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Ischemic heart disease is one of the leading causes of morbidity and death worldwide. Consequently, myocardial infarctions are often encountered in clinical and forensic autopsies, and diagnosis can be challenging, especially in the absence of an acute coronary occlusion. Precise histopathological identification and timing of myocardial infarction in humans often remains uncertain while it can be of crucial importance, especially in a forensic setting when third person involvement or medical responsibilities are in question. A proper post-mortem diagnosis requires not only up-to-date knowledge of the ischemic coronary and myocardial pathology, but also a correct interpretation of such findings in relation to the clinical scenario of the deceased. For these reasons, it is important for pathologists to be familiar with the different clinically defined types of myocardial infarction and to discriminate myocardial infarction from other forms of myocardial injury. This article reviews present knowledge and post-mortem diagnostic methods, including post-mortem imaging, to reveal the different types of myocardial injury and the clinical-pathological correlations with currently defined types of myocardial infarction.

Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the heart weight, size, and thickness as well as a systematic use of cut off values for normality by age, gender, and body weight and height are needed. For these reasons, recommendations have been written on behalf of the Association for European Cardiovascular Pathology. The diagnostic work up implies the search for pressure and volume overload conditions, compensatory hypertrophy, storage and infiltrative disorders, and cardiomyopathies. Although some gross morphologic features can point to a specific diagnosis, systematic histologic analysis, followed by possible immunostaining and transmission electron microscopy, is essential for a final diagnosis. If the autopsy is carried out in a general or forensic pathology service without expertise in cardiovascular pathology, the entire heart (or pictures) together with mapped histologic slides should be sent for a second opinion to a pathologist with such an expertise. Indication for postmortem genetic testing should be integrated into the multidisciplinary management of sudden cardiac death.

In sudden cardiac death, an autopsy is an essential step in establishing a diagnosis of inherited cardiac disease and identifying families that require cardiac screening. To evaluate aspects of post-mortem practice in Europe, a questionnaire was designed and circulated to both clinical and forensic pathologists. There was a 48% response rate and information was obtained from 17 countries. The results showed a wide variety in the management of sudden cardiac death, with a general tendency towards a lack of thorough investigation. In up to 40% of cases, autopsies were not performed in subjects less than 50 years who may have died from cardiac disease. Reasons for this were lack of finance and lack of interest from police, legal authorities, and doctors. Only 50% of pathologists seem to follow a standard protocol for autopsy examination, apparently due to lack of expertise and/or training. When autopsies were performed, histology and toxicology were almost always taken, genetic studies were generally available and retention of the heart for specialist study was usually permitted. Our results suggest that although the standard of practice is appropriate in many centres, many more cases should have autopsies, especially in sudden deaths in subjects less than 50 years.

Stomach content analyses are a valuable tool in human forensic science to interpret perimortem events. While the identification of food components of plant and animal origin has traditionally been conducted by macro- and microscopical approaches in case of incomplete digestion, molecular methods provide the potential to increase sensitivity and taxonomic resolution. In particular, DNA metabarcoding (PCR-amplification and next generation sequencing of complex DNA mixtures) has seen a rapid growth in the field of wildlife ecology to assess species’ diets from faecal and gastric samples. Despite clear advantages, molecular approaches have not yet been established in routine human forensics to investigate the last meal components of deceased persons. In this pilot study we applied for the first time a DNA metabarcoding approach to assess both plant and vertebrate components of 48 human stomach content samples taken during medicolegal autopsies. We obtained a final dataset with 34 vertebrate and 124 vegetal unique sequences, that were clustered to 9 and 33 operational taxonomic units (OTUs), respectively. Our results suggest that this approach can provide crucial information about circumstances preceding death, and open promising perspectives for biomedical dietary surveys based on digested food items found in the gastrointestinal tract.

Sudden cardiac death (SCD) related to atherosclerotic coronary artery disease (ACAD) resulting in myocardial infarction is the most prevalent cause of death in western countries. In clinical practice, coronary artery calcium score (CACS) is considered an independent predictor of coronary events, closely related to atherosclerotic burden and is quantified radiologically by the Agatston score being calculated through computed tomography. Postmortem computed tomography (PMCT) allows the visualization and quantification of coronary calcifications before the autopsy. However, it was reported that some patients who died from severe ACAD had a zero CACS in PMCT. In this study, a retrospective evaluation of CACS in adult’s myocardial infarction cases related to ACAD, with available CACS and histological slides of coronary arteries, was performed in order to gain a deeper understanding of coronary calcifications and their role in myocardial infarction cases. The CACS was calculated by using the software Smartscore 4.0 after the radiological examination on a 64-row CT unit using a specific cardiac protocol. Thirty-six cases were identified out of 582 autopsies, recorded during a 2-year study period (29 men, 7 women; age 56.3 ± 11.7). CACS was 0–10 in 5 cases (5 men, 44.8 ± 13.7), 11–100 in 8 cases (6 men, 2 women, 53.1 ± 7.7), 101–400 in 13 cases (11 men, 2 women, 57.4 ± 9.6), and > 400 in 10 cases (9 men, 1 woman, 63.1 ± 11.9). Coronary thrombosis was found in 28 cases, histologically identified as plaque erosions in 6 cases and as plaque ruptures in 22 cases. Statistical analyses showed that CACS increases significantly with age (p-value < 0.05) and does not show significant correlation with gender, body weight, body mass index, and heart weight. CACS was significantly higher in plaque ruptures than in plaque erosions (p-value < 0.01). Zero or low CACS on unenhanced PMCT cannot exclude the presence of myocardial infarction related to ACAD. This paradoxical discrepancy between imaging and autopsy findings can be explained considering the histological aspect of fatal coronary plaques.

The goal of this study was to evaluate the diagnostic value of postmortem multi-computed tomography (MDCT) and MDCT-angiography for sudden cardiac deaths related to ischemic heart disease. Twenty three cases were selected based on clinical history and the results of native MDCT, multiphase post-mortem CT-angiography and conventional autopsy were compared. Radiological examination showed calcification of coronary arteries in 78% of the cases, most of which were not detailed at autopsy. MDCT-angiography allowed better visualization of the coronary arteries than MDCT and permitted the evaluation of stenoses and occlusions. Of the 14 cases of coronary thrombosis detected at conventional autopsy, 11 were visible as stop of perfusion with CT-angiography and three were found to be partly perfused. One case had an old thrombosis with collateral circulation. One case had a coronary artery postmortem clot found with MDCT-angiography. Coronary artery calcifications are more easily detected and documented with radiological examination than with conventional autopsy. MDCT is of limited diagnostic value for ischemic heart disease. MDCT-angiography, when correctly interpreted, is a reasonable tool to view the morphology of coronary arteries, rule out significant coronary artery stenoses, identify occlusions and direct sampling for histological examination.

In the past 2 decades, modern radiological methods, such as multiple detector computed tomography (MDCT), MDCT-angiography, and cardiac magnetic resonance imaging (MRI) were introduced into postmortem practice for investigation of sudden death (SD), including cases of sudden cardiac death (SCD). In forensic cases, the underlying cause of SD is most frequently cardiovascular with coronary atherosclerotic disease as the leading cause. There are many controversies about the role of postmortem imaging in establishing the cause of death and especially the value of minimally invasive autopsy techniques. This paper discusses the state of the art for postmortem radiological evaluation of the heart compared to classical postmortem examination, especially in cases of SCD. In SCD cases, postmortem CT is helpful to estimate the heart size and to visualize haemopericardium and calcified plaques and valves, as well as to identify and locate cardiovascular devices. Angiographic methods are useful to provide a detailed view of the coronary arteries and to analyse them, especially regarding the extent and location of stenosis and obstruction. In postsurgical cases, it allows verification and documentation of the patency of stents and bypass grafts before opening the body. Postmortem MRI is used to investigate soft tissues such as the myocardium, but images are susceptible to postmortem changes and further work is necessary to increase the understanding of these radiological aspects, especially of the ischemic myocardium. In postsurgery cases, the value of postmortem imaging of the heart is reportedly for the diagnostic and documentation purposes. The implementation of new imaging methods into routine postmortem practice is challenging, as it requires not only an investment in equipment but, more importantly, investment in the expertise of interpreting the images. Once those requirements are implemented, however, they bring great advantages in investigating cases of SCD, as they allow documentation of the body, orientation of sampling for further analyses and gathering of other information that cannot be obtained by conventional autopsy such as a complete visualization of the vascular system using postmortem angiography. Key points There are no established guidelines for the interpretation of postmortem imaging examination of the heart At present, postmortem imaging methods are considered as less accurate than the autopsy for cardiac deaths Postmortem imaging is useful as a complementary tool for cardiac deaths There is still a need to validate postmortem imaging in cardiac deaths by comparing with autopsy findings

Sudden cardiac death (SCD) represents a considerable percentage of cardiovascular deaths worldwide. The most frequent pathological substrate of SCD is atherosclerotic coronary artery disease (CAD). The other, less common, pathologies which can cause SCD include cardiomyopathies, congenital diseases (including abnormal anatomy), and arrhythmias such as channelopathies, many of which are genetically determined. Autopsies of SCD victims are generally performed by forensic pathologists. In some cases, a third person responsibility could be invoked. While CAD diagnosis at post-mortem examination is not a major challenge for the forensic pathologist, the other rarer diseases may be. In such instances, referral of the hearts to specialized centers with recognized expertise is recommended, and this is particularly important in cases of SCDs of young people. Moreover, in order to avoid the frequent overdiagnosis of a pathological heart, an expert opinion should be sought for even in the presence of a morphologically normal heart. In cases where retention of the heart is not feasible, it is essential to provide an extensive photographic documentation, with the indication of the sampling sites for histological examination. However, some practical aspects, as the criteria for case selection in routine forensic practice are missing. In this paper, we present the recommendations for heart retention for a second expert opinion and the alternative of documentation and sampling for cases where retention is not possible.

Innate lymphoid cells type 2 (ILC2s) are key regulators of tissue homeostasis and inflammation. In cancer, ILC2s can exhibit pro-tumoral functions by increasing the myeloid derived suppressor cells (MDSC)/T-cell ratio. Nevertheless, the upstream ILC2 triggers remain poorly defined. Here, we identify nerve growth factor (NGF) as the driver of ILC2 pro-tumoral functions in patients with bladder cancer. We show that ILC2s express the NGF receptor TrkA and respond to NGF by secreting type-2 cytokines. In the tumor microenvironment, NGF-producing mast cells accumulate and activate ILC2s to induce regulatory T cells (Tregs), ultimately fostering tumor growth. In patients, NGF levels inversely correlate with survival in ILC2-rich tumors, underscoring the clinical significance of this axis. In vivo administration of a selective TrkA inhibitor improves survival in orthotopic tumor-bearing female mice and sensitizes them to immune checkpoint blockade (ICB). Overall, we identify NGF as an ILC2 activator that shapes pro-tumoral ILC2 functions. The blockade of TrkA + ILC2s might represent a targetable strategy to improve survival, particularly in ICB-resistant patients. Neurotrophic factor Nerve Growth Factor (NGF) is involved in bladder physiopathology. Here the authors report that mast-cell derived NGF sustains the pro-tumoral functions of ILC2s in bladder cancer (BC), showing that selective targeting of the NGF receptor TrkA improves survival and response to immune checkpoint blockade in BC models.

The medical autopsy (also called hospital or clinical autopsy) is a highly specialised medical procedure, which requires professional expertise and suitably equipped facilities. To ensure high standards of performance, the Working Group of Autopsy Pathology of the European Society of Pathology (ESP) suggests a code of practice as a minimum standard for centres performing medical autopsies. The proposed standards exclusively address autopsies in adults, and not forensic autopsies, perinatal/or paediatric examinations. Minimum standards for organisation, standard of premises, and staffing conditions, as well as minimum requirements for level of expertise of the postmortem performing specialists, documentation, and turnaround times of the medical procedure, are presented. Medical autopsies should be performed by specialists in pathology, or by trainees under the supervision of such specialists. To maintain the required level of expertise, autopsies should be performed regularly and in a number that ensures the maintenance of good practice of all participating physicians. A minimum number of autopsies per dedicated pathologist in a centre should be at least 50, or as an average, at least one autopsy per working week. Forensic autopsies, but not paediatric/perinatal autopsies may be included in this number. Turnaround time for final reports should not exceed 3 weeks (14 working days) for autopsies without fixation of brain/spinal cord or other time-consuming additional examinations, and 6 weeks (30 working days) for those with fixation of brain/spinal cord or additional examinations.