Inflammatory aortic wall development after EVAR: case report

peer reviewe

Investigation into the in vivo and in vitro effects of anti-angiogenic therapy on abdominal aortic aneurysms

Medical therapy to prevent abdominal aortic aneurysm (AAA) development and progression is not currently available. Angiogenesis and extracellular signal-related kinase (ERK) pathway are key modulators of matrix metallo proteinases (MMPs) during AAA formation. The aim of the study described in this thesis is to evaluate the effects of Sorafenib (a multikinase inhibitor with antiangiogenic and ERK inhibitory properties) on experimental AAAs, and its in-vitro equivalent, 5-Br SU6668, on co-cultures of human AAA smooth muscle cells (SMCs) with aortic endothelial cells (AECs).To study in vivo effects, Apolipoprotein E knock out (ApoE-/-) mice were assigned to either 28 days of angiotensin-II (AngII) infusion alone (Group 1); AngII+Sorafenib from day-1 (Group 2); AngII+Sorafenib from day-10 (Group 3); or saline infusion (negative control, Group 4). Sorafenib reduced the development (Group-2 versus Group-1, P=0.001) and progression (Group-3 versus Group-1, P=0.0002) of AAAs. Mice treated with Sorafenib resulted in greater preservation of elastin and collagen layers within their aortic wall and significantly reduced angiogenesis (CD34 cells), inflammatory infiltrates, expression of pro-angiogenic genes (Raf1, Nras, Pi3k, Akt3, Vegf, Il6) and MMP-2 and -9 protein expressions (all PIn-vitro, 5-Br SU6668 prevented ERK phosphorylation and reduced gene expression of pro-angiogenic cytokine {Interleukin -6 (IL-6), P=0.04} and protein levels of pro-angiogenic peptides {Monocyte Chemotactic Protein-1(MCP-1) and MMP2, PTargeting the angiogenic pathway via inhibition of ERK phosphorylation is a potential therapy to prevent AAA growth. Whether anti-angiogenic therapy reduces human AAA development and growth warrants further investigation.</div

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March - May 2020, "period 1"), and then again between May and June ("period 2") and June and July 2020 ("period 3"). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries' first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic "normal" by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries