Early Embolization After Carotid Artery Stenting with Mesh-Covered Stent: Role of Diffusion-Weighted Magnetic Resonance Imaging as Pre-procedural Predictor and Discriminant Between Intra- and Post-procedural Events.

OBJECTIVES: To evaluate the incidence and the time of onset of early micro-embolism after CAS (carotid artery stenting) with two different mesh-covered stents and to assess the role of DW-MRI (Diffusion-weighted magnetic resonance imaging) in their prediction. METHODS: Single-institution prospective study including 50 patients (33 male, median age 74 years) who underwent CAS with Roadsaver® or CGuard™. All patients with primary stenosis (37/50, 74%) had carotid plaque DW-MRI pre-procedure, with both qualitative evaluation of the hyperintensity and ADC (apparent diffusion coefficient) measurement of the plaque. All patients had brain DW-MRI pre-procedure, at 1 h, 24 h and 30 days post-procedure to evaluate the appearance of hyperintense lesions over time. Imaging analysis was performed in a double-blinded fashion by two radiologists. RESULTS: There were no statistically significant differences between the two stents both in the incidence at 1 h (P = 0.23) and 24 h (P = 0.36) and in the volume of new DWI hyperintense brain lesions at 24 h (P = 0.27). Thirty-four new asymptomatic lesions in 19 patients (38%) were reported: 4 (11.8%) at 1 h, 30 (88.2%) at 24 h. The 30-day DWI-MR showed complete resolution of all lesions and no evidence of new lesion. The incidence of new lesions at 24 h resulted significantly higher in patients with DWI hyperintense carotid plaques (12/16, 75% vs. 0/21, 0%, P < 0.0001). This result was paralleled by the difference in ADC value (0.83 ± 0.21 vs. 1.42 ± 0.52). CONCLUSION: The majority of early asymptomatic brain lesion occurred during the first 24 h after CAS. Pre-procedure high DWI signal of the plaque was associated with an increased incidence of post-procedure microembolizations.

Contrast enhanced ultrasound in atherosclerotic carotid artery disease.

AIM: The traditional morphological parameters for the description of a carotid atherosclerotic plaque (degree of stenosis, echogenicity, systolic peak velocity etc.) are insufficient for the prediction of the risk of embolization. Contrast enhanced ultrasound (CEUS), based on the theory of inflammation and neoangiogenesis, seems to have a great potential for the detection of unstable plaques. The purpose of our work was to compare echogenicity of the plaque (evaluated with the Grey Scale Median; GSM), the degree of stenosis and CEUS with the histopathological findings. METHODS: Patients with indication for internal carotid endarterectomy (CEA) underwent a preoperative imaging study with B-mode echo Doppler Ultrasound and with CEUS. The contrast enhancement of the plaque was described with two parameters: the maximum and mean signal intensity (SImax, SImean). After the surgical operation the removed plaque is sent to the pathology laboratory for the measurement of the neoangiogenesis (vessel density, VD). RESULTS: Fifty-one consecutive patients were enrolled (12 symptomatic, 39 asymptomatic). Analysis pointed out significant differences between symptomatic and asymptomatic patients for: GSM median 14 (I quartile 11.5; III quartile 23) versus 32.5 (27-42.25) (P=0.012); SI (%) SImax 30 (29-35.5) versus 24 (19.7-27) (P<0.001) and SImean 23 (20.5-27) versus 15 (8-18.25) (P<0.001); VD (vessels/mm2) 41.5 (30-70) versus 12.6 (7-18.6) (P<0.001), respectively. Moreover, a cut-off value was determined between the two groups for each parameter: GSM:25, SImax:28%, SImean:20%, and VD: 25/mm2. Combined analysis showed that plaques with greater contrast enhancement had more newly formed capillaries and that plaques with lower GSM values correlated with greater vascularization. CONCLUSION: The study confirms that in vitro neoangiogenesis, contrast enhancement and stability of the plaque are strongly connected and CEUS appears to be one of the most promising tools for the stratification of the carotid plaque vulnerability.

Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma in a general population study.

Differences in response to carcinogenic agents are due to the allelic variants of the genes that control it. Key genes are those involved in the repair of the DNA damage caused by such agents. This paper describes the results of a case-control epidemiological study designed to determine the genotypes of four of these genes in persons exposed to a single genotoxic factor, i.e. asbestos, who had or had not developed malignant mesothelioma (MM). Our working hypothesis was that an imperfect DNA repair, as revealed by subtle polymorphic variants, could reduce protection against the chronic DNA insult provoked by asbestos and eventually result in mutagenesis and cancer. Seven variants (i.e. XRCC1-R399Q-NCBI SNP, XRCC1-R194W, XRCC3-T241M, XRCC3-IVS6-14, XPD-K751Q, XPD-D312N, OGG1-S326C) were investigated in 81 patients and 110 age and sex-matched controls, all residents at Casale Monferrato, a Piedmontese town highly exposed to asbestos pollution. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When considered as a categorical variable, XRCC1-399Q showed an increased OR both in heterozygotes (OR=2.08; 95% CI=1.00-4.33) and homozygotes (2.38; 95% CI=0.82-6.94), although individual ORs were not significant. When it was considered as a continuous variable OR was significant (OR=1.68; 95% CI: 1.02-2.75). When genotypes were divided into "non-risk" and "risk" genotypes, i.e. those thought to be associated with increased risk in the light of the functional significance of the variants, XRCC1-399Q (Q homozygotes+Q/R heterozygotes versus R homozygotes) had an OR=2.147 (95% CI: 1.08-4.28), whereas that of XRCC3-241T (T homozygotes+M/T heterozygotes versus M homozygotes) was 4.09 (95% CI: 1.26-13.21) and that of OGG1-326C was increased, though not significantly. None of the haplotypes showed a significantly different frequency between patients and controls. This is the first report of an association between polymorphisms in DNA repair genes and asbestos-associated MM. Our data indicate that genetic factors are involved in MM development.