An update of the Italian Stroke Organization-Stroke Prevention Awareness Diffusion Group guidelines on carotid endarterectomy and stenting: a personalized medicine approach

Although proof-based medicine has generated much valid evidence for the drawing up of guidelines and recommendations for best clinical practice in symptomatic and asymptomatic carotid stenosis, whether and when it is better to employ endarterectomy or stenting as the intervention of choice still remain matters of debate. Moreover, guidelines have been targeted up to now to the 'representative' patient, as resulting from the statistical analyses of the studies conducted on the safety and efficacy of both interventions as well as on medical therapy alone. The Italian Stroke Organization (ISO) and Stroke Prevention and Awareness Diffusion (SPREAD) group has thus decided to update its statements for an 8th edition. To this end, a multidisciplinary team of authors representing Italian scientific societies in the neurology, neuroradiology, vascular and endovascular surgery, interventional cardiology, and general medicine fields re-examined the literature available on stroke. Analyses and considerations on patient subgroups have allowed to model the risks/benefits of endarterectomy and stenting in the individual. Accordingly, the guideline's original methodology has been revised to follow the new SIGN (Scottish Intercollegiate Guideline Network) Grade-like approach, integrating it with new considerations on Precision, or Personalized Medicine. Therefore, this guideline offers recommendations on precision medicine for the single patient, and can be followed in addition to the more standard guidelines.

Continuous monitoring of noise levels in the Gulf of Catania (Ionian Sea). Study of correlation with ship traffic.

Acoustic noise levels were measured in the Gulf of Catania (Ionian Sea) from July 2012 to May 2013 by a low frequency (<1000Hz) hydrophone, installed on board the NEMO-SN1 multidisciplinary observatory. NEMO-SN1 is a cabled node of EMSO-ERIC, which was deployed at a water depth of 2100m, 25km off Catania. The study area is characterized by the proximity of mid-size harbors and shipping lanes. Measured noise levels were correlated with the passage of ships tracked with a dedicated AIS antenna. Noise power was measured in the frequency range between 10Hz and 1000Hz. Experimental data were compared with the results of a fast numerical model based on AIS data to evaluate the contribution of shipping noise in six consecutive 1/3 octave frequency bands, including the 1/3 octave frequency bands centered at 63Hz and 125Hz, indicated by the Marine Strategy Framework Directive (2008/56/EC).

Differential Influence of Carotid Stenosis and White Matter Disease on Motor and Cognitive Activation.

BACKGROUND: Cognitive and motor performance can be supported, especially in older subjects, by different types of brain activations, which can be accurately studied by functional magnetic resonance imaging (fMRI). Vascular risk factors (VRFs) are extremely important in the development of cognitive impairment, but few studies have focused on the fMRI cortical activation characteristics of healthy subjects with and without silent cerebrovascular disease including white matter hyperintensities (WMH) and carotid stenosis (CS) performing cognitive tasks. METHODS: Thirty-five volunteers with and without asymptomatic unilateral carotid stenosis above 70% and variable degrees of WMH underwent performance of a simple motor and cognitive task during an fMRI session. RESULTS: While the performance of the motor task resulted in a cortical activation dependent of age but not of WMH and carotid stenosis, performance of the cognitive task was accompanied by a significantly increased activation independently correlated with age, presence of WMH as well as of carotid stenosis. CONCLUSIONS: in this study, cognitive domains regulating attention and working memory appear to be activated with a pattern influenced by the presence of carotid stenosis as well as by white matter hyperintensities. The impairment of these cognitive abilities is of high relevance in Alzheimer's disease pathology. The fMRI pattern shown in patients with asymptomatic but significant carotid stenosis might be related to chronic cerebrovascular hypoperfusion, a critical pathophysiological mechanisms in AD. In these patients, carotid endoarterectomy should be considered also for AD prevention and might be recommended.

Physician-initiated prospective Italian Registry of carotid stenting with the C-Guard mesh-stent: the IRON-Guard registry. Rationale and design.

According to the World Health Organization, every year, 5 million peoples die for stroke and another 5 million are permanently disabled. Although there are many causes of acute stroke, a common treatable cause of acute stroke is atheromatous narrowing at the carotid bifurcation. Carotid endarterectomy is still the standard of car, even if carotid artery stenting (CAS) has become an effective, less invasive alterantive. Unfortunately, CAS procedure is not yet perfect; regardless the use of an embolic protection device (EPD), percutaneous treatment has been correlated with a risk of cerebral ischemic events related to distal embolization. The objective of the IRON-Guard Registry is to evaluate the clinical outcome of treatment by means of stenting with the C-Guard (InspireMD, Boston, MA, USA) in subjects requiring CAS due to significant extracranial carotid artery stenosis with a physician-initiated, Italian, prospective, multicenter, single-arm study. A total of 200 enrolled subjects divided over different centers are planned to be enrolled. CAS will performed by implanting of C-Guard stent. Procedure will be performed according to the physician's standard of care. Standard procedures will be followed based on the Instructions for Use, for the C-Guard device of Inspire. The primary endpoint of this study is the 30-day rate of major adverse events (MAE), defined as the cumulative incidence of any periprocedural (≤30 days postprocedure) death, stroke or myocardial infarction. Secondary endpoints are rate of late ipsilateral stroke (31 through 365 days), system technical success, device malfunctions, major adverse events (MAEs), serious device-related and procedure-related adverse events, target lesion revascularization, and in-stent restenosis rates.

A new ethical and medico-legal issue: vascular surgery and the postoperative cognitive dysfunction.

Patients undergoing major surgery are at risk for postoperative cognitive dysfunction (POCD). The consciousness of the POCD arises new ethical and medico-legal issues that should be identified, managed and, if possible, prevented. Elderly patients still represent a real challenge for physicians and medical science. This challenge can be surmounted not only through technical progress but also by safeguarding the correct ethical behavior at the base of each relationship between a patient and his physician. Effective communication with the elderly patient is a prerequisite for clear and complete information, involving family members and caregivers when necessary. In every case, the identification of patients with pre-existing risk factors of POCD, shortening the period of time preceding the surgery and a proper technique of the procedure as well as physical and intellectual exercises, nutrition and medication play an important role in decreasing the incidence of neurocognitive deficits in the elderly.

An atypical case of contrast-induced encephalopathy after carotid artery stenting.

Neurotoxicity caused by contrast agents is a rare and less known complication of percutaneous carotid and coronary interventions. Radiological signs, such as cortical enhancement and brain edema, are of utmost importance in diagnosis. A 70-year-old female patient underwent left carotid artery stenting to treat a post-traumatic asymptomatic carotid dissection. Three hours after intervention, a mild aphasia developed with no brain alteration on diffusion-weighted magnetic resonance imaging (DW-MRI). Twelve hours after intervention, symptoms worsened but a new DW-MRI scan showed no pathological findings. Since a contrast-induced encephalopathy was diagnosed, fluid administration was raised to 2 mL/kg/h and the neurological status progressively improved. In the following three days, neurological deficit slowly regressed. Two weeks after intervention, aphasia had disappeared and a further cerebral DW-MRI scan detected no brain alteration. Typical radiological signs are described in association to contrast encephalopathy. Nevertheless, vascular interventional physicians should be well aware of this condition also when those signs are lacking.

Acute left arm ischemia associated with floating thrombus in the proximal descending aorta: combined endovascular and surgical therapy.

Free floating thrombus in the proximal descending aorta is an uncommon and dangerous condition that can be associated with acute peripheral embolization. The few cases described were solved with surgical and/or medical therapy. We report the case of a patient with acute left arm ischemia secondary to the presence of floating thrombus in the proximal descending aorta extending into the left subclavian artery, solved with combined endovascular and surgical therapy. Treatment was successfully performed with thrombembolectomy combined with temporary deployment, into the descending aorta, of a Wallstent in a "basket-fashion" to avoid distal embolization secondary to thrombus fragmentation. At 1 year follow-up the patient remained symptom-free.

SPREAD Italian Guidelines for stroke. Indications for carotid endarterectomy and stenting.

This multidisciplinary guideline provides an overview of the current evidence on the benefits obtained by endoarterectomy and stenting for the surgical treatment of patients with symptomatic and asymptomatic carotid stenosis. A hundred forty-six authors, 37 Italian scientific societies and two Italian patients' associations participated in drafting the Stroke Prevention and Educational Awareness Diffusion (SPREAD) document, which has become the national guideline for the prevention and treatment of stroke in Italy. For the surgical therapy section of this document, the main trials on carotid endoarterectomy and stenting were critically reviewed following The Scottish Intercollegiate Guideline Network Oxford Centre for Evidence-Based Medicine methodology in order to formulate recommendations and syntheses for these procedures. The final document was peer reviewed and approved by all the participants. Recommendations and syntheses are presented for the referral of patients to either carotid endoarterectomy or stenting on the basis of whether carotid stenosis is symptomatic or asymptomatic, on the presence of various risk factors such as degree of arterial narrowing, and on concomitant pathology (cardiopathy and acute stroke).

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.

Early carotid endarterectomy after ischemic stroke: the results of a prospective multicenter Italian study.

OBJECTIVES: To evaluate safety of early carotid endarterectomy (CEA) in patients with acute brain ischemia presenting to the emergency department stroke units (EDSU). METHODS: The 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. RESULTS: The 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. CONCLUSION: Our 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.

Vascular knowledge in medieval times was the turning point for the humanistic trend.

OBJECTIVE: Knowledge of the history of our surgical specialty may broaden our viewpoint for everyday practice. We illustrate the scientific progress made in medieval times relevant to the vascular system and blood circulation, progress made despite prevailing religious and philosophical dogma. METHODS: We located all articles concerning vascular knowledge and historical reviews in databases such as MEDLINE, EMBASE and the database of abstracts of reviews (DARE). We also explored the database of the register from the French National Library, the French Medical Inter-University (BIUM), the Italian National Library and the French and Italian Libraries in the Vatican. All data were collected and analysed in chronological order. RESULTS: Medieval vascular knowledge was inherited from Greek via Byzantine and Arabic writings, the first controversies against the recognized vascular schema emanating from an Arabian physician in the 13th century. Dissection was forbidden and clerical rules instilled a fear of blood. Major contributions to scientific progress in the vascular field in medieval times came from Ibn-al-Nafis and Harvey. CONCLUSION: Vascular specialists today may feel proud to recall that once religious dogma declined in early medieval times, vascular anatomic and physiological discoveries led the way to scientific progress.

What is the best management for abdominal aortic aneurysm in patients at high surgical risk? A single-center review.

AIM: To determine the best treatment for high-risk patients with abdominal aortic aneurysms (AAA). METHODS: We reviewed a prospective database of all patients who underwent conventional (OPEN) or endovascular aneurysm repair (EVAR) between January 1998 and December 2002. Patients were preoperatively classified according to the American Society of Anesthesiology (ASA). Comorbidities and medical risk factors were categorized according to the Ad Hoc Committee on Reporting Standards. Perioperative mortality and morbidity rates were analyzed according to the type of surgical procedure (OPEN vs EVAR) and ASA class. Patients in ASA classes I and II were excluded. Continuous data were expressed as mean +/- standard deviation. All data were calculated using the cumulated actuarial method of event outcome probability. Kaplan-Meier curves were constructed and the log-rank statistic and chi squared test were used for comparative data. P values less than 0.05 were considered to indicate statistical significance. RESULTS: Of the total 375 patients who underwent AAA repair, 168 (45%) belonged in ASA classes III and IV (85 submitted OPEN and 83 EVAR to repair). Among general risk factors only coronary artery disease differed significantly between the 4 groups (P = 0.04). The Bonferroni correction identified a statistically significant difference between ASA classes III and IV for the OPEN technique and for EVAR (P = 0.007 and P = 0.012). Neither 30-day morbidity or mortality differed significantly according to ASA class and surgical technique. The median follow-up was 19 months (range 5-60 months). The overall survival was 78% at 60 months. Survival rates during follow-up differed significantly in the 2 risk classes (ASA III 5/123, 4% vs ASA IV 9/38, 24%), (P = 0.0001). The deaths in the ASA class 4 patients (12/14; 86%) were caused by preexisting medical comorbidities (in 9 patients cardiovascular, in 1 cancer and in 2 cirrhosis). CONCLUSIONS: Except patients with small aneurysms (< 6 cm), in whom the risk of death at 1-year due to comorbidities exceeds the risk of a ruptured aneurysm, all patients at high surgical risk (ASA class IV) benefit from AAA repair. Patients with small aneurysms must undergo strict surveillance to assess growth and aneurysmal wall changes to prevent unexpected rupture.

[Atheroembolic syndrome due to isolated infrarenal abdominal aorta stenosis and endovascular treatment: case report and review of literature]. / Ateroembolia da lesione stenosante isolata dell'aorta addominale sottorenale e trattamento endovascolare: caso clinico e revisione della letteratura.

One of the most common source of lower extremity atheroembolization is the aorta and particularly the infrarenal segment. Complex atherosclerotic plaque can lead the patient to gangrene and major amputation. When the origin of embolization is a focal lesion, endoluminal methods could be an alternative to surgical treatment. Although the experience with aortic stent is limited, the results obtained so far seem to be encouraging. The case of a mid-age heavy smoker woman with a history of the abrupt onset of painfull cyanotic toes in the left foot and subsequent complete gangrene of the first digit in the same foot is herein reported. Angiography and CT scan revealed an high-grade calcified aortic infrarenal plaque. Because of the discrete characteristic of the lesion, an endovascular approach with a Palmaz stent was elected. The stenosis was successfully treated: the patient experienced the complete resolution of the toe painfull cyanosis within 3 months, the stent remained patent through a 24 months follow-up and no subsequent embolic episodes were observed.

Dysregulated apoptosis in primary varicose veins.

OBJECTIVE: Programmed cell death plays a critical role in various physiological processes. To investigate its possible pathogenic role in primary varicose veins we studied histological changes in surgical specimens from human varicose veins. In varicose and healthy veins, we also determined the number of cells in apoptosis, and investigated mediators regulating the intrinsic apoptotic mitochondrial pathway (Bax and caspase 9). METHODS: A total 23 varicose veins were obtained from 18 patients undergoing lower-extremity varicose vein surgery for primary varicose disorders. We used nine healthy veins obtained from nine patients undergoing distal arterial bypass grafting surgery as controls. The venous segment analysed was the distal part of the greater saphenous vein. Specimens for histological examination were stained with hematoxylin and eosin, trichromic and Victoria blue. Cell apoptoses and mediators of the mitochondrial pathway were detected in the media by immunohistochemistry using antibodies to peroxidase in situ apoptosis, Bax and caspase 9. Results were expressed as indexes for the three antibodies tested. The Mann-Whitney test was used to compare the results obtained in the two groups. RESULTS: Varicose vein specimens exhibited a more disorganised architecture than healthy veins and showed an increased number of collagen fibres and a decrease in the density and size of elastic fibres. All anti-apoptotic antibodies tested detected significantly fewer immunoreactive cells in tissue sections from the media of varicose veins than of healthy veins (peroxidase in situ, varicose veins (VV) median 2.4% (inter-quartile range 1.6-3.9) versus control (C) 14% (IQR 8.8-19); Bax, VV 1.4% (IQR 0.36-2.4) versus C 11% (IQR 7.6-15); and caspase 9, VV 1.7% (IQR 0.06-3.4) versus C 10% (IQR 9.1-12), P=0.0001 (Mann-Whitney test). CONCLUSION: Apoptosis is down regulated in the medial layer of varicose veins. This dysregulation of the cellular mechanism that maintains normal tissue integrity is mediated through the intrinsic apoptotic pathway and may be among the causes of primary varicose veins.

Interposition vein cuff and intimal hyperplasia: an experimental study.

OBJECTIVE: There is some evidence to suggest that prosthetic distal bypass graft patency can be improved, and the risk of intimal hyperplasia diminished, by interposing a distal vein cuff. We studied intimal remodeling in an end-to-side distal prosthetic anastomosis constructed with and without a vein cuff. METHODS: Twenty-four prosthetic bypasses were constructed with (N=12) or without (N=12) a distal vein cuff in 12 pigs. At 10 weeks, the 20 anastomoses and adjacent arteries from the surviving 10 pigs were studied by histology, immunohistochemistry and morphometry. RESULTS: Intimal hyperplasia was significantly less on all zones of the arterial floor and all suture zone of arteries anastomosed with a vein cuff than within arteries anastomosed without a vein cuff (0.11 versus 0.34; p=0.001 and 0.35 versus 1.19; p=0.0001, respectively). Intimal hyperplasia was also more prominent within the vein cuff than within the recipient artery, with or without a vein cuff (1.35 versus 0.38; p=0.0001). CONCLUSION: An interposition vein cuff at the distal anastomosis between a prosthesis and an artery alters the distribution of intimal hyperplasia. By acting as an expansion chamber where intimal hyperplasia can develop harmlessly, the vein cuff may protect the arterial anastomosis from stenosis.

Aneurysm of the pancreaticoduodenal arteries with a celiac trunk lesion: current management.

OBJECTIVE: We report a ruptured aneurysm of the pancreaticoduodenal arteries without acute or chronic pancreatitis but associated with a median arcuate ligament division that compressed the celiac trunk, an exceptional event, thus far described in only 11 patients. We also conducted a targeted review to seek information about clinical presentation, to hasten diagnosis and assist in therapeutic management. METHODS: A 54-year-old man with retroperitoneal hemorrhage associated with an arcuate ligament division, documented on computed tomographic scans, underwent diagnostic arteriography and embolization to treat the bleeding aneurysm. In a second elective operation the causative arcuate ligament was sectioned to decompress the celiac artery, to prevent aneurysm recurrence. RESULTS: Embolization stopped the aneurysmal bleeding, and arteriograms showed that surgical sectioning resolved the celiac trunk stenosis. At 1-year follow-up the patient had no signs of complications or recurrence of disease. CONCLUSION: Ruptured aneurysm of the pancreaticoduodenal arteries associated with stenosis of the celiac trunk is a surgical emergency. Although a literature review disclosed no significant difference between outcomes after open surgery and radiologic arterial embolization, our experience in this case suggests immediate embolization during arteriography as the most effective treatment. Later, to prevent recurrence, the arcuate ligament should be surgically sectioned and the celiac artery stenosis treated.

Patency and limb salvage after distal prosthetic bypass associated with vein cuff and arteriovenous fistula.

OBJECTIVE: To assess the usefulness of vein cuff with or without arteriovenous fistula interposition as adjuvant techniques for improving patency and limb salvage in patients undergoing femorodistal bypass surgery using prosthetic grafts. METHOD: We undertook a retrospective study of 65 consecutive patients treated over a 5-year period with 67 prosthetic femorodistal bypasses with vein cuff, in whom an arteriovenous fistula was constructed at the distal anastomosis in 35. Patients were followed for a median time period of 23 months. RESULTS: Primary patency rates were 68, 53 and 44% at 1, 2 and 3 years, respectively. The corresponding figures for secondary patency, limb survival and patients' survival were 73, 64 and 58% for 1 year, 78, 76 and 73% for 2 years and 72, 66 and 63% for 3 years. None of the criteria analyzed influenced patency or limb salvage on prosthetic bypasses using adjuvant techniques. No statistical differences were found between patency and limb salvage rates in patients for whom the vein cuff was constructed with or without an arteriovenous fistula. But patients who managed with a supplementary arteriovenous fistula had significantly fewer distal residual arteries in the limb (p=0.001). CONCLUSION: Although results in patients treated with adjunctive techniques differed little from those in patients treated with direct prosthetic bypasses procedures, those who eventually had an adjunctive procedure had inferior runoff. This indicates that an arteriovenous fistula might be a valuable supplement in patients with poor runoff who have distal revascularisation using a prosthetic graft.

Popliteal artery entrapment associated with cannabis arteritis.

OBJECTIVE: To report popliteal artery entrapment in a patient with distal necrosis and cannabis-related arteritis, two rare or exceptional disorders never described in association. To conduct a targeted review and especially to seek information on the clinical presentation with characteristics specific to each disorder so as to hasten the diagnosis and choose appropriate management. MATERIAL AND METHODS: A 19-year-old man who presented with plantar claudication associated with necrosis in a toe underwent diagnostic arteriography and surgery for popliteal artery entrapment type III. RESULTS: Surgical clearance resolved the popliteal artery entrapment but left the clinical symptoms unchanged. Closer questioning disclosed a history of cannabis consumption and intravenous vasodilatory therapy was started. After the 21-day course of vasodilator agents the pain disappeared and the toe necrosis regressed. The patient stopped taking cannabis and had no signs of recurrence. CONCLUSION: Whereas a popliteal artery entrapment, albeit a rare event, is well described and responds to standardized treatment, popliteal artery entrapment associated with cannabis-induced arteritis is an exceptional event that could confuse management. Because young people-the age group mainly at risk for popliteal artery entrapment-increasingly use cannabis, cannabis arteritis could become a more frequent event associated with other arterial disorders that may confuse the diagnosis and complicate management. Our experience in a young patient suggests that coexisting popliteal artery entrapment and distal necrosis in a young patient should raise a strong suspicion of an associated vascular disorder possibly related to cannabis consumption. Intravenous vasodilatation treatment is successful provided that cannabis use is discontinued.