uptake in the acute phase primarily in the descending aorta, but also involving the aortic arch and ascending aorta, indicating an inflammatory response in the whole aorta. Inflammation subsides early in the ascending aorta and arch (three months), whereas it stabilised later in the descending aorta (nine to 12 months). MRI signs of inflammation were more frequent in patients who later needed surgical treatment and merit further investigation.

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  • 15.
    Marek, Kuzniar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Longitudinal assessment of inflammatory activity in type B aortic dissection with integrated FDG PET/MR imagingManuscript (preprint) (Other academic)
  • 16. Nordanstig, Joakim
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Manne
    Andersson, Mattias
    Danielsson, Peter
    Gillgren, Peter
    Delle, Martin
    Engström, Jan
    Fransson, Torbjörn
    Hamoud, Maher
    Hilbertson, Anna
    Johansson, Patrik
    Karlsson, Lars
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindgren, Hans
    Ludwigs, Karin
    Mellander, Stefan
    Nyman, Niklas
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Sigvant, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Skoog, Per
    Starck, Joachim
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Toivola, Asko
    Truedson, Maria
    Wahlgren, Carl-Magnus
    Wallinder, Jonas
    Öjersjö, Andreas
    Falkenberg, Mårten
    Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease2020In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 383, no 26, p. 2538-2546Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.

    METHODS: We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality.

    RESULTS: No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).

    CONCLUSIONS: In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up.

  • 17.
    Shehab, Maysam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Umeå Univ, Dept Surg & Perioperat Sci, Div Surg, Umeå, Sweden.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Kuzniar, Marek
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    In situ laser fenestration of the Thoraflex Hybrid frozen elephant trunk for emergent revascularization of the left subclavian artery and laser fenestration for spinal cord perfusion2024In: Journal of Vascular Surgery Cases and Innovative Techniques, E-ISSN 2468-4287, Vol. 10, no 2, article id 101426Article in journal (Refereed)
    Abstract [en]

    In situ laser fenestration (ISLF) has emerged as a promising technique for emergent revascularization of the left subclavian artery in the case of thoracic endovascular aortic repair coverage, presenting excellent technical success rates in most studies. We describe a case of ISLF of the Thoraflex Hybrid frozen elephant trunk device to achieve immediate left subclavian artery revascularization. We demonstrate the feasibility and technical success of using ISLF in this setting, providing a less invasive alternative to conventional surgical revascularization when required.

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  • 18.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Abdominal Aortic Aneurysm: Molecular Imaging Studies of Pathophysiology2013Doctoral 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.

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  • 19.
    Tegler, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Ericson, Katharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Inflammation in the walls of asymptomatic abdominal aortic aneurysms is not associated with increased metabolic activity detectable by 18-fluorodeoxglucose positron-emission tomography2012In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 56, no 3, p. 802-807Article in journal (Refereed)
    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.

  • 20.
    Tegler, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Autoradiography screening of potential positron emission tomography tracers for asymptomatic abdominal aortic aneurysms2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 229-235Article in journal (Refereed)
    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.

  • 21.
    Tegler, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Savicheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Detection of aortic graft infection by 18-fluorodeoxyglocose positron emission tomography combined with computed tomography2007In: Journal of Vascular Surgery, ISSN 0741-5214, Vol. 45, no 4, p. 828-830Article in journal (Refereed)
    Abstract [en]

    Functional in vivo molecular imaging is provided with 18-fluorodeoxyglucose positron emission tomography (FDG-PET), which can detect cells with high glucose turnover. FDG-PET is an established imaging tool in oncology but has also been used in infectious and inflammatory diseases. PET combined with computed tomography (PET/CT) shows the metabolic activity with precise anatomic localization. More than 2000 scanners have now been installed worldwide, and with better availability, this hybrid method has the potential to become an important imaging tool in the management of suspected aortic graft infections, especially in patients with low-grade graft infection. We report a patient with a suspected aortic graft infection that was confirmed and anatomically localized by FDG-PET/CT. An extra-anatomic bypass and extirpation of the aortic graft was performed. The perioperative location of the graft infection coincided exactly with the place of FDG uptake shown on PET/CT. The patient had an uneventful postoperative recovery and did well during 6 months of follow-up.

  • 22.
    Tegler, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Ericson, Katharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    4D-PET/CT with [11C]-PK11195 and [11C]-D-deprenyl does not identify the chronic inflammation in asymptomatic abdominal aortic aneurysms2013In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 45, no 4, p. 351-356Article in journal (Refereed)
    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.

  • 23.
    Tegler, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wallgren, AnnaCarin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    [18F]fluciclatide- Autoradiography study of angiogenesis in abdominal aortic aneurysm2013Manuscript (preprint) (Other academic)
  • 24.
    Yu, Hok Yee Harry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Asciutto, Giuseppe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala Univ, Dept Surg Sci, Sect Vasc Surg, Uppsala, Sweden..
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    An updated systematic review and meta-analysis of pre-emptive aortic side branch embolization to prevent type II endoleaks after endovascular aneurysm repair2023In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 77, no 6, p. 1815-1821Article in journal (Refereed)
    Abstract [en]

    Objective: Pre-emptive embolization of aortic side branches may be effective in preventing type II endoleaks (T2EL) based on a previous systematic review and meta-analysis by our group. Data up to 2019 was, however, only based on retrospective studies. The aim of the current study was to update the meta-analysis and evaluate the current evidence on this treatment strategy.

    Methods: A systematic literature search was performed with the same keywords and strategies used in the previous study. The complementary search included all articles published from January 1, 2019, through May 29, 2022. The incidence of aneurysm sac growth was the primary outcome of interest.

    Results: Four new studies were identified, including one randomized controlled study and one nationwide registry-based retrospective study. Overall, the incidence of sac size enlargement was 4.3% in the embolization group compared with 6.8% in the control group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.26-0.55), the incidence of T2EL was 19.7% vs 37.4% (OR, 0.38; 95% CI, 0.30-0.47), and the incidence of reintervention for T2EL was 1.2% vs 11.2% (OR, 0.12; 95% CI, 0.06-0.23).

    Conclusions: Current evidence confirms lower incidence of aneurysm sac growth, T2EL, and reinterventions when preemptive embolization of aortic side branches is performed in conjunction with endovascular aneurysm repair, compared with no embolization. However, a higher level of evidence is still required to support a broad change of practice, including data on cost-effectiveness and on the potential effect on rupture.

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  • 25.
    Yu, Hok Yee Harry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Ruttonjee Hosp, Dept Surg, Hong Kong, Peoples R China.;Tang Shiu Kin Hosp, Dept Surg, Hong Kong, Peoples R China..
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Baderkhan, Hassan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Systematic review and meta-analysis of prophylactic aortic side branch embolization to prevent type II endoleaks2020In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 72, no 5, p. 1783-+Article, review/survey (Refereed)
    Abstract [en]

    Objective: Type II endoleaks are the most common type of endoleak after endovascular aneurysm repair (EVAR) and may cause late sac expansion and rupture. To prevent this, prophylactic embolization of aortic side branches has been suggested. The aim of this review was to assess the current evidence for this prophylactic treatment and its association with sac size enlargement as well as rate of and reintervention for type II endoleak. Methods: This was a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The MEDLINE and Scopus databases were used to search for related articles until March 2019. After screening, original studies reporting outcome comparing patients having prophylactic embolization with those undergoing EVAR without prophylactic embolization were included. An assessment of the quality of the included studies as well as data extraction was performed by two independent observers. Statistical analysis was performed using Review Manager 5.3 (The Nordic Cochrane Center, Copenhagen, Denmark). Results: There were 3777 publications identified. After elimination of duplicate entries and review of titles and abstracts, 13 retrospective cohort studies including 1427 patients comparing prophylactic embolization with standard EVAR therapy were identified. No randomized trials were available. Five of these 13 studies reported sac growth, with a frequency of 7.4%(14/90) in the embolization group vs 13.4% in controls (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.29-1). The rate of type II endoleak was 18.5% (100/540) in the embolization group vs 38.6% in the control group (342/887; OR, 0.34; 95% CI, 0.26-0.44). Based on 10 studies, the rate of reinterventionwas 1.5%(7/468) in the embolization group vs 12.4%(80/646) in the control group (OR, 0.12; 95% CI, 0.06-0.24). Nine of these 13 studies showed that technical success of inferior mesenteric artery and lumbar artery embolization was 82.3% and 69.1%, respectively. Regarding complications, 10 of 108 patients (9.3%) in one study reported nonspecific abdominal pain after embolization, and all resolved with overnight rehydration. Only one patient, who previously had right hemicolectomy, died after inferior mesenteric artery embolization of ischemic colitis. Conclusions: This systematic review and meta-analysis suggests that prophylactic aortic side branch embolization may be associated with lower rate of sac enlargement, incidence of type II endoleaks, and reinterventions. However, high-quality unbiased studies are lacking in this field, and this review and meta-analysis may be affected by selection bias and residual confounders remaining in the retrospective studies. To conclude whether prophylactic embolization should be routinely performed, a prospective, randomized trial is required.

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