Safety of urgent endarterectomy in acute non-disabling stroke patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: International recommendations advocate that carotid endarterectomy (CEA) should be performed within 2 weeks from the index event in symptomatic carotid artery stenosis (sCAS) patients. However, there are controversial data regarding the safety of CEA performed during the first 2 days of ictus. The aim of this international, multicenter study was to prospectively evaluate the safety of urgent (0-2 days) in comparison to early (3-14 days) CEA in patients with sCAS. METHODS: Consecutive patients with non-disabling (modified Rankin Scale scores ≤2) acute ischaemic stroke or transient ischaemic attack due to sCAS (≥70%) underwent urgent or early CEA at five tertiary-care stroke centers during a 6-year period. The primary outcome events included stroke, myocardial infarction or death during the 30-day follow-up period. RESULTS: A total of 311 patients with sCAS underwent urgent (n = 63) or early (n = 248) CEA. The two groups did not differ in baseline characteristics with the exception of crescendo transient ischaemic attacks (21% in urgent vs. 7% in early CEA; P = 0.001). The 30-day rates of stroke did not differ (P = 0.333) between patients with urgent (7.9%; 95% confidence interval 3.1%-17.7%) and early (4.4%; 95% confidence interval 2.4%-7.9%) CEA. The mortality and myocardial infarction rates were similar between the two groups. The median length of hospitalization was shorter in urgent CEA [6 days (interquartile range 4-6) vs. 10 days (interquartile range 7-14); P < 0.001]. CONCLUSIONS: Our findings highlight that urgent CEA performed within 2 days from the index event is related to a non-significant increase in the risk of peri-procedural stroke. The safety of urgent CEA requires further evaluation in larger datasets.

Cranial Nerve Injury After Carotid Endarterectomy: Incidence, Risk Factors, and Time Trends.

OBJECTIVE/BACKGROUND: To review the incidence of post-carotid endarterectomy (CEA) cranial nerve injury (CNI), and to evaluate the risk factors associated with increased CNI risk. METHODS: The study was a meta-analysis. Pooled rates with 95% confidence intervals (CIs) were calculated for CNIs after primary CEA. Odds ratios (ORs) were calculated for potential risk factors. A fixed-effects model or a random effects model (Mantel-Haenszel method) was used for non-heterogeneous and heterogeneous data, respectively. Meta-regression analysis was performed to examine the influence of publication year upon CNI rate. RESULTS: Twenty-six articles, published between 1970 and 2015, were included in the meta-analysis, corresponding to 20,860 CEAs. Meta-analysis revealed that the vagus nerve was the most frequently injured cranial nerve (pooled injury rate 3.99%, 95% CI 2.56-5.70), followed by the hypoglossal nerve (3.79%, 95% CI 2.73-4.99). Fewer than one seventh of these injuries are permanent (vagus nerve: 0.57% [95% CI 0.19-1.10]; hypoglossal nerve: 0.15% [95% CI 0.01-0.39]). A statistically significant influence of publication year on the vagus and hypoglossal nerve injury rate was found, with the injury rate having decreased from about 8% to 2% and 1%, respectively, over the last 35 years. Urgent procedures (OR 1.59, 95% CI 1.21-2.10; p = .001), as well as return to the operating room for a neurological event or bleeding (OR 2.21, 95% CI 1.35-3.61; p = .002) were associated with an increased risk of CNI, whereas no statistically significant association was found between CNIs and the type of anaesthesia, the use of a patch, redo operation, and the use of a shunt. CONCLUSION: The vagus nerve appears to be the most frequently injured cranial nerve after CEA, followed by the hypoglossal nerve, with only a small proportion of these injuries being permanent. The CNI rate has significantly decreased over the past 35 years to a point indicating that CNIs should not be considered a major influencing factor in the decision making process between CEA and stenting.

A Review of Open and Endovascular Treatment of Superior Vena Cava Syndrome of Benign Aetiology.

BACKGROUND: The widespread use of central venous catheters, ports, pacemakers, and defibrillators has increased the incidence of benign superior vena cava syndrome (SVCS). This study aimed at reviewing the results of open and endovascular treatment of SVCS. METHOD: Medical literature databases were searched for relevant studies. Studies with more than five adult patients, reporting separate results for the SVC were included. Nine studies reported the results of endovascular treatment of SVCS including 136 patients followed up for a mean of 11-48 months. Causes of SVCS were central venous catheters and pacemakers (80.6%), mediastinal fibrosis (13.7%), and other (5.6%). Percutaneous transluminal angioplasty (PTA) and stenting was performed in 73.6%, PTA only in 17.3%, and thrombolysis, PTA, and stenting in 9%. Four studies reported the results of open repair of SVCS including 87 patients followed up between 30 months and 10.9 years. The causes were mediastinal fibrosis (58.4%), catheters and pacemakers (28.5%), and other (13%). Operations performed included a spiral saphenous interposition graft, other vein graft, PTFE graft, and human allograft. Thirteen patients required re-operations (15%) before discharge mainly for graft thrombosis. RESULTS: In the endovascular group technical success was 95.6%. Thirty day mortality was 0%. Regression of symptoms was reported in 97.3%. Thirty-two patients (26.9%) underwent 58 secondary procedures. In the open group the 30 day mortality was 0%. Symptom regression was reported in 93.5%. Twenty-four patients (28.4%) underwent a total of 33 secondary procedures. CONCLUSIONS: Endovascular is the first line treatment for SVCS caused by intravenous devices, whereas surgery is most often performed for mediastinal fibrosis. Both treatments show good results regarding regression of the symptoms and mid-term primary patency, with a significant incidence of secondary interventions.

Protamine Reduces Bleeding Complications without Increasing the Risk of Stroke after Carotid Endarterectomy: A Meta-analysis.

OBJECTIVES: The aim was to evaluate the safety and efficacy of heparin reversal with protamine after completion of carotid endarterectomy (CEA), summarising the available data from both randomised and non-randomised studies. METHODS: The study was a meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated for the outcomes of stroke and wound haematoma among patients receiving or not receiving protamine after CEA. Meta-regression analysis was performed to examine whether the documented differences were modified by potentially meaningful patient related or procedure related predictors, namely publication year, general anesthesia used, number of patients treated, mean age (years), males, neurological symptoms, use of patch, and use of shunt. RESULTS: Seven studies were included in the meta-analysis reporting on 3,817 patients receiving protamine after CEA and 6,070 patients not receiving protamine for heparin reversal. Only one study was randomised. A statistically significant reduction in wound haematoma requiring re-operation was recorded after heparin reversal with protamine in patients undergoing CEA (OR, 0.42, 95% CI, 0.22-0.80, p = .008). In contrast, no significant difference was observed in stroke rates between groups of patients that received and did not receive protamine (OR, 0.71, 95% CI, 0.49-1.03, p = .07). Meta-regression analysis did not reveal any significant effect mediated by the modifiers examined. CONCLUSION: On the basis of the available data, heparin reversal with protamine seems to reduce the risk of wound haematoma, without increasing the risk of procedural stroke. However, taking into account the limitations of the analysis, further studies are needed to increase the level of evidence provided by the current meta-analysis.

Bilateral lingual-facial trunk: anatomic and clinical implications.

Common origin of lingual and facial artery is a relatively frequent anatomic varia-tion. Instead, bilateral lingual-facial trunk has been described only sparsely in the literature. In this report authors describe and analyse a case of bilateral common lingual-facial trunk in the context of its anatomical, clinical and embryological implications. We also describe possible consequences in performance of elective and emergent surgical operations and modification in surgical techniques that should be considered. We believe that surgeons should be suspicious for this variation's existence and keep alternative solutions in their armentarium.

Factors Predisposing to Endograft Limb Occlusion after Endovascular Aortic Repair.

OBJECTIVES: The aim of this study was to investigate risk factors for endograft limb occlusion after endovascular abdominal aneurysm repair (EVAR), using a case control design. METHODS: All patients presenting with endograft limb occlusion after elective EVAR between January 2010 and June 2013, along with age, sex, and type of endograft matched controls were included in the study. The impact of atherosclerotic risk factors, anatomic characteristics of the aneurysm, procedural details, and antiplatelet therapy was investigated. Multivariate logistic regression analysis and conditional logistic regression analysis for 1:3 matched pairs deriving adjusted odds ratios (ORs) with 95% confidence intervals (CIs) in order to detect significant risk factors for endograft limb occlusion among cases and controls were modeled. RESULTS: Of the 439 patients treated by EVAR, 18 patients (4.1%) presented with endograft limb occlusion. These patients were compared to 54 matched controls. Limb occlusion was associated with iliac artery angulation ≥ 60° (OR = 5.76, 95% CI =1.24-26.74; p = .03) or perimeter calcification ≥ 50% (OR =5.87, 95% CI = 1.10-31.32; p = .04). Limb occlusion was also associated with ≥ 15% endograft oversizing in the common iliac artery (OR = 5.54, 95% CI = 1.11-27.60; p = .04). No other risk factors for limb occlusion were recognized. CONCLUSIONS: The presence of significant angulation and calcification of the iliac arteries as well as excessive limb oversizing appear to be independent predictors of endograft limb occlusion after EVAR.

New possibility of AAA treatment with E-vita abdominal device.

The most dramatic shift in the management of abdominal aortic aneurysms (AAAs) occurred in 1991, when the first endovascular AAA repair was reported. Endovascular aneurysm repair has revolutionized the treatment of infrarenal AAAs. In the last few years, the companies have developed renewed models of grafts and have modified delivery systems tending to make them more atraumatic and flexible in order to deal with difficult anatomies and severely atheromatous and tortuous vessels. The aim of the present paper was to analyze the technical characteristics and properties of the new stent-graft system E-vita abdominal XT and to review the current literature. The E-vita abdominal XT stent-graft seems to be safe and reliable; however, long-term results are needed.

Current knowledge on EVAR with the ultra-low profile Ovation Abdominal Stent-graft System.

Endovascular aneurysm repair (EVAR) has revolutionized the treatment of infrarenal abdominal aortic aneurysms (AAAs). The continuous collaboration of surgeons and bioengineers in the improvement of the devices the last two decades, lead to a continuous redesigning and improvement of the various endografts. In the last few years, the majority of companies have developed renewed models of grafts and have modified delivery systems tending to lower profile in order to deal with difficult anatomies. The ultra low profile 14F OD Ovation (Trivascular) Abdominal Stent-graft System with innovative sealing technology achieved through inflatable sealing rings, allows treatment of AAAs with small in diameter access vessels that might be unsuitable for EVAR with other currently available stent-grafts. The aim of the present paper was to analyze the technical characteristics and properties of this endograft and to review the current literature.

The chimney graft technique for preserving renal arteries in stent-graft sealing zones.

Patients with juxtarenal aneurysms require complex surgical open repair, which is associated with increased mortality and morbidity. An alternative procedure that can be used is the "chimney graft" technique. Three cases of abdominal aortic aneurysms were successfully treated in our department with this technique. One type-Ia endoleak occurred which was successfully treated with coiling and biological glue infusion. All of the chimney grafts have remained patent for the period of observation. The "chimney" technique has good results as a bail out procedure in complex EVAR or in well planned difficult cases. Long-term data is necessary to determine the efficacy of this technique.

The European Society for Vascular Surgery guidelines for carotid intervention: an updated independent assessment and literature review.

BACKGROUND AND PURPOSE: Many medical societies now recommend carotid stenting as an alternative to endarterectomy which raises the question of whether the ESVS guidelines are still valid. This review addresses the validity of the ESVS guidelines that refer to carotid stenting based on the evidence available today. METHODS: We conducted a review and meta-analysis based on the original ESVS guidelines paper and articles published over the past 2 years. RESULTS: For symptomatic patients, surgery remains the best option, since stenting is associated with a 61% relative risk increase of periprocedural stroke or death compared to endarterectomy. However, centres of excellence in carotid stenting may achieve comparable results. In asymptomatic patients, there is still no good evidence for any intervention because the stroke risk from an asymptomatic stenosis is very low, especially with the best modern medical treatment. CREST and CAVATAS have verified that mid-term stroke prevention after successful stenting is similar to endarterectomy. EVA-3S, SPACE, ICSS and CREST have provided additional evidence regarding the role of age in choosing therapeutic modality. The role of the cerebral protection devices is challenged by the imaging findings of small randomised trials but supported by large systematic reviews. CONCLUSIONS: The ESVS guidelines that refer to carotid stenting not only remain valid but also have been further strengthened by the latest available clinical data. An update of these guidelines including all of the recent evidence is needed to provide an objective and up-to-date interpretation of the data.

Association between plaque echogenicity and embolic material captured in filter during protected carotid angioplasty and stenting.

OBJECTIVES/DESIGN: The aim of the study was to investigate debris captured in filter embolic protection devices (EPDs) during carotid artery stenting (CAS) and its possible correlation with plaque echogenicity and other risk factors. MATERIALS/METHODS: Between June 2010 and March 2011, 51 consecutive CAS patients (11 females, mean age 71.2 ± 7, 10 symptomatic) who underwent 53 procedures were included in this prospective study. Ultrasonographic Gray-Weale plaque type (I-V, echolucent to echogenic) characterisation was obtained in all cases. The same type of stent and filter EPD was used. Filters were collected and, after macroscopic evaluation, they were examined using the Thin-Prep(®) liquid-based cytology (LBC) technique. RESULTS: Technical success was 100%. Thirty-day stroke and death rates were 1.8% (1/53) and 0%, respectively. Visible debris was detected in eight (15%) filters, whereas LBC revealed the presence of embolic material particles in 30 filters (56.6%). The presence of embolic material into the filter EPD was 2.38-fold increased for every category change from type IV to type I carotid plaques (OR = 2.38, 95%CI = 1.15-4.93). This association remained robust even after adjustment for age, gender and known atherosclerotic disease risk factors (OR = 2.26, 95%CI = 1.02-5.02). In multivariate analysis for risk factors, hypertension was associated with increased presence of embolic material detection in filter EPD (OR = 20.4, 95%CI = 1.28-326.1). The time distance from symptom to CAS was inversely correlated with debris quantity in EPD (Spearman rho -0.716; p = 0.02). CONCLUSIONS: Echolucent plaques, smaller time frame from last symptom and hypertension were associated with increased presence of embolic material.

Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.

BACKGROUND: To compare eversion (ECEA) and conventional (CCEA) carotid endarterectomy from randomised and non-randomised studies. METHODS: Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) and numbers needed to treat (NNTs) were appropriately calculated. A sub-analysis was performed on studies directly comparing ECEA vs. patch CEA (PCEA). Meta-regression analysis was performed to examine the effect of potentially meaningful patient-related, procedure-related and definition-related modifiers. Power calculations were also conducted. RESULTS: A total of 21 studies were deemed eligible (8530 ECEA and 7721 CCEA procedures), seven of which were randomised and 14 non-randomised. ECEA was associated with significant reduction in perioperative stroke (OR = 0.46, 95%CI: 0.35-0.62, NNT = 68, 95%CI: 56-96), death (OR = 0.49, 95%CI: 0.34-0.69, NNT = 100, 95%CI: 85-185) and stroke-related death (OR = 0.40, 95%CI: 0.23-0.67, NNT = 147, 95%CI: 115-270); the results were replicated at the sub-analysis on PCEA. Concerning long-term outcomes, ECEA presented with a significant reduction in late carotid artery occlusion (OR = 0.48, 95%CI: 0.25-0.90, NNT = 143, 95%CI: 100-769) and late mortality (OR = 0.76, 95%CI: 0.61-0.94, NNT = 40, 95%CI: 25-167); the sub-analysis on PCEA replicated only the finding on late mortality. Meta-regression analysis did not point to significant effects mediated by the examined modifiers. Power calculations suggested adequate statistical power. CONCLUSIONS: ECEA compared to CCEA may be associated with a lower incidence in both short-term and long-term outcomes, which does not seem to be hampered by potentially meaningful modifiers.

The role of ex-vivo gene therapy of vein grafts with Egr-1 decoy in the suppression of intimal hyperplasia.

OBJECTIVES: To test the hypothesis that vein graft intimal hyperplasia can be significantly suppressed by a single intra-operative transfection of the graft with a decoy oligonucleotide (ODN) binding the transcription factor Egr-1. DESIGN: Experimental study. MATERIALS AND METHODS: Jugular vein to carotid artery interposition grafts in rabbits were treated with Egr-1 decoy, mutant decoy ODN, vehicle alone, using a non-distending pressure of 300 mm Hg for 20 min, or were left untreated. All animals were fed a 2% cholesterol diet. The animals were sacrificed after 48h, 6 weeks and 12 weeks. Paraffin-embedded vein sections were subjected to angiometric analysis. RESULTS: Successful delivery of the ODN was confirmed by DAPI staining. Quantitative real-time PCR revealed a 60% decrease of the Egr-1 gene expression in the animals in which the Egr-1 decoy ODN was delivered. Cellular proliferation was also significantly decreased as indicated by the Ki-67 labelling index. An increase in intimal and medial thickness was found in all vein grafts. However, intimal thickness was significantly reduced in the grafts treated with Egr-1 decoy ODN, whereas luminal area was significantly increased. CONCLUSION: A single intra-operative pressure-mediated transfection of vein grafts with Egr-1 decoy ODN significantly suppresses intimal hyperplasia in a rabbit hypercholesterolaemic model.

Beneficial changes of serum calcification markers and contralateral carotid plaques echogenicity after combined carotid artery stenting plus intensive lipid-lowering therapy in patients with bilateral carotid stenosis.

OBJECTIVES/DESIGN: In symptomatic patients treated with ipsilateral carotid artery stenting (CAS) plus intensive lipid lowering, we assessed the changes of osteopontin (OPN), osteoprotegerin (OPG) and the Gray-Scale Median (GSM) score contralateral to symptomatic carotid stenosis. MATERIALS/METHODS: Forty-six symptomatic patients (group A) with significant carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial (NASCET): >70%) underwent ipsilateral CAS. Those patients had simultaneously contralateral low-grade carotid stenosis (NASCET: 30-69%). Group B included 67 symptomatic patients with low-grade bilateral carotid stenosis (NASCET: 30-69%), but without indications for revascularisation. All patients were treated with atorvastatin (10-80mg) to target low-density lipoprotein (LDL)<100mgdl(-1). Blood samples and plaques' GSM score contralateral to brain infarct were assayed at baseline and after 6 months. RESULTS: At baseline, there were no significant differences between groups (p>0.05). Six-month atorvastatin treatment equivalently improved lipid profile in both groups (p<0.05). The parameters hsCRP, OPN and OPG were significantly down-regulated within both groups, but to a greater extent in group A (p<0.05). Besides this, contralateral GSM score was significantly improved from baseline in both groups (p<0.01), but that increment was more pronounced in group A (vs. group B; p=0.041). These changes were inversely correlated with changes in OPN (p=0.014), OPG (p=0.011) and LDL (p=0.041). CONCLUSION: Ipsilateral CAS plus intensive lipid-lowering therapy was associated with enhanced contralateral carotid plaque stability and attenuated inflammatory burden and calcification inhibitors to a greater extent than atorvastatin therapy alone in patients with bilateral carotid stenosis.

Analysis of the evidence behind the ESVS guidelines for the invasive treatment of carotid stenosis.

The European Society for Vascular Surgery has recently published updated guidelines for the invasive treatment of carotid disease. The recommendations were rated according to the level of evidence (A: randomized controlled trials, B: well-conducted clinical studies, C: expert opinion). The following document summarizes the evidence on which these recommendations were based, in order to keep physicians from various disciplines updated on the advances in the field of the invasive management of carotid disease.

Inflammation and Chlamydia pneumoniae infection correlate with the severity of peripheral arterial disease.

BACKGROUND: Our aim was to investigate the association of inflammation and Chlamydia pneumoniae infection with the presence and severity of peripheral arterial disease. METHODS: Twenty-eight patients whose initial claudication distance (ICD) in the traditional constant-load treadmill test was <200 m, underwent femoral endarterectomy as part of their interventional treatment (group A). Group B consisted of 23 patients whose ICD was >200 m and were put on medication and a daily exercise program. The control group consisted of 30 non-vascular patients of the Ophthalmology Department (group C). We measured the levels of C-reactive protein, fibrinogen, vascular cell adhesion molecule-1 and tumor necrosis factor-alpha, and the titers of IgA and IgG antibodies against C. pneumoniae in the serum of all the patients. Finally, the atheromas and vein segments of group A patients, were immunohistochemically (IHC) examined for the presence of C. pneumoniae. RESULTS: Peripheral arterial disease (PAD) patients, had significantly higher CRP (p=0.026) and anti-Cp IgA levels (p=0.001) when compared to control subjects, after a multiple linear regression analysis. The odds ratio for the prevalence of femoral atherosclerosis was 3.16 for IgA seropositive patients (CI 1.15-8.67). When comparing group A and group B patients, CRP (p=0.003) and IgA (p=0.011), were significantly correlated with severe PAD. Group A patients with positive immunohistochemical examination of the plaque, had higher anti-Cp IgA levels (p=0.023) and TNF-alpha values (p=0.031), compared to the IHC negative patients. C. pneumoniae was detected in 50% of the femoral atheromas, but in only 3.6% of the veins. CONCLUSION: This study supports the hypothesis that inflammation (CRP) and chronic C. pneumoniae infection (IgA seropositivity), have an important role in lower limb atherosclerosis and correlate with the severity of the disease.

Inflammation and atherosclerosis.

PURPOSE: The aim of this article is to discuss the role of inflammation in atherosclerosis. SUMMARY: An initial chemical, mechanical or immunological insult induces endothelial dysfunction. This triggers a cascade of inflammatory reactions, in which monocytes, macrophages, T lymphocytes and vascular smooth muscle cells participate. Leukocyte adhesion molecules, cytokines, growth factors and metalloproteinases participate in all stages of atherogenesis. Almost all of the traditional risk factors for atherosclerosis are associated with and participate in the inflammatory process. Many infectious agents, mainly Chlamydia pneumoniae, have been proposed as potential triggers of the cascade. The immune system has been implicated in plaque formation, through the activation of cellular and humoral immunity against innate or microbial heat shock protein 60. Methods of detection of systemic or local plaque inflammation have been developed and research is being conducted on the potential use of anti-inflammatory and antibiotic drugs in atherosclerosis.