Target Organs of Metals Released from Metal-on-Polyethylene Knee and Hip Arthroplasty Implants: Implications for Tissue Metal Profiles.

Metals are used in orthopedic implants. The wear of arthroplasty implant can lead to the release of arthroprosthetic metals, both locally and systemically, after migration into the organs. While the toxicity of metal-on-metal arthroplasty implants is well-known and monitored, the toxicity associated with metal-on-polyethylene (MoP) ones is not as comprehensively understood. This study aimed to investigate the release of metals from MoP arthroplasty implants and their impact on the tissue metal profile in autopsied individuals, comparing them to deceased controls without prostheses. High-resolution ICP-MS was employed to analyze 39 metals in the blood, urine, hair, organs, and periprosthetic tissue of 25 deceased individuals with arthroplasty implants and 20 control subjects (Prometox study, protocol ID: APHP180539, NCT03812627). Eight metals (beryllium, chromium, cobalt, lanthanum, molybdenum, nickel, tellurium, titanium) exhibited significant impacts in arthroplasty implant wearers across various organs. Increased concentrations of La and Be were observed, the origin of which could not be precisely defined within the scope of this study. Notably, the lungs emerged as the primary target organ for metallic ions contained in implants. This study suggests that MoP arthroplasty implants, even when functional and not visibly worn, release arthroprosthetic metals into the body, potentially causing disturbances. Furthermore, considering the presence of an arthroplasty implant in autopsy reports may be relevant, as the released metals could influence the tissue metal profile.

Evaluation of the cardiovascular risk induced by cannabis use from a series of 43 autopsy cases.

The aim of this monocentric observational autopsy study was to confirm the existence of a link between cannabis use and cardiovascular risk. It was based on the analysis of autopsy findings, cardiovascular pathological findings, and toxicological data in 43 autopsy cases of people who died with tetrahydrocannabinol (THC) in their blood over a 2-year period. Hair analysis was performed when available (n = 40) to distinguish between occasional and chronic cannabis use and to take into account other possible exposures, including smoking, drug consumption, and the use of other drugs of abuse (mainly cocaine, heroin, and amphetamine). A statistically significant association (Fisher's exact test, p < 0.001) was found between cannabis use, an undetermined manner of death, and the presence of an arrhythmogenic cardiac condition. An association was also found between cannabis use and the presence of advanced coronary heart disease (p = 0.01), heart disease (including ischemic heart disease, p = 0.003), or cardiomyopathy (p = 0.01). Through its systemic vascular action, cannabis could be a factor in triggering sudden death in subjects with arrhythmogenic cardiac conditions. In view of this finding, the mode of death of subjects who died in the presence of THC in the blood would in most cases be an "accident." These results highlight the potential adverse cardiac effects associated with cannabis use.

Trace elements repartition in body fluids, hair and organs in an autopsied population evaluated by ICP-MS high resolution.

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.

Pannexin-1 channel opening is critical for COVID-19 pathogenesis.

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-1ß release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE2, and IL-1ß 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.

Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy.

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.

Traumatic rupture of deep neck structures in hanging: two case reports.

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.

A glimpse into the early origins of medieval anatomy through the oldest conserved human dissection (Western Europe, 13(th) c. A.D.).

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.

Are suicide rates higher in the cancer population? An investigation using forensic autopsy data.

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.

Neck pseudo-bruising secondary to acute aortic dissection.

We report a case of lethal acute aortic dissection revealed by a large ecchymotic area at the root of the neck; the subject was an 86-year-old man who died suddenly in his hospital room. His medical history included ischemic heart disease with pacemaker implantation and an aortic surgical prosthesis. Forensic autopsy showed a major subcutaneous hemorrhage in the neck and large left pleural and pericardial adhesions secondary to thoracic surgery. The cause of death was an acute aortic dissection. Large adhesions led to an extensive mediastinal hemorrhage, spreading to the subcutaneous tissues of the neck. This case report highlights the difficulties in differentiating between traumatic and pseudo-bruising during a death scene investigation. The etiologies of pseudo-bruising are reviewed.

Survival time estimation using Injury Severity Score (ISS) in homicide cases.

The aim of our study was to assess the value of ISS to estimate survival time in a retrospective study of all homicidal deaths in the Western suburbs of Paris between 1994 and 2008. Stab wounds were the most common cause of death. Survival time between assault and death, determined in 107 cases out of 511 homicide cases, ranged from 0 min to 25 days (mean 39 h). There was an overall significant association between the survival time and the ISS score. ISS and survival time were strongly associated with male victims and a clear trend was seen with women. Regarding the type of wounds, a trend was seen with gunshot wounds and blunt injuries, but not with stab wounds. There was no influence of blood toxicological results and resuscitation attempts. Overall, ISS was a good predictor of a survival under 30 min.

Frequency and nature of testicular and paratesticular lesions in forensic autopsies.

The aim of our study was to determine the frequency and nature of testicular and paratesticular lesions in forensic autopsies. A retrospective study was carried out on 495 adult male cases that underwent forensic autopsy from January 2008 to December 2011 in our Department. For each case, the following parameters were reported: age, body mass index, nature of testicular and paratesticular lesions, associated lesions in external genitalia, testicle weight, cause of death, manner of death, resuscitation attempts and prior medical history. Mean age of the studied population was 47.8 years (range 18-96). Mean body mass index was 25.3 kg/m(2) (range 15-46.2). Testicular lesions and/or paratesticular were found in 16.4% of the cases (n = 81). The most frequent lesions were, respectively, testicular atrophy (n = 38) and trauma (n = 28). In three cases showing traumatic lesions, associated traumatic lesions were found in external genitalia. Most frequent cause of death was blunt trauma (19.9% of the cases). Manner of death most frequently associated with testicular trauma was, respectively, road traffic accident (n = 11) and suicidal fall (n = 6). Mean testicular weight was, respectively, 17.9 g for the right and 20.8 g for the left (range 2-38). Atrophy was associated with testicular weight less than 10 g. A significant association between testicular atrophy and age was found, the risk of atrophy increasing quite linearly with age. No significant statistical link between prior medical history and testicular pathology was found. There was also no influence of body mass index. Resuscitation attempts were not statistically associated with testicular traumatic lesions.

Is post-mortem ultrasonography a useful tool for forensic purposes?

PURPOSE: To investigate the interest of post-mortem ultrasonography in the diagnosis of pathological background, and manner and cause of death. METHODS: Post-mortem ultrasonography exams were carried out on 38 fresh human adult cadavers referred to the Department of Forensic Medicine and Pathology (Garches, France). Data obtained from ultrasonography were independently compared with further forensic autopsy findings. RESULTS: Two important limitations relative to ultrasound utilization appeared: hyper-echoic abdominal and thoracic walls, with gas distension of the whole digestive tube and subcutaneous tissues (due to precocious putrefactive gas releasing); and difficulty in accessing lateral and posterior structures (i.e. liver, spleen, kidneys, lung bases, aorta) due to rigor mortis and evident non-compliance of the subject. Post-mortem diagnoses (moderate ascites, gallbladder stones, bladder globe, chronic kidney disease, cirrhosis, thyroid gland cysts and hypertrophy, intrauterine device), were strongly limited. False negative diagnoses comprised fatty liver, pleural effusion, thoracic aortic dissection, and focal organ and/or soft tissues lesions (for example, wounds or infarcts). CONCLUSION: According to the results, post-mortem ultrasonography seems to have a very limited role for forensic purposes. Other post-mortem utilizations are cited, proposed, and discussed.

The embalmed heart of Richard the Lionheart (1199 A.D.): a biological and anthropological analysis.

During the Middle Ages, the partition of the cadaver of the elite members was a current practice, with highly technical treatment given to symbolic organs such as the heart. Considered mostly from a theoretical point of view, this notion of dilaceratio corporis has never been biologically explored. To assess the exact kind of embalming reserved to the heart, we performed a full biomedical analysis of the mummified heart of the English King Richard I (1199 A.D.). Here we show among other aspects, that the organ has been embalmed using substances inspired by Biblical texts and practical necessities of desiccation. We found that the heart was deposed in linen, associated with myrtle, daisy, mint, frankincense, creosote, mercury and, possibly, lime. Furthermore, the goal of using such preservation materials was to allow long-term conservation of the tissues, and good-smelling similar to the one of the Christ (comparable to the odor of sanctity).

Death, cadavers and post-mortem biomedical research: a point of view from a Christian community.

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.

Is suicide risk correlated to thyroid weight?

Disturbances in some endocrine hormones have been implicated in the pathophysiology of depression and psychosis. We consider here further the hypothesis that there may be a correlation between suicide risk and the weight of the thyroid gland. The thyroid weight and other relevant information (sex, BMI) were collected retrospectively from 576 autopsies including 299 cases of completed suicide, analyzed in the west area of Paris between 1994 and 2010. Multiple regression model, adjusted on sex and BMI, confirmed that only for subjects more than 60 years of age, deceased by suicide, had a significant decrease in their weight of thyroid compared to those who deceased for another cause (decrease of around 3g, p=0.03, for age class 60 and over). Our hypothesis is that there could exist an anatomical correlate (thyroid weight) among people who have committed suicide, especially old individuals. Various hypotheses regarding the hypothalamus-pituitary-thyroid axis dysfunction and the physiopathology of major depression are proposed and discussed. Further studies will be necessary in order to confirm that such a tendency exists on other populations.

Rectal wall hemorrhage in hanging autopsy cases.

The aim of our study was to analyze hemorrhagic lesions of the rectal wall in hanging autopsy cases. All autopsy reports regarding hanging from January 1st, 2008 to December 31st, 2010 were retrospectively reviewed. One hundred and two hanging cases were selected out of 1379 autopsy cases. Rectal wall hemorrhage was found in about 4% of the cases (n=4). Two of these 4 cases (50%) were associated with bowel wall hemorrhage, suggesting a similar possible etiology by abdominal congestion during the agonal phase. Another etiology could be an hemorrhagic lividity in the rectum. As it is not possible to determine with certainty the etiology, even with the use of histology, the detection of rectal wall hemorrhage cannot be used as another sign of vital hanging. Such rectum changes raise the possibility of sexual assault. Forensic pathologists should be aware of such an occurrence and avoid potential harmful misinterpretation.

Diagnosis of aortic dextroposition on human skeletal remains.

The fine macroscopic observation of a young adult female skeleton recovered from a Roman graveyard in Romania revealed distinctive flattening of the vertebra related to a right-sided aorta. Associated bone anomalies may be related to a Kartagener syndrome. This case highlights the fact that visceral anomalies may be diagnosed even on skeletal remains. Such lesions could be useful for osteo-archaeologists, of course, but also for forensic anthropologist investigators dealing with skeletonized remains (for example during the identification process of a dead body, through comparison with known medical data for missing people). More, hypotheses about cause and/or manner of death may be given, and a possibility of genetic confirmation exists.

Ethics requirements and impact factor.

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 <10. We carried out a short study looking at the relationship between the IF of a journal and the ethics requirements in its instructions to authors. We show that the IF of a biomedical journal bears a direct relationship to its ethics requirements. Such results should improve the ethics requirements of all biomedical journals, especially those with low IF, so that they are internationally standardised to the higher standard required by journals with higher IF.