Review of imaging biomarkers for the vulnerable carotid plaque.

Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. As a result of the rapid technological evolution in medical imaging, several important steps have been taken in the field of carotid plaque imaging allowing us to visualize the carotid atherosclerotic plaque and its composition in great detail. For computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound scan, evidence has accumulated on novel imaging-based markers that confer information on carotid plaque vulnerability, such as intraplaque hemorrhage and lipid-rich necrotic cores. In terms of the imaging-based identification of individuals at high risk of stroke, routine assessments of such imaging markers are the way forward for improving current clinical practice. The current review highlights the main characteristics of the vulnerable plaque indicating their role in the etiology of ischemic stroke as identified by intensive plaque imaging.

Volume of White Matter Hyperintensities, and Cerebral Micro-Bleeds.

PURPOSE: In the past years the significance of white matter hyperintensities (WMH) has gained raising attention because it is considered a marker of severity of different pathologies. Another condition that in the last years has been assessed in the neuroradiology field is cerebral microbleeds (CMB). The purpose of this work was to evaluate the association between the volume of WMH and the presence and characteristics of CMB. MATERIAL AND METHODS: Sixty-five consecutive (males 45; median age 70) subjects were retrospectively analyzed with a 1.5 Tesla scanner. WMH volume was quantified with a semi-automated procedure considering the FLAIR MR sequences whereas the CMB were studied with the SWI technique and CMBs were classified as absent (grade 1), mild (grade 2; total number of CMBs: 1-2), moderate (grade 3; total number of CMBs: 3-10), and severe (grade 4; total number of CMBs: >10). Moreover, overall number of CMBs and the maximum diameter were registered. RESULTS: Prevalence of CMBs was 30.76% whereas WMH 81.5%. Mann-Whitney test showed a statistically significant difference in WMH volume between subjects with and without CMBs (p < 0.001). Pearson analysis showed significant correlation between CMB grade, number and maximum diameter and WMH. The better ROC area under the curve (Az) was obtained by the hemisphere volume with a 0.828 (95% CI from 0.752 to 0,888; SD = 0.0427; p value = 0.001). The only parameters that showed a statistically significant association in the logistic regression analysis were Hemisphere volume of WMH (p = 0.001) and Cholesterol LDL (p = 0.0292). CONCLUSION: In conclusion, the results of this study suggest the presence of a significant correlation between CMBs and volume of WMH. No differences were found between the different vascular territories.

Does Carotid Artery Tortuosity Play a Role in Stroke?

PURPOSE: To explore the association between carotid artery length and tortuosity, and the occurrence of stroke. MATERIAL AND METHODS: In this retrospective study, IRB approved, 411 consecutive patients (males: 245; median age: 56 ± 12 years, age range: 21-93 years) with anterior circulation ischemic stroke were included. Only patients that underwent CTA within 7 days were considered and stroke caused by cardiac embolism and thoracic aorta embolism were excluded. For each patient, both carotid arteries were considered, and the ICA, CCA-ICA length and tortuosity were calculated. Inter-observer analysis was quantified with the Bland-Altman test. Mann-Whitney test and logistic regression analysis were also calculated to test the association between length and tortuosity with the occurrence of stroke. RESULTS: In the final analysis, 166 patients (males: 72; median age: 54 ± 12 years, age range: 24-89 years) with anterior circulation ischemic stroke that were admitted to our hospital between February 2008 and December 2013 were included. The results showed a good concordance for the length of the vessels with a mean variation of 0.7% and 0.5% for CCA-ICA and ICA length respectively an for the tortuosity with a mean variation of 0.2% and -0.4% for CCA-ICA and ICA respectively. The analysis shows a statistically significant association between the tortuosity index of the ICA and CCA-ICA sides with stroke (P value = 0.0001 in both cases) and these findings were confirmed also with the logistic regression analysis. CONCLUSION: Results of this study suggest that tortuosity index is associated with the presence of stroke whereas the length of the carotid arteries does not play a significant role.

White-matter hyperintensities in patients with carotid artery stenosis: An exploratory connectometry study.

BACKGROUND: White-matter lesions (WMLs) are frequently found in magnetic resonance imaging (MRi), and the WML load tends to be higher in patients affected by cervical internal carotid artery (cICA) stenosis. PURPOSE: This study aimed to investigate whether and how WMLs influence cerebral networking in patients with asymptomatic cICA stenosis eligible for carotid endarterectomy (CEA) by exploiting the connectometry technique. METHODS: The study was designed as a cross-sectional exploratory investigation, and 28 patients with cICA stenosis eligible for CEA were enrolled. All patients received an MRI scan, including a T1-weighted, a FLAIR and a diffusion-weighted (DW) sequence. The T1 and FLAIR sequences were analysed for quantification of WML burden (WMLB) and total number of WMLs (TNWMLs). The DW data were reconstructed in the MNI space using q-space diffeomorphic reconstruction, and were grouped to create a connectometry database. The connectometry analysis evaluated the influence of both the WMLB and TNWMLs to local connectivity in a multiple regression model that included age, WMLB and TNWMLs, adopting three different T-score thresholds (1, 2 and 3). A p-value corrected for false discovery rate of <0.05 was adopted as a threshold to identify statistically significant results. RESULTS: The connectometry analysis identified several white-matter bundles negatively correlated with WMLB; no statistically significant correlation was found for TNWMLs. CONCLUSION: Results of our study suggest that WMLs influence brain connectivity measured by the connectometry technique in patients with cICA stenosis eligible for CEA. Further studies are warranted to understand the role of WMLs better as a marker of disease in patients with cICA stenosis.

Extracranial Carotid Artery Stenosis: The Effects on Brain and Cognition with a Focus on Resting-State Functional Connectivity.

Extracranial carotid artery stenosis (ECAS) due to the presence of atherosclerotic plaque is a well-known risk factor for stroke. Several structural imaging studies have investigated the effect of ECAS on the brain, focusing on structural damage (in particular cerebral small vessel disease) and on the rearrangement of the cerebral circulation. For example, it is known from the literature an association between carotid stenosis and cerebral small vessel disease, and it is also noted that a series of compensatory mechanisms are activated by the cerebrovascular system in order to overcome the cerebral hypoperfusion that is induced by the ECAS. Several neurocognitive studies have also investigated the association of ECAS with cognitive deficits. While the evidence tends to favor a direct association between ECAS and cognition, the actual relationship remains controversial. In the last decade, various resting-state functional connectivity (rs-fc) magnetic resonance (MR) studies have tried to elucidate the "in vivo" mechanisms underlying the cognitive impairment observed in these patients. Although these studies have been performed on small cohorts of patients without standardized protocols, it is plausible that in the future, such studies will help find early stage markers of cognitive impairment. This could permit an extension of indications for revascularization for the treatment of cognitive impairment in selected patients. The aim of this narrative review is to discuss the current knowledge on the effects of ECAS on brain and cognition by analyzing the main evidence from animal and clinical studies, with a special focus on rs-fc MR studies.

Association between carotid artery plaque inflammation and brain MRI.

PURPOSE: To explore the association between presence of inflammatory cells in the carotid plaques surgically treated and brain MRI findings. MATERIAL AND METHODS: Forty consecutive patients were prospectively analyzed. Brain MRI was performed with a 1.5 Tesla scanner and infacts (lacuna and non-lacunar) pertinence of the anterior circulation were recorded. All patients underwent carotid endarterectomy "en bloc"; carotid plaques histological sections were prepared and immuno-cytochemical analysis was performed to characterize and quantify the presence of inflammatory cells. ROC curve analysis, Pearson Rho correlation and Mann-Whitney test were applied. RESULTS: The immuno-cytochemical analysis demonstrated that plaques of symptomatic patients (stroke\TIA; n = 25) had more inflammatory cells, mainly macrophages (CD68) compared with plaques of patients without symptoms (Mann-Whitney = P < 0.001, ROC curve area = 0.901). Correlation analysis showed a statistically significant association between the number of brain non-lacunar infarcts and the entity of macrophages (P < 0.001); whereas no association with lacunar infarcts (P = 0.1934) was found. CONCLUSION: Results of this preliminary study suggest that the presence and amount of inflammatory cells within carotid artery plaque is associated with cerebrovascular events and with the number of MRI brain detectable infarct.

Carotid artery imaging: The study of intra-plaque vascularization and hemorrhage in the era of the "vulnerable" plaque.

Intraplaque hemorrhage (IPH) is one of the main factors involved in atherosclerotic plaque (AP) instability. Its recognition is crucial for the correct staging and management of patients with carotid artery plaques to limit ischemic stroke. Imaging plays a crucial role in identifying IPH, even if the great variability of intraplaque vascularization and the limitations of our current imaging technologies make it difficult. The intent of this review is to give a general overview of the main features of intraplaque vascularization and IPH on Ultrasound (US), Computed Tomography (CT), Magnetic Resonance (MR) and Nuclear Medicine, and a brief description on the future prospectives.

Carotid artery stenosis and brain connectivity: the role of white matter hyperintensities.

PURPOSE: It is under debate how white matter hyperintensities (WMH) affects the brain connectivity. The objective of this research study is to validate the hypothesis, if and how the WMH influences brain connectivity in a population with carotid artery stenosis (CAS), which are eligible for carotid endarterectomy (CEA). We used resting state functional connectivity (rs-fc) magnetic resonance (MR) to validate our hypothesis, focusing on the effects of the total number of WMH (TNWMH) and of the WMH Burden (WMHB). METHODS: Twenty-three patients (sixteen males and seven females, mean age 74.34 years) with mono or bilateral carotid stenosis eligible for carotid endarterectomy (CEA), underwent an MR examination on a 1.5-T scanner. The protocol included a morphologic T1-3D isotropic, an EPI functional sequence for rs-fc MR analysis, and a 3D isotropic FLAIR sequence. For each patient, the TNWMH and the WMHB were obtained using two online tools-volBrain and lesionBrain. The rs-fc region-of-interest to region-of-interest (ROI-to-ROI) analysis was performed with the CONN toolbox v18a: two different multiple regression analyses including both WMHB and TNWMH as second-level covariates evaluated the individual effects of WMHB (Analysis A) and TNWMH (Analysis B), adopting a p value corrected for false discovery rate (p-FDR) < 0.05 to identify statistically significant values. RESULTS: Both analyses A and B identified several statistically significant positive and negative correlations associated with WMHB and TNWMH. CONCLUSION: WMH influence functional connectivity in patients with carotid artery stenosis eligible for CEA; further, WMHB and TNWMH influence differently functional connectivity.

Reorganization of brain networks following carotid endarterectomy: an exploratory study using resting state functional connectivity with a focus on the changes in Default Mode Network connectivity.

OBJECTIVES: To assess whether there is mid-term reorganization in brain networks connectivity after Carotid Endarterectomy (CEA) using resting state functional connectivity Magnetic Resonance (fc-rsMR), with a special focus on the Default Mode Network (DMN). MATERIALS AND METHODS: In this prospective exploratory study, 14 asymptomatic consecutive patients (10 males and 4 females, mean age 73.5) with unilateral, significant ICA stenosis eligible for CEA according to European Society for Vascular Surgery guidelines were prospectively recruited. The week before CEA procedure, each patient underwent both neurocognitive and rs-fcMR evaluations on the same day; the neurocognitive test consisted on a Mini Mental State Examination (MMSE). The same neurocognitive test and rs-fcMR examination were repeated on follow-up between 3-6 months after CEA. MMSE scores were compared using paired T-Student Test. Rs-fcMR Region Of Interest (ROI-to-ROI) and Seed-to-voxel group analysis were conducted using the CONN toolbox v18 and the SPM 12 software. RESULTS: Patients showed improvements in MMSE scores from before to after CEA (p-value = 0.0001). ROI-to-ROI analysis revealed several statistically significant connectivity changes following CEA, both in terms of positive and negative correlations; Seed-to-Voxel focusing on DMN revealed increased connectivity between medial prefrontal cortex (mPFC) and three different clusters of voxels. CONCLUSIONS: CEA procedure is associated with an improvement in neurocognitive performance (according to MMSE testing) and reorganization of functional connectivity, including the DMN. These results represent a starting point in order to design further studies for a better understanding of the reorganization of brain networks following CEA, and to investigate the potential role of CEA as a therapeutic procedure for cognitive impairments in selected patients with critical ICA stenosis.

Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study.

This research investigated local brain connectivity changes following Carotid Endarterectomy (CEA) by connectometry. Seventeen subjects (15 males and 2 females, mean age 74.1 years), all eligible for CEA, were prospectively recruited in this exploratory study. On the same day within the week before the CEA, each patient underwent a cognitive evaluation with a Mini Mental State Examination (MMSE) and a Magnetic Resonance Imaging (MRI) exam that included a DTI sequence for the connectometry analysis. A second MMSE and the same MRI protocol were performed on follow-up, 3-6 months after CEA. The MMSE scores were analyzed using T-Student tests. The connectometry analysis was performed using a multiple regression model to consider the effect of CEA, choosing three different T-score threshold (T-threshold) values (1, 2 and 3). Results were considered statistically valid for p value adjusted for False Discovery Rate (p-FDR) < 0.05. Comparison of pre-CEA and post-CEA MMSE scores showed improvement of MMSE scores after CEA. Connectometry analysis revealed no areas of statistically significant increased connectivity related to CEA for T-threshold value = 1 and 2, but showed statistically significant increase of connectivity after CEA in both cerebellar hemispheres and corpus callosum for T-threshold value = 3 (p-FDR = 0.0106667). The network property analysis showed improved small worldness (2.14%), clustering coefficient (1.64%), local (1.94%) and global efficiency (0.56%), and reduced characteristic path length (-0.52%) after CEA. These results suggest that CEA is associated both with cognitive performance improvement and changes in interhemispheric local connectivity in the corpus callosum and cerebellum.

Volumetric Distribution of the White Matter Hyper-Intensities in Subject with Mild to Severe Carotid Artery Stenosis: Does the Side Play a Role?

PURPOSE: The purpose of this paper was to assess the difference in the distribution of white matter hyperintensities (WMHs) on left and right sides of the brain hemispheres of subjects with mild to severe carotid artery stenosis. MATERIAL AND METHODS: Eighty consecutive patients (mean age 71 ± 6 years, males 66) with carotid artery stenosis were prospectively recruited. FLAIR-WMH lesion volume was performed using a semiautomated segmentation technique (Jim, Xinapse System, Leicester, UK). The Wilcoxon test was applied to verify the differences in the volume of WMHs between the right and left hemispheres. RESULTS: A statistically significant difference was found in the middle cerebral artery (MCA) territory for the volume of the lesions (median volume of WMHs of the left side = 889.5 mm3; median volume of WMHs on the right side = 580.5 mm3; P = .0416); no statistically significant difference was found on the other territories by taking into considerations the lesions. By analyzing the degree of stenosis, we found a higher degree of stenosis of the left side (67.9%; 95% confidence interval [CI], 64.8%-70.9%) compared with the right side (65.7%; 95% CI, 62.4%-68.9%), but the Mann-Whitney test did not show a statistically significant difference (P = .3235). CONCLUSIONS: Results of our study suggest that there is a difference in the distribution of WMHs in the brain hemispheres according to the left/right side on the MCA territories and for the periventricular white matter in subjects with mild to severe carotid artery stenosis.

Relationship between Carotid Computed Tomography Dual-Energy and Brain Leukoaraiosis.

BACKGROUND: The purpose of this study was to assess if there is a correlation between the carotid computed tomography (CT) Hounsfield unit (HU)-based plaque attenuation values measured using dual-energy CT (DECT) scanner and brain leukoaraiosis (LA). METHODS: Fifty consecutive patients (34 males, 16 females; mean age, 69 years; age range, 46-84 years) who underwent carotid CT and brain magnetic resonance imaging were included in the study. CT examinations were performed with a DECT scanner, and LA lesion volume quantification was performed using a semiautomated segmentation technique. RESULTS: We found an inverse statistically significant correlation between the HU-based carotid artery plaque attenuation and the LA lesion volume. Because of the presence of calcified plaques, a second model was calculated at low kiloelectron volt levels from 66 to 100 and 100 kV by taking into consideration the fatty and mixed plaques, and this further led to the associations between HU-based attenuation and LA volume in brain and vascular territories. CONCLUSIONS: The results of our study suggest that the associations between HU attenuation of the carotid artery plaques (with the exclusion of calcified plaques) and the volume of LA are emphasized at low keV energy levels.

Relationship between white matter hyperintensities volume and the circle of Willis configurations in patients with carotid artery pathology.

PURPOSE: We aimed to assess if there is a difference of distribution and volume of white matter hyperintensities (WMH) in the brain according to the Circle of Willis (CoW) configuration in patients with carotid artery pathology. MATERIAL AND METHODS: One-hundred consecutive patients (79 males, 21 females; mean age 70 years; age range 46-84 years) that underwent brain MRI before carotid endarterectomy (CEA) were included. FLAIR-WMH lesion volume was performed using a semi-automated segmentation technique and the status of the circle of Willis was assessed by two neuroradiologists in consensus. RESULTS: We found a prevalence of 55% of variants in the CoW configuration; 22 cases had one variants (40%); 25 cases had two variants (45.45%) and 8 cases showed 3 variants (14.55%). The configuration that was associated with the biggest WMH volume and number of lesions was the A1+PcoA+PcoA. The PcoA variants were the most prevalent and there was no statistically significant difference in number of lesions and WMH for each vascular territory assessed and the same results were found for AcoA and A1 variants. CONCLUSION: Results of our study suggest that the more common CoW variants are not associated with the presence of an increased WMH or number of lesions whereas uncommon configurations, in particular when 2 or more segment are missing increase the WMH volume and number of lesions. The WHM volume of the MCA territory seems to be more affected by the CoW configuration.

Volumetric Analysis of Carotid Plaque Components and Cerebral Microbleeds: A Correlative Study.

PURPOSE: The purpose of this work was to explore the association between carotid plaque volume (total and the subcomponents) and cerebral microbleeds (CMBs). MATERIALS AND METHODS: Seventy-two consecutive (male 53; median age 64) patients were retrospectively analyzed. Carotid arteries were studied by using a 16-detector-row computed tomography scanner whereas brain was explored with a 1.5 Tesla system. CMBs were studied using a T2*-weighted gradient-recalled echo sequence. CMBs were classified as from absent (grade 1) to severe (grade 4). Component types of the carotid plaque were defined according to the following Hounsfield unit (HU) ranges: lipid less than 60 HU; fibrous tissue from 60 to 130 HU; calcification greater than 130 HU, and plaque volumes of each component were calculated. Each carotid artery was analyzed by 2 observers. RESULTS: The prevalence of CMBs was 35.3%. A statistically significant difference was observed between symptomatic (40%) and asymptomatic (11%) patients (P value = .001; OR = 6.07). Linear regression analysis demonstrated an association between the number of CMBs and the symptoms (P = .0018). Receiver operating characteristics curve analysis found an association between the carotid plaque subcomponents and CMBs (Az = .608, .621, and .615 for calcified, lipid, and mixed components, respectively), and Mann-Whitney test confirmed this association in particular for the lipid components (P value = .0267). CONCLUSIONS: Results of this study confirm the association between CMBs and symptoms and that there is an increased number of CMBs in symptomatic patients. Moreover, we found that an increased volume of the fatty component is associated with the presence and number of CMBs.

Quality of Life in Carotid Atherosclerosis: The Role of Co-morbid Mood Disorders.

INTRODUCTION/OBJECTIVE: To study in severe carotid atherosclerosis (CA): the frequency of mood disorders (MD); the impairment of quality of life (QoL); the role of co-morbid MD in such impairment. METHODS: Case-control study. CASES: consecutive in-patients with CA (stenosis ≥ 50%). CONTROLS: subjects with no diagnosis of CA randomized from a database of a community survey. Psychiatric diagnosis according to DSM-IV made by clinicians and semi-structured interview, QoL measured by the Short Form Health Survey (SF-12). RESULTS: This is the first study on comorbidity on CA disease and MD in which psychiatric diagnoses are conducted by clinicians according to DSM-IV diagnostic criteria. Major Depressive Disorder (MDD) (17.4% vs 2.72%, P <0.0001) but not Bipolar Disorders (BD) (4.3% vs 0.5%, P = 0.99) was higher in cases (N=46) than in controls (N= 184). SF-12 scores in cases were lower than in controls (30.56±8.12 vs 36.81±6:40; p <0.001) with QoL comparable to serious chronic diseases of the central nervous system. The burden of a concomitant MDD or BD amplifies QoL impairment. CONCLUSION: Comorbid MD aggravates the impairment of QoL in CA. Unlike autoimmune diseases or degenerative diseases of the Central Nervous System, CA shows a strong risk of MDD than BD.

Relationship between leukoaraiosis, carotid intima-media thickness and intima-media thickness variability: Preliminary results.

OBJECTIVE: To assess the relationship between the degree of leukoaraiosis (LA), carotid intima-media thickness (IMT) and intima-media thickness variability (IMTV). MATERIALS AND METHODS: Sixty-one consecutive patients, who underwent a brain MRI examination and a carotid artery ultrasound, were included in this retrospective study, which conformed with the Declaration of Helsinki. Written informed consent was waived. In each patient, right/left carotid arteries and brain hemispheres were assessed using automated software for IMT, IMTV and LA volume. RESULTS: The mean hemispheric LA volume was 2,224 mm3 (SD 2,702 mm3) and there was no statistically significant difference in LA volume between the right and left hemispheres (p value = 0.628). The mean IMT and IMTV values were 0.866 mm (SD 0.170) and 0.143 mm (SD 0.100), respectively, without significant differences between the right and left sides (p values 0.733 and 0.098, respectively). The correlation coefficient between IMTV and LA volume was 0.41 (p value = 0.0001), and 0.246 (p value = 0.074) between IMT and LA volume. CONCLUSIONS: IMTV significantly correlates with LA volume. Further studies are warranted to verify whether this parameter can be used clinically as a marker of cerebrovascular risk. KEY POINTS: • Intima-media thickness variability (IMTV) significantly correlates with leukoaraiosis volume. • IMTV could be used as a marker for cerebrovascular risk. • IMTV seems to be a better predictor of weighted mean difference than IMT.

Is there an association between leukoaraiosis volume and diabetes?

OBJECTIVES: The relation between white matter loss (WML) and diabetes is still debated. The aim of this study was to investigate the correlation between typical WML- and diabetes-related magnetic resonance imaging (MRI) findings in a cohort of patients scheduled for carotid endarterectomy (CEA). MATERIALS AND METHODS: Ninety-three consecutive patients (mean age 71±9years; male 71) were included in a single-centre retrospective study. All the patients underwent MRI as baseline evaluation prior to CEA. A neuroradiologist blinded to the presence of risk factors calculated WML volume and number of lesions on FLAIR images using a semi-automated segmentation technique. Receiver operating characteristics analysis was performed to search for any association between WML volume and the number of WML lesions. The Mann-Whitney tests were used to determine significant WML differences between diabetic and non-diabetic patients. Logistic regression analysis was performed to evaluate the potential association of other variables. RESULTS: The prevalence of diabetes was 20.4% (n=19). WML volume and number of WML lesions were significantly associated with diabetes (P=0.001). A statistically significant difference in WML volume was found between diabetic and non-diabetic patients (P<0.0001). Only diabetes, among all the investigated variables (WML volume, CAD status, age, smoking status, gender, hypertension, hyperlipidemia, diabetes) was significantly associated with WML (P=0.0001). CONCLUSION: Our results demonstrate a strong statistical correlation between diabetes and WML. Future scientific challenges could include the identification of potential therapeutic targets and the creation of dedicated screening protocols for WML in diabetic patients other than the simple measurement of leukoaraiosis total burden.

Longitudinal assessment of carotid atherosclerosis after Radiation Therapy using Computed Tomography: A case control Study.

OBJECTIVES: To study the carotid artery plaque composition and its volume changes in a group of patients at baseline and 2 years after head and neck radiation therapy treatment (HNXRT). METHODS: In this retrospective study, 62 patients (41 males; mean age 63 years; range 52-81) who underwent HNXRT and 40 patients (24 males; mean age 65) who underwent surgical resection of neoplasm and did not undergo HNXRT were assessed, with 2-year follow-up. The carotid artery plaque volumes, as well as the volume of the sub-components (fatty-mixed-calcified), were semiautomatically quantified. Mann-Whitney and Wilcoxon tests were used to test the hypothesis. RESULTS: In the HNXRT group, there was a statistically significant increase in the total volume of the carotid artery plaques (from 533 to 746 mm(3); p = 0.001), in the fatty plaques (103 vs. 202 mm(3); p = 0.001) and mixed plaque component volume (328 vs. 419 mm(3); p = 0.034). A statistically significant variation (from 21.8 % to 27.6 %) in the percentage of the fatty tissue was found. CONCLUSIONS: Results of this preliminary study suggest that HNXRT promotes increased carotid artery plaque volume, particularly the fatty plaque component. KEY POINTS: HNXRT increases carotid plaque volume. Plaque volume increase is mainly due to increase.in fatty plaque component. Patients who undergo HNXRT have a progression of carotid artery disease.

Patients with carotid atherosclerosis who underwent or did not undergo carotid endarterectomy: outcome on mood, cognition and quality of life.

BACKGROUND: To compare the six-month outcome on mood, cognition and quality of life (QoL) in patients with severe carotid atherosclerosis (CA) who underwent carotid endarterectomy (CEA) with subjects who refused treatment. METHODS: Cohort study on consecutive inpatients with CA (stenosis ≥ 50 %) (N = 46; age 72.56 ± 7.26; male 65.2 %). Intervention cohort: subjects who decided to undergo CEA (N = 35); Control cohort patients who refused CEA (N = 11). DSM-IV-Psychiatric diagnosis made by clinicians using interviews, QoL measured by Short Form Health Survey (SF-12); cognitive performance by WAIS Intelligent Coefficient (IC). RESULTS: The study showed a better improvement during six months in Overall IC, Performance IC and Verbal IC in the group that underwent CEA. QoL in the two cohorts did not reach statistical significance. Percentages of patients who improved in the CEA group were significantly higher with regard to Overall and Verbal IC scores, and at the limits of statistical significance in Performance IC. The differences of subject with improvement in SF-12 score in the two groups did not reach statistical significance. Ages below 68 were found to be determinant of a good outcome in Overall IC score. Limit: study conducted with a small sample size. CONCLUSIONS: Patients with severe carotid atherosclerosis who underwent CEA enhanced their cognitive performance.

Acquired factor VIII inhibitor and subsequent development of non-Hodgkin's lymphoma: a case report and review of the literature.

Acquired hemophilia A (AHA) is a rare disorder caused by the development of factor VIII autoantibodies. It can induce acute and major hemorrhages in patients with negative personal and family history of bleeding. AHA is frequently associated with hematologic malignancies. This study describes the first case of AHA in a patient who developed a mantle cell lymphoma after a year and half of complete remission. It also provides an example of an initial wrong approach in terms of diagnosis and treatment, as well as of a very long course of the disease. Further, a review of AHA-associated lymphomas from 1974 to 2014 is also presented.Clinical and laboratory staff should be alert to the possibility of such an event when the medical history of patients is enriched with new symptoms or signs. A follow-up of at least 2 years might therefore be required.