Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo.

Numerous gene and cell therapy strategies are being developed for the treatment of neurodegenerative disorders. Many of these strategies use constitutive expression of therapeutic transgenic proteins, and although functional in animal models of disease, this method is less likely to provide adequate flexibility for delivering therapy to humans. Ligand-inducible gene expression systems may be more appropriate for these conditions, especially within the central nervous system (CNS). Mifepristone's ability to cross the blood-brain barrier makes it an especially attractive ligand for this purpose. We describe the production of a mifepristone-inducible vector system for regulated expression of transgenes within the CNS. Our inducible system used a lentivirus-based vector platform for the ex vivo production of mifepristone-inducible murine neural progenitor cells that express our transgenes of interest. These cells were processed through a series of selection steps to ensure that the cells exhibited appropriate transgene expression in a dose-dependent and temporally controlled manner with minimal background activity. Inducible cells were then transplanted into the brains of rodents, where they exhibited appropriate mifepristone-inducible expression. These studies detail a strategy for regulated expression in the CNS for use in the development of safe and efficient gene therapy for neurological disorders.

Optimizing the outcome of vascular intervention for Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TA) predisposes to the development of arterial stenoses and aneurysms, and is associated with considerable morbidity and mortality amongst young patients. The aims of this study were to analyse indications and outcomes of surgical intervention, and to assess the potential benefits of immunosuppression and the use of perioperative imaging. METHODS: This was a retrospective review of patients with TA referred between 2001 and 2012. RESULTS: A series of 97 patients with TA, seen at a single tertiary centre, is reported. Immunosuppression was required in 87 patients (90 per cent). Thirty-seven (38 per cent) underwent 64 procedures: 27 patients underwent 33 open surgical procedures and 20 patients had 31 endovascular procedures. After a median follow-up of 6 years, the overall success rate was 79 per cent for open surgery (mean graft patency 9.4 years) and 52 per cent for endovascular procedures (P = 0.035). Procedural failure was significantly reduced in patients receiving preoperative immunosuppression, and particularly endovascular procedures (P = 0.001). In addition to clinical examination and measurement of acute-phase reactants, combination non-invasive imaging including Doppler ultrasonography, [18F]fluorodeoxyglucose combined positron emission and computed tomography (CT), magnetic resonance angiography and CT angiography was used to identify arterial lesions, establish the diagnosis and monitor treatment outcomes. CONCLUSION: Outcomes of vascular intervention in TA may be improved by detailed preoperative assessment including measurement of disease activity, and by ensuring optimal immunomodulatory therapy before and after the procedure.

Takayasu arteritis: criteria for surgical intervention should not be ignored.

Takayasu aortoarteritis is a rare, chronic granulomatous panarteritis with significant morbidity amongst young patients. Current challenges include a lack of awareness about the condition, delays in diagnosis due to its varied presentation, and suboptimal methods for assessing disease activity. The development of noninvasive imaging including magnetic resonance angiography and positron emission tomography is aiding earlier diagnosis. Early initiation of immunosuppressive treatment is crucial to control active inflammation and minimize arterial injury. Recent studies investigating biological agents such as tumour necrosis factor- α antagonists are encouraging. Surgical revascularization should only be undertaken following careful consideration, as restenosis is common. The indications for considering intervention include uncontrolled hypertension due to renal artery stenosis, severe symptomatic coronary artery or cerebrovascular disease, severe aortic regurgitation, stenotic or occlusive lesions resulting in critical limb ischemia, and aneurysms at risk of rupture. In these cases, the risk benefit ratio for intervention is good. Open surgery, at present, has better outcomes compared to endovascular techniques. However, technological advances in endovascular treatment are continually improving. Controlling disease activity prior to and following revascularization is key to preventing complications. A multidisciplinary approach to the diagnosis and management of Takayasu arteritis is essential to achieve satisfactory patient outcomes.

Hybrid repair of the aortic arch in patients with extensive aortic disease.

OBJECTIVE: To evaluate the outcome of hybrid treatment of the aortic arch with supra-aortic debranching and endovascular stent-graft repair in a selected group of patients with complex disease. DESIGN: Case series study with retrospective analysis of prospectively collected non-randomised data. METHODS: Patients with hybrid repair of complex arch disease at a single centre over a 6-year period were enrolled in the study. Only patients with extensive arch pathologies requiring debranching of at least the left carotid artery were considered. Patients were divided into those who underwent complete and partial supra-aortic revascularisation. The χ2 test was used to evaluate differences in outcomes. Logistic regression analyses were applied to identify predictors of poor outcome. RESULTS: A total of 33 patients were included in the study. Complete and partial arch repair was performed in nine and 24 patients, respectively. The aortic disease extended to the thoracic and abdominal aorta in 39% and 52% of the patients, respectively. One-third of the patients (30%) were treated on an urgent/emergency basis. Elective 30-day mortality and morbidity rates were 13% and 35%, respectively. Early mortality was significantly higher in the complete arch repair group (p=0.046). Pre-existing renal impairment was identified as a poor prognostic factor. All extra-anatomic bypasses remained patent and no aortic disease-related deaths occurred during a mean follow-up period of 23 months (range, 1.5-58 months). Complete arch repair was associated with an increased incidence of late endoleak (p=0.018). CONCLUSIONS: Hybrid treatment of the aortic arch provides a feasible alternative treatment in patients who are high risk for conventional open surgical repair. Careful selection of patients is required to achieve satisfactory results.

Hybrid treatment of complex aortic arch disease with supra-aortic debranching and endovascular stent graft repair.

BACKGROUND: Aortic arch disease has conventionally been the domain of open surgical repair. Hybrid open and endovascular repair has evolved as an alternative, less invasive, treatment option with promising results. A systematic literature review and analysis of the reported outcomes was undertaken. METHODS: An Internet-based literature search using MEDLINE was performed to identify all studies reporting on hybrid aortic arch repair with supra-aortic branch revascularisation and subsequent stent graft deployment. Debranching should involve at least one carotid artery, so that patients merely requiring a carotid-subclavian bypass were not included. Only reports of five patients or more were included in the analysis. Outcome measures were technical success, perioperative, 30-day and late morbidity and mortality. RESULTS: Eighteen studies fulfilled our search criteria, and data from 195 patients were entered for the analysis. No comparative studies of hybrid aortic arch repair with other conventional or innovative treatment modalities were identified. Complete arch repair was performed in 122 patients (63%). The overall technical success rate was 86% (167/195). The most common reason for technical failure was endoleak (9%, 17/195). Overall perioperative morbidity and mortality rates were 21% (41/195) and 9% (18/195), respectively. The most common perioperative complication was stroke (7%, 14/195). Four aneurysm-related deaths were reported during follow-up (2%). No long-term data on hybrid aortic arch repair were identified. CONCLUSIONS: Hybrid repair of complex aortic arch disease is an alternative treatment option with acceptable short-term results. Stroke remains a frequent complication and mortality rates are significant. Further research with large comparative studies and longer follow-up is required.

Assessment of surgical competence at carotid endarterectomy under local anaesthesia in a simulated operating theatre.

BACKGROUND: Methods of surgical training that do not put patients at risk are desirable. A high-fidelity simulation of carotid endarterectomy under local anaesthesia was tested as a tool for assessment of vascular surgical competence, as an adjunct to training. METHODS: Sixty procedures were performed by 30 vascular surgeons (ten junior trainees, ten senior trainees and ten consultants) in a simulated operating theatre. Each performed in a non-crisis scenario followed by a crisis scenario. Performance was assessed live by means of rating scales for technical and non-technical skills. RESULTS: There was a significant difference in technical skills with ascending grade for both generic and procedure-specific technical skill scores in both scenarios (P < 0.001 for all comparisons). Similarly, there was also a significant difference in non-technical skill with ascending grade for both scenarios (P < 0.001). There was a highly significant correlation between technical and non-technical performance in both scenarios (non-crisis: r(s) = 0.80, P < 0.001; crisis: r(s) = 0.85, P < 0.001). Inter-rater reliability was high (alpha > or = 0.80 for all scales). CONCLUSION: High-fidelity simulation offers competency-based assessment for all grades and may provide a useful training environment for junior trainees and more experienced surgeons.

The visceral hybrid repair of thoraco-abdominal aortic aneurysms--a collaborative approach.

OBJECTIVE: To report the collaborative data of 3 major European Vascular Units using the 'visceral hybrid' procedure for thoraco-abdominal aortic aneurysms and dissections. METHODS: A consecutive series of 107 urgent and elective high-risk patients were included in a prospectively collected database. RESULTS: All stents involved the entire thoracic and abdominal aorta with left subclavian coverage in 19 and revascularisation in 12. The distal landing zone was in the infra-renal aorta in 75% and in the iliac artery in 25%. The 30-day mortality rate was 16/107 (14.95%). 13/107 (12.1%) of the patients suffered spinal cord ischaemia which was complete and permanent in 9/12 (8.4%). 4 patients (3.7%) required long term dialysis and a segment of gut infarction requiring resection occurred in 3 (2.8%). Most patients had visceral bypass grafting and aortic stent-grafting performed in one stage. In 18 patients the stenting was performed later. Three of these patients ruptured before the stenting procedure was undertaken. CONCLUSION: These early results of visceral hybrid repair for high-risk patients with complex thoraco-abdominal aortic aneurysms are encouraging, in a group of patients in whom fenestrated/branched stent-grafting is not an option and open surgery hazardous.

Long-term AAV vector gene and protein expression in mouse brain from a small pan-cellular promoter is similar to neural cell promoters.

The neurogenetic, lysosomal enzyme (LSE) deficiency diseases are characterized by storage lesions throughout the brain; therefore, gene transfer needs to provide widespread distribution of the normal enzyme. Adeno-associated virus (AAV) vectors can be effective in the brain despite limited transduction because LSEs are exported to neighboring cells (cross-correction) to reverse the metabolic deficit. The extent of correction is determined by a combination of the total amount of LSE produced by a vector and the spatial distribution of the vector within the brain. Neuron-specific promoters have been used in the brain because AAV predominantly transduces neurons. However, these promoters are large, using up a substantial amount of the limited cloning capacity of AAV vector genomes. A small promoter that is active in all cells, from the LSE beta-glucuronidase (GUSB), has been used for long-term expression in AAV vectors in the brain but the natural promoter is expressed at very low levels. The amount of LSE exported from a cell is proportional to the level of transcription, thus more active promoters would export more LSE for cross-correction, but direct comparisons have not been reported. In this study, we show that in long-term experiments (>6 months) the GUSB minimal promoter (hGBp) expresses the hGUSB enzyme in brain at similar levels as the neuron-specific enolase promoter or the promoter from the latency-associated transcript of herpes simplex virus. The hGBp minimal promoter thus may be useful for long-term expression in the central nervous system of large cDNAs, bicitronic transcription units, self-complimentary or other designs with size constraints in the AAV vector system.

Prevention of paraplegia during thoracoabdominal aortic aneurysm repair.

Paraplegia affects up to 22% of patients undergoing thoarcoabdominal aneurysm surgery, producing long-term morbidity and a significant burden to healthcare. This article discusses the mechanisms that may lead to paraplegia during open and endovascular repair from an anatomical and physiological perspective. There are many adjuncts that must be considered to reduce the risk of spinal cord injury, such as revascularisation of intercostal arteries, maintenance of high mean blood pressure, spinal cord drainage and cooling. These adjuncts are discussed, highlighting the evidence available for each method and the practical ways in which they may be used.

Gaining consent for carotid surgery: a simulation-based study of vascular surgeons.

AIM: Despite no formal training in consenting patients, surgeons are assumed to be competent if they are able to perform an operation. We tested this assumption for carotid endarterectomy (CEA). METHODS: Thirty-two surgeons [Group 1: junior surgical trainees--performed 0 CEA's (n=11); 2: senior vascular trainees--1-50 CEA's (n=11); 3: consultant vascular surgeons - > 50 CEA's (n=10)] consented two patients (trained actors) for a local anaesthetic CEA. The performance was assessed at post hoc video review by two independent assessors using a validated rating scale and checklist of risk factors. RESULTS: There was no difference in performance between the junior and senior trainees (1: median 91 range 64-121; 2: median 100.5 range 66-125; p=0.118 1 vs. 2 Mann-Whitney). There was a significant improvement between senior trainees and consultant surgeons (3: median 120 range 89-1 142; p=0.001 2 vs. 3). Few junior (1/11) and senior (2/11) trainees, and most (8/11) consultants, were competent. Inter-rater reliability was high (alpha=0.832). Consultant surgeons were significantly more likely to discuss cranial nerve injuries (p<0.0001 Chi-square test) as well as personal or hospital specific stroke risk (p<0.0001) than their junior counterparts. They were less likely to discuss infection (p<0.0001). CONCLUSION: Senior trainees, despite being able to perform a CEA, were not competent in consent. The majority of consultant surgeons had developed competence in consenting even though they had no formal training.

Treatment of complex aneurysmal disease with fenestrated and branched stent grafts.

OBJECTIVES: To describe our experience of treating juxtarenal (JRAAA's <4mm neck) and thoracoabdominal aortic aneurysms (TAAA's) using fenestrated and branched stent graft technology. DESIGN: Prospective single centre experience. METHODS: Since 2005, 29 fenestrated/branched procedures have been performed. 15 patients are studied with JRAAAs (n=7; median neck length 0mm (IQR 0-3.8)) or TAAAs (type I (n=2), III (n=2), IV (n=4)). ASA grade III in 12/15. Maximum diameter of aneurysm 64 mm (56-74 mm). Aneurysms were excluded using covered stents or branches from the main body to patent visceral vessels (40 target vessels total). Pre-operative and follow-up CT scans (1, 3, and 12 months) were analysed by a single Vascular Interventional Radiologist. RESULTS: Technical success for cannulation and stenting of target vessels was 98%. In-hospital mortality was 0%. One patient underwent conversion to open repair. Five had major complications including one paraplegia (type III TAAA) with subsequent recovery. Median length of stay was 9 days (IQR 7-18.75). At a median follow-up of 12 months (9-14), CT confirmed 36/37 (97%) target vessels remain patent. Sac size increased >5 mm in one patient only. There were no type I endoleaks, three type II endoleaks (one embolised, two under surveillance) and three type III endoleaks (two successfully treated percutaneously, one aneurysm ruptured 18 months after endografting and died). CONCLUSION: In selected patients, fenestrated and branched stents appear to be a safe and effective alternative to surgery for juxtarenal and thoracoabdominal aneurysms. The complication and mortality rates are low. The long-term durability of this procedure, however, needs to be proven.

Apparent diffusion coefficient reveals gray and white matter disease, and T2 mapping detects white matter disease in the brain in feline alpha-mannosidosis.

BACKGROUND AND PURPOSE: Methods to locate and identify brain pathology are critical for monitoring disease progression and for evaluating the efficacy of therapeutic intervention. The purpose of this study was to detect cell swelling, abnormal myelin, and astrogliosis in the feline model of the lysosomal storage disease alpha-mannosidosis (AMD) by using diffusion and T2 mapping. MATERIALS AND METHODS: Average apparent diffusion coefficient (ADC(av)) and T2 were measured by imaging the brains of five 16-week-old cats with feline AMD on a 4.7T magnet. ADC(av) and T2 data from affected cats were compared with data from age-matched normal cats. Brains were collected from both affected and normal cats following imaging, and histology was compared with quantitative imaging data. RESULTS: Gray matter from AMD cats demonstrated a 13%-15% decrease in ADC(av) compared with that in normal cats. White matter from AMD cats exhibited an 11%-16% decrease in ADC(av) and a 5%-12% increase in T2 values compared with those in normal control cats. Histologic evidence of neuronal and glial swelling, abnormal myelin, and astrogliosis was consistent with changes in ADC(av) and T2. CONCLUSION: ADC(av) and T2 data can be used to quantify differences in the gray and white matter in the feline AMD brain and may serve as surrogate markers of neuronal swelling, abnormal myelin, and astrogliosis associated with this disease. These studies may be helpful in assessing the efficacy of experimental therapies for central nervous system disease associated with lysosomal storage diseases.

European continuing medical education in vascular surgery: 5-year results of congresses approved by the Union Européenne des Médecins Spécialistes Section of Vascular Surgery.

AIM: Continuing medical education (CME) can be defined as ''educational activities that serve to maintain, develop, or increase the knowledge, skills and professional performance of a physician to provide services for patients, the public, or the profession''. CME is a major professional responsibility. The European Board of Vascular Surgery of the Union Européenne des Médecins Spécialistes (UEMS) Section of Vascular Surgery has, through its European Vascular CME (EVCME) Committee, accredited 74 congresses during the 5-year period from 2000-2004. METHODS: Official evaluation forms were completed by the congress participants for a personal appraisal of the quality of the activities. The data in this manuscript focused on questions that were the most relevant and of the greatest interest to the participants. A statistical analysis of the results was performed utilizing ANOVA and Robust tests of equality of means as well as a posthoc analysis for further investigation, and non parametric Wilcoxon signed ranks test. RESULTS: The educational needs of participants regarding new diagnostic and therapeutic modes were stated as ''important'' and ''extremely important'' in the responses at over 80% in total. Over 75% of the participants answered ''extremely important'' and ''important'' to the question ''how important is evidence-based practice to your practice''. CONCLUSION: This survey indicates that the EVCME approved congresses had a positive impact for the vascular surgeon by updating overall knowledge on vascular surgery; the majority of comments by the participants also indicates that EVCME is fulfilling its aim to bring as much evidence-based practice as possible into the daily work schedule of the surgeon by turning knowledge acquired by CME into performance of the participants.

Magnetic resonance imaging as a tool for monitoring stem cell migration.

Noninvasive monitoring of stem cells is an important step in developing stem-cell-based therapies. Among several imaging techniques available, magnetic resonance imaging (MRI) provides an effective way to detect implanted stem cells in live animals. In this mini-review, we discuss the available MRI contrast agents and different cell-labeling strategies used for detection of stem cell migration in the brain. The potential effects of MRI contrast agents on stem cell viability and differentiation are also discussed.

Competence assessment of senior vascular trainees using a carotid endarterectomy bench model.

BACKGROUND: Competency-based assessment is being introduced to surgical training. The value of bench-top technical skills assessment using a synthetic carotid endarterectomy (CEA) model was evaluated in vascular trainees and consultants. METHODS: Forty-one surgeons (13 junior trainees, 15 senior trainees and 13 experienced consultants with experience of more than 50 CEAs) performed a three-throw knot-tying exercise on a jig and a CEA on the bench model. A composite score for knot-tying was calculated, incorporating electromagnetic motion analysis. CEA technical skill was assessed using validated rating scales by blinded video analysis. RESULTS: Senior trainees performed better than junior trainees in knot-tying (P = 0.025) as well as generic (P < 0.001) and procedural (P < 0.001) skills on CEA model assessment. There was no difference between senior trainees and consultants on any of these measures. The CEA model interobserver reliability was high for all rating scales (generic alpha = 0.974, procedural alpha = 0.952, end-product alpha = 0.976). CONCLUSION: Senior trainees achieved the same score as consultants, suggesting a similar level of basic technical skill and knowledge required to perform CEA, and were significantly better than junior trainees. Performance on the bench model could provide an early assessment for suitability to proceed to operative training in a competency-based training and assessment programme.

AAA benchmarking by Dr Foster: a cause for concern?

INTRODUCTION: The publication of interpretable performance data for hospitals is an important service. In November 2002, the medical benchmarking company Dr Foster published a league table based on the results of abdominal aortic aneurysm (AAA) repair. The purpose of our study was to establish the validity of the data used in benchmarking. PATIENTS AND METHODS: Data on elective infra-renal AAA (IRAAA) repair was obtained from three sources. Data used by Dr Foster was based on the hospital PAS system. The databases for both Dr Foster and PAS were analysed and cross-referenced to the vascular unit database maintained by a separately employed audit co-ordinator. RESULTS: Of 395 total aortic aneurysm repairs, 223 (56%) were identified as elective IRAAA repairs on the unit database. Of these, 125 were identified on the PAS database and 115 on the Dr Foster database. The number of deaths was the same in both the unit and Dr Foster databases (n = 11) but the Dr Foster database included deaths in patients who had undergone juxtarenal (n = 1), Type III TAAA (n = 2) and Type IV TAAA (n = 4) repairs and omitted 7 deaths following IRAAA. The sensitivity and specificity for the PAS dataset was 0.51 and 0.93, respectively. For Dr Foster, the results were worse with a sensitivity and specificity of 0.41 and 0.86, respectively. The accuracy of the data was 0.6 and 0.69 for Dr Foster and PAS, respectively. Standardised mortality ratios (SMRs) were used to rank hospitals. Dr Foster's published SMR for elective AAA repair for our unit was 160. The actual SMR was 67. CONCLUSIONS: Robust and accurate published league tables should be supported and commended but currently available data appear to be misleading and may cause unnecessary concern to patients.

Training for carotid intervention: preparing the next generation.

BACKGROUND: Carotid interventions are performed to reduce the cumulative risk of stroke. The success of the procedure is dependent upon maintaining low operative risk. This article reviews the current state of training for both carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAS). METHODS: Medline searches were performed to identify articles with the combination of the following key words: carotid, endarterectomy, stent, training, assessment and simulation. Manual searches of the reference lists and related papers was conducted. RESULTS: Training and assessment for CEA and CAS follows the traditional apprenticeship model. There is no formal training protocol or objective means of assessment for either carotid endarterectomy or stenting. Models and simulators to allow for training and assessment away from the operative theatre have been developed, and exist for both CEA and CAS. CONCLUSION: The technology exists to allow for both training and assessment of competency to take place in a controlled and objective environment for both CEA and CAS. The use of simulation needs to be robustly evaluated and assessed to both complement and augment existing training programs to ensure that the highest standards of care are maintained for treatment of carotid territory disease. Objective competency based training and assessment is no longer unattainable. Simulators augment this process and without them operative exposure is sporadic and crisis management infrequent.

Critical limb ischemia in the dialysis-dependent patient: infrainguinal vein bypass is justified.

The combination of critical limb ischemia and end-stage renal failure (ESRF, ie, dialysis- dependent) represents severe systemic atherosclerosis and is associated with a very poor medium-term survival. Many nephrologists and surgeons advocate primary amputation. We examined the recent experience in this unit to determine whether infrainguinal bypass in these patients can be justified. Retrospective study of all patients with critical limb ischemia and ESRF undergoing surgery in a regional vascular and renal unit between January 1996 and May 2003. Forty-two patients with ESRF (median age 65 years) were referred with critical limb ischemia. Seventeen patients underwent 24 (7 bilateral) infrainguinal bypasses (17 autologous vein, 7 polytetrafluoroethylene [PTFE] conduit; tissue loss in 21/24, 88%), and 25 patients had primary major amputations of 32 limbs. Early occlusion occurred in 5 grafts (21%, all 5/5 PTFE). In-hospital mortality was 13% in the bypass group, 24% in the amputation group. Median in-hospital stay was 59 days in the bypass group, 46 days in the amputation group. Thirty-day, 1- and 2-year survival was 88%, 50%, and 33% in the bypass group; 83%, 39%, and 35% in the amputation group. The limb salvage rate was 66% at 1 year. Seventy-five percent (18/24) of operated on limbs (15/17 of vein grafts) avoided major amputation at follow-up (median 18 months) or death. The combination of critical limb ischemia and end- stage renal failure carries a poor medium-term survival independent of primary amputation or surgical revascularization. Infrainguinal bypass in selected cases with vein conduit can, however, allow the majority of these patients to avoid major limb amputation.

The examination assessment of technical competence in vascular surgery.

BACKGROUND: The European Board of Surgery Qualification in Vascular Surgery is a pan-European examination for vascular surgeons who have attained a national certificate of completion of specialist training. A 2-year study was conducted before the introduction of a technical skills assessment in the examination. METHODS: The study included 30 surgeons: 22 candidates and eight examiners. They were tested on dissection (on a synthetic saphenofemoral junction model), anastomosis (on to anterior tibial artery of a synthetic leg model) and dexterity (a knot-tying simulator with electromagnetic motion analysis). Validated rating scales were used by two independent examiners. Composite knot-tying scores were calculated for the computerized station. The stations were weighted 35, 45 and 20 percent, respectively. RESULTS: Examiners performed better than candidates in the dissection (P<0.001), anastomosis (P=0.002) and dexterity (P=0.005) stations. Participants performed consistently in the examination (dissection versus anastomosis: r=0.79, P<0.001; dexterity versus total operative score: r=-0.73, P<0.001). Interobserver reliability was high (alpha=0.91). No correlation was seen between a candidate's technical skill and oral examination performance or logbook-accredited scores. CONCLUSION: Current surgical examinations do not address technical competence. This model appears to be a valid assessment of technical skills in an examination setting. The standards are set at a level appropriate for a specialist vascular surgeon.