Endovascular Repair of Juxtarenal and Pararenal Abdominal Aortic Aneurysms Using a Novel Low-Profile Fenestrated Custom-Made Endograft: Technical Details and Short-Term Outcomes.

INTRODUCTION: The aim of this study is to share preliminary experiences and outcomes with a novel custom-made fenestrated TREO® Abdominal Stent-Graft System to treat juxtarenal and pararenal abdominal aortic aneurysms (AAAs). METHODS: Juxtarenal and pararenal AAA patients treated with the custom-made fenestrated TREO® Abdominal Stent-Graft System were included from 4 high-volume European academic medical centers from June 2021 to September 2023. Technical success and 30-day/in-hospital mortality and complications were analyzed. Technical success was defined as successful endovascular implantation of the stent graft with preservation of antegrade flow to the target vessels, and absence of type 1 or 2 endoleak (EL) at the first postoperative computed tomography angiography (CTA). RESULTS: Forty-two consecutive patients were included. The majority of the devices were constructed with 2 (N=4; 9.5%), 3 (N=9; 21.4%), or 4 (N=27; 64%) fenestrations. In 1 case, the device was constructed with a single fenestration (2.4%) and 1 device contained 5 fenestrations (2.4%); 17% had previous AAA repair. Target vessel cannulation with placement of a bridging stent was successful in all but 1 vessel (99, 3%). One aneurysm-related death occurred in the direct postoperative period and 2 limb occlusions necessitated reintervention during admission. In the median follow-up period of 101 (2-620) days, 3 more patients died due to non-aneurysm-related causes. Technical success was achieved in 90% of the cases. Nineteen ELs were seen on the first postoperative CT scan: 1 type 1b EL (N=1; 2%), 15 type 2 ELs (N=15; 36%), and 3 type 3 ELs (N=3%). Eleven patients received more than 1 CT scan during a median follow-up of 361 days (82-620): 3 type 2 ELs resolved and 1 type 3 EL was treated in this period. In the follow-up, 1 patient had a coagulation disorder that caused occlusions of the branches. CONCLUSION: The results of the first experiences using the custom-made fenestrated TREO® Abdominal Stent-Graft System in Europe are promising. There was a low short-term mortality and morbidity rate in these patients of which 17% had previous AAA repair. Mid-term and long-term follow-up data are needed to evaluate endograft durability and performance. CLINICAL IMPACT: This study shows the first experiences and short-term results of a novel low-profile custom-made device: the custom-made fenestrated TREO® Abdominal Stent-Graft System. Showing these results and experiences can help the physicians in clinical decision-making for their patients.

Impact of temporal variability of radon concentration in workplaces on the actual radon exposure during working hours.

For workplaces where significant diurnal variations in radon concentrations are likely, measurements to evaluate average radon concentration during working hours could be useful for planning an optimized protection of workers according to the 2013/59/Euratom Directive. However, very few studies on this subject, generally limited to periods of few weeks, have been published. Therefore, a study has been conducted to evaluate the actual long-term radon exposure during working hours for a sample of 33 workplaces of four different types (postal offices, shops, restaurants, municipal offices), mainly located at the ground floor, and with expected considerable air exchange rate occurring during working hours due to frequent entrance/exit of persons or mechanical ventilation. The results show that the difference between the average radon level during working hours and that one during the whole day is about 20% on average and ranges from 0 to 50%. These observed differences, generally smaller compared with those found in other similar studies, are nearly the same if the analysis is restricted to workplaces with annual radon level higher than 300 Bq m-3, and therefore natural or mechanical ventilation normally present during working hours of the monitored workplaces cannot be considered an effective mitigation measure. However, the costs and time-response characteristics of the active monitors, as those used for the present study, will probably allow using more frequently a similar measurement strategy in workplaces.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies.

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

A Matched Case-Control Study on Open and Endovascular Treatment of Popliteal Artery Aneurysms.

OBJECTIVE: To compare early and late results of open and endovascular management of popliteal artery aneurysm in a retrospective single-center matched case-control study Methods: From 1981 to 2015, 309 consecutive interventions for popliteal artery aneurysm were performed in our institution, in 59 cases with endovascular repair and in 250 cases with open repair. Endovascular repair was preferred in older asymptomatic patients, while open repair was offered more frequently to patients with a thrombosed popliteal artery aneurysm and a poor run-off status. A one-to-one coarsened exact matching on the basis of the baseline demographic, clinical, and anatomical covariates significantly different between the two treatment options was performed and two equivalent groups of 56 endovascular repairs and open repairs were generated. The two groups were compared in terms of perioperative results with χ2 test and of follow-up outcomes with the Kaplan-Meier curves and log-rank test. RESULTS: There were no differences between the two groups in terms of perioperative outcomes. Median duration of follow-up was 38 months. Five-year survival rates were 94% in endovascular repair group and 89.5% in open repair group (p = 0.4, log-rank 0.6). Primary patency rates at 1, 3, and 5 years were 81%, 78%, and 72% in endovascular repair group and 82.5%, 80%, and 64% in open repair group (p = 0.8, log-rank 0.01). Freedom from reintervention at 5 years was 65.5% in endovascular repair group and 76% in open repair group (p = 0.2, log-rank 1.2). Secondary patency at 1, 3, and 5 years was 94%, 86%, and 74% in endovascular repair group, and 94%, 89%, and 71% in open repair group, respectively (p = 0.9, log-rank 0.01). The rates of limb preservation at 5 years were 94% in endovascular repair group and 86.4% in open repair group (p = 0.3, log-rank 0.8). CONCLUSION: Open repair and endovascular repair of popliteal artery aneurysms provided in this retrospective single-center experience similar perioperative and follow-up results in equivalent groups of patients.

EVAR and OPEN treatment of abdominal aortic aneurysm: What is the role of MMP-9 in the follow-up?

INTRODUCTION: The aim of our study is to verify the role of metalloproteinases in endovascular repair (EVAR) and OPEN surgery treatment for abdominal aortic aneurysm (AAA). Postoperatively, these enzymes could represent an important biomarker to adapt diagnostic tests and further investigations during follow-up. MATERIAL AND METHOD: From 2004 to 2008, 55 patients were considered with AAA. Of these, 33 patients (mean age: 70.1 years), (mean AAA diameter: 5.4cm) were treated with OPEN surgery (group A) and 22 (mean age: 74.1 years) (mean AAA diameter: 5.1cm) were treated with EVAR. In 17 of them, there were no signs of endoleak (group B1), while in 5 patients, a presence of endoleak (group B2) was detected. Plasma samples were collected in order to determine MMP-9 activity. Enzyme immunoassay was performed preoperatively at 1, 3, 6 and 12 months. Patients treated conventionally were clinically examined after 1 and 12 months by ultrasound. Patients undergoing EVAR treatment were clinically examined by CT scan after 1, 3, 6 and 12 months. The analysis was done by assessing the interaction over time of the MMP-9 value in B1 and B2 groups. RESULTS: The average values observed for MMP-9 were preoperatively and at 1, 3, 6 and 12 months, respectively: in group A 150.8ng/mL (SD=30.5), 252.5ng/mL (SD=25.2), 315.4ng/mL (SD=22.7), 295.3ng/mL (SD=26.8), 210.7ng/mL (SD=30.2); in group B1 105ng/mL (SD=10.8), 125.6ng/mL (SD=18), 85.8ng/mL (SD=19.9), 95ng/mL (SD=20.2), 80.4ng/mL (SD=15.6); in group B2 149ng/mL (29.2), 375.4ng/mL (SD=40.2), 215ng/mL (SD=35.9), 180ng/mL (SD=20.2), 175ng/mL (SD=33.4). The MMP-9 level was higher in group B2 compared to group B1 (P=0.01), suggesting a correlation with the presence of the endoleak. CONCLUSIONS: This preliminary study shows that MMP-9 may be a biomarker of the presence of endoleak. Other further investigations and larger series are needed to show that metalloproteases could play a role in the follow-up of EVAR treated patients.

Italian Percutaneous EVAR (IPER) Registry: outcomes of 2381 percutaneous femoral access sites' closure for aortic stent-graft.

AIM: The aim of this paper was to report outcomes of endovascular aneurysm repair with percutaneous femoral access (pEVAR) using Prostar XL and Proglide closure systems (Abbot Vascular, Santa Clara, CA, USA), from the multicenter Italian Percutaneous EVAR (IPER) registry. METHODS: Consecutive patients affected by aortic pathology treated by EVAR with percutaneous access (pEVAR) between January 2010 and December 2014 at seven Italian centers were enrolled in this multicenter registry. All the operators had an experience of at least 50 percutaneous femoral access procedures. Data were prospectively collected into a dedicated online database including patient's demographics, anatomical features, intra- and postoperative outcomes. A retrospective analysis was carried out to report intraoperative and 30-day technical success and access-related complication rate. Uni- and multivariate analyses were performed to identify factors potentially associated with an increased risk of percutaneous pEVAR failure. RESULTS: A total of 2381 accesses were collected in 1322 patients, 1249 (94.4%) male with a mean age of 73.5±8.3 years (range 45-97). The overall technical success rate was 96.8% (2305/2381). Major intraoperative access-related complications requiring conversion to surgical cut-down were observed in 3.2% of the cases (76/2381). One-month pEVAR failure-rate was 0.25% (6/2381). Presence of femoral artery calcifications resulted to be a significant predictor of technical failure (OR: 1.69; 95% CI: 1.03-2.77; P=0.036) at multivariate analysis. No significant association was observed with sex (P=0.28), obesity (P=0.64), CFA diameter (P=0.32), level of CFA bifurcation (P=0.94) and sheath size >18 F (P=0.24). The use of Proglide was associated with a lower failure rate compared to Prostar XL (2.5% vs. 3.3%) despite not statistically significant (P=0.33). CONCLUSION: The results of the IPER registry confirm the high technical success rate of percutaneous EVAR when performed by experienced operators, even in presence of demanding anatomies. Femoral calcification represents the only predictor of percutaneous access failure.

Energy-selective neutron imaging for morphological and phase analysis of iron-nickel meteorites.

We propose energy-selective neutron imaging as a new and non-destructive method to investigate rare metallic meteorites. It is based on attenuation of a neutron beam of limited spectral distribution in a sample depending on the elemental composition and crystalline structure. Radiography and tomography allow obtaining the presence, morphology and orientation information in the bulk of mineral inclusions, oxide crust and crystalline structure. Its usage in classification and meteor formation studies would be of great value.

Endovascular treatment of aorto-iliac aneurysms: four-year results of iliac branch endograft.

INTRODUCTION: The aim of this report was to analyse early and mid-term outcomes of endovascular treatment (endovascular aneurysm repair, EVAR) for aorto-iliac aneurysms with the use of an iliac branch device (IBD). REPORT: A total of 85 EVAR procedures with IBD were electively carried out in 81 patients between September 2007 and August 2012. Technical success was obtained in 98.7% of the cases. The mean follow-up duration was 20.4 months (SD ± 15.4). There was one IBD occlusion (1.2%). Estimated 48 months' survival, freedom from re-intervention and branch occlusion were 76.7%, 88.3% and 98%, respectively. CONCLUSIONS: EVAR for aorto-iliac aneurysms using IBD is an effective procedure with low complication and re-intervention rates at mid-term follow-up.

Comparison of open and endovascular treatments of post-carotid endarterectomy restenosis.

AIM OF THE STUDY: To compare early and long term results of open and endovascular treatment of post-carotid endarterectomy (CEA) restenosis in a single centre experience. METHODS: From January 2005 to December 2011, ninety-nine consecutive interventions for primary severe post-CEA restenosis were performed: in 41 cases (41%, Group 1) open repair was carried out, whereas the remaining 58 patients (59%, group 2) underwent an endovascular treatment. Data concerning these interventions were prospectively collected in a dedicated database containing main pre, intra and postoperative variables. Early results in terms of 30-day stroke and death rates were analysed and compared with χ(2) test. Follow-up results were analysed with Kaplan Meier curves and compared with log-rank test. RESULTS: Mean time from primary CEA was 75 months in group 1 and 42 months in group 2 (p = 0.002; 95% CI 12-52). There were no differences between the two groups in terms of demographic data, comorbidities, risk factors for atherosclerosis, preoperative clinical status or degree of stenosis on the operated side. In group 1 interventions consisted of redo-CEA in 37 patients and of carotid bypass in the remaining 4; all the patients in group 2 underwent stent placement with cerebral protection device. No perioperative deaths and ipsilateral neurological events occurred in both groups. One patient in group 1 suffered from a non-fatal acute myocardial infarction. Other six patients (14.5%) experienced transient cranial nerve injuries, with complete regression at 1-month follow-up; two patients had postoperative dysphagia due to neck haematoma, which was medically managed. Neither access-related nor systemic complications were recorded in group 2. Follow-up was available in 98% of the patients with a median duration of 24 months (range 3-72). There were no differences in terms of 4-year estimated survival and stroke-free survival, whereas patients in group 1 were more likely to develop severe (>80%) secondary restenosis (28.3% and 6.5%, respectively, p = 0.01, log rank 6.3) and to undergo secondary reintervention (22% and 11%, respectively p = 0.01, log rank 6). CONCLUSIONS: despite the selection limits and bias of this study, in our experience open and endovascular surgery provided similar perioperative results in the management of post-CEA restenosis. Long term outcomes are similar, too, despite a slight increase in secondary restenosis and recurrent reinterventions among open surgery patients, warranting further studies and analysis.

Alterations of haemorheological parameters in patients with peripheral arterial disease.

Peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis. Advances on the development of such vascular disease have described with a number of novel risk factors. Hyperviscosity, due to alterations of blood cells and plasma components, may play a role on the pathogenesis of the disease. Aim of this study was to evaluate the possible association between hemorheological variables and PAD. The hemorheological variables [whole blood viscosity (WBV), erythrocyte deformability index (DI), plasma viscosity (PLV)] were analyzed in 90 patients and in 180 healthy subjects. WBV and PLV were measured by a Rotational Viscosimeter and DI by a filtrometer. DI and PLV were significantly different in patients as compared to controls. To investigate the possible association between these parameters and the disease we divided the study population into tertiles. At the univariate analysis, we found a significant association between the highest tertiles of PLV, of DI and the disease. A model adjusted for traditional risk factors showed an association between highest tertiles of PLV and PAD. After adjustment for confounding parameters highest tertiles of PLV remained to be significantly associated with the disease. Our data indicate that an alteration of plasma viscosity may modulate the predisposition to PAD.

A 20-year experience with surgical management of true and false internal carotid artery aneurysms.

AIM OF THE STUDY: The aim of this study was to retrospectively analyse early and late results of surgical management of internal carotid artery (ICA) true and false aneurysms in a single-centre experience. MATERIALS AND METHODS: From January 1988 to December 2011, 50 consecutive interventions for ICA aneurismal disease were performed; interventions were performed for true ICA aneurysm in 19 cases (group 1) and for ICA post-carotid endarterectomy (CEA) pseudo-aneurysm in the remaining 31 (group 2). Early results (<30 days) were evaluated in terms of mortality, stroke and cranial nerves' injury and compared between the two groups with χ(2) test. Follow-up results (stroke free-survival, freedom from ICA thrombosis and reintervention) were analysed with Kaplan-Meier curves and compared with log-rank test. RESULTS: All the patients in group 1 had open repair of their ICA aneurysm; in group 2 open repair was performed in 30 cases, while three patients with post-CEA aneurysm without signs of infection had a covered stent placed. There were no perioperative deaths. Two major strokes occurred in group 1 and one major stroke occurred in group 2 (p = 0.1). The rates of postoperative cranial nerve injuries were 10.5% in group 1 and 13% in group 2 (p = 0.8). Median duration of follow-up was 60 months (range 1-276). Estimated 10-year stroke-free survival rates were 64% in group 1 and 37% in group 2 (p = 0.4, log rank 0.5); thrombosis-free survival at 10 years was 66% in group 1 and 34% in group 2 (p = 0.2, log rank 1.2), while the corresponding figures in terms of reintervention-free survival were 68% and 33%, respectively (p = 0.2, log rank 1.8). CONCLUSIONS: Surgical treatment of ICA aneurismal disease provided in our experience satisfactory early and long-term results, without significant differences between true and false aneurysms. In carefully selected patients with non-infected false aneurysm, the endovascular option seems to be feasible.

Urgent carotid endarterectomy in patients with recent/crescendo transient ischaemic attacks or acute stroke.

OBJECTIVES: Objective of this study was to review the results of urgent carotid endarterectomy (CEA) performed in patients with recent (< 24 h) or crescendo (at least 2 episodes in 24 h) transient ischaemic attack (TIA) or with acute stroke in a single centre experience. MATERIALS AND METHODS: From January 2000 to December 2008, 75 patients underwent urgent CEA for severe internal carotid artery stenosis and recent/crescendo TIA (51 patients, TIA group) or acute stroke (24 patients, stroke group). In patients with acute stroke the intervention was proposed on the basis of clinical and instrumental features (patient conscious, patency of middle cerebral artery, no lesions or limited brain infarction at CT scan) according to neurologists' suggestion. Data from all the interventions were prospectively collected in a dedicated database, which included main pre-, intra- and postoperative parameters. Independent neurological assessment with National Institute of Health Stroke Scale (NIHSS) score calculation was performed before the operation and within the 30th postoperative day. Early (< 30 days) results were evaluated in terms of mortality, modifications in NIHSS values and stroke and death rates. The surveillance program consisted of clinical and ultrasonographic examinations at 1, 6 and 12 months and yearly thereafter. Follow-up results (survival, occurrence of ipsilateral stroke in TIA group, recurrence of stroke in stroke group) were analysed by Kaplan-Meier curves. RESULTS: Among patients presenting with TIA, 28 had crescendo TIAs and 23 had a recent TIA; In stroke group, two patients had a stroke in evolution, eight patients had a recent major non-disabling stroke and 14 patients had a recent minor stroke. Preoperative mean value of NIHSS score in stroke group was 4.7 (SD 3.2). There were 2 perioperative (< 30 days) deaths, both in stroke group, in one case due to acute respiratory failure and to fatal stroke in the other one (preoperative NIHSS value 9, postoperative 17), with a cumulative 30-day mortality rate of 2.7%, significantly higher in stroke group (8.3%) than in TIA group (no death, p = 0.03). No postoperative cerebral haemorrhage occurred. In TIA group one postoperative major stroke occurred, with a 30-day stroke and death rate of 1.9%. In surviving patients of stroke group NIHSS value improved in 13 cases, with a mean improvement of 2 points (SD 0.9); in 8 cases the value remained unchanged, while in the remaining case it increased from 2 to 4. Mean postoperative NIHSS score in stroke group was 3.9 (SD 3.7), significantly reduced in comparison with preoperative value (p < 0.001). Mean duration of follow-up was 34 months (SD 28.1). No ipsilateral stroke in patients of TIA group occurred; in stroke group a recurrent fatal stroke at 1 postoperative month was recorded. Estimated 48-month stroke-free survival rate TIA group was 95% and 79% in stroke group (p = 0.02). CONCLUSIONS: Urgent CEA in patients with recent/crescendo TIA provided in our experience excellent results, with low rates of perioperative and late stroke. In selected patients with acute stroke early surgery seems to provide acceptable results.

Endovascular repair of a ruptured popliteal artery aneurysm associated with popliteal arteriovenous fistula.

Popliteal artery aneurysms (PAAs) represent the most common peripheral arterial aneurysm and are a significant cause of patient morbidity and limb loss. Complications of PAA include distal embolisation, thrombosis and, rarely, rupture. Whereas open surgical repair remains the gold standard, endovascular exclusion has been demonstrated to be a valid alternative in selected patients. We present an unusual case of ruptured PAA associated with popliteal vein arteriovenous fistula that was successfully treated with an endovascular approach. In our opinion, higher-risk patients as well as patients presenting with rupture may constitute a subgroup warranting an endovascular approach whenever possible.

Carotid artery disease: novel pathophysiological mechanisms identified by gene-expression profiling of peripheral blood.

OBJECT: The pathogenesis of carotid artery stenosis (CAS) as well as the mechanisms underlying the different localisation of the atherosclerotic lesions remains poorly understood. We used microarray technology to identify novel systemic mediators that could contribute to CAS pathogenesis. Moreover, we compared gene-expression profile of CAS with that of patients affected by abdominal aortic aneurysm (AAA), previously published by our group. METHODS AND RESULTS: By global gene-expression profiling in a pool of 10 CAS patients and 10 matched controls, we found 82 genes differentially expressed. Validation study in pools used for profiling and replication study in larger numbers of CAS patients (n = 40) and controls (n = 40) of 14 genes by real-time polymerase chain reaction (RT-PCR) confirmed microarray results. Fourteen out of 82 genes were similarly expressed in AAA patients. Gene ontology analysis identified a statistically significant enrichment in CAS of differentially expressed transcripts involved in immune response and oxygen transport. Whereas alteration of oxygen transport is a common tract of the two localisations, alteration of immune response in CAS and of lipid metabolic process in AAA represents distinctive tracts of the two atherosclerotic diseases. CONCLUSIONS: We describe the systemic gene-expression profile of CAS, which provides an extensive list of potential molecular markers.

Hybrid treatment of aortic arch aneurysms.

AIM: Aim of this study was to retrospectively analyze the experience of a single center in the hybrid treatment of aortic arch aneurysms. METHODS: From January 2005 to August 2008 a hybrid treatment for complex aortic aneurysms (aortic arch, thoracoabdominal aorta or thoracic and abdominal segments at the same time) was performed in 34 patients. In 11 cases a hybrid exclusion of an aortic arch aneurysm was carried out. Perioperative results in terms of morbidity and mortality were assessed. Follow-up examination consisted of computed tomography scan and chest X-ray at discharge, 6 and 12 months, and yearly thereafter. Mid-term survival and graft-related complications were analyzed. RESULTS: All the patients were males with a mean age of 74 years, range 68-81. Intraoperative technical success was achieved in all the cases. At 30 days one patient died for an acute stroke. The overall 30-day mortality rate was 9.1%. One frenic nerve paralysis and one acute re-spiratory failure with pneumonia were observed with an overall 30-day major morbidity rate of 18.2%. During follow-up (mean duration 19.3 months, range 1-36) no death, reintervention, conversion, aneurysm-related complication or graft thrombosis were recorded. CONCLUSION: Hybrid approaches to the treatment of complex aortic lesions involving the arch can be successfully used. However, perioperative complications remain still not irrelevant and long-term efficacy has to be proved.

In vivo effects of rosiglitazone in a human neuroblastoma xenograft.

BACKGROUND: Neuroblastoma (NB) is the most common extra-cranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. There is in vitro evidence that the peroxisome proliferator-activated receptor gamma (PPARgamma) might be a target for pharmacological intervention in NB. We have previously demonstrated that the PPARgamma agonist rosiglitazone (RGZ) exerts strong anti-tumoural effects in the human NB cell line, SK-N-AS. The aim of this study was to evaluate whether RGZ maintains its anti-tumoural effects against SK-N-AS NB cells in vivo. METHODS AND RESULTS: For this purpose, tumour cells were subcutaneously implanted in nude mice, and RGZ (150 mg kg(-1)) was administered by gavage daily for 4 weeks. At the end of treatment, a significant tumour weight inhibition (70%) was observed in RGZ-treated mice compared with control mice. The inhibition of tumour growth was supported by a strong anti-angiogenic activity, as assessed by CD-31 immunostaining in tumour samples. The number of apoptotic cells, as determined by cleaved caspase-3 immunostaining, seemed lower in RGZ-treated animals at the end of the treatment period than in control mice, likely because of the large tumour size observed in the latter group. CONCLUSIONS: To our knowledge, this is the first demonstration that RGZ effectively inhibits tumour growth in a human NB xenograft and our results suggest that PPARgamma agonists may have a role in anti-tumoural strategies against NB.

Gene expression profiling of peripheral blood in patients with abdominal aortic aneurysm.

OBJECT: Abdominal aortic aneurysm (AAA) pathogenesis remains poorly understood. This study investigated the gene expression profile of peripheral blood from patients with AAA using microarray technology. METHODS AND RESULTS: We determined gene expression profiles in pooled RNA from 10 AAA patients and 10 matched controls with arrays representing 14,000 transcripts. Microarray data for selected genes were confirmed by real-time PCR in two different AAA (n=36) and control (n=36) populations and integrated with biochemical data. We identified 91 genes which were differentially expressed in AAA patients. Gene Ontology analysis indicated a significant alteration of oxygen transport (increased hemoglobin gene expression) and lipid metabolism [including monoglyceride lipase and low density lipoprotein receptor-related protein 5 (LRP5) gene]. LRP5 expression was associated inversely with serum lipoprotein(a) [Lp(a)] concentration. CONCLUSIONS: Increased expression of hemoglobin chain genes as well as of genes involved in erythrocyte mechanical stability were observed in the AAA RNA pools. The association between low levels of LRP5 gene expression and increased levels of Lp(a) in AAA patients suggests a potential role of LRP5 in Lp(a) catabolism. Our data underline the power of microarrays in identifying further molecular perturbations associated with AAA.

Protein Z-dependent protease inhibitor and protein Z in peripheral arterial disease patients.

SUMMARY INTRODUCTION: Protein Z is a vitamin K-dependent protein that serves as a cofactor for the inhibition of activated factor X by the serpin protein Z-dependent protease inhibitor (ZPI). Protein Z plasma levels have been shown to be reduced in patients with peripheral arterial disease (PAD), but ZPI levels have not yet been reported. The aim of this study was to more fully assess the protein Z-ZPI system in individuals with atherosclerosis selected by the presence of symptomatic PAD. MATERIALS AND METHODS: Protein Z and ZPI levels were determined in 95 PAD patients (73 males; 22 females) [median age: 73 years (range, 50-86 years)] and in 190 controls comparable for age and gender. Protein Z was measured using a commercial immunoassay, and ZPI was measured with a homemade immunoassay and a functional assay. RESULTS: Protein Z antigen, ZPI antigen and ZPI function were found to be significantly lower in PAD patients with respect to controls [protein Z, median 72.5% (range: 3.4-123.7%) vs. 90.7% (range: 32.1-203.2%), P < 0.0001; ZPI antigen, 86.1% (range: 25.1-149.5%) vs. 93.2% (range: 48.9-171.3%), P = 0.004; ZPI function, 83.5% (range: 21.1-135.2%) vs. 97.2% (range: 50.5-175.5%), P < 0.0001]. The lowest tertiles of protein Z antigen [odds ratio (OR) 5.4, 95% confidence interval (CI) 2.2-13.5, P < 0.0001] and ZPI function (OR 2.4, 95% CI 1.1-5.5, P = 0.03) were associated with PAD on multivariate analysis after adjustment for age, gender, and traditional cardiovascular risk factors. A significant inverse relationship was also observed between protein Z and ZPI levels and the number of traditional cardiovascular risk factors and the clinical severity of disease (Fontaine stage). CONCLUSIONS: Low levels of protein Z antigen and protein Z activity are significantly associated with the occurrence and severity of atherosclerotic PAD.

Genetic analysis of 56 polymorphisms in 17 genes involved in methionine metabolism in patients with abdominal aortic aneurysm.

BACKGROUND: Previous studies suggested an association between abdominal aortic aneurysm (AAA) and hyperhomocysteinaemia, a complex trait determined by genetic and environmental factors. Our hypothesis was that polymorphisms in genes directly or indirectly involved in methionine metabolism may contribute to AAA susceptibility. METHOD: We studied 56 polymorphisms in MTHFR, MTR, MTRR, CBS, MTHFD1, SLC19A1, NNMT, TCN2, AHCY, BHMT, BHMT2, FOLH1, TYMS, ENOSF1, SHMT1, PON1, PON2 genes according to their demonstrated/putative function, localisation in promoter or regulatory and coding regions and/or heterozygosity values >0.300. Polymorphisms were evaluated by using a primer extension based microarray technology in 423 AAA patients and 423 matched controls. RESULTS: All polymorphisms resulted in Hardy-Weinberg equilibrium in patients and controls. At the multiple logistic regression analysis adjusted for traditional cardiovascular risk factors (sex, age, hypertension, smoking habit, dyslipidaemia, diabetes) and chronic obstructive pulmonary disease (COPD), rs8003379 MTHFD1 (odds ratio (OR) 0.41, 95% confidence interval (CI) 0.26 to 0.65) and rs326118 MTRR (OR 0.47, 95% CI 0.29 to 0.77) polymorphisms resulted in independent susceptibility factor for AAA. CONCLUSIONS: After haplotype reconstruction, logistic regression analyses adjusted for traditional risk factors and COPD showed a significant association among AAA and AHCY, FOLH1, MTHFD1, MTR, NNMT, PON1 and TYMS haplotypes. Our findings offer new insights into the pathogenesis of AAA.