Antiplatelet Therapy in Carotid Artery Stenting and Carotid Endarterectomy in the Asymptomatic Carotid Surgery Trial-2.

OBJECTIVE: Strokes are infrequent but potentially serious complications following carotid intervention, but antiplatelet therapy can reduce these risks. There are currently no specific guidelines on dose or duration of peri-procedural antiplatelet treatment for patients undergoing carotid intervention. Within the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), this study aimed at assessing the current use of antiplatelet therapy before, during, and after CEA and CAS in patients with asymptomatic carotid stenosis. METHODS: Questionnaires were sent to ACST-2 collaborators seeking information about the use of antiplatelet therapy during the pre-, peri-, and post-operative periods in patients undergoing carotid intervention at 77 participating sites and also whether sites tested for antiplatelet therapy resistance. RESULTS: The response rate was 68/77 (88%). For CAS, 82% of sites used dual antiplatelet therapy (DAPT) pre-operatively and 86% post-operatively with a mean post-procedural duration of 3 months (range 1-12), while 9% continued DAPT life-long. For CEA only 31% used DAPT pre-operatively, 24% post-operatively with a mean post-procedural duration of 3 months (range 1-5), while 10% continued DAPT life-long. For those prescribing post-procedural mono antiplatelet (MAPT) therapy (76%), aspirin was more commonly prescribed (59%) than clopidogrel (6%) and 11% of centres did not show a preference for either aspirin or clopidogrel. Eleven centres (16%) tested for antiplatelet therapy resistance. CONCLUSION: There appears to be broad agreement on the use of antiplatelet therapy in ACST-2 patients undergoing carotid artery stenting and surgery. Although evidence to help guide the duration of peri-procedural antiplatelet therapy is limited, long-term treatment with DAPT appears similar between both treatment arms.

Transealing: a novel and simple technique for embolization of type 2 endoleaks through direct sac access from the distal stent-graft landing zone.

OBJECTIVE: Type 2 endoleak (T2EL) is the Achilles' heel of endovascular abdominal aortic aneurysm repair. Experience with transealing, an alternative technique for the treatment of T2ELs, is described. METHODS: The outcome of a group of patients treated with transealing has been reviewed. Femoral access was obtained with a 9-Fr sheath. A super-stiff guide wire and a stiff hydrophilic wire were placed inside the stent-graft and a Piton GC catheter inserted. The stiff hydrophilic wire was retrieved to allow the catheter to regain its curvature and the catheter tip was placed against the iliac wall, at the edge of the stent-graft. The hydrophilic wire was then forced between the stent-graft and arterial wall into the sac. A 5/6-Fr introducer was inserted inside the sac and angiography was performed to evaluate the leak. Coils, cyanoacrylate, or fibrin glue were deployed. After removal of the catheters, the iliac limb was ballooned. RESULTS: Seventeen patients were treated between February 2009 and April 2013. It was possible to access the aneurysm in 16/17 attempts. One patient treated with acrylic glue suffered from colon ischemia. One intraoperative secondary type 1b endoleak was treated with an iliac extension. Mean follow-up was 21.5 months. Three months of follow-up were completed in 14 patients with a 53% freedom from endoleak rate. At 1 year, the rate was 45%. During the study period, there was one surgical conversion, one aneurysm growth, and one re-embolization procedure. The remaining leaks remained stable. CONCLUSIONS: This study shows that transealing is feasible and represents a valid alternative in selected patients. The advantages of this technique are mainly its low invasiveness, reduced costs, and ease of use.

Delayed open conversion after endovascular abdominal aortic aneurysm: device-specific surgical approach.

OBJECTIVES: Despite several advances in endoluminal salvage for failed endovascular abdominal aortic repair (EVAR), in our experience an increasing number of cases necessitate delayed open conversion (dOC). METHODS: EVAR patients requiring delayed (>30 days) conversion were prospectively collected in a computerized database including demographics, details of aortoiliac anatomy, procedural and clinical success, and postoperative complications. RESULTS: Between 2005 and 2011, 54 patients were treated for aortic stent-graft explantation. Indications included 34 type I and III endoleaks, 13 type II endoleaks with aneurysm growth, 4 cases of material failures, and 3 stent-graft infections. All fit-for-surgery patients with type I/III endoleak underwent directly dOC. Different surgical approaches were used depending on the type of stent-graft. Overall 30-day mortality was 1.9%. Overall morbidity was 31% mainly due to acute renal failure (13 cases). Mean hospitalization was 6 days (range, 5-27 days). Overall survival at mean follow-up of 19 months was 78%. CONCLUSIONS: In recent years, the use of EVAR has increased dramatically, including in young patients regardless of their fitness for open repair. dOC after endovascular abdominal aortic aneurysm seems to be a lifesaving procedure with satisfactory initial and mid-term results.

Diagnostic laparoscopy for early detection of acute mesenteric ischaemia in patients with aortic dissection.

INTRODUCTION: Recognition of acute mesenteric ischaemia (AMesI) in patients with aortic dissection (AoD) may be a challenge and exploratory laparotomy is often performed. METHODS: We retrospectively analysed our experience with the use of diagnostic laparoscopy (DL) for the early detection of AMesI in patients with AoD, either undergoing medical treatment or after open/endovascular interventions. RESULTS: Between 2004 and 2011, 202 consecutive AoDs were treated in our centre (71 acute type A AoD; 131 acute and chronic type B AoD). Among the 17 (8.4%) patients in which AMesI was suspected, nine (52.9%) were selected for DL. Three DLs were performed during medical treatment of patients with acute type B AoD, six after treatment of AoD (both surgical and endovascular). Three second-look DLs were also performed. Eight DLs were negative, three showed AMesI and the patients underwent successful emergent revascularisation. One DL was not conclusive and laparotomy was required. Among the eight patients not submitted to DL, one case of bowel infarction was recorded. CONCLUSIONS: In our series DL was feasible and safe. The low invasiveness and repeatability were the main advantages. Although additional experience is mandatory, DL seems a promising technique for the detection of AMesI in patients with AoD.

A new idea for a safer approach to the supra-aortic trunks: the Piton™ catheter.

Carotid artery disease is among the most common causes of stroke, and stroke is the third leading cause of death in industrialized countries. Thus the personal health and socioeconomic burden of carotid artery disease is significant. Carotid artery disease accounts for approximately 5-12% of new strokes in patients amenable to revascularization therapy. Atherosclerosis is the main reason for stroke and accounts for approximately one third of all cases. Carotid stenting is nowadays considered a valid standard alternative to surgical carotid endarterectomy, especially in patients having a high perioperative risk. The first carotid balloon angioplasty was carried out in 1979 and the first carotid balloon-expandable bare metal stents were implanted 10 years later, in 1989. However, carotid stenting at that time was associated with major complications, due to extrinsic compression and subsequent to the steel stents used. The Piton™ GC (carotid guide catheter) is intended to facilitate the introduction and placement of interventional devices (e.g., guidewires, stent delivery systems, dilation balloons, angiographic- or micro-catheters, etc.) into the human vasculature to treat vascular obstructive disease, including but not limited to the supra-aortic vessels.

Mechanical thrombectomy in in-stent restenosis: preliminary experience at the iliac and femoropopliteal arteries with the Rotarex System.

AIM: Iliac and femoropopliteal arterial stenting remains controversial due to frequent restenosis. This study aims to evaluate the efficacy of a mechanical rotational thrombectomy procedure with the Rotarex Mechanical Thrombectomy System (Straub Medical, Wangs, CH) and percutaneous transluminal angioplasty (PTA) in terms of technical success, patency rates and limb salvage. METHODS: From May 2006 to March 2010, 32 selected patients with sub-acute or chronic in-stent restenosis at the iliac or femoropopliteal arteries were treated with a Rotarex and then PTA procedure. RESULTS: Technical success was 100%. Intra-procedural complications included a superficial femoral artery (SFA) dissection (1), SFA (1) and external iliac (1) perforations and a groin hematoma (1). There was no incidence of embolization in this series. One patient required reintervention (3.1%); an attempted surgical bypass and amputation. Secondary reinterventions were required in 17 patients (53.1%). Limb salvage rate at 12 months was 90.6%. Primary patency at 30 days was 96.8%. Primary, primary assisted and secondary patency rates at 6 months were 75%, 75% and 89.6% and at 12 months were 58.1%, 58.1% and 75.5%, respectively. Late mortality was 18.75% at an average follow-up of 13.1 months (3-45) due to the severe disease state of these patients.. CONCLUSION: This treatment seems promising in terms of technical success and embolization risk. Reinterventions are frequently required but mid-term limb salvage rates are encouraging. Larger, randomised studies are needed to determine the cost/benefit advantage and long-term results.

Management of thoracic endograft infection.

Thoracic endovascular aortic repair (TEVAR) has emerged as a promising, less invasive alternative to conventional open surgery for the treatment of thoracic aortic pathology. Most surveillance after TEVAR concentrates on the technical aspects of the procedure, including endoleak, device migration and endograft rupture; so far, the knowledge on endograft infectious complications is limited to anecdotal reports. Several etiopathogenetic factors may play a role in thoracic endograft infections (TEIs), including perioperative contamination, hematogenous seeding, and local bacterial translocation. Moreover, fistulization with the esophagus or the bronchial tree is a common mechanism of secondary TEI, and it represents a dramatic event requiring a multidisciplinary management. Risk factors assessment and prevention have a key role in avoiding the development of new TEIs. When a TEI is established, treatment is demanding, and includes several medical therapies associated with various surgical options. Patients are usually severely compromised by sepsis, and in most cases they are considered unfit for surgery for general clinical conditions or local concerns. Thus, results of different therapeutic strategies for TEI are still burdened with very high morbidity and mortality. In this paper, we reviewed the English literature regarding the main strategies proposed for operative management of TEI, we reported and analyzed our personal series of 7 patients treated at our institution for TEI from 1999 to 2009, and we summarized results from the data collected during a recent Italian multicenter national survey, performed to investigate aortoesophageal and aortobronchial fistulae treated with TEVAR or developed following TEVAR.

Demonstration of the Adamkiewicz artery by multidetector computed tomography angiography analysed with the open-source software OsiriX.

OBJECTIVE: To evaluate the feasibility of the Adamkiewicz artery (AKA) detection by multidetector computed tomography (CT) data analysis without the need of a dedicated workstation, using low-cost hardware and the freeware OsiriX. METHODS: CT scans of 67 patients undergoing a thoracic or thoraco-abdominal aortic procedure between April 2006 and August 2008 were evaluated with respect to detection rate and AKA level and side using the OsiriX software version 3.2 on Mac OS X computer and compared to results obtained by standard workstation analysis, in a fully blinded analysis. The results were also compared with data compiled from a review of the English-language literature on this topic. RESULTS: (1) AKA identification showed a substantial agreement of 85.07% between the methods (k=0.636). (2) The comparison of AKA level showed a substantial agreement (weighted k=0.661), with consensus in 70.14%. (3) From the literature review, we found that recognition of the AKA was achieved in 466 of 555 cases (83.96%). (4) In 384 (83.3%) cases the AKA originated from a left intercostal artery. (5) The proposed method and literature-compiled data showed a similar AKA level distribution. CONCLUSIONS: Noninvasive AKA location with open-source software and low-cost hardware is feasible. The OsiriX software allows to effectively navigate through CT data not only to study the aorta, but also to detect the AKA, as in the case of the standard method and the literature data. Its availability and ease of use may contribute to make identification of the AKA part of the routine evaluation of CT scans in patients with aortic disease, even where dedicated workstations are not available, with potential benefits for planning therapeutic procedures.

Advancements in the Mo.Ma system procedure during carotid artery stenting.

AIM: The aim of this paper was to reduce the incidence of clamping intolerance, asystolia, immediate mortality and neurological complications associated with carotid artery stenting (CAS) using the Mo.Ma system (Invatec, Roncadelle Brescia, Italy) embolic protection device (EPD). METHODS: CAS was perfomed using the Mo.Ma system in 312 patients between January 2002-October 2009. From October 2008 variations to the standard technique were introduced. A total of 214 patients were treated with the standard technique, and 88 with the new technique. Improvements include the engagement of the guidewire's floppy tip through the lesion whilst the cerebral blood flow is maintained, a slow release post-dilation (1 atm/2 s), a quicker manual aspiration procedure following post-dilation, a redirection of blood flow into the external carotid artery (ECA) with the post-dilation balloon inflated in the internal carotid artery (ICA), and a further manual aspiration and the subsequent release of the Mo.Ma system. RESULTS: This study reports reduced incidence of clamping intolerance (7.9% vs. 4.5%), asystolia (0 vs. 1.9%), immediate mortality (0 vs. 0.9%) and neurological complications (1.1% vs. 3.7%). The only neurological complication associated with the new technique was a transient ischemic attack (TIA). CONCLUSIONS: The new variations of the standard Mo.Ma technique seem rational in the improvement of the safety and efficacy of CAS using an EPD, in reducing the incidence of clamping intolerance and asystolia, immediate mortality and neurological complications. This series indicates a positive trend for this revised technique, but a multicentre registry is required to validate these promising results.

In vivo and in vitro skin permeation of butyl methoxydibenzoylmethane from lipospheres.

Lipid microparticles (lipospheres) loaded with butyl methoxydibenzoylmethane (BMDBM), a widely used UV-A sunscreen agent, were prepared by melt technique and evaluated for skin permeation both in vivo, by tape stripping method, and in vitro, by a flow-through diffusion chamber. Following in vivo human skin application of an O/W emulsion containing 2% of BMDBM loaded in lipospheres, 15% of the applied sunscreen accumulated in the uppermost layers of the stratum corneum without remarkably modifying the skin permeation of the unencapsulated sunscreen. These results were found to be predicted by an in vitro methodology involving the diffusion of BMDBM through a lipophilized synthetic membrane into a hydrophilic receptor phase, simulating the viable epidermis better than an ethanolic receptor phase.

PRIAMUS--proximal flow blockage cerebral protectIon during carotid stenting: results from a multicenter Italian registry.

AIM: The aim of this Italian prospective registry was to evaluate the applicability and efficacy of the Mo.Ma Device (Invatec, Roncadelle, Italy) for the prevention of cerebral embolization during carotid artery stenting (CAS) in a real world population. METHODS: In 4 Italian centers, 416 patients (300 men; mean age 71.6+/-9 years) between October 2001 and March 2005 were enrolled in a prospective registry. Two-hundred and sixty-four symptomatic (63.46%) with >50% diameter stenosis and 152 (36.54%) asymptomatic patients with >70% diameter stenosis were included. The Mo.Ma Proximal Flow Blockage Embolic Protection System was used to perform protected CAS, achieving cerebral protection by endovascular clamping of the common carotid artery (CCA) and of the external carotid artery (ECA). RESULTS: Technical success, defined as the ability to establish protection with the Mo.Ma device and to deploy the stent, was achieved in 412 cases (99.03%). The mean duration of flow blockage was 4.91+/-1.1 min. Transient intolerances to flow blockage were observed in 24 patients (5.76%), but in all cases the procedure was successfully completed. No peri-procedural strokes and deaths were observed. Complications during hospitalization included 16 minor strokes (3.84%), 3 transient ischemic attacks (0.72%), 2 deaths (0.48%) and 1 major stroke (0.24%). This resulted in a cumulative rate at discharge of 4.56% all strokes and deaths, and of 0.72% major strokes and deaths. All the patients underwent thirty-day follow-up. At thirty-day follow-up, there were no deaths and no minor and major strokes, confirming the overall cumulative 4.56% incidence of all strokes and deaths rate, and of 0.72% rate of major strokes and deaths at follow up. In 245 cases (58.89%) there was macroscopic evidence of debris after filtration of the aspirated blood. CONCLUSIONS: This Italian multicenter registry confirms and further supports the efficacy and applicability of the endovascular clamping concept with proximal flow blockage in a broad patient series. Results match favorably with current available studies on carotid stenting with cerebral protection.

Effectiveness and safety of carotid endarterectomy under remifentanil.

AIM: The aim of this study was to evaluate the effectiveness and safety of carotid endarterectomy (CEA) with conscious sedation under remifentanil (Remifentanil anesthesia - RA) vs conventional loco-regional anesthesia (Conventional-LRA) in the current practice of a vascular surgery unit. METHODS: We introduced the ''Remifentanil-RA'' in our practice according to a two-step protocol. In the first step we performed a pilot prospective study to assess the procedure's safety and reproducibility in our setting on 60 consecutive patients with symptomatic and/or high-grade (>70%) internal carotid artery stenosis and alternately assigning them either to ''Remifentanil-RA'' or ''Conventional-LRA'' CEA. In the second step we analysed our routine operative records as to effectiveness and safety on 533 patients who consecutively underwent ''Remifentanil-RA'' CEA. We compared them with 533 age- and sex-matched historical controls who underwent ''Conventional-LRA'' CEA. RESULTS: The patients' mean age was 71.2+/-6.8 vs 71.8+/-6.1 (''Remifentanil-RA'' vs ''Conventional-LRA''). About 73% of them were male and 56% had a symptomatic carotid stenosis. Neither the pilot study nor second step comparison showed differences in outcome measures. We found only higher peri-operative nausea/ vomit (3.6% vs 0.4% ''Remifentanil-RA'' vs ''Conventional-LRA'', P<0.0002) and fewer re-operations for post-operative hematomas (3% vs 5.4% respectively, P=0.048). CONCLUSIONS: We found that ''Remifentanil-RA'' CEA was safe, effective and satisfactory. Nevertheless, with the potential problems of intubation and those already found with side effects, a randomized control trial (RCT) is needed in order to prove that this method is superior to ''Conventional-LRA'' CEA.

Effects of RGH 2202 on cognitive and motor behavior of the rat.

The behavioral activity of the thyrotropin-releasing hormone (TRH) analogue, L-6-ketopiperidine-2-carbonyl-leucyl-L-prolinamide (RGH 2202), has been studied in animal models of central neurotransmission disruption. In 24-month-old rats, repeated administration of the peptide (5 or 10 mg/kg/day, injected IP for 20 days) was followed by a facilitated acquisition of active avoidance behavior in the shuttle-box test and retention of passive avoidance reaction in a step-through passive avoidance task. Also, ambulation in an open field was increased and motor performance and co-ordination in the rotorod test was facilitated by the treatment. Scopolamine-induced amnesia was reverted by RGH 2202 in adult rats tested both in active and passive avoidance tasks. Cognitive deficits induced in rats by prenatal manipulation with methylazoxymethanol (MAM) were reduced in adulthood by repeated administration with RGH 2202. These results indicate that the TRH-analogue, RGH 2202 may improve cognitive and motor disturbances in aging or induced by central neurotransmission disruption. It is possible that the peptide is functioning, at least in part, by intervening with the central cholinergic neurotransmission.

Effect of lesions of the nucleus basalis magnocellularis and of treatment with posatirelin on cholinergic neurotransmission enzymes in the rat cerebral cortex.

The effect of 4 and 8 weeks of treatment with the thyrotropin releasing hormone (TRH), analogue posatirelin (L-6-ketopiperidine-2-carbonyl-L-leucyl-proline amide), on the changes of cholinergic neurotransmission enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), caused by lesions of the nucleus basalis magnocellularis (NBM), was investigated in the rat frontal cortex. ChAT and AChE were demonstrated with immunohistochemical and histochemical techniques, respectively associated with image analysis and microdensitometry. Monolateral and bilateral lesions of NBM area caused a significant loss of ChAT-immunoreactive nerve cell bodies in the NBM, as well as a remarkable decrease of ChAT-immunoreactive fibres and of AChE reactivity in the frontal cortex ipsilateral to the lesion or of both sides, respectively. The number of ChAT-immunoreactive nerve cell bodies in the lesioned NBM was higher in posatirelin-treated rats for 8 weeks in comparison with control NBM-lesioned rats. Moreover, the compound increased the number of ChAT-immunoreactive fibres in the frontal cortex of monolaterally and bilaterally NBM-lesioned rats at 8 weeks after lesion, but was without effect on these fibres in sham-operated rats. The same is true for AChE reactivity, developed in the neuropil of the frontal cortex, which was restored in part by an 8-week treatment with posatirelin in NBM-lesioned rats. These findings suggest that treatment with posatirelin rescues cholinergic neurons of the NBM and cholinergic projections to the cerebral cortex affected by lesioning of the NBM. The functional relevance of these observations and their possible applications should be evaluated in future studies.

Behavioral changes induced by the thyrotropin-releasing hormone analogue, RGH 2202.

The behavioral activity of the thyrotropin-releasing hormone (TRH) analogue, L-6-ketopiperidine-2- carbonyl-leucyl-L-prolinamide (RGH 2202), has been studied in the rat. The number of errors in a radial maze test was reduced after acute intraperitoneal (IP) injection of RGH 2202 at the dose of 5 or 10 mg/kg. Grooming activity was increased with a lower dose, 1 mg/kg. Hypoxia-induced amnesia, as assessed with active and passive avoidance behavior tests, was reversed in rats treated with 5 or 10 mg/kg of the drug. The loss of learning and memory capacity shown by aged rats in the same behavioral tests was also reduced after injection of RGH 2202. In a test for sexual activity of male rats, the higher dose of the drug induced a facilitation of mounting and ejaculations, while smaller doses were ineffective. The rotorod test revealed a decreased number of falls in animals treated with 5 or 10 mg/kg of RGH 2202. In all behavioral tests, the same doses of natural thyrotropin-releasing hormone (TRH) were less effective, indicating that this analogue may be qualified as a potentially active drug in human pathologies.

The thyrotropin releasing hormone analogue, RGH 2202, reverses experimental haemorrhagic shock in rats.

Hypovolemic shock was produced in rats by withdrawing about 50% of the estimated total blood volume. Following mean arterial pressure stabilization in the range of 22-23 mm Hg, the rats were given an i.v. bolus injection of L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202) to be compared with thyrotropin-releasing hormone (TRH). RGH-2202, administered within 5 min following shock induction, dose dependently improved the mean arterial pressure and survival of the rats. The activity of RGH-2202 was superior to that of TRH after i.v. administration; both drugs showed a lower activity after i.m. administration.

Neuroprotective activity of alpha-dihydroergocryptine in animal models.

alpha-Dihydroergocryptine (alpha-DHEC) is a well known dopaminergic agent successfully employed in the treatment of Parkinson's disease. alpha-DHEC showed a neuroprotective activity against total cerebral ischemia induced by MgCl2 in mice and histocytic anoxia by NaCN in mice and rats. Moreover the drug promoted the recovery of locomotor activity in rats after cerebral ischemic damage and protected mice against convulsions induced by intracerebroventricular injections of NMDA and glutamate. alpha-DHEC showed a protective activity on neuronal degeneration induced by MPTP in monkeys, as evaluated through animal's behaviour and morphological-cytochemical changes in the substantia nigra, suggesting a preservative effect on neuronal morphology and brain architecture. In the MPTP-treated monkeys, the alpha-DHEC administration induced a restoration of the unstimulated MDA values to control levels. The neuroprotective activity of alpha-DHEC is related to its peculiar activity on antioxidative enzymes of GSH system and to reduction of lipid-peroxide-induced cellular degeneration.

Distribution of drugs in polymers loaded by swelling.

Ethylene:vinyl acetate pellets were loaded at 20 degrees C by swelling the polymer with 1 and 3% (w/v) chloroformic solutions of tolbutamide. The energy dispersive X-ray analysis showed different concentrations of the tolbutamide sulfur in the pellets sections according to the loading time. At the beginning of the loading process, the sulfur in the pellets showed two concentration peaks which later joined in the center of the section before reaching a homogeneous distribution. The concentration peaks might depend on a drug sieving process as the solution flow reaches a less swollen inner area. Therefore, the concentration distribution of the drug would be affected by the size of the polymer network, which is related to the volume of the solvent in the polymer. Another possible explanation of these concentration profiles is that they could be a result of the solvent evaporation process. The concentration distribution of the drug becomes homogeneous only after the complete swelling of all of the polymer.

Alginate microparticles for enzyme peroral administration.

In order to protect protein and peptide drugs against inactivation by different barriers in the gastro-intestinal tract and to improve their absorption, alginate microparticles as a carrier of L-lactate dehydrogenase, were developed by spray-drying technique. However, alginate complexation and spray-drying conditions led to enzyme activity loss. Such a drawback was overcome by using protectant additives (carboxymethylcellulose sodium salt, polyacrylic acid sodium salt, lactose) preventing the enzyme inactivation by both interaction with alginate and experimental conditions, lactose having the most protective effect. Nevertheless, only polyacrylic acid sodium salt provided a microparticulate structure required for the target of the Peyer's patches.