Long-term outcome of cervical artery dissection.

OBJECTIVE: The aim of the study is to evaluate the natural history of extracranial cervical artery dissection (CAD) including comorbidities, symptoms at presentation, recurrence of symptoms, and long-term outcome following different treatment approaches. METHODS: A retrospective review of patients treated for acute CAD was performed over a 5-year period from January 2017 to April 2022. RESULTS: Thirty-nine patients were included in the study, 25 (64.1%) with acute internal carotid artery dissection and 14 (35.9%) with acute vertebral artery dissection. Thirty-four patients (87.1%) had spontaneous CAD, and five patients (12.8%) had traumatic CAD. The mean age of the cohort was 54.2 years. The mean time from symptom onset to presentation was 4.34 days. The most common symptoms in internal carotid artery dissection were unilateral weakness (44%), headache (44%), slurred speech (36%), facial droop (28%), unilateral paraesthesia (24%), neck pain (12%), visual disturbance (8%), and Horner's syndrome (8%). The most common symptoms in vertebral artery dissection were headache (35.7%), neck pain (35.7%), vertigo (28.57%), ataxia (14.28%), and slurred speech (14.28%). The imaging modalities used for diagnosis included computed tomography angiography (48.7%), magnetic resonance angiography (41%), and duplex ultrasound (10.2%). In patients with carotid artery dissection, 57% had severe stenosis, 24% had moderate stenosis, and 20% had mild stenosis. All patients treated were managed conservatively with either anticoagulation or antiplatelets. Long-term clinical follow-up was available for 33 patients (84.6%). Thirty patients (90.9%) reported complete resolution of symptoms, and three patients (9%) reported persistent symptoms. Anatomic follow-up with imaging was available for 17 patients (43.58%). Thirteen patients (76.47%) had complete resolution of dissection, two patients (11.76%) had partial resolution of dissection, and two patients (11.76%) had persistent dissection. There was one death unrelated to CAD in a multi-trauma patient. There were four early recurrent symptoms in the first 3 to 8 weeks post discharge. The mean follow-up time was 308.27 days. CONCLUSIONS: The majority of CADs can be managed conservatively with good clinical and anatomical outcome and low rates of recurrence.

Necrotising fasciitis in the COVID-19 era: A consequence of caution - A case series.

Necrotising fasciitis (NF) is a severe soft tissue infection that is associated with a high risk of morbidity and mortality. During the coronavirus disease 19 (COVID-19) pandemic, the population has been actively discouraged from presenting to emergency medical services unless absolutely necessary. While this was an important step in allowing for preservation of limited resources in a time of crisis, it may have resulted in immeasurable 'secondary victims' of the pandemic as patients with time-critical conditions delay hospital presentation. In this case series, we describe three patients that noted symptoms of soft tissue infection, but delayed seeking healthcare advice due to concerns regarding COVID-19 exposure. All three progressed to NF, requiring highly morbid wide surgical debridement and prolonged hospital admission, with a high risk of potential mortality. The findings of this series demonstrate the importance of consistently delivering appropriate and timely healthcare interventions to patients with non-COVID-19-related conditions. While efforts must be made to ensure preservation of valuable healthcare resources in a global pandemic, patients must also be empowered to seek timely care for non-COVID-19-related conditions even in this time of crisis.

Effect of Pseudomonas colonisation on lower limb venous ulcer healing: a systematic review.

OBJECTIVE: Pseudomonas aeruginosa is a Gram-negative bacillus that commonly colonises lower limb venous ulcers. Its effects on venous ulcer healing are widely debated. It produces exotoxins and elastase, as well as forming biofilms in hard-to-heal wounds. It is postulated that these virulence factors lead to slower healing times in patients with lower limb venous ulcers colonised with Pseudomonas. This review aimed to summarise the available evidence pertaining to this topic. METHOD: A systematic review was performed in August 2019, where the Pubmed, Cochrane and Embase databases were searched for relevant literature according to PRISMA guidelines. Retrospective and prospective studies examining the effect of Pseudomonas colonisation on any measure of ulcer healing were included. RESULTS: Some 282 articles were screened, of which seven studies including 491 patients were ultimately included for analysis. Of these, no study demonstrated a significant association between Pseudomonas colonisation and delayed healing of venous ulcers. In five of the seven studies, the effect of Pseudomonas aeruginosa on initial ulcer size at presentation was recorded. CONCLUSION: All the studies demonstrated an association between ulcer size and the presence of Pseudomonas aeruginosa. While Pseudomonas aeruginosa may colonise larger ulcers or those with a worse prognosis, no evidence was found to support the hypothesis that this colonisation had a negative impact on lower limb venous ulcer healing.

Outcomes of Acute Limb Ischaemia in Patients with Underlying Malignancy: A Systematic Review.

OBJECTIVE: Previous studies have demonstrated amputation and mortality rates to be 14.3% - 30% and 11.4% - 28.9%, respectively, for all patients presenting with acute limb ischaemia (ALI). Rates of ALI are higher in patients with malignancy than in those without. Despite this, there remains uncertainty with regards to the most appropriate management for patients with cancer presenting with ALI. This is because of previously published high rates of associated morbidity and mortality in this population. The aim of this review was to summarise the available evidence reporting on outcomes of ALI in patients with underlying malignancy. METHOD: A systematic review was performed in August 2020 in accordance with the PRISMA guidelines. The Medline, Scopus, Cochrane, and Embase databases were searched with the following search string ((acute limb ischaemia) OR (acute limb ischemia)) AND ((cancer) OR (malignancy)). A total of 849 papers were identified and reviewed; six studies were included. Studies were assessed for bias using the National Institute of Health/National Heart, Lung and Blood Institute Quality Assessment Tool. Data including demographics, Rutherford classification, baseline performance scores, method of revascularisation, and peri-procedural outcomes were extracted and analysed. Data were pooled based on outcomes of interest and pooled prevalence was reported with 95% confidence intervals (CI). RESULTS: Six studies with 284 patients with cancer were included for analysis. The pooled overall risk of amputation was 15% (95% CI 5.9 - 26.9). The pooled 30 day mortality rate was 24% (95% CI 14.7 - 34.6). CONCLUSION: Despite limitations of interstudy selection bias and some clinical heterogeneity, the included studies demonstrated acceptable short and medium term outcomes for patients with cancer undergoing revascularisation for acute limb ischaemia. This is in line with current recommendations that patients with underlying malignancy should be considered strongly for revascularisation.

Rescue of Failed Aortic Repair with Fenestrated Endovascular Device.

INTRODUCTION: The incidence of failed endovascular (EVAR) and open repair (OR) is increasing. Redo aortic repair is required in 10% of patients. Extension of the proximal sealing zone above the visceral arteries to adequate, healthier thoracic aorta using a fenestrated graft (FEVAR) can rescue a failing repair. A custom-made device can treat proximal type 1a endoleaks or proximal dilatation post endovascular or open repair, respectively. The aim of this investigation was to present a single-centre experience with FEVAR for patients with a failing aortic repair. METHODS: A prospectively maintained database of FEVAR patients treated with a ZenithⓇ Fenestrated endovascular (ZFEN) device (Cook Medical LLC, Bloomington, Indiana, USA) was interrogated for individuals who had the device implanted as a rescue therapy after prior endovascular (EVAR) or open repair (OR). Statistical analysis was performed with SPSS v 25 software. RESULTS: Between January 1, 2011 and March 31, 2019, 17 ZFEN devices were implanted. 10 patients had a type 1a endoleak from a prior EVAR and 7 patients had proximal disease progression after prior OR. There were 12 males and 5 females, median age of 75 (interquartile range, IQR 7). 76.4% (n = 13) of patients had an American Society of Anaesthesiologists (ASA) grade of 3. Primary technical success was 70.5% (n = 12). Of the remainder, 4 cases (24%) had a type III endoleak at completion angiogram; of which, 2 patients (12%) required re-intervention within 30 days. One further case (6%) had primary assisted technical success as stenting of a flow limiting dissection flap in an iliac vessel was required. Peri-operative rate of deployment related complications and systemic complications were 5.8% (n = 1) and 35% (n = 6), respectively. Median length of hospital stay was 11 days (IQR 11). There was no mortality within the study follow up. Overall 30-day re-intervention rate was 23.5%. Overall survival was 92% at one year. CONCLUSION: FEVAR is a safe but technically challenging option for rescue of failing aortic repairs. These are a high-risk group of patients and this is reflected in the high post-operative morbidity rate. Technical success was high and 30-day mortality was low.

Open repair of a type II endoleak facilitated by temporary disconnection of graft components.

Endoleaks are a frequent indication for reintervention after endovascular repair of an abdominal aortic aneurysm. Here we present a method of open repair of a persistent type II endoleak involving graft component separation and reconstruction, in a patient with symptomatic interval aneurysmal sac enlargement despite endovascular coiling and embolization. This case report demonstrates an alternative open technique of endograft component separation and reconstruction that may be required in cases where open repair with sac exploration and vessel oversewing is hindered by the graft position.

Systematic review on the incidence and management of endovenous heat-induced thrombosis following endovenous thermal ablation of the great saphenous vein.

OBJECTIVE: A systematic review and meta-analysis was performed to determine the incidence of endovenous heat-induced thrombosis (EHIT) and evaluate its management after endovenous thermal ablation of the great saphenous vein (GSV). METHODS: MEDLINE and Embase were searched for studies with at least 100 patients who underwent great saphenous vein endovenous thermal ablation and had duplex ultrasound follow-up within 30 days. Data were gathered on the incidence of thrombotic complications and on the management of cases of EHIT. The primary outcome for the meta-analysis was EHIT types 2 to 4 and secondary outcomes were deep venous thrombotic events (which we defined as types 2-4 EHIT plus deep vein thrombosis [DVT]), DVT, and pulmonary embolism (PE). Pooled proportions were calculated using random effects modelling. RESULTS: We included 75 studies (23,265 patients). EHIT types 2 to 4 occurred in 1.27% of cases (95% confidence interval [CI], 0.74%-1.93%). Deep venous thrombotic events occurred in 1.59% (95% CI, 0.95%-2.4%). DVT occurred in 0.28% (95% CI, 0.18%-0.4%). Pulmonary embolism occurred in 0.11% (95% CI, 0.06%-0.18%). Of the 75 studies, 24 gave a description of the management strategy and outcomes for EHIT and there was inconsistency regarding its management. Asymmetrical funnel plots of studies that reported incidence of EHIT 2 to 4 and DVT suggest publication bias. CONCLUSIONS: The recently published guidelines on EHIT from the Society for Vascular Surgery/American Venous Forum provide a framework to direct clinical decision-making. EHIT and other thrombotic complications occur infrequently and have a benign course.

An international experience of electronic communication and implementation of eHealth solutions in a vascular surgery clinic.

INTRODUCTION: Communication is key to any successful relationship with the patient-physician partnership being no different. Recent advances in technology have provided us with an array of new communication tools such as the mobile phone, computer, internet, and email. This new technology has revolutionized communications; however, limitations to their widespread use include access, literacy, and willingness for both the physician and patient to change. METHODS: To gather international data, questionnaires were completed by patients attending vascular surgery outpatient clinics in hospitals in Ireland and Canada. RESULTS: Five hundred ninety-seven patients participated in the study. Of the participants, 83.2% were over 50 years old. The mean age was 63.1 years, with a range of 18-95 years. Overall, home phone call was the most preferred method of communication with 41.0% of patients selecting this option. Of the patients, 82.4% had a mobile phone but just 48.5% use text message. In those over the age of 70, 72.1% use a mobile phone and just 25.3% use text message. Of the participants, 64.1% had access to a computer, and 67.2% had access to the internet with a decline in the usage of both with increasing age. DISCUSSION: Within this patient population, the use of technologies decreases with increasing age of the patients. This demonstrates a large population of service users who are contented with conventional methods of communication. Change within healthcare ICT is inevitable, and therefore, these patients need to be guided and educated to allow a smooth transition from the old to the new.

Hybrid covered endovascular reconstruction of the aortic bifurcation (CERAB) procedure is preferable to aortobifemoral bypass for limb-threatening aortoiliac occlusive disease during the COVID-19 crisis.

The COVID-19 pandemic is disrupting the provision of acute vascular surgery across the globe. Limited evidence of the impact of nosocomial infection on patient outcomes as well as concerns about critical care capacity will likely have an impact on surgical decision-making. Endovascular therapy offers a way by which perioperative risk can be reduced for vascular patients while also reducing the impact of acute surgery on intensive care unit capacity. This case report describes the management of a patient with complex aortoiliac occlusive disease by a hybrid endovascular approach in light of these constraints, with a successful outcome.

Correlating Ex Vivo Carotid Calcification Measurements With Cerebrovascular Symptoms: A Proof-of-Concept Study.

BACKGROUND AND PURPOSE: The purpose of this study is to examine the ability of ex vivo derived Agatston, Volume, and Density-Volume calcium scores or calcium density measurements to differentiate between carotid plaques based on preoperative cerebrovascular symptomatology. METHODS: Thirty-eight carotid plaques were acquired from standard endarterectomy. Micro-computed tomography was performed on the ex vivo samples. Image series were downsampled to represent the resolution of clinical multidetector computed tomography. Agatston, Volume, and Density-Volume carotid calcium scores were then calculated using coronary methodologies. The fractions of low- and high-density calcification were also determined. RESULTS: The coronary calcium scores could not differentiate between carotid plaques from asymptomatic versus symptomatic patients. However, plaques from asymptomatic patients contained significantly lower fractions of low-density calcification and higher fractions of high-density calcification. CONCLUSIONS: Screening for carotid calcium density in noncontrast computed tomography could reflect plaque stability.

Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities.

BACKGROUND: Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI. METHODS: Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs. RESULTS: A high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy. CONCLUSIONS: The results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.

Transient iatrogenic Horner's syndrome following carotid endarterectomy.

We present a case of a 72-year-old man who developed a transient Horner's syndrome in the immediate postoperative period after right carotid endarterectomy which resolved within 3 months. Although Horner's syndrome has been reported with several disorders of the carotid artery, our case documents a rare iatrogenic oculosympathetic paresis after elective carotid endarterectomy.

Relating the mechanical properties of atherosclerotic calcification to radiographic density: A nanoindentation approach.

Calcification morphology can determine atherosclerotic plaque stability and is associated with increased failures rates for endovascular interventions. Computational efforts have sought to elucidate the relationship between calcification and plaque rupture in addition to predicting tissue response during aggressive revascularisation techniques. However, calcified material properties are currently estimated and may not reflect real tissue conditions. The objective of this study is to correlate calcification mechanical properties with three radiographic density groups obtained from corresponding Computed Tomography (CT) images. Seventeen human plaques extracted from carotid (n = 10) and peripheral lower limb (n = 7) arteries were examined using micro-computed tomography (µCT), simultaneously locating the calcified deposits within their internal structure and quantifying their densities. Three radiographic density groups were defined based on the sample density distribution: (A) 130-299.99 Hounsfield Units (HU), (B) 300-449.99 HU and (C) >450 HU. Nanoindentation was employed to determine the Elastic Modulus (E) and Hardness (H) values within the three density groups. Results reveal a clear distinction between mechanical properties with respect to radiographic density groups (p < 0.0005). No significant differences exist in the density-specific behaviours observed between carotid and peripheral samples. Previously defined calcification classifications indicate an association with specific radiographic density patterns. Scanning Electron Microscopy (SEM) examination revealed that density group A regions consist of both calcified and non-calcified tissues. Further research is required to define the radiographic thresholds which identify varying degrees of tissue calcification. This study demonstrates that the mechanical properties of fully mineralised atherosclerotic calcification emulate that of bone tissues (17-25 GPa), affording computational models with accurate material parameters. STATEMENT OF SIGNIFICANCE: Global mechanical characterisation techniques disregard the heterogeneous nature of atherosclerotic lesions. Previous nanoindentation results for carotid calcifications have displayed a wide range. This study evaluates calcification properties with respect to radiographic density obtained from Micro-CT images. This is the first work to characterise calcifications from peripheral lower limb arteries using nanoindentation. Results demonstrate a strong positive correlation between radiographic density and calcification mechanical properties. Characterising calcifications using their density values provides clarity on the variation in published properties for calcified tissues. Furthermore, this study confirms the hypothesis that fully calcified plaque tissue behaviour similar to that of bone. Appropriate material parameters for calcified tissues can now be employed in computational simulations.

A Systematic Review and Meta-analysis of Thrombotic Events Following Endovenous Thermal Ablation of the Great Saphenous Vein.

OBJECTIVES: A systematic review and meta-analysis was performed to determine the incidence of thrombotic events following great saphenous vein (GSV) endovenous thermal ablation (EVTA). METHODS: MEDLINE, Embase and conference abstracts were searched. Eligible studies were randomised controlled trials and case series that included at least 100 patients who underwent GSV EVTA (laser ablation or radiofrequency ablation [RFA]) with duplex ultrasound (DUS) within 30 days. The systematic review focused on the complications of endovenous heat induced thrombosis (EHIT), deep venous thrombosis (DVT), and pulmonary embolism (PE). The primary outcome for the meta-analysis was deep venous thrombotic events which were defined as DVT or EHIT Type 2, 3, or 4. Secondary outcomes for the meta-analysis were EHIT Type 2, 3, or 4, DVT and PE. Subgroup analyses were performed for both the RFA and EVLA groups. Pooled proportions were calculated using random effects modelling. RESULTS: Fifty-two studies (16,398 patients) were included. Thrombotic complications occurred infrequently. Deep venous thrombotic events occurred in 1.7% of cases (95% CI 0.9-2.7%) (25 studies; 10,012 patients; 274 events). EHIT Type 2, 3, or 4 occurred in 1.4% of cases (95% CI 0.8-2.3%) (26 studies; 10,225 patients; 249 events). DVT occurred in 0.3% of cases (95% CI = 0.2%-0.5%) (49 studies; 15,676 patients; 48 events). PE occurred in 0.1% of cases (95% CI = 0.1-0.2%) (29 studies; 8223 patients; 3 events). Similar results were found when the RFA and EVLA groups were analysed separately. CONCLUSION: Thrombotic events occur infrequently following GSV EVTA. Given the large numbers of procedures worldwide and the potential for serious consequences, further research is needed on the burden of these complications and their management.

On the influence of wall calcification and intraluminal thrombus on prediction of abdominal aortic aneurysm rupture.

OBJECTIVE: Parameters other than maximum diameter that predict rupture of abdominal aortic aneurysms (AAAs) may be helpful for risk-benefit analysis in individual patients. The aim of this study was to characterize the biomechanical-structural characteristics associated with AAA walls to better identify the related mechanistic variables required for an accurate prediction of rupture risk. METHODS: Anterior AAA wall (n = 40) and intraluminal thrombus (ILT; n = 114) samples were acquired from 18 patients undergoing open surgical repair. Biomechanical characterization was performed using controlled circumferential stretching tests combined with a speckle-strain tracking technique to quantify the spatial heterogeneity in deformation and localized strains in the AAA walls containing calcification. After mechanical testing, the accompanying microstructural characteristics of the AAA wall and ILT types were examined using electron microscopy. RESULTS: No significant correlation was found between the AAA diameter and the wall mechanical properties in terms of Cauchy stress (rs = -0.139; P = .596) or stiffness (rs = -0.451; P = .069). Quantification of significant localized peak strains, which were concentrated in the tissue regions surrounding calcification, reveals that peak strains increased by a mean of 174% as a result of calcification and corresponding peak stresses by 18.2%. Four ILT types characteristic of diverse stages in the evolving tissue microstructure were directly associated with distinct mechanical stiffness properties of the ILT and underlying AAA wall. ILT types were independent of geometric factors, including ILT volume and AAA diameter measures (ILT stiffness and AAA diameter [rs = -0.511; P = .074]; ILT stiffness and ILT volume [rs = -0.245; P = .467]). CONCLUSIONS: AAA wall stiffness properties are controlled by the load-bearing capacity of the noncalcified tissue portion, and low stiffness properties represent a highly degraded vulnerable wall. The presence of calcification that is contiguous with the inner wall causes severe tissue overstretching in surrounding tissue areas. The results highlight the use of additional biomechanical measures, detailing the biomechanical-structural characteristics of AAA tissue, that may be a helpful adjunct to improve the accuracy of rupture prediction.

Can a Neutrophil-Lymphocyte Ratio Derived from Preoperative Blood Tests Predict Arteriovenous Fistula Maturation?

BACKGROUND: To evaluate the association between inflammatory markers expressed as neutrophil-lymphocyte ratio (NLR) and process of arteriovenous fistula (AVF) maturation. METHODS: A retrospective review of patients with end-stage renal disease referred for formation of a new AVF in one center. Patients referred to the vascular service in the University Hospital of Limerick for creation of vascular access between 2009 and 2013. The association between NLR, calculated from preoperative blood tests, and functional fistula maturation, as determined by successful use of the AVF for 6 consecutive hemodialysis sessions, was investigated using univariate and logistic regression analyses. A logistic regression analysis was carried out to assess potential influence from other factors related to AVF maturation. Stepwise regression test was performed including the NLR. RESULTS: Overall AVF functional maturation rate in our study was 53.7% (66/123). Patients with matured AVFs had an NLR of 4.850 (1.8-15.7) compared with 3.554 (1.7-15.0); this difference was found to be significant (P = 0.024). Female gender (P = 0.008) and a history of kidney transplant (P = 0.004) were the only independent factors of fistula maturation outcome in a logistic regression model. CONCLUSION: Increased level of NLR was found to be associated with fistula maturation; however, more studies are needed to validate this finding.

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

BACKGROUND: Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. METHODS/DESIGN: Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). DISCUSSION: RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.