Coronary CT angiography for the assessment of atherosclerotic plaque inflammation: postmortem proof of concept with histological validation.

To evaluate the diagnostic utility of multiphase postmortem CT angiography (PMCTA) to detect plaque enhancement as a surrogate marker of inflammation, using fatal coronary plaques obtained from autopsies following sudden cardiac death. In this retrospective study, we included 35 cases (12 women, 34%; median [IQR] age, 52 [11] years), with autopsy-proven coronary thrombosis, histological examination, and multiphase PMCTA. Two radiologists blinded towards histological findings assessed PMCTA for plaque enhancement of the culprit lesion in consensus. Two forensic pathologists determined the culprit lesion and assessed histological samples in consensus. Cases with concomitant vasa vasorum density increase and intraplaque and periadventital inflammation were considered positive for plaque inflammation. Finally, we correlated radiology and pathology findings. All 35 cases had histological evidence of atherosclerotic plaque disruption and thrombosis; 30 (85.7%) had plaque inflammation. Plaque enhancement at multiphase PMCTA was reported in 21 (60%) and resulted in a PPV of 95.2% (77.3-99.2%) and an NPV of 28.6% (17-43.9%). Median histological ratings indicated higher intraplaque inflammation (p = .024) and vasa vasorum density (p = .032) in plaques with enhancement. We found no evidence of a difference in adventitial inflammation between CT-negative and CT-positive plaques (p = .211). Plaque enhancement was found in 2/3 of fatal atherothrombotic occlusions at coronary postmortem CT angiography. Furthermore, plaque enhancement correlated with histopathological plaque inflammation and increased vasa vasorum density. Plaque enhancement on multiphase CT angiography could potentially serve as a noninvasive marker of inflammation in high-risk populations. Phenotyping coronary plaque more comprehensively is one of the principal challenges cardiac imaging is facing. Translating our ex vivo findings of CT-based plaque inflammation assessment into clinical studies might help pave the way in defining high-risk plaque better. • Most thrombosed coronary plaques leading to fatality in our series had histological signs of inflammation. • Multiphase postmortem CT angiography can provide a noninvasive interrogation of plaque inflammation through contrast enhancement. • Atherosclerotic plaque enhancement at multiphase postmortem CT angiography correlated with histopathological signs of plaque inflammation and could potentially serve as an imaging biological marker of plaque vulnerability

Application of postmortem imaging modalities in cases of sudden death due to cardiovascular diseases-current achievements and limitations from a pathology perspective : Endorsed by the Association for European Cardiovascular Pathology and by the International Society of Forensic Radiology and Imaging.

Postmortem imaging (PMI) is increasingly used in postmortem practice and is considered a potential alternative to a conventional autopsy, particularly in case of sudden cardiac deaths (SCD). In 2017, the Association for European Cardiovascular Pathology (AECVP) published guidelines on how to perform an autopsy in such cases, which is still considered the gold standard, but the diagnostic value of PMI herein was not analyzed in detail. At present, significant progress has been made in the PMI diagnosis of acute ischemic heart disease, the most important cause of SCD, while the introduction of postmortem CT angiography (PMCTA) has improved the visualization of several parameters of coronary artery pathology that can support a diagnosis of SCD. Postmortem magnetic resonance (PMMR) allows the detection of acute myocardial injury-related edema. However, PMI has limitations when compared to clinical imaging, which severely impacts the postmortem diagnosis of myocardial injuries (ischemic versus non-ischemic), the age-dating of coronary occlusion (acute versus old), other potentially SCD-related cardiac lesions (e.g., the distinctive morphologies of cardiomyopathies), aortic diseases underlying dissection or rupture, or pulmonary embolism. In these instances, PMI cannot replace a histopathological examination for a final diagnosis. Emerging minimally invasive techniques at PMI such as image-guided biopsies of the myocardium or the aorta, provide promising results that warrant further investigations. The rapid developments in the field of postmortem imaging imply that the diagnosis of sudden death due to cardiovascular diseases will soon require detailed knowledge of both postmortem radiology and of pathology

Altered levels of blood proteins in Alzheimer\u27s disease longitudinal study: Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort

Introduction A blood-based biomarker panel to identify individuals with preclinical Alzheimer\u27s disease (AD) would be an inexpensive and accessible first step for routine testing. Methods We analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort. Results Levels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P =.0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P =.0008). Discussion These data suggest that apoJ may have potential in the context of use (COU) of AD diagnostics, I-309 may be specifically useful in the COU of identifying individuals at greatest risk for progressing toward AD. This work takes an initial step toward identifying blood biomarkers with potential use in the diagnosis and prognosis of AD and should be validated across other prospective cohorts. © 2017 The Author

The Origins of Bagan: The archaeological landscape of Upper Burma to AD 1300.

The archaeological landscape of Upper Burma from the middle of the first millennium BC to the Bagan period in the 13th-14th century AD is a landscape of continuity. Finds of polished stone and bronze artifacts suggest the existence of early metal-using cultures in the Chindwin and Samon River Valleys, and along parts of the Ayeyarwady plain. Increasing technological and settlement complexity in the Samon Valley suggests that a distinctive culture whose agricultural and trade success can be read in the archaeological record of the Late Prehistoric period developed there. The appearance of the early urban "Pyu" system of walled central places during the early first millennium AD seems to have involved a spread of agricultural and management skills and population from the Samon. The leaders of the urban centres adopted Indic symbols and Sanskrit modes of kingship to enhance and extend their authority. The early urban system was subject over time to a range of stresses including siltation of water systems, external disruption and social changes as Buddhist notions of leadership eclipsed Brahmanical ones. The archaeological evidence indicates that a settlement was forming at Bagan during the last centuries of the first millennium AD. By the mid 11th century Bagan began to dominate Upper Burma, and the region began a transition from a system of largely autonomous city states to a centralised kingdom. Inscriptions of the 11th to 13th centuries indicate that as the Bagan Empire expanded it subsumed the agricultural lands that had been developed by the Pyu

A change in inflammatory foot print precedes plaque instability: A systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis

Transplant surger

Evaluation of silver bio-functionality in a multicellular in vitro model: towards reduced animal usage in implant-associated infection research

Background: Despite the extensive use of silver ions or nanoparticles in research related to preventing implant-associated infections (IAI), their use in clinical practice has been debated. This is because the strong antibacterial properties of silver are counterbalanced by adverse effects on host cells. One of the reasons for this may be the lack of comprehensive in vitro models that are capable of analyzing host-bacteria and host-host interactions. Methods and results: In this study, we tested silver efficacy through multicellular in vitro models involving macrophages (immune system), mesenchymal stem cells (MSCs, bone cells), and S. aureus (pathogen). Our model showed to be capable of identifying each element of culture as well as tracking the intracellular survival of bacteria. Furthermore, the model enabled to find a therapeutic window for silver ions (AgNO3) and silver nanoparticles (AgNPs) where the viability of host cells was not compromised, and the antibacterial properties of silver were maintained. While AgNO3 between 0.00017 and 0.017 µg/mL retained antibacterial properties, host cell viability was not affected. The multicellular model, however, demonstrated that those concentrations had no effect on the survival of S. aureus, inside or outside host cells. Similarly, treatment with 20 nm AgNPs did not influence the phagocytic and killing capacity of macrophages or prevent S. aureus from invading MSCs. Moreover, exposure to 100 nm AgNPs elicited an inflammatory response by host cells as detected by the increased production of TNF-α and IL-6. This was visible only when macrophages and MSCs were cultured together. Conclusions: Multicellular in vitro models such as the one used here that simulate complex in vivo scenarios can be used to screen other therapeutic compounds or antibacterial biomaterials without the need to use animals

Application of postmortem imaging modalities in cases of sudden death due to cardiovascular diseases–current achievements and limitations from a pathology perspective

Postmortem imaging (PMI) is increasingly used in postmortem practice and is considered a potential alternative to a conventional autopsy, particularly in case of sudden cardiac deaths (SCD). In 2017, the Association for European Cardiovascular Pathology (AECVP) published guidelines on how to perform an autopsy in such cases, which is still considered the gold standard, but the diagnostic value of PMI herein was not analyzed in detail. At present, significant progress has been made in the PMI diagnosis of acute ischemic heart disease, the most important cause of SCD, while the introduction of postmortem CT angiography (PMCTA) has improved the visualization of several parameters of coronary artery pathology that can support a diagnosis of SCD. Postmortem magnetic resonance (PMMR) allows the detection of acute myocardial injury-related edema. However, PMI has limitations when compared to clinical imaging, which severely impacts the postmortem diagnosis of myocardial injuries (ischemic versus non-ischemic), the age-dating of coronary occlusion (acute versus old), other potentially SCD-related cardiac lesions (e.g., the distinctive morphologies of cardiomyopathies), aortic diseases underlying dissection or rupture, or pulmonary embolism. In these instances, PMI cannot replace a histopathological examination for a final diagnosis. Emerging minimally invasive techniques at PMI such as image-guided biopsies of the myocardium or the aorta, provide promising results that warrant further investigations. The rapid developments in the field of postmortem imaging imply that the diagnosis of sudden death due to cardiovascular diseases will soon require detailed knowledge of both postmortem radiology and of pathology