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The Forkhead box P2 (FOXP2) is an evolutionary conserved transcription factor involved in the maintenance of neuronal networks, implicated in language disorders. Some evidence suggests a possible link between FOXP2 genetic variability and frontotemporal dementia (FTD) pathology and related endophenotypes. To shed light on this issue, we analysed the association between single-nucleotide polymorphisms (SNPs) in FOXP2 and FTD in 113 patients and 223 healthy controls. In addition, we investigated SNPs in two putative targets of FOXP2, CNTNAP2, Contactin-associated protein-like 2 and PRNP, prion protein genes. Overall, 27 SNPs were selected by a tagging approach. FOXP2-rs17213159-C/T resulted associated with disease risk (OR = 2.16, P = 0.0004), as well as with age at onset and severity of dementia. Other FOXP2 markers were associated with semantic and phonological fluency scores, cognitive levels (MMSE) and neuropsychological tests. Associations with language, cognitive and brain atrophy measures were found with CNTNAP2 and PRNP genetic variability. Overall, although preliminary, results here presented suggest an influence of regulatory pathways centred on FOXP2 as a molecular background of FTD affecting neurological function of multiple brain areas.

Background: Benefit from carotid revascularization is supposed to be lower in women due to increased periprocedural risks. The aim of this study was to investigate the risk of stroke/death after carotid intervention in women treated within 15 days from last neurological event., Methods: Data from 282 consecutive patients treated during 2009-2015 by carotid endarterectomy or carotid stenting within 15 days from neurological symptoms were analyzed by sex and stratified according to treatment delay toward symptoms onset., Results: Eighty women (28.4%) underwent carotid stenosis correction: in 37 treatment was performed within 7 days from symptoms (in 12 within 48 hr); the remaining underwent carotid disease correction between day 8 and day 15 after the index event. Baseline comorbidity profile, presenting symptoms (stroke, transient ischemic attack, and recurrent symptoms) and treatment delay were comparable between sexes. The 30-day stroke/death rate was 2.5% in women (2/80) and 3.5% (7/202) in men (P = 1.00). There was no 30-day death or cerebral hemorrhage in women and in patients treated within the first 48 hours. In adjusted analyses, female sex was not associated with increased stroke/death risk. At 4 years, for women and men survival was 93.9% vs. 79.2% (P = 0.047) and freedom from stroke 92.6% vs. 92.2% (P = 0.76)., Conclusions: Women with symptomatic carotid stenosis may benefit as men from intervention when performed within the acute (15 days) or hyperacute (48 hr) period after neurological event. Thirty-day stroke/death rate in this experience is lower or comparable to men's and treatment appears to be effective in preventing new strokes at midterm., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Sex differences in presentation and outcomes of abdominal aortic aneurysms (AAA) with increased mortality rates in women are suggested. This study aimed to assess mortality risk after repair of ruptured AAA (rAAA) in women in the endovascular abdominal aortic repair (EVAR) era., Methods: Patients treated between 2006 and 2015 for rAAA were included in a prospective database. Characteristics at presentation and outcomes were compared between women and men. Multivariable logistic regression and Cox proportional analyses were performed to identify the effect of sex adjusted for other predictors on mortality., Results: One hundred thirteen patients were identified; of these, 17.7% (20/113) of the patients were women. Forty-four procedures (38.9%) were by EVAR, with comparable rates in women (45%) and men (37.6%, P = 0.62). On admission, women and men shared similar comorbidities and presentation (shock 45% vs. 43.0%, P = 0.81; free rupture 65.0% vs. 67.7%, P = 0.80) and comparable mean aneurysm diameter (76.5 vs. 78.8 mm, P = 0.68), but women were older (mean age 86.4 + 5.5 vs. 75.2 ± 10.6 years, P < 0.0001) and octogenarian women were twice as likely as men (90% vs. 40%, P < 0.0001). Perioperative mortality was comparable between women and men (40.0% vs. 38.7%) either after EVAR (22.2% vs. 40.0% in women and men respectively; odds ratio [OR] 0.45, 95% confidence interval [CI] 0.77-2.37) or after open surgery (54.5% vs. 37.9%; OR 2.0, 95% CI 0.54-7.21), even though there was a trend for lower mortality in women with EVAR. In adjusted analyses, female sex was not associated with perioperative mortality as it was for older age (octogenarians: OR 6.6, 95% CI 2.08-20.82, P = 0.001) and free rupture (OR 4.2, 95% CI 1.29-13.73, P = 0.02). Mean follow-up was 34.32 months. After controlling for age, surgical repair, free rupture, cardiac disease, and shock at presentation, female sex was not a predictor of late mortality., Conclusions: AAA repair is often delayed in women and applied at older age; nevertheless, currently women do not show increased perioperative mortality risks from rAAA treatment after the introduction of EVAR., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Repair of isolated iliac aneurysm with stent-graft implantation and internal iliac coverage may induce significant type II endoleak from patent internal iliac refilling leading to ongoing aneurysm growth. Subsequent treatment of such complication can be challenging especially in case of bilateral iliac involvement. Open repair is technically demanding and often a high risk procedure, while embolization via transfemoral approach is unviable due to the stent-graft coverage precluding direct antegrade access between the common and the internal iliac lumen. Percutaneous retrograde embolization from superior gluteal artery is a feasible technique in case of impossible access through the origin of internal iliac artery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Elderly patients are often turned down from receiving treatment for descending thoracic aortic diseases (DTADs) because of the uncertain benefits, especially in acute settings. This study investigated the impact of old age and timing of thoracic endovascular aortic repair (TEVAR) on outcomes of DTAD in patients older than 75 years of age., Methods: Patients from a prospective TEVAR database were dichotomized by age (75 and 80 years of age). Older and young patients were compared in three timing scenarios: (1) elective procedures, (2) any emergency (within 15 days from onset), and (3) acute ruptures (any emergency subgroup). Primary outcome was perioperative mortality assessed at 30 and 90 days., Results: Between 2003 and 2015, 141 consecutive TEVARs (71.6% men) were performed. Fifty-seven patients (40.4%) were older than 75 years of age; 28 were octogenarians. Eighty-three TEVARs were performed electively and 58 emergently. Among overall emergencies, 42 TEVARs were for acute ruptures. In the elective scenario, the 30-day mortality rate was 5.0% vs 0 (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.98-1.1; P = .23), and 90-day mortality was 7.5% vs 0, for patients older than 75 years of age vs those who were younger than 75, respectively (P = .11). No octogenarian died. In the emergency scenario, 30-day mortality was 41.2% vs 9.8%, for patients older than 75 years of age vs those who were younger than 75, respectively (OR, 6.5; 95% CI, 1.6-26.6; P = .01) with unchanged rates at 90 days. The mortality rate was 50% for octogenarians. In the acute rupture scenario, 30-day mortality was 40% vs 11.1% (OR, 5.3; 95% CI, 1.10-25.99; P = .05) for patients older than 75 years of age vs those younger than 75 years of age and 46% vs 10% (OR, 7.5; 95% CI, 1.47-37.46; P = .016) for octogenarians vs younger patients. Rates remained unchanged at 90 days. Patients older than age 75 survived for a mean of 53.98 ± 7.7 months after TEVAR., Conclusions: In the elderly patient population with DTAD, mortality risks from TEVAR are strongly related to timing and age. When compared to younger patients, those older than 75 years of age have three to five times the risk of mortality after urgent or emergent TEVAR. However, older patients should still be considered for emergent life-saving treatment, given that the majority survives., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective/background: A consistent number of elderly patients with ruptured abdominal aortic aneurysms (rAAAs) are deemed unfit for repair and excluded from any treatment. The objective of this study was to examine the impact on survival of endovascular repair and open surgery with restricted turndown in acute AAA repair., Methods: A prospective database for patients treated for rAAA was established. None of the patients admitted alive with rAAA were denied treatment. Multivariate regression models, the predictive risk assessment Glasgow Aneurysm Score (GAS), and subgroup analyses in older patients were applied to identify indicators of excessive 30 day mortality risk that could affect the decision for turndown., Results: From 2006 to 2015, 113 consecutive patients (93 males; mean age 77.2 years) with rAAAs were treated (69 open surgery; 44 EVAR). Overall peri-operative (30 day) mortality was 38.9% (44/113): 40.6% (28/69), and 36.4% (16/44) after open surgery and EVAR, respectively (p = .70). Multivariate logistic regression identified old age as an indicator of increased peri-operative mortality (odd ratio [OR] 1.2, 95% confidence interval [CI] 1.1-1.3; p = .001), as well as free aneurysm rupture (OR 5.0, 95% CI 1.3-19.9; p = .02). GAS was higher in patients who died (97.75 vs. 86.62), but the score failed to identify increased peri-operative mortality risk in adjusted analyses (OR 1.0; p = .06). Almost two thirds of the patients (n = 71) were older than 75 at the time of aneurysm rupture (48.6% octogenarians) and EVAR was more commonly applied than open surgery (86.4% vs. 47.8%; p < .0001). Peri-operative mortality in > 75 year old patients was 46.5% compared with 26.2% in younger patients (p = .05), with rates increased after open surgery (54.5% vs. 27.8%, p = .03) but not after EVAR (39.5% vs. 16.7%; p = .39). According to Kaplan-Meier estimates, mean survival was 39.7 ± 4.8 months. Patients older than 75 years of age survived for a mean of 23.0 ± 4.47 months after rupture., Conclusion: In this study aggressive treatment with a very restricted or no turndown strategy for any rAAA, also applied to older patients, allowed for an additional mean 40 months of survival after aneurysm rupture. In the contemporary endovascular era the decision to deny repair arbitrarily to older patients with rAAAs must be revisited., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

The concept of risk assessment and the identification of surgical unfitness for vascular intervention is a particularly controversial issue today as the minimally invasive surgical population has increased not only in volume but also in complexity (comorbidity profile) and age, requiring an improved pre-operative selection and definition of high risk. A practical step by step (three steps, two points for each) approach for surgical risk assessment is suggested in this review. As a general rule, the identification of a "high risk" patient for vascular surgery follows a step by step process where the risk is clearly defined, quantified (when too "high"?), and thereby stratified based on the procedure, the patient, and the hospital, with the aid of predictive risk scores. However, there is no standardized, updated, and objective definition for surgical unfitness today. The major gap in the current literature on the definition of high risk in vascular patients explains the lack of sound validated predictive systems and limited generalizability of risk scores in vascular surgery. In addition, the concept of fitness is an evolving tool and many traditional high risk criteria and definitions are no longer valid. Given the preventive purpose of most vascular procedures performed in elderly asymptomatic patients, the decision to pursue or withhold surgery requires realistic estimates not only regarding individual peri-operative mortality, but also life expectancy, healthcare priorities, and the patient's primary goals, such as prolongation of life versus maintenance of independence or symptom relief. The overall "frailty" and geriatric risk burden, such as cognitive, functional, social, and nutritional status, are variables that should be also included in the analyses for stratification of surgical risk in elderly vascular patients., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to investigate outcomes of patients treated with endovascular repair (ER) with the use of fenestrated and branched stent grafts or open surgery (OS) for thoracoabdominal aortic aneurysm (TAAA) in a current series of patients., Methods: All TAAA patients undergoing repair at three centers between January 2007 and December 2014 were included in a prospective database. Patients were stratified according to treatment by ER or OS, and outcomes were compared using propensity score matching (1:1). Covariates included age, sex, aneurysm extent, hypertension, coronary disease, chronic pulmonary disease, diabetes, and renal function. The primary end points were mortality and paraplegia. Secondary end points included any spinal cord ischemia (SCI), renal and respiratory insufficiency, and a composite of these complications or death at 30 days. All-cause survival and freedom from reintervention were compared in the two groups., Results: Of 341 patients, 84 (25%) underwent ER and 257 underwent OS (75%). After propensity score matching (65 patients per group), no significant differences were observed in rates of 30-day mortality (7.7% in ER and 6.2% in OS; P = 1) and paraplegia (9.2% and 10.8%; P = 1). Any SCI, renal insufficiency, and respiratory insufficiency were 12.3% and 20% (P = .34), 9.2% and 12.3% (P = .78), and 0% and 12.3% (P = .006) in ER and OS, respectively. The incidence of the composite end point was significantly lower in ER patients (18.5% in ER vs 36.0% in OS; P =.03). According to Kaplan-Meier estimates, all-cause survival at 24 months was 82.8% in ER and 84.9% in OS, with rates unchanged at 42 months (P = .9). Rates of freedom from reintervention were 91.0% vs 89.7% at 24 months and 80.0% vs 79.9% at 42 months in ER vs OS, respectively (P = .3)., Conclusions: A propensity score analysis in patients with TAAA undergoing repair suggests an early benefit from ER compared with OS with regard to the composite end point because of reduced 30-day respiratory complications. No significant differences were found in SCI and renal insufficiency at 30 days and in survival and reintervention rates at midterm., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Age is a main risk factor for stroke and perioperative risk. This study aims to analyze the effect of age by symptomatic status in young patients receiving carotid revascularization., Methods: Consecutive carotid revascularization procedures performed during the period 2001-2009 were reviewed. Patients were analyzed by age using the 70-year threshold as suggested by trials. Primary end point was perioperative stroke or death rate. Secondary end points included survival and late stroke incidence at 6 years., Results: A total of 2,196 procedures (1,080 by carotid artery stenting [CAS] and 1,116 by carotid endarterectomy [CEA]) were analyzed. Symptomatic patients (n = 684) showed higher perioperative stroke or death risks (24 of 684 [3.5%] versus 29 of 1,512 [1.9%], odds ratio [OR] 1.8; 95% confidence interval [CI] 1.07-3.22; P = 0.034) and lower 6-year survival (74% vs. 82%, P < 0.0001) or freedom from late stroke (93% vs. 97%, P = 0.001) when compared with asymptomatic patients with similar differences detected within CEA or CAS procedure. Overall 949 procedures were in patients with 70 years or less at the time of intervention (500 CEA and 449 CAS); 282 were in patients symptomatic for minor stroke or transient ischemic attack within 6 months before revascularization. For young symptomatic patients, primary end point rates were <2.5% after both CEA and CAS procedure. Perioperative stroke or death rates were 2.4% in symptomatic versus 1.5% in asymptomatic (4 of 170 vs. 5 of 330; OR 1.57; 95% CI 0.42-5.91; P = 0.50) within the CEA group and 1.8% in symptomatic versus 1.2% in asymptomatic (2 of 112 vs. 4 of 337; OR 1.51; 95% CI 0.27-8.38; P = 0.64) within the CAS group. At 6 years, symptomatic young patients showed survival (89.5% vs. 89%, P = 0.76) and freedom from late stroke (97% vs. 98%, P = 0.56) rates comparable to those found in asymptomatic patients, with similar incidences after CAS or CEA procedure., Conclusions: Outcomes after carotid revascularization are related to patients' age. At younger ages (<70 years), after carotid revascularization, symptomatic patients show low perioperative risks of stroke or death, comparable with those in asymptomatic patients. The same, 2.5% or lower, threshold for perioperative stroke or death risk related to asymptomatic carotid procedures must be applied today to symptomatic patients when younger than age of 70 years., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The objective of this multicenter registry was to review current treatments and late results of repair of aneurysm of aberrant right subclavian artery (AARSA)., Methods: All consecutive AARSA repairs from 2006 to 2013 in seven centers were reviewed. End points were 30-day and late mortality, reintervention rate, and AARSA-related death., Results: Twenty-one AARSA repairs were included (57% men; mean age, 67 years); 3 ruptures (14%) required emergent treatment; 12 (57%) were symptomatic for dysphagia (33%), dysphonia (24%), or pain (19%). Eight cases (38%) presented with thoracic aortic aneurysm, two with intramural hematoma, and one with acute type B aortic dissection. Mean AARSA diameter was 4.2 cm; a single bicarotid common trunk was present in 38% of cases. The majority of patients underwent hybrid intervention (n = 15; 71%) consisting of single (n = 2) or bilateral (n = 12) subclavian to carotid transposition or bypass or ascending aorta to subclavian bypass (n = 1) plus thoracic endovascular aortic repair (TEVAR); 19% of cases underwent open repair and 9% simple TEVAR with AARSA overstenting. Perioperative death occurred in two patients (9%): in one case after TEVAR in ruptured AARSA, requiring secondary sternotomy and aortic banding; and in an elective case due to multiorgan failure after a hybrid procedure. Median follow-up was 30 (interquartile range, 15-46) months. The Kaplan-Meier estimate of survival at 36 months was 90% (standard error, 0.64). Late AARSA-related death in one case was due to AARSA-esophageal fistula presenting with continuing backflow from distal AARSA and previous TEVAR. At computed tomography controls, one type I endoleak and one type II endoleak were detected; the latter required reintervention by aneurysm wrapping and ligature of collaterals. AARSA-related death was more frequent after TEVAR, a procedure reserved for ruptures, compared with elective open or hybrid repair., Conclusions: Hybrid repair is the preferred therapeutic option for patients presenting with AARSA. Midterm results show high rates of clinical success with low risk of reintervention. Simple endografting presents high risk of related death; these findings underline the importance of achieving complete sealing to avoid treatment failures., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: This study analyzed total aortic arch reconstruction in a contemporary comparison of current open and endovascular repair., Methods: Endovascular (group 1) and open arch procedures (group 2) performed during 2007 to 2013 were entered in a prospective database and retrospectively analyzed. Endovascular repair (proximal landing zones 0-1), with or without a hybrid adjunct, was selected for patients with a high comorbidity profile and fit anatomy. Operations involving coverage of left subclavian artery only (zone 2 proximal landing: n = 41) and open hemiarch replacement (n = 434) were excluded. Early and midterm mortality and major complications were assessed., Results: Overall, 100 (78 men; mean age, 68 years) consecutive procedures were analyzed: 29 patients in group 2 and 71 in group 1. Seven group 1 patients were treated with branched or chimney stent graft, and 64 with partial or total debranching and straight stent graft. The 29 patients in group 2 were younger (mean age, 61.9 vs 70.3; P = .005), more frequently females (48.2% vs 11.3; P < .001) with less cardiac (6.9% vs 38.2%; P = .001), hypertensive (58.5% vs 88.4%; P = .002), and peripheral artery (0% vs 16.2%; P = .031) disease. At 30 days, there were six deaths in group 1 and four in group 2 (8.5% vs 13.8%; odds ratio, 1.7; 95% confidence interval, 0.45-6.66; P = .47), and four strokes in group 1 and one in group 2 (odds ratio, 0.59; 95% confidence interval, 0.06-5.59; P = 1). Spinal cord ischemia occurred in two group 1 patients and in no group 2 patients. Three retrograde dissections (1 fatal) were detected in group 1. During a mean follow-up of 26.2 months, two type I endoleaks and three reinterventions were recorded in group 1 (all for persistent endoleak), and one reintervention was performed in group 2. According to Kaplan Meier estimates, survival at 4 years was 79.8% in group 1 and 69.8% in group 2 (P = .62), and freedom from late reintervention was 94.6% and 95.5%, respectively (P = .82)., Conclusions: Despite the older age and a higher comorbidity profile in patients with challenging aortic arch disease suitable and selected for endovascular arch repair, no significant differences were detected in perioperative and 4-year outcomes compared with the younger patients undergoing open arch total repair. An endovascular approach might also be a valid alternative to open surgery in average-risk patients with aortic arch diseases requiring 0 to 1 landing zones, when morphologically feasible. However, larger concurrent comparison and longer follow-up are needed to confirm this hypothesis., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: This study analyzed predictors and the long-term consequence of type II endoleak in a large series of elective endovascular abdominal aneurysm repairs (EVARs)., Methods: Baseline characteristics and operative and follow-up data of consecutive patients undergoing EVAR were prospectively collected. Patients who developed type II endoleak according to computed tomography angiography and those without type II endoleak were compared for baseline characteristics, mortality, reintervention, conversion, and aneurysm growth after repair., Results: In 1997-2011, 1412 consecutive patients (91.4% males; mean age, 72.9 years) underwent elective EVAR and were subsequently followed up for a median of 45 months (interquartile range, 21-79 months). Type II endoleak developed in 218. Adjusted analysis failed to identify significant independent predictors for type II endoleak with the exception of age (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .003) and intraluminal thrombus (odds ratio, 0.69; 95% confidence interval, 0.53-0.92; P = .010). Type II endoleak rates were comparable regardless of the device model. Late aneurysm-related survival was comparable (98.4% vs 99.5% at 60 months; P = .73) in patients with and without type II endoleak. However, at 60 months after EVAR, rates of aneurysm sac growth >5 mm (35.3% vs 3.3%; P < .0001) were higher in patients with type II endoleak. Cox regression identified type II endoleak as an independent predictor of aneurysm growth along with age and cardiac disease. The presence of type II endoleak led to reinterventions in 40% of patients and conversion to open surgery in 8%. However, assessment of these patients after reintervention showed similar 60-month freedom rates of persisting type II endoleak (present in more than two after computed tomography angiography scan studies) among those with and without reinterventions (49.8% vs 45.6%; P = .639). Aneurysm growth >5 mm persisted with comparable rates in type II endoleak patients after reintervention and in those who remained untreated (42.9% vs 57.4% at 60 months; P = .117)., Conclusions: Reintervention for type II endoleak was common in our practice, yet such intervention did not reliably prevent the continued expansion of the abdominal aortic aneurysm. Our data indicate type II endoleak appears to be a marker of EVAR failure that is difficult to predict and treat effectively., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Current data supporting the effect of anticoagulation drug use on aneurysm sealing and the durability of endovascular abdominal aneurysm repair (EVAR) are conflicting. This study assessed the safety of chronic anticoagulation therapy after EVAR., Methods: Records of 1409 consecutive patients having elective EVAR during 1997-2011 who were prospectively followed were reviewed. Survival, reintervention, conversion, and endoleak rates were analyzed in patients with and without chronic anticoagulants. Cox proportional hazards models were used to estimate the effect of anticoagulation therapy on outcomes., Results: One-hundred and three (7.3%) patients were on chronic anticoagulation drugs (80 on vitamin K antagonists) at the time of EVAR. An additional 46 patients started on anticoagulants after repair were identified. Patients on chronic anticoagulation therapy at repair (mean age 73.6 years; 91 males) had more frequent cardiac disease (74.8% vs. 44.2%; p < 00001), but no other differences in demographic and major baseline comorbidities with respect to the others. At baseline, mean abdominal aortic aneurysm (AAA) diameter was 56.43 mm vs. 54.65 mm (p = .076) and aortic neck length 26.54 mm vs. 25.21 mm (p = .26) in patients with and without anticoagulants, respectively. At 5 years, freedom from endoleak rates were 55.5% vs. 69.9% (p < .0001), and freedom from reintervention/conversion rates were 69.4% vs. 82.4% (p < .0001) in patients with (including those with delayed drug use) and without chronic anticoagulants, respectively. Controlling for covariates with the Cox regression method, at a mean follow-up of 64.3 ± 45.2 months after EVAR, use of anticoagulation drugs was independently associated with an increased risk of endoleak (odds ratio, OR 1.6; 95% confidence interval, CI: 1.23-2.07; p < .0001) and reintervention or late conversion rates (OR 1.8; 95% CI: 1.31-2.48; p < .0001)., Conclusions: The safety of anticoagulation therapy after EVAR is debatable. Chronic anticoagulation drug use risks exposure to a poor long-term outcome. A critical and balanced decision-making approach should be applied to patients with AAA and cardiac disease who may require prolonged anticoagulation treatment., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Epidemiologic evidence suggests that patients with diabetes may have a lower incidence of abdominal aortic aneurysm (AAA); however, the link between diabetes and AAA development and expansion is unclear. The aim of this review is to analyze updated evidence to better understand the impact of diabetes on prevalence, incidence, clinical outcome, and expansion rate of AAA. A systematic review of literature published in the last 20 years using the PubMed and Cochrane databases was undertaken. Studies reporting appropriate data were identified and a meta-analysis performed using the generic inverse variance method. Sixty-four studies were identified. Methodological quality was "fair" in 16 and "good" in 44 studies according to a formal assessment checklist (Newcastle-Ottawa). In 17 large population prevalence studies there was a significant inverse association between diabetes and AAA: pooled odds ratio (OR) 0.80; 95% confidence intervals (CI) 0.70-0.90 (p = .0009). An inverse association was also confirmed by pooled analysis of data from smaller prevalence studies on selected populations (OR 0.59; 95% CI 0.35-0.99; p = .05), while no significant results were provided by case-control studies. A significant lower pooled incidence of new AAA in diabetics was found over six prospective studies: OR 0.54; 95% CI 0.31-0.91; p = .03. Diabetic patients showed increased operative (30-day/in-hospital) mortality after AAA repair: pooled OR 1.26; 95% CI 1.10-1.44; p = .0008. The increased operative risk was more evident in studies with 30-day assessment. In the long-term, diabetics showed lower survival rates at 2-5 years, while there was general evidence of lower growth rates of small AAA in patients with diabetes compared to non-diabetics. There is currently evidence to support an inverse relationship between diabetes and AAA development and enlargement, even though fair methodological quality or unclear risk of bias in many available studies decreases the strength of the finding. At the same time, operative and long-term survival is lower in diabetic patients, suggesting increased cardiovascular burden. The higher mortality in diabetics raises the question as to whether AAA repair should be individualized in selected diabetic populations at higher AAA rupture risk., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: Currently, the best approach to the aortic arch remains unsupported by robust evidence. Most of the available data rely on small sample numbers, heterogeneous settings, and limited follow-up. The objective of this study was to evaluate early and midterm results of arch debranching and endovascular procedures., Methods: From 2005 through 2013, 104 consecutive patients underwent elective arch treatment with debranching and thoracic endovascular aortic repair. Rates of perioperative (30-day) mortality and neurological complications, and mortality, endoleak, supra-aortic vessel patency, and arch diameter changes at 5 years were analyzed., Results: Patients' mean age was 69.8 years, and 90 were males. Twenty arches were repaired for dissection. Nineteen patients required total debranching for diseases extended to zone 0. In 59, debranching and thoracic endovascular aortic repair procedures were staged. At 30 days, death, stroke, and spinal cord ischemia occurred in six, four, and three patients, respectively. Extension to ascending aorta (zone 0 landing) was the only multivariate independent predictor for perioperative mortality (odds ratio, 9.6; 95% confidence interval, 1.54-59.90; P = .015), but not for stroke. Four retrograde dissections, two fatal, occurred during the perioperative period. At 1, 3, and 5 years, Kaplan-Meier survival rates were 89.0%, 82.8%, and 70.9%, and freedom from persistent endoleak rates were 96.1%, 92.5%, and 88.3%, respectively. Over 5-year follow-up, 34 aneurysms shrank ≥ 5 mm, and four grew. Five reinterventions were required. Two supra-aortic vessel occlusions and no late aorta-related mortalities were recorded., Conclusions: Despite the perioperative mortality risk, the late outcome of endovascular arch repair presents a low rate of aorta-related deaths and reinterventions and acceptable midterm survival. Furthermore, more than one-third of the aneurysms' diameters decrease over 5 years as a measure of the long-term efficacy of treatment. Retrograde type A dissection remains a major concern in the perioperative period and careful arch approach is required., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Regression of the aneurysmal sac after endovascular repair of abdominal aortic aneurysm (AAA) is an accepted indicator of aneurysm exclusion. This study evaluated the spontaneous decrease in sac diameter over a 10-year period in patients undergoing endovascular aneurysm repair (EVAR) with different stentgrafts., Methods: 1,450 patients (mean age 73.1 ± 7.7 years; 1,325 male) undergoing EVAR and with a minimum of 1-year computed tomography (CT) imaging were included. Different implanted stentgrafts (n = 622 [42.9%] Zenith, n = 236 [16.3%] AneuRx, n = 179 [12.3%] Talent, n = 83 [5.7%] Endurant, n = 236 [16.3%] Excluder, n = 36 [2.5%] Fortron, 53 [3.7%] Anaconda, n = 5 [0.3%] others) were employed. "Persisting shrinkage" was measured as ≥ 5 mm AAA diameter regression spontaneously persisting or increasing until the end of follow-up without reintervention. Persisting shrinkage among devices was compared with survival and Cox regression analyses., Results: During a median follow-up of 45 months (interquartile range, IQR, 21-79) persisting shrinkage was detected in 768 (53%) aneurysms. Kaplan-Meier estimates of persisting shrinkage were 25.8% at 1 year, 63% at 3 years and 72.6% at 10 years. Persisting shrinkage rates were significantly higher for Zenith (p < .0001), Endurant (p = .013) and new generation Excluder (p < .0001) devices. Cox analyses confirmed that persisting shrinkage rates were independently associated with Zenith (OR 1.33; 95% CI: 1.176-1.514) and Endurant (OR 1.52; 95% CI: 1.108-2.092) stentgrafts and negatively associated with the AneuRx (OR 0.57; 95% CI: 0.477-0.688) device. Survival rates were higher in the persisting shrinkage group: 84.1% vs. 77.8% at 3 years, and 53% vs. 38.1% at 10 years (p < .0001). Freedom from AAA-related-death rate was 100% at 3 years and 99.7% at 10 years in the persisting shrinkage group., Conclusions: Aneurysm diameter shrinkage can be achieved in most current EVARs with persisting effect at 10 years from repair and indicates the benefit and safety of treatment. Last generation devices seem to be important factors in inducing aneurysm sac shrinkage with similar clinically relevant effects among single models., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Women are recognized to experience inferior outcomes following open surgery for elective or ruptured abdominal aortic aneurysm (rAAA) when compared with men. The objective of this review was to assess whether there is a sex difference on mortality in patients receiving endovascular aneurysm repair (EVAR) for rAAA., Methods: A systematic literature review from 2005 to 2012 was performed to investigate early mortality risk of ruptured endovascular aneurysm repair (rEVAR) stratified by sex. Data were analyzed with random-effect meta-analysis; pooled odds ratios (ORs) were calculated for women compared with men., Results: Thirteen studies provided the required information; in most (n = 9), data stratified by sex was identified through unpublished data from direct contact with authors. No study was randomized; there were four prospective and 10 retrospective series. Three were United States population studies. The number of women was limited in most articles. Data were available for 5580 patients treated with rEVAR; 1339 were women (23.9%). Perioperative mortality with rEVAR occurred in 473/1339 women (pooled rate 35.6%; 95% confidence interval [CI], 33.1-38.2) and in 1334/4241 men (pooled rate 31.7%; 95% CI, 30.3-33.1) without significant difference between sex categories (pooled odds ratio 1.22; 95% CI, 0.97-1.54; P = .09). There was no increased mortality risk in women vs men in ancillary analyses stratified by study size and after excluding unpublished data., Conclusions: Women may benefit as much as men from EVAR for rAAA. Nevertheless, current evidence supporting EVAR for female patients with rAAA is weak and requires confirmation by further experiences with a larger female representation., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Operator training is a key factor for the safety of carotid stenting (CAS). Whether institutional practice is associated with improved individual operator outcomes is debated., Objective: To evaluate the effect of the institutional experience on outcomes of new trainees with CAS, a retrospective analysis of a prospectively held database was performed., Methods: The overall study period, 2004-2012, was divided into two sequential time frames: 2004-April 2006 (leaders-team phase) and May 2006-2012 (expanded team phase). In the first frame, a single leader-operators team that first approached CAS and passed the original institutional learning curve, performed all the procedures; in the following expanded-team phase, five new trainees joined. Institutional CAS training for new trainees was based on a team-working approach including selection of patients, devices and techniques and collegial meetings with critical review and discussion of all procedural steps and imaging., Results: A total of 431 CAS procedures were performed in the leaders-team phase and 1026 in the sequential expanded-team phase. Periprocedural complication rates in the two time frames were similar: stroke/death (3.0% vs. 2.1%; P = 0.35), stroke (2.8% vs. 2.1%; P = 0.45) major stroke (0.9% vs. 0.6%, P = 0.49), death (0.2% vs. 0%; P = 0.29) during the leaders-team and expanded-team phase, respectively. However, rates of CAS failure requiring surgical conversions (3.7% vs. 0.8%; P < 0.0001) and mean contrast use (91.6 vs. 71.1 ml; P = 0.0001) decreased in the expanded phase. In the expanded-team frame (May 2006-2012), there was no mortality, and stroke rates were comparable between the leader and new operator teams: 2.6% vs. 1.2%; P = 0.17., Conclusions: Institutional experience, including instruction on selection of patients and materials best suited for the procedure, is a primary factor driving outcomes of CAS. An effective team-working approach can reliably improve the training of new trainees preserving CAS safety and efficacy., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: This study aims to investigate the impact of diabetes in the management of patients with small abdominal aortic aneurysms (AAA)., Methods: Three-hundred sixty patients with small AAA (4.1-5.4 cm), enrolled in a randomized trial comparing early endovascular repair versus surveillance and delayed repair (after achievement of >5.5 cm or growth>1 cm/yr), were analyzed with standard survival methods to assess the relation between diabetes and risk of all-cause mortality, complications, and aneurysm growth (on computed tomography as per trial protocol) at 36 months. Baseline covariates were selected with partial likelihood stepwise method to investigate factors (demographic, morphologic, medications) associated with risk of aneurysm growth during surveillance., Results: Prevalence of diabetes was 13.6%. The hazard ratio (HR) for all-cause mortality at 36 months was higher in diabetic compared with nondiabetic patients: (HR, 7.39; 95% confidence interval [CI], 1.55-35.13; P=.012). Baseline aneurysm diameter was comparable between diabetic and nondiabetic patients enrolled in the surveillance arm and was related to subsequent aneurysm growth in covariance analyses adjusted for diabetes (49.3 mm for nondiabetic; 50.2 mm for diabetic). Cox analyses found diabetes as the strongest independent negative predictor of 63% lower probability of aneurysm growth>5 mm during surveillance (HR, 0.37; 95% CI, 0.15-0.92; P=.003). Kaplan-Meier cumulative probability of aneurysm growth>5 mm at 36 months was 40.8% in diabetics versus 85.1% in nondiabetics (HR, 0.32; 95% CI, 0.17-0.61)., Conclusions: Progression of small AAA seems to be more than 60% lower in patients with diabetes. This may help to identify high-risk subgroups at higher likelihood of AAA enlargement, such as nondiabetics, for surveillance protocols in patients with small AAA., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Invasive management of patients ≥80 years of age with carotid stenosis may be questionable. The higher likelihood of stroke needs to be balanced with the increased perioperative risk and the reduced life expectancy of this ageing population. The purpose of this study was to evaluate the clinical relevance of carotid stenosis revascularisation in octogenarians., Methods: All patients ≥80 years of age who received carotid revascularisation in 2001-2010 were reviewed for perioperative and 5-year outcomes. The experience was comprehensive of carotid endarterectomy (CEA) and carotid stenting (CAS) performed during the training frame when age was not a contraindication for this procedure. Mortality rates were compared to those of octogenarians of the same geographical territory according to all-cause and stroke-related mortality national statistics datasets., Results: A total of 348 procedures performed in ≥80-year-old patients (272 males) were reviewed: 162 (46.6%) were by CAS and 169 (48.6%) were for symptomatic disease. Perioperative stroke/death rate was 5.5% and was non-significantly higher for symptomatic disease (7.1% vs. 3.9% asymptomatic; p = 0.24), after CAS (6.2% vs. 4.8% CEA; p = 0.64) and in females (6.6% vs. 5.1% males; p = 0.57). At median follow-up of 36.18 months, 95 deaths and 21 new ischaemic strokes (12 fatal) occurred with 5-year Kaplan-Meier freedom from stroke of 84.8% (78.7%, symptomatic vs. 90.3% asymptomatic; p = 0.003). According to national datasets, in 80-85-year-old resident population 5-year mortality was 29.9% (23.4% females, 40.6% males) and ischaemic stroke-related mortality was 14.9% (16.8% females, 13.0% males). Corresponding figures from treated population showed a 5-year mortality of 49.4%, higher in males (39.5% females, 52.5% males) and ischaemic stroke-related mortality of 20.2%, higher in females (40.0% females, 15.6% males). Comparing data from the study population with residents' figures, ischaemic stroke-related mortality hazard was significantly higher in the study females: odds ratio (OR) 3.2, 95% confidence interval (CI) 1.16-9.17; p = 0.029 (for males: OR 0.97, 95%CI 0.89-1.10; p = 0.99)., Conclusions: Despite perioperative stroke/death risks being lower compared with CAS, the benefit of surgical carotid revascularisation in old patients remains controversial due to limited life expectancy and high fatality of stroke in this ageing population. Invasive treatment of carotid stenosis may not be warranted in most patients ≥80 years of age with carotid stenosis, especially when female and asymptomatic., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Paradoxical pulmonary embolisms are uncommon emergencies and can occur as a consequence of an aortocaval fistula due to unrecognized dislodgement of thrombus from aortic sac into pulmonary circulation. This study reviewed current literature and therapeutic options in this emergency condition requiring prompt management and repair., Methods: Literature was systematically searched for paradoxical pulmonary embolism associated with aortocaval rupture., Results: Eight published cases were identified. However, many other paradoxical pulmonary emboli could have remained undiagnosed due to challenging clinical presentation. Symptoms of high-output cardiac failure and respiratory distress in the presence of large aortoiliac aneurysm and venous hypertension are findings of a possible major abdominal arteriovenous fistula with paradoxical pulmonary embolism. Successful treatment depends on prevention of new embolism and proper management of perioperative hemodynamics and massive bleeding during fistula repair. Endovascular procedures have been recently used as useful tools in this field. Cava filter placement may be a first step to prevent further thrombus dislodgements during aortocaval repair. Immediate subsequent aortic stent-grafting can allow repair of aortocaval communication and exclusion of the abdominal aortic aneurysm from circulation with successful reversal of altered hemodynamic features. However, experience (especially in the long-term) is limited., Conclusions: Paradoxical pulmonary embolism from aortocaval fistula represents an extremely rare but true clinical emergency with high fatality rate. Recent advances in diagnostic technology and endovascular techniques can substantially improve outcomes of the disease. Clinical competence in early detection and diagnosis is essential for appropriate emergent management., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Background: Iliac branch device (IBD) technique has been introduced as an appealing and effective solution to avoid complications occurring during repair of aorto-iliac aneurysm with extensive iliac involvement. Nevertheless, no large series with long-term follow-up of IBD are available. The aim of this study was to analyse safety and long-term efficacy of IBD in a consecutive series of patients., Methods: Between 2006 and 2011, 100 consecutive patients were enrolled in a prospective database on IBD. Indications included unilateral or bilateral common iliac artery aneurysms combined or not with abdominal aneurysms. Patients were routinely followed up with computed tomography. Data were reported according to the Kaplan-Meier method., Results: There were 96 males, mean age 74.1 years. Preoperative median common iliac aneurysm diameter was 40 mm (interquartile range (IQR): 35-44 mm). Sixty-seven patients had abdominal aortic aneurysm >35 mm (IQR: 40-57 mm) associated with iliac aneurysm. Eleven patients presented hypogastric aneurysm. Twelve patients underwent isolated iliac repair with IBD and 88 patients received associated endovascular aortic repair. Periprocedural technical success rate was 95%, with no mortality. Two patients experienced external iliac occlusion in the first month. At a median follow-up of 21 months (range 1-60) aneurysm growth >3 mm was detected in four iliac (4%) arteries. Iliac endoleak (one type III and two distal type I) developed in three patients and buttock claudication in four patients. Estimated patency rate of internal iliac branch was 91.4% at 1 and 5 years. Freedom from any reintervention rate was 90% at 1 year and 81.4% at 5 years. No late ruptures occurred., Conclusions: Long-term results show that IBD use can ensure persistent iliac aneurysm exclusion at 5 years, with low risk of reintervention. This technique can be considered as a first endovascular option in patients with extensive iliac aneurysm disease and favourable anatomy., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Diabetes is prevalent in most patients undergoing carotid revascularization and is suggested as a marker of poor outcome after carotid endarterectomy (CEA). Data on outcome of diabetic patients undergoing carotid artery stenting (CAS) are limited. The aim of this study was to investigate early and 6-year outcomes of diabetic patients undergoing carotid revascularization with CAS and CEA., Methods: The database of patients undergoing carotid revascularization for primary carotid stenosis was queried from 2001 to 2009. Diabetic patients were defined as those with established diagnosis and/or receiving oral hypoglycemic or insulin therapy. Multivariate and Kaplan- Meier analyses, stratified by type of treatment, were performed on perioperative (30 days) and late outcomes., Results: A total of 2196 procedures, 1116 by CEA and 1080 by CAS (29% female, mean age 71.3 years), were reviewed. Diabetes was prevalent in 630 (28.7%). Diabetic patients were younger (P < .0001) and frequently had hypertension (P = .018) or coronary disease (P = .019). Perioperative stroke/death rate was 2.7% (17/630) in diabetic patients vs 2.3% (36/1566) in nondiabetic, (P = .64); the rate was 3.4% in diabetic CEA group and 2.1% in diabetic CAS group (P = .46). At multivariate analyses, diabetes was a predictor of perioperative stroke/death in the CEA group (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.05-7.61; P = .04) but not in the CAS group (P = .72). Six-year survival was 76.0% in diabetics and 80.8% in nondiabetics (P = .15). Six-year late stroke estimates were 3.2% in diabetic and 4.6% in nondiabetic patients (P = .90). The 6-year risk of restenosis was similar (4.6% % vs 4.2%) in diabetic and nondiabetic patients (P = .56). Survival, late stroke, and restenosis rates between diabetics and nondiabetics were similar in CAS and CEA groups., Conclusions: Diabetic patients are not at greater risk of perioperative morbidity and mortality or late stroke after CAS, however, the perioperative risk can be higher after CEA. This may help in selecting the appropriate technique for carotid revascularization in patients best suited for the type of procedure., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Structured follow-up after revascularisation for chronic critical limb ischaemia (CLI) aims at sustained treatment success and continued best patient care. Thereby, efforts need to address three fundamental domains: (A) best medical therapy, both to protect the arterial reconstruction locally and to reduce atherosclerotic burden systemically; (B) surveillance of the arterial reconstruction; and (C) timely initiation of repeat interventions. As most CLI patients are elderly and frail, sustained resolution of CLI and preserved ambulatory capacity may decide over independent living and overall prognosis. Despite this importance, previous guidelines have largely ignored follow-up after CLI; arguably because of a striking lack of evidence and because of a widespread assumption that, in the context of CLI, efficacy of initial revascularisation will determine prognosis during the short remaining life expectancy. This chapter of the current CLI guidelines aims to challenge this disposition and to recommend evidentially best clinical practice by critically appraising available evidence in all of the above domains, including antiplatelet and antithrombotic therapy, clinical surveillance, use of duplex ultrasound, and indications for and preferred type of repeat interventions for failing and failed reconstructions. However, as corresponding studies are rarely performed among CLI patients specifically, evidence has to be consulted that derives from expanded patient populations. Therefore, most recommendations are based on extrapolations or subgroup analyses, which leads to an almost systematic degradation of their strength. Endovascular reconstruction and surgical bypass are considered separately, as are specific contexts such as diabetes or renal failure; and critical issues are highlighted throughout to inform future studies., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients. Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated. In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds. CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines. Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted. Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed. This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

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 <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

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 end-stage 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 (TcPO(2)) 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., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)