Radiolabeled native low-density lipoprotein injected into patients with carotid stenosis accumulates in macrophages of atherosclerotic plaque

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

Urgent carotid endarterectomy to prevent recurrence and improve neurologic outcome in mild-to-moderate acute neurologic events

Objectives: This study evaluated the safety and benefit of urgent carotid endarterectomy (CEA) in patients with carotid disease and an acute stable neurologic event. Methods: The study involved patients with acute neurologic impairment, defined as >= 4 points on the National Institutes of Health Stroke Scale (NIHSS) evaluation related to a carotid stenosis >= 50% who underwent urgent CEA. Preoperative workup included neurologic assessment with the NIHSS on admission or immediately before surgery and at discharge, carotid duplex scanning, transcranial Doppler ultrasound imaging, and head computed tomography or magnetic resonance imaging. End points were perioperative (30-day) neurologic mortality, significant NIHSS score improvement or worsening (defined as a variation >= 4), and hemorrhagic or ischemic neurologic recurrence. Patients were evaluated according to their NIHSS score on admission (4-7 or >= 8), clinical and demographic characteristics, timing of surgery (before or after 6 hours), and presence of brain infarction on neuroimaging. Results: Between January 2005 and December 2009, 62 CEAs were performed at a mean of 34.2 +/- 50.2 hours (range, 2-280 hours) after the onset of symptoms. No neurologic mortality nor significant NIHSS score worsening was detected. The NIHSS score decreased in all but four patients, with no new ischemic lesions detected. The mean NIHSS score was 7.05 +/- 3.41 on admission and 3.11 +/- 3.62 at discharge in the entire group (P = 8 on admission had a bigger score reduction than those with a lower NIHSS score (NIHSS 4-7; mean 4.95 +/- 1.03 preoperatively vs 1.31 +/- 1.7 postoperatively, NIHSS >= 8 10.32 +/- 1.94 vs 4.03 +/- 3.67; P < .001). Conclusions: In patients with acute neurologic event, a high NIHSS score does not contraindicate early surgery. To date, guidelines recommend treatment of symptomatic carotid stenosis <= 2 weeks from onset of symptoms to minimize the neurologic recurrence. Our results suggest that minimizing the time for intervention not only reduces the risk of recurrence but can also improve neurologic outcome. (J Vasc Surg 2011;53:622-8.

Peri-procedural brain lesions prevention in CAS (3PCAS). Randomized trial comparing CGuard™ stent vs. wallstent

Background: Aim of this study was to evaluate peri-procedural incidence of new diffusion-weighted-magneticresonance- imaging (DWMRI) brain lesions in CAS patients treated by carotid mesh stent (CGuard™) or closed-cell stent (Wallstent™). Methods: Consecutive patients with asymptomatic carotid stenosis ≥ 70% were submitted to preoperative DWMRI scan, to exclude the presence of preoperative silent cerebral lesions. Patients were randomized to CGuard orWallstent. DWMRI was performed immediately after the intervention and at 72-hour postoperatively. Moreover, pre and postoperative Mini-Mental-State-Examination Test (MMSE) and aMontreal-Cognitive-Assessment (MoCA) test were conducted, and S100β and NSE neurobiomarkers were measured at 5-time points (preoperatively, 2, 12, 24, and 48 h postoperatively). Results: From January 2015 to October 2016, sixty-one consecutive eligible patients were submitted to preoperative DWMRI scan. Three patients were excluded because of preoperative silent cerebral lesions. In 29 CGuard patients, 1 developed a minor stroke and 8 silent newlesionswere observed in the 72 h-DWMRI (31%): 4 lesions were ipsilateral, and 4 lesions were contra or bilateral. In 29 Wallstent patients, 7 clinically-silent new lesions were found in the 72 h-DWMRI (24.1%; p = 0.38). In 4 cases lesions were ipsilateral and in 3 cases contra or bilateral. S100B values doubled at 48 h in 24 patients, and among them 12 presented new DWMRI lesions. 48-h S100B increase was significantly related to 72-h DWMRI lesions (p= 0.012). Conclusions: In our experience both stents showed an acceptable rate of subclinical neurological events with no significant differences at 72-hour DWMRI between groups. Bilateral/contralateral lesions suggest that periprocedural neurological damage may have extra-carotid sources

Aneurysm of the Pancreaticoduodenal Arteries Associated with a Cœliac Artery Lesion

IntroductionA ruptured aneurysm of the pancreaticoduodenalarteries without acute or chronic pancreatitis butassociated with a median arcuate ligament divisionis an exceptional event described in only 11 cases. Thecase of a ruptured pancreaticoduodenal artery aneur-ysm, associated with a cœliac artery lesion which wedescribe, illustrates the difficulty in diagnosing theserare events promptly and in instituting urgent treat-ment to arrest the bleeding followed by an electiveprocedure to prevent recurrence.Case ReportA 54-year-old man with no history of vascular diseasewas admitted to a district hospital for investigation ofvague abdominal pain mainly affecting the rightabdomen, hypotension corrected by infusion ofcrystalloid and no fever. Laboratory blood chemicalfindings including a normal hemoglobin, raisedleukocyte count and high C-reactive protein concen-tration. This presentation raised the suspicion of a gallbladder infection and the patient was kept under closeobservation overnight. The next day, hypotensiondeveloped and the patient complained of pain in theright iliac quadrant. An abdominal ultrasound scanshowed a large iliac fluid collection, but no lesionsinvolving the gall bladder or liver. Appendicitis wasdiagnosed and the patient underwent a McBurneyoperation. During surgery blood was found in theabdomen. An exploratory laparotomy revealed a largeretroperitoneal hematoma. The patient was trans-ferred to our vascular surgery unit. A CT scan aftercontrast injection revealed an intact retroperitonealhematoma (16 £ 9 £ 15 cm), with no bleeding from theaorta or the visceral arteries, and a median arcuateligament division that compressed the origin of thecœliac trunk. Because these findings suggested aruptured pancreaticoduodenal artery aneurysm arter-iography was planned to confirm the diagnosis andtreat the aneurysm by embolization. The patient, whowas by now haemodynamically stable, was kept underobservation in the ITU and transferred to the vascularsurgical unit. On day 1, a CT scan showed that thehematoma had enlarged. The patient was kept undersurveillance in the vascular unit and arteriographywas planned for the following day. During the night,the patient collapsed but responded to more IVcrystalloid and was immediately transferred to theradiological unit. While the patient was being pre-pared for arteriography, a new CT scan showed thehematoma had now increased in size and had spreadto the intraperitoneal space, filling the peri-hepaticand peri-splenic areas as well as the pelvis.The patient underwent selective arteriography tovisualize the stenosis caused by compression of thecœliac axis, to localize the bleeding pancreaticoduo-denal artery aneurysm and to proceed to treatment byembolization. Under local anesthesia, a 5-F introduce

Locoregional versus general anesthesia in carotid surgery: Is there an impact on peri-operative myocardial ischemia? Results of a prospective monocentric randomized trial.

PURPOSE: The incidence of cardiac morbidity and mortality in patients who undergo carotid surgery ranges from 0.7% to 7.1%, but it still represents almost 50% of all perioperative complications. Because no data are available in literature about the impact of the anesthetic technique on such complications, a prospective randomized monocentric study was undertaken to evaluate the role of local anesthesia (LA) and general anesthesia (GA) on cardiac outcome. METHODS: From November 1995 to February 1998, 107 patients were classified by the cardiologist as cardiac patients (IHD; history of myocardial infarction, previous myocardial revascularization procedures, or myocardial ischemia documented by means of positive electrocardiogram [ECG] stress test results) or noncardiac patients (NIHD; no history of chest pain or negative results for an ECG stress test). The patients were operated on after the randomization for the type of anesthesia (general or local). Continuous computerized 12-lead ECG was performed during the operative procedure and 24 hours postoperatively. The end points of the study were ECG modifications (upsloping or downsloping more than 2 mm) of the sinus tachycardia (ST) segment. RESULTS: Fifty-five patients were classified as IHD, and 52 were classified as NIHD. Twenty-seven of the 55 IHD patients (49%) and 24 of 52 NIHD patients (46%) were operated on under GA. Thirty-six episodes of myocardial ischemia occurred in 22 patients (20.5%). Episodes were slightly more frequent (58%) and longer in the postoperative period (intraoperative, 10 +/- 5 min; postoperative, 60 +/- 45 min; P <. 001). As expected, the prevalence of myocardial ischemia was higher in the group of cardiac patients than in noncardiac group (15 of 55 patients [27%] vs 7 of 52 patients [13%]; P <.02). By comparing the two anesthetic techniques in the overall population, we found a similar prevalence of patients who had myocardial ischemia (GA, 12 of 52 [23%]; LA, 10 of 55 [18%]; P = not significant) and a similar number of ischemic episodes per patient (GA, 1.5 +/- 0.4; LA, 1.8 +/- 0.6; P = not significant). Episodes of myocardial ischemia were similarly distributed in intraoperative and postoperative periods in both groups. It is relevant that under GA, IHD patients represent most of the population who suffered myocardial ischemia (83%). On the contrary, in the group of patients operated on under LA, the prevalence was equally distributed in the two subpopulations. CONCLUSION: The results confirm the different hemodynamic impact of the two anesthetic techniques. Patients who received LA had a rate of myocardial ischemia that was half that of patients who had GA. The small number of cardiac complications do not permit us to make any definitive conclusion on the impact of the two anesthetic techniques on early cardiac morbidity, but the relationship between perioperative ischemic burden and major cardiac events suggests that LA can be used safely, even in high-risk patients undergoing carotid endarterectomy

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

Could new dual layer carotid artery stent provide a safe carotid artery stenting (CAS) treatment in patients with acute cerebral ischemia?

Epidemiological and observational data demonstrated that carotid artery stenosis is responsible of 5% to 7% of acute cerebral ischemia in patients hospitalized in the stroke units of emergency departments. In these cases, international guidelines recommend early carotid endarterectomy (within 2 weeks) to remove the embolic plaque because in case of hemodynamically significant stenosis a recurrent neurologic symptom may occur in more than 20% of the cases in the first 24 h [1]. On the other side, prompt carotid endarterectomy, in well-selected patients, brings no more risk if compared to elective carotid surgery [2]. In the last decade, carotid artery stenting has gained a relevant role in treatment of carotid artery stenosis both asymptomatic and symptomatic and nowadays is an alternative to carotid endarterectomy in patients with appropriate anatomical condition. The rapid and widespread diffusion of carotid stenting mainly depends on its low invasiveness. Nevertheless, in case of early symptomatic carotid plaque, carotid artery stenting did not reach the same diffusion if compared to carotid endarterectomy because the results of the all trials comparing carotid stenting and surgery in this setting, disclosed worse results of the former. A recent review of the results of four randomized trials [3] showed that only 2.3% of the patients underwent carotid stenting (287/4187) within 7 days from sentinel event and perioperative complication rate was 8.6% vs. 1.3% in 223 patients who underwent carotid surgery in the same interval of time (RR (95% IC): 6.74 (2.07-21.92); p=0.002). Yet, the results of carotid stenting in early symptomatic patients coming from high volume centers disclose a perioperative stroke/death rates ranging from 5% to 2.7% operated on within 14 days [4-7]. These data demonstrate room for carotid stenting in the acute setting. Nonetheless, remains concern to treat by stenting a recently symptomatic carotid plaque due to the possibility of prolapse of carotid plaque from the stent struts and the risk of cerebral hemorrhage related to the double antiplatelet therapy after stent implantation. Regarding the occurrence of prolapse of portion of plaque through the struts of the stent, a new generation of carotid stent entered into the clinical practice (dual layer carotid stents). Yet, their double layer of mesh or membrane reduces the dimensions of the struts up to less than 200-micron permanently covering thrombus or portion of plaque, as demonstrated by Optical Coherence Tomography in vivo studies [8]. Recent papers report the effectiveness of these stents in prevention of the embolization just after stent implantation both in asymptomatic and in symptomatic patients [9,10]. However, the use of this type of stents to treat acutely symptomatic carotid plaque is scant in the literature, in fact, there are only sporadic and small series, but results from these reports seem promising, as peri-procedural embolic complications are low [11,12]. Finally, the risk of a high occurrence of cerebral hemorrhage due to double antiplatelet therapy after stenting in the setting of a recently symptomatic stenosis, the available data of real world clinical practice in the literature demonstrate that this risk is overestimated. In fact, post-procedural brain hemorrhage in three papers dealing with carotid stenting in the setting of patients recently symptomatic related to carotid plaque (within 14 days from index event) ranges from 0% to 2.2%, compared to 0% to 3% in patients operated on later than 14 days [4-7]. In conclusion, the answer to the abovementioned question is probably yes. It is time to check the effectiveness of this new generation stents by a multicenter register first, and by a prospective multicenter randomized trial comparing surgery to implantation of these new stents, thereafter