Early Carotid Endarterectomy after Ischemic Stroke: The Results of a Prospective Multicenter Italian Study

ObjectivesTo evaluate safety of early carotid endarterectomy (CEA) in patients with acute brain ischemia presenting to the emergency department stroke units (EDSU).MethodsThe neurologists, neuroradiologists and vascular surgeons on duty in emergency departments enrolled 96 patients who underwent very early CEA according to a predefined protocol within two years. The protocol included evaluation of neurological status by National Institute of Health Stroke Scale (NIHSS), neuroimaging assessment, ultrasound of the carotid arteries and Transcranial Doppler. Patients with NIHSS>22 or whose neuroimaging showed brain infarct >2/3 of the middle cerebral artery territory were excluded. All eligible patients underwent CEA as soon as possible. Primary end points of the study were mortality, neurological morbidity by NIHSS and postoperative hemorrhagic conversion on neuroimaging. Statistical analysis was performed by univariate analysis.ResultsThe mean time elapsing between the onset of stroke and endarterectomy was 1.5 days (±2 days). The overall 30-day morbidity mortality rate was 7.3% (7/96). No neurological mortality occurred. On hospital discharge, three patients (3%) experienced worsening of the neurological deficit (NIHSS score 1 to 2, 1 to 3 and 9 to 10 respectively). Postoperative CT demonstrated there were no new cerebral infarcts nor hemorrhagic transformation. At hospital discharge 9/96 patients (9%) had no improvement in NHISS scores, 37 were asymptomatic and 45 showed a median decrease of 4.5 NIHSS points (range 1–18). By univariate analysis none of the considered variables influenced the clinical outcome.ConclusionOur protocol selected patients who can safely undergo very early (<1.5 days) surgery after acute brain ischemia. Large randomized multicenter prospective trials are warranted to compare very early CEA versus best medical therapy

Association of Primary Varicose Veins with Dysregulated Vein Wall Apoptosis

BACKGROUND: Disordered programmed cell death may play a role in the development of superficial venous incompetence. We have determined the number of cells in apoptosis, and the mediators regulating the intrinsic and extrinsic pathways in specimens of varicose vein. METHODS: Venous segments were obtained from 46 patients undergoing surgical treatment for primary varicose veins. Controls samples were obtained from 20 patients undergoing distal arterial bypass grafting surgery. Segments of the distal and proximal saphenous trunk as well as tributaries were studied. Cell apoptoses and mediators of the mitochondrial and trans membrane pathway were evaluated with peroxidase in situ apoptosis detection, Bax and Fas detection, caspase-9 and 8 detection in the medial layer. RESULTS: Disorganised histological architecture was observed in varicose veins. Primary varicose veins also contained fewer peroxidase in situ-positive cells than control veins (2.6% S.D. 0.2% versus 12% S.D. 0.93%, P=.0001, Mann-Whitney u test), fewer Bax positive cells (2.1.% S.D. 0.3% versus 13% S.D. 0.9%, P=.0001) and fewer Caspase 9 positive cells (3.2% S.D. 1% versus 12% S.D. 1.3%, P=.0001). Similar findings were observed in saphenous trunk, main tributaries and accessory veins. In patients with recurrent varicose veins in whom the saphenous trunk had been preserved showed similar findings to primary varicose veins. Residual varicose veins contained fewer peroxidase in situ-positive cells than healthy veins (3.2% S.D. 0.6% versus 11% S.D. 2%, P=.0001), fewer Bax positive cells (2.2% S.D. 0.3% versus 12% S.D. 0.7%, P=.0001) and fewer Caspase 9 positive cells (2.6% S.D. 0.6% versus 12% S.D. 1%, P=.0001). Immunohistochemical detection for Fas and caspase 8 remained equal was the same in the varicose vein and control groups. CONCLUSION: Apoptosis is down regulated in the medial layer of varicose veins. This dysregulation is attributable to a disorder of the intrinsic pathway and involves the great saphenous vein trunk, major tributaries and accessory veins. This process may be among the causes of primary varicose veins

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Radiolabeled native low-density lipoprotein injected into patients with carotid stenosis accumulates in macrophages of atherosclerotic plaque: Effect of vitamin E supplementation

Background-Accumulation of LDL within the arterial wall appears to play a crucial role in the initiation and progression of atherosclerotic plaque. The dynamic sequence of this event has not been fully elucidated in humans. Methods and Results-In 7 patients with previous transient ischemic attack or stroke and critical (>70%) carotid stenosis, autologous native [I-125]-labeled LDL or [I-125]-labeled human serum albumin were injected 24 to 72 hours before endarterectomy. Carotid specimens obtained at endarterectomy were analyzed by autoradiography and immunohistochemistry, Autoradiographic study showed that LDL was localized prevalently in the foam cells of atherosclerotic plaques, whereas the accumulation in the lipid core was negligible. Immunohistochemistry revealed that foam cells that had accumulated radiolabeled LDL were mostly CD68 positive, whereas a small number were alpha-actin positive. No accumulation of the radiotracer was detected in atherosclerotic plaques after injection of radiolabeled human serum albumin. In 3 patients treated for 4 weeks with vitamin E (900 mg/d), an almost complete suppression of radiolabeled LDL uptake by macrophages was observed. Conclusions-This study shows that circulating LDL rapidly accumulates in human atherosclerotic plaque. The prevalent accumulation of LDL by macrophages provides strong support to the hypothesis that these cells play a crucial role in the pathogenesis of atherosclerosis

EcoDoppler Transcranico con tecnica CPS e SonoVue nella valutazione della perfusione cerebrale. Nuove prospettive diagnostiche

EcoDoppler Transcranico con tecnica CPS e SonoVue nella valutazione della perfusione cerebrale. Nuove prospettive diagnostich

Radiolabeled native low-density lipoprotein injected into patients with carotid stenosis accumulates in macrophages of atherosclerotic plaque: Effect of vitamin E supplementation

Background-Accumulation of LDL within the arterial wall appears to play a crucial role in the initiation and progression of atherosclerotic plaque. The dynamic sequence of this event has not been fully elucidated in humans. Methods and Results-In 7 patients with previous transient ischemic attack or stroke and critical (>70%) carotid stenosis, autologous native [I-125]-labeled LDL or [I-125]-labeled human serum albumin were injected 24 to 72 hours before endarterectomy. Carotid specimens obtained at endarterectomy were analyzed by autoradiography and immunohistochemistry, Autoradiographic study showed that LDL was localized prevalently in the foam cells of atherosclerotic plaques, whereas the accumulation in the lipid core was negligible. Immunohistochemistry revealed that foam cells that had accumulated radiolabeled LDL were mostly CD68 positive, whereas a small number were alpha-actin positive. No accumulation of the radiotracer was detected in atherosclerotic plaques after injection of radiolabeled human serum albumin. In 3 patients treated for 4 weeks with vitamin E (900 mg/d), an almost complete suppression of radiolabeled LDL uptake by macrophages was observed. Conclusions-This study shows that circulating LDL rapidly accumulates in human atherosclerotic plaque. The prevalent accumulation of LDL by macrophages provides strong support to the hypothesis that these cells play a crucial role in the pathogenesis of atherosclerosis