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Funding Information: On behalf of the Public and Community Oversight Group (PCOG) of the Health Protection Research Unit in Chemical and Radiation Threats and Hazards: Ian Wright; John Phipps; Colette Kelly; Robert Goundry; Eve Smyth; Andrew Wood; Paul Dale (also of the Scottish Environment Protection Agency). On behalf of the Society and College of Radiographers Patient Advisory Group: Lynda Johnson; Philip Plant; Michelle Carmichael – Specialist Senior Staff Nurse Guy's and St Thomas’ NHS Foundation trust.

Objective: Management of antithrombotic therapy in patients undergoing elective fenestrated branched endovascular aortic repair (F-BEVAR) is not standardised, nor are there any recommendations from current guidelines. By designing an international expert based Delphi consensus, the study aimed to create recommendations on the pre-, intra-, and post-operative management of antithrombotic therapy in patients scheduled for elective F-BEVAR in high volume centres.Methods: Eight facilitators created appropriate statements regarding the study topic that were voted on, using a four point Likert scale, by a selected panel of international experts using a three round modified Delphi consensus process. Based on the experts’ responses, only those statements reaching Grade A (full agreement ≥ 75%) or B (overall agreement ≥ 80% and full disagreement < 5%) were included in the final document. The round answers’ consistency was graded using Cohen's k, the intraclass correlation coefficient, and, in case of double re-submission, the Fleiss k.Results: Sixty-seven experts were included in the final analysis and voted the initial 43 statements related to pre- (n = 15), intra- (n = 10), and post-operative (n = 18) management of antithrombotic drugs. At the end of the process, six statements (13%) were rejected, 20 statements (44%) received a Grade B consensus, and 18 statements (40%) reached a Grade A consensus. Most statements (27; 71%) exhibited very high or high consistency grades, and 11 (29%) a fair or poor grading. The intra-operative statements mostly concentrated on threshold for and monitoring of proper heparinisation. The pre- and post-operative statements mainly focused on indications for dual antiplatelet therapy and its management, considering the possible need for cerebrospinal fluid drainage.Conclusion: Based on the elevated strength and high consistency of this international expert based Delphi consensus, most of the statements might guide current clinical management of antithrombotic therapy for elective F-BEVAR. Future studies are needed to clarify the debated issues.

Percutaneous endovascular aneurysm repair (PEVAR) is becoming increasingly popular due to fewer access-related complications, shorter procedural times and length of stay (LOS). Our aim was to explore factors associated with access-related complications and their impact on procedural time and LOS.We retrospectively analyzed consecutive aorto-iliac endovascular procedures in a tertiary hub comprising 2 institutions and 18 consultant vascular surgeons and interventional radiologists between 2016-2017. Access-related complications were defined as: bleeding requiring cutdown or return to theatre, acute limb ischemia or common femoral artery (CFA) pseudoaneurysm requiring intervention and wound infection or dehiscence needing hospitalization.Of 511 patients, 354 (69%) had a percutaneous approach via 589 CFA access sites. In this percutaneous group, access-related complications occurred in 11% of sites (65/589); Their rate varied with procedure type ranging between 3.6% to 17.6%. The most common complication was bleeding due to closure device failure in 8.5% (50/589) of access sites. When uncomplicated, percutaneous interventions were faster compared to open surgical access (P0.0001). Operation time and median LOS (3 vs. 2 days) were longer for elective standard EVAR patients experiencing access-related complications (P=0.033). In the percutaneous group, multivariate regression analysis demonstrated significant associations between access-related complications and eGFR (odds ratio (OR) 0.984 [0.972-0.997], P=0.014), CFA depth (OR 1.026 [1.008-1.045], P=0.005), device used (Prostar vs. Proglide (OR 2.177 [1.236-3.832], P=0.007) and procedural type (complex vs. standard EVAR) (OR 2.017 [1.122-3.627], P=0.019). We developed a risk score which had reasonably good predictive power (C-statistic 0.716 [0.646-0.787], P0.0001) for avoiding access complications.Physiological (low eGFR level), anatomical (increased CFA depth) and technical factors (choice of device and complex procedures) were identified as predictors of access-related complications in this large retrospective series. These are important for safe selection of patients that would benefit from percutaneous access.

MINI: The objective of this study was to evaluate the outcome of endovascular repair of chronic aortic arch dissecting aneurysms with a custom-made branched endograft during follow-up after acute type A aortic dissection open repair. Unmatched outcomes are reported in a population at high risk for a redo sternotomy. OBJECTIVE The objective of this study was to evaluate the outcome of endovascular aortic arch repair for chronic dissection with a custom-made branched endograft. BACKGROUND Acute type A aortic dissections are often treated with prosthetic replacement of the ascending aorta. During follow-up, repair of an aneurysmal evolution of the false lumen distal to the ascending prosthesis can be a challenge both for the surgeon and the patient. METHODS We conducted a multicenter, retrospective study of consecutive patients from 14 vascular units treated with a custom-made, inner-branched device (Cook Medical, Bloomington, IN) for chronic aortic arch dissection. Rates of in-hospital mortality and stroke, technical success, early and late complications, reinterventions, and mortality during follow-up were evaluated. RESULTS Seventy consecutive patients were treated between 2011 and 2018. All patients were considered unfit for conventional surgery. In-hospital combined mortality and stroke rate was 4% (n = 3), including 1 minor stroke, 1 major stroke causing death, and 1 death following multiorgan failure. Technical success rate was 94.3%. Twelve (17.1%) patients required early reinterventions: 8 for vascular access complication, 2 for endoleak correction, and 2 for pericardial effusion drainage. Median follow-up was 301 (138-642) days. During follow-up, 20 (29%) patients underwent secondary interventions: 9 endoleak corrections, 1 open repair for prosthetic kink, and 10 distal extensions of the graft to the thoracic or thoracoabdominal aorta. Eight patients (11%) died during follow-up because of nonaortic-related cause in 7 cases. CONCLUSIONS Endovascular treatment of aortic arch chronic dissections with a branched endograft is associated with low mortality and stroke rates but has a high reintervention rate. Further follow-up is required to confirm the benefits of this novel approach.

Introduction Paraplegia post-thoracoabdominal aortic aneurysm (TAAA) repair remains both a devastating and poorly understood complication. We related temporal changes in cellular and protein composition of cerebrospinal fluid (CSF) to neurological outcomes after TAAA repair to gain mechanistic insights driving paraplegia. Method Patients undergoing TAAA repair (open or endovascular) with a CSF drain were prospectively recruited between 2016-2018. CSF was collected pre-operatively and 24-hourly until removal. Daily neurological examinations were performed by blinded neurologists to the study. CSF cell content was characterised by flow cytometry and proteome analysed by tandem-mass-tag proteomics. An in-vivo rat model was modified using 15 minutes of aortic occlusion to produce consistent paraplegia. Rats were analysed neuro-behaviourally and histologically. Result CSF was analysed from 52 patients (age: 70.27+/-11.4; 66% male; open (n=9), endovascular (n=43)). 12 developed paraplegia of whom 5 remained permanently-paraplegic. Demographics were comparable between paraplegics, those who recovered and without post-op neurology. Permanent paraplegia was associated with a significant infiltration of CSF CD45+ leucocytes (P3-fold higher in permanent-paraplegics CSF versus those who recovered (P=0.0008). ADVS-1 >15ng/ml predicted permanent paraplegia with 100% specificity. Pre-treatment with ADVS-1 inhibition significantly improved walking ( Conclusion Permanent paraplegia is associated with shedding of ADVS-1 from parenchymal cord into CSF and blood/spinal-cord barrier disruption leading to cord oedema/leucocyte infiltration. Pre-treatment with ADVS-1 inhibition led to neurobehavioural and histological improvements offering translational hope for this devastating complication. Take-home message ADVS-1 is a novel biomarker of paraplegia where accurate biomarkers have proven challenging but more importantly it has proven a therapeutic target with genuine translational potential.

Objective: To evaluate the technique and outcomes of intentional occlusion of directional branches (DBs) using endovascular plugs during branched endovascular aortic repair using off-the-shelf Zenith t-Branch thoracoabdominal (TAAA) stent grafts. Methods: We reviewed the clinical data and outcomes of all consecutive patients treated by branched endovascular aortic repair using off-the-shelf Zenith t-Branch TAAA stent-graft (Cook Medical, Bloomington, Ind) in seven academic centers from 2013 to 2019. All patients had at least one DB intentionally occluded using extension of the branch with balloon or self-expandable covered stent, followed by placement of endovascular plugs. Intentional occlusion was indicated in patients with variations in the normal four-vessel renal-mesenteric anatomy, pre-existing dialysis, or in those who failed catheterization of a target vessel. End points were 30-day/in-hospital mortality, major adverse events, secondary interventions, target artery (TA) patency, TA instability, and patient survival. Results: There were 100 patients, 65 male and 35 female, with median age of 71 years (interquartile range [IQR], 66-75 years). Of these, 31 patients (31%) had urgent/emergent operations for symptomatic/contained ruptured aneurysms. The median aneurysm diameter was 72 mm (IQR, 61-85 mm). A total of 290 renal-mesenteric arteries were incorporated with a median of three (IQR, 3-3) vessels/patient. Indications for DB occlusion were less than four suitable renal-mesenteric targets in 84 patients or pre-existing dialysis and inability to catheterize a target vessel in eight patients each. There were 110 DBs occluded by vascular plugs, including 48 celiac axis, one superior mesenteric artery, and 61 renal DBs. Thirty-day/in-hospital mortality was 10%, including 9% for elective and 13% for urgent/emergent procedures. Major adverse events occurred in 44 patients (44%), including acute kidney injury in 19 patients (19%), estimated blood loss >1 L in 12 patients (12%), respiratory failure and new onset dialysis in six patients (6%) each, bowel ischemia in five patients (5%), and myocardial infarction and paraplegia in two patients (2%) each. The median follow-up was 5 months (range, 1-13 months). Eighteen patients (18%) required secondary interventions, none for problems related to the occluded DB. There were no endoleaks related to the occluded DB. At 2 years, primary and secondary patency and freedom from TA instability were 93% ± 3%, 97% ± 2%, and 91% ± 4%, respectively. Freedom from secondary interventions and patient survival were 75% ± 6% and 63% ± 7%, respectively. Conclusion: Intentional occlusion of DBs using endovascular plugs allows versatile use of a four-vessel off-the-shelf multi-branched TAAA stent graft in patients with variations in the normal renal and mesenteric anatomy or when technical difficulties prevent successful target vessel stenting. There were no endoleaks or secondary interventions associated with the occluded DB.

Venous valve (VV) failure causes chronic venous insufficiency, but the molecular regulation of valve development is poorly understood. A primary lymphatic anomaly, caused by mutations in the receptor tyrosine kinase EPHB4, was recently described, with these patients also presenting with venous insufficiency. Whether the venous anomalies are the result of an effect on VVs is not known. VV formation requires complex 'organization' of valve-forming endothelial cells, including their reorientation perpendicular to the direction of blood flow. Using quantitative ultrasound we identified substantial VV aplasia and deep venous reflux in patients with mutations in EPHB4. We used a GFP reporter, in mice, to study expression of its ligand, ephrinB2, and analysed developmental phenotypes following conditional deletion of floxed Ephb4 and Efnb2 alleles. EphB4 and ephrinB2 expression patterns were dynamically regulated around organizing valve-forming cells. Efnb2 deletion disrupted the normal endothelial expression patterns of the gap junction proteins connexin37 and connexin43 (both required for normal valve development) around reorientating valve-forming cells, and produced deficient valve-forming cell elongation, reorientation, polarity, and proliferation. Ephb4 was also required for valve-forming cell organization, and subsequent growth of the valve leaflets. These results uncover a potentially novel cause of primary human VV aplasia.

Purpose Reoperative open surgical repair (OSR) of thoracoabdominal aortic aneurysms (TAAAs) is associated with high morbidity and mortality. The aim of this study was to analyze outcomes of fenestrated–branched endovascular aneurysm repair (F-BEVAR) for the treatment of intercostal or visceral aortic patch aneurysms after OSR of TAAAs. Methods We reviewed the clinical data and outcomes of consecutive patients treated at 8 academic centers by F-BEVAR for visceral and intercostal aortic patch aneurysms after OSR of TAAAs (2011-2019). All patients had involvement of at least one target vessel requiring incorporation by a fenestration or directional branch. End points were technical success, 30-day and/in-hospital mortality, major adverse events, patient survival, target vessel patency/instability, and freedom from reintervention. Results There were 29 patients with a median age of 70 (interquartile range, 63-74) years. Seven patients (24%) had connective tissue disorders. Technical success was 100%. There were no 30-day/in-hospital mortalities. Major adverse events occurred in 5 patients (17%), including estimated blood loss >1 L in 3 patients (10%), acute kidney injury and respiratory failure in 2 patients (7%) each, and transient paraparesis in 1 patient (3%). Median follow-up was 14 (interquartile range, 7-37) months. At 2 years, primary and secondary patency, freedom from target artery instability, freedom from reintervention, and patient survival were 95%, 100%, 83%, 61%, and 96%, respectively. Conclusions F-BEVAR could be considered as an alternative to reoperative OSR in patients with visceral or intercostal aortic patch aneurysms. This series showed no mortality and a low rate of major adverse events, but a significant need for reintervention.

Background increasing numbers of older people are undergoing vascular surgery. Preoperative comprehensive geriatric assessment and optimisation (CGA) reduces postoperative complications and length of hospital stay. Establishing CGA-based perioperative services requires health economic evaluation prior to implementation. Through a modelling-based economic evaluation, using data from a single site clinical trial, this study evaluates whether CGA is a cost-effective alternative to standard preoperative assessment for older patients undergoing elective arterial surgery. Methods an economic evaluation, using decision-analytic modelling, comparing preoperative CGA and optimisation with standard preoperative care, was undertaken in older patients undergoing elective arterial surgery. The incremental net health benefit of CGA, expressed in terms of quality-adjusted life-years (QALYs), was used to evaluate cost-effectiveness. Results CGA is a cost-effective substitute for standard preoperative care in elective arterial surgery across a range of cost-effectiveness threshold values. An incremental net benefit of 0.58 QALYs at a cost-effectiveness threshold of £30k, 0.60 QALYs at a threshold of £20k and 0.63 QALYs at a threshold of £13k was observed. Mean total pre- and postoperative health care utilisation costs were estimated to be £1,165 lower for CGA patients largely accounted for by reduced postoperative bed day utilisation. Conclusion this study demonstrates a likely health economic benefit in addition to the previously described clinical benefit of employing CGA methodology in the preoperative setting in older patients undergoing arterial surgery. Further evaluation should examine whether CGA-based perioperative services can be effectively implemented and achieve the same clinical and health economic outcomes at scale.

Purpose: To report the outcomes from the observational SURPASS registry, which was created to assess the performance of the Conformable TAG (CTAG) stent-graft with the Active Control System (ACS) in patients undergoing thoracic endovascular aortic repair (TEVAR) in a real-world setting. Materials and Methods: The SURPASS registry (ClinicalTrials.gov; identifier NCT03286400) was an observational, prospective, single-arm, post-market, international study that enrolled patients undergoing TEVAR using the CTAG with ACS for both acute and chronic thoracic aortic disease between October 2017 and July 2018. The CTAG with ACS features 2-stage deployment of the stent-graft and an optional angulation mechanism that modifies only the proximal end of the stent-graft. During the observation period, 127 patients (mean age 67.1±12.1 years, range 27-86; 92 men) were enrolled and treated for an array of aortic pathologies, including chronic and acute lesions and 4 ruptured descending thoracic aneurysms. The primary outcome of this study was technical success; secondary outcomes were clinical success and major adverse events at 30 days and 12 months. The numbers of 2-stage device deployments and applications of the angulation mechanism were recorded, along with the reasons for use. Results: Technical success of the TEVAR was 97.6% owing to unintentional partial coverage of supra-aortic branches in 3 cases (the vessels were patent on imaging). The stent-graft was repositioned at its intermediate diameter in 79 patients (62.2%), and the angulation feature was applied in 64 cases (50.4%), mainly to improve proximal wall apposition and orthogonality in the aorta. The desired effect was achieved in 60 cases (93.8%). There was no device compression, bird-beak configuration, fracture, or graft occlusion. The 30-day and 12-month clinical success rates were 97.6% and 92.9%, respectively. There were 3 aorta-related deaths at 30 days and a further 3 at 12 months. Fatalities were due to a retrograde type A dissection (0.8%), paraplegia, bowel ischemia, sepsis in the setting of a mycotic aneurysm, aneurysm rupture post aortoesophageal fistula, and multiorgan dysfunction syndrome. Three endoleaks (2 type Ia and 1 type III) required reintervention. Conclusion: In the SURPASS registry, the use of the CTAG device with ACS showed promising outcomes despite the challenging pathologies. The new delivery system enables a controlled staged delivery with in situ adjustments during positioning, facilitating the treatment of complex aortic disease. On behalf of the SURPASS Registry Collaborators.

To evaluate short term outcomes related to the use of the Zenith TX2 Dissection Endovascular Graft (ZDEG) and the Zenith Dissection Bare stent (ZDES) for the treatment of Stanford type B aortic dissections.This retrospective multicenter case cohort study collated data from 10 European institutions for patients with both complicated and uncomplicated type B aortic dissection treated with ZDEG and ZDES between 2011 and 2018. The primary end point was mortality at 30 and 90 days. Secondary end points included complications related to TEVAR, such as, type Ia endoleak, stroke, paraparesis, paraplegia, and retrograde type A dissection (RTAD). Statistical analysis was carried out using the t test, or one-way analysis of variance and the χWe treated 120 patients (87 male; mean age, 62.7 ± 12.2years) either in the acute 76 (63.3%), subacute 16 (13.3%), or chronic 28 (23.3%) phase. Seven patients (5.8%) died within 30 days after the index procedure and two (1.7%) between 30 and 90 days. There was one instance of postoperative RTAD in a patient treated for rupture. Stroke and paraplegia occurred in three (2.5%) and five (4.2%), patients, respectively. Eight patients (6.7%) had a type Ia endoleak in the perioperative period. There were no instances of paraplegia, no permanent dialysis, and no requirement for adjunctive superior mesenteric or celiac artery stenting in the 33 patients (27.5%) who were treated by concurrent placement of ZDES distal to the ZDEG. The length and distal oversizing of ZDEG components used was less in this group.The present series demonstrates a low (1%) RTAD rate and favorable morbidity and mortality. The lower rate of paraplegia, dialysis, and visceral artery stenting in the cohort that had adjunctive use of ZDES is compelling and merits further assessment.

Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced unprecedented technical and medical developments in the field. Despite this, there is a great need, and great opportunities, to further explore the area. In this review, we have identified important areas that need to be further studied and selected priority aortic disease trials. There is a pressing need to update the AAA natural history and the role for endovascular AAA repair as well as to define biomarkers and genetic risk factors as well as influence of gender for development and progression of aortic disease. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at small AAA, to prevent AAA expansion and need for surgical repair, as well as to reduce the risk for aortic rupture. Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted. In addition, the role of endovascular treatment for ascending pathologies and for uncomplicated type B aortic dissection needs to be clarified.

Peripheral arterial disease (PAD) is a powerful marker of the risk of cardiovascular events such as stroke and myocardial infarction, even in asymptomatic patients. The development of PAD is underpinned by both modifiable risk factors, including smoking, diabetes, dyslipidaemia, hypertension and obesity and non-modifiable risk factors, including male gender and increased age. Optimizing medical management of risk factors, with tight control of diabetes, antiplatelet therapy and exercise, can significantly reduce risk of cardiovascular morbidity and mortality.

Supplemental Digital Content is available in the text., Background: Radiation exposure during fluoroscopically guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR. Methods: Expression of the DNA damage/repair marker, γ-H2AX and DNA damage response marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infrarenal, branched, and fenestrated) and open aortic repair using flow cytometry. These markers were separately measured in the same operators but this time wearing leg lead shielding in addition to upper body protection and compared with those operating with unprotected legs. Susceptibility to radiation damage was determined by irradiating operators’ blood in vitro. Results: γ-H2AX and pATM levels increased significantly in operators immediately after branched endovascular aortic repair/fenestrated endovascular aortic repair (P

IntroductionWalking exercise is a recommended but underused treatment for intermittent claudication caused by peripheral arterial disease (PAD). Addressing the factors that influence walking exercise may increase patient uptake of and adherence to recommended walking. The primary aim of this randomised controlled trial (RCT) is to evaluate the efficacy of a physiotherapist-led behavioural change intervention on walking ability in adults with intermittent claudication (MOtivating Structured walking Activity in people with Intermittent Claudication (MOSAIC)) in comparison with usual care.Methods and analysisThe MOSAIC trial is a two-arm, parallel-group, single-blind RCT. 192 adults will be recruited from six National Health Service Hospital Trusts. Inclusion criteria are: aged ≥50 years, PAD (Ankle Brachial Pressure Index ≤0.90, radiographic evidence or clinician report) and intermittent claudication (San Diego Claudication Questionnaire), being able and willing to participate and provide informed consent. The primary outcome is walking ability (6 min walking distance) at 3 months. Outcomes will be obtained at baseline, 3 and 6 months by an assessor blind to group allocation. Participants will be individually randomised (n=96/group, stratified by centre) to receive either MOSAIC or usual care by an independent randomisation service. Estimates of treatment effects will use an intention-to-treat framework implemented using multiple regression adjusted for baseline values and centre.Ethics and disseminationThis trial has full ethical approval (London—Bloomsbury Research Ethics Committee (17/LO/0568)). It will be disseminated via patient forums, peer-reviewed publications and conference presentations.Trial registration numberISRCTN14501418

Introduction This review aims to provide an update on the management of deep vein thrombosis (DVT). Sources of data A systematic search of PubMed, Google Scholar and Cochrane databases was carried out. Areas of agreement Direct oral anticoagulants (DOACs) are as effective and easier to use than vitamin K antagonists for the treatment of DVT. Catheter-directed thrombolysis can reduce post thrombotic syndrome in patients with iliofemoral DVT. Compression bandaging can help heal a venous ulcer. Areas of controversy Compression hosiery to prevent post thrombotic syndrome. Long-term evidence to show clinical benefit of using endovenous therapies to restore deep vein patency. Growing points Developing imaging methods to identify patients who would benefit from venous thrombolysis. The evolution of dedicated venous stents. Areas timely for developing research Understanding the mechanisms that lead to stent occlusion and investigation into the appropriate treatments that could prevent in-stent thrombosis is required.

Deep vein thrombosis and common complications, including pulmonary embolism and post-thrombotic syndrome, represent a major source of morbidity and mortality worldwide. Experimental models of venous thrombosis have provided considerable insight into the cellular and molecular mechanisms that regulate thrombus formation and subsequent resolution. Here, we critically appraise the ex vivo and in vivo techniques used to assess venous thrombosis in these models. Particular attention is paid to imaging modalities, including magnetic resonance imaging, micro–computed tomography, and high-frequency ultrasound that facilitate longitudinal assessment of thrombus size and composition.

We note with disappointment Doss’s suggestion that occupational radiation exposure should be considered as potentially beneficial. This comes at a time when the entire interventionist community is trying to impress on their young trainees, many of whom will be exposed to radiation several times a week, performing in some cases lengthy fluoroscopically guided procedures over a 40-year career, the importance of protecting against this exposure. We are aware that Doss and his group extol the virtues of not sparing irradiation to ensure proper screening, diagnosis, and treatment of patients. Although we would not advocate avoiding the use of radiation …

BACKGROUND: Hypoxia within acute venous thrombi is thought to drive resolution through stabilisation of hypoxia inducible factor 1 alpha (HIF1α). Prolyl hydroxylase domain (PHD) isoforms are critical regulators of HIF1α stability. Non-selective inhibition of PHD isoforms with l-mimosine has been shown to increase HIF1α stabilisation and promote thrombus resolution. OBJECTIVE: The aim of this study was to investigate the therapeutic potential of PHD inhibition in venous thrombus resolution. METHODS: Thrombosis was induced in the inferior vena cava of mice using a combination of flow restriction and endothelial activation. Gene and protein expression of PHD isoforms in the resolving thrombus was measured by RT-PCR and immunohistochemistry. Thrombus resolution was quantified in mice treated with pan PHD inhibitors AKB-4924 and JNJ-42041935 or inducible all-cell Phd2 knockouts by micro-computed tomography, 3D high frequency ultrasound or endpoint histology. RESULTS: Resolving venous thrombi demonstrated significant temporal gene expression profiles for PHD2 and PHD3 (P 0.05). CONCLUSIONS: This data suggests that PHD-mediated thrombus neovascularisation has a limited role in the resolution of venous thrombi. Directly targeting angiogenesis alone may not be a viable therapeutic strategy to enhance venous thrombus resolution. ispartof: THROMBOSIS RESEARCH vol:169 pages:105-112 ispartof: location:United States status: published

ObjectivesSpinal cord ischaemia (SCI) following endovascular thoracoabdominal aortic aneurysm (TAAA) repair is a devastating and unpredictable complication. This study describes a single unit's experience of SCI in patients who have had endovascular TAAA repair.MethodsA prospectively maintained database of patients having endovascular TAAA repair using branched and fenestrated stent grafts between 2008 and 2014 at a single high volume centre was reviewed. Patients who developed neurological symptoms and signs related to SCI were identified and factors associated with onset and recovery of neurology were analysed.ResultsSixty-nine patients (median age 73 years, 52 male; Crawford classification type I [n = 4], type II [n = 11], type III [n = 33], type IV [n = 14], type V [n = 7]) underwent endovascular TAAA repair. Twelve patients developed neurological symptoms/signs related to SCI but this was successfully reversed in eight patients, leaving four (5.8%) with permanent paraplegia. The median length of aorta covered was not significantly different in the 12 patients who developed SCI compared with the cohort that did not. Eleven of the patients who developed SCI had an intraoperative mean arterial pressure (MAP) below 80 mmHg. Cutaneous atheroemboli were noted in half of the patients in the SCI group compared with 11% of the non-SCI group (p

IntroductionAtherosclerotic plaque analysis using computed tomography angiography (CTA) has been found to be accurate and reproducible in the coronary and carotid arteries. The aim of our study was to assess the utility of this technique in predicting outcome following lower limb endovascular interventions.MethodsPre-procedural CTA was retrospectively analysed in 50 patients who had undergone femoropopliteal (F–P) angioplasty (and/or stenting). Plaque analysis was performed using TeraRecon workstation by two observers blinded to the long-term outcome. Using the Hounsfield units (HU) scale atherosclerotic plaque composition was subdivided into volumes of soft (–100–100 HU) fibrocalcific (101–300 HU) or calcified (300–1000 HU) components. The relationship between plaque composition, clinical and procedural variables, and the study end points (vessel patency, binary restenosis rate, and Amputation-Free Survival [AFS]) were assessed using multivariate analysis.ResultsThe technical success rate of the endovascular procedure was 98%, with 48% of patients receiving F–P stents. The AFS was 90%, primary patency 84%, assisted primary patency 88%, and binary restenosis 44% all at 1 year. A significantly greater total volume of calcified plaque (1.1 [.01–3.2] cm3 vs. .11 [0–1.86] cm3, p 50%) compared with those who did not. Patients with a calcified plaque volume greater than 1.1 cm3 had a significantly worse AFS than those with a volume less than 1.1 cm3 (p = .0038). Multivariate analysis showed that the percentage calcified plaque (p = .003, HR 11.4, 95% CI 1.45–37.29) was an independent predictor of binary restenosis at 12 months, and that absolute volume of calcified plaque (p = .001, HR 3.56, 95% CI 1.64–7.7) was independently associated with AFS.ConclusionsThe burden of calcified plaque, but not soft or fibrocalcific plaque is related to restenosis, reintervention, and AFS. Computed tomography plaque analysis may form an important non-invasive tool for risk stratification in patients undergoing F–P endovascular procedures.

Surgery is associated with an increased risk of venous thromboembolic events (VTE) including deep vein thrombosis and pulmonary embolism. Although the current treatment regiments such as mechanical manipulation and administration of pharmacological prophylaxis significantly reduced the incidence of postsurgical VTE, they remain a major cause of postoperative morbidity and mortality worldwide. The pathophysiology of venous thrombosis traditionally emphasizes the series of factors that constitute Virchow triad of factors. However, inflammation can also be a part of this by giving rise to a hypercoagulable state and endothelial damage. The inflammatory response after surgery, which is initiated by a cytokine "storm" and occurs within hours of surgery, creates a prothrombotic environment that is further accentuated by several cellular processes including neutrophil extracellular traps formation, platelet activation, and the generation of tissue factor-bearing microparticles. Although such inflammatory markers are elevated in undergoing surgery, the precise mechanism by which they give rise to venous thrombosis is poorly understood. Here, we discuss the potential mechanisms linking inflammation to thrombosis, and highlight strategies that may minimize surgical inflammation and reduce the incidence of postoperative VTE.

Objective Increasing numbers of older patients are undergoing surgery. Older surgical patients are at a higher risk of perioperative complications and mortality. Multimorbidity, frailty, and physiological changes of ageing contribute to adverse outcomes. These complications are predominantly medical, rather than directly surgical. Guidelines recommend preoperative assessment of comorbidity, disability, and frailty in older patients undergoing surgery and closer perioperative collaboration between surgeons and geriatricians. We conducted a survey to assess knowledge and beliefs of surgical trainees toward common perioperative problems encountered in older surgical patients. Design Paper-based survey. Setting Unselected UK surgical training-grade physicians (CT1-ST8) attending the 2013 Congress of The Association of Surgeons of Great Britain and Ireland, Glasgow, UK, May 1-3, 2013. Participants A total of 160 eligible UK surgical trainees attending the conference were invited to participate in the survey. Of them, 157 participated. Results Of the trainees, 68% ( n = 107) reported inadequate training and 89.2% ( n = 140) supported the inclusion of geriatric medicine issues in surgical curricula. Of the respondents, 77.2% ( n = 122) were unable to correctly identify the key features required to demonstrate mental capacity, and only 3 of 157 respondents were familiar with the diagnostic criteria for delirium. Support from geriatric medicine was deemed necessary (84.7%, n = 133) but often inadequate (68.2%, n = 107). Surgical trainees support closer collaboration with geriatric medicine and shared care of complex, older patients (93.6%, n = 147). Conclusions UK surgical trainees believe that they receive inadequate training in the perioperative management of complex, older surgical patients and are inadequately supported by geriatric medicine physicians. In this survey sample, trainee knowledge of geriatric issues such as delirium and mental capacity was poor. Surgical trainees support the concept of closer liaison and shared care of complex, older patients with geriatric medicine physicians. Changes to surgical training and service development are needed.

Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic functions that include chemotaxis, adhesion, and proliferation, which also have a role in wound healing. The aim of this study was to determine whether suPAR and its cleaved fragments are present in venous ulcers and whether their levels are associated with healing.Ulcer exudates were collected from patients with venous leg ulcers (n = 30). Healing was defined as complete re-epithelialization within 6 months of compression therapy. Time-resolved fluorescence immunoassays were validated for quantification of suPAR and its fragments in ulcer exudates. The effect of exudates on keratinocyte migration was analyzed by an in vitro scratch assay.Ulcer exudates from patients who healed (n = 9) had approximately threefold higher levels of intact suPAR (P = .005), twofold higher levels of suPARI (P = .03), and approximately threefold higher levels suPARII-III (P.0001) compared with nonhealers (n = 21). Exudate from healing ulcers stimulated keratinocyte migration (P = .02), whereas depletion of suPAR from exudates resulted in cell apoptosis.We conclude that suPAR and its fragments are present in the environs of venous ulcers and may act as indicators of the propensity of venous ulcers to heal, with suPARII-III being the best discriminator. We speculate that suPAR and its fragments may have a role in the maintenance of an optimal ulcer-healing environment.

Introduction: The poor retention of cells delivered into ischemic tissue is a hurdle that needs to be addressed for cell therapy to be effective. We have previously shown that CD16+ monocytes expressing upregulated cell adhesion markers are mobilized in critical limb ischemia (CLI) and salvage limbs in pre-clinical studies of hindlimb ischemia (HLI). We hypothesized that these cells are well retained following delivery into ischemic muscle. Methods and Results: CD16+ and CD16- monocytes were isolated from CLI patients, fluorescently labeled with QuantumDots and injected into the adductor muscle of nude athymic mice following HLI (n=15/group). Flow cytometric analysis of cell suspensions from injected muscle showed higher 3 and 7 day retention of CD16+ compared with CD16- monocytes (P7 ) were radiolabeled with Indium 111 and injected into ischemic legs. Cells were tracked at 30mins, 2, 24 and 72 hours using whole-body γ-camera imaging: radiodecay-corrected retention percentages were 60.0, 37.4, 29.9 and 22.0% respectively with evidence of “washout” into the liver. Analysis of muscle biopsies showed >85% viability of the cells at 10 days and areas of increased arteriogenesis compared with remote, non-injected muscle. Conclusion: CD16+ Mo are preferentially retained within ischemic muscle in experimental HLI. This first in man study shows these cells remain viable in ischemic tissue. Isolation of sufficient numbers of these cells for delivery directly into poorly perfused muscle may provide a more effective cell therapy for CLI patients.

Introduction: Cell therapy using unselected mononuclear cell populations has had modest benefits in patients with critical limb ischemia (CLI). We hypothesized that tissue-remodeling monocytes, identified by their expression of CD16 (CD16+ Mo), may be a novel cellular therapy for CLI. Methods and Results: Flow cytometry showed that the proportion of circulating CD16+ Mo was greater in CLI patients (n=25) compared with matched controls (n=15, P6 cells injected into the adductor muscles of nude athymic mice following femoral artery excision. More ischemic hindlimbs were salvaged when treated with CD16+ compared with CD16- Mo (83% [10/12] vs 17% [2/12] limbs, P Conclusion: Circulating CD16+ Mo from CLI patients have increased expression of adhesion markers, are preferentially retained within ischemic muscle and promote robust arteriogenesis and limb salvage in experimental HLI. This monocyte subset may be an effective cellular therapy for CLI.

Objective/Background To develop a procedure specific global rating scale for assessment of operator competence in endovascular aortic repair (EVAR). Methods A Delphi approach was used to achieve expert consensus. A panel of 32 international experts (median 300 EVAR procedures, range 200–3000) from vascular surgery (n = 21) and radiology (n = 11) was established. The first Delphi round was based on a review of endovascular skills assessment papers, stent graft instructions for use, and structured interviews. It led to a primary pool of 83 items that were formulated as global rating scale items with tentative anchors. Iterative Delphi rounds were executed. The panellists rated the importance of each item on a 5 point Likert scale. Consensus was defined as 80% of the panel rating an item 4 or 5 in the primary round and 90% in subsequent rounds. Consensus on the final assessment tool was defined as Cronbach's alpha > .8 after a minimum of three rounds. Results Thirty-two of 35 invited experts participated. Three rounds of surveys were completed with a completion rate of 100% in the first two rounds and 91% in round three. The 83 primary assessment items were supplemented with five items suggested by the panel and reduced to seven pivotal assessment items that reached consensus, Cronbach's alpha = 0.82. The seven item rating scale covers key elements of competence in EVAR stent placement and deployment. Each item has well defined grades with explicit anchors at unacceptable, acceptable, and superior performance on a 5 point Likert scale. Conclusion The Delphi methodology allowed for international consensus on a new procedure specific global rating scale for assessment of competence in EVAR. The resulting scale, EndoVascular Aortic Repair Assessment of Technical Expertise (EVARATE), represents key elements in the procedure. EVARATE constitutes an assessment tool for providing structured feedback to endovascular operators in training.