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SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome. Platelets containing SARS-CoV-2 might originate from bone marrow and lung megakaryocytes (MKs), the platelet precursors, which were found infected by SARS-CoV-2 in COVID-19 autopsies. Accordingly, MKs undergoing shortened differentiation and expressing anti-viral IFITM1 and IFITM3 RNA as a sign of viral sensing were enriched in the circulation of deadly COVID-19. Infected MKs reach the lung concomitant with a specific MK-related cytokine storm rich in VEGF, PDGF and inflammatory molecules, anticipating fatal outcome. Lung macrophages capture SARS-CoV-2-containing platelets in vivo. The virus contained by platelets is infectious as capture of platelets carrying SARS-CoV-2 propagates infection to macrophages in vitro, in a process blocked by an anti-GPIIbIIIa drug. Altogether, platelets containing infectious SARS-CoV-2 alter COVID-19 pathogenesis and provide a powerful fatality marker. Clinical targeting of platelets might prevent viral spread, thrombus formation and exacerbated inflammation at once and increase survival in COVID-19.

Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.

We report 2 unusual autopsy cases with head handgun wounds using defective firearms in a suicidal context. In the first case, a 78-year-old man was found hanged from a tree, with a Lefaucheux revolver lying on the tree. In the right temporal region, there was an entrance wound with a bullet still in place, responsible for a mild cerebral contusion, without bone defect. The main cause of death was hanging. In the second case, a 60-year-old man died at home after shooting himself in the head several times with a 22-long rifle revolver. The autopsy showed 13 entrance wounds on the scalp. Most of the bullets remained along the skull vault. In each of 2 cases, the manner of death, the feasibility of suicidal gesture, and the consequences of a brain injury on the time to the occurrence of incapacity were questioned. These unusual autopsy cases underline how important it is to take into account the defective nature of firearms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE2, and IL-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE2, and IL-1β levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy., Graphical abstract, Cell biology; Molecular physiology; Virology

Exposure to metals and trace elements (TE) is universal and can cause toxicity in case of excessive exposure. We evaluated the concentrations and tissue distribution of 39 TE using high-resolution ICP-MS after total mineralization by microwave in twenty autopsied French subjects. We found a globally homogeneous distribution of TE in the body, with some accumulations in agents, involved in respiratory pathologies and classified as carcinogens, in the lungs. The liver, an organ of metabolism, appeared to concentrate Co, Fe, La, Mn, Mo, Pb and Zn. Fe seemed to accumulate in the spleen, the organ of hematopoiesis. The kidney showed high concentrations of some TE, which can cause nephrotoxicity. The use of microwave mineralization and high-resolution ICP-MS allowed accurate quantification and a very high sensitivity, without spectral interferences. The results obtained in this study could be used to support the interpretation of post-mortem metal concentrations in tissues.

Untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) techniques have become indispensable tools for systematic toxicological analysis. They allow the research of an almost unlimited number of drugs within a single analytical cycle, but shared mass spectra libraries are still missing to identify newly marketed compounds, along with defined analytical procedures. This article describes the optimization, validation, and application of an untargeted screening method devoted to hair analysis using data-dependent analysis (DDA) and a shared HRMS database. This method used an ultra-high performance liquid chromatography coupled to a benchtop Orbitrap. Raw MS data were processed with Compound Discoverer software coupled to the mzCloud™ library. Optimizations were performed on blank hair spiked with 19 analytes having different physical and chemical properties. To validate the effectiveness of a shared spectra database, 20 compounds spectra were added and then retrospectively screened. Sensitivity and reliability were evaluated on 317 compounds of interest in toxicology. The method was then applied to 11 hair samples. The matrix effect range by ion suppression/enhancement was 40%-110%. The method allows the detection of 284 among the 317 screened compounds, including 72 new psychoactive substances (NPS). Lower limit of identification (LLOI) and lower limit of detection (LLOD) were 1 to 1000 pg/mg and 1 to 500 pg/mg, respectively. The method was successfully applied to 11 clinical cases and 144 compounds were identified including 24 NPS including AKB48-5F for the first time in hair. We developed and validated an LC-HRMS untargeted screening of 284 compounds and successfully applied it to 11 real hair samples.

Resume Le cannabis est le stupefiant le plus consomme en France. Sa toxicite neuropsychiatrique est bien connue et la litterature recente semble evoquer une toxicite cardiaque. Entre 2001 et 2016, nous avons identifie 33 deces pour lesquels une origine cardiaque etait identifiee ou envisagee a l’autopsie et/ou a l’examen anatomopathologique et pour lesquels seul un cannabinoide a ete mis en evidence dans le sang au niveau de l’analyse toxicologique de recherche de causes de deces. L’etude de ces cas a montre qu’il s’agissait majoritairement de sujets masculins (90 %) avec un âge median de 37 ans [IQ25–75 = 29–44]. Du (−)−Δ9 tetrahydrocannabinol (THC) et du 11-nor-tetrahydrocannabinol carboxylique (THC-COOH) ont ete retrouves dans le sang pour l’ensemble des cas avec des concentrations medianes (intervalle interquartile IQ25–75) respectives de 2,9 ng/mL (IQ25–75 1,5–6,5) pour le THC et 28 ng/mL (IQ25–75 12–43) pour le THC-COOH. Le 11-hydroxy-tetrahydrocannabinol (11-OH-THC) a ete mis en evidence chez 21 personnes avec une concentration mediane de 1,55 ng/mL (IQ25–75 0,8–2,8), temoignant d’une derniere prise recente avant le deces. Parmi ces 33 personnes, 14 ont pu etre identifiees comme etant des consommateurs chroniques et 2 comme etant des consommateurs occasionnels de cannabis. Il n’existait pas de donnees pour les autres. Les causes de deces observees etaient majoritairement des maladies coronariennes (n = 20) mais il a egalement ete mis en evidence des cardiomyopathies (n = 8), des myocardites (n = 2) et des causes autres (n = 3). L’etude de l’evolution des cas semble en faveur d’une tendance a l’augmentation pouvant eventuellement etre mise en relation avec l’evolution des teneurs en cannabinoides des plantes et resines observee ces dernieres annees. Bien que le mecanisme d’action de cette cardiotoxicite ne soit pas encore elucide, plusieurs liens semblent exister entre le systeme endocannabinoide et le systeme cardiovasculaire. Le cannabis pourrait donc apparaitre comme un facteur de risque cardiovasculaire a prendre en compte et dont la consommation devrait etre recherchee notamment chez les sujets jeunes presentant des troubles cardiovasculaires.

Summary Adipocere formation requires very particular conditions of humidity and pH, but when it is formed, it can persist for very long periods. To date, there are very few cases with toxicological analyses performed on adipocere. We report two cases with a long delay between death and the discovery of the body (24 days and 12 years) associated with adipocere formation. In both cases a screening was carried out by GC-MS and LC-DAD. Additionally, a LC-MS/MS screening for drug facilitated sexual assault was performed allowing the detection of psychotropic substances at very low levels. Adipocere samples were hydrolyzed with a lipase buffer before liquid-liquid extraction. In the first case, diazepam, nordazepam and flunitrazepam were found at 2.1 ng/g, 1.8 ng/g and 1.2 ng/g, respectively. In case 2, phenobarbital was found at 26 μg/g in adipocere and 59 μg/g in liver. Although the post-mortem delay was important and the environmental conditions may have affected the measured concentrations, we were able to highlight the presence of 3 benzodiazepines and a barbiturate. The interpretation of these results remains complicated because of the lack of data in the literature.

Suicide is one of the most disastrous outcomes for psychiatric disorders. Recent advances in biological psychiatry have suggested a positive relationship between some specific brain abnormalities and specific symptoms in psychiatric disorders whose organic bases were previously completely unknown. Microglia, immune cells in the brain, are regarded to play crucial roles in brain inflammation by releasing inflammatory mediators and are suggested to contribute to various psychiatric disorders such as depression and schizophrenia. Recently, activated microglia have been suggested to be one of the possible contributing cells to suicide and suicidal behaviors via various mechanisms especially including the tryptophan-kynurenine pathway. Animal model research focusing on psychiatric disorders has a long history, however, there are only limited animal models that can properly express psychiatric symptoms. In particular, to our knowledge, animal models of human suicidal behaviors have not been established. Suicide is believed to be limited to humans, therefore human subjects should be the targets of research despite various ethical and technical limitations. From this perspective, we introduce human biological studies focusing on suicide and microglia. We first present neuropathological studies using the human postmortem brain of suicide victims. Second, we show recent findings based on positron emission tomography (PET) imaging and peripheral blood biomarker analysis on living subjects with suicidal ideation and/or suicide-related behaviors especially focusing on the tryptophan-kynurenine pathway. Finally, we propose future perspectives and tasks to clarify the role of microglia in suicide using multi-dimensional analytical methods focusing on human subjects with suicidal ideation, suicide-related behaviors and suicide victims.

A manner of death may be ruled undetermined by the forensic pathologist when there is insufficient information about the circumstances surrounding the death to make a ruling. The aim of our study was to retrospectively analyze a series of autopsy cases that were classified as undetermined manner of death after complete investigations. In all, 48 cases were examined. In 23 cases (48%), the cause of death was determined. The most frequent cause of death was toxic death (n = 11). More than one manner of death was deemed conceivable for most cases (n = 39). The most frequent and the most probable manner of death was accident (n = 37). Homicide was not excluded in about 23% of the cases. Our study showed that the manner of death may remain undetermined despite an established cause of death, and even when two or more conceivable causes of death are considered. Our study pointed out that undetermined manner of death covers a wide range of situations and that homicide may be underestimated.

The aim of our study was to highlight the epidemiological difference in adult sudden death between males and females. The type of pathologies found in adult victims of sudden death was compared to control cases in order to determine the most significant pathologies involved in sudden death. Among all autopsies performed between 1995 and 2009, 534 adult cases of sudden death and 154 cases who violently died were respectively selected. For each case, a complete autopsy was carried out, including systematic histological examination of all major organs. The sudden death population was composed of 369 males and 165 females. There was no statistical difference regarding age between males and female. Sudden death took place more often at home in women than in men (p 0.0001). A stressful event was more frequently found in men than in women (p = 0.03). Deaths caused by cardiovascular diseases were more frequent in males than in females, especially Coronary Artery Disease (CAD) (p 0.0001). Cardiomyopathy was more often the cause of death in women, particularly Arrythmogenic Right Ventricular Cardiomyopathy (ARVC). Cardiac pathologies were found in 45% of the control cases. CAD and ARVC were statistically more frequent in the sudden death group than in the control group. According to our study, profile of sudden death is different between males and females. Those data seem to be important for clinicians involved in prevention programs of sudden death, as they can adapt their screening according to the gender.

Determination of the manner of death is a major issue in forensic practice. Differentiating the injuries caused by falls from a low height from injuries due to the deliberate application of a blunt object can be difficult. A few studies suggested the use of certain criteria, such as the hat brim line rule, to help in differentiating between falls and blows. Unfortunately they are not consistent. All autopsy cases from a 16-year period (1996–2012) were analyzed retrospectively. Three groups were defined: homicide cases (n = 31), sudden natural deaths involving a fall (n = 103), and accidental fall cases (n = 30). The three groups were statistically compared across a wide range of parameters including general characteristics, presence, and characteristics of different types of wounds (lacerations, deep bruises, fractures, intracranial trauma, and defense injuries) as well as their respective anatomical site. There were marked differences in wounds between homicide and fall cases, e.g., wounds were more numerous and larger in homicides. We did not confirm the hat brim line rule as a reliable discriminating parameter. A simple and highly effective multivariate model was found, which included the presence of lacerations, deep bruises, and intracranial trauma. This study underlines the importance of autopsy findings in providing an indication of the manner of death. Conversely, the limitations of the hat brim line rule have been highlighted.

We present the case of a reciprocal homicide by stabbing that occurred within an unmarried couple without known history of spousal violence. Each partner killed the other one at the same time and at the same place using kitchen knives. They were both found dead at home lying on the floor after the neighbors heard an argument and screams coming from the couple's apartment, so they called the police and the fire department. The door was locked from the inside, and the fire department was forced to break the door. Two kitchen knives supporting blood traces were found at the scene. At autopsy, both bodies showed multiple stab wounds, and the lethal ones were due to heart injuries. Defense injuries were also found in both bodies. To our knowledge, this is the first case of reciprocal homicide described in the literature. Other manners of death are discussed, including homicide by a third party, homicide-suicide, and suicide pact.

Injuries to the neck structures are various in case of hanging. Soft tissue lesions generally consist in sternocleidomastoid and subhyoid muscle hemorrhages. Traumatic ruptures of deep neck structures are rare. We report 2 cases of partial and complete ruptures of sternocleidomastoid muscles after suicidal hanging. Both were typical and complete hanging. In 1 case, muscle laceration was associated with common carotid rupture on the same side. Hemorrhage at the rupture site was only found at the microscopic level. Such injuries may result from the ligature's compression and depend on duration of suspension. Heavy body weight, rigid rope material, and fall after a jump may promote their occurrence.

INTRODUCTION Medieval autopsy practice is very poorly known in Western Europe, due to a lack of both descriptive medico-surgical texts and conserved dissected human remains. This period is currently considered the dark ages according to a common belief of systematic opposition of Christian religious authorities to the opening of human cadavers. MATERIAL AND METHODS The identification in a private collection of an autopsied human individual dated from the 13(th) century A.D. is an opportunity for better knowledge of such practice in this chrono-cultural context, i.e. the early origins of occidental dissections. A complete forensic anthropological procedure was carried out, completed by radiological and elemental analyses. RESULTS The complete procedure of this body opening and internal organs exploration is explained, and compared with historical data about forensic and anatomical autopsies from this period. During the analysis, a red substance filling all arterial cavities, made of mercury sulfide (cinnabar) mixed with vegetal oil (oleic and palmitic acids) was identified; it was presumably used to highlight vascularization by coloring in red such vessels, and help in the preservation of the body. CONCLUSIONS Of particular interest for the description of early medical and anatomical knowledge, this "human preparation" is the oldest known yet, and is particularly important for the fields of history of medicine, surgery and anatomical practice.

Previous population-based studies have identified increased suicide rates among cancer patients. Available post mortem data on the contribution of cancer to completed suicide are limited, however. This study examines forensic autopsy data in order to assess whether cancer is significantly more frequent in a suicide population compared with a control population. In total, 232 cases were included in both the suicide and the control groups. Based on a complete standard histological examination, cancer was significantly more often found in the suicide group than in the control one (8.6% vs. 3.9%, p=0.03). The multivariate analysis also showed that the presence of cancer increased the risk of suicide. Moreover, cancer was not known to the deceased in 70% of cases, while the most frequent mental disease found in cancer-related suicide cases was depression (75%). In the 20 cancer-related suicide cases analysed herein, it was difficult to ascertain whether malignancy was the only motive for committing suicide, as cancer could be considered to be either a major causative factor for suicide or an incidental finding. Therefore, further research is warranted with the help of the psychological autopsy method to investigate the link between suicide and cancer further.

The assessment of post-mortem interval is of major importance in forensic pathology. Many methods have been used in the early post-mortem period but remain rough. To test the hypothesis of an increased rate of apoptosis increasing with post-mortem interval, TUNEL method was applied in rats to study the relationship between the number of apoptotic cells in skin samples and the post-mortem interval. Our study showed that the post-mortem processes were associated with apoptosis in skin cells. The apoptosis rate was statistically correlated with post-mortem interval in the early post-mortem (less than 48 hours after death). The application of the TUNEL method for estimating the post-mortem interval in forensic pathology is discussed.

Objectif : Entierement automatisable et couple a la spectrometrie de masse, l’extraction en ligne est un outil alliant rapidite et sensibilite. Le but de cette etude a ete de developper une methode de dosage dans le plasma d’un analogue structural de la ketamine, la methoxetamine (MXE), par LC/MS/MS precedee d’une extraction en ligne utilisant le systeme Turboflow®. Methodes : 100 μ L de plasma sont ajoutes au meme volume d’une solution de travail de ketamine-d4 dans l’acetonitrile utilise comme etalon interne (EI). Apres centrifugation, 20 μ L du surnageant sont injectes sur une colonne d’extraction C18 XL (50 × 0,5-mm). Les analytes retenus sont transferes de la colonne d’extraction vers une colonne analytique Hypersil GOLD (50 × 3-mm; diametre des particules : 3 μ m) puis elues grâce a un gradient de phase mobile tampon formiate/acetonitrile. La MXE et l’EI sont ionises grâce a une source electrospray en mode positif. Les ions parents [M + H]+ sont m /z 248,1 pour la MXE et m /z 242,1 pour l’EI. L’ion fils le plus abondant apres fragmentation est utilise pour la quantification, soit m/z 203,1 pour la MXE et 224,1 pour l’EI. Resultats : La justesse est comprise entre 96,8 % et 108,8 % et les CV intra- et inter-jour Le systeme Turboflow® couple a la LC/MS/MS permet une quantification rapide de composes comme la MXE dans le plasma sans extraction prealable et sans effet matrice. Cette methode a permis avec succes la confirmation analytique d’une intoxication aigue a la MXE, montrant chez le patient une concentration plasmatique de 136,0 ng/mL.

Facing modern developments of medicine and biomedical researches, religious communities are a strong source of ethics principles and orientations. Human dignity does not disappear after life, in a context of biomedical research on cadavers. Moral, political, social and scientific aspects of research on human cadavers (mainly autopsies) have been widely discussed in biomedical publications, whereas the religious ones (which could be predominant for some) have rarely been analyzed and presented. This article will present the results of a survey carried out a French Benedictine Abbey (relative to death, cadaver's status and biomedical research) and subsequent Christian background according to canonic texts and practical cases from anthropological, historical, archeological and biomedical origin.

Gunshot wounds are among the most complex traumatic lesions encountered in forensic pathology. At the time of autopsy, careful scrutiny of the wounds is essential for correct interpretation of the lesions. Complementary pathological analysis has many interests: differentiation between entrance and exit wounds, estimation of firing distance, differentiation between vital and post mortem wounds and wounds dating. In case of multiple headshots, neuropathological examination can provide arguments for or against suicide. Sampling of gunshot wounds at autopsy must be systematic. Pathological data should be confronted respectively to autopsy and death scene investigation data and also ballistic studies. Forensic pathologist must be aware of the limits of optic microscopy.

Forensic pathologists involved in the ICTY missions could be subjected to ethical tensions. In order to study the nature of such tensions, review of the literature and analysis of forensic material available from the trial transcripts relative to Srebrenica massacre were carried out. Forensic evidence used in ICTY trials is weakened by many factors, including especially the difficulties in the interpretation of the autopsy findings and the possibility of a biased selection of exhumations by the Office of the Prosecutor. Although discrepancies exist between forensic evidence and facts established by ICTY judgments about Srebrenica events, genocide charge was not challenged by ICTY, conflicting with the idea that reliably established facts are the foundation of legal analysis. The degree of ethical conflicts in forensic pathologist’s community depends on their level of knowledge respectively about the fundamental principles of the law subverted by ICTY and the political implications of international justice. Ethical guidelines are needed to ease such ethical tensions.

The aim of this study was to determine the frequency and nature of cervical trauma in the case of low-height falls (up to 2.50 m). A retrospective study was carried out on 114 autopsy cases that died after low-height falls. For each case, age, sex, manner and cause of death, estimated height of fall, ground type, type of primary impact, type of laryngeal and hyoid bone trauma, presence of associated local trauma in the neck and cephalic region, and toxicological data were reported. Fractures of the hyoid bone and/or of the laryngeal cartilages were present in 2.5% of the cases (n = 3). Cervical soft tissue bruising was found in 13% of the cases (n = 15). About 6% of the cases (n = 7) showed blunt cervical vertebral column trauma, including 3 cases with ruptured intervertebral disk. Interpretation and mechanisms of these lesions are discussed.

Objectif : Le cannabis, drogue la plus consommee dans le monde, engendre de nombreux troubles notamment comportementaux. Le cannabis contient, outre le Δ 9 -THC habituellement etudie, du cannabidiol et du cannabinol. Les effets des cannabinoides semblant se poursuivre au-dela de leur presence dans le sang, un decalage de cinetique entre cerveau et sang pourrait exister pour ces molecules. Methode : Apres mise au point et validation d’une technique permettant le dosage, par CPG/SM, du Δ 9 -THC, de ses metabolites, du cannabinol et du cannabidiol, nous avons effectue des cinetiques de ces composes dans le sang, dans les hemispheres cerebraux et dans le cervelet chez la souris. Nous avons egalement dose ces composes dans le sang, les urines et sept zones de cerveau chez des patients autopsies. Resultats : Nous avons mis en evidence la presence de cannabidiol dans le cerveau de souris alors qu’il n’est plus present dans le sang. Une telle persistance a egalement ete retrouvee pour le cannabidiol, mais egalement le THC et le cannabinol, sur des prelevements de cerveau de personnes decedees. Conclusion : il semble que certains cannabinoides persistent dans le cerveau apres disparition du sang. Cette persistance pourrait expliquer certains troubles spatio-temporaux durables des personnes consommatrices de cette drogue.

Impaired arginine vasopressin (AVP) synthesis and release by the neurohypophyseal system, which includes the neurohypophysis and magnocellular neurons of the paraventricular and supraoptic nuclei, have been postulated in septic shock, but changes in this system have never been assessed in human septic shock, and only partially experimentally. We investigated AVP synthesis and release by the neurohypophyseal system in 9 patients who died from septic shock and 10 controls, and in 20 rats with fecal peritonitis-induced sepsis and 8 sham-operation controls. Ten rats died spontaneously from septic shock, and the others were sacrificed. In patients with septic shock, as in rats that died spontaneously following sepsis induction, AVP immunohistochemical expression was decreased in the neurohypophysis and supraoptic magnocellular neurons, whereas it was increased in the paraventricular magnocellular neurons. No significant change was observed in AVP messenger RiboNucleic Acid (mRNA) expression assessed by in situ hybridization in either paraventricular or supraoptic magnocellular cells. This study shows that both in human and experimental septic shock, AVP posttranscriptional synthesis and transport are differently modified in the magnocellular neurons of the supraoptic and paraventricular nuclei. This may account for the inappropriate AVP release in septic shock and suggests that distinct pathogenic mechanisms operate in these nuclei.

The forensic community does not agree on the need to perform histological examination at forensic autopsy. The aim of our study was to determine the usefulness of systematic standard histology in forensic autopsies. A prospective study was carried out on 428 autopsy cases for which standard histological examination was systematic. Mechanism of death not shown by gross anatomic findings was discovered by histology in about 40% of the cases. Cause of death was established by only histology in 8.4% of the cases. Microscopic findings affected the manner of death in 13% of the cases. Histology provided complementary information about prior medical condition of the deceased in about 49% of the cases. Traumatic lesions were better documented by histology in about 22% of the cases. According to the results of our study, systematic standard histology for the main organs should be used in routine forensic autopsies.

The macroscopic study of cranial sutures is one of the methods that may be used in forensic anthropology to estimate age at the time of death. The present study aims at assessing the value of a microscopic analysis of the fronto-sphenoidal suture (FSS) sampled at autopsy, to determine both the physiological mechanisms responsible for the FFS closing during ageing and its value in the estimation of age at the time of death. We assessed the vascular capital as well as the apoptosis of conjunctive cells intervening as parameters in the physiological mechanism involved in cell ageing, in a population of individuals, whose gender and age was known. The FSS analysis was performed after decalcification and standard histological study, respectively with immunohistochemistry (Factor Von Willebrand antibody) VWF and (TdT-mediated dUTP nick end labelling) TUNEL method and caspase-3 immunohistochemical expression. In this study we found a significant reversed correlation between the degree of vascular expression of VWF and age at the time of death. There was also a significant positive correlation between the degree of apoptosis in the conjunctive cells of the FSS and age at the time of death. According to these results, suture closing during ageing can be explained by these two combined mechanisms of conjunctival apoptosis and vascular involution. Thus, the findings justify the study of closing sutures to estimate age at the time of death. Besides, it also enabled us to establish linear regressions. The vascular expression of the VWF enables to estimate an individual's age at the time of his death more or less at about 1.55 years, offering an interesting perspective both in forensic pathology and anthropology.

A 54-year-old man was found dead with a bottle containing a brownish fluid near him. A toxicological screening was carried out in blood, urine, and stomach content. Only dichlorvos (2,2 dichlorovinyl 0-0 dimethylphosphate or DDVP) was found. A simple and rapid method, using DDVP-D 6 as an internal standard, was developed for the determination of DDVP by gas chromatography/mass spectrometry (GC/MS). The method was linear from 1 to 10 mg/L. Intraday and interday precisions were all

In this study, we evaluated the potential direct role of enterovirus (EV) cardiac infections in the pathogenesis of myocardial infarction (MI).Enteroviruses (Picornaviridae) have been suspected to play a role in the development of acute MI.The presence of EV ribonucleic acid (RNA) sequences and capsid viral protein 1 (VP1) and the virus-mediated focal disruption of dystrophin were retrospectively investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry assays in endomyocardial tissues of patients who died suddenly of acute MI by comparison with similar samples of control patients matched for gender, residence area, and year of death.Enterovirus infection markers were detected in 20 (40%) of 50 patients who died suddenly of MI, 2 (4%) of 50 matched subjects without cardiac disease (p0.001), and 4 (8%) of 50 matched patients exhibiting a noncoronary chronic cardiopathy (p0.001). All of the EV RNA-positive patients exhibited VP1, which provided evidence of viral protein synthesis activity. The VP1 gene sequences amplified after cloning from myocardial or coronary samples of 8 of the MI patients and showed a strong homology with sequences of coxsackievirus B2 and B3 serotypes. Moreover, in the endomyocardial tissue of these 8 patients, immunohistochemical analyses demonstrated that there was disruption of the sarcolemmal localization of dystrophin in the same tissue areas that were infected by coxsackieviruses.Our findings demonstrate a significantly higher proportion of active coxsackievirus B cardiovascular infections in patients who suddenly died of MI compared with matched control subjects, suggesting that these EVs may significantly contribute to the pathogenesis of acute MI by a focal disruption of the dystrophin-glycoprotein complex.

Understanding of sepsis-induced brain dysfunction remains poor, and relies mainly on data from animals or post-mortem studies in patients. The current study provided findings from magnetic resonance imaging of the brain in septic shock. Nine patients with septic shock and brain dysfunction [7 women, median age 63 years (interquartile range 61–79 years), SAPS II: 48 (44–56), SOFA: 8 (6–10)] underwent brain magnetic resonance imaging including gradient echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), T2-weighted and diffusion isotropic images, and mapping of apparent diffusion coefficient. Brain imaging was normal in two patients, showed multiple ischaemic strokes in two patients, and in the remaining patients showed white matter lesions at the level of the centrum semiovale, predominating around Virchow–Robin spaces, ranging from small multiple areas to diffuse lesions, and characterised by hyperintensity on FLAIR images. The main lesions were also characterised by reduced signal on diffusion isotropic images and increased apparent diffusion coefficient. The lesions of the white matter worsened with increasing duration of shock and were correlated with Glasgow Outcome Score. This preliminary study showed that sepsis-induced brain lesions can be documented by magnetic resonance imaging. These lesions predominated in the white matter, suggesting increasedblood–brain barrier permeability, and were associated with poor outcome.

Sudden death is now currently described as natural unexpected death occurring within 1h of new symptoms. Most studies on the subject focused on cardiac causes of death because most of the cases are related to cardiovascular disease, especially coronary artery disease. The incidence of sudden death varies largely as a function of coronary heart disease prevalence and is underestimated. Although cardiac causes are the leading cause of sudden death, the exact incidence of the other causes is not well established because in some countries, many sudden deaths are not autopsied. Many risk factors of sudden cardiac death are identified: age, gender, heredity factors such as malignant mutations, left ventricular hypertrophy and left ventricle function impairment. The role of the police surgeon in the investigation of sudden death is very important. This investigation requires the interrogation of witnesses and of the family members of the deceased. The interrogation of physicians of the rescue team who attempted resuscitation is also useful. Recent symptoms before death and past medical history must be searched. Other sudden deaths in the family must be noted. The distinction between sudden death at rest and during effort is very important because some lethal arrhythmia are triggered by catecholamines during stressful activity. The type of drugs taken by the deceased may indicate a particular disease linked with sudden death. Sudden death in the young always requires systematic forensic autopsy performed by at least one forensic pathologist. According to recent autopsy studies, coronary artery disease is still the major cause of death in people aged more than 35 years. Cardiomyopathies are more frequently encountered in people aged less than 35 years. The most frequent cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The postmortem diagnosis of cardiomyopathies is very important because the family of the deceased will need counseling and the first-degree relatives may undergo a possible screening to prevent other sudden deaths. In each case of sudden death, one important duty of the forensic pathologist is to inform the family of all autopsy results within 1 month after the autopsy. Most of the recent progress in autopsy diagnosis of sudden unexpected death in the adults comes from molecular biology, especially in case of sudden death without significant morphological anomalies. Searching mutations linked with functional cardiac pathology such as long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now the best way in order to explain such sudden death. Moreover, new syndromes have been described by cardiologists, such as short-QT syndrome and revealed in some cases by a sudden death. Molecular biology is now needed when limits of morphological diagnosis have been reached.

Resume Avec la circulaire du 30 juillet 2004, pour la premiere fois un texte est specifiquement consacre a l’architecture de la salle d’autopsie. Cette circulaire reprend a son compte certaines des prescriptions techniques de l’arrete du 7 mai 2001 applicables aux chambres mortuaires des etablissements de sante. Elle le complete ou le modifie, en particulier pour le traitement des effluents liquides, ce qui va necessiter de nouveaux travaux dans les chambres mortuaires et de nouvelles depenses pour les hopitaux. Elle met en avant le principe de precaution et oblige a repenser la prise en charge du cadavre en salle d’autopsie.

Trois cent cinquante-huit prelevements post-mortem, representant 30 mois d'expertises toxicologiques, ont ete analyses afin de determiner l'interet des resultats dans le cadre des recherches de causes de deces. Nous avons pour cela compare les resultats d'analyses aux conclusions etablies lors de l'autopsie lorsque celle-ci etaitpratiquee (n = 292). Dans 66 cas, l'autopsie n'a pas ete effectuee, les prelevements ayant ete realises lors de "levee de corps". La presence d'au moins un xenobiotique est retrouvee dans 272 cas (76%) sur les 358 deces. Sur les 80 deces pour lesquels la conclusion de l'autopsie etait une origine toxique probable, 68 (85%) ont ete confirmes par l'analyse, 12 cas (15%) ne revelantpas de toxiques. Sur les 181 deces pour lesquels la cause etait evidente a l'autopsie et a priori d'origine non toxique, parexemple par noyade, homicide ou pendaison, 112 (61,8%) ont revele l'absence de tout toxique et 69 (34,2%) montraient la presence de toxiques pouvant avoir joue un role dans les circonstances du deces. Sept de ces deces pouvaient meme etre directement expliques par la seule presence des toxiques. Enfin, sur les 31 deces d'origine naturelle probable, 27 (87%) ont montre l'absence de tout toxique et 4 (13%) ont revele un deces d'origine toxique. Les medicaments sont les substances les plus souvent rencontrees (168 deces, soit 61, 7%), essentiellement representes par les benzodiazepines (27%) et les antidepresseurs (16,2%). L'alcool est retrouve dans 158 cas (58%). Les stupefiants sont retrou ves dans 62 cas (22,7%), le cannabis etant le plus souvent rencontre (n = 50), devant la morphine (n-21), dont 15 imputables a une prise d'heroine (presence de 6-MAM et codeine).

An original liquid chromatography method with photodiode-array detection (DAD) is presented for the determination of strychnine in blood. This sensitive method allows the use of only 0.1 ml of sample. The strychnine was isolated from blood using a liquid-liquid extraction procedure and chloroquine as an internal standard. The limits of detection (LOD) and quantification were 0.06 and 0.5 mg/l, respectively. The recovery was 94% and the coefficients of variation (CV) ranged from 5.9 to 10.8%. A fatal case of strychnine poisoning is presented, with a lethal blood concentration of 25 mg/l.

A new rapid and sensitive high-performance liquid chromatography method has been developed for the screening and determination in human plasma of the 11 most commonly prescribed nontricyclic antidepressants and two metabolites: fluoxetine, norfluoxetine, sertraline, paroxetine, citalopram, fluvoxamine, moclobemide, mirtazapine, milnacipram, toloxatone, venlafaxine, desmethyl venlafaxine, and viloxazine. It involves liquid-liquid extraction procedures followed by liquid chromatography coupled to photodiode-array UV detection with three fixed wavelengths (220, 240, and 290 nm). Compounds were separated on a 5-microm Hypurity C18 (ThermoHypersil) analytic column (250 x 4.6 mm i.d.) using a gradient of acetonitrile-phosphate buffer pH 3.8 at a flow rate of 1.0 mL/min. The total analysis time was only 18 min per sample. Extraction recoveries were in the 74-109% range for 11 compounds but were of only 59% for moclobemide and less than 10% for toloxatone. Calibration curves were linear in the 25 to 1000 ng/mL range for all compounds, all of them with coefficients of determination (r2 values) > or = 0.999. Limits of detection (LODs) ranged from 2.5 to 5 ng/mL except for toloxatone (10 ng/mL). Intraassay and interassay precision and accuracy were studied at two concentration levels (50 and 500 ng/mL). The intraassay coefficients of variation (CVs) for all compounds were < or = 7.6%, and all interassay CVs were below 11.5% except for milnacipram (14.8%). The intraassay and interassay accuracies for all compounds were found to be within 88.4% and 105.9% at 50 ng/mL and within 87.2% and 100.5% at 500 ng/mL. The performance of the method allows the therapeutic drug monitoring of the most prescribed nontricyclic antidepressant drugs as well as its use in toxicologic screening.

The laryngeal cartilages undergo age changes, including mineralization and ossification. Keen and Wainwright defined, in male and female subjects, recognizable stages of radiopacity of the thyroid, cricoid, and arytenoid cartilages. The present study analyzed quantitatively the degree of laryngeal radiopacity to determine whether radiography of the larynx can be used routinely in forensic pathology to estimate age at death. In each of 82 subjects, the larynx was removed during forensic autopsy and subjected to radiography in an anteroposterior orientation. Each radiograph was independently scored by two observers. For each case, the degree of laryngeal radiopacity was evaluated according to the classification of Keen and Wainwright. There was a positive correlation between the total score of laryngeal radiopacity and age (correlation coefficient = 0.74). It was concluded that this method is simple, fast, and nondestructive and has a good reproducibility between observers. Because there was a wide interindividual variability in the same age class, this method must be associated with more accurate methods.

Un cas de deces a la strychnine, pour lequel nous ne possedions qu 'un faible prelevement de sang, a entraine la mise au point d'une technique de dosage par chromatographie liquide haute performance couplee a une detection par barrette de diodes ne necessitant que 0,1 ml d'echantillon. Cette technique a egalement ete appliquee a un echantillon de liquide gastrique et au liquide contenu dans une cannette de biere trouvee a cote du corps. La strychnine a ete isolee a partir de ces echantillons par une technique d'extraction liquide-liquide, avec la chloroquine comme etalon interne. Les limites de detection et de quantification sont respectivement de 0,06 mg/l et 1 mg/l. Le rendement d'extraction est de 94 % et les coefficients de variation sont compris entre 5,9 et 10,8 %. La concentration de strychnine observee dans le sang (25 mg/l) etait mortelle.

Do all clinical research publications show strong application of ethics principles and respect for biomedical law? We examined, for the year 2009, the ethics requirements displayed on the website of 30 leading medical journals with an impact factor (IF) >10, and 30 others with an IF

This article describes the case of a sudden death in a 45-year-old female consecutive to acute and extensive arterial dissection in a context of Ehlers-Danlos syndrome type IV. The interest of this case report is that autopsy findings led to the suspicion of a clinical diagnosis prompting as carrying out a genetic testing which definitively confirms the diagnosis, opening the way to genetic council for family members. Criteria for this disease diagnosis and full methodology are described, that may help forensic practitioners.