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Aim To assess the effect of the bisphosphonate etidronate on choroidal neovascular (CNV) activity in patients with pseudoxanthoma elasticum (PXE). Methods This is an ancillary study in a single center, randomized, double-blind placebo-controlled trial (RCT) in which 74 patients with PXE were assigned to either one-year etidronate or placebo treatment. Spectral domain optical coherence tomography (SD-OCT) imaging and color fundus photography were performed every three months for one year and were systematically assessed on signs of CNV activity. Results In the etidronate group, 11 (30%) of the patients had CNV activity at baseline, compared to 25 (67%) of the patients in the placebo group (P = 0.005). The proportion of eyes with CNV activity during the study ranged from 18-33% in the etidronate group and 42-56% in the placebo group and no significant difference in improvement or worsening of CNV activity was found (P = 0.168). Using a generalized mixed model for repeated measures, there was a protective effect of etidronate in crude analysis (RR 0.86, 95% CI 0.75-0.98) that disappeared when adjusting for baseline CNV activity (RR 0.97, 95% CI 0.84-1.13). Conclusion In this post-hoc RCT analysis we did not observe a protecting or deteriorating effect of etidronate on CNV activity in patients with PXE after adjustment for baseline CNV. [ABSTRACT FROM AUTHOR]

Background: Calcifications within the hippocampus were recently described for the first time on computed tomography (CT). These calcifications appeared in patients older than 50 years, the prevalence increases with age and they may be associated with cognitive decline. The aim of this study was to determine the histological basis (the presence, severity and location) of these CT-detected hippocampal calcifications of post-mortem brains. Methods: CT scans of seven post-mortem brains were scored for the presence and severity (mild, moderate, severe) of hippocampal calcification. After this, samples from nine hippocampi (bilateral in two brains, unilateral in five brains) were stained with hematoxylin and eosin (HE) to indicate the cytoarchitecture, with Elastica van Gieson to analyse the elastic connective tissue of the vessel walls and with von Kossa for detection of calcium. Results: In four brains (six hippocampi), calcifications were both found on CT and in corresponding histology. In three brains (three hippocampi), calcifications were absent on CT and corresponding histology. In histology, mild calcifications were located in the tail and severe calcifications involved the tail, body and sometimes the head of the hippocampus. The calcifications co-localised with precapillaries, capillaries and arteries of the molecular and granular layers of the dentate gyrus and the Cornu Ammonis 1. Conclusions: In this study, calcifications of the hippocampus as seen on CT scans were histologically located in vascular structures of the tail, body and head of the hippocampus. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the frequency of aortic calcifications at the outer edge of the false lumen and the frequency of fully circular aortic calcifications in a consecutive series of patients with aortic dissection who underwent contrast-enhanced CT. Methods: The study population compromised of 69 consecutive subjects aged 60 years and older with a contrast-enhanced CT scan demonstrating an aortic dissection. All CT scans were evaluated for the frequency of aortic calcifications at the outer edge of the false lumen and the frequency of fully circular aortic calcifications by two experienced observers. Between observer reliability was evaluated by using Cohen’s Kappa. Differences between groups were tested using unpaired T test and Chi-square test. Results: Presumed media calcifications were observed in 22 (32%) patients of 60 years and older and were found more frequently in chronic aortic dissection (N = 12/23, 52%) than in acute aortic dissection (N = 10/46, 22%). Conclusion: As the intima has been torn away by the aortic dissection it is highly likely that CT scans can visualize the calcifications in the tunica media of the aorta. [ABSTRACT FROM AUTHOR]

Objective: To investigate the added diagnostic value of 3.0 Tesla breast MRI over conventional breast imaging in the diagnosis of in situ and invasive breast cancer and to explore the role of routine versus expert reading. Materials and Methods: We evaluated MRI scans of patients with nonpalpable BI-RADS 3–5 lesions who underwent dynamic contrast-enhanced 3.0 Tesla breast MRI. Initially, MRI scans were read by radiologists in a routine clinical setting. All histologically confirmed index lesions were re-evaluated by two dedicated breast radiologists. Sensitivity and specificity for the three MRI readings were determined, and the diagnostic value of breast MRI in addition to conventional imaging was assessed. Interobserver reliability between the three readings was evaluated. Results: MRI examinations of 207 patients were analyzed. Seventy-eight of 207 (37.7%) patients had a malignant lesion, of which 33 (42.3%) patients had pure DCIS and 45 (57.7%) invasive breast cancer. Sensitivity of breast MRI was 66.7% during routine, and 89.3% and 94.7% during expert reading. Specificity was 77.5% in the routine setting, and 61.0% and 33.3% during expert reading. In the routine setting, MRI provided additional diagnostic information over clinical information and conventional imaging, as the Area Under the ROC Curve increased from 0.76 to 0.81. Expert MRI reading was associated with a stronger improvement of the AUC to 0.87. Interobserver reliability between the three MRI readings was fair and moderate. Conclusions: 3.0 T breast MRI of nonpalpable breast lesions is of added diagnostic value for the diagnosis of in situ and invasive breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke. Methods: We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r). Results: Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35–90)), followed by dissection (35 (20–40), p = 0.05), cardioembolism (35 (5–45), p = 0.013) and unknown subtype (25 (2–40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = −0.368, p = 0.09) and fibrin (r = −0.073, p = 0.75). Conclusions: The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management. [ABSTRACT FROM AUTHOR]

Background and Purpose: Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke. Methods: We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement. Results: Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps. Conclusion: Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the reliability of semiquantitative Vertebral Fracture Assessment (VFA) on chest Computed Tomography (CT). Methods: Four observers performed VFA twice upon sagittal reconstructions of 50 routine clinical chest CTs. Intra- and interobserver agreement (absolute agreement or 95% Limits of Agreement) and reliability (Cohen's kappa or intraclass correlation coefficient(ICC)) were calculated for the visual VFA measures (fracture present, worst fracture grade, cumulative fracture grade on patient level) and for percentage height loss of each fractured vertebra compared to the adjacent vertebrae. Results: Observers classified 24–38% patients as having at least one vertebral fracture, giving rise to kappa's of 0.73–0.84 (intraobserver) and 0.56–0.81 (interobserver). For worst fracture grade we found good intraobserver (76–88%) and interobserver (74–88%) agreement, and excellent reliability with square-weighted kappa's of 0.84–0.90 (intraobserver) and 0.84–0.94 (interobserver). For cumulative fracture grade the 95% Limits of Agreement were maximally ±1,99 (intraobserver) and ±2,69 (interobserver) and the reliability (ICC) varied from 0.84–0.94 (intraobserver) and 0.74–0.94 (interobserver). For percentage height-loss on a vertebral level the 95% Limits of Agreement were maximally ±11,75% (intraobserver) and ±12,53% (interobserver). The ICC was 0.59–0.90 (intraobserver) and 0.53–0–82 (interobserver). Further investigation is needed to evaluate the prognostic value of this approach. Conclusion: In conclusion, these results demonstrate acceptable reproducibility of VFA on CT. [ABSTRACT FROM AUTHOR]

Background: Current smokers have an increased cardiovascular disease (CVD) risk compared to ex-smokers due to reversible as well as irreversible effects of smoking. We investigated if current smokers remain to have an increased CVD risk compared to ex-smokers in subjects with a long and intense smoking history. We in addition studied if the effect of smoking continuation on CVD risk is independent of or modified by the presence of cardiovascular calcifications. Methods: The cohort used comprised a sample of 3559 male lung cancer screening trial participants. We conducted a case-cohort study using all CVD cases and a random sample of 10% (n = 341) from the baseline cohort (subcohort). A weighted Cox proportional hazards model was used to estimate the hazard ratios for current smoking status in relation to CVD events. Results: During a median follow-up of 2.6 years (max. 3.7 years), 263 fatal and non-fatal cardiovascular events (cases) were identified. Age, packyears and cardiovascular calcification adjusted hazard ratio of current smokers compared to former smokers was 1.33 (95% confidence interval 1.00–1.77). In additional analyses that incorporated multiplicative interaction terms, neither coronary nor aortic calcifications modified the association between smoking status and cardiovascular risk (P = 0.08). Conclusions: Current smokers have an increased CVD risk compared to former smokers even in subjects with a long and intense smoking history. Smoking exerts its hazardous effects on CVD risk by pathways partly independent of cardiovascular calcifications. [ABSTRACT FROM AUTHOR]

Introduction: Lacunar lesions (LLs) and white matter lesions (WMLs) affect cognition. We assessed whether lesions located in specific white matter tracts were associated with cognitive performance taking into account total lesion burden. Methods: Within the Second Manifestations of ARTerial disease Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed on 516 patients with manifest arterial disease. We applied an assumption-free voxel-based lesion-symptom mapping approach to investigate the relation between LL and WML locations on 1.5 Tesla brain MRI and compound scores of executive functioning, memory and processing speed. Secondly, a multivariable linear regression model was used to relate the regional volume of LLs and WMLs within specific white matter tracts to cognitive functioning. Results: Voxel-based lesion-symptom mapping identified several clusters of voxels with a significant correlation between WMLs and executive functioning, mostly located within the superior longitudinal fasciculus and anterior thalamic radiation. In the multivariable linear regression model, a statistically significant association was found between regional LL volume within the superior longitudinal fasciculus and anterior thalamic radiation and executive functioning after adjustment for total LL and WML burden. Conclusion: These findings identify the superior longitudinal fasciculus and anterior thalamic radiation as key anatomical structures in executive functioning and emphasize the role of strategically located vascular lesions in vascular cognitive impairment. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of clinically relevant unrequested extra-cardiac imaging findings on cardiac Computed Tomography (CT) and explanatory factors thereof. Methods: A systematic review of studies drawn from online electronic databases followed by meta-analysis with meta-regression was performed. The prevalence of clinically relevant unrequested findings and potentially explanatory variables were extracted (proportion of smokers, mean age of patients, use of full FOV, proportion of men, years since publication). Results: Nineteen radiological studies comprising 12922 patients met the inclusion criteria. The pooled prevalence of clinically relevant unrequested findings was 13% (95% confidence interval 9-18, range: 3-39%). The large differences in prevalence observed were not explained by the predefined (potentially explanatory) variables. Conclusions: Clinically relevant extra-cardiac findings are common in patients undergoing routine cardiac CT, and their prevalence differs substantially between studies. These differences may be due to unreported factors such as different definitions of clinical relevance and differences between populations. We present suggestions for basic reporting which may improve the interpretability and comparability of future research. [ABSTRACT FROM AUTHOR]

Background: Routine computed tomography (CT) examinations contain an abundance of findings unrelated to the diagnostic question. Those with prognostic significance may contribute to early detection and treatment of disease, irrelevant findings can be ignored. We aimed to assess the association between unrequested chest CT findings in lungs, mediastinum and pleura and future cardiovascular events. Methods: Multi-center case-cohort study in 5 tertiary and 3 secondary care hospitals involving 10410 subjects who underwent routine chest CT for non-cardiovascular reasons. 493 cardiovascular hospitalizations or deaths were recorded during an average follow-up time of 17.8 months. 1191 patients were randomly sampled to serve as a control subcohort. Hazard ratios and annualized event rates were calculated. Results: Abnormalities in the lung (26-44%), pleura (14-15%) and mediastinum (20%) were common. Hazard ratios after adjustment for age and sex were for airway wall thickening 2.26 (1.59-3.22), ground glass opacities 2.50 (1.72-3.62), consolidations 1.97 (1.12-3.47), pleural effusions 2.77 (1.81-4.25) and lymph-nodes 2.04 (1.40-2.96). Corresponding annual event rates were 5.5%, 6.0%, 3.8%, 10.2% and 4.4%. Conclusions: We have identified several common chest CT findings that are predictive for future risk of cardiovascular events and found that other findings have little utility for this. The added value of the non-vascular predictors to established vascular calcifications on CT remains to be determined. [ABSTRACT FROM AUTHOR]