Indoxyl sulphate-initiated activation of cardiac fibroblasts is modulated by aryl hydrocarbon receptor and nuclear factor-erythroid-2-related factor 2.

In the last decade, extensive attention has been paid to the uremic toxin indoxyl sulphate (IS) as an inducer of cardiac fibroblast (cFib) activation and cardiac fibrosis in chronic kidney disease. At cellular level, IS engages aryl hydrocarbon receptor (AhR) and regulates many biological functions. We analysed how AhR inhibition by CH-223191 (CH) and overexpression of non-functional (dominant negative, DN) nuclear factor-erythroid-2-related factor 2 (NRF2), a transcription factor recruited by AhR, modulate the response of neonatal mouse (nm) cFib to IS. We also evaluated nm-cardiomyocytes after incubation with the conditioned medium (CM) of IS±CH-treated nm-cFib. IS induced activation, collagen synthesis, TLR4 and-downstream-MCP-1, and the genes encoding angiotensinogen, angiotensin-converting enzyme, angiotensin type 1 receptor (AT1r) and neprilysin (Nepr) in nm-cFib. CH antagonized IS-initiated nm-cFib activation, but did not affect or even magnified the other features. IS promoted NRF2 nuclear translocation and expression the NRF2 target Nqo1. Both pre-incubation with CH and transfection of DN-NRF2 resulted in loss of NRF2 nuclear localization. Moreover, DN-NRF2 overexpression led to greater TLR4 and MCP-1 levels following exposure to IS. The CM of IS-primed nm-cFib and to a larger extent the CM of IS+CH-treated nm-cFib upregulated AT1r, Nepr and TNFα and myostatin genes in nm-cardiomyocytes. Hence, IS triggers pro-inflammatory activation of nm-cFib partly via AhR, and AhR-NRF2 counteract it. Strategies other than AhR inhibition are needed to target IS detrimental actions on cardiac cells.

Endovascular aortic repair impact on myocardial contractility: A prospective study.

BACKGROUND: This study aimed to estimate if the altered sphygmic wave transmission may affect the left ventricular (LV) contractile function in patients undergoing endovascular aortic repair (EVAR). METHODS: A prospective single-centre study was carried out on consecutive patients undergoing EVAR for abdominal aortic aneurysm. A preoperative and 6-month single photon emission computed tomography (SPECT) with arterial stiffness measurement were performed to evaluate variations in pressure wave curve and myocardial perfusion parameters. RESULTS: From 2018 to 2020 a total of 16 patients were included in the study. Among the parameters evaluated, we found a measurable reduction of the reflected wave transit time from pre- to postoperative period, for both stress (115.13 ± 7.2 ms-111.1 ± 7.0 ms, p = .08) and rest SPECT acquisitions (115.3 ± 6.2 ms-112.2 ± 5.6 ms, p = .1). Unidirectional increase of both LV end-systolic volume (34 ± 9 mL-39 ± 8 mL, p = .02) and end-diastolic volume (85 ± 34 mL-89 ± 29 mL, p = .6) was also observed. Lastly, the ratio between the end-systolic pressure and the end-systolic volume (maximal systolic myocardial stiffness) decreased from 3.6 ± 1.5 mmHg/mL to 2.66 ± .74 mmHg/mL (p = .03). CONCLUSIONS: Our data showed that EVAR induced an altered transmission of the sphygmic wave associated with an early LV contractile impairment.

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.

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.

Initial Clinical Experience With a New Conformable Abdominal Aortic Endograft: Aortic Neck Coverage and Curvature Analysis in Challenging Aortic Necks.

OBJECTIVES: Aim of this work was to investigate precision of deployment and conformability of a new generation GORE EXCLUDER Conformable Endoprosthesis with active control system (CEXC Device, W.L. Gore and Associates, Flagstaff, AZ, USA) by analyzing aortic neck coverage and curvature. METHODS: All consecutive elective patients affected by abdominal aortic aneurysm or aortoiliac aneurysm treated at our institution between November 2018 and June 2019 with the new CEXC Device were enrolled. Validated software was adopted to determine the available apposition surface area into the aortic neck, apposition of the endograft to the aortic wall, shortest apposition length (SAL), shortest distance between the endograft fabric and the lowest renal arteries (SFD) and between the endograft fabric and the contralateral renal artery (CFD). Pointwise centerline curvature was also computed. RESULTS: Twelve patients (10 men, median age 78 years (71.75, 81.0)) with available pre- and postoperative computed tomography angiography (CTA) were included. Technical success was obtained in all the cases. Preoperative median length of the proximal aortic neck was 16.1 mm (10.7, 21.7) and suprarenal (α) and infrarenal (ß) neck angulation were, respectively, 28.9° (15.7°, 47.5°) and 75.0° (66.9°, 81.4°). Postoperative median apposition surface coverage was 79% (69.25%, 90.75%) of the available apposition surface. SFD and CFD were 1.5 mm (0.75, 5.25) and 7 mm (4.5, 21.5), respectively. Average curvature over the infrarenal aorta decreased from 25 m-1 (21.75, 29.0) to 22.5 m-1 (18.75, 24.5) postoperatively (p=0.02). Maximum curvature did not decrease significantly from 64.5 m-1 (54.25, 92.0) to 62 m-1 (41.75, 71.5) (p=0.1). CONCLUSIONS: Our early experience showed that deployment of the CEXC Device is safe and effective for patients with challenging proximal aortic necks. Absence of significant changes between pre- and postoperative proximal aortic neck angulations and curvature confirms the high conformability of this endograft.

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.

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.

The TAXINOMISIS Project: A multidisciplinary approach for the development of a new risk stratification model for patients with asymptomatic carotid artery stenosis.

INTRODUCTION: Asymptomatic carotid artery stenosis (ACAS) may cause future stroke and therefore patients with ACAS require best medical treatment. Patients at high risk for stroke may opt for additional revascularization (either surgery or stenting) but the future stroke risk should outweigh the risk for peri/post-operative stroke/death. Current risk stratification for patients with ACAS is largely based on outdated randomized-controlled trials that lack the integration of improved medical therapies and risk factor control. Furthermore, recent circulating and imaging biomarkers for stroke have never been included in a risk stratification model. The TAXINOMISIS Project aims to develop a new risk stratification model for cerebrovascular complications in patients with ACAS and this will be tested through a prospective observational multicentre clinical trial performed in six major European vascular surgery centres. METHODS AND ANALYSIS: The risk stratification model will compromise clinical, circulating, plaque and imaging biomarkers. The prospective multicentre observational study will include 300 patients with 50%-99% ACAS. The primary endpoint is the three-year incidence of cerebrovascular complications. Biomarkers will be retrieved from plasma samples, brain MRI, carotid MRA and duplex ultrasound. The TAXINOMISIS Project will serve as a platform for the development of new computer tools that assess plaque progression based on radiology images and a lab-on-chip with genetic variants that could predict medication response in individual patients. CONCLUSION: Results from the TAXINOMISIS study could potentially improve future risk stratification in patients with ACAS to assist personalized evidence-based treatment decision-making.

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.

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.

In Vivo Morphological Changes of the Femoropopliteal Arteries due to Knee Flexion After Endovascular Treatment of Popliteal Aneurysm.

Purpose: To evaluate morphological changes of the femoropopliteal (FP) arteries due to limb flexion in patients undergoing endovascular treatment of popliteal artery aneurysms (PAAs). Materials and Methods: Seven male patients (mean age 68 years) underwent endovascular treatment of PAA with a Viabahn stent-graft between January 2013 and December 2017. During follow-up, one contrast-enhanced computed tomography angiography (CTA) scan of the lower limbs was acquired for each recruited patient. A standardized CTA protocol for acquisitions in both straight-leg and bent-leg positions was used to visualize changes in artery shape due to limb flexion. Three-dimensional reconstruction of the FP segment was performed to compute mean diameter and eccentricity of the vascular lumen and to measure length, tortuosity, and curvature of the vessel centerline in 3 arterial zones: (A) between the origin of the superficial femoral artery and the proximal end of the stent-graft, (B) within the stent-graft, and (C) from the distal end of the stent-graft to the origin of the anterior tibial artery. Results: After limb flexion, all zones of the FP segment foreshortened: 6% in zone A (p=0.001), 4% in zone B (p=0.001), and 8% in zone C (p=0.07), which was the shortest (mean 4.5±3.6 cm compared with 23.8±5.7 cm in zone A and 23.6±7.4 cm in zone B). Tortuosity increased in zone A (mean 0.03 to 0.05, p=0.03), in zone B (0.06 to 0.15, p=0.005), and in zone C (0.027 to 0.031, p=0.1). Mean curvature increased 15% (p=0.05) in zone A, 27% (p=0.005) in zone B, and 95% (p=0.06) in zone C. In all zones, the mean artery diameter and eccentricity were not significantly affected by limb flexion. Conclusion: Limb flexion induces vessel foreshortening and increases mean curvature and tortuosity of the FP segment both within and outside the area of the stent-graft.

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.

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.

Serum lipoprotein (a) predicts acute coronary syndromes in patients with severe carotid stenosis.

BACKGROUND: Different cut-off values of serum lipoprotein (a) [Lp (a)] were recently identified to better stratify cardiovascular risk categories. Both pathophysiological and prognostic values of Lp (a) remain unclear. MATERIALS AND METHODS: Here, the prognostic value of Lp (a) and its correlation with intraplaque features were assessed in patients with severe carotid artery stenosis undergoing endarterectomy (n = 180). The cut-off value of 10 mg/dL for serum Lp (a) was selected to predict 24-month follow-up acute coronary syndrome (ACS). In addition, the association between serum Lp (a) and intraplaque lipids, collagen, inflammatory and vascular cells was assessed. Serum Lp (a) levels were measured by nephelometric assay. RESULTS: Patients with high Lp (a) had similar comorbidities, medications and laboratory parameters as compared to low Lp (a) levels. At 24-month follow-up, patients with high Lp (a) had more ACS as compared to low levels. Histological parameters within plaques were comparable in the study groups. No significant correlation between Lp (a) serum levels and intraplaque parameters was found, except for a weak positive association with smooth muscle cells in upstream plaque portions. When adjusted for gender, the presence of dyslipidaemia and chronic coronary artery disease, Lp (a) ≥10 mg/dL remained predictive for ACS. CONCLUSIONS: Lp (a) determination could be a useful tool to predict ACS in patients with severe carotid stenosis.

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.

Inflammatory Response Modulation through a PPARγ Agonist during Surgically Induced Visceral Ischemia in an Animal Model.

BACKGROUND: Ischemia/reperfusion (I/R) injury represents one of the most severe complications in vascular surgery where cross-clamping of the aorta and subsequent visceral ischemia are a recurrent issue. The literature describes a family of nuclear receptors, that is, peroxisome proliferator-activated receptors (PPARs), in particular PPARγ isoform, which are important modulators of vascular inflammation resulting from I/R injury. The aim of our study is to evaluate how PPARγ agonist administration could reduce local and systemic inflammatory response after I/R injury during aortic supraceliac clamping in animal model. METHODS: Our model includes 16 rats divided as follows: 8 rats in the placebo control group (PlacG) were operated on without having been administered of any drugs during the preoperative period, whereas the 8 rats in the pioglitazone group (PioG) were pretreated with pioglitazone. Renal and visceral ischemias were induced in the rats by supraceliac aortic clamping. Rats were sacrificed after surgery, and then, we collected blood samples to measure serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and one of the kidneys and a segment of the liver to perform histological analysis. RESULTS: Considering both cytokines in the PioG, there has been a negative trend in serum concentrations, whereas in the PlacG, we observed an increasing trend. The high standard deviation observed in our study is mainly due to the small population of the cohort. Histologic examination of the kidney showed more severe damage in the placebo group as compared to the PioG with more evident differences in tubular and tubulointerstitial scores. CONCLUSIONS: Our observations show that administering pioglitazone can partially reduce secondary inflammatory response in the ischemic insult especially in endothelial and perivascular tissues.

Treatment with aromatase inhibitors and markers of cardiovascular disease.

PURPOSE: The cardiovascular effects of estrogen deprivation induced by aromatase inhibitors are unknown. We carried out a cross-sectional study to evaluate the effect of estrogen deprivation induced by aromatase inhibitors on markers of cardiovascular risk. METHODS: We enrolled 410 postmenopausal women: 200 consecutive breast cancer patients treated with aromatase inhibitors for a median of 53 months (range 23-122) and 210 volunteer controls. Carotid intima-media thickness, presence of carotid stenosis, and presence of abdominal aortic aneurism were evaluated through an ultrasound examination. RESULTS: Average carotid intima-media thickness was 0.97 ± 0.02 mm and 1.08 ± 0.02 mm for breast cancer group and control group, respectively (p < 0.005). The incidence of carotid stenosis in the two groups was similar: 24.2 % in the breast cancer group and 28.6 % in the control group (OR 0.80; 95 % CI 0.51-1.25; p = 0.32). No aneurismatic dilatation of the aorta was recorded. Average abdominal aortic diameter was 14.9 ± 2.4 mm in the breast cancer group and 15.0 ± 2.4 mm in the control group. CONCLUSIONS: Our study showed no association between treatment with aromatase inhibitors for five or less years and increased carotid intima-media thickness and higher prevalence of carotid stenosis or abdominal aortic aneurism. The lack of impact on these markers suggests that cardiovascular risk is not increased by treatment with aromatase inhibitors.

A Single-Center Experience of Aortic and Iliac Artery Aneurysm Treated with Multilayer Flow Modulator.

BACKGROUND: The aim of this study was to analyze our series of endovascular treatments using a multilayer flow modulator (MFM) and to show the midterm results. METHODS: At our institution, 8 patients were treated with an MFM. Four patients presented with an aortic aneurysm (2 type II thoracoabdominal aortic aneurysms [TAAAs], 1 type IV TAAA, and 1 juxtarenal abdominal aortic aneurysm) and 4 with an aneurysm involving the common iliac artery. Mortality, rupture and secondary intervention, major complications, patency of collateral vessels, and volume analysis were evaluated. Treated patients were followed up with computed tomography angiography at 1, 3, 6, and 12 months. RESULTS: Results showed no 30-day mortality or major complications; technical success was achieved in 87.5% of patients, patency of collateral vessels was reached in all cases at intraoperative completion angiography. Mean follow-up was 22.1 months (range, 18-30), survival rate was 87.5%, and one case of death unrelated to MFM treatment was reported. During follow-up, MFM and collateral vessel patency were observed in all cases. Secondary endovascular or open surgical procedures were not needed during follow-up. Volume analysis showed a slight increase in patients with aortic aneurysm, and an overall trend to increase in thrombosis was observed in all cases. CONCLUSIONS: Endovascular treatment of aneurysms with MFM seems to have encouraging midterm results. Should our results be confirmed by larger series and longer follow-up studies, MFM may become a viable alternative to other endovascular approaches.

In Vitro Evaluation of Upstream and Downstream Influences on Blood Pressure of the Hybrid Treatment of Thoracoabdominal Aortic Aneurysms.

BACKGROUND: The aim of our study was to assess, by means of an experimental model, whether different geometries in retrograde bypass and stent-graft deployment may affect upstream and downstream blood pressure in hybrid treatment. METHODS: An in vitro model of the arterial circulation has been prepared, which consists of a peristaltic pump, silicon tubes with geometrical and mechanical properties close to realistic arteries, a terminal reservoir kept at constant pressure, and a sequence of pressure transducers. The system allows us to study the pressure wave propagation in physiological conditions and simulate the patient's conditions as a result of debranching in 2 different configurations. RESULTS: In configuration 1, the mean pressure value (Kpa) was 4.72 in silicone tube before stent graft and debranching, 4.59 in visceral and renal bypass, and 4.38 in silicone tube after stent graft and debranching. In configuration 2, the mean pressure value (Kpa) was 5.22 in silicone tube before stent graft and debranching, 4.48 in visceral and renal bypass, and 4.99 in silicone tube after stent graft and debranching. CONCLUSION: The experimental data suggest that the debranching geometry and the material of the grafts and stent grafts change significantly the physiological arterial pressure possibly leading to an augmented pressure upstream of the stent grafts, owing to retrograde pressure waves toward the heart, and a decreased pressure downstream visceral and renal arteries.

Intraplaque Expression of C-Reactive Protein Predicts Cardiovascular Events in Patients with Severe Atherosclerotic Carotid Artery Stenosis.

Serum c-reactive protein (CRP) was suggested for the assessment of intermediate cardiovascular (CV) risk. Here, systemic or intraplaque CRP levels were investigated as predictors of major adverse cardiovascular events (MACEs) in patients with severe carotid stenosis. CRP levels were assessed in the serum and within different portions (upstream and downstream) of carotid plaques of 217 patients undergoing endarterectomy. The association between CRP and intraplaque lipids, collagen, neutrophils, smooth muscle cells (SMC), and macrophage subsets was determined. No correlation between serum CRP and intraplaque biomarkers was observed. In upstream portions, CRP content was directly correlated with intraplaque neutrophils, total macrophages, and M1 macrophages and inversely correlated with SMC content. In downstream portions, intraplaque CRP correlated with M1 and M2 macrophages. According to the cut-off point (CRP > 2.9%) identified by ROC analysis in upstream portions, Kaplan-Meier analysis showed that patients with high CRP levels had a greater rate of MACEs. This risk of MACEs increased independently of age, male gender, serum CRP, and statin use. In conclusion, in patients with severe carotid artery stenosis, high CRP levels within upstream portions of carotid plaques directly and positively correlate with intraplaque inflammatory cells and predict MACEs at an 18-month follow-up period.