Coronary Artery Calcification: Current Concepts and Clinical Implications.

Coronary artery calcification (CAC) accompanies the development of advanced atherosclerosis. Its role in atherosclerosis holds great interest because the presence and burden of coronary calcification provide direct evidence of the presence and extent of coronary artery disease; furthermore, CAC predicts future events independently of concomitant conventional cardiovascular risk factors and to a greater extent than any other noninvasive biomarker of this disease. Nevertheless, the relationship between CAC and the susceptibility of a plaque to provoke a thrombotic event remains incompletely understood. This review summarizes the current understanding and literature on CAC. It outlines the pathophysiology of CAC and reviews laboratory, histopathological, and genetic studies, as well as imaging findings, to characterize different types of calcification and to elucidate their implications. Some patterns of calcification such as microcalcification portend increased risk of rupture and cardiovascular events and may improve prognosis assessment noninvasively. However, contemporary computed tomography cannot assess early microcalcification. Limited spatial resolution and blooming artifacts may hinder estimation of degree of coronary artery stenosis. Technical advances such as photon counting detectors and combination with nuclear approaches (eg, NaF imaging) promise to improve the performance of cardiac computed tomography. These innovations may speed achieving the ultimate goal of providing noninvasively specific and clinically actionable information.

How to improve epidemiological trustworthiness concerning abdominal aortic aneurysms.

BACKGROUND: Research on degenerative abdominal aortic aneurysms (AAA) is hampered by complex pathophysiology, sub-optimal pre-clinical models, and lack of effective medical therapies. In addition, trustworthiness of existing epidemiological data is impaired by elements of ambiguity, inaccuracy, and inconsistency. Our aim is to foster debate concerning the trustworthiness of AAA epidemiological data and to discuss potential solutions. METHODS: We searched the literature from the last five decades for relevant epidemiological data concerning AAA development, rupture, and repair. We then discussed the main issues burdening existing AAA epidemiological figures and proposed suggestions potentially beneficial to AAA diagnosis, prognostication, and management. RESULTS: Recent data suggest a heterogeneous scenario concerning AAA epidemiology with rates markedly varying by country and study cohorts. Overall, AAA prevalence seems to be decreasing worldwide while mortality is apparently increasing regardless of recent improvements in aortic-repair techniques. Prevalence and mortality are decreasing in high-income countries, whereas low-income countries show an increase in both. However, several pieces of information are missing or outdated, thus systematic renewal is necessary. Current AAA definition and surgical criteria do not consider inter-individual variability of baseline aortic size, further decreasing their reliability. CONCLUSIONS: Switching from flat aortic-size thresholds to relative aortic indices would improve epidemiological trustworthiness regarding AAAs. Aortometry standardization focusing on simplicity, univocity, and accuracy is crucial. A patient-tailored approach integrating clinical data, multi-adjusted indices, and imaging parameters is desirable. Several novel imaging modalities boast promising profiles for investigating the aortic wall. New contrast agents, computational analyses, and artificial intelligence-powered software could provide further improvements.

The Role of Copper Overload in Modulating Neuropsychiatric Symptoms.

Copper is a transition metal essential for growth and development and indispensable for eukaryotic life. This metal is essential to neuronal function: its deficiency, as well as its overload have been associated with multiple neurodegenerative disorders such as Alzheimer's disease and Wilson's disease and psychiatric conditions such as schizophrenia, bipolar disorder, and major depressive disorders. Copper plays a fundamental role in the development and function of the human Central Nervous System (CNS), being a cofactor of multiple enzymes that play a key role in physiology during development. In this context, we thought it would be timely to summarize data on alterations in the metabolism of copper at the CNS level that might influence the development of neuropsychiatric symptoms. We present a non-systematic review with the study selection based on the authors' judgement to offer the reader a perspective on the most significant elements of neuropsychiatric symptoms in Wilson's disease. We highlight that Wilson's disease is characterized by marked heterogeneity in clinical presentation among patients with the same mutation. This should motivate more research efforts to disentangle the role of environmental factors in modulating the expression of genetic predisposition to this disorder.

Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy.

BACKGROUND: Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). RESULTS: One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively. CONCLUSION: Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.

Artificial intelligence-based preventive, personalized and precision medicine for cardiovascular disease/stroke risk assessment in rheumatoid arthritis patients: a narrative review.

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP3) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™-aiP3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized.

The Post-Translational Modifications of Human Salivary Peptides and Proteins Evidenced by Top-Down Platforms.

In this review, we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. In the beginning, we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section, the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteomes. Three sections are dedicated to the description of glycation and enzymatic glycosylation. Citrullination and N- and C-terminal post-translational modifications (PTMs) and miscellaneous other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed throughout the sections of the manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

Combined Salivary Proteome Profiling and Machine Learning Analysis Provides Insight into Molecular Signature for Autoimmune Liver Diseases Classification.

Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are autoimmune liver diseases that target the liver and have a wide spectrum of presentation. A global overview of quantitative variations on the salivary proteome in presence of these two pathologies is investigated in this study. The acid-insoluble salivary fraction of AIH and PBC patients, and healthy controls (HCs), was analyzed using a gel-based bottom-up proteomic approach combined with a robust machine learning statistical analysis of the dataset. The abundance of Arginase, Junction plakoglobin, Desmoplakin, Hexokinase-3 and Desmocollin-1 decreased, while that of BPI fold-containing family A member 2 increased in AIHp compared to HCs; the abundance of Gelsolin, CD14, Tumor-associated calcium signal transducer 2, Clusterin, Heterogeneous nuclear ribonucleoproteins A2/B1, Cofilin-1 and BPI fold-containing family B member 2 increased in PBCp compared to HCs. The abundance of Hornerin decreased in both AIHp and PBCp with respect to HCs and provided an area under the ROC curve of 0.939. Machine learning analysis confirmed the feasibility of the salivary proteome to discriminate groups of subjects based on AIH or PBC occurrence as previously suggested by our group. The topology-based functional enrichment analysis performed on these potential salivary biomarkers highlights an enrichment of terms mostly related to the immune system, but also with a strong involvement in liver fibrosis process and with antimicrobial activity.

Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging.

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature.

Primary endometrial squamous cell carcinoma (PESCC) is a rare entity. As the clinicopathologic features and the immunophenotype have not been completely defined yet, here we report our experience and review of the literature on this topic. A 73-yr-old nulliparous woman presented with pelvic pain and vaginal bleeding. Endometrial biopsy showed a carcinoma with squamous differentiation infiltrating the myometrium. Total hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed. Definitive diagnosis was squamous carcinoma of the endometrium, with one lymph node metastasis (stage IIIC1). Immunohistochemistry evidenced immunoreactivity of the tumor cells for cytokeratin 5, p63, cytokeratin 7, PAX8, PTEN, and cyclin D1, aberrant p53 overexpression, and Ki-67 reactivity in ~70% of the tumor cells. Estrogen and progesterone receptor, PAX2, WT1, and p16 were negative. Our case was the first PAX8-positive PESCC in the literature, underlining the Mullerian system origin of this neoplasm. Abnormal p53 expression of this case confirmed its role in the pathogenesis of PESCC. Further studies on a large number of cases are needed to better understand the pathologic features and the immunophenotype of PESCC.

Understanding the Behaviour of Human Cell Types under Simulated Microgravity Conditions: The Case of Erythrocytes.

Erythrocytes are highly specialized cells in human body, and their main function is to ensure the gas exchanges, O2 and CO2, within the body. The exposure to microgravity environment leads to several health risks such as those affecting red blood cells. In this work, we investigated the changes that occur in the structure and function of red blood cells under simulated microgravity, compared to terrestrial conditions, at different time points using biochemical and biophysical techniques. Erythrocytes exposed to simulated microgravity showed morphological changes, a constant increase in reactive oxygen species (ROS), a significant reduction in total antioxidant capacity (TAC), a remarkable and constant decrease in total glutathione (GSH) concentration, and an augmentation in malondialdehyde (MDA) at increasing times. Moreover, experiments were performed to evaluate the lipid profile of erythrocyte membranes which showed an upregulation in the following membrane phosphocholines (PC): PC16:0_16:0, PC 33:5, PC18:2_18:2, PC 15:1_20:4 and SM d42:1. Thus, remarkable changes in erythrocyte cytoskeletal architecture and membrane stiffness due to oxidative damage have been found under microgravity conditions, in addition to factors that contribute to the plasticity of the red blood cells (RBCs) including shape, size, cell viscosity and membrane rigidity. This study represents our first investigation into the effects of microgravity on erythrocytes and will be followed by other experiments towards understanding the behaviour of different human cell types in microgravity.

Thymosin ß4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis.

Thymosin ß4 (Tß4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tß4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tß4 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of Tß4 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of Tß4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, Tß4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tß4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tß4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled Tß4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.

Multicenter Study on COVID-19 Lung Computed Tomography Segmentation with varying Glass Ground Opacities using Unseen Deep Learning Artificial Intelligence Paradigms: COVLIAS 1.0 Validation.

Variations in COVID-19 lesions such as glass ground opacities (GGO), consolidations, and crazy paving can compromise the ability of solo-deep learning (SDL) or hybrid-deep learning (HDL) artificial intelligence (AI) models in predicting automated COVID-19 lung segmentation in Computed Tomography (CT) from unseen data leading to poor clinical manifestations. As the first study of its kind, "COVLIAS 1.0-Unseen" proves two hypotheses, (i) contrast adjustment is vital for AI, and (ii) HDL is superior to SDL. In a multicenter study, 10,000 CT slices were collected from 72 Italian (ITA) patients with low-GGO, and 80 Croatian (CRO) patients with high-GGO. Hounsfield Units (HU) were automatically adjusted to train the AI models and predict from test data, leading to four combinations-two Unseen sets: (i) train-CRO:test-ITA, (ii) train-ITA:test-CRO, and two Seen sets: (iii) train-CRO:test-CRO, (iv) train-ITA:test-ITA. COVILAS used three SDL models: PSPNet, SegNet, UNet and six HDL models: VGG-PSPNet, VGG-SegNet, VGG-UNet, ResNet-PSPNet, ResNet-SegNet, and ResNet-UNet. Two trained, blinded senior radiologists conducted ground truth annotations. Five types of performance metrics were used to validate COVLIAS 1.0-Unseen which was further benchmarked against MedSeg, an open-source web-based system. After HU adjustment for DS and JI, HDL (Unseen AI) > SDL (Unseen AI) by 4% and 5%, respectively. For CC, HDL (Unseen AI) > SDL (Unseen AI) by 6%. The COVLIAS-MedSeg difference was < 5%, meeting regulatory guidelines.Unseen AI was successfully demonstrated using automated HU adjustment. HDL was found to be superior to SDL.

A previously undescribed variant of cutaneous clear-cell squamous cell carcinoma with psammomatous calcification and intratumoral giant cell granulomas.

Cutaneous clear-cell squamous cell carcinoma (ccSCC) is a rare variant of SCC composed of clear cells that lack cytoplasmic glycogen or evidence of tricholemmal keratinization. We report a previously undescribed variant of ccSCC with psammomatous calcification and intratumoral giant cell granulomas. The differential diagnosis with trichilemmal carcinoma is outlined according to the criteria of the fourth edition of World Health Organization (WHO) classification. Our findings outline that psammomatous calcification may occur inside the keratinous pearls of the neoplastic lobules triggering an intratumoral giant cell granulomatous reaction. The prognostic significance of this histopathological presentation is unknown but the potential for formation of psammoma bodies in cSCC should be considered to avoid diagnostic pitfalls.

Saliva, a bodily fluid with recognized and potential diagnostic applications.

Human whole saliva is a bodily fluid that can be obtained easily by noninvasive techniques. Specimens can be collected by the patient also at home in order to monitor health status and variations of several analytes of clinical interest. The contributions to whole saliva include secretions from salivary glands and, among others, from the gingival crevicular fluid that derives from the epithelial mucosa. Therefore, saliva is currently a relevant diagnostic fluid for many substances, including steroids, nonpeptide hormones, therapeutic drugs, and drugs of abuse. This review at first briefly describes the different contributions to whole saliva. A section illustrates the procedures for the collection, handling, and storage of salivary specimens. Another section describes the present use of whole saliva for diagnostic purposes and its specific utilization for the diagnosis of several local and systemic diseases. The final sections illustrate the future opportunities offered by various not conventional techniques with a focus on the most recent -omic investigations. It describes the various issues that have to be taken into account to avoid false positives and negatives, such as the strength of the experimental plan, the adequacy of the number of samples under study, and the proper choice of controls.

Stress hormones kinetics in ventricular fibrillation cardiac arrest and resuscitation: Translational and therapeutic implications.

BACKGROUND: Knowing the kinetics of endogenous stress hormones during cardiac arrest and cardiopulmonary resuscitation (CRP) will help to optimize personalized physiology-guided treatment. The aim of this study was to examine the dynamic changes in stress hormones in a swine model of ventricular fibrillation (VF) cardiac arrest. METHODS: Ventricular fibrillation was induced in 10 healthy Landrace/Large White piglets, which were subsequently left untreated for 8 min. All animals were resuscitated according to the 2015 European Resuscitation Council guidelines. The concentration of adrenalin, noradrenalin, and cortisol was measured at baseline and at the 4th and 8th minute of VF-cardiac arrest, as well as at 30-min, 60-min, 24 h and 48 h post-ROSC. RESULTS: By the end of the 4th min of VF, the animals of the ROSC group exhibited significantly higher adrenaline levels compared to those of the no-ROSC group (7264 pg/ml vs. 1648 pg/ml, p = 0.03). Noradrenaline was higher in the ROSC group at the 4th min of VF (3021 pg/ml vs. 1626 pg/ml, p = 0.02). Cortisol levels in the ROSC group were significantly lower by the end of the 8th min of VF [16.25 ng/ml vs. 92.82 ng/ml, p = 0.03]. With a cut-off point of 5970 pg/ml, adrenaline at the 4th min of VF exhibited 100% sensitivity and 80% specificity for predicting ROSC. CONCLUSION: Higher endogenous adrenaline and lower endogenous cortisol levels were associated with ROSC.

Anatomical distribution and expression of CYP in humans: Neuropharmacological implications.

The cytochrome P450 (CYP450) superfamily is responsible for the metabolism of most xenobiotics and pharmacological treatments generally used in clinical settings. Genetic factors as well as environmental determinants acting through fine epigenetic mechanisms modulate the expression of CYP over the lifespan (fetal vs. infancy vs. adult phases) and in diverse organs. In addition, pathological processes might alter the expression of CYP. In this selective review, we sought to summarize the evidence on the expression of CYP focusing on three specific aspects: (a) the anatomical distribution of the expression in body districts relevant in terms of drug pharmacokinetics (liver, gut, and kidney) and pharmacodynamics, focusing for the latter on the brain, since this is the target organ of psychopharmacological agents; (b) the patterns of expression during developmental phases; and (c) the expression of CYP450 enzymes during pathological processes such as cancer. We showed that CYP isoforms show distinct patterns of expression depending on the body district and the specific developmental phases. Of particular relevance for neuropsychopharmacology is the complex regulatory mechanisms that significantly modulate the complexity of the pharmacokinetic regulation, including the concentration of specific CYP isoforms in distinct areas of the brain, where they could greatly affect local substrate and metabolite concentrations of drugs.

Zinc as a Drug for Wilson's Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury.

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.

Mapping of Transglutaminase-2 Sites of Human Salivary Small Basic Proline-Rich Proteins by HPLC-High-Resolution ESI-MS/MS.

Because of the distinctive features of the oral cavity, the determination of the proteins involved in the formation of the "oral protein pellicle" is demanding. The present study investigated the susceptibility of several human basic proline-rich peptides, named P-H, P-D, P-F, P-J, and II-2, as substrates of transglutaminase-2. The reactivity of the P-C peptide and statherin was also investigated. Peptides purified from human whole saliva were incubated with the enzyme in the presence or in the absence of monodansyl-cadaverine. Mass spectrometry analyses of the reaction products highlighted that P-H and P-D (P32 and A32 variants) were active substrates, II-2 was less reactive, and P-F and P-J showed very low reactivity. P-C and statherin were highly reactive. All of the peptides formed cyclo derivatives, and only specific glutamine residues were involved in the cycle formation and reacted with monodansyl-cadaverine: Q29 of P-H, Q37 of P-D, Q21 of II-2, Q41 of P-C, and Q37 of statherin were the principal reactive residues. One or two secondary glutamine residues of only P-H, P-D P32, P-C, and statherin were hierarchically susceptible to the reaction with monodansyl-cadaverine. MS and MS/MS data were deposited to the ProteomeXchange Consortium ( http://www.ebi.ac.uk/pride ) via the PRIDE partner repository with the data set identifier PXD014658.

Integration of cardiovascular risk assessment with COVID-19 using artificial intelligence.

Artificial Intelligence (AI), in general, refers to the machines (or computers) that mimic "cognitive" functions that we associate with our mind, such as "learning" and "solving problem". New biomarkers derived from medical imaging are being discovered and are then fused with non-imaging biomarkers (such as office, laboratory, physiological, genetic, epidemiological, and clinical-based biomarkers) in a big data framework, to develop AI systems. These systems can support risk prediction and monitoring. This perspective narrative shows the powerful methods of AI for tracking cardiovascular risks. We conclude that AI could potentially become an integral part of the COVID-19 disease management system. Countries, large and small, should join hands with the WHO in building biobanks for scientists around the world to build AI-based platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors.

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.