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OBJECTIVE: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS: A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2. The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses. PATIENTS AND METHODS: Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution. RESULTS: We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries. CONCLUSIONS: Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The ongoing Coronavirus pandemic (COVID-19) showed similar characteristics with the severe acute respiratory syndrome (SARS). In the most compromised cases, COVID-19 infection leads to death due to severe respiratory complications. COVID-19-related acute respiratory distress syndrome (ARDS) is the primary cause of death in these patients. In the present study, we show an ultrastructural analysis on the lungs of a patient affected by COVID-19. PATIENTS AND METHODS: Lung specimens obtained at autopsy from a 63-years old patient affected by COVID-19 were fixed in 1% paraformaldehyde. Slices of 300 µm thickness were dehydrated and dried by Critical Point Drying in CO2. Slices were covered with a conductive gold film approximately 30 nm thick and observed at a Zeiss Sigma 300 SEM FEG in the secondary electron (SE) and backscattered electron (BSE) modes. As case control a lung biopsy from a 60-year-old man was considered. RESULTS: At low power in all COVID-19 lung specimens severe changes in the pulmonary architecture were found, due to the collapse of air spaces. Moreover, alveolar cavities were covered by large membranes. At high power, alveolar membranes showed a fibrillar structure, suggestive of a loose network of fibrin. It has been also found that intra-alveolar red blood cells were frequently present in the alveolar spaces, surrounded by a reticular fibrin network, suggestive for fibrin-hemorrhagic alveolitis. Alveolar changes were constantly associated with pathological features related to the pulmonary vessels. Vascular changes were prominent, including endothelial damage and thrombosis of large pulmonary vessels. Fibrinous microthrombi were frequently detected in the inter-alveolar septal capillaries. In addition, it has been frequently detected capillary proliferation in the alveolar septa with finding suggestive for intussusceptive neo-angiogenesis. CONCLUSIONS: In conclusion, our electron microscopy analysis showed that COVID-19-related lung disease is characterized by a substantial architectural distortion, with the interactions between alveolar and vascular changes. Intra-alveolar hyaline membranes are associated with macroand micro-thrombotic angiopathy, ending with capillary proliferation. The new blood vessel formation originates from the septa and extends into the surrounding parenchyma. Our findings confirm previous reports on the specificity of the multiple and complex morphological pattern typical, and apparently specific, of COVID-19-related lung disease. [ABSTRACT FROM AUTHOR]

The risk stratification of young adults between subjects who will develop a mild form of atherosclerosis and subjects who will undergo a severe disease remains inaccurate. In the eighties of the previous century, David JP Barker has demonstrated the relationship between fetal conditions and occurrence of pathologies in adulthood. In this paper, the multiple evidence that might explain the increased susceptibility to severe forms of atherosclerosis, including stroke and cardiac infarct, in subjects who underwent intrauterine growth restriction (IUGR) will be analyzed. Specifically, we will review those inter-connected data indicating an association between a low weight at birth and an adult phenotype which might favor a severe outcome of atherosclerosis. Young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of atherosclerosis. Given that low birth weight (LBW) may be considered a surrogate of IUGR, this phenotypic feature could be considered among those indispensable clinical data collected in every patient presenting with atherosclerosis, irrespectively of age. According to the hypothesis that structural arterial changes might represent the link between LBW and susceptibility to atherosclerosis later in life, we suggest that the prevention of atherosclerosis should begin at birth. Regenerative and physiological substances such as thymosin Beta-4 could be challenged for a new "arterial regenerative medicine" in the perinatal period. The goal of this new approach should be the reinforcement of the structure of the arterial wall, allowing LBW newborns to avoid the most severe complications of atherosclerosis later in life: a dream that our research could contribute to bringing to life. [ABSTRACT FROM AUTHOR]

The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of “at risk subjects”, more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARSCOV- 2 infection, irrespectively of his/her age. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Vaccine-induced immune thrombocytopenia (VITT) is a new syndrome occurring primarily in healthy young adults, with a female predominance, after receiving the first dose of ChAdOx1 nCoV-19 vaccine. We describe VITT syndrome characterized by severe thrombosis and thrombocytopenia found in our patient, with fatal outcome. CASE REPORT: A 5 8-year-old m an, a fter 13 days from the first administration of ChAdOx1 nCoV-19 vaccine (AstraZeneca), presented with abdominal pain, diarrhea and vomitus. Laboratory tests revealed a severe thrombocytopenia, low fibrinogen serum levels and marked increase of D-dimer serum levels. The patient quickly developed a multiple organ failure, till death, three days after the hospital admission. RESULTS: At histology, in the lungs, interalveolar septa appeared thickened with microthrombi in the capillaries and veins. Interalveolar septa appeared thickened and showed vascular proliferation. Thrombi were detected in the capillaries of glomerular tufts. In the hearth, thrombi were observed in veins and capillaries. In the liver, voluminous fibrin thrombi were diffusely observed in the branches of the portal vein. Microthrombi were also found in the vasa vasorum of the wall of abdominal aorta. In the brain, microthrombi were observed in the capillaries of the choroid plexuses. Diffuse hemorrhagic necrosis was observed in the intestinal wall with marked congestion of the venous vessels. CONCLUSIONS: In our patient, the majority of data necessary for a VITT final diagnosis were present: thrombocytopenia and thrombosis in pulmonary, portal, hepatic, renal and mesenteric veins, associated with a marked increase of D-dimer serum levels. The finding of cerebral thrombosis in choroid plexuses, is a new finding in VITT. These features are suggestive for a very aggressive form of VITT. [ABSTRACT FROM AUTHOR]

Multiple epidemiological studies have suggested that industrialization and progressive urbanization should be considered one of the main factors responsible for the rising of atherosclerosis in the developing world. In this scenario, the role of trace metals in the insurgence and progression of atherosclerosis has not been clarified yet. In this paper, the specific role of selected trace elements (magnesium, zinc, selenium, iron, copper, phosphorus, and calcium) is described by focusing on the atherosclerotic prevention and pathogenesis plaque. For each element, the following data are reported: daily intake, serum levels, intra/extracellular distribution, major roles in physiology, main effects of high and low levels, specific roles in atherosclerosis, possible interactions with other trace elements, and possible influences on plaque development. For each trace element, the correlations between its levels and clinical severity and outcome of COVID-19 are discussed Moreover, the role of matrix metalloproteinases, a family of zinc-dependent endopeptidases, as a new medical therapeutical approach to atherosclerosis is discussed. Data suggest that trace element status may influence both atherosclerosis insurgence and plaque evolution toward a stable or an unstable status. However, significant variability in the action of these traces is evident: some - including magnesium, zinc, and selenium - may have a protective role, whereas others, including iron and copper, probably have a multi-faceted and more complex role in the pathogenesis of the atherosclerotic plaque. Finally, calcium and phosphorus are implicated in the calcification of atherosclerotic plaques and in the progression of the plaque toward rupture and severe clinical complications. In particular, the role of calcium is debated. Focusing on the COVID-19 pandemia, optimized magnesium and zinc levels are indicated as important protective tools against a severe clinical course of the disease, often related to the ability of SARS-CoV-2 to cause a systemic inflammatory response, able to transform a stable plaque into an unstable one, with severe clinical complications. [ABSTRACT FROM AUTHOR]

Wilson's disease (WD) is caused by the excessive accumulation of copper in the brain and liver, leading to death if not diagnosed early. WD shows its prevalence as white matter hyperintensity (WMH) in MRI scans. It is challenging and tedious to classify WD against controls when comparing visually, primarily due to subtle differences in WMH. This Letter presents a computer-aided design-based automated classification strategy that uses optimised transfer learning (TL) utilising two novel paradigms known as (i) MobileNet and (ii) the Visual Geometric Group-19 (VGG-19). Further, the authors benchmark TL systems against a machine learning (ML) paradigm. Using four-fold augmentation, VGG-19 is superior to MobileNet demonstrating accuracy and area under the curve (AUC) pairs as 95.46 ± 7.70%, 0.932 (p < 0.0001) and 86.87 ± 2.23%, 0.871 (p < 0.0001), respectively. Further, MobileNet and VGG-19 showed an improvement of 3.4 and 13.5%, respectively, when benchmarked against the ML-based soft classifier – Random Forest. [ABSTRACT FROM AUTHOR]