An ultrasound multiparametric method to quantify liver fat using magnetic resonance as standard reference.

BACKGROUND & AIMS: There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference. METHODS: Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis. RESULTS: The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73). CONCLUSIONS: Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.

Magnetic resonance imaging Locus Coeruleus abnormality in amnestic Mild Cognitive Impairment is associated with future progression to dementia.

BACKGROUND AND PURPOSE: Human neuropathological studies indicate that the pontine nucleus Locus Coeruleus (LC) undergoes significant and early degeneration in Alzheimer's disease. This line of evidence alongside experimental data suggests that the LC functional/structural decay may represent a critical factor for Alzheimer's disease pathophysiological and clinical progression. In the present prospective study, we used Magnetic Resonance Imaging (MRI) with LC-sensitive sequence (LC-MRI) to investigate in vivo the LC involvement in Alzheimer's disease progression, and whether specific LC-MRI features at baseline are associated with prognosis and cognitive performance in amnestic Mild Cognitive Impairment. METHODS: LC-MRI parameters were measured at baseline by a template-based method on 3.0-T magnetic resonance images in 34 patients with Alzheimer's disease dementia, 73 patients with amnestic Mild Cognitive Impairment, and 53 cognitively intact individuals. A thorough neurological and neuropsychological assessment was performed at baseline and 2.5-year follow-up. RESULTS: In subjects with Mild Cognitive Impairment who converted to dementia (n = 32), the LC intensity and number of LC-related voxels were significantly lower than in cognitively intact individuals, resembling those observed in demented patients. Such a reduction was not detected in Mild Cognitive Impairment individuals, who remained stable at follow-up. In Mild Cognitive Impairment subjects converting to dementia, LC-MRI parameter reduction was maximal in the rostral part of the left nucleus. Structural equation modeling analysis showed that LC-MRI parameters positively correlate with cognitive performance. CONCLUSIONS: Our findings highlight a potential role of LC-MRI for predicting clinical progression in Mild Cognitive Impairment and support the key role of LC degeneration in the Alzheimer clinical continuum.

A Deep Learning-Based and Fully Automated Pipeline for Thoracic Aorta Geometric Analysis and Planning for Endovascular Repair from Computed Tomography.

Feasibility assessment and planning of thoracic endovascular aortic repair (TEVAR) require computed tomography (CT)-based analysis of geometric aortic features to identify adequate landing zones (LZs) for endograft deployment. However, no consensus exists on how to take the necessary measurements from CT image data. We trained and applied a fully automated pipeline embedding a convolutional neural network (CNN), which feeds on 3D CT images to automatically segment the thoracic aorta, detects proximal landing zones (PLZs), and quantifies geometric features that are relevant for TEVAR planning. For 465 CT scans, the thoracic aorta and pulmonary arteries were manually segmented; 395 randomly selected scans with the corresponding ground truth segmentations were used to train a CNN with a 3D U-Net architecture. The remaining 70 scans were used for testing. The trained CNN was embedded within computational geometry processing pipeline which provides aortic metrics of interest for TEVAR planning. The resulting metrics included aortic arch centerline radius of curvature, proximal landing zones (PLZs) maximum diameters, angulation, and tortuosity. These parameters were statistically analyzed to compare standard arches vs. arches with a common origin of the innominate and left carotid artery (CILCA). The trained CNN yielded a mean Dice score of 0.95 and was able to generalize to 9 pathological cases of thoracic aortic aneurysm, providing accurate segmentations. CILCA arches were characterized by significantly greater angulation (p = 0.015) and tortuosity (p = 0.048) in PLZ 3 vs. standard arches. For both arch configurations, comparisons among PLZs revealed statistically significant differences in maximum zone diameters (p < 0.0001), angulation (p < 0.0001), and tortuosity (p < 0.0001). Our tool allows clinicians to obtain objective and repeatable PLZs mapping, and a range of automatically derived complex aortic metrics.

Pitfalls in surgical repair of Fallot's tetralogy: The "ventricular subaortic pouch".

Fallot-type ventricular septal defect (VSD) is characterized by anterior malalignment of the outlet septum with variable degree of aortic dextroposition. Correct identification of the borders of the defect is crucial to achieve an optimal surgical repair. We describe a particular postsurgical lesion, identified by cardiac magnetic resonance and cardiac computed tomography, which results from an improper surgical closure technique of anterior malaligned VSD. Based on its anatomical features we defined this entity "subaortic pouch." A comprehensive description of this defect is here provided along with an in-depth analysis of the proper operative technique for Fallot-type VSD repair.

Deep learning to diagnose cardiac amyloidosis from cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is part of the diagnostic work-up for cardiac amyloidosis (CA). Deep learning (DL) is an application of artificial intelligence that may allow to automatically analyze CMR findings and establish the likelihood of CA. METHODS: 1.5 T CMR was performed in 206 subjects with suspected CA (n = 100, 49% with unexplained left ventricular (LV) hypertrophy; n = 106, 51% with blood dyscrasia and suspected light-chain amyloidosis). Patients were randomly assigned to the training (n = 134, 65%), validation (n = 30, 15%), and testing subgroups (n = 42, 20%). Short axis, 2-chamber, 4-chamber late gadolinium enhancement (LGE) images were evaluated by 3 networks (DL algorithms). The tags "amyloidosis present" or "absent" were attributed when the average probability of CA from the 3 networks was ≥ 50% or < 50%, respectively. The DL strategy was compared to a machine learning (ML) algorithm considering all manually extracted features (LV volumes, mass and function, LGE pattern, early blood-pool darkening, pericardial and pleural effusion, etc.), to reproduce exam reading by an experienced operator. RESULTS: The DL strategy displayed good diagnostic accuracy (88%), with an area under the curve (AUC) of 0.982. The precision (positive predictive value), recall score (sensitivity), and F1 score (a measure of test accuracy) were 83%, 95%, and 89% respectively. A ML algorithm considering all CMR features had a similar diagnostic yield to DL strategy (AUC 0.952 vs. 0.982; p = 0.39). CONCLUSIONS: A DL approach evaluating LGE acquisitions displayed a similar diagnostic performance for CA to a ML-based approach, which simulates CMR reading by experienced operators.

Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography.

BACKGROUND: Few studies, and with conflicting results, have evaluated the potential effects of iodinated contrast media on children's thyroid function. OBJECTIVE: To investigate the effects of iodinated contrast medium on thyroid function in neonates, infants and young children with congenital heart disease undergoing cardiac computed tomography (CT). MATERIALS AND METHODS: We retrospectively evaluated 10 neonates (group 1) and 23 infants and young children (group 2) without thyroid or renal disease for serum levels of thyroid-stimulating hormone, free triiodothyronine and free thyroxine before contrast-enhanced cardiac CT, 48 h after CT and at discharge from the hospital. Cardiac CT was performed with intravenous administration of 1.14±0.17 mL/kg of body weight of iopromide (containing 370 mg of iodine/mL). RESULTS: Group 1 had a reduction of thyroid-stimulating hormone from baseline to 48 h post injection (P=0.002). Group 2 had a reduction of thyroid-stimulating hormone median levels from baseline to 48 h post injection and an increase from 48 h to discharge (P=0.0005 and P=0.0001, respectively). CONCLUSION: Intravenous iodinated contrast medium in children with congenital heart disease caused transient thyroid-stimulating hormone decrease 48 h after CT, with thyroid-stimulating hormone returning to normal range at discharge.

Accelerating 4D flow MRI by exploiting low-rank matrix structure and hadamard sparsity.

PURPOSE: To develop accelerated 4D flow MRI by exploiting low-rank matrix structure and Hadamard sparsity. THEORY AND METHODS: 4D flow MRI data can be represented as the sum of a low-rank and a sparse component. To optimize the sparse representation of the data, it is proposed to incorporate a Hadamard transform of the velocity-encoding segments. Retrospectively and prospectively, undersampled data of the aorta of healthy subjects are used to assess the reconstruction accuracy of the proposed method relative to k-t SPARSE-SENSE reconstruction. Image reconstruction from eight-fold prospective undersampling is demonstrated and compared with conventional SENSE imaging. RESULTS: Simulation results revealed consistently lower errors in velocity estimation when compared with k-t SPARSE-SENSE. In vivo data yielded reduced error of peak flow with the proposed method relative to k-t SPARSE-SENSE when compared with two-fold SENSE ( 2.5±4.6% versus 10.2±8.5% in the ascending aorta, 3.6±8.4% versus 9.2±9.0% in the descending aorta). Streamline visualization showed more consistent flow fields with the proposed technique relative to the benchmark methods. CONCLUSION: Image reconstruction by exploiting low-rank structure and Hadamard sparsity of 4D flow MRI data improves the reconstruction accuracy relative to current state-of-the-art methods and holds promise to reduce the long scan times of 4D flow MRI. Magn Reson Med 78:1330-1341, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

3D-Flair sequence at 3T in cochlear otosclerosis.

PURPOSE: To assess the capability of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences in detecting signal alterations of the endolabyrinthine fluid in patients with otosclerosis. MATERIALS AND METHODS: 3D-FLAIR before and after (-/+) gadolinium (Gd) administration was added to the standard MR protocol and acquired in 13 patients with a clinical/audiological diagnosis of severe/profound hearing loss in otosclerosis who were candidates for cochlear implantation and in 11 control subjects using 3-T magnetic resonance imaging (MRI) equipment. The MRI signal of the fluid-filled cochlea was assessed both visually and calculating the signal intensity ratio (SIR = signal intensity cochlea/brainstem). RESULTS: We revealed no endocochlear signal abnormalities on T1-weighted -/+ Gd images for either group, while on 3D-FLAIR we found bilateral hyperintensity with enhancement after Gd administration in eight patients and bilateral hyperintensity without enhancement in one patient. No endocochlear signal abnormalities were detected in other patients or the control group. CONCLUSION: Using 3-T MRI equipment, the 3D-FLAIR -/+ Gd sequence is able to detect the blood-labyrinth barrier (BLB) breakdown responsible for alterations of the endolabyrinthine fluid in patients with cochlear otosclerosis. We believe that 3D-FLAIR +/- Gd is an excellent imaging modality to assess the intra-cochlear damage in otosclerosis patients. KEY POINTS: • Gd-enhanced T1-weighted MRI has limited application to detect intra-cochlear damage. • 3D-FLAIR is less sensitive to flux artefacts and allows multiplanar reconstruction. • Post-Gd 3D-FLAIR is advantageous as it may highlight the BLB breakdown. • Using 3D-FLAIR -/+ Gd, we were able to identify intra-cochlear signal hyperintensities. • 3D-FLAIR might be applied for monitoring disease progression and treatment response.

Diabetes-Related Changes in Carotid Wall Properties: Role of Triglycerides.

Background/Objectives: This study compares the power of the radiofrequency (RF) signal reflected from the media layer (media power) of the common carotid artery (CCA) and the CCA stiffness between individuals with and without type 2 diabetes mellitus (T2DM). It also evaluates the associations of CCA media power with plasma glucose and lipid levels, as well as carotid stiffness. Methods: A total of 540 individuals, 115 with and 425 without T2DM (273 males, mean age = 64 ± 8 years) were studied using RF-based tracking of the right CCA. The following parameters were measured: CCA media thickness, luminal diameter, wall tensile stress (WTS), local pulse wave velocity (PWV), and media power. Results: Compared to the non-diabetic individuals, the T2DM patients had significantly higher CCA media thickness (652 ± 122 vs. 721 ± 138 microns, p < 0.005), luminal diameter (6.12 ± 0.78 vs. 6.86 ± 0.96 mm, p < 0.0005), media power (36.1 ± 4.8 vs. 39.3 ± 4.6, p < 0.0001), and PWV (7.65 ± 1.32 vs. 8.40 ± 1.89 m/s; p < 0.01), but comparable WTS (32.7 ± 10.4 vs. 33.1 ± 10.7 kPa; p = 0.25). In the entire population, CCA media power was independently associated with male sex, pulse pressure, current smoking, and T2DM; when T2DM was not included in the model, triglycerides emerged as an independent determinant of media power. The CCA PWV was independently associated with age, pulse pressure, media power, and T2DM. Conclusions: Our findings suggest the presence of structural changes in the arterial media of T2DM patients, leading to carotid stiffening and remodeling, aiming to preserve WTS. T2DM-related changes in arterial wall composition may be driven by high plasma triglyceride levels, which have previously been associated with both arterial stiffening and the incidence of CV events.

A multimarker study of degenerative aortic valve disease: stenoinsufficiency shows more indices of bad prognosis.

OBJECTIVES: It was the aim of this study to assess the pathophysiological, prognostic role of aortic regurgitation (AR) in the 'mixed pictures' of degenerative aortic valve stenoinsufficiency (ASI) by a multimarker clinical approach. METHODS: We enrolled 112 consecutive surgical PATIENTS: 19 with pure valve stenosis (PAS), 39 with mild regurgitation, 29 with severe regurgitation, and 25 controls with annulo-ectatic AR. All underwent complete echocardiography, carotid ultrasound and aortic/coronary multislice computed tomography calcium score evaluation. We determined tissue semiquantitative osteopontin, metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and circulating brain natriuretic peptide. We evaluated major adverse cardiac events and cardiovascular early, long-term mortality after bioprosthetic valve implantation. RESULTS: Tissue calcification, carotid and coronary atherosclerotic disease were prevalent in PAS versus ASI and AR patients. The multislice computed tomography calcium score (Agatston) was comparable between PAS and ASI (PAS 3,507.3 + 2,442.6; mild AR 4,270.7 + 2,213.5; severe AR 3,568.5 + 1,823.4), but much lower in AR (1,247.8 + 2,708.6). In ASI, a plasma/tissue 'profibrotic' MMP/TIMP balance prevailed, with circulating and echocardiographic indices of myocardial dysfunction. Percentages of major adverse cardiac events and early, long-term mortality were higher in ASI. CONCLUSIONS: In ASI, different, still unknown, genetic and dysplastic factors could work synergically with cardiovascular risk factors, determining a much more adverse myocardial and valve remodeling, resulting in worse clinical outcome.

Association between Low-Density Lipoprotein Cholesterol and Vascular Biomarkers in Primary Prevention.

Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48-0.92, p = 0.01), CAC score > 100 (1.59; 1.08-2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19-3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population.

Information load dynamically modulates functional brain connectivity during narrative listening.

Narratives are paradigmatic examples of natural language, where nouns represent a proxy of information. Functional magnetic resonance imaging (fMRI) studies revealed the recruitment of temporal cortices during noun processing and the existence of a noun-specific network at rest. Yet, it is unclear whether, in narratives, changes in noun density influence the brain functional connectivity, so that the coupling between regions correlates with information load. We acquired fMRI activity in healthy individuals listening to a narrative with noun density changing over time and measured whole-network and node-specific degree and betweenness centrality. Network measures were correlated with information magnitude with a time-varying approach. Noun density correlated positively with the across-regions average number of connections and negatively with the average betweenness centrality, suggesting the pruning of peripheral connections as information decreased. Locally, the degree of the bilateral anterior superior temporal sulcus (aSTS) was positively associated with nouns. Importantly, aSTS connectivity cannot be explained by changes in other parts of speech (e.g., verbs) or syllable density. Our results indicate that the brain recalibrates its global connectivity as a function of the information conveyed by nouns in natural language. Also, using naturalistic stimulation and network metrics, we corroborate the role of aSTS in noun processing.

Intravenous Contrast Material for Cardiac Computed Tomography: Results From the Open-label Multicenter, Multivendor Italian Registry of Contrast Material Use in Cardiac Computed Tomography.

PURPOSE: The Italian Registry of Contrast Material use in Cardiac Computed Tomography (iRCM-CCT) is a multicenter, multivendor, observational study on the use of contrast media (CM) in patients undergoing cardiac computed tomography (CCT). The aim of iRCM-CCT is to assess image quality and safety profile of intravenous CM compounds. MATERIALS AND METHODS: iRCM-CCT enrolled 1842 consecutive patients undergoing CCT (≥50 per site) at 20 cluster sites with the indication of suspected coronary artery disease. Demographic characteristics, CCT, and CM protocols, clinical indications, safety markers, radiation dose reports, qualitative (ie, poor vascular enhancement) and quantitative (ie, HU attenuation values) image parameters were recorded. A centralized coordinating center collected and assessed all image parameters. RESULTS: The cohort included 891 men and 951 women (age: 63±14 y, body mass index: 26±4 kg/m2) studied with ≥64 detector rows computed tomography scanners and different iodinated intravenous CM protocols and compounds (iodixanol, iopamidol, iohexol, iobitridol, iopromide, and iomeprol). The following vascular attenuation was reported: 504±147 HU in the aorta, 451±146 HU in the right coronary artery, 474±146 HU in the left main, 451±146 HU in the left anterior descending artery, and 441±149 HU in the circumflex artery. In 4% of cases the image quality was not satisfactory due to poor enhancement. The following adverse reactions to CM were recorded: 6 (0.3%) extravasations and 17 (0.9%) reactions (11 mild, 4 moderate, 2 severe). CONCLUSIONS: In a multicenter registry on CM use during CCT the prevalence of CM-related adverse reactions was very low. The appropriate use of CM is a major determinant of image quality.

Comparison between Carotid Distensibility-Based Vascular Age and Risk-Based Vascular Age in Middle-Aged Population Free of Cardiovascular Disease.

The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction.

Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation.

Introduction: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev-Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev-Rem during the late postoperative period. Methods: Primary MR patients (n = 19; age, 45-71 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev-Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev-Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, -21-5p, -133a, and -208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 µM for 48 h). Results: Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, p = 0.016), who showed lower cardiac mass index (-11%, p = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (p < 0.05). In vitro, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition. Summary/Conclusion: High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev-Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev-Rem after successful early surgical MVR.

Multimodality Approach to a Complex Scimitar Syndrome: How Advanced Diagnostics Can Guide Therapeutic Strategies.

We report an unusual association of scimitar syndrome with right diaphragmatic hernia, left-sided aortic arch with "aberrant right subclavian artery" in a 2-year-old boy who underwent stepwise transcatheter occlusion of a significant aortopulmonary collateral followed by surgical treatment for the repair of the diaphragmatic hernia and esophageal compression. (Level of Difficulty: Advanced.).

Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?

Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582-0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807-0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis.

Big gamma-glutamyltransferase is associated with epicardial fat volume and cardiovascular outcome in the general population.

AIMS: Gamma-glutamyltransferase (GGT) has been recognized as a cardiovascular risk factor, and its highest molecular weight fraction [big GGT (b-GGT)] is found in vulnerable atherosclerotic plaques. We explored the relationship between b-GGT, computed tomography findings, and long-term outcomes in the general population. METHODS AND RESULTS: Between May 2010 and October 2011, subjects aged 45-75 years living in a Tuscan city and without known cardiac disease were screened. The primary endpoint was a composite of cardiovascular death or acute coronary syndrome requiring urgent coronary revascularization. Gamma-glutamyltransferase fractions were available in 898 subjects [median age 65 years (25th-75th percentile 55-70), 46% men]. Median plasma GGT was 20 IU (15-29), and b-GGT was 2.28 (1.28-4.17). Coronary artery calcium (CAC) score values were 0 (0-60), and the volume of pro-atherogenic epicardial fat was 155 mL (114-204). In a model including age, sex, low-density lipoprotein (LDL) cholesterol, current or previous smoking status, hypertension, diabetes, obesity, b-GGT independently predicted epicardial fat volume (EFV) (r = 0.162, P < 0.001), but not CAC (P = 0.198). Over a 10.3-year follow-up (9.6-10.8), 27 subjects (3%) experienced the primary endpoint. We evaluated couples of variables including b-GGT and a cardiovascular risk factor, CAC or EFV. Big GGT yielded independent prognostic significance from age, LDL cholesterol, current or previous smoking status, hypertension, diabetes, obesity, but not CAC or EFV. Conversely, GGT predicted the primary endpoint even independently from CAC and EFV. CONCLUSION: Big GGT seemed at least as predictive as the commonly available GGT assay; therefore, the need for b-GGT rather than GGT measurement should be carefully examined.

Detecting the vulnerable carotid plaque: the Carotid Artery Multimodality imaging Prognostic study design.

BACKGROUND: Carotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography. OBJECTIVES: The Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques. STUDY DESIGN: We will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727).