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Rationale Macrophages in atherosclerotic plaques are a heterogeneous population. To uncover signatures of classical (M1) or alternative (M2) macrophage polarisation during plaque instability, we compared cytokine and chemokine production via Luminex profiling in asymptomatic human carotid plaques with carotid plaques in the territory of recent focal neurological symptomatology. Methodology Carotid endarterectomy specimens were collected from 50 consenting patients (26 symptomatic, 24 asymptomatic). Fresh specimens were divided symmetrically along their long axis, allowing for representative undertaking of both immunohistochemistry and plaque cell culture (Monaco et al. PNAS USA 2004; 101 :5634–9). Automated image analysis (Clemex Vision) quantified CD68 staining. Cells were isolated via enzymatic dissociation to produce a viable mixed cell suspension and cultured for 24 h. Macrophage was the predominant cell type in the mixed cell culture. Supernatants were interrogated with a panel of 22 cytokines and chemokines on a Luminex 100 platform. Results CD68 immunopositivity was significantly higher in symptomatic than in asymptomatic plaques (p=0.0075). Luminex detected 17 of the 22 analytes, with a predominance of myeloid-derived cytokines over lymphoid-derived cytokines, in keeping with the predominance of macrophage in culture. Tumour necrosis factor α, interleukin (IL)-1α, IL-1β, IL-6, granulocyte-macrophage colony-stimulating factor, CCL2, CCL5 and IL-10 levels were significantly higher in symptomatic plaques. Conclusions Our data demonstrate that symptomatic atherosclerotic carotid disease is associated with a cytokine pattern consistent with the predominance of proinflammatory M1-type macrophage polarisation. M2-dependent cytokine IL-10 was also part of this inflammatory response, suggesting macrophage heterogeneity. Our study has implications for future therapeutic and diagnostic applications for high-risk atherosclerosis.

s / International Journal of Surgery 8 (2010) 501–578 515 Results: 100% of patients recruited were high risk of malnutrition on admission. Overall average daily calorie intake over 3 days was 446.2 kCal average protein intake was 16.1 g. Intake for each group was well below recommended target intake of 1810 kCal and 46.5 g, p < 0.05. Discussion: Only 5% of 40 patients, all high risk for malnutrition, received dietician input and oral supplementation. Recorded nutritional intake was well below target nutrient intakes, this is likely to be detrimental to surgical outcome. Conclusion: Despite NICE nutrition guidance, acutely unwell, malnourished patients are not receiving their basic nutritional requirements. THE INFLUENCE OF JUNCTIONAL COMPETENCE ON PRIMARY SAPHENOUS REFLUX L. Wing, A. Macdonald, M.I. Qureshi, C.S. Lim, M. Ellis, I.J. Franklin, A.H. Davies. Imperial College, London The aetiology of venous incompetence remains uncertain. We analysed patterns of saphenous incompetence to ascertain support for the ascending/descending theory. Duplex ultrasonography (VDU) reports of patients referred with venous signs and symptoms between 2005 and 2007 were reviewed. Limbs with evidence of invasive treatment, DVT, congenital abnormality, or inadequate data were excluded. Frequencies of six saphenous patterns were determined: competent great saphenous vein (GSV); incompetent above-knee GSV (pGSV); incompetent below-knee GSV (dGSV); incompetent pGSV and dGSV (pdGSV); competent short saphenous vein (SSV); and incompetent SSV. Findings were compared between those with competent and incompetent saphenous junctions using Chi-squared test (P < .05 considered significant). In total, 2725 limbs underwent VDU. Following exclusion, 1400 limbs from 1044 patients (389 male, 655 female, mean age 51 years) were analysed. The incompetent SFJ was associated with pdGSV reflux: 73% (543/747) versus 22% (145/653), (P < 0.0001). However, dGSV reflux was the most prevalent competent SFJ abnormality: 36% (234/653) versus 3% (24/747), (P < 0.0001). Most limbs with SPJ reflux showed SSV incompetence (169/262; 65%) versus 21% (234/ 1138), (P < 0.0001). Saphenous reflux is more extensive in the presence of junctional reflux, however the ascending/descending theory cannot account for all disease patterns. Multifocal initiation may play a significant role in venous incompetence. INCIDENCE OF FATAL VTE FOLLOWING PRIMARY LOWER LIMB JOINT REPLACEMENT J. Marciniak, S. Bonczek, N. Bejjanki, N. Hunt. York District Hospitals NHS Trust Introduction: The use of chemical prophylaxis in preventing venous thromboembolism (VTE) is a well accepted practice for lower limb arthroplasty. The rate of Pulmonary Embolism (PE) is quoted between 0.34–2% worldwide following these procedures, with fatalities due to PE in 1–5%. We looked at 2318 patients over 3 years to investigate whether use of only mechanical prophylaxis alone is beneficial. Method: Retrospective study of elective primary joint replacements; 1182 hip and 1136 knee. All patients were offered intermittent pneumatic compression and thromboembolism deterrent stockings (TEDs) and early mobilisation post operatively. Low molecular weight heparins (LMWHs) were reserved for patients with past history of VTE or malignancy. Results: Total rates of symptomatic VTE according to NICE guidelines is quoted as 2.7%. Our studies total incidence of symptomatic VTE in 1.68% (95% CI: 0.52%). The incidence of fatal PE in three months was 0.09% (95% CI: 0.12%). Fatal PE occurred in 0.13% (95% CI: 0.15%) six months post operatively. Conclusion: In elective primary hip and knee replacements, the incidence of VTE and fatal PE is not significantly influenced by the addition of LMWHs. We recommend that LMWHs are used in patients refusing mechanical prophylaxis or with past history of VTE or malignancy. EFFECT OF DELAY TO SURGERY ON MORTALITY, LENGTH OF STAY AND POST-OPERATIVE COMPLICATIONS IN HIP FRACTURE PATIENTS Reshid Berber, Chris Boulton, Christopher Moran. Queen's Medical Center, Nottingham University Hospital Objectives: To determine whether a delay to surgery affects mortality rate, length of stay and post-operative complications following hip fracture surgery in elderly patients. Prospective Observational Study. Participants: 7398 patients who underwent hip fracture surgery. Results: The 30 day mortality was 10.2%. At 90-days, mortality was 20.1% and at 1-year it was 32.4%. In patients declared fit for surgery on admission (n 1⁄4 5665), 30-day mortality was 7.1% in those operated on without delay, rising to 10.3% at over 4-days delay (p1⁄4 0.117). However, those operated on after 5-days delay, 30-day mortality equalled 13.6% (p 1⁄4 0.009). Those declared fit for surgery on admission stayed a total 18.99 days if operated within 48hours, rising to 22.25 days with over 48hours delay (p < 0.001). An increase in the rate of chest (8.6 vs. 11.9%, p < 0.001) and Clostridium Difficile infection (0.4 vs. 0.8%, p 1⁄4 0.027) was 48hours delay. This is not seen when fit patients only are considered. Conclusions: The 30-daymortality following hip fracture surgery is 10.2%. Patients admitted without co-morbidities have significantly increased mortality when surgery is delayed by over 5-days. A 48hour delay to surgery significantly increases length of stay, however no correlation was seen between delay to surgery and post-operative complications in fit patients. THE INFLUENCE OF AMBIENT TEMPERATURE, ATMOSPHERIC PRESSURE AND WATER VAPOUR PRESSURE ON EPISTAXIS ADMISSION RATE Venkat M. Reddy , Owen Judd , Hisham S. Khalil . 1 Royal Cornwall Hospitals NHS Trust; University Hospitals Leicester NHS Trust; 3 Plymouth Hospitals NHS Trust Objective: To investigate the relationship between weather variables (atmospheric pressure, temperature, water vapour pressure) and epistaxis admission rates at Derriford Hospital, Plymouth, UK. Method: Retrospective observational study using hospital inpatient information databases to identify all patients admitted with epistaxis from April 1999 to March 2009 inclusive. Meteorological data for the same period was retrieved from the University of Plymouth Meteorological Archive. Epistaxis admissions were investigated for correlation with weather variables using Pearson correlation, and stepwise multiple regression analysis was performed. Results: During the study period there were 1071 admissions accounted for by 978 patients (501 males (mean age 64 years) and 477 females (mean age 72 years)). Multivariate regression analysis revealed that less than 10% of the variance in epistaxis admissions is explained by the maximum

The management of patients with intermittent claudication has focused on improving symptoms caused by restricted blood flow through a limb. However, the goals of managing the condition have recently been broadened to include prevention of coronary and cerebrovascular events. Intermittent claudication is underrecognised as a risk factor for coronary and cerebrovascular events. Sixty per cent of people with claudication die from coronary heart disease, and 10% of them die from stroke.1 Treating the person with claudication, therefore, is likely to pay high dividends in terms of reducing deaths from myocardial infarction and stroke. Morbidity and mortality in these patients can be improved by various strategies. Exercise is widely held to be beneficial to patients with intermittent claudication, but it has been applied with little enthusiasm. In experimental models, however, exercising ischaemic muscle improved muscle performance within a short period of time. A meta-analysis of 21 studies of the effects of exercise on patients with intermittent claudication suggested that the average improvement in the distance that patients could walk was 122%.2 Programmes in which …

Background The aim of this study was to determine the primary management of patients presenting with a new diagnosis of transient ischaemic attack (TIA) or stroke by general practitioners and to establish whether practice was uniform across the UK, and to determine whether initial management influenced the performance of carotid endarterectomy (CEA) across the health regions of the UK. Methods Information on regional reporting of new cases of TIA and stroke between 1992 and 1996 was obtained from the General Practice Research Database, a database of six million patients from 450 practices. Analysis of data from the primary care database and routine data sources was undertaken. Main outcome measures were incidence of TIA and stroke, rates of referral for specialist opinion, prescription of antiplatelet agents and rates of CEA. Results There were twofold differences (P < 0·00005, χ2 test) in the incidence of cerebrovascular disease between Regional Health Authorities (RHAs) between the years 1992 and 1996 and also for each year. Mean stroke incidence per annum was 143 per 100 000 and TIA incidence 183 per 100 000. Yorkshire had the highest incidence at 170 (stroke) and 206 (TIA) per 100 000 of the population compared with 95 and 98 per 100 000 for Oxford. Some 37 per cent of new patients with stroke and 19 per cent of patients with TIA were referred for specialist opinion following initial diagnosis. These rates did not change over time. There was no positive correlation between disease incidence and referral rate; Yorkshire referred the least (14 per cent) and Oxford the most (26 per cent). The majority of referrals for TIA were made to general medicine (39 per cent); 6 per cent of patients were referred directly for surgical opinion. Mean prescription rate of antiplatelet medication over the time period was 17 per cent for patients with stroke and 35 per cent for those with TIA. Mean CEA rate for English RHAs for the time interval was 15·5 per 100 000. There was a positive correlation between the incidence of disease and rate of CEA, with the regions with the highest incidence of disease tending to perform the most CEAs. Conclusion The incidence of cerebrovascular disease varies significantly across health regions in the UK. There was no correlation between the regional incidence of disease and the number of patients referred for specialist opinion, but CEA rates were generally correlated with the regional difference in incidence of disease. The low referral rate may be a factor in the perceived underperformance of CEA in the UK and the low usage of antiplatelet medication is surprising.

Objectives The peri-operative use of antiplatelet, anticoagulant and other drugs for patients undergoing carotid endarterectomy (CEA) is unclear and consensus is lacking. This study aimed to assess the current peri-operative practice of European vascular surgeons with respect to antiplatelet and other medications for patients undergoing CEA. Design Online questionnaire study. Methods Members of the Vascular Society of Great Britain & Ireland and European Society for Vascular Surgery were invited to complete an online survey in March 2008. Surgeons were asked about their preferences for the peri-operative administration of antiplatelet, statin and other medications for patients undergoing carotid endarterectomy. Results Partial or complete responses were received from 399/650 (61.4%) surgeons with a collective annual throughput of >11500 CEA procedures. For symptomatic and asymptomatic patients, 20/392 (5%) and 47/392 (12%) of surgeons would stop aspirin before surgery and 170/392 (43%) and 217/392 (55%) of surgeons would stop Clopidogrel prior to CEA. Of surgeons who would stop Clopidogrel, 84/170 (49%) and 124/217 (57%) would do so >7 days before surgery for symptomatic and asymptomatic patients respectively. 12/393 (3%) surgeons would prescribe one 75 mg dose of Clopidogrel on the evening before surgery. Intra-operative Dextran was used selectively by 40/395 (10%). Only 78/393 (20%) would delay surgery to commence a statin. Intra-operatively, 348/394 (88%) used intravenous heparin, which was reversed routinely by 47/348 (13%) and selectively by 60/348 (17%). Conclusions There appears to be broad consensus between vascular surgeons in the pharmacological management of patients undergoing carotid endarterectomy, although some variations do exist. Further clinical studies may help clarify the optimum management strategy in this patient group.

Objectives: false femoral artery aneurysm is an occasional complication of percutaneous cardiovascular radiological procedures. Compression ultrasonography causes thrombosis non-invasively, reducing need for operative intervention. The technique fails in a proportion of cases. Analysis was undertaken to identify causes of failure. Design: prospective open study. Materials and Methods: patients presenting with false femoral artery aneurysm since 1984 were identified from a computerised database (BIPAS). Since 1993 compression ultrasonography has been performed as first line treatment according to a standard protocol. Prospectively collected ultrasonographic data and case notes were reviewed to identify causes of failed compression. Results: false femoral artery aneurysm occurred as a complication in 32/26 687 (0.12%) cardiovascular radiological procedures. Eighteen aneurysms were treated by compression. The technique was successful in 11/18 (61%) cases but primary failure occurred in seven cases. Six out of seven had bleeding abnormalities (Chi-squared analysis with Yates correction 10.55, p=0.0012), four were anticoagulated and compression was subsequently successful following reversal of warfarin therapy in three of these patients. In 4/18 cases surgical repair was necessary. Conclusions: compression ultrasonography is an effective treatment of false femoral aneurysms, however, hypocoagulability is a significant cause of failure. For patients in whom anticoagulation cannot be reversed, primary surgical repair should be considered.

Background No randomized controlled trials exist to show whether simple venous surgery benefits healing or maintenance of healing of venous ulcers. Methods Some 121 consecutive patients with new episodes of venous ulceration were identified; 45 patients were unfit or unwilling for randomization. The remaining 76 (39 women) were assigned randomly to received a four-layer bandage (n = 39) or simple venous surgery (n = 37). All patients were followed for a minimum of 6 months. Outcome was assessed at a minimum of 6 months as healing and health-related quality of life (HRQL). Results The two groups had similar co-morbidity and pattern of venous incompetence. There were no major complications in either group. The healing rate was 64 per cent (25 of 39) in the conservatively treated group and 68 per cent (25 of 37) in the operated group (P = 0·75, Pearson χ2 test). There was no significant difference between time to ulcer healing in the two treatment groups (log rank statistic = 0·69, P = 0·41). Patterns of venous incompetence did not affect the healing rate. There were no major differences in HRQL between the two groups. Conclusion This pilot study suggests that simple venous surgery gives no adjuvant benefit to four-layer bandaging in venous ulceration from the point of view of healing rate and quality of life.

Background: Intermittent claudication (IC) carries an increased risk of vascular death compared with that in age-matched controls. The role of antiplatelets and statins in the reduction of this risk in new claudicants was evaluated in an observational study of a prospectively gathered database, the General Practice Research Database (GPRD), with 430 practices contributing 8 million patients in the UK. Methods: All patients aged 40–79 years with newly diagnosed IC and no history of previous peripheral vascular disease were identified using recognized GPRD OXMIS codes. Prescription of antiplatelet therapy (APT) up to 12 months before or after diagnosis, and the use of statin therapy (ST) at the time of diagnosis, of IC was noted. Odds ratios (ORs) adjusted for APT, ST, sex, age, smoking, diabetes, and coexisting cardiac and cerebrovascular disease were calculated. Patients with critical limb ischaemia were excluded. Outcome measures were all-cause death, fatal stroke and fatal myocardial infarction (MI) up to 5 years after diagnosis of IC. Results: Between 1988 and 1993, 20 474 patients with newly diagnosed IC were identified. The Table summarizes the results. Pharmacotherapy and outcome in intermittent claudication, P. F. S. Chong, H. Seaman, J. Golledge, R. Gibbs, R. Lawrenson, R. M. Greenhalgh and A. H. Davies APT No APT Adjusted ORfor APT* ST No ST Adjusted ORfor ST* Combined APT + ST Values in parentheses are percentages or * 95 per cent confidence intervals. † P < 0·05 Total patients 7652 (37·4) 12 822 (62·6) 498 (2·4) 19 976 (97·6) 340 (1·7) Fatal MI 233 (3·0) 300 (2·3) 0·53 (0·42–0·69)† 6 (1·2) 527 (2·6) 0·69 (0·26–1·86) 2 (0·6) Fatal stroke 181 (2·4) 181 (1·4) 0·79 (0·62–1·01) 2 (0·4) 360 (1·8) 0·37 (0·08–1·66) 2 (0·6) All deaths 1210 (15·8) 1 720 (13·4) 0·94 (0·87–1·03) 23 (4·6) 2 907 (14·6) 0·29 (0·19–0·45)† 15 (4·4) Conclusion: Prescription rates of statins and antiplatelets in new claudicants in the UK are low and could be improved. These results suggest that ST is associated with a significant reduction in all-cause mortality rate in new claudicants. Patients receiving APT demonstrated a significant reduction in death from MI. © 2001 British Journal of Surgery Society Ltd

Background Carotid endarterectomy (CEA) is a proven method of stroke prevention in patients with symptomatic and asymptomatic high-grade internal carotid artery stenosis. This study examined whether site of residence affects access to CEA in Scotland. Methods Scottish Morbidity Record hospital discharge data were collected by the Information and Statistics Division of the National Health Service in Scotland and analysed for the interval 1 January 1989 to 31 December 1995. The number of CEAs performed in the hospitals of each of the 15 regional Health Boards, and CEA rate per 100 000 population resident in each Health Board region, were determined. Results In 1989, 65 CEAs were performed in the hospitals of five Health Boards and in 1995, 431 CEAs were performed in nine Health Boards. In 1989, the CEA rate per 100 000 resident population varied between 0 (four regions) and 4 (one region), with one region significantly different from Scotland as a whole (P

Serial measurements of extracellular fluid (ECF), and plasma volumes were evaluated in dogs before and during general anaesthesia with sodium pentobarbitone and under controlled conditions of arterial pH, pO2, pCO2, and blood pressure. Sodium pentobarbitone anaesthesia caused an early, significant rise in ECF volume with a fall in haematocrit, plasma protein, and plasma potassium concentrations. Plasma osmolality and sodium concentrations were unchanged. The lack of change in ECF sodium concentration suggests that the total ECF sodium content increased in parallel with the expansion of this compartment. Sodium bound to macromolecules in the interstitial space or to bone is suggested as a possible source of sodium ions. It is unlikely that intracellular sodium stores contribute to a significant extent in these changes. During prolonged anaesthesia plasma volume progressively increased while total ECF volume returned towards control values. This work clarifies previous observations and suggests that major fluid movements occur during sodium pentobarbitone anaesthesia primarily associated with altered cell membrane properties and generalised haemodynamic changes.

Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning.Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and endstage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO2) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality.Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed.

Background: Hypoxia may contribute to the pathogenesis of various diseases of the vascular wall. Hypoxia-inducible factors (HIFs) are nuclear transcriptional factors that regulate the transcription of genes that mediate cellular and tissue homeostatic responses to altered oxygenation. This article reviews the published literature on and discusses the role of the HIF pathway in diseases involving the vascular wall, including atherosclerosis, arterial aneurysms, pulmonary hypertension, vascular graft failure, chronic venous diseases, and vascular malformation. Methods: PubMed was searched with the terms "hypoxia-inducible factor" or "HIF" and "atherosclerosis," "carotid stenosis," "aneurysm," "pulmonary artery hypertension," "varicose veins," "venous thrombosis," "graft thrombosis," and "vascular malformation." Results: In atherosclerotic plaque, HIF-1α was localized in macrophages and smooth muscle cells bordering the necrotic core. Increased HIF-1α may contribute to atherosclerosis through alteration of smooth muscle cell proliferation and migration, angiogenesis, and lipid metabolism. The expression of HIF-1α is significantly elevated in aortic aneurysms compared with nonaneurysmal arteries. In pulmonary hypertension, HIF-1α contributes to the increase of intracellular K+ and Ca2+ leading to vasoconstriction of pulmonary smooth muscle cells. Alteration of the HIF pathway may contribute to vascular graft failure through the formation of intimal hyperplasia. In chronic venous disease, HIF pathway dysregulation contributes to formation of varicose veins and venous thromboembolism. However, whether the activation of the HIF pathway is protective or destructive to the venous wall is unclear. Increased activation of the HIF pathway causes aberrant expression of angiogenic factors contributing to the formation and maintenance of vascular malformations. Conclusions: Pathologic vascular wall remodelling of many common diseases of the blood vessels has been found to be associated with altered activity of the HIF pathway. Therefore, understanding the role of the HIF pathway in diseases of the vascular wall is important to identify novel therapeutic strategies in the management of these pathologies. © 2013 by the Society for Vascular Surgery.

Background Guidelines and protocols assist in the clinical management of patients, helping to utilise available resources efficiently, however, there is limited documented guidance on surveillance of patients following open arterial surgery. The frequency of clinical follow up, Doppler ultrasound measurements and radiological imaging should all be justified. Here we review the available literature to offer an evidenced based approach to postoperative care. Method An electronic search was made of Medline and Embase databases through September 2009 revealing over 2300 studies in the initial searches. Following title and abstract screening, the relevant medical literature concerning post-operative surveillance of open vascular procedures was reviewed (300 papers). 42 papers were included in this review. Surveillance recommendations were constructed from the evidence presented. Results and conclusion Detailed anatomical imaging is available for the technical assessment in the majority of patients' postoperative management; however there is little Level 1 evidence to guide modality or timing. Grades B and C recommendations form the majority of surveillance recommendations. Clinical review remains the mainstay of surveillance following open peripheral arterial surgery. Duplex scanning is the imaging modality of choice when indicated in most instances. Minimal data exists to quantify quality of life or intervention efficacy.

Background Recurrent varicose veins (RVV) occur in 13% to 65% of patients following treatment, and remain a debilitating and costly problem. RVV were initially thought largely to be due to inadequate intervention, however, more recently neovascularization and other factors have been implicated. This review aims to provide an overview of the current understanding of the etiology and pathogenesis of RVV. Methods A systematic search of the PubMed database was performed using the search terms including "recurrent," "varicose veins," and "neovascularization." Results Three types of RVV have been reported, namely residual veins, true RVV, and new varicose veins, although the definitions varied between studies. RVV are attributable to causes including inadequate treatment, disease progression, and neovascularization. Using duplex ultrasonography, neovascularization has been observed in 25% to 94% of RVV. These new vessels appear in various size, number, and tortuosity, and they reconnect previously treated diseased veins to the lower limb venous circulation. Histologically, these vessels appear primitive with incomplete vein wall formation, decreased elastic component, and lack of valves and accompanying nerves. Although the rate of RVV following open surgery and endovenous treatment appears similar, neovascularization seems less common following endothermal ablation. Other causes of RVV following endovenous treatment include recanalization and opening of collaterals. Conclusions Recurrence remains poorly understood following treatment of varicose veins. Neovascularization is an established and common cause of RVV, although other factors may contribute.

In recent years, many important discoveries have been made to challenge current policy, guidelines, and practice regarding how best to prevent stroke associated with atherosclerotic stenosis of the origin of the internal carotid artery. The United States Center for Medicare and Medicaid Services (CMS), for instance, is calling for expert advice as to whether its current policies should be modified. Using a thorough review of literature, 41 leading academic stroke-prevention clinicians from the United States and other countries, have united to advise CMS not to extend current reimbursement indications for carotid angioplasty/stenting (CAS) to patients with asymptomatic carotid stenosis or to patients with symptomatic carotid stenosis considered to be at "low or standard risk from carotid endarterectomy (CEA)." It was concluded that such expansion of reimbursement indications would have disastrous health and economic consequences for the United States and any other country that may follow such inappropriate action. This was an international effort because the experts to best advise CMS are relatively few and scattered around the world. In addition, US health policy, practice, and research have tended to have strong influences on other countries.

Objective. Exercise advice is the main treatment for symptom relief in the UK for patients with mild to moderate Intermittent Claudication (IC). Would a weekly exercise and motivation class for 6 months offer adjuvant benefit over written and verbal exercise advice alone?Patients and methods. Fifty-nine patients attending a regional vascular centre for whom IC was the main factor affecting mobility were randomised to either exercise advice alone (n=30) or exercise advice with a once a week 45 min supervised exercise/motivation class (n=29). The mean age was 68 years. Baseline and 6-month assessment included a Quality of Life Questionnaire—the Short-Form-36, the Charing Cross Symptom Specific Claudication Questionnaire (CCCQ) and treadmill walking distance (3.5 km/h 12%).Results. At 6-month follow-up the supervised exercise group had improved their treadmill walking by 129% compared to 69% in the advice alone group (p=0.001). This significant improvement was maintained at the subsequent 9 and 12-month follow-up assessments. By the 9-month stage the advice only group CCCQ score had improved 16% from baseline, while the supervised exercise group had a significantly better 43% improvement in base line score (p

Background: Maintenance of luminal area is essential for the optimal performance of venous bypass grafts. However, injury and response to the arterial circulation evoke vascular remodelling that favors intimal hyperplasia, with luminal encroachment and inward remodelling. Potassium channel-opening drugs reduce tissue workload and peripheral vascular resistance and through these mechanisms could favor outward or expansive remodelling of vein grafts. We tested the hypothesis that levcromakalim, a potassium channel opener, would enhance expansive remodelling in vein grafts. Methods: A randomized, double-blind, placebo-controlled trial was conducted in 33 rats with vena cava-to-aorta bypass grafts. Drugs were administered via osmotic pump for 7 days after surgery. Half the cohort had bromodeoxyuridine (BrdU) infused at day 6. Morphometric analysis was conducted of pressure perfusion-fixed grafts harvested at 1 week and 4 weeks. Results: At 1 week, lumen area was similar in both groups (1.82 ± 0.39 mm2 placebo vs 1.85 ± 0.36 mm2 levcromakalim), although medial cell density and BrdU staining were significantly increased in the placebo group. At 4 weeks, lumen area was unchanged in the placebo group (1.88 ± 0.51 mm2) but had increased to 2.32 ± 0.46 mm2 in the levcromakalim group (P = .039 vs 1 week), with a very significant reduction in the intimal area (levcromakalim, 0.06 ± 0.02 mm2 vs placebo, 0.33 ± 0.17 mm2; P = .001). Conclusions: Early, short-term treatment with levcromakalim favors expansive remodelling of experimental vein grafts to mimic the effect of external stenting. This expansive remodelling was associated with a reduction in medial cell proliferation at 1 week. Clinical Relevance: Critical limb ischemia can be treated by bypass surgery or angioplasty, but inward remodelling with restenosis is a common problem. There has been little previous experimental work to identify treatments associated with expansive remodelling, which would increase the chances of vessel patency. Here, in a randomized trial, we show that short-term treatment with a potassium channel opener (a class of drug that can be used to treat hypertension) results in strong, expansive remodelling, with increases the lumen area and graft size of experimental vein grafts by >25%. © 2006 The Society for Vascular Surgery.

Objective the ability of colour duplex to accurately locate incompetent venous sites has been widely published; its value in pre-operative marking in simple primary varicose vein surgery is evaluated in this study. Design of study prospective randomised controlled trial. Setting regional vascular service, hospital patients. Subjects consecutive patients (149) undergoing primary varicose vein surgery where the only difference was one group of patients received duplex marking prior to surgery. Six weeks and 12 months post-operatively all patients had a colour duplex scan to determine the accuracy of surgery and the presence of residual/recurrent varicose veins and completed the Aberdeen, SF-36, and EuroQol quality of life questionnaires. Interventions varicose vein surgery. Main outcome measures Duplex evidence of venous incompetence, quality of life measures using the SF-36 and Aberdeen Varicose Veins Questionnaire. Results pre-operative marking of primary varicose veins by skilled duplex ultrasonography does not improve the accuracy or recurrence rate following surgery. Quality of life improved significantly following surgery in both groups, however there was no difference in this improvement between the groups. Conclusion the trial has not demonstrated any additional benefit of pre-operative colour duplex marking over that of clinical and hand held Doppler marking in terms of satisfactory varicose vein surgery performance at 6 weeks or 12 months in patients with primary varicose veins of the long saphenous system. It role in the short saphenous system is less clear.

ObjectiveThe wide variety of outcome measures to evaluate patients with varicose veins poses significant difficulties when comparing clinical trials. In addition, the relationship between different outcome measures is poorly understood. The aim of this study was to compare anatomical, hemodynamic, and clinical outcomes with disease-specific quality-of-life tools in patients undergoing treatment for varicose veins.MethodsPatients undergoing treatment for symptomatic veins in a single unit were studied. Assessments included duplex ultrasonography, digital photoplethysmography, evaluation of Venous Clinical Severity Scores and CEAP scores, generic (Short Form 12 [SF12]) and disease-specific (Aberdeen Varicose Vein Questionnaire [AVVQ], and Specific Quality-of-life and Outcome Response-Venous [SQOR-V]) questionnaires. Patients were reviewed at 6 weeks when hemodynamic, clinical, and quality-of-life assessments were repeated. The relationships between these outcomes were assessed.ResultsThe AVVQ showed a strong positive correlation with the SQOR-V (Spearman coefficient 0.702; P < .001) and weaker, but significant correlations with the SF12 physical and mental component scores and the Venous Clinical Severity Score (VCSS) (P < .001, P = .019, and P < .001, respectively, Spearman correlation). No correlations were observed between the AVVQ and photoplethysmography results (Spearman coefficient −0.042; P = .606), and weak correlations were observed with the AVVQ and anatomical reflux. At 6 weeks, functional, clinical, and hemodynamic measurements were all responsive to changes following interventions; however, correlations observed between changes in disease-specific quality-of-life and generic, clinical, and hemodynamic outcomes were weak.ConclusionsBoth the AVVQ and SQOR-V questionnaire are sensitive and responsive disease-specific questionnaires, which correlate with generic and clinical outcomes to some extent. Anatomical and hemodynamic measurements correlated poorly with functional outcomes both preoperatively and following interventions.

Objective To assess each of the scoring systems used to diagnose and classify post-thrombotic syndrome, a common chronic complication of deep vein thrombosis. The design of the study was a systematic review of the literature pertaining to post-thrombotic syndrome. Methods A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by a search of PubMed (1948 to September 2011) using the search terms "post-thrombotic syndrome," "postthrombotic syndrome," "post-phlebitic syndrome," and "postphlebitic syndrome." A manual reference list search was also carried out to identify further studies that would be appropriate for inclusion. The various scoring systems in use were identified and assessed against a list of criteria to determine their validity for use. For outcome measures, each scoring system was assessed for specific criteria, including interobserver reliability, association with ambulatory venous pressures, ability to assess severity of post-thrombotic syndrome, ability to assess change in condition over time, and association with patient-reported symptom severity. Results The Villalta, Ginsberg, Brandjes, Widmer, CEAP, and Venous Clinical Severity Score systems all were assessed for the stated outcome measures. From their use in the literature, only the Villalta score was able to fulfill all the criteria described. The main criticism of the Villalta score in the literature appears to be its use of subjective measures. To that end, we propose that use of a venous disease-specific quality-of-life questionnaire in combination with the Villalta score may help standardize the subjective criteria. Conclusions The Villalta score, combined with a venous disease-specific quality-of-life questionnaire, should be considered the "gold standard" for the diagnosis and classification of post-thrombotic syndrome.

Objectives Imbalance of matrix metalloproteinase enzymes (MMP) and their inhibitors (TIMPs) may contribute to the development of varicose veins. We hypothesised that, histological changes in varicose vein wall correlate with alterations in expression of MMP/TIMP. Methods Varicose veins ( n = 26) were compared with great saphenous vein (GSV) segments ( n = 11) from arterial bypass, and with arm and neck veins from fistula and carotid operations ( n = 13). Varicose vein wall thickness was measured, enabling categorisation as atrophic and hypertrophic. MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry. Results There was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus 0.41% for TIMP-3). Conclusions This study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by suppression of protease activity.

Venous disorder is common in the general population. Uncomplicated varicose veins represent a significant proportion of the disease burden, and can impact considerably on quality of life, producing a wide spectrum of symptoms. Little is known about the natural course of the disease at this stage and the treatment strategy employed is often not based on robust scientific evidence.The aim of this article is to elucidate the options to manage uncomplicated varicose veins. There are likely to be significant geographic differences in the treatment strategy employed, and it is hoped that we will arouse discussion among physicians regarding the management of this very common medical condition. The reader will be asked for their preferred treatment choice for a given clinical case vignette.

Introduction Aneurysms of the superior mesenteric branch arteries are rare. The natural history is unknown and there is no consensus on management. We report a case of right colic artery aneurysm rupture. Report A 70-year-old male presented with a two week history of right flank pain and syncope. On admission he was hypotensive, but responded to fluid resuscitation and was discharged after a two day observation period. He attended his family doctor with bruising in the right groin and abdominal distension. CT confirmed a 2 cm aneurysm arising from a branch of the right colic artery with a large associated haematoma and active extravasation. Discussion Mesenteric artery aneurysms are rare and often misdiagnosed. Management options include embolisation or open surgery. The mesentery can act to tamponade in some cases resulting in a delayed diagnosis of rupture.

The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels

Background Atherosclerosis is an inflammatory disease with possible contributions from bacterial antigens. We aimed to investigate the role of oral bacteria as inducers of inflammatory cascades in smooth muscle cells from carotid endarterectomy patients (AthSMCs) and healthy controls (HSMCs). Findings Inactivated Streptococcus mitis, S. sanguinis, S. gorgonii, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were used to stimulate inflammation in HSMCs and AthSMCs. Tumor necrosis factor-α (TNFα) was used as a positive control in all stimulations. Interleukin-6 (IL-6) levels were determined from cell culture supernatants and microRNA expression profiles from cells after 24 h of bacterial stimulation. Genome wide expression (GWE) analyses were performed after 5 h stimulation. All studied bacteria induced pro inflammatory IL-6 production in both SMCs. The most powerful inducer of IL-6 was A. actinomycetemcomitans (p

BackgroundApproximately 20% of strokes are attributable to carotid stenosis. However, the number of asymptomatic patients needed to prevent one stroke or death with endarterectomy is high at 17 to 32. There is a clear need to identify asymptomatic individuals at high risk of developing future ischemic events to improve the cost-effectiveness of surgery. Our aim was to examine the evidence for subclinical microembolization and silent brain infarction in the prediction of stroke in asymptomatic carotid stenosis using transcranial Doppler (TCD), computed tomography (CT), and magnetic resonance imaging (MRI).MethodsThe review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Articles regarding humans between 1966 and 2010 were identified through systematic searches of Pubmed, MEDLINE, and EMBASE electronic databases using a predetermined search algorithm.ResultsFifty-eight full text articles met the inclusion criteria. A median of 28% of microemboli positive patients experienced a stroke or transient ischemic attack during follow-up compared with 2% of microemboli negative patients (P = .001). The same was true for the end point of stroke alone with a median of 10% of microemboli positive patients experiencing a stroke vs 1% of microemboli negative patients (P = .004). A specific pattern of silent CT infarctions was related to future stroke risk (odds ratio [OR] = 4.6; confidence interval [CI] = 3.0-7.2; P < .0001). There are no prospective MRI studies linking silent infarction and stroke risk.ConclusionsThere is level 1 evidence for the use of TCD to detect microembolization as a risk stratification tool. However, this technique requires further investigation as a stroke prevention tool and would be complemented by improvements in carotid plaque imaging.

Objective: Free-floating thrombus (FFT) of the carotid artery is a rare condition of currently unknown etiology. Less than 150 cases have been described in the published world literature to date. Design and Setting: We present 6 consecutive cases of carotid FFT, identified prospectively from 5000 carotid duplex scans over a 34-month period in a single tertiary center for vascular surgery. Results: All 6 cases involved the left carotid bifurcation in neurologically symptomatic individuals. In 5 of the 6 cases, FFT occurred in the absence of a significantly stenosing atheromatous plaque and was not associated with an elevation in velocity on duplex. The patients were all treated with surgical thromboendarterectomy, with good result. Conclusions: Duplex imaging can underestimate the degree of stenosis. Free-floating thrombus presents a challenge in diagnosis due to its rapidly evolving nature. The management of FFT by acute thromboendarterectomy appears to be safe and effective in limiting further focal neurological sequelae.

Background Treatment of head and neck malignancy commonly involves radiotherapy, which is associated with the development of carotid artery stenosis. There is little evidence to guide clinicians on how to intervene in significant postradiotherapy carotid stenosis. This systematic review collated data pertaining to perioperative outcomes of carotid artery surgery and carotid stenting in postradiotherapy carotid stenosis to aid the clinical decision-making process. Methods A systematic review of the literature, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines, was performed. We screened 575 articles related to carotid artery surgery or stenting in postradiotherapy carotid stenosis, from which 21 studies were included for quantitative analysis. The primary outcome was stroke or death ≤30 days of the procedure. Secondary outcomes included cranial nerve injury, restenosis, stroke, and death at >30 days. Results Nine publications recorded 211 surgical procedures in 179 patients. In symptomatic patients, the 30-day mortality rate was 2.6% and the stroke or death rate was 2.7%. In asymptomatic patients, the 30-day mortality rate was 0% and the stroke or death rate was 1.1%. Permanent cranial nerve palsy was experienced by 0.6% of patients. Twelve publications recorded 510 carotid artery stenting procedures in 482 patients. In symptomatic patients, the 30-day mortality rate was 5.1%, and the stroke or death rate was 5.1%. In asymptomatic patients, the 30-day mortality rate was 1.4%, and the stroke or death rate was 2.1%. There was no statistically significant difference in 30-day stroke or death rate between surgical revascularization and carotid artery stenting in all (odds ratio [OR], 0.54; 95% confidence interval [CI] 0.17-1.70; P = .43), symptomatic (OR, 0.52; 95% CI, 0.14-1.98; P = .38), or asymptomatic patients (OR, 0.55; 95% CI, 0.06-5.42; P = .99). Conclusions The published outcomes from high-volume centers demonstrate that surgical revascularization and stenting are both technically feasible in postradiotherapy carotid stenosis and have similar safety profiles to nonirradiated necks. Radiation should therefore not be considered a contraindication to surgical intervention.

Introduction: As yet, there is no patient-assessed, condition-specific instrument for the assessment of health-related quality of life in intermittent claudication. We evaluated the intermittent claudication questionnaire (ICQ) for properties required of a measure of health outcome. Methods and Results: Interviews with patients with intermittent claudication and vascular specialist opinion produced a pool of statements used to itemize a self-completed ICQ. This was piloted in 20 patients for practicality and then administered to 124 stable claudicants. Reliability was assessed through a retest in 63 (51%) patients at 14 days and analysis of Cronbach's α for internal consistency. Spearman's correlation coefficient was used to assess construct validity in comparisons between the ICQ and ankle brachial pressure index, treadmill-walking distances, the walking impairment questionnaire, the EuroQol, and the Short Form-36. Responsiveness of the ICQ to changes in health was assessed in 60 patients treated conservatively and 40 patients undergoing angioplasty. The standardized response mean was used to identify the most responsive instrument in the study. A 16-item ICQ with a test-retest intraclass correlation of 0.95 and Cronbach's α of .94 was produced. One hundred twenty-one (98%) patients completed the ICQ (mean time, 3.7 minutes). The ICQ correlated better with the EuroQol (r = 0.58) and 7 out of 8 subscales of the Short Form-36 (r = 0.33-0.68) compared with the walking impairment questionnaire. The ICQ demonstrated the largest standardized response mean in relation to health transition compared with the other instruments. Conclusions: The patient-assessed ICQ is a practical, reliable, valid, and responsive measure of patient health-related quality of life in intermittent claudication. (J Vasc Surg 2002;36:764-71.)