Search

Objective/background: The objective was to investigate renal outcomes following endovascular repair of thoraco-abdominal aortic aneurysms (TAAA) comparing fenestrations with branches for the renal arteries., Methods: Renal outcomes following TAAA endovascular repair performed with renal branches were collected from five high volume European centers and compared with renal outcomes following TAAA endovascular repair performed with renal fenestrations at one center. Renal re-intervention and occlusion rates, and freedom from any renal outcome and death were analyzed by patient and target vessel. Estimated glomerular filtration rate (eGFR) was calculated and collected pre-operatively and at the last available follow up., Results: In total, 449 patients were included in this retrospective study (235 treated with branched devices [BEVAR] and 214 with fenestrated devices [FEVAR]). Altogether, 856 renal vessels were analyzed (445 perfused by branches and 411 by fenestrations). Both groups were comparable except for sex and smoking habits. Technical success rates were 95% and 99%, respectively. Mean ± SD follow up was 19 ± 18 months after BEVAR and 24 ± 20 months after FEVAR. During follow up, renal re-intervention rates were similar in both groups (4.7% vs. 5.2%). The renal occlusion rate was significantly higher following BEVAR (9.6% vs. 2.3%; p < .01), and the 2 year freedom for renal occlusion rate was 90.4% (SE 85.8-95.3%) following BEVAR and 97.1% (SE 94.6-99.7%) following FEVAR (p < .01). During follow up, a 12% median decrease in eGFR was observed following BEVAR versus 9% following FEVAR (non-significant). The 2 year survival rates were 73.4% (SE 66.6-80.9%) and 81.8% (SE 76.1-87.9%) following BEVAR and FEVAR, respectively., Conclusion: Mid-term renal outcomes following endovascular repair of TAAA are satisfactory. Endograft designs incorporating renal fenestrations rather than renal branches are associated with significantly lower occlusion rates. A prospective trial is now required to confirm these results., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: The use of branched stent grafts for the treatment of thoracoabdominal aneurysms [TAAA] is increasing, but mating stent graft choice has not been studied. This study combined experience of five high volume centres to assess a preferred mating stent., Methods: Data from five centres were retrospectively combined. Patients were included if they underwent stent graft for treatment of TAAA that used only branches to mate with visceral and renal vessels. All patients with fenestrations in their device were excluded. Perioperative details, reintervention, occlusion, and death were recorded. Outcome of occlusion or reintervention, as well as a composite outcome of any death, occlusion, or reintervention was planned using a per-patient, and per-branch analysis., Results: In 235 included patients, there were 940 vessels available for placement of mating stent. The average age of included patients was 70 years (SD 7.9), and 179 of the 235 were male. Medical comorbidities included diabetes in 29/234 (12.4%), current smoker in 81/233 (34.8%), and COPD in 77/234 (32.9%). The primary stent deployed was self-expanding in 556 branches, balloon expandable in 231 branches, and was unknown in 92 branches. After a mean of 20.7 months (SD 25) follow-up, there have been 44 incidents of occlusion or reintervention, of which 40 culprit stents are known. Where the stent placed is known, the event rate in renal branches (35/437, 8%) is higher than that of visceral branches (8/443, 1.8%). There is no difference in occlusion or reintervention between self-expanding and balloon expandable stents (HR 0.95, p = .91) but there is a statistically significant difference between renal and visceral artery occlusions (HR 3.51, p = 0.001)., Conclusion: There appears to be no difference in occlusion or reintervention rate for branch vessels mated with balloon expandable compared with self-expanding stents. Renal events appear to outnumber visceral events in this population., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

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., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Use of blood oxygenation level-dependent cardiovascular magnetic resonance (BOLD-CMR) to assess perfusion in the lower limb has been hampered by poor reproducibility and a failure to reliably detect post-revascularization improvements in patients with critical limb ischemia (CLI)., Objectives: This study sought to develop BOLD-CMR as an objective, reliable clinical tool for measuring calf muscle perfusion in patients with CLI., Methods: The calf was imaged at 3-T in young healthy control subjects (n = 12), age-matched control subjects (n = 10), and patients with CLI (n = 34). Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperemia (Grad). BOLD-CMR was used to assess changes in perfusion following revascularization in 12 CLI patients. Muscle biopsies (n = 28), obtained at the level of BOLD-CMR measurement and from healthy proximal muscle of patients undergoing lower limb amputation (n = 3), were analyzed for capillary-fiber ratio., Results: There was good interuser and interscan reproducibility for Grad and SRi (all p < 0.0001). The ischemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched control subjects, and young control subjects (p < 0.001 for all comparisons). Successful revascularization resulted in improvement in Grad (p < 0.0001) and SRi (p < 0.0005). There was a significant correlation between capillary-fiber ratio (p < 0.01) in muscle biopsies from amputated limbs and Grad measured pre-operatively at the corresponding level., Conclusions: BOLD-CMR showed promise as a reliable tool for assessing perfusion in the lower limb musculature and merits further investigation in a clinical trial., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (© 2015 American Heart Association, Inc.)

Introduction: The assessment of thrombus size following treatments directed at preventing thrombosis or enhancing its resolution has generally relied on physical or histological methods. This cross-sectional design imposes the need for increased numbers of animals for experiments. Micro-computed tomography (microCT) has been used to detect the presence of venous thrombus in experimental models but has yet to be used in a quantitative manner. In this study, we investigate the use of contrast-enhanced microCT for the longitudinal assessment of experimental venous thrombus resolution., Materials and Methods: Thrombi induced by stenosis of the inferior vena cava in mice were imaged by contrast-enhanced microCT at 1, 7 and 14 days post-induction (n=18). Thrombus volumes were determined longitudinally by segmentation and 3D volume reconstruction of microCT scans and by standard end-point histological analysis at day 14. An additional group of thrombi were analysed solely by histology at 1, 7 and 14 days post-induction (n=15)., Results: IVC resident thrombus was readily detectable by contrast-enhanced microCT. MicroCT-derived measurements of thrombus volume correlated well with time-matched histological analyses (ICC=0.75, P<0.01). Thrombus volumes measured by microCT were significantly greater than those derived from histological analysis (P<0.001). Intra- and inter-observer analyses were highly correlated (ICC=0.99 and 0.91 respectively, P<0.0001). Further histological analysis revealed noticeable levels of contrast agent extravasation into the thrombus that was associated with the presence of neovascular channels, macrophages and intracellular iron deposits., Conclusion: Contrast-enhanced microCT represents a reliable and reproducible method for the longitudinal assessment of venous thrombus resolution providing powerful paired data., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Spinal 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., Methods: A 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., Results: Sixty-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 < .05). Strategies used to reverse SCI included raising MAP, cerebrospinal fluid drainage, angioplasty of stenosed internal iliac arteries, and restoring perfusion to the aneurysm sac., Conclusions: This series highlights some of the risk factors associated with the development of SCI after endovascular repair of TAAAs. It also illustrates the importance of a dedicated institutional protocol aimed at ensuring the early diagnosis of SCI and prompt intervention to reverse permanent paraplegia in the majority of cases., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: Atherosclerotic 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., Methods: Pre-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., Results: The 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] cm(3) vs. .11 [0-1.86] cm(3), p < .001) was found in patients developing restenosis (>50%) compared with those who did not. Patients with a calcified plaque volume greater than 1.1 cm(3) had a significantly worse AFS than those with a volume less than 1.1 cm(3) (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., Conclusions: The 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., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

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., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the advantages and disadvantages of dual antiplatelet therapy. We conducted a systematic review and network meta-analysis of available randomized controlled trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine, Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or in combination with aspirin) in PAD patients (PROSPERO public database; CRD42014010299).We collated evidence from previous relevant meta-analyses and searched online databases. Primary efficacy endpoints were: (1) the composite rate of major adverse cardiovascular events (MACE; including vascular deaths, non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major leg amputations. The primary safety endpoint was the rate of severe bleeding events. Bayesian models were employed for multiple treatment comparisons and risk-stratified hierarchies of comparative efficacy were produced to aid medical decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are reported in case of significant results. We analyzed 49 RCTs comprising 34,518 patients with 88,358 person-years of follow-up with placebo as reference treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in reducing MACE. A significant MACE reduction was noted with Ticagrelor plus aspirin (RR: 0.67; 95%CrI: 0.46-0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI: 0.58-0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58-0.96, NNT = 87), and Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61-0.99, NNT = 98). Dual antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46-0.99 compared to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with Ticlopidine (RR: 5.03; 95%CrI: 1.23-39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI: 1.22-2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05-2.10, NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm profile (79% cumulative rank probability best and 77% cumulative rank probability safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce the rate of major leg amputations following revascularization, but carries a slightly higher risk of severe bleeding.

Purpose: The purpose of this study was to evaluate medium-term outcomes following endovascular repair of abdominal aortic aneurysms (EVAR) with unfavourable neck anatomy using stent grafts with a 36 mm or larger proximal diameter., Materials and Methods: A retrospective review of 27 patients who underwent elective EVAR between 2006 and 2008 using a stent graft with a 36 mm or larger proximal diameter was carried out. All patients had computed tomography angiography (CTA) for procedure planning, and detailed assessment of the aneurysm neck was performed using a three-dimensional CTA workstation. Patients were followed up with CTA at 3 and 12 months and annual duplex thereafter., Results: The median aneurysm diameter was 7 cm, and the median aneurysm neck diameter was 31 mm. Cook Zenith stent grafts were used in all patients, with a proximal diameter of 36 mm (n = 25) and 40 mm (n = 2). Primary and assisted primary technical success rates were 74 and 93%, respectively. The follow-up period ranged from 62 to 84 months, with a median of 72 months. 15 patients died during follow-up. Two patients died from aortic rupture, and the remaining patients died from cardiac disease (n = 4), chest sepsis (n = 6), cancer (n = 2) and renal failure (n = 1). Complications included type I endoleak (n = 5), limb occlusion (n = 2), limb stenosis (n = 2), limb kinking (n = 1), dissection of an artery (n = 1), occlusion of a femorofemoral cross-over graft (n = 1) and poor attachment of a distal limb (n = 1)., Conclusions: EVAR using stent grafts in the presence of an unfavourable neck has a high risk of complications. Medium-term survival in this group is low but mainly due to patient co-morbidities.

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., (Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Increased stiffening of the aortic wall could contribute to the development of abdominal aortic aneurysm (AAA). We investigated regional aortic wall pulse wave velocity (PWV) in patients with AAA., Methods: Forty-six men diagnosed with a small AAA and 42 control men were recruited from the AAA surveillance and screening programmes at Guy's and St Thomas' Hospital. Phase-contrast cardiovascular MRI was performed to determine regional PWV along the thoracic (PWVTHOR) and abdominal aorta (PWVABD). PWV over the total aorta (PWVTOTAL) was calculated from the combined regions., Results: PWVTOTAL was significantly higher in patients with AAA compared to controls (10.0 ± 2.1 versus 8.4 ± 1.6 m/s, respectively; P < 0.0001). The difference in total aortic PWV between groups was explained by increased thoracic PWV in patients with AAA compared to controls (PWVTHOR 9.9 ± 2.8 versus 8.1 ± 2.5 m/s, respectively; P < 0.01). In contrast, there was no difference in PWV measured over the abdominal region in AAA patients compared with controls (PWVABD 10.7 ± 3.3 and 10.1 ± 3.3 m/s, in AAA and control groups, respectively; P = 0.40). In multiple regression analysis, including the whole cohort, abdominal aortic diameter remained significantly associated with PWVTOTAL and PWVTHOR (standardized regression coefficients 0.22 and 0.19, respectively; each P < 0.05 after adjustment for age and mean arterial pressure), but not with PWVABD., Conclusion: AAA patients have a greater PWV in the thoracic but not abdominal aorta compared to control individuals. Greater abdominal aortic diameter in patients with AAA is likely to offset effects of intrinsic stiffening of the abdominal aorta on PWV.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives/background: The increased complexity of endovascular aortic repair necessitates longer procedural time and higher radiation exposure to the operator, particularly to exposed body parts. The aims were to measure directly exposure to radiation of the bodies and heads of the operating team during endovascular repair of thoracoabdominal aortic aneurysms (TAAA), and to identify factors that may increase exposure., Methods: This was a single-centre prospective study. Between October 2013 and July 2014, consecutive elective branched and fenestrated TAAA repairs performed in a hybrid operating room were studied. Electronic dosimeters were used to measure directly radiation exposure to the primary (PO) and assistant (AO) operator in three different areas (under-lead, over-lead, and head). Fluoroscopy and digital subtraction angiography (DSA) acquisition times, C-arm angulation, and PO/AO height were recorded., Results: Seventeen cases were analysed (Crawford II-IV), with a median operating time of 280 minutes (interquartile range 200-330 minutes). Median age was 76 years (range 71-81 years); median body mass index was 28 kg/m(2) (25-32 kg/m(2)). Stent-grafts incorporated branches only, fenestrations only, or a mixture of branches and fenestrations. A total of 21 branches and 38 fenestrations were cannulated and stented. Head dose was significantly higher in the PO compared with the AO (median 54 μSv [range 24-130 μSv] vs. 15 μSv [range 7-43 μSv], respectively; p = .022), as was over-lead body dose (median 80 μSv [range 37-163 μSv] vs. 32 μSv [range 6-48 μSv], respectively; p = .003). Corresponding under-lead doses were similar between operators (median 4 μSv [range 1-17 μSv] vs. 1 μSv [range 1-3 μSv], respectively; p = .222). Primary operator height, DSA acquisition time in left anterior oblique (LAO) position, and degrees of LAO angulation were independent predictors of PO head dose (p < .05)., Conclusions: The head is an unprotected area receiving a significant radiation dose during complex endovascular aortic repair. The deleterious effects of exposure to this area are not fully understood. Vascular interventionalists should be cognisant of head exposure increasing with C-arm angulation, and limit this manoeuvre., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Therapeutic neovascularization is a novel approach used to salvage critically ischemic limbs that are not amenable to conventional treatments. Initial efforts were based on single injections of angiogenic factors but there is now a realization that delivering angiogenic cells is more likely to achieve effective revascularization. Clinical studies to date have mostly used mixtures of mononuclear cells harvested from the bone marrow or peripheral blood. The modest results achieved with these cells, only a proportion of which are angiogenic, has stimulated a search for more potent cell types. Preclinical studies have identified several candidates, including adipose derived, embryonic and induced pluripotent stem cells. This review provides an update on the current status of angiogenic cell therapy for the ischemic limb and outlines efforts aimed at enhancing the clinical efficacy of treatments.

Introduction: The formation of new vascular channels within and around venous thrombus contributes to its resolution. Neovascularisation arising from the surrounding vein may facilitate this process. Treatment of cancer patients with anti-angiogenic agents can lead to increased incidence of venous thromboembolic events, but the effect of these agents on the processes that govern thrombus resolution are unclear. The aim of this study was to determine the effect of anti-angiogenic treatment with 2-methoxyestradiol (2ME) on (i) angiogenic response in the thrombosed vein and (ii) venous thrombus resolution., Materials and Methods: Venous thrombus was induced in the inferior vena cava (IVC) of 36 adult male BALB/C mice. Thrombosed mice received either the anti-angiogenic agent, 2ME (150 mg/kg/day, i/p), or vehicle control (n=18/group). In the thrombosed IVC of both groups: hypoxia-inducible factor (HIF) 1α, and its angiogenic targets, vascular endothelial growth factor (VEGF) and placental growth factor (PLGF), were quantified using enzyme-linked immunosorbent assays at days 1 and 10 post-thrombus induction (n=6/group); and inflammatory cell content, cell proliferation, and vein recanalisation were quantified using immunostaining and image analysis at day 10 (n=6/group)., Results: In the IVC of mice treated with 2ME compared with control: HIF1α (P<0.005 and P<0.02), VEGF (P<0.005 and P<0.02), and PLGF levels (P<0.01 and P<0.001) were reduced at days 1 and 10 post-thrombus induction respectively, and macrophage content (P<0.005), neutrophil content (P<0.01), vein recanalistion (P<0.05), and thrombus resolution (P<0.001) were also reduced at day 10., Conclusions: Anti-angiogenic treatment with 2ME supressed the HIF1-mediated angiogenic drive in local vein wall and attenuated venous thrombus resolution. The potential pro-thrombotic effect of anti-angiogenic agents should be carefully considered when managing venous thromboembolic events in cancer patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus' fibrin content in vivo and for the identification of thrombus suitable for thrombolysis., Approach and Results: Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0 μmol/kg) with 12 mice at each time point used to correlate fibrin contrast uptake with thrombus' histological stage and fibrin content. Six mice at each time point were immediately subjected to intravascular thrombolytic therapy (10 mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for control purpose. Contrast uptake was correlated positively with the fibrin content of the thrombus measured by Western blotting (R(2)=0.889; P<0.001). Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus size on late gadolinium enhancement inversion recovery MRI pre-EP-2104R and post-EP-2104R injection were the best predictors for successful thrombolysis (area under the curve, 0.989 [95% confidence interval, 0.97-1.00] and 0.994 [95% confidence interval, 0.98-1.00] respectively)., Conclusions: MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis., (© 2014 American Heart Association, Inc.)

Objective: Venous thromboembolism is a common complication in patients with cancer, resulting in significant morbidity and mortality. Clinical studies suggest that the incidence of venous thromboembolic events increased after treatment of these patients with antiangiogenic agents. Thrombi resolve through a process of remodeling, involving the formation of microvascular channels within the thrombus. Our aim was to determine whether inhibiting angiogenesis affects venous thrombus resolution., Approach and Results: Thrombus was induced in the inferior vena cava of mice. These mice were treated with axitinib (50 mg/kg per day), 2-methoxyestradiol (2ME, 150 mg/kg per day), or vehicle control. Thrombus size, recanalization, neovascularization, inflammatory cell content, and collagen content were assessed after axitinib (days 3, 10, 17) and 2ME (day 10 only) treatment (n=6/group). Axitinib treatment resulted in reduced thrombus resolution (P<0.002) and vein recanalization (P<0.001) compared with vehicle-treated controls. This was associated with inhibition of organization as seen through reduced thrombus neovascularization (P<0.0001) and collagen (P<0.0001) content, as well as reduced macrophage accumulation in the thrombus (P<0.001). Treatment with a second antiangiogenic agent, 2ME, mirrored these findings, with a similar order of magnitude of effect of treatment over vehicle control in all of the parameters measured, with the exception of neutrophil content, which was significantly reduced after 2ME treatment but not affected by axitinib., Conclusions: Antiangiogenic therapy (using axitinib and 2ME) inhibits the resolution of venous thrombi, which could lead to persistent venous obstruction and the possibility of thrombus extension. This potential prolongation of venous occlusion by antiangiogenic agents should therefore be taken into consideration in trials of these agents and when managing the complications of venous thromboembolic events in patients with cancer.

Sac perfusion may be helpful in preventing or reversing spinal cord injury after endovascular repair of thoracoabdominal aneurysms and it has been used as an adjunct to the standard physiologic measures of sustained hypertension and cerebrospinal fluid drainage. Coagulopathy as a result of endoleak after endovascular aneurysm repair has been reported, and very rare cases of treatment after repair of these endoleaks have been described. We report a 73-year-old man who had endovascular repair of a type II thoracoabdominal aneurysm with a branched stent graft. Sac reperfusion was initiated to manage postoperative paraplegia. The paraplegia partially resolved but severe hemorrhagic complications developed that were attributed to sac perfusion-related hyperfibrinolysis. Discontinuation of sac perfusion resolved the coagulopathy but resulted in paraplegia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To measure the radiation exposure of the operating team during endovascular aortic procedures, and to determine factors that predict high exposures., Materials and Methods: Electronic dosimeters placed over and under protective lead garments, were used to prospectively record radiation exposure during endovascular aortic repairs performed in a designated interventional radiology suite. Univariate and multivariate linear regression analyses of predictors of radiation exposure were performed., Results: A total of 26 infra-renal and 10 thoracic endovascular cases were studied. Median (IQR) patient age and body mass index were 76.0 (70.0-81.8) years and 26.2 (23.9-28.9) kg/m(2) respectively. Over-lead exposure to the operator was higher for thoracic than for infra-renal procedures (421.0 [233.8-597.8] μSv vs. 52.5 [27.8-179.8] μSv, p = .0003), reflecting a significant exposure to unprotected parts of the body. Under-lead exposures for operator and assistant were 5.5 (2.0-14.2) μSv and 1.0 (0.0-2.3) μSv respectively, which for an average caseload would comply with total body effective dose limits. Type of case and percentage of digital subtraction angiography (DSA) time in left anterior oblique angulations predicted dose to the operator (p < .0001)., Conclusions: Thoracic procedures, DSA runs and obliquity of the C-arm are strong predictors of radiation exposure during endovascular aortic repairs. Understanding scatter radiation dynamics and instigating measures to minimise radiation exposure should be mandatory., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The magnetic resonance longitudinal relaxation time (T1) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T1 signal in venous thrombi and whether changes in T1 relaxation time are informative of the susceptibility to lysis., Methods and Results: Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T1 relaxation time correlated with thrombus composition. The mean T1 relaxation time of thrombus was shortest at 7 days following thrombus induction and returned to that of blood as the thrombus resolved. T1 relaxation time was related to thrombus methemoglobin formation and further processing. Studies in inducible nitric oxide synthase (iNOS(-/-))-deficient mice revealed that inducible nitric oxide synthase mediates oxidation of erythrocyte lysis-derived iron to paramagnetic Fe3+, which causes thrombus T1 relaxation time shortening. Studies using chemokine receptor-2-deficient mice (Ccr2(-/-)) revealed that the return of the T1 signal to that of blood is regulated by removal of Fe3+ by macrophages that accumulate in the thrombus during its resolution. Quantification of T1 relaxation time was a good predictor of successful thrombolysis with a cutoff point of <747 ms having a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively., Conclusions: The source of the T1 signal in the thrombus results from the oxidation of iron (released from the lysis of trapped erythrocytes in the thrombus) to its paramagnetic Fe3+ form. Quantification of T1 relaxation time appears to be a good predictor of the success of thrombolysis.

A third of patients with critical limb ischemia (CLI) will eventually require limb amputation. Therapeutic neovascularization using unselected mononuclear cells to salvage ischemic limbs has produced modest results. The TIE2-expressing monocytes/macrophages (TEMs) are a myeloid cell subset known to be highly angiogenic in tumours. This study aimed to examine the kinetics of TEMs in patients with CLI and whether these cells promote neovascularization of the ischemic limb. Here we show that there are 10-fold more circulating TEMs in CLI patients, and removal of ischemia reduces their numbers to normal levels. TEM numbers in ischemic muscle are two-fold greater than normoxic muscle from the same patient. TEMs from patients with CLI display greater proangiogenic activity than TIE2-negative monocytes in vitro. Using a mouse model of hindlimb ischemia, lentiviral-based Tie2 knockdown in TEMs impaired recovery from ischemia, whereas delivery of mouse macrophages overexpressing TIE2, or human TEMs isolated from CLI patients, rescued limb ischemia. These data suggest that enhancing TEM recruitment to the ischemic muscle may have the potential to improve limb neovascularization in CLI patients., (Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.)

Background: Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis., Methods and Results: Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; PANOVA<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10(-3) mm(2)/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10(-3) mm(2)/s])., Conclusions: MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention.

Background: The UK prevalence of thoracic aneurysm is estimated at 10.4 per 100,000 person-years. Progressive and unpredictable enlargement can lead to rupture. Endovascular repair of thoracic aortic aneurysms involves a stent graft system being introduced via the femoral artery and manipulated within the aorta under radiological guidance. Following endograft deployment, a seal is formed at the proximal and distal landing zones to exclude the aneurysm sac from the circulation. With the increasing popularity of endovascular repair there has been an increase in the number of commercially available stent graft designs on the market., Objectives: This review aimed to assess the different stent graft types for endovascular repair of thoracic aortic aneurysms., Search Methods: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and CENTRAL (2012, Issue 11). Trial databases were searched by the TSC for details of ongoing and unpublished studies., Selection Criteria: All published and unpublished randomised controlled trials (RCTs) of stent graft types in the repair of thoracic aortic aneurysms were sought without language restriction., Data Collection and Analysis: Data collection and analysis was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: No studies were identified that met the inclusion criteria., Authors' Conclusions: Unfortunately, no data exist regarding direct comparisons of the performance of different stent graft types. Therefore, this review cannot recommend guidance to clinicians in their selection of stent graft types. High quality RCTs evaluating stent graft types in thoracic endovascular aneurysm repair are required.

Background: The UK prevalence of abdominal aortic aneurysm (AAA) is estimated at 4.9% in over 65-year olds. Progressive and unpredictable enlargement can lead to rupture. Endovascular repair of AAAs involves a stent graft system being introduced via the femoral artery and manipulated within the aorta under radiological guidance. Following endograft deployment, a seal is formed at the proximal and distal landing zones to exclude the aneurysm sac from the circulation. With the increasing popularity of endovascular repair there has been an increase in the number of commercially available stent graft designs on the market., Objectives: This review aimed to assess the different stent graft types for endovascular repair of AAA., Search Methods: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and CENTRAL (2012, Issue 10). Trial databases were searched by the TSC for details of ongoing and unpublished studies., Selection Criteria: All published and unpublished randomised controlled trials (RCTs) of stent graft types in the repair of AAAs were sought without language restriction and in consultation with the Peripheral Vascular Disease Group TSC., Data Collection and Analysis: We planned to conduct data collection and analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: No studies were identified that met the inclusion criteria., Authors' Conclusions: Unfortunately, no data exist regarding direct comparisons of the performance of different stent graft types. Therefore, this review cannot recommend guidance to clinicians in their selection of stent graft types. High quality randomised controlled trials evaluating stent graft types in abdominal endovascular aneurysm repair are required.

Critical limb ischaemia is a severe manifestation of peripheral arterial disease characterised by intractable pain and tissue gangrene. Conventional treatments include percutaneous angioplasty and surgical bypass but up to one third of patients are not amenable to these interventions and will ultimately require amputation. Therapeutic neovascularisation has been proposed as an alternative treatment in these 'no option' patients and both cytokines and cells have shown impressive efficacy in the laboratory. Clinical trials in man, however, have had modest results. This discrepancy has put into question the relevance of the pre-clinical assays that are used to test potential agents. One of the most widely used of these assays is the hind limb ischaemia model that is often performed in young, healthy animals. This review critiques the techniques used to induce and assess ischaemia in this model and outlines the reasons why healthy rodents cannot fully recapitulate critical limb ischaemia in aged patients. Strategies that may produce a hind limb model that better simulates the human condition are proposed., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Hybrid repair constitutes supra-aortic debranching before thoracic endovascular aortic repair (TEVAR). It offers improved short-term outcome compared with open surgery; however, longer-term studies are required to assess patient outcomes and patency of the extra-anatomic bypass grafts., Methods: A prospectively maintained database of 380 elective and urgent patients who had undergone TEVAR (1997-2011) was analyzed retrospectively. Fifty-one patients (34 males; 17 females) underwent hybrid repair. Median age was 71 (range, 18-90) years with mean follow-up of 15 (range, 0-61) months., Results: Perioperative complications included death: 10 % (5/51), stroke: 12 % (6/51), paraplegia: 6 % (3/51), endoleak: 16 % (8/51), rupture: 4 % (2/51), upper-limb ischemia: 2 % (1/51), bypass graft occlusion: 4 % (2/51), and cardiopulmonary complications in 14 % (7/51). Three patients (6 %) required emergency intervention for retrograde dissection: (2 aortic root repairs; 2 innominate stents). Early reintervention was performed for type 1 endoleak in two patients (2 proximal cuff extensions). One patient underwent innominate stenting and revision of their bypass for symptomatic restenosis. At 48 months, survival was 73 %. Endoleak was detected in three (6 %) patients (type 1 = 2; type 2 = 1) requiring debranching with proximal stent graft (n = 2) and proximal extension cuff (n = 1). One patient had a fatal rupture of a mycotic aneurysm and two arch aneurysms expanded. No bypass graft occluded after the perioperative period., Conclusions: Hybrid operations to treat aortic arch disease can be performed with results comparable to open surgery. The longer-term outcomes demonstrate low rates of reintervention and high rates of graft patency.

Objective: The study aims to assess a novel thermosensitive polymer (LeGoo(®)) for distal vessel control during infra-popliteal (crural/pedal) bypass surgery in severe leg ischaemia., Method: Retrospective analysis of all distal bypasses from October 2009 to February 2012. Technical success, patency, limb salvage and amputation-free survival rates were analysed., Results: Fifty-four infra-popliteal bypasses using the polymer were performed in 46 patients. The distal anastomosis was at the anterior tibial (n = 15, 28%), posterior tibial (n = 12, 22%), peroneal (n = 8, 15%), tibio-peroneal trunk (n = 8, 15%) and dorsalis pedis arteries (n = 11, 20%). Technical success was achieved in 51/54 (94.4%; failures: two inadequate haemostasis, one un-dissolved polymer). In-hospital duplex of the distal anastomosis showed a significant stenosis in two cases (4.3%). Outflow angioplasty was performed in three cases (two distal anastomotic, one run-off vessel, 5.6%). The 1-year patency rate was 76.2% (standard error (SE) 6.7%), limb salvage rate 79.3% (SE 6.7%). Amputation-free survival was 93.5% at 30 days (SE 3.6%) and 67.5% at 1 year (SE 7.5%)., Conclusion: This thermosensitive polymer is a potentially safe and useful atraumatic device to achieve a blood-less distal anastomotic field in infra-popliteal bypasses. The technique avoids other potentially traumatic methods of vessel control, which may be particularly important in patients with calcified distal vessels., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: The quality improvement framework for major amputation was developed with the aim of improving outcomes and reducing the perioperartive mortality to less than 5% by 2015. The aim of the study was to assess our compliance with the framework guidelines and look for the reasons for non-compliance., Method: All major amputations performed between 2008 and 2010 were included. The following data were collected: presence of infection ± tissue loss, status of arterial supply, revascularisation attempts, time to surgery, type of amputation, morbidity and mortality., Results: A total of 81 patients were included (42 BKAs, 39 AKAs). Ninety percentage had formal preoperative arterial investigations and 84% had an attempted revascularisation procedure. Patients who were transferred late from non-vascular units (n = 12) had a 30-day mortality of 50% whereas patients who presented directly to our unit had a 30-day mortality of 7.2%. The number of amputations has decreased over the last 3 years from 34 to 21 per year, coinciding with the doubling of crural revascularisation procedures performed (from 60 to 120 per year). Ten patients underwent a revision from BKA to AKA because of an inadequate profunda femoris artery (PFA), whereas all those with a healed BKA stump either had a good PFA or a named crural vessel., Conclusion: The overall number of amputations is decreasing from year to year. By doubling our crural revascularisation procedures we are saving more limbs. Thirty-day mortality is higher than expected, particularly in patients who present late. Expeditious referral may potentially improve the mortality rate among this group of patients., (© 2012 Blackwell Publishing Ltd.)

Background and Purpose: Hematopoietic progenitor cells (HPCs) may attenuate the response to vascular injury by maintaining endothelial integrity and function. Our aim was to determine whether circulating HPC number and function correlate with restenosis after carotid endarterectomy., Methods: HPC number (CD34(+)/CD133(+) cells), early colony-forming units, migratory capacity, and senescence were analyzed in blood collected preoperatively, 1 day, and 6 weeks postoperatively. Mobilizing cytokine levels were also measured. Stenosis was assessed by duplex scanning., Results: HPC numbers (P<0.001) and early colony-forming unit count (P=0.001) fell rapidly 24 hours postoperatively. Restenosis at 6 months correlated negatively with the magnitude of postoperative falls in HPC numbers (R=-0.38, P=0.013) and early colony-forming unit counts (R=-0.42, P=0.008). The migratory capacity of preoperative HPCs correlated negatively with restenosis (R=-0.48, P=0.007). Preoperative SDF1 levels correlated with falls in HPC number (R=0.42, P=0.044) and early colony-forming unit counts (R=0.56, P=0.004)., Conclusions: HPC function appears to be linked to the development of carotid artery restenosis after endarterectomy. These data support the concept that HPCs have a role in regulating remodeling of the injured arterial wall.

Therapeutic neovascularisation using angiogenic cells has been hampered by the loss of cells from the target tissue. Encapsulation of these cells within a semi-permeable membrane could improve their retention within the ischaemic tissue without affecting the excretion of the angiogenic growth factors produced. Bio-spraying is a novel cell-handling technique that does not adversely affect cell viability. We used this technique to encapsulate human peripheral blood monocytes and found that cell viability, cell phenotype and functional downstream angiogenic signalling were preserved. Encapsulation of monocytes with macrophage-colony stimulating factor resulted in increased vascular-endothelial growth factor production and enhanced angiogenic function. Bio-spraying/encapsulation has the potential to enhance the efficacy of current angiogenic cell therapy strategies and merits further investigation.

Objective: Exposure to radiation doses above 2 Gray (Gy) can cause skin burns. There is also a lifetime cancer risk of ≈5.5% for every Sievert (Sv) of radiation. We assessed the radiation burden associated with endovascular treatment of the aorta., Method: Thoracic (TEVAR), Infra-renal (IEVAR) and branched/fenestrated (BEVAR/FEVAR) endovascular aortic repairs were studied. The prospectively recorded dosimetric parameters included: fluoroscopy time and dose area product (DAP). Exposure films, placed underneath 10 patients intra-operatively, recorded skin dose and were used to calculate skin (Gy) and tissue (Sv) doses., Results: The TEVAR cohort (n = 232) were younger (p < 0.0001) than BEVAR/FEVAR (n = 53) and IEVAR (n = 630). The median DAP was higher (p = 0.004) in the BEVAR/FEVAR group compared with IEVAR and TEVAR: 32,060 cGy cm(2) (17,207-213,322) vs 17,300 cGy cm(2) (10,940-33,4340) vs 19,440 cGy cm2 (11,284-35,101), respectively. The equivalent skin doses were BEVAR/FEVAR: 1.3 Gy (0.71-8.75); IEVR: 0.71 Gy (0.44-13.7); TEVAR: 0.8 Gy (0.46-1.44). The whole body effective doses were BEVAR/FEVAR: 0.096 Sv (0.052-0.64); IEVR: 0.053 Sv (0.033-1.00); TEVAR: 0.058 Sv (0.034-0.11)., Conclusions: The radiation exposure during endovascular aortic surgery is relatively low for the majority but some patients are exposed to very high doses. Efforts to minimise intra-operative exposure and graft surveillance methods that do not use radiation may reduce the cumulative lifetime malignancy risk., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Endovascular graft designs incorporating sidebranches, fenestrations and scallops offer a minimally-invasive alternative to open surgery and hybrid approaches for thoracoabdominal aortic aneurysms (TAAA). Our unit has offered total endovascular TAAA repair to selected higher-risk patients since 2008. We report the largest UK series to date of total endovascular TAAA repair., Methods: Retrospective analysis of a prospectively-maintained operative database., Results: 31 patients (21 male, 10 female) median age 71 years (range 58-84), with TAAA (12 Crawford type I, 13 type III, 6 type IV), median diameter 6.4 (4.3 (mycotic)- 9.9) underwent endovascular TAAA repair (total 48 sidebranches, 26 fenestrations, 13 scallops) between July 2008 and January 2011. Median operating time 225 min (65-540 min), X-ray screening time 58 min (4-212 min), contrast dose 175 ml (70-500 ml), blood loss 325 ml (100-400 ml). Median post-operative length of hospital stay 6 days (2-22 days). Three patients (3/31, 9.7%) died within 30 days of operation: multisystem organ failure (1) acute renal failure and paraplegia (1) and paraplegia (1). There were no other cases of in-hospital organ failure, paraplegia or major complications. The median change in pre-discharge from pre-operative renal function was 3.4% deterioration in eGFR (range: 32.7% deterioration to 73.0% improvement) One patient presented with late-onset paraparesis, a second developed acute renal failure 8 months after repair. One early high-pressure endoleak (type 3) required correction. Three patients had died by median follow-up 12 months (1-36), 2 from heart disease and one from haemopericardium secondary to acute dissection of the ascending aorta (the dissection did not involve, nor extend close to, the endovascular graft)., Conclusions: Total endovascular repair of TAAA offers patients a minimally-invasive alternative to open surgery with early results at least comparable to those seen with open or hybrid surgical approaches., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess whether deployment of an endograft limb in the external iliac artery (EIA) increases the rate of limb occlusion following endovascular aneurysm repair (EVAR)., Methods: Interrogation of a prospectively maintained database identified 661 patients (596 men; median age 73 years, range 37-93) with infrarenal abdominal aortic aneurysm who underwent EVAR between 1996 and 2010 using Zenith stent-grafts predominately. Of these, 567 patients [56 (9.9%) women] had both endograft limbs deployed in the CIA (1203 limbs at risk), while 94 patients [9 (9.6%) women] had at least 1 limb in the EIA (22 bilateral; 116 limbs at risk). An adjunctive bare metal stent was used in 8 (9%) limbs deployed in the EIA., Results: There were 31 limb occlusions, all unilateral: 17 (3%) patients in the CIA group had an occluded limb (1% of limbs at risk) vs. 14 (15%) patients in the EIA group (12% of limbs at risk; p<0.0001). The median time to occlusion was 3 months (0-60) in the CIA group and 1 month (0-36) in the EIA group. The majority of occlusions were treated by extra-anatomical revascularization, most often a femorofemoral crossover bypass. No legs were amputated following occlusion of a limb placed in the CIA, but there were 3 amputations in the EIA group (p=0.003)., Conclusion: Deployment of endograft limbs into the EIA led to a higher rate of occlusion and leg amputation. Increased tortuosity of the EIA and a smaller caliber vessel are likely to account for the increased risk.

Introduction: Venous thrombus resolution may be regulated by an angiogenic process that involves the surrounding vein wall. The aims of this study were to determine whether: (i) thrombosis stimulates activation of the angiogenic transcription factor, hypoxia-inducible factor (HIF) 1α, and downstream expression of growth factors in vein wall; and (ii) upregulation of HIF1α in vein wall leads to increased growth factor expression and enhanced thrombus resolution., Materials and Methods: HIF1α, vascular endothelial growth factor (VEGF), and placental growth factor (PLGF) were quantified in mouse inferior vena cava (IVC) at days 1, 3, 7, and 14 after thrombus formation (n = 10-13 per group). An additional group of thrombosed mice were treated with the prolyl-hydroxylase domain (PHD) inhibitor, L-mimosine (L-mim) or vehicle control. HIF1α, VEGF, and PLGF in IVC were measured at days 1 and 7; and vein recanalisation and thrombus resolution were measured at days 7 and 10 (n = 6-7 per group)., Results: HIF1α was expressed in thrombosed IVC and its levels remained relatively constant throughout natural resolution. The levels of VEGF in thrombosed IVC were elevated at days 1 (P < 0.0001) and 3 (P < 0.05); and PLGF at days 1 (P < 0.0001), 3 (P < 0.0001), and 7 (P < 0.0001). Treatment with L-mim led to: increased HIF1α (P<0.05), VEGF (P < 0.005), and PLGF (P < 0.001) levels in the IVC; decreased thrombus size (P < 0.01); and increased vein recanalisation (P < 0.001)., Conclusions: HIF1α levels in vein wall are not affected by thrombosis and it appears that the angiogenic drive in the vein surrounding resolving thrombus is regulated independently of HIF1α. Stimulating HIF1α levels in the vein wall leads to an increased angiogenic drive and promotes vein recanalisation and thrombus resolution., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Tissues require an adequate supply of oxygen in order to maintain normal cell function. Low oxygen tension (hypoxia) is characteristic of a number of conditions, including cancer, atherosclerosis, rheumatoid arthritis, critical limb ischaemia, peripheral vascular disease, and ischaemic heart disease. Tissue hypoxia is found in tumours, atherosclerotic plaque, and ischaemic myocardium. There is a growing interest in methods to detect and assess hypoxia, given that hypoxia is important in the progression of these diseases. Hypoxia can be assessed at the level of the whole organ, tissue, or cell, using both invasive and non-invasive methods, and by a range of immunohistochemical, biochemical, or imaging techniques. This review describes and critiques current methods of assessing hypoxia that are used at the bench and in clinical practice.

Background: Endoluminal repair of thoracic aortic pathology has become established in clinical practice, but is associated with significant neurological complications. The aim of this study was to identify factors that were predictive of stroke and paraplegia., Methods: Prospective data was collected for a cohort of 293 consecutive patients having thoracic aortic endovascular repair between August 1997 and September 2009. Patient and procedural characteristics were related to the incidence of stroke and paraplegia using multivariate logistic regression analysis., Results: The median age was 68 years (18-87), there were 191 men and 102 women. Mortality was 5.1% for 195 elective and 13.4% for 98 urgent patients. Stroke affected 16 (5.5%) patients: 11 affected the anterior and 5 the posterior circulation. Coverage of the left subclavian artery with no revascularisation was the only significant factor predictive of stroke (OR 5.34 (1.42-20.40) P = 0.01). Paraplegia affected 16 patients (5.5%) but no independent risk factor was identified: 12 were identified perioperatively and 4 were delayed by up to 6 months., Conclusion: Covering the left subclavian artery without revascularisation increases the risk of stroke following endoluminal repair of thoracic pathology. Paraplegia appears to be more complex and no independent precipitating factor was identified., (Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Observational studies have shown that inflammatory cells accumulate within the thrombus and surrounding vein wall during the natural history of venous thrombosis. More recent studies have begun to unravel the mechanisms that regulate this interaction and have confirmed that thrombosis and inflammation are intimately linked. This review outlines our current knowledge of the complex relationship between inflammatory cell activity and venous thrombosis and highlights new areas of research in this field. A better understanding of this relationship could lead to the development of novel therapeutic targets that inhibit thrombus formation or promote its resolution.

Objective: Angiogenic factors are expressed within thrombus during resolution, but the primary stimulus for neovascularization is unknown. Our aims were to determine whether (1) hypoxia and hypoxia-inducible factor 1α (HIF1α) are induced in resolving thrombus, (2) this stimulates angiogenic factor production, and (3) upregulating HIF1α enhances thrombus resolution and vein recanalization., Methods and Results: Oxygen tension in the thrombus was negatively correlated with HIF1α levels (Spearman correlation [RS] = -0.77, P<0.0001), whereas HIF1α levels positively correlated with vascular endothelial growth factor (VEGF) expression (Pearson correlation [R] = 0.85, P<0.0005), during resolution in a murine model. HIF1α (P<0.005), VEGF (P<0.005), and VEGF receptor 1 (VEGFR1) (P<0.05) expression was 2-fold greater in the thrombus of mice treated with the prolyl hydroxylase domain inhibitor L-mimosine compared with controls. The levels of 13 other HIF1-mediated angiogenic factors were also increased. Thrombus weight (P<0.001) and volume (P<0.05) were reduced by a third in l-mimosine-treated mice compared with controls, whereas vein recanalization (P<0.005) and thrombus neovascularization (P<0.001) were 2-fold greater, and this was associated with increased inflammatory cell content., Conclusions: Hypoxia and HIF1α are induced in the naturally resolving thrombus and correlate with increased angiogenic factor expression. Upregulation of HIF1α enhances thrombus resolution and vein recanalization. HIF1α may represent a novel target for treatments that promote resolution and recanalization and reduce the incidence of post-thrombotic syndrome.

Purpose: To examine the feasibility of an automated 2-dimensional (2D) to 3- dimensional (3D) image registration system to simplify the navigational challenges faced in complex endovascular aortic procedures., Methods: An automated 2D-3D image registration system was used to overlay pre-acquired 3D computed tomography images onto fluoroscopy images taken during endovascular aneurysm repair. Errors between the 3D overlay and digital subtraction angiograms were measured and correlated with aortic neck angulation. A mean discrepancy < or =3 mm was considered clinically acceptable., Results: There was a strong correlation between maximum neck angulation and maximum registration error (Pearson's r = 0.75). Aortas with a maximum neck angulation < or =30 degrees had a mean error of 2.5+/-1.2 mm, whereas aortas with neck angulation >30 degrees had a mean error of 6.2+/-2.5 mm (p<0.0001)., Conclusion: The major source of registration errors is aortic deformation caused by the presence of the introducer and endovascular graft. Further work is required if this technology is to be routinely applied to severely angulated aortic anatomy.

Background: Our previous studies showed that the direct injection of an adenovirus construct expressing urokinase-type plasminogen activator (uPA) into experimental venous thrombi significantly reduces thrombus weight. The systemic use of adenovirus vectors is limited by inherent hepatic tropism and inflammatory response. As macrophages are recruited into venous thrombi, it is reasonable to speculate that these cells could be used to target the adenovirus uPA (ad-uPA) gene construct to the thrombus. The aims of this study were to determine whether macrophages transduced with ad-uPA have increased fibrinolytic activity and whether systemic injection of transduced cells could be used to target uPA expression to the thrombus and reduce its size., Methods: The effect of up-regulating uPA was examined in an immortalized macrophage cell line (MM6) and macrophages differentiated from human blood monocyte-derived macrophages (HBMMs). Cells were infected with ad-uPA or blank control virus (ad-blank). Fibrinolytic mediator expression, cell viability, and cytokine expression were measured by activity assays and enzyme-linked immunosorbent assays. Monocyte migration was measured using a modified Boyden chamber assay. A model of venous thrombosis was developed and characterized in mice with severe combined immunodeficiency (SCID). This model was used to study whether systemically administered macrophages over-expressing uPA reduced thrombus size. Uptake of HBMMs into the thrombus induced in these mice was confirmed by a combination of PKH2-labeled cell tracking and colocalization with human leukocyte antigen (HLA) by immunohistology., Results: Compared with ad-blank, treated HBMMs transduction with ad-uPA increased uPA production by >1000-fold (P = .003), uPA activity by 150-fold (P = .0001), and soluble uPA receptor (uPAR) by almost twofold (P = .043). Expression of plasminogen activator inhibitor (PAI-1) and PAI-2 was decreased by about twofold (P = .011) and threefold (P = .005), respectively. Up-regulation of uPA had no effect on cell viability or inflammatory cytokine production compared with ad-blank or untreated cells. Ad-uPA transduction increased the migration rate of HBMMs (about 20%, P = .03) and MM6 cells (>twofold, P = .005) compared with ad-blank treated controls. Human macrophage recruitment into the mouse thrombus was confirmed by the colocalization of HLA with the PKH2-marked cells. Systemic injection of uPA-up-regulated HBMMs reduced thrombus weight by approximately 20% compared with ad-blank (P = .038) or sham-treated controls (P = .0028)., Conclusion: Transduction of HBBM with ad-uPA increases their fibrinolytic activity. Systemic administration of uPA up-regulated HBBMs reduced thrombus size in an experimental model of venous thrombosis. Alternative methods of delivering fibrinolytic agents are worth exploring.

Background: The aim was to assess the quality of life (QoL) of patients who had surgery for primary lymphoedema., Methods: A QoL questionnaire was administered to patients who had surgery between 1981 and 2003 (retrospective group) and between 2003 and 2006 (prospective group)., Results: The response rate was 70.3 per cent (109 of 155 patients): 88 patients had limb reduction (78, retrospective; ten, prospective) and 21 had genital reduction (13, retrospective; eight, prospective). Forty-nine patients (63 per cent) who had limb reduction studied retrospectively reported satisfaction with the procedure and most of these would opt for surgery again. In the prospectively studied group, nine of ten patients reported improved limbs, and seven would opt for surgery again. Nineteen of 21 patients who had genital reduction would choose to have surgery again if needed (11 of the retrospectively assessed group and all of the prospective group). Patients' perception that surgery was worthwhile was greater in both of the prospectively assessed groups (P = 0.013)., Conclusion: Surgery for severe lymphoedema improved QoL at early assessment. This, however, may not be sustained. Genital reduction appeared to provide greater benefit than limb reduction.

Objective: Large sessile rectal adenomas are often difficult to excise and several different techniques have been described. This study evaluates the results of adenoma excision by endoscopic transanal resection using the urological resectoscope by a single surgeon in a UK district general hospital., Method: Between January 1989 and November 2004, data on all patients treated by endoscopic transanal resection of benign rectal tumours using a urological resectoscope (ETAR) were prospectively collected and analysed., Results: Forty patients (50% male, median age 72 years) underwent a total of 81 endoscopic transanal resections. The tumour characteristics were: size > 2 cm (83%), location in lower 2/3 of rectum (83%) and extensive circumferential carpet-like appearances (13%). Fifty percent of the patients required only one procedure to achieve clearance. Mean operative time was 26 min (range 10-65 min). Seventy-eight percent of the patients were discharged home within 24 h. Postoperative morbidity was 8% and in-hospital mortality was zero. Histology revealed severe dysplasia in 48% of the tumours and five patients were incidentally found to have foci of rectal adenocarcinoma. With a median follow-up of 47 months (range 2-162 months), local recurrences occurred in 13% (n = 5) of patients. All, except one, were treated successfully with further endoscopic transanal resections., Conclusion: ETAR is simple and safe for managing rectal adenomas.

It is now clear that the monocyte/macrophage has a crucial role in the development of atherosclerosis. This cell appears to be involved in all stages of atherosclerotic plaque development and is increasingly seen as a candidate for therapeutic intervention and as a potential biomarker of disease progression and response to therapy. The main mechanisms related to the activity of the monocyte/macrophage that have been targeted for therapy are those that facilitate recruitment, cholesterol metabolism, inflammatory activity and oxidative stress. There is also increasing evidence that there is heterogeneity within the monocyte/macrophage population, which may have important implications for plaque development and regression. A better insight into how specific phenotypes may influence plaque progression should facilitate the development of novel methods of imaging and more refined treatments.