Reconsidering the Impact of Endovascular Repair on Short-Term and Mid-Term Outcomes in Peripheral Arterial Disease: A Retrospective Analysis.

BACKGROUND: The aim of the study is to compare the short-term and medium-term outcomes in patients who underwent open repair (OR) or endovascular repair (ER) for peripheral arterial disease (PAD) also including stratifications based on severity and year of the first intervention. METHODS: We conducted an observational retrospective single-center cohort study. We evaluated patients with PAD that primarily underwent ER, OR, minor, and major amputations in a single center from 2005 to 2020. The patients were then subdivided according to the type of intervention (OR versus ER), and stratified according to the International Classification of Diseases 9 code reported in the operating documents and to the year intervention. Mortality, minor, and major amputation rates occurring at 30 days, 2 years, and 5 years after the first intervention were evaluated as primary outcomes and compared between patient groups in both stratifications. Moreover, Kaplan-Maier curves were analyzed for these outcomes. RESULTS: One thousand four hundred ninety two patients (67.0% males) with PAD were evaluated. Their clinical presentations were intermittent claudication in 51.4% of cases, rest pain in 16.8%, ulcers in 10.3%, and gangrene in 21.5%. Nine hundred ninety seven (66.8%) underwent OR and 495 (33.2%) ER as first intervention for PAD. No statistical differences were observed in terms of mortality in the 2 groups (OR versus ER, P = 1,000, P = 0.357, and P = 0.688 at 30 days, 2 years, and 5 years, respectively). The rate of minor amputations was significantly higher (P < 0.012, P < 0.002, and P < 0.007 at 30 days, 2 years, and 5 years, respectively) for ER group in any of the observed follow-up periods. Also, we have observed that OR and ER do not have any significant short-term and medium-term major amputation rate differences. CONCLUSIONS: In our experience, the impact of ER does not significantly change short-term and mid-term major outcomes in patients with PAD.

Use of target vessel ballooning to facilitate endovascular treatment in the case of branched endovascular aneurysm repair with a retrograde approach.

A case of a new technique for branched endovascular aneurysm repair with a retrograde approach and ostial stenosis of the target vessel is reported. An angioplasty balloon was placed within the target vessel and used to give added stability to catheter advancement to place the stiff guidewire needed for placement of a bridging stent graft. In brief, a standard guidewire was first placed inside the target vessel through the retrograde approach. Next, the balloon was placed from outside the stent graft, again through a contralateral retrograde approach. Then, the angioplasty balloon was inflated, and a support catheter was advanced to the balloon and then slowly deflated to allow the catheter to advance. Finally, the stiff guidewire was placed. Subsequently, the bridging stent was placed and deployed. This technique is feasible and can be used in selected cases to use a retrograde approach when ostial stenosis of the target vessel is present.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Renal Ischemia/Reperfusion Early Induces Myostatin and PCSK9 Expression in Rat Kidneys and HK-2 Cells.

During visceral interventions, the transient clampage of supraceliac aorta causes ischemia/reperfusion (I/R) in kidneys, sometime resulting in acute renal failure; preclinical studies identified redox imbalance as the main driver of I/R injury. However, in humans, the metabolic/inflammatory responses seem to prevail on oxidative stress. We investigated myostatin (Mstn) and proprotein convertase subtilisin/kexin type 9 (PCSK9), proatherogenic mediators, during renal I/R. Compared to sham-operated animals, the kidneys of rats who had experienced ischemia (30 min) had higher Mstn and PCSK9 expression after 4 h of reperfusion. After 24 h, they displayed tubular necrosis, increased nitrotyrosine positivity, and nuclear peroxisome proliferator-activated receptor gamma coactivator-1alpha relocation, markers of oxidative stress and mitochondria imbalance. Mstn immunopositivity was increased in tubuli, while PCSK9 immunosignal was depleted; systemically, PCSK9 was higher in plasma from I/R rats. In HK-2 cells, both ischemia and reperfusion enhanced reactive oxygen species production and mitochondrial dysfunction. H2O2 upregulated Mstn and PCSK9 mRNA after 1 and 3.5 h, respectively. Accordingly, ischemia early induced Mstn and PCSK9 mRNA; during reperfusion Mstn was augmented and PCSK9 decreased. Mstn treatment early increased PCSK9 expression (within 8 h), to diminish over time; finally, Mstn silencing restrained ischemia-induced PCSK9. Our study demonstrates that renal I/R enhances Mstn and PCSK9 expression and that Mstn induces PCSK9, suggesting them as therapeutic targets for vascular protection during visceral surgery.

Position Paper on Young Vascular Surgeons Training of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS): State of the Art and Perspectives.

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty.

Endovascular Versus Open Surgical Repair for Ruptured Descending Aortic Pathologies: A Systematic Review and Meta-Analysis of Observational Studies.

PURPOSE: Ruptured descending thoracic aorta (rDTA) is an harmful condition requiring emergent treatment. Thoracic endovascular aortic repair (TEVAR) is replacing the traditional open repair in the majority of descending thoracic aortic disease. An unanimous agreement regarding the optimal approach to treat rDTA has not been reached yet due to the lack of evidences supporting the improvement of long-term survival. The present meta-analysis of observational cohort studies aims to estimate the outcome of endovascular (TEVAR) versus surgical (OR) approach in the treatment of rDTA. METHODS: Prisma Statement for performing and reporting meta-analysis has been used. MEDLINE, Scopus and the Cochrane Library databases were searched. A meta-analysis of observational cohort studies that examined the outcomes after OR and TEVAR for the management of rDTA was performed. RESULTS: A total of 10,466 patients with rDTA were screened. Endovascular therapy was associated with a lower risk of in-hospital mortality compared with open repair (Risk Ratio[RR] 0.63; 95% CI0.57-0.70). The risk of stroke rate was not statistically different between endovascular versus open approach (RR0.86; 95% CI0.62-1.19). Endovascular treatment had benefits on paraplegia (RR0.70; 95% CI0.55-0.91) and other neurological complications (RR0.24; 95% CI0.10-0.56). TEVAR was associated with lower renal failure, cardiac complications and vascular injuries. Late mortality (Hazard Ratio[HR] 0.84; 95% CI0.63-1.13) and re-intervention rate (RR1.48; 95% CI0.80-2.74) were not significantly different between TEVAR and OR. CONCLUSIONS: TEVAR seems to offer advantages in terms of early mortality and complications rate. Moreover, data on late mortality and re-intervention are encouraging to consider endovascular treatment comparable to open repair for acute thoracic aorta emergency on long-term follow-up.

Prediction model of isolated iliac and abdominal aneurysms.

OBJECTIVES: We analyse the cardiovascular risk factors in patients undergoing screening for Isolated Iliac Aneurysm (IIA) and Abdominal Aortic Aneurysm (AAA) and propose a logistic regression model to indicate patients at risk of IIA and/or AAA. METHODS: A screening programme was carried out to identify the presence of aneurysm based on Duplex scan examination. Cardiovascular risk factors information was collected from each subject. A descriptive analysis for the incidence of IIA and AAA stratified by age and sex was carried out to evaluate factors incidence. A logistic regression model was developed to predict the probability of developing an aneurysm based on the observed risk factor levels. A threshold probability of aneurysm risk for a datum patient was also identified to effectively direct screening protocols to patients most at risk. RESULTS: A cohort of 10 842 patients was evaluated: 1.52% affected by IIA, 2.69% by AAA and 3.90% by at least one. Risk factors analysis showed that: IIA was correlated with cardiological status, diabetes, cardiovascular disease family history, and dyslipidaemia; AAA was correlated with cardiological status, body mass index, hypertension, and dyslipidaemia; diabetes and dyslipidaemia were the most relevant factors with at least one aneurysm. The prediction tool based on the logistic regression and the threshold probability predict the presence of IIA and AAA in 69.7% and 83.8% of cases, under k-fold cross-validation. CONCLUSIONS: The proposed regression model can represent a valid aid to predict IIA and AAA presence and to select patients to be screened.

COVID-19 Impact on Vascular Surgery Practice: Experience From an Italian University Regional Hub Center for Vascular Pathology.

BACKGROUND: The aim of the study is to evaluate the impact of COVID-19 pandemic on vascular surgery practice in a regional hub center for complex vascular disease. METHODS: This is an observational single-center study in which we collected clinical and surgical data during (P1) and after (P2) the COVID-19 outbreak and the lockdown measures implemented in Northern Italy. We compared those data with the two-month period before the pandemic (P0). RESULTS: Compared to P0, ambulatory activities were severely reduced during P1 and limited to hospitalized patients and outpatients with urgent criteria. We performed 61 operations (18 urgent and 43 elective), with a decrease in both aortic (-17.8%), cerebrovascular (-53.3%), and peripheral artery (-42.6%) disease treatments. We also observed a greater drop in open procedures (-53.2%) than in endovascular ones (-22%). All the elective patients were treated for notdeferrable conditions and they were COVID-19 negative at the ward admission screening; despite this one of them developed COVID19 during the hospital stay. Four COVID-19 positive patients were treated in urgent setting for acute limb ischemia. Throughout P2 we gradually rescheduled elective ambulatory (+155.5%) and surgical (+18%) activities, while remaining substantially lower than during P0 (respectively -45.6% and -25.7%). CONCLUSIONS: Despite COVID-19 pandemic, our experience shows that with careful patient's selection, dedicated prehospitalization protocol and proper use of personal protective equipment it is possible to guarantee continuity of care.

Ficolin-2 serum levels predict the occurrence of acute coronary syndrome in patients with severe carotid artery stenosis.

BACKGROUND AND PURPOSE: erosion of vulnerable atherosclerotic plaques may cause life-threatening thromboembolic complications. There is indeed an urgent need to recognize a clear-cut biomarker able to identify vulnerable plaques. Here, we focused on circulating proteins belonging to the lectin pathway (LP) of complement activation. METHODS: we analyzed mannose-binding lectin (MBL), ficolin-1, -2 and -3 (LP initiators) levels by ELISA in sera from n = 240 of an already published cohort of patients undergoing endarterectomy for severe carotid stenosis and followed-up until 18 months after surgery. Immunofluorescence followed by confocal and polarized light microscopy was used to detect LP initiator intraplaque localization. Spearman's rank test was drawn to investigate correlation between serum LP levels and circulating inflammatory proteins or intraplaque components. Survival analyses were then performed to test the predictive role of LP on long-term adverse outcome. RESULTS: ficolins, but not MBL, correlated positively with 1) high circulating levels of inflammatory markers, including MPO, MMP-8, MMP-9, ICAM-1, osteopontin, neutrophil elastase, and; 2) immune cell intraplaque recruitment. Immunofluorescence showed ficolins in calcified plaques and ficolin-2 in cholesterol-enriched plaque regions in association with macrophages. In the multivariate survival analysis, ficolin-2 serum levels predicted a major adverse cardiovascular event during the follow-up, independently of symptomatic status and inflammatory markers (hazard ratio 38.6 [95 % CI 3.9-385.2]). CONCLUSIONS: ficolins support intraplaque immune cell recruitment and inflammatory processes ultimately leading to plaque vulnerability. Especially for ficolin-2 a strong predictive value toward adverse cardiovascular events was demonstrated. This evidence offers potentially new pharmacological target to dampen the inflammatory mechanisms leading to plaque vulnerability.

3D Automatic Segmentation of Aortic Computed Tomography Angiography Combining Multi-View 2D Convolutional Neural Networks.

PURPOSE: The quantitative analysis of contrast-enhanced Computed Tomography Angiography (CTA) is essential to assess aortic anatomy, identify pathologies, and perform preoperative planning in vascular surgery. To overcome the limitations given by manual and semi-automatic segmentation tools, we apply a deep learning-based pipeline to automatically segment the CTA scans of the aortic lumen, from the ascending aorta to the iliac arteries, accounting for 3D spatial coherence. METHODS: A first convolutional neural network (CNN) is used to coarsely segment and locate the aorta in the whole sub-sampled CTA volume, then three single-view CNNs are used to effectively segment the aortic lumen from axial, sagittal, and coronal planes under higher resolution. Finally, the predictions of the three orthogonal networks are integrated to obtain a segmentation with spatial coherence. RESULTS: The coarse segmentation performed to identify the aortic lumen achieved a Dice coefficient (DSC) of 0.92 ± 0.01. Single-view axial, sagittal, and coronal CNNs provided a DSC of 0.92 ± 0.02, 0.92 ± 0.04, and 0.91 ± 0.02, respectively. Multi-view integration provided a DSC of 0.93 ± 0.02 and an average surface distance of 0.80 ± 0.26 mm on a test set of 10 CTA scans. The generation of the ground truth dataset took about 150 h and the overall training process took 18 h. In prediction phase, the adopted pipeline takes around 25 ± 1 s to get the final segmentation. CONCLUSION: The achieved results show that the proposed pipeline can effectively localize and segment the aortic lumen in subjects with aneurysm.

Geometrical Evaluation of Aortic Sac Remodeling During Two-Step Thoracoabdominal Aortic Aneurysm Endovascular Repair.

BACKGROUND: The present study evaluates aneurysmal sac remodeling and the loss of the intercostal arteries after the first step of staged treatment of thoracoabdominal aortic aneurysms (TAAAs). The purpose of this approach is to keep the aneurysmal sac temporarily perfused to induce progressive thrombosis of the aneurysm while simultaneously allowing the spinal cord to establish adequate perfusion thereby promoting the development of collateral circulation. METHODS: All patients with type II or type III TAAAs, having undergone 2-step endovascular treatment with at least a 2-branch endoprosthesis at our institution between April 2017 and May 2019, were retrospectively evaluated. Thirty-day mortality and spinal cord ischemia was assessed. The mean number of the intercostal and lumbar arteries, coverage length between the left subclavian artery and the stent graft proximal landing zone, total volume of the aneurysmal sac, lumen volume, and thrombosis volume were measured by preoperative and first-step postoperative computed tomography angiography. Patients were also grouped based on the chosen endoprosthesis (group A: double-branch aneurysmal sac reperfusion; group B: single-branch aneurysmal sac reperfusion). RESULTS: Eleven patients (mean age: 76.5 years; range: 61-86) were considered. No 30-day mortality was observed after the first-step procedure, and 1 patient died after second-step treatment. No permanent paraplegia was observed after either the first or second endovascular steps. The lumen volume significantly decreased (27%; P < 0.001) after first-step endovascular treatment although there was a significant increase in aneurysm thrombosis (34% to 54%). The mean number of the intercostal arteries decreased from 19.7 to 9.3 (P < 0.001) after first-step endovascular treatment. Volume variations and percentage of intercostal loss did not significantly differ between the 2 groups. CONCLUSIONS: Although aneurysm volume continued to increase after first-step treatment, two-step endovascular treatment is a feasible alternative to reduce the risk of severe ischemia in patients with extended TAAAs.

Late open conversion after endovascular abdominal aortic aneurysm repair: experience of three-high volume centers.

BACKGROUND: Accumulated endovascular aneurysm repair (EVAR) procedures will increase number of patients requiring conversion to open repair of abdominal aortic aneurysms (AAA). In most cases, patients undergo late open surgical conversion (LOSC), many months, or years, after initial EVAR. The aim of this study is to analyze results of LOSC after EVAR in elective and urgent setting, including presenting features, surgical techniques, as well as to review the clinical outcomes and their predictors. METHODS: Retrospective review of all consecutive patients undergoing LOSC after EVAR was performed at three distinct, high volume, vascular centers. Patients that required primary conversion within 30 days after EVAR have not been included in this study. Between January 1st 2010 and January 1st 2017 total of 31 consecutive patients were treated. LOSC were performed either in elective or in urgent setting, thus dividing patients in two groups. Primary outcome was 30-day mortality and secondary postoperative complications. RESULTS: LOSC rate after EVAR was 4.51%. Most common indication for LOSC was type I endoleak (N.=20, 64.51%). All patients that presented with ruptured AAA had some form of endoleak (type I endoleak was present in five from six cases). Most common site for aortic cross-clamping was infrarenal (51.61%). Stent-graft was removed completely in 18 patients (58.06%) and partially in 13 (41.93%). 30-day mortality rate was 16.12% (5 patients) and most common cause of death was myocardial infarction (60%). Following univariate factors were isolated as predictors for 30-day mortality: preoperative coronary artery disease, chronic obstructive pulmonary disease, urgent LOSC, prolonged time until LOSC, ruptured AAA, supraceliac clamp, higher number of red blood cell transfusion, postoperative myocardial infarction, and prolonged intubation (more than 48 hours). CONCLUSIONS: LOSC seems to be safe and effective procedure when preformed in elective manner. On the other side, urgent LOSC after EVAR is associated with very high postoperative mortality and morbidity. Endoleak remains the main indication for open conversion. Further studies are necessary to standardize timing and treatment options for failing EVAR.

Endovascular Treatment of an Internal Iliac Artery Aneurysm in a Patient with Previous Aortic Surgery Using a Novel Covered Stent Graft.

BACKGROUND: We report endovascular treatment of a patient with an isolated Internal Iliac Artery (IIA) aneurysm who was treated by positioning a novel covered stent that could adapt to different proximal and distal diameters. CASE REPORT: A 68-year-old man who had already had several previous aortic surgeries underwent endovascular treatment for a 41 mm isolated right IIA aneurysm. Two Viabahn VBX (W. L. Gore & Associates, Flagstaff, AZ) covered stents (7 × 79 mm and 8Lx59 mm) were placed from a 6 mm gluteal artery to an 11 mm Dacron hypogastric artery via contralateral femoral surgical access. No complications occurred. One-month follow-up computed tomography angiography (CTA) scan showed the complete exclusion of the aneurysmal sac with spontaneous endoleak resolution and patency of the covered stents. Geometric analysis of the postoperative CTA highlighted VBX conformability to the native vessel. Maximum stented vessel diameter ranged between 9 and 13 mm, and circularity was maintained along the whole stent length, even in zones of higher centerline curvature. CONCLUSIONS: The Viabahn VBX covered stent could be used to treat aneurysms of the IIA.

Kidney Preservation Using Renal Heterotopic Autotransplantation during Fenestrated Endovascular Aortic Repair for Complex Residual Type-A Aortic Dissection.

The treatment of type A acute aortic dissection is a challenge for the surgeon, and serious late complications may occur even after surgical repair. We report treatment after a type A postdissection thoracoabdominal aneurysm in a patient who previously underwent ascending aortic reconstruction using a biological aortic valve and Dacron prosthetic graft implantation in emergency conditions. The multistaged approach involved removing the right kidney and performing a heterotopic autotransplantation in the left iliac fossa before positioning a fenestrated endograft (celiac trunk, superior mesenteric artery, and left renal artery). The final step should have been the implantation of an aorto-bifurcated endograft, which, however, was postponed because the patient was injured during rehabilitation therapy. After 12 months, the computed tomography angiography scan showed complete thrombosis of the false lumen associated with large iliac entry tear closure and aortic diameter stability. These findings prompted us to desist from completing the aorto-bi-iliac implantation. This case demonstrates that in selected patients in whom treatment of a postdissection thoracoabdominal aneurysm with fenestrated endoprosthesis requires a challenging revascularization of the renal artery, a heterotopic kidney transplant using a mini-invasive technique may represent a viable and sufficiently safe alternative that guarantees renal blood perfusion.

Twelve-year Follow-up Post-Thoracic Endovascular Repair in Type B Aortic Dissection Shown by Three-dimensional Printing.

BACKGROUND: Thoracic endovascular repair (TEVAR) is currently considered the therapy of choice for complicated type B acute aortic dissection (TBAAD). Although several papers have reported good outcomes at short- and medium-term follow-up, some questions still remain regarding the long-term durability and re-intervention rate during follow-up. METHODS: We describe a case of a patient originally treated with TEVAR for TBAAD complicated by impending aortic rupture. RESULTS: Endovascular repair successfully excluded the flow through the primary entry tear but during the 12-year follow-up period the patient experienced several complications and re-interventions. Various full-size three-dimensional (3D) models of the patient-specific vasculature were printed to better explain the different interventional interventions over the 12 years of follow-up and as a hands-on tool for medical education. CONCLUSIONS: The present case report, involving long-term follow-up, provides an example of the effectiveness and the safety of TEVAR for the treatment of complicated TBAAD shown at short and medium-term follow-up. However, the long-term complications that were observed in this patient during follow-up support the importance of lifelong CTA surveillance. Furthermore, this study confirms the capability of 3D printing technology as a powerful tool to support communication with patients and residents' education through the physical analysis of the real cases.

Assessment of geometrical remodelling of the aortic arch after hybrid treatment.

OBJECTIVES: The aim of this study was to measure the morphological remodelling of the ascending aorta, aortic arch and thoracic aorta after aortic arch hybrid treatment including debranching and stent graft implantation. METHODS: Preoperative, 1-month and 1-year follow-up of computed tomography angiography scans of 22 patients were analysed to compute the lumen centreline from the aortic root to the coeliac trunk, and the following measurements were derived: the total centreline length, distance from the aortic root to the left subclavian artery, distance from the left subclavian artery to the distal landing zone. For both pre- and postoperative centrelines, the pointwise curvature was measured at the proximal and the distal landing zones. The mean curvature values of the whole aortic segment and the endografting region of the ascending and the descending aorta were measured. Surface outerline was computed as well, and curvature values at the endograft landing points were extracted. RESULTS: At the 1-month follow-up, centreline length were already significantly increased (382.66 ± 48.69 to 388.1 ± 50.75 mm; P = 0.01). Centreline pointwise curvature increased in the proximal (+29%, P = 0.011) and the distal zones (+63%, P = 0.004). Similarly, pointwise curvature of the outerline significantly increased in the proximal (+77%, P = 0.01) and the distal landing zones (+100%, P = 0.04). The centreline mean curvature increased in the ascending aorta (+7%, P = 0.02) and decreased in the endografting region (-3.3%, P = 0.004). No evidence of a relationship of such a remodelling with the type of endograft and the type of pathology was observed. This remodelling trend was confirmed by the analysis of 1-year computed tomography angiographies. CONCLUSIONS: Hybrid arch repair was associated with a significant elongation of the vessel and a significant increase in the curvature on the ascending aorta and the descending aorta and on the endograft proximal and the distal landing zones.

Resistin exerts a beneficial role in atherosclerotic plaque inflammation by inhibiting neutrophil migration.

BACKGROUND: Neutrophil functions have been shown to be modulated by adipocytokines during atherogenesis. The immuno-regulatory role of resistin on neutrophil-mediated activities in atherosclerotic patients remains elusive. Here, we aimed at exploring the association between serum levels of resistin and neutrophil products either in the systemic circulation or within plaques in a cohort of patients with severe carotid plaque stenosis undergoing endarterectomy. In addition, we assessed the effects of resistin on neutrophil pro-atherosclerotic functions in vitro. METHODS: Inflammatory biomarkers, neutrophil products and resistin levels were assessed in patients' sera and carotid plaques by ELISA and immunohistochemistry analysis. In vitro, human primary neutrophils isolated from healthy donors were assessed on different substrate cultures for: degranulation (by ELISA), migration (by microchemotaxis Boyden chamber), F-actin polymerization (by fluorescent assay), integrin and chemokine receptor expression (by flow cytometry) and apoptosis (by both morphologic analysis and flow cytometry). RESULTS: Serum resistin was positively correlated with serum levels of neutrophil granule products, but inversely with intraplaque neutrophil and MMP-9 contents. In vitro, resistin was detected in supernatants of degranulating neutrophils and positively correlated with other granule products. Although resistin did not affect neutrophil degranulation, apoptosis and integrin or chemokine receptor expression, pre-incubation with human recombinant resistin abrogated CXCL8-induced neutrophil migration and F-actin polymerization by inhibiting ERK2 phosphorylation. CONCLUSION: Resistin can be released by degranulating neutrophils and blunts neutrophil plaque infiltration by modulating their migration towards known atherosclerotic mediators. These results suggest a potential immunoregulatory role of resistin in inhibiting neutrophil-mediated atherosclerotic activities.

Midterm Follow-up Geometrical Analysis of Thoracoabdominal Aortic Aneurysms Treated with Multilayer Flow Modulator.

BACKGROUND: Aim of our study is the analysis of clinical results and aneurysmal sac evolution after multilayer flow modulator (MFM) placement, in patients with thoracoabdominal aortic aneurysms (TAAs). METHODS: All patients with asymptomatic TAA treated at our institution between 2012 and 2014 with MFM were retrospectively analyzed. Thirty-day evaluated outcomes were mortality and complications. Follow-up evaluated outcomes were mortality, aneurysm collateral branches patency, and reintervention. A geometrical analysis of 2-year follow-up computed tomography scans was carried out to evaluate the total aneurysm volume, the percentage of aneurysm growth, and the evolution of maximum aneurysm diameter. RESULTS: Seven patients (mean age: 71.8 years, range: 63-85 years) were considered in the study. Mean preoperative aneurysm diameter was 6.8 cm (range 6-8.3 cm). No 30-day mortality or complications were observed. Mean follow-up was 29.4 months. During follow-up, 3 deaths (42.8%) were observed, not related to MFM complications. Reintervention rate was 42.8%, occurred in all cases after 2-year follow-up; in 2 cases, the reintervention was necessary due to an excessive increase of the aneurysmal sac. During the follow-up, a mean growth rate of 6 mm/year (4 patients) for the diameter of the aneurysm external wall and a total aneurysm volume increase from 2.45 × 105 mm3 to 3.50 × 105 mm3 (4 patients) was evaluated. CONCLUSIONS: Our results have shown no mortality related to aneurysm rupture during the follow-up and high rate of reinterventions after MFM placement. Further geometrical analyses, based on the proposed approach, regarding a larger group of patients with long-term follow-up are required to draw indications about the MFM use.

Serum PCSK9 levels predict the occurrence of acute coronary syndromes in patients with severe carotid artery stenosis.

BACKGROUND: The pharmacological inhibition of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has shown to dramatically impact on low-density lipoprotein-cholesterol (LDL-C) levels and associated cardiovascular (CV) diseases. However, the potential use of PCSK9 serum levels as a CV risk biomarker remains to be clarified. METHODS: 189 patients with severe carotid artery atherosclerosis undergoing carotid endarterectomy (CEA) and whose clinical records and serum sample aliquots for PCSK9 level measurement were available both directly before CEA and at 24-month follow-up were included in the present pilot study. The study endpoint was to determine whether PCSK9 serum levels prior to CEA would predict the occurrence of acute coronary syndromes (ACS) at 24-month follow-up. RESULTS: PCSK9 serum levels were significantly accurate in predicting ACS at 24-month follow-up, as assessed by ROC curve analysis (AUC: 0.719 [95% CI 0.649-0.781]). According to the cut-off point indicated by Youden's index, PCSK9 values >431.3 ng/mL were correlated with a higher risk of ACS occurrence (Log Rank test, p = 0.0003). At Cox regression analysis, the predictive ability of high serum PCSK9 was confirmed also after adjustment for age, gender, baseline statin treatment and active smoking, dyslipidemia, and chronic coronary artery disease (HR 17.04 [95% CI 3.34-86.81]; p = 0.001). CONCLUSIONS: High serum PCSK9 levels predict ACS occurrence at 24-month follow-up after CEA in patients with severe carotid artery stenosis. Larger clinical studies are needed to evaluate whether PCSK9 serum levels could be used towards predicting the risk of ACS in patients with advanced carotid atherosclerosis.

Early evaluation of precise deployment with the new low-profile Zenith Alpha Thoracic Endoprosthesis in thoracic aortic disease.

BACKGROUND: Endovascular treatment of thoracic aortic disease currently allows to treat high-risk patients with better results than open repair. It represents the first option for treatment according to the most recent guidelines. The aim of the study is to evaluate the early results of the low-profile Zenith Alpha Thoracic Endoprosthesis (ZATE). METHODS: Between October 2012 and July 2015, 14 asymptomatic patients were treated with ZATE. 10 patients were male, mean age was 71, 7 years (range 58-85 years). 8 patients presented with atherosclerotic aortic aneurysm (7 thoracic aneurysm and 1 type I thoracoabdominal aneurysm), 2 chronic type B aortic dissection, 1 type IV endoleak 5 years after TEVAR, 3 aortic arch penetrating ulcers complicated by pseudoaneurysm. Hybrid staged procedures in 11 patients included 7 total aortic arch debranching (1 single [innominate] chimney stent-graft + carotid-carotid-subclavian), 2 carotid-carotid-subclavian artery bypass, 2 carotid-subclavian artery bypass. RESULTS: No 30-day mortality or major complications were observed. The mean length of stay was 7.3 days (range 4-14 days). Mean procedure time, X ray time and Contrast load were 115 minutes (range 90-150 minutes), 20 minutes (range 10-30) and 79 mL (range 40-120 mL) respectively. 25 stent-grafts were implanted. The mean follow-up was 21 months (range 14-32 months). No mortality and no major complications were observed during the follow-up. In case of arch debranching with landing 0 and 1 zone the mean distance between the beginning of the endoprosthesis and the debranching inflow vessel was 5.5±2.4 mm. CONCLUSIONS: The use of ZATE could be a viable alternative for treating patients with aortic arch proximal landing zone to facilitate the precise deployment. Larger case studies and longer follow-up are needed.