Atherosclerotic plaque instability in carotid arteries: miR-200c as a promising biomarker.

Early recognition of vulnerable carotid plaques could help in identifying patients at high stroke risk, who may benefit from earlier revascularisation. Nowadays, different biomarkers of plaque instability have been unravelled, among these miRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two miRNAs involved in atherosclerosis progression. The goal of the present study was to determine whether miR-200c could be an atherosclerosis biomarker. Carotid plaques of patients that underwent carotid endarterectomy (CEA) were assayed for miR-200c expression. miR-200c was up-regulated in carotid plaques (n=22) and its expression was higher in unstable (n=12) compared with stable (n=10) plaques. miR-200c positively correlated with instability biomarkers (i.e. monocyte chemoattractant protein-1, cicloxigenase-2 (COX2), interleukin 6 (IL6), metalloproteinase (MMP) 1 (MMP1), 9 (MMP9)) and miR-33a/b. Moreover, miR-200c negatively correlated with stability biomarkers (i.e. zinc finger E-box binding homoeobox 1 (ZEB1), endothelial nitric oxide (NO) synthase (eNOS), forkhead boxO1 (FOXO1) and Sirtuin1 (SIRT1)) (stable plaques = 15, unstable plaques = 15). Circulating miR-200c was up-regulated before CEA in 24 patients, correlated with miR-33a/b and decreased 1 day after CEA. Interestingly, 1 month after CEA, circulating miR-200c is low in patients with stable plaques (n=11) and increased to control levels, in patients with unstable plaques (n=13). Further studies are needed to establish whether miR-200c represents a circulating biomarker of plaque instability. Our results show that miR-200c is an atherosclerotic plaque progression biomarker and suggest that it may be clinically useful to identify patients at high embolic risk.

Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience.

BACKGROUND: The aim of this study is to analyze the effects of peripheral blood mononuclear cells (PBMNCs) therapy in diabetic patients with critical limb ischemia (CLI), with particular regard to its application, as adjuvant therapy in patients underwent endovascular revascularization. METHODS: Fifty diabetic patients affected by CLI were enrolled. All patients underwent PBMNCs therapy. Thirty-two patients underwent PBMNCs therapy associated with endovascular revascularization (adjuvant therapy group). In 18 patients, who were considered nonrevascularizable or underwent unsuccessful revascularization, regenerative therapy with PBMNCs was performed as the therapeutic choice (PBMNCs therapy group). RESULTS: The median follow-up period was 10 months. The baseline and end point results in adjuvant group were as follows. The mean transcutaneous partial pressure of oxygen (TcPO2) improved from 25 ± 9.2 mmHg to 45.6 ± 19.1 mmHg (P < 0.001), and visual analogue scale (VAS) score means decreased from 8.6 ± 2.1 to 3.8 ± 3.5 (P = 0.001). In PBMNCs therapy group, the mean TcPO2 improved from 16.2 ± 7.2 mmHg to 23.5 ± 8.4 mmHg (P < 0.001), and VAS score means decreased from 9 ± 1.1 to 4.1 ± 3.3 (P = 0.001). Major amputation was observed in 3 cases (9.4%), both in adjuvant therapy group and in PBMNCs therapy one (16.7%) (P = 0.6). CONCLUSIONS: The role of cellular therapy with PBMNCs is decisive in the patients that are not susceptible to revascularization. In diabetic patients with CLI and healing resistant ulcers, the adjuvant PBMNCs therapy could represent a valid therapeutic option.

The Role of the Profundoplasty in the Modern Management of Patient with Peripheral Vascular Disease.

BACKGROUND: The occlusion of superficial femoris artery (SFA) is a common feature in peripheral vascular disease, so the profunda femoris artery (PFA) is a crucial collateral pathway for the perfusion of the lower limb. The purpose of this study is to discuss the safety, clinical, and hemodynamic efficacy of profundoplasty on the basis of limb salvage, patency, and freedom from reintervention rates. Furthermore, this study aims to identify the risk factors linked to the failure of the procedure. METHODS: The study is based on a retrospective analysis of prospectively collected data of identified patients who underwent profundoplasty from March 2005 to October 2015. All patients showed a hemodynamic stenosis, extended from the posterior wall of the common femoral artery (CFA) into the origin of the PFA and concomitant occlusion of SFA. Endarterectomy with patch angioplasty was performed in all cases. In patients with concomitant iliac occlusive disease, a hybrid treatment was carried out to restore an adequate inflow through an endovascular approach. RESULTS: Seventy-four profundoplasty were performed during the study period. Isolate profundoplasty was performed in 56 cases (75.7%), while in the remaining 18 cases (24.3%), concomitant endovascular treatment of iliac lesions was performed. Hemodynamic success was achieved in 90.5% of the cases. The mean ankle-brachial index significantly improved, rising from 0.36 ± 0.17 preoperatively to 0.57 ± 0.20 postoperatively (P < 0.001). The median follow-up period was 33 months. Primary patency rate was 98.5% at 12, 36, and 60 months. Freedom from reintervention rate was 97% at 1 year and 95.3% at 3 and 5 years. Limb salvage rate was 96.9% at 1 year and 92.7% at 3 and 5 years. Survival rates were 86%, 60%, and 47.4% at 1, 3, and 5 years, respectively. Multivariate analysis identified Rutherford class 5 or 6 lesions as the strongest predictors of major amputation or reintervention (odds ratio, 9.37; confidence interval: 0.98-89.27; P = 0.05). CONCLUSIONS: Profundoplasty is a durable, safe, and effective procedure in terms of clinical and hemodynamic results for patients characterized by occlusion of SFA and stenosis of CFA extended to profunda ostium. For patients with Rutherford category 5 and 6 ischemia, the only profundoplasty does not seem to be adequate, and concomitant distal bypass should be necessary to improve limb salvage and decrease reintervention rate.

Carotid Endarterectomy or Stenting in Octogenarians in a Monocentric Experience.

BACKGROUND: Carotid artery stenting (CAS) has emerged as an alternative to carotid endarterectomy (CEA) in patients at high risk for complications from surgery. The very elderly (≥80-year-old) are 1 subgroup of patients identified as being at increased risk for carotid surgery. However, there is concern that the very elderly are also at increased risk for complications of CAS. A stroke and death rate of 12% were reported in very elderly patients during the roll-in phase of Carotid Revascularization Endarterectomy versus Stent Trial. We are reporting on a clinical series of CAS and CEA with independent neurologic assessment in the very elderly. The aim of this article is to evaluate early and mild-term results obtained in the treatment of the carotid artery stenosis in symptomatic and asymptomatic octogenarians, comparing the data of CEA and CAS in academic hospital. METHODS: Between 2002 and 2013, a consecutive series of 129 CAS and 45 CEA patients (≥80-year-old) were treated in our academic hospital, a center with extensive carotid revascularization experience. Independent neurologic assessment was performed before and after procedures. Exclusion criteria were cerebral hemorrhage diagnosed within 6 months, cerebral tumors and dementia. Hostile aortic arches were nevertheless treated with alternative approaches like cervical or radial access. All the procedures have been performed by the senior authors. RESULTS: The average age was 86.9 years. Most patients were male (56%), and the target lesion carotid stenosis was asymptomatic in 80% of patients. No significant differences were obtained regarding gender, symptoms, risk factors or comorbidities, and evident CT lesions among the 2 groups of different treatments. Embolic protection devices were used in all cases with the CAS procedure. The overall 30-day incidence of stroke and death was 2.3% (3 of 129) in CAS group and 4.4% (2 of 45) in CEA group. CONCLUSIONS: Exclusion of high-risk patients from CAS, based on age alone, seems to be unjustified. Octogenarians are not at increased risk of periprocedural adverse events after CAS compared with younger patients. The key to obtain satisfactory results is CAS to be performed by an experienced team able to use not only standard filter protected CAS but also familiar with all the other types of access and protection techniques.

Hybrid treatment for thoracoabdominal aortic aneurysms in patients with Marfan syndrome.

Marfan syndrome is a heritable disorder of connective tissue leading to aortic aneurysms and other cardiovascular complications associated with reduced life expectancy. Although contemporary management of ascending aortic disease requires open surgical reconstruction, the combined retrograde visceral revascularization and endovascular exclusion (hybrid procedure) of entire thoracoabdominal aorta has been introduced for the management of descending thoracic and abdominal aortic pathology. The present experience reports 2 cases of thoracoabdominal aortic aneurysms, in Marfan patients, previously submitted to major cardiovascular surgical procedures, through a hybrid approach.

Trans-Atlantic Inter-Society Consensus II C and D iliac lesions can be treated by endovascular and hybrid approach: a single-center experience.

PURPOSE: To evaluate the long-term results of endovascular and hybrid treatment in patients with Trans-Atlantic Inter-Society Consensus (TASC) II type "C" and "D" aortoiliac lesions and to highlight, in contrast to TASC II guidelines, the importance to analyze individually the lesions of a single iliac axis. METHODS: From January 2008 to December 2012, 50 patients with TASC II type C and D aortoiliac lesions underwent endovascular or hybrid treatment. In 38 patients (76%), the lesions were treated by endovascular approach, while in 12 (24%) patients surgical treatment was adopted. All patients underwent a postoperative surveillance program at 1, 3, and 6 months for the first year and every 6 months thereafter. RESULTS: Technical success was achieved in all patients (100%). The postoperative complication rate was 4%. Primary patency rate was 93.3% at 1 year, 90.2% at 2 years, and 86.6% at 3 years. Cumulative secondary patency rate was 97.7% at 1, 2, and 3 years. Survival after 1 and 2 years was 94.8% and after 3 years was 91.1%. Limb salvage was 100% for the entire period of follow-up. CONCLUSIONS: In contrast to TASC II guidelines, the endovascular or hybrid treatment should be considered a valid approach for type C and D lesions. The hybrid treatment, in selected cases, is an effective method to improve the runoff, which plays a key role in the success of the treatment of multilevel stenoocclusive lesions. In TASC II C to D iliac lesions, a specific overview of each axis is necessary in order to select the most appropriate treatment.