Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.

RATIONALE: Aversive learning and memory are essential to cope with dangerous and stressful stimuli present in an ever-changing environment. When this process is dysfunctional, however, it is associated with posttraumatic stress disorder (PTSD). The endocannabinoid (eCB) system has been implicated in synaptic plasticity associated with physiological and pathological aversive learning and memory. OBJECTIVE AND METHODS: The objective of this study was to review and discuss evidence on how and where in the brain genetic or pharmacological interventions targeting the eCB system would attenuate aversive/traumatic memories through extinction facilitation in laboratory animals and humans. The effect size of the experimental intervention under investigation was also calculated. RESULTS: Currently available data indicate that direct or indirect activation of cannabinoid type-1 (CB1) receptor facilitates the extinction of aversive/traumatic memories. Activating CB1 receptors around the formation of aversive/traumatic memories or their reminders can potentiate their subsequent extinction. In most cases, the effect size has been large (Cohen's d ≥ 1.0). The brain areas responsible for the abovementioned effects include the medial prefrontal cortex, amygdala, and/or hippocampus. The potential role of cannabinoid type-2 (CB2) receptors in extinction learning is now under investigation. CONCLUSION: Drugs augmenting the brain eCB activity can temper the impact of aversive/traumatic experiences by diverse mechanisms depending on the moment of their administration. Considering the pivotal role the extinction process plays in PTSD, the therapeutic potential of these drugs is evident. The sparse number of clinical trials testing these compounds in stress-related disorders is a gap in the literature that needs to be addressed.

An anatomical review of spinal cord blood supply.

Knowledge of the spinal cord (SC) vascular supply is important in patients undergoing procedures that involve the thoracic and thoracoabdominal aorta. However, the SC vasculature has a complex anatomy, and teaching is often based only on anatomical sketches with highly variable accuracy; historically, this has required a "leap of faith" on the part of aortic surgeons. Fortunately, this "leap of faith" is no longer necessary given recent breakthroughs in imaging technologies and postprocessing software. Imaging methods have expanded the non-invasive diagnostic ability to determine a patient's SC vascular pattern, particularly in detecting the presence and location of the artery of Adamkiewicz. CT is the imaging modality of choice for most patients with thoracic and thoracoabdominal aortic disease, proving especially useful in the determination of feasibility and planning of endovascular treatment. Thus the data set required for analysis of SC vascular anatomy is usually already available. We have concentrated our efforts on CT angiography, which offers particularly good imaging capabilities with state-of-the-art multidetector scanners. Multidetector row helical CT provides examinations of an extensive range in the craniocaudal direction with thin collimation in a short time interval, giving excellent temporal and spatial resolution. This paper provides examples of the SC vasculature imaging quality that can be obtained with 64 row scanners and appropriate postprocessing. Knowledge of the principal anatomical features of the SC blood supply of individual patients undergoing open or endovascular thoracoabdominal procedures has several potential benefits. For open surgery, analysis of the SC vasculature could tell us the aortic region that feeds the Adamkiewicz artery and thus needs to be reimplanted. For endovascular procedures, we can determine whether the stent-graft will cover the Adamkiewicz artery, thus avoiding unnecessary coverage. CT data can also be used to stratify risk of SC ischemia and guide the selective use of spinal cord injury prevention strategies.

Clinical use of extra-large self-expanding stents.

The aim of this study is to describe our clinical experience with an extra-large self-expandable stent specifically designed to treat aortic lesions (E-XL, Jotec GmbH, Hechingen, Germany), now commercially available in Europe. The E-XL was used at our Institution in 14 patients (mean age, 56±12 years; 9 males) with the following indications: improve proximal fixation (4 cases), type I endoleak (2 cases), aortic dissection with static malperfusion (1 case) and dynamic malperfusion (7 cases). Early results have been shown to be safe and effective in different clinical settings, including in emergency cases. This peculiar aortic stent could be useful in the armamentarium of the endovascular surgeon.

Redo surgery in ascending aorta and aortic arch.

AIM: Reinterventions following previous ascending aorta and aortic arch repair are uncommon, but technically challenging and often burdened with high morbidity and mortality. The aim of this article is to present a single-center experience in the treatment of this complex pathology, using different surgical approaches. METHODS: Between 1999 and 2014, 17 patients (14 males, mean age 73±16 years) underwent ascending aorta and aortic arch redo surgery at our Department. A prospectively maintained database including thoracic aortic procedures was reviewed retrospectively to collect data on redo patients. RESULTS: In 13 cases the index procedure was an endovascular or hybrid procedure on the aortic arch performed at our Department, for an in-house reintervention rate of 6.9% (13/188). In 10 cases the cause of reintervention was stent-graft distal migration, treated by means of endovascular relining in all cases, associated with adjunctive supra-aortic trunks debranching via sternotomy in 6 cases. In 5 cases the cause of reintervention was retrograde ascending aortic dissection, in 1 case ascending aortic anastomotic pseudoaneurysm following supra-aortic trunk debranching, and in 1 case mediastinitis following implantation of an endovascular plug previously used to treat an ascending aortic pseudoaneurysm. In these last 7 cases, all patients were treated by means of ascending and arch surgical replacement under deep hypothermic circulatory arrest (DHCA) and antegrade cerebral perfusion (ACP). No 30-day mortality was observed. Major perioperative morbidity included 1 paraplegia, 1 minor stroke, 1 bleeding requiring reintervention, and 3 cases of respiratory failure requiring prolonged intubation (2) or tracheostomy (1). CONCLUSION: In our experience, incidence of serious complications requiring reinterventions following ascending aorta or aortic arch repair is not negligible. Redo surgery in ascending aorta and aortic arch is feasible in high-volume and experienced centers, as it often requires hybrid repair via midline sternotomy, or surgical replacement under DHCA and ACP.

Technical features of the INCRAFT™ AAA Stent Graft System.

The INCRAFT® AAA Stent Graft System is the advanced endovascular aneurysm repair (EVAR) technology for the treatment of infrarenal abdominal aneurysms. This new system is designed to address the unmet needs of current endografts by combining unique features and adding new refinements compared to existing endografts delivered through a flexible 14-Fr ultra-low system. The INCRAFT® AAA Stent Graft System introduces innovative features without deviating from proven stent-graft design principles. It is a three-piece modular system, made of low porosity polyester and segmented nitinol stents. However, the introduction of cap-free delivery and partial proximal repositioning enhances the ability of the device to better match individual aortoiliac anatomy with a high deliverability and placement accuracy in a easy to use system. Moreover, the INCRAFT® System allows a "customization" of the implant during the procedure with bilateral in-situ length adjustment features. The present data from the ongoing clinical trials confirm excellent results with this system, but postmarket studies will be necessary to verify the effectiveness of this system in the real-world setting.

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.

The best treatment of juxtarenal aortic occlusion is and will be open surgery.

Occlusion of the infrarenal aorta (IAO) represents from 3% to 8.5% of aortoiliac occlusive diseases, and is a variant of TransAtlantic Inter-Society Consensus (TASC) Type D lesions. Two different patterns of IAO can be identified: Distal and proximal, or iuxtarenal. The former typically spares the origin of the inferior mesenteric artery, and is associated with the classic Leriche clinical triad. The latter extends cephalad approaching the level of the renal arteries, and may also cause acute renal failure, intestinal infarction, and even paraplegia due to the proximal propagation of aortic thrombosis. Endovascular treatment for TASC Type C and D lesions as a whole provides impressive results in terms of periprocedural morbidity, secondary patency rates, and of course less invasivity in comparison to open surgery. However, when complete aortic occlusions, and particularly juxtarenal occlusion, are specifically addressed, the reported results are in fact sobering, both in terms of technical success rates, and perioperative complications. Surgery repair of juxtarenal aortic occlusion, namely aortic endarterectomy and bypass grafting, is a challenging procedure that requires almost invariably aortic cross-clamping above the level of the renal arteries, and may be associated with significant morbidity and mortality. Nevertheless, it currently provides unmatched perioperative and long-term results, and should be regarded as the treatment of choice.

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.

Analysis of stroke after TEVAR involving the aortic arch.

OBJECTIVE: To analyse the incidence of stroke after thoracic endovascular aortic repair (TEVAR) for aortic arch disease. METHODS: In the last decade, 393 patients received TEVAR at our Institution; in 143 cases the aortic arch was involved (32 zones '0', 35 zones '1' and 76 zone '2'). The left subclavian artery (LSA) was revascularised selectively in 75 cases; the proximal LSA was ligated or occluded with a plug in 55 cases before endograft (EG) deployment. RESULTS: Initial clinical success, perioperative mortality, spinal cord ischaemia and stroke in TEVAR patients with or without arch involvement were, respectively, 86.7% vs. 94.4%, 4.2% vs. 2.4%, 2.1% vs. 3.6% and 2.8% vs. 1.2%. The stroke rate was 9.4% (P < 0.02) in 'zone 0', 0% in 'zone 1' and 1.3% in 'zone 2' with scans showing severe atheroma and/or thrombus in all cases. Stroke was observed in patients with 2.6% or without 2.9% LSA revascularisation; however, it was never observed in patients in whom the LSA was occluded before EG deployment and in 4.5% of patients in whom it was patent at the time of EG deployment. CONCLUSIONS: Stroke after TEVAR is not infrequent especially when the arch is involved. Careful patient selection together with a strategy to reduce embolisation such as occlusion of supra-aortic trunks before EG deployment may play a beneficial role.

Protein synthesis in dorsal hippocampus supports the drug tolerance induced by prior elevated plus-maze experience.

Tolerance to the anxiolytic-like effect of drugs may develop because of a memory derived from prior experience in certain apparatuses such as the elevated plus-maze (EPM). Activity in basolateral amygdala was shown to be required for consolidating this knowledge. The dorsal hippocampus (DH) is also implicated in long-term memory consolidation, a process relying on new protein synthesis. It is unknown, however, whether the DH protein synthesis disruption would prevent the phenomenon rendering animals unresponsive to benzodiazepines in the EPM retest. To address this, we bilaterally infused the protein synthesis inhibitor anisomycin (ANI) into the rat DH 0, 3 or 6 h after, or 15 min before, the EPM test. DH infusion of ANI (80 µg) around the time of EPM testing preserved the anxiolysis of the midazolam (MDZ; 0.5 mg/kg, i.p.) in rats retested in the EPM 24 h later, suggesting that information consolidated by DH protein synthesis impacts on the subsequent animal's responsiveness to this drug. To examine whether impaired memory acquisition could also contribute to the prevention of MDZ tolerance seen in EPM-experienced animals infused with ANI before testing, the EPM retest was performed 3 h after testing to coincide with the temporal window in which short-term memory remains, for the reason that this process does not require protein synthesis for its formation. The pretest DH anisomycin infusion's ability to prevent the MDZ tolerance on retesting was now missing. This result confirms a specific action of the ANI on memory consolidation. We also found that rats express further avoidance to open-arms in the EPM retest. However, neither pretest nor posttest DH ANI infusion interfered with this pattern of results exhibited by EPM-experienced rats.