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Cyclosporin A (CSA) is a potent immunosuppressive agent in pharmacologic studies. However, there is evidence for side effects, specifically in regard to vascular dysfunction. Its mode of action inducing endothelial cell toxicity is partially unclear, and a connection with an adverse outcome pathway (AOP) is not established yet. Therefore, we designed this study to get deeper insights into the mechanistic toxicology of CSA on angiogenesis. Stem cells, especially induced pluripotent stem cells (iPSCs) with the ability of differentiation to all organs of the body, are considered a promising in vitro model to reduce animal experimentation. In this study, we differentiated iPSCs to endothelial cells (ECs) as one cell type that in other studies would allow to generate cells or organoids from single donors. Flow cytometry and immunostaining confirmed our scalable differentiation protocol. Then dose and time course experiments assessing CSA cytotoxicity on iPS derived endothelial cells were performed. Transcriptomic data suggested CDA dependent induction of reactive oxygen species (ROS) and mitochondrial dysfunction, which was confirmed by in vitro experiments. Additionally, CSA impaired angiogenesis via ROS induction. Finally, we combined this information into an AOP, was developed based on here observed and literature based evidence for CSA-mediated endothelial cell toxicity. This AOP will help to design in vitro test batteries, model events observed in human toxicity studies, as well for predictive toxicology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zahra Mazidi reports was provided by Evercyte GmbH. Zahra Mazidi reports a relationship with Evercyte GmbH that includes: employment., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Despite the increasing number of fenestrated and branched endovascular aortic repair (F/B-EVAR) procedures, evidence on post-operative antiplatelet therapy is very limited. This study aimed to investigate the role of single antiplatelet therapy (SAPT) vs. double antiplatelet therapy (DAPT) after F/B-EVAR in 30 day and follow up outcomes., Methods: A multicentre retrospective analysis was conducted, including F/B-EVAR patients managed from 1 January 2018 to 31 December 2022. Comparative outcomes were assessed according to post-operative antiplatelet therapy. The cohort was divided into the SAPT group (acetylsalicylic acid [ASA] or clopidogrel) and DAPT group (ASA and clopidogrel). The duration of SAPT or DAPT was one to six months. Primary outcomes were 30 day death, and cardiovascular ischaemic and major haemorrhagic events. Secondary outcomes were survival and target vessel (TV) patency during follow up., Results: A total of 1 430 patients were included: 955 under SAPT and 475 under DAPT. The 30 day mortality rate was similar (SAPT 2.1% vs. DAPT 1.5%; p = .42). Cardiovascular ischaemic events were lower in the DAPT group (SAPT 11.9% vs. DAPT 8.2%; p = .040), with DAPT being an independent protector for acute mesenteric (p = .009) and lower limb ischaemia (p = .020). No difference was found in 30 day major haemorrhagic events (SAPT 7.5% vs. DAPT 6.3%; p = .40). The mean follow up was 21.8 ± 2.9 months. Cox regression showed no survival confounders, with similar rates between groups (log rank p = .71). DAPT patients enjoyed higher TV patency (SAPT 93.4%, standard error [SE] 0.7% vs. DAPT 97.0%, SE 0.6%; log rank p = .007) at thirty six months. Cox regression revealed B-EVAR as a predictor of worse TV patency (hazard ratio 2.03, 95% confidence interval 1.36 - 3.03; p < .001). DAPT was related to higher patency within B-EVAR patients (SAPT 87.2%, SE 2.1% vs. DAPT 94.9%, SE 1.9%; p < .001)., Conclusion: DAPT after F/B-EVAR was associated with lower risk of cardiovascular ischaemic events and higher TV patency, especially in B-EVAR cases. No difference in major haemorrhagic events was observed at 30 days., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Bridging stentgrafts (BSGs) are one of the primary limiting factors regarding long-term results after fenestrated endovascular aortic repair (fEVAR). This study aims to report for the first time the outcome of a novel BSG called iCover from a national, multicentric retrospective database., Methods: A cohort of 58 patients received 212 BSGs for the renovisceral arteries in fEVAR. Patients were followed-up clinically and with computed-tomography angiography. Study end points were mortality, occurrence of complications, technical success of the BSG implantation, defined as successful deployment with vessel patency and absence of type 1c, 3b, and 3c endoleak, and stability over the follow-up., Results: Three BSG unrelated mortalities (5.1 %), four BSG unrelated major complications (6.8 %) and five minor complications (8.6 %) occurred. The technical success of iCover was 207/212 (97.6 %), target vessel patency was 100 % over a follow-up of 4.0 months, and no late BSG related endoleak was detected. In two cases, the BSG was dislodged from the balloon and could be parked in a safe position without further sequelae (0.9 %)., Conclusion: The iCover represents a feasible BSG for fEVAR with an excellent safety profile and technical success rate in the early phase. Prudent post-dilatation and monitoring of the proximal and distal stent ends can potentially further improve outcome. Longer follow-up series are necessary., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: Abdominal aortic aneurysm (AAA) development is driven by inflammation, in particular myeloid cells, which represent attractive biomarker candidates. Yet to date, the maximum aortic diameter is the only clinically applied predictor of AAA progression and indicator for surgical repair. We postulated that aortic inflammation is reflected in a systemic change of monocyte populations, which we investigated regarding marker potential in AAA diagnosis and prognosis., Methods: We conducted a single-center retrospective cohort study in a diagnostic setting, measuring monocyte subsets by flow cytometry in peripheral blood samples of 47 AAA patients under surveillance, matched with 25 healthy controls and 25 patients with peripheral artery disease (PAD). In a prognostic setting, we acquired longitudinal data of 60 AAA patients including aneurysm growth assessment by computed tomography at 6-month intervals., Results: Blood levels of total monocytes, CD16 + monocytes and particularly intermediate monocytes were significantly increased in AAA patients versus healthy individuals and were also elevated compared to PAD patients. The combination of intermediate monocyte and D-dimer blood levels outperformed the individual diagnostic marker values. Additionally, the elevated concentrations of total monocytes, intermediate monocytes, and monocyte-platelet aggregates (MPA) were suited to predict rapid AAA progression over short-term periods of six months. Of note, MPA were identified as independent predictor of AAA disease progression in multivariable analysis., Conclusion: Circulating monocyte subsets are elevated in AAA patients and support diagnosis and prediction of aneurysm progression. Monocyte subsets and D-dimer reflect different hallmarks (inflammation and hemostasis) of AAA pathology and when combined, may serve as improved biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Klopf, Zagrapan, Brandau, Lechenauer, Candussi, Rossi, Celem, Ziegler, Fuchs, Hayden, Krenn, Eilenberg, Neumayer and Brostjan.)

Purpose: Co-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency., Methods: A retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort., Results: Between 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association., Conclusion: In this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level., (© 2023. The Author(s).)

Neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, are released by neutrophils in response to pathogens but are also recognized for their involvement in a range of pathological processes, including autoimmune diseases, cancer, and cardiovascular diseases. This review explores the intricate roles of NETs in different cardiovascular conditions such as thrombosis, atherosclerosis, myocardial infarction, COVID-19, and particularly in the pathogenesis of abdominal aortic aneurysms. We elucidate the mechanisms underlying NET formation and function, provide a foundational understanding of their biological significance, and highlight the contribution of NETs to inflammation, thrombosis, and tissue remodeling in vascular disease. Therapeutic strategies for preventing NET release are compared with approaches targeting components of formed NETs in cardiovascular disease. Current limitations and potential avenues for clinical translation of anti-NET treatments are discussed.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA), located in adventitia and intraluminal thrombus. We compared the therapeutic potential of targeting upstream or downstream effector molecules of NET formation in 2 murine AAA models based on angiotensin II or peri-adventitial elastase application. In both models, NETs were detected in formed aneurysms at treatment start. Although NET inhibitors failed in the elastase model, they prevented progression of angiotensin II-induced aneurysms with thrombus, which resembles established human disease (including thrombus development). Blockade of upstream NET mediators was more effective than interference with downstream NET molecules., Competing Interests: This research was funded in whole by the Austrian Science Fund (FWF) [F 5409-B21 issued to Dr Brostjan]. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. Dr Bailey is personally supported by the British Heart Foundation (FS/18/12/33270) and Ms Knöbl by the DocFund program (DOC 59-833) of the Austrian Science Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Abdominal aortic aneurysm (AAA) and peripheral artery disease (PAD) share pathophysiological mechanisms including the activation of the fibrinolytic and innate immune system, which explains the analysis of D-dimer and myeloperoxidase (MPO) in both conditions. This study evaluates the diagnostic marker potential of both variables separately and as a combined MPO/D-dimer score for identifying patients with AAA versus healthy individuals or patients with PAD. Plasma levels of MPO and D-dimer were increased in PAD and AAA compared to healthy controls (median for MPO: 13.63 ng/mL [AAA] vs. 11.74 ng/mL [PAD] vs. 9.16 ng/mL [healthy], D-dimer: 1.27 μg/mL [AAA] vs. 0.58 μg/mL [PAD] vs. 0.38 μg/mL [healthy]). The combined MPO/D-dimer score (median 1.26 [AAA] vs. -0.19 [PAD] vs. -0.93 [healthy]) showed an improved performance in distinguishing AAA from PAD when analysed using the receiver operating characteristic curve (area under the curve) for AAA against the pooled data of healthy controls + PAD: 0.728 [MPO], 0.749 [D-dimer], 0.801 [score]. Diagnostic sensitivity and specificity ranged at 82.9% and 70.2% (for score cut-off = 0). These findings were confirmed for a separate collective of AAA patients with 35% simultaneous PAD. Thus, evaluating MPO together with D-dimer in a simple score may be useful for diagnostic detection and the distinction of AAA from athero-occlusive diseases like PAD.

Objective: To assess the early experience with modified version of simplified bare-wire target vessel (SMART) technique, implying delivery of bridging stent grafts without historically established sheath support, and to compare its outcome to standard endovascular aortic repair procedures with fenestrated/branched devices., Methods: A retrospective analysis of 102 consecutive patients treated with fenestrated/branched devices from January 2020 to December 2022 was undertaken. The study population was divided into three groups-a sheath group (SG), SMART group, and nonsheath group (NSG). Primary end points were radiation exposure (dose-area product), fluoroscopy time, dose of contrast agent, operation time, and incidence of intraoperative target vessel (TV) complications and additional procedures. Freedom from secondary TV related reinterventions at the three follow-up phases were defined as secondary end points., Results: A total of 183 TVs (38.8% visceral arteries [VA]; 56.3% renal arteries [RA]) in the SG, 36 TVs (44.4% VA, 55.6% RA) in the SMART group, and 168 TVs (47.6% VA; 50% RA) in the NSG were accessed. The mean number of fenestrations and bridging stent grafts was equally distributed in all three groups. The SMART group only included cases treated with fenestrated devices. The dose-area product was significantly lower in the SMART (median, 203 Gy × cm 2 ; interquartile range [IQR], 179-365 Gy × cm 2 ) and NSG (median, 340 Gy × cm 2 ; IQR, 220-651 Gy × cm 2 ) groups vs the SG (median, 464 Gy × cm 2 ; IQR, 267-871 Gy × cm 2 ; P = .007). Operation time was also significantly lower in the NSG (median, 265 minutes; IQR, 221-337 minutes) and SMART (median, 292 minutes; IQR, 234-351 minutes) groups vs the SG (median, 326 minutes; IQR, 277-375 minutes; P = .004), respectively. Intraoperative TV-related complications were most frequently observed in the SG (9/183 TVs; P = .008)., Conclusions: This study reports the outcomes of three currently available TV stenting approaches. Previously reported SMART technique, and its modified version (NSG) proved to be a safe alternative to historically established TV stenting technique with sheath support (SG)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

There is accumulating evidence that pro-inflammatory features are inherent to mitochondrial DNA and oxidized DNA species. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most frequently studied oxidatively generated lesion. Modified DNA reaches the circulation upon cell apoptosis, necrosis or neutrophil extracellular trap (NET) formation. Standard chromatography-based techniques for the assessment of 8-oxodGuo imply degradation of DNA to a single base level, thus precluding the attribution to a nuclear or mitochondrial origin. We therefore aimed to establish a protocol for the concomitant assessment of oxidized mitochondrial and nuclear DNA from human plasma samples. We applied immunoprecipitation (IP) for 8-oxodGuo to separate oxidized from non-oxidized DNA species and subsequent quantitative polymerase chain reaction (qPCR) to assign them to their subcellular source. The IP procedure failed when applied directly to plasma samples, i.e. isotype control precipitated similar amounts of DNA as the specific 8-oxodGuo antibody. In contrast, DNA isolation from plasma prior to the IP process provided assay specificity with little impact on DNA oxidation status. We further optimized sensitivity and efficiency of qPCR analysis by reducing amplicon length and targeting repetitive nuclear DNA elements. When the established protocol was applied to plasma samples of abdominal aortic aneurysm (AAA) patients and control subjects, the AAA cohort displayed significantly elevated circulating non-oxidized and total nuclear DNA and a trend for increased levels of oxidized mitochondrial DNA. An enrichment of mitochondrial versus nuclear DNA within the oxidized DNA fraction was seen for AAA patients. Regarding the potential source of circulating DNA, we observed a significant correlation of markers of neutrophil activation and NET formation with nuclear DNA, independent of oxidation status. Thus, the established method provides a tool to detect and distinguish the release of oxidized nuclear and mitochondrial DNA in human plasma and offers a refined biomarker to monitor disease conditions of pro-inflammatory cell and tissue destruction., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Monitoring of abdominal aortic aneurysms (AAAs) is currently based on serial measurements of maximum aortic diameter. Additional assessment of aneurysm volume has previously been proposed to possibly improve growth prediction and treatment decisions. To evaluate the use of supplementing volume measurements, the authors aimed to characterise the growth distribution of AAA volume and to compare the growth rates of the maximum diameter and volume at the patient level., Methods: Maximum diameter and volume were monitored every 6 months in 84 patients with small AAAs, with a total of 331 computed tomographic angiographies (with initial maximum diameters of 30-68 mm). A previously developed statistical growth model for AAAs was applied to assess the growth distribution of volume and to compare individual growth rates for volume and for maximum diameter., Results: The median (25-75% quantile) expansion in volume was 13.4 (6.5-24.7) % per year. Cube root transformed volume and maximum diameter showed a closely linear association with a within-subject correlation of 0.77. At the surgery threshold maximum diameter of 55 mm, the median (25-75% quantile) volume was 132 (103-167) ml. In 39% of subjects, growth rates for volume and maximum diameter were equivalent, in 33% growth was faster in volume and in 27% growth was faster in maximum diameter., Conclusion: At the population level, volume and maximum diameter show a substantial association such that the average volume is approximately proportional to the average maximum diameter raised to a power of three. At the individual level, however, in the majority of patient's AAAs grow at different pace in different dimensions. Hence, closer monitoring of aneurysms with sub-critical diameter but suspicious morphology may benefit from complementing maximum diameter by volume or related measurements., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This retrospective study evaluates the performance of UK National Institute for Health and Care Excellence (NICE) Guidelines on management of ruptured abdominal aortic aneurysms in a "real world setting" by emulating a hypothetical target trial with data from two European Aortic Centers., Methods: Clinical data was retrospectively collected for all patients who had undergone ruptured endovascular aneurysm repair (rEVAR) and ruptured open surgical repair (rOSR). Survival analysis was performed comparing NICE compliance to usual care strategy. NICE compliers were defined as: female patients undergoing rEVAR; male patients >70 years old undergoing rEVAR; and male patients ≤70 years old undergoing rOSR. Hemodynamic instability was considered additionally., Results: This multicenter study included 298 patients treated for rAAA. The majority of patients were treated with rOSR (186 rOSR vs. 112 rEVAR). Overall, 184 deaths (68 [37%] with rEVAR and 116 [63%] with rOSR) were observed during the study period. Overall survival under usual care was 69.2% at 30 days, 56.5% at one year, and 42.4% at 5 years. NICE compliance gave survival outcomes of 73.1% at 30 days, 60.2% at 1 year and 42.9% at 5 years. The risk ratios at these time points, comparing NICE-compliance to usual care, were 0.88, 0.92 and 0.99, respectively., Conclusions: We support NICE recommendations to manage men below the age of 71 years and hemodynamic stability with rOSR. There was a slight survival advantage for NICE compliers overall, in men >70 years and women of all ages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Eilenberg, Waduud, Davies, Bailey, Scott, Wolf, Sotir, Lakowitsch, Kaider, Heinze, Brostjan, Domenig and Neumayer.)

Objective: Endovascular aortic repair (EVAR) with fenestrated (F-EVAR) or branched (B-EVAR) endografts represents an indispensable tool of modern patient care in vascular surgery. The purpose of this retrospective study was to evaluate the center's initial experience of F/B-EVAR procedures performed under biplane angiography guidance compared with a historical control group., Methods: From January 2020 to March 2022, 80 consecutive patients underwent F/B-EVAR under general anesthesia at a single institution. As from January 2021, the deployment of complex stent grafts was performed using an alternative intraoperative imaging modality-a biplane fluoroscopy and angiography. The cohort was divided into monoplane (MPA) and biplane (BPA) groups according to the imaging modality applied. The end points were operation time, fluoroscopy time, radiation exposure, dose of contrast agent, and technical success., Results: The MPA group included 59 patients (78% male; median age; 74 years; interquartile range [IQR], 66-78 years) and the BPA group 21 patients (85.7% males; median age, 75 years; IQR, 69-79 years). Operation time (median, 320 minutes; IQR, 266-376 minutes) versus (median, 275 minutes; IQR, 216-333 minutes) was significantly lower in the BPA group (P = .006). The median fluoroscopy time (median, 82 minutes; IQR, 57-110 minutes vs median, 68 minutes; IQR, 54-92 minutes), contrast agent volume applied (median, 220 mL; IQR, 179-250 mL vs median, 200 mL; IQR, 170-250 mL), and radiation dose (dose-area product, median, 413 Gy × cm 2 ; IQR, 249-736 Gy × cm 2 ; vs median, 542 Gy × cm 2 ; IQR, 196-789 Gy × cm 2 ) were similar in both groups. Technical success of 96.6% (57/59 cases) versus 100% (21/21 cases) could be achieved in MPA and BPA group, respectively., Conclusions: F/B-EVAR procedures performed under BPA guidance were associated with a significant decrease in operation time., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Complex endovascular aortic repair (coEVAR) of thoracoabdominal aortic aneurysms (TAAA) has greatly evolved in the past decades. Despite substantial improvements of postoperative care, spinal cord injury (SCI) remains the most devastating complication of coEVAR being associated with impaired patient outcome and having an impact on long-term survival. The rising number of challenges of coEVAR, essentially associated with an extensive coverage of critical blood vessels supplying the spinal cord, resulted in the implementation of dedicated SCI prevention protocols. In addition to maintenance of adequate spinal cord perfusion pressure (SCPP), early detection of SCI plays an integral role in intra- and postoperative patient care. However, this is challenging due to difficulties with clinical neurological examinations during patient sedation in the postoperative setting. There is a rising amount of evidence, suggesting that subclinical forms of SCI might be accompanied by an elevation of biochemical markers, specific to neuronal tissue damage. Addressing this hypothesis, several studies have attempted to assess the potential of selected biomarkers with regard to early SCI diagnosis. In this review, we discuss biomarkers measured in patients undergoing coEVAR. Once validated in future prospective clinical studies, biomarkers of neuronal tissue damage may potentially add to the armamentarium of modalities for early SCI diagnosis and risk stratification.

Background: Abdominal aortic aneurysm (AAA) is a multifactorial vascular disease associated with high morbidity and mortality. Currently, surgical intervention is the only treatment option, and there is no drug therapy available for AAA. Hence, surveillance of AAA until indication for surgery may impact patient quality of life (QoL). There is a paucity of high-quality observational data on health status and QoL, particularly among AAA patients participating in randomized controlled trials. The objective of this study was to compare the QoL scores of AAA patients on surveillance to those of AAA patients enrolled in the MetAAA trial., Material and Methods: Overall, 54 MetAAA trial patients and 23 AAA patients under regular surveillance for small AAA (part of a longitudinal monitoring study) were asked to complete three established and validated (in total 561 longitudinally collected) QoL questionnaires: the 36-Item Short Form Health Survey (SF-36), the Aneurysm Symptom Rating Questionnaire (ASRQ), and the Aneurysm-Dependent Quality of Life questionnaire (ADQoL)., Results: A superior health status and QoL was found in AAA patients participating in the MetAAA trial compared to AAA patients under regular surveillance. In detail, MetAAA trial patients showed superior general health perception ( P =0.012), higher energy level ( P =0.036) as well as enhanced emotional well-being ( P =0.044) and fewer limitations due to general malaise ( P =0.021), which was subsequently reflected in an overall superior current QoL score ( P =0.039) compared to AAA patients under regular surveillance., Conclusion: AAA patients enrolled in the MetAAA trial showed superior health status and QoL compared to AAA patients under regular surveillance., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pharmacotherapy for abdominal aortic aneurysm (AAA) can be useful for prevention, especially in people at higher risk, for slowing down AAA progression, as well as for post-surgery adjuvant treatment. Our review focuses on novel pharmacotherapy approaches targeted towards slowing down progression of AAA, known also as secondary prevention therapy. Guidelines for AAA are not specific to slow down the expansion rate of an abdominal aortic aneurysm, and therefore no medical therapy is recommended. New ideas are urgently needed to develop a novel medical therapy. We are hopeful that in the future, pharmacologic treatment will play a key role in the prevention and treatment of AAA.

Background: To optimize our strategic planning, we aimed to investigate the impact of the COVID-19 pandemic on the treatment of patients with peripheral artery disease (PAD) at our tertiary care hospital. Methods: We performed a retrospective single-center cohort study. In total, 1210 patients were included: 611 patients admitted between March and December 2020, compared to retrospective data from 599 patients from the same period in 2019. Results: Emergency admissions involving patients with advanced stage PAD increased significantly during the pandemic period of 2020, compared to the same period in 2019 (p < 0.0098). This increase was accompanied by increased limb amputations performed during the first lockdown, post-lockdown and the second lockdown in 2020, compared to respective time periods in 2019 (p < 0.0003, p < 0.0004, p = 1). No SARS-CoV-2 infection was observed among patients with PAD during the observation period. Conclusions: Strict lockdown protocols adversely affected the care of PAD patients, with persisting aftereffects, including increased emergency admission with unsuccessful revascularization attempts leading to limb amputation, even after the peak of the pandemic had passed. We believe that providing continuous care to PAD patients, even in times of global pandemics, will prevent the unfavorable outcomes observed during the COVID-19 pandemic in 2020.

The maximal aortic diameter is the only clinically applied predictor of abdominal aortic aneurysm (AAA) progression and indicator for surgical repair. Circulating biomarkers resulting from AAA pathogenesis are attractive candidates for the diagnosis and prognosis of aneurysmal disease. Due to the reported role of interleukin 33 in AAA development, we investigated the corresponding circulating receptor molecules of soluble suppression of tumorigenesis 2 (sST2) in AAA patients regarding their marker potential in diagnosis and prognosis. We conducted a single-center retrospective cohort study in a diagnostic setting, measuring the circulating serum sST2 protein levels of 47 AAA patients under surveillance, matched with 25 peripheral artery disease (PAD) patients and 25 healthy controls. In a prognostic setting, we analyzed the longitudinal monitoring data of 50 monitored AAA patients. Slow versus fast AAA progression was defined as a <2 or ≥2 mm increase in AAA diameter over 6 months and a <4 or ≥4 mm increase over 12 months. Additionally, the association of circulating serum sST2 and AAA growth was investigated using a specifically tailored log-linear mixed model. Serum sST2 concentrations were significantly increased in AAA patients compared with healthy individuals: the median of AAA patient cohort was 112.72 ng/mL (p = 0.025) and that of AAA patient cohort 2 was 14.32 ng/mL (p = 0.039) versus healthy controls (8.82 ng/mL). Likewise, PAD patients showed significantly elevated sST2 protein levels compared with healthy controls (the median was 12.10 ng/mL; p = 0.048) but similar concentrations to AAA patients. Additionally, sST2 protein levels were found to be unsuited to identifying fast AAA progression over short-term periods of 6 or 12 months, which was confirmed by a log-linear mixed model. In conclusion, the significantly elevated protein levels of sST2 detected in patients with vascular disease may be useful in the early diagnosis of AAA but cannot distinguish between AAA and PAD or predict AAA progression.

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse models, are applied to advance the understanding of the disease pathogenesis and to identify potential therapeutic targets. Testing novel drug candidates to block AAA growth in these models generally requires repeated drug administration during the time course of the experiment. Here, we describe a compiled protocol for AAA induction, insertion of an intravenous catheter to facilitate prolonged therapy, and serial AAA monitoring by 3D ultrasound. Aneurysms are induced in apolipoprotein E (ApoE) deficient mice by angiotensin II release over 28 days from osmotic mini-pumps implanted subcutaneously into the mouse back. Subsequently, the surgical procedure for external jugular vein catheterization is conducted to allow for daily intravenous drug treatment or repeated blood sampling via a subcutaneous vascular access button. Despite the two dorsal implants, the monitoring of AAA development is readily facilitated by sequential semi-automated 3D ultrasound analysis, which yields comprehensive information on the expansion of aortic diameter and volume and on aneurysm morphology, as illustrated by experimental examples.

Objective: The purpose of this study was to assess the associations between malignancy, therapeutic regimens, and aorto-iliac aneurysm (i.e., abdominal aortic aneurysm [AAA]) growth rates., Methods: A retrospective single centre analysis identified patients with an AAA plus cancer. Patients who had two or more computed tomography angiograms over six months or more and additional malignancy were included. Clinical data and aneurysm diameters were analysed. AAA growth under cancer therapy (chemotherapy or radiation) was compared with a non-cancer AAA control cohort and to meta-analysis data. Statistics included t tests and a linear regression model with correction for initial aortic diameter and type of treatment., Results: From 2003 to 2020, 217 patients (median age 70 years; 92% male) with 246 aneurysms (58.8% AAA) and 238 malignancies were identified. Prostate (26.7%) and lung (15.7%) cancer were most frequently seen. One hundred and fifty-seven patients (72.3%) received chemotherapy, 105 patients (48.4%) radiation, and 79 (36.4%) both. Annual AAA growth (mean ± standard deviation) was not statistically significantly different for cancer and non-cancer patients (2.0 ± 2.3 vs. 2.8 ± 2.1 mm/year; p = .20). However, subgroup analyses revealed that radiation was associated with a statistically significantly reduced mean aneurysm growth rate compared with cancer patients without radiation (1.1 ± 1.3 vs. 1.6 ± 2.1 mm/year; p = .046) and to the non-cancer control cohort (1.7 ± 1.9 vs. 2.8 ± 2.1 mm/year; p = .007). Administration of antimetabolites resulted in statistically significantly increased AAA growth (+ 0.9 mm/year; p = .011), while topoisomerase inhibitors (- 0.8 mm/year; p = .17) and anti-androgens (- 0.5 mm/year; p = .27) showed a possible trend for reduced growth. Similar observations were noted for iliac aneurysms (n = 85). Additionally, the effects persisted for chemotherapy combinations (2.6 ± 1.4 substances/patient)., Conclusion: Patients with cancer and concomitant aortic aneurysms may require intensified monitoring when undergoing specific therapies, such as antimetabolite treatment, as they may experience an increased aneurysm growth rate. Radiation may be associated with reduced aneurysm growth., (Copyright © 2022 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Available mouse models for abdominal aortic aneurysms (AAAs) differ substantially in the applied triggers, associated pathomechanisms and rate of vessel expansion. While maximum aortic diameter (determined after aneurysm excision or by 2D ultrasound) is commonly applied to document aneurysm development, we evaluated the sensitivity and reproducibility of 3D ultrasound to monitor aneurysm growth in four distinct mouse models of AAA., Methods: The models included angiotensin-II infusion in ApoE deficient mice, topical elastase application on aortas in C57BL/6J mice (with or without oral administration of β-aminoproprionitrile) and intraluminal elastase perfusion in C57BL/6J mice. AAA development was monitored using semi-automated 3D ultrasound for aortic volume calculation over 12 mm length and assessment of maximum aortic diameter., Results: While the models differed substantially in the time course of aneurysm development, 3D ultrasound measurements (volume and diameter) proved highly reproducible with concordance correlation coefficients > 0.93 and variations below 9% between two independent observers. Except for the elastase perfusion model where aorta expansion was lowest and best detected by diameter increase, all other models showed high sensitivity of absolute volume and diameter measurements in monitoring AAA formation and progression by 3D ultrasound. When compared to standard 2D ultrasound, the 3D derived parameters generally reached the highest effect size., Conclusion: This study has yielded novel information on the robustness and limitations of semi-automated 3D ultrasound analysis and provided the first direct comparison of aortic volume increase over time in four widely applied mouse models of AAA. While 3D ultrasound generally proved highly sensitive in detecting early AAA formation, the 3D based volume analysis was found inferior to maximum diameter assessment in the elastase perfusion model where the extent of inflicted local injury is determined by individual anatomical features., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ibrahim, Bleichert, Klopf, Kurzreiter, Knöbl, Hayden, Busch, Stiglbauer-Tscholakoff, Eilenberg, Neumayer, Bailey and Brostjan.)

Background: In this study, we evaluate the outcome of renal function in patients undergoing juxtarenal abdominal aortic aneurysm repair with or without division of the left renal vein with special focus on the role of the communicating lumbar vein., Methods: A retrospective analysis of prospectively collected data of 110 patients undergoing elective juxtarenal abdominal aortic aneurysm repair between 2000 and 2018 was performed. The demographic characteristics and comorbidities were reviewed in detail and the renal function was analysed pre- and post-operatively. The cohort of patients was split into group A (left renal vein divided) and B (left renal vein mobilised). Group A was further sub-analysed regarding the presence of a communicating lumbar vein on preoperative imaging data (group A+ = vein present, group A- = no communicating lumbar vein present)., Results: The patients were matched well regarding their demographic characteristics and comorbidities. In the analysis of renal function, no statistically significant difference could be detected between group A and B. In the sub-analysis of group A, the group with a communicating lumber vein (group A+) turned out to have a significantly better renal function in the long term (sCrea 0.87 vs. 1.51; p = 0.016)., Conclusion: Ligation of the left renal vein is a safe procedure in surgery of juxtarenal aortic aneurysms regarding the outcome of the renal function. A communicating lumbar vein between the left renal vein and the left ascending lumbar vein seems to play a key role to provide venous drainage after division of the left renal vein., (© 2022. The Author(s).)

Purpose: To compare bridging stent graft (BSG) implantation in downward oriented branches in branched endovascular aortic repair (bEVAR), using a commercially available steerable sheath from an exclusively femoral access (TFA) with traditional upper extremity access (UEA)., Methods: In a retrospective cohort study, 7 patients with 19 branches in the TFA cohort received BSG insertion using the Medtronic Heli FX steerable sheath from a femoral access, and 10 patients with 32 branches in the UEA cohort from a brachial approach. Technical success, total intervention time, fluoroscopy time, branch cannulation time, and complication rate were recorded., Results: Technical success was 19/19 branches in the TFA and 31/32 in the UEA cohort. The mean branch cannulation time was considerably shorter in the TFA group (17 vs. 29 min, p = 0.003), and total intervention time tended to be shorter (169 vs. 217 min, p = 0.176)., Conclusion: Using a commercially available steerable sheath allowed successful cannulation of all branches in this cohort and was associated with significantly shorter branch cannulation times. Potentially, this technique can lower the stroke and brachial puncture site complication risk as well as reduce total intervention time and radiation dose., Level of Evidence: 2b, retrospective cohort study., (© 2022. The Author(s).)

Objective: The maximal aortic diameter is currently the only clinically applied predictor of abdominal aortic aneurysm (AAA) progression. It is known that the risk of rupture is associated with aneurysm size; hence, accurate monitoring of AAA expansion is crucial. Aneurysmal vessel wall calcification and its implication on AAA expansion are insufficiently explored. We evaluated the vascular calcification using longitudinal computed tomography angiographies (CTA) of patients with an AAA and its association with AAA growth., Methods: We conducted a retrospective study of 102 patients with an AAA with a total of 389 abdominal CTAs at 6-month intervals, treated and followed at the Division of Vascular Surgery, Department of General Surgery, Medical University of Vienna. Digitally stored CTAs were reviewed for vascular calcification (volume and score) of the infrarenal aorta and common iliac arteries as well as for morphometric AAA analysis. In the prognostic setting, slow versus fast AAA progression was defined as a less than 2 mm or a 2-mm or greater increase in AAA diameter over 6 months. In addition, to analyze the association of vascular calcification and the AAA growth rate with longitudinal monitoring data, a specifically tailored log-linear mixed model was used., Results: An inverse relation of increased abdominal vessel wall calcification and short-term AAA progression was detected. Compared with fast progressing AAA, the median calcification volume of the infrarenal aorta (1225.3 mm³ vs 519.8 mm³; P = .003), the median total calcification volume (2014.1 mm³ vs 1434.9 mm³; P = .008), and the median abdominal total customized Agatston calcium (cAC) score (1663.5 vs 718.4; P = .003) were significantly increased in slow progressing AAA. Importantly, a log-linear mixed model efficiently predicted AAA expansion based on current diameter and abdominal total cAC score (P = .042)., Conclusions: We assessed the prognostic value of CTA-measured vascular calcification for AAA progression. Increased vascular calcification stabilizes the aortic aneurysmal wall and likely protects against progressive AAA expansion, resulting in a significant decrease of aneurysm growth over time. As a consequence, this may have implications for rupture risk, mortality, morbidity, and cost., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The most relevant determinant in scheduling monitoring intervals for abdominal aortic aneurysms (AAAs) is maximum diameter. The aim of the study was to develop a statistical model that takes into account specific characteristics of AAA growth distributions such as between-patient variability as well as within-patient variability across time, and allows probabilistic statements to be made regarding expected AAA growth., Methods: CT angiography (CTA) data from patients monitored at 6-month intervals with maximum AAA diameters at baseline between 30 and 66 mm were used to develop the model. By extending the model of geometric Brownian motion with a log-normal random effect, a stochastic growth model was developed. An additional set of ultrasound-based growth data was used for external validation., Results: The study data included 363 CTAs from 87 patients, and the external validation set comprised 390 patients. Internal and external cross-validation showed that the stochastic growth model allowed accurate description of the distribution of aneurysm growth. Median relative growth within 1 year was 4.1 (5-95 per cent quantile 0.5-13.3) per cent. Model calculations further resulted in relative 1-year growth of 7.0 (1.0-16.4) per cent for patients with previously observed rapid 1-year growth of 10 per cent, and 2.6 (0.3-8.3) per cent for those with previously observed slow growth of 1 per cent. The probability of exceeding a threshold of 55 mm was calculated to be 1.78 per cent at most when adhering to the current RESCAN guidelines for rescreening intervals. An online calculator based on the fitted model was made available., Conclusion: The stochastic growth model was found to provide a reliable tool for predicting AAA growth., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Neutrophil extracellular traps (NETs) are DNA-protein structures released by neutrophils in response to various stimuli, including oxidized, low-density lipoprotein (oxLDL). Accumulating evidence suggests a role for NETs in the pathogenesis of abdominal aortic aneurysm (AAA). In this study, we investigated the potential association of lipoprotein particles and NETs in AAA in comparison to non-AAA control groups. The concentrations of neutrophil myeloperoxidase (MPO), the NET parameters citrullinated histone H3 (citH3) and circulating cell-free DNA (cfDNA), as well as of blood lipids were determined in plasma or serum of patients with AAA ( n = 40), peripheral artery occlusive disease (PAD; n = 40) and healthy donors ( n = 29). A sandwich ELISA detecting oxidized phosphatidylcholine in association with apolipoprotein B-100 (oxPL/apoB) was applied to measure oxidized phospholipids in circulation. The effect of lipoparticles on NET formation was tested using a DNA release assay with isolated human neutrophils. Plasma MPO, citH3 and cfDNA levels were significantly increased in AAA patients in comparison to healthy donors and PAD patients. Plasma concentrations of citH3 positively correlated with serum oxPL/apoB in AAA patients. In functional in vitro assays, the addition of oxLDL induced NET formation in pre-stimulated neutrophils. In conclusion, our data suggest a promoting role of oxLDL on NET formation in AAA patients.

Despite declining incidence and mortality rates in many countries, the abdominal aortic aneurysm (AAA) continues to represent a life-threatening cardiovascular condition with an overall prevalence of about 2-3% in the industrialized world. While the risk of AAA development is considerably higher for men of advanced age with a history of smoking, screening programs serve to detect the often asymptomatic condition and prevent aortic rupture with an associated death rate of up to 80%. This review summarizes the current knowledge on identified risk factors, the multifactorial process of pathogenesis, as well as the latest advances in medical treatment and surgical repair to provide a perspective for AAA management.

Background: Stroke and neurological injury are a complication of thoracic endovascular aortic repair (TEVAR). Cerebral microbleeds (CMBs) are common in patients with white matter damage to the brain secondary to chronic vasculopathy. The aim of this study was to examine the occurrence of CMBs after TEVAR, and to evaluate their association with patient and procedural factors., Methods: Patients who underwent TEVAR between September 2018 and January 2020 in two specialist European aortic centres were analysed. All patients underwent postoperative susceptibility-weighted MRI. The location and number of CMBs were identified, and analysed with regard to procedural aspects, clinical outcome, and Fazekas score as an indicator of pre-existing vascular leucoencephalopathy., Results: Some 91 patients were included in the study. A total of 1531 CMBs were detected in 58 of 91 patients (64 per cent). In the majority of affected patients, CMBs were found bilaterally (79 per cent). Unilateral CMBs in the right or left hemisphere occurred in 16 and 5 per cent of patients respectively (P < 0.001). More CMBs were found in the middle cerebral than in the vertebrobasilar/posterior and anterior cerebral artery territories (mean(s.d.) 3.35(5.56) versus 2.26(4.05) versus 0.97(2.87); P = 0.045). Multivariable analysis showed an increased probability of CMBs after placement of TEVAR stent-grafts with a proximal diameter of at least 40 mm (odds ratio (OR) 6.85, 95 per cent c.i. 1.65 to 41.59; P = 0.007) and in patients with a higher Fazekas score on postoperative T2-weighted MRI (OR 2.62, 1.06 to 7.92; P = 0.037)., Conclusion: CMBs on postoperative MRI are common after endovascular repair in the aortic arch. Their occurrence appears to be associated with key aspects of the procedure and pre-existing vascular leucoencephalopathy., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)