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Objectives: Abdominal aortic aneurysm (AAA) is defined as a localized dilatation of an aortic vessel. Though predominantly asymptomatic, it is a chronic degenerative condition associated with life-threatening risk of rupture. The early diagnosis of AAA, ie, before it ruptures, is therefore important; a simple, effective diagnostic method is ultrasound examination. To assess the benefit of screening in Italy, we developed a cost-effective Markov model comparing screening vs nonscreening scenarios. Methods: A 13-health-states Markov model was developed to compare two cohorts of 65- to 75-year-old men: the first group undergoing screening for AAA by means of ultrasound (US), the second following the current practice of incidental detection. The following health states were distinguished: no AAA, unknown small AAA (3-3.9 cm), followed-up small AAA (1 year), unknown medium-sized AAA (4-4.9 cm), followed-up medium-sized AAA (6 months), unknown large AAA (>5 cm), elective repair, emergency repair, postelective-repair AAA, postemergency-repair AAA, rejected large AAA, and death. Transitions between health states were simulated by using 6-month cycles. Transition probabilities were derived from a literature review of relevant randomized controlled trial and from a screening program that is currently ongoing at San Martino Hospital in Genoa, Italy. The Italian National Health Service (NHS) perspective was adopted and incremental cost per life-year saved was calculated with a lifetime horizon; costs and health benefits were discounted at an annual rate of 3% from year 2 onward. Uncertainty surrounding the model inputs was tested by means of univariate, multivariate, and probabilistic sensitivity analyses. Results: Considering an attendance rate of 62%, the individual cost per invited subject was €60 (US $83.2); 0.011 additional quality adjusted life years (QALY) were gained per patient in the screened cohort, corresponding to an incremental cost-effectiveness ratio (ICER) of €5673/QALY (US $7870/QALY). The results were sensitive to some parameter variations but consistent with the base case scenario. They suggest that on the basis of a willingness-to-pay threshold of €50,000/QALY, screening for AAA is cost-effective, with a probability approaching 100%. Conclusions: As in economic evaluations developed in other countries, such as the UK, Canada, and The Netherlands, setting up a screening program for AAA can be considered cost-effective from the Italian NHS perspective. [Copyright &y& Elsevier]

• Patient-specific hemodynamics simulations are performed for femoro-popliteal artery in both straight- and bent-leg position. • Size mismatch between overlapping stents induces intra-stent lumen discontinuity. • Proximal stent has larger caliber, lower velocity, lower wall shear stress, and lower helicity than distal one. • Intra-stent thrombosis has helical shape that correlates with helicity pattern computed by flow simulations. • Leg bending increases of arterial tortuosity, reduces the flow velocity, promoting low wall shear stress. Intra-stent thrombosis is one of the major failure modes of popliteal aneurysm endovascular repair, especially when the diseased arterial segment is long and requires overlapping stent-grafts having different nominal diameters in order to accommodate the native arterial tapering. However, the interplay between stent sizing, post-operative arterial tortuosity, luminal diameter, local hemodynamics, and thrombosis onset is not elucidated, yet. In the present study, a popliteal aneurysm was treated with endovascular deployment of two overlapped stent-grafts, showing intra-stent thrombosis at one-year follow-up examination. Patient-specific computational fluid-dynamics analyses including straight- and bent-leg position were performed. The computational fluid-dynamics analysis showed that the overlapping of the stent-grafts induces a severe discontinuity of lumen, dividing the stented artery in two regions: the proximal part, affected by thrombosis, is characterized by larger diameter, low tortuosity, low flow velocity, low helicity, and low wall shear stress; the distal part presents higher tortuosity and smaller lumen diameter promoting higher flow velocity, higher helicity, and higher wall shear stress. Moreover, leg bending induces an overall increase of arterial tortuosity and reduces flow velocity promoting furtherly the luminal area exposed to low wall shear stress. [ABSTRACT FROM AUTHOR]

As endocrine organ, adipose tissue may modulate inflammatory response by releasing a wide range of mediators, known as adipocytokines. Due to the complex balance between pro- and anti-inflammatory activity their pathophysiological and prognostic role in cardiovascular (CV) diseases still remains debated. Here, we consider the potential associations of circulating adipocytokines adiponectin, leptin and their ratio (LAR), with metabolic and inflammatory profiles in 217 patients with severe carotid stenosis. A prospective analysis investigating their predictive role toward acute coronary syndromes (ACS) was also drawn over a 12-month follow-up period. Serum leptin was positively associated with fasting insulinemia and HOMA-IR, but not with lipid profile and inflammation. Conversely, adiponectin was negatively associated with glucose, insulin, HOMA-IR, triglycerides and both systemic and intraplaque inflammatory markers whereas a positive association with high-density lipoprotein cholesterol (HDL-c) was observed. Accordingly, a significant association with metabolic profile was reported for LAR. According to the cut-off point identified by ROC curve, adiponectin values ≤ 2.56 μg/mL were correlated with a higher risk of ACS occurrence at 12 months' follow-up ( p -value for Log Rank test = 0.0003). At Cox regression analysis the predictive ability of low serum adiponectin was confirmed also after adjustment for age, male gender and diabetes. In conclusion, adiponectin may be considered a biomarker of metabolic compensation, inversely associated with chronic low-grade inflammation. Circulating adiponectin is also associated with lower risk of adverse CV events in patients with severe carotid stenosis. [ABSTRACT FROM AUTHOR]

The role of Vitamin D system in cardiovascular diseases remains controversial. Here, we investigated whether intraplaque levels of vitamin D receptor (VDR) predicted major adverse cardiovascular events (MACEs) at 18 month-follow-up and correlated with macrophage subsets in 164 patients undergoing endarterectomy for carotid stenosis. In human carotid plaque portions upstream and downstream the blood flow, VDR, lipid, collagen, as well as macrophage subsets were determined. Human primary monocytes were then differentiated in vitro to M1 and M2 macrophages and treated with 1,25(OH) 2 D 3 . Intraplaque VDR positively correlated with total and M1 macrophages. According to the result of ROC curve analysis, downstream portions of plaques having high VDR expression were characterized by increased M1 macrophages. Kaplan-Meier analysis showed that the risk of MACEs was greater in patients having low downstream VDR levels (8.2% vs. 1.3%; p = 0.005). Cox proportional hazard regression analyses confirmed that MACE risk decreased with increasing downstream VDR (adjusted HR 0.78 [95% CI 0.62–0.98]; p = 0.032). In vitro, VDR expression was prevalent in M1, but not M2. Incubation of M1 macrophages with 1,25(OH) 2 D 3 , increased VDR expression and suppressed toll-like receptor 4 expression. These results suggest that low intraplaque VDR expression predict MACEs in patients with carotid stenosis potentially involving M1 macrophages. [ABSTRACT FROM AUTHOR]

Ischemia-Reperfusion (I/R) damage is one of the major challenges in cardiothoracic surgeries and in a pathological manner, is identified by exacerbated damage signals resulted from blood supply restriction and subsequent flow restoration and re‑oxygenation. I/R damage includes cellular dysfunction and death, impairing tissue and organ function. Inflammation and oxidative stress are known to underlie either ischemia or reperfusion, leaded by HIF, TNF-α, NF-κB, IL-6 and ROS formation. However, the available approaches to prevent I/R damage has been unsuccessful so far. As agonists of peroxisome-proliferation activation receptor (PPAR) are described as transcription factors related to anti-inflammatory factors, we proposed to observe the effects of novel dual agonist, GQ-11, in I/R-related damage. Male, Wistar rats, 60 days age and 305 g body weight average were treated with vehicle, pioglitazone or GQ-11 (20 mg/kg) for 7 consecutive days and were submitted to aorta clamping for 30 min followed by 3 h of reperfusion. 18F-fluorodeoxyglucose (18F-FDG), an analog of glucose associated with inflammation when accumulated, was observed in liver and bowel by positron emission tomography (PET). RESULTS: GQ-11 decreased 18F-FDG uptake in liver and bowel when compared to vehicle and pioglitazone. The treatment also modulated inflammatory markers IL-10, TGF-β, IL-6, IL1-β, TNFα, and CCL-2, besides antioxidant enzymes such as catalase, GPx and SOD. Inflammation and oxidative stress showed to be important processes to be regulated in I/R in order to prevent exacerbated responses that leads to cell/tissue dysfunction and death. PPAR agonists – including GQ-11 - might be promising agents in a strategy to avoid tissue dysfunction and death after cardiothoracic surgeries. [ABSTRACT FROM AUTHOR]