COVID-19 in the autopsy room-requirements, safety, recommendations and pathological findings.

Modern technologies enable the exchange of information about the expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the continually increasing number of the coronavirus disease 2019 (COVID-19) cases almost in real time. The gravity of a current epidemiological situation is represented by the mortality rates, which are scrupulously updated daily. Performing autopsies on patients with either suspected or confirmed COVID-19 is of high importance since these might not only improve clinical management but also reduce the risk of SARS-CoV-2 infection expansion. The following paper aimed to present the most crucial aspects of SARS-CoV-2 infection from the point of view of forensic experts and pathologists, recommendations and safety precautions regarding autopsies, autopsy room requirements, possible techniques, examinations used for effective viral detection, recommendations regarding burials, and gross and microscopic pathological findings of the deceased who died due to SARS-CoV-2 infection. Autopsies remain the gold standard for determining the cause of death. Therefore, it would be beneficial to perform autopsies on patients with both suspected and confirmed COVID-19, especially those with coexisting comorbidities.

Autopsy Services and Emergency Preparedness of a Tertiary Academic Hospital Mortuary for the COVID-19 Public Health Emergency: The Yale Plan.

Pathology Autopsy and Mortuary Services have been front and center in the severe acute respiratory syndrome coronavirus 2 (SARS-Co-V-2) pandemic. The sheer number of fatalities from the pandemic have been unlike any other in recent memory and needed the rapid creation of new protocols and paradigms to manage the situation. This required rapidly escalating mortuary capacity to manage the increased fatalities from the pandemic with the establishment of lines of communication and networking with governmental entities, institution of new policies for patient flow, and implementation of worker infection control and well-being plans. Autopsies also assumed a crucial role, both to provide insight into the pathomechanisms of a novel disease and to allow tissue retrieval necessary to power research directed towards finding a vaccine. We here outline the plan adopted by the Yale Autopsy and Mortuary Services, in alignment with the institutional mission of high-quality patient care, education, research and health care worker safety and well-being, as the Corona Virus Disease of 2019 (COVID-19) pandemic surged in Connecticut. In the early response phase, ensuring sufficient mortuary capacity necessarily took center stage. As we enter the recovery and plateau phase of the pandemic, setting up a process for a rapid and safe autopsy, that will meet educational and research needs while ensuring the safety of our workforce is being implemented.

Reliability of police reports when assessing health information at the forensic post-mortem examination-using schizophrenia as a model.

Autopsies continue to be the most reliable source of mortality statistics; however, more and more death certificates are based on the post-mortem external examination (PME) alone. Forensic PMEs differ from clinical PMEs, because the forensic pathologist usually has no preceding knowledge of the health of the decedent and must rely on information from authorities in the form of the police report. It is useful at the forensic PME to know whether the decedent suffered from a mental illness; however, it is unknown how valid such a diagnosis is, when based upon information in the police report alone. This study compared tentative diagnoses of schizophrenia from 500 forensic PMEs with a reference database based on the Danish National Patient Registry. We found that 19.3% of schizophrenia cases were missed, and 9.1 % of identified cases were false positives. Overall, 11.4% of all assessments were incorrect. Subgroup analysis showed that marital status as 'single' and the finding of illegal substances at the scene were predictors for both correctly identified and overlooked schizophrenia cases. The most reliable source of information was the decedent's general practitioner, whereas friends and neighbors were the most unreliable. Future studies should be aware of the risk of assigning a wrong diagnosis and use as many sources of information as possible. Taking the decedent's social history and observations about the scene into account may add to the diagnostic accuracy.

Automatic rib unfolding in postmortem computed tomography: diagnostic evaluation of the OpenRib software compared with the autopsy in the detection of rib fractures.

OBJECTIVES: The main objective of this study was to evaluate the diagnostic performance of the OpenRib software against the gold standard of autopsy in the detection of rib fractures. The secondary objective was to measure inter-rater agreement between each radiological reader. MATERIALS AND METHODS: Thirty-six subjects who underwent postmortem CT and autopsy were included in this study. Rib fractures were first assessed during the autopsy by carefully dissecting and examining each rib. They were also independently evaluated by three readers using OpenRib software. This software produces from postmortem CT images a reformat of the rib cage and a display of all ribs in a single plane. Each reader was asked to determine if the rib was fractured and, if so, whether the fracture was single or multiple. RESULTS: After exclusions, 649 ribs were included in the statistical analysis. The two readers with a similar level of experience showed a satisfactory inter-rater agreement and a sensitivity of 0.73 and 0.83 with a specificity of 0.95 and 0.91. However, the experienced reader diagnosed significantly more fractures than the autopsy and the other two readers (p < 0.001). CONCLUSION: The use of automatic rib unfolding software in postmortem CT allows an efficient and accurate assessment of rib fractures and enables the diagnosis of fractures that cannot be detected during a standard autopsy. For now, this method seems to be the simplest that can be routinely performed; however, it requires training time in order to be sufficiently effective.

Position Paper: Recommendations for the Investigation, Diagnosis, and Certification of Deaths Related to Opioid and Other Drugs.

The National Association of Medical Examiners convened an expert panel to update the association's evidence-based recommendations for investigating and certifying deaths associated with opioids and other misused substances to improve death certificate and mortality data for public health surveillance. The recommendations are as follows:1. Autopsy provides the best information on a decedent's medical condition for optimal interpretation of toxicology results, circumstances surrounding death, medical history, and scene findings. The panel considers autopsy an essential component of investigating apparent overdose deaths.2. Scene investigation includes reconciling prescription information and medication counts. Investigators should note drug paraphernalia or other evidence of using intoxicating substances.3. Retain blood, urine, and vitreous humor whenever available. Blood from the iliofemoral vein is preferable to blood from more central sites.4. A toxicological panel should be comprehensive, including potent depressant, stimulant, and antidepressant medications. Detecting novel substances present in the community may require special testing.5. When death is attributed to a drug or combination of drugs (as cause or contributing factor), the certifier should list the drugs by generic name in the autopsy report and death certificate.6. The best classification for manner of death in an overdose without any apparent intent of self-harm is "accident."

COVID-19: Postmortem Diagnostic and Biosafety Considerations.

As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (eg, cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there is a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for medical examiner-coroner offices encountering COVID-19 at autopsy.

[On the quality of the external post-mortem examination in cases of fatal head trauma : A comparison of death certificate and forensic autopsy]. / Zur Qualität der ärztlichen Leichenschau bei todesursächlichem Schädel­Hirn­Trauma : Ein Vergleich von Todesbescheinigung und gerichtlicher Obduktion.

BACKGROUND: In Germany it is required by law that basically every type of physician needs to be capable of executing a correct external post-mortem examination of a corpse. In recent years, numerous investigations on external post-mortem examinations repeatedly reported systematic mistakes and erroneous procedures in various clinical and medicolegal case groups. Accordingly, the completion of death certificates is frequently performed incorrectly. As one of the typical unnatural death cases, decedents dying from fatal head trauma (FHT) represent a special autopsy case group, which is expected to be correctly recognized during the primary external post-mortem examination because the external injuries are mostly obvious. OBJECTIVE: The present study aimed at investigating the quality of the external post-mortem examination in medicolegal FHT cases by means of comparison of death certificates and autopsy reports from a 10-year period. MATERIAL AND METHODS: In a retrospective study design all autopsy cases from the Institute of Legal Medicine of the University Hospital Münster in the years 2006-2015 (n = 3611) were analyzed as to the presence of FHT. A total of 328 cases with FHT and the concomitant presence of a death certificate filled out before the autopsy were identified. Subsequently, the cause of death according to the death certificate was compared with the cause of death according to the autopsy. The degree of agreement was classified into six different categories from I to VI. While category I represented a complete lack of agreement, category VI was assigned to cases with full agreement. RESULTS: In 58.5% of the cases (category VI) FHT was identified correctly during the external post-mortem examination. In 1.5% of the cases, a completely different cause of death was determined during the external post-mortem examination (category I). In 19.2% of the cases, no cause of death or the statement "unclear" was given as the cause of death in the death certificate (categories II and III). Cross-analyses and intuitive heatmap visualization were generated to identify case constellations with an increased risk for discrepancies. These analyses revealed that among all discrepant cases (categories I-V), falls were found significantly more often than in the nondiscrepant cases (p < 0.01), especially falls of women older than 57 years (median age of women) or falls considered as accidents by the examiner. In addition, traffic-associated FHT of men older than 44.5 years (median age of men) was identified more frequently in the external post-mortem examination. CONCLUSION: Despite the fact that FHT should be a cause of death that is comparably easy to identify during external post-mortem examination, more than one third of the cases were not sufficiently recognized. Therefore, special attention must still be paid to certain case constellations during the external post-mortem examination. Typical examples of such cases are burned bodies, cases of advanced putrefaction and falls.

Immunohistochemical Study of Dark and Progenitor Carotid Body Cells: Artefacts or Real Subtypes?

Postmortem changes occurring in human carotid body were simulated on the Wistar rat model. It was shown that light, dark, and pyknotic (progenitor) subtypes of human carotid body cells are an artifact and cannot be used in clinical practice to study the characteristics of various human diseases. The differences between the control group of healthy individuals and individuals with the various pathologies are most likely due to the different levels of premortal hypoxia that the tissue had been exposed to. Moreover, widespread antigens used in practice were divided into 2 groups by their tolerance to autolysis: stable and unstable ones. This can be useful for the development of immunohistochemical test algorithms for the diagnostics on autopsy material.

[Provisional guidelines on autopsy practice for deaths associated with COVID-19].

COVID-19 has been included in Category B infectious diseases and is prevented and controlled according to Category A infectious diseases. In order to establish a diagnosis or conduct further research, a post-mortem examination may be desired on a possible COVID-19 death. To guide the personnel engaged in the autopsy to carry out the correct operation, and ensure the safety of the pathologists and disease control staffs during the epidemic, the Chinese Pathological Society, the Chinese Pathologist Association and the Pathology and Pathophysiology national key discipline at Shantou University Medical College, formulated this guidance for the autopsy for deaths associated with COVID-19 during the prevention and control period of COVID-19 in China.

A standardized autopsy protocol for arthrogryposis (multiple congenital contractures).

Arthrogryposis multiplex congenita (AMC) describes disorders with multiple joint contractures that arise from neurological, neuromuscular, or mechanical origin. Although impaired fetal movement is the typical clinical presentation, the etiology underlying this phenotype for a number of conditions remains unknown. In an effort to better characterize and define the etiologies underlying these disorders, we recommend a standardized autopsy protocol that will allow for appropriate diagnosis and a methodical approach for examination that will facilitate subsequent study by investigators across disciplines. To further support investigation, we have also established an AMC autopsy registry to bank tissue obtained at autopsy for subsequent study.

Monitoring progress in reducing maternal mortality using verbal autopsy methods in vital registration systems: what can we conclude about specific causes of maternal death?

Reducing maternal mortality is a key focus of development strategies and one of the indicators used to measure progress towards achieving the Sustainable Development Goals. In the absence of medical certification of the cause of deaths that occur in the community, verbal autopsy (VA) methods are the only available means to assess levels and trends of maternal deaths that occur outside health facilities. The 2016 World Health Organization VA Instrument facilitates the identification of eight specific causes of maternal death, yet maternal deaths are often unsupervised, leading to sparse and generally poor symptom reporting to inform a reliable diagnosis using VAs. There is little research evidence to support the reliable identification of specific causes of maternal death in the context of routine VAs. We recommend that routine VAs are only used to capture the event of a maternal death and that more detailed follow-up interviews are used to identify the specific causes.

An integrated approach to processing WHO-2016 verbal autopsy data: the InterVA-5 model.

BACKGROUND: Verbal autopsy is an increasingly important methodology for assigning causes to otherwise uncertified deaths, which amount to around 50% of global mortality and cause much uncertainty for health planning. The World Health Organization sets international standards for the structure of verbal autopsy interviews and for cause categories that can reasonably be derived from verbal autopsy data. In addition, computer models are needed to efficiently process large quantities of verbal autopsy interviews to assign causes of death in a standardised manner. Here, we present the InterVA-5 model, developed to align with the WHO-2016 verbal autopsy standard. This is a harmonising model that can process input data from WHO-2016, as well as earlier WHO-2012 and Tariff-2 formats, to generate standardised cause-specific mortality profiles for diverse contexts. The software development involved building on the earlier InterVA-4 model, and the expanded knowledge base required for InterVA-5 was informed by analyses from a training dataset drawn from the Population Health Metrics Research Collaboration verbal autopsy reference dataset, as well as expert input. RESULTS: The new model was evaluated against a test dataset of 6130 cases from the Population Health Metrics Research Collaboration and 4009 cases from the Afghanistan National Mortality Survey dataset. Both of these sources contained around three quarters of the input items from the WHO-2016, WHO-2012 and Tariff-2 formats. Cause-specific mortality fractions across all applicable WHO cause categories were compared between causes assigned in participating tertiary hospitals and InterVA-5 in the test dataset, with concordance correlation coefficients of 0.92 for children and 0.86 for adults. The InterVA-5 model's capacity to handle different input formats was evaluated in the Afghanistan dataset, with concordance correlation coefficients of 0.97 and 0.96 between the WHO-2016 and the WHO-2012 format for children and adults respectively, and 0.92 and 0.87 between the WHO-2016 and the Tariff-2 format respectively. CONCLUSIONS: Despite the inherent difficulties of determining "truth" in assigning cause of death, these findings suggest that the InterVA-5 model performs well and succeeds in harmonising across a range of input formats. As more primary data collected under WHO-2016 become available, it is likely that InterVA-5 will undergo minor re-versioning in the light of practical experience. The model is an important resource for measuring and evaluating cause-specific mortality globally.

Sudden intrauterine unexplained death: time to adopt uniform postmortem investigative guidelines?

BACKGROUND: Worldwide approximately 2.6 million are stillborn, mostly occurring in developing countries. In the great part these deaths are inexplicable. The evenness and standardisation of the diagnostic criteria are prerequisites to understand their pathogenesis. The core goal of this article is to propose new evidence based investigative post-mortem guidelines that should be adopted in all the Institutions especially when a fetal death, after a routine autopsy procedure, is diagnosed as "unexplained". The proposed protocol is mainly focused on the anatomopathological examination of the autonomic nervous system and in particular of the brainstem where the main centers that control vital functions are located. METHODS: Updated investigative guidelines for the examination of unexplained stillbirths, prevalently focused on the histological examination of the brainstem, where the main centers that are involved in monitoring the vital functions are located, are here presented. A section of this protocol concerns the Immunohistochemical evaluation of specific functional markers such as the neuronal nuclear antigen, nicotinic acetylcholine receptors, serotonin, orexin, apoptosis and gliosis. The important role of risk factors, having regard in particular to maternal smoking and air pollution is also contemplated in these guidelines. RESULTS: Specific morphological and/or functional alterations of vital brainstem structures have been found with high incidence in over 100 cases of unexplained fetal death sent to the "Lino Rossi Research Center" of the Milan University according to the Italian law. These alterations were rarely detected in a group of control cases. CONCLUSIONS: We hope this protocol can be adopted in all the Institutions notably for the examination of unexplained fetal deaths, in order to make uniform investigations. This will lead to identify a plausible explanation of the pathogenetic mechanism behind the unexplained fetal deaths and to design preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians. TRIAL REGISTRATION: not applicable for this study.

Joint European Society of Paediatric Radiology (ESPR) and International Society for Forensic Radiology and Imaging (ISFRI) guidelines: paediatric postmortem computed tomography imaging protocol.

Postmortem CT for investigating childhood deaths is increasingly utilised as a noninvasive adjunct or alternative to standard autopsy; however there are no standardised published imaging protocols. This article describes a standardised imaging protocol that has been developed based on current practices of international postmortem imaging practitioners and experts. This recommendation is expected to be useful for postmortem imaging centres wishing to update their existing practices and for those starting paediatric postmortem CT as a new service.

Minimal amount of tissue-based pH measurement to improve quality control in neuropsychiatric post-mortem brain studies.

AIM: Tissue pH and RNA integrity are crucial quality-control indicators of human post-mortem brain tissues in the identification of the pathogeneses of neuropsychiatric disorders, but pH has not been measured as often due to limitations in the amount of tissue available. This study was designed to develop and validate a protocol for tissue pH evaluation using a minimal amount of human post-mortem tissues. METHODS: A procedure that included a proper ratio of brain tissue weight to water for homogenization and the duration of homogenization was designed based on preliminary experiments using mouse brain tissues. The minimal (10 mg) and typical (100 mg) amounts of post-mortem brain tissue from 52 subjects were homogenized in 5 volumes (50 µL/10 mg tissue) and 10 volumes (1000 µL/100 mg tissue) of nuclease-free water and subjected to pH measurements using an InLab Ultra micro pH electrode. RESULTS: The pH values based on the new protocol using a minimal amount of tissue significantly correlated with measurements of the standard protocol (r2 = 0.86). The correlation coefficients of the pH values between gray and white matter of the same brain region, and the values between different brain regions were 0.73 and 0.54, respectively. CONCLUSION: The proposed protocol used one-tenth of the tissue amount of current standard protocol and enabled us to evaluate the exact quality of post-mortem brain tissue subjected to subsequent analyses. The application of this protocol may improve the detection of biological phenomena of interest in post-mortem brain studies by diminishing confounding factors.

The WHO 2016 verbal autopsy instrument: An international standard suitable for automated analysis by InterVA, InSilicoVA, and Tariff 2.0.

BACKGROUND: Verbal autopsy (VA) is a practical method for determining probable causes of death at the population level in places where systems for medical certification of cause of death are weak. VA methods suitable for use in routine settings, such as civil registration and vital statistics (CRVS) systems, have developed rapidly in the last decade. These developments have been part of a growing global momentum to strengthen CRVS systems in low-income countries. With this momentum have come pressure for continued research and development of VA methods and the need for a single standard VA instrument on which multiple automated diagnostic methods can be developed. METHODS AND FINDINGS: In 2016, partners harmonized a WHO VA standard instrument that fully incorporates the indicators necessary to run currently available automated diagnostic algorithms. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality. This VA instrument offers the opportunity to harmonize the automated diagnostic algorithms in the future. CONCLUSIONS: Despite all improvements in design and technology, VA is only recommended where medical certification of cause of death is not possible. The method can nevertheless provide sufficient information to guide public health priorities in communities in which physician certification of deaths is largely unavailable. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality.

Performance of InSilicoVA for assigning causes of death to verbal autopsies: multisite validation study using clinical diagnostic gold standards.

BACKGROUND: Recently, a new algorithm for automatic computer certification of verbal autopsy data named InSilicoVA was published. The authors presented their algorithm as a statistical method and assessed its performance using a single set of model predictors and one age group. METHODS: We perform a standard procedure for analyzing the predictive accuracy of verbal autopsy classification methods using the same data and the publicly available implementation of the algorithm released by the authors. We extend the original analysis to include children and neonates, instead of only adults, and test accuracy using different sets of predictors, including the set used in the original paper and a set that matches the released software. RESULTS: The population-level performance (i.e., predictive accuracy) of the algorithm varied from 2.1 to 37.6% when trained on data preprocessed similarly as in the original study. When trained on data that matched the software default format, the performance ranged from -11.5 to 17.5%. When using the default training data provided, the performance ranged from -59.4 to -38.5%. Overall, the InSilicoVA predictive accuracy was found to be 11.6-8.2 percentage points lower than that of an alternative algorithm. Additionally, the sensitivity for InSilicoVA was consistently lower than that for an alternative diagnostic algorithm (Tariff 2.0), although the specificity was comparable. CONCLUSIONS: The default format and training data provided by the software lead to results that are at best suboptimal, with poor cause-of-death predictive performance. This method is likely to generate erroneous cause of death predictions and, even if properly configured, is not as accurate as alternative automated diagnostic methods.

Prospective study of device-related complications in intensive care unit detected by virtual autopsy.

BACKGROUND: There has been increasing use of invasive techniques, such as extracorporeal organ support, in intensive care units (ICU), and declining autopsy rates. Thus, new measures are needed to maintain high-quality standards. We investigated the potential of computed tomography (CT)-based virtual autopsy to substitute for medical autopsy in this setting. METHODS: We investigated the potential of virtual autopsy by post-mortem CT to identify complications associated with medical devices in a prospective study of patients who had died in the ICU. Clinical records were reviewed to determine the number and types of medical devices used, and findings from medical and virtual autopsies, related and unrelated to the medical devices, were compared. RESULTS: Medical and virtual autopsies could be performed in 61 patients (Group M/V), and virtual autopsy only in 101 patients (Group V). In Group M/V, 41 device-related complications and 30 device malpositions were identified, but only with a low inter-method agreement. Major findings unrelated to a device were identified in about 25% of patients with a high level of agreement between methods. In Group V, 8 device complications and 36 device malpositions were identified. CONCLUSIONS: Device-related complications are frequent in ICU patients. Virtual and medical autopsies showed clear differences in the detection of complications and device malpositions. Both methods should supplement each other rather than one alone for quality control of medical devices in the ICU. Further studies should focus on the identification of special patient populations in which virtual autopsy might be of particular benefit. CLINICAL TRIAL REGISTRATION: NCT01541982.

Investigations After Death in Children.

OBJECTIVES: To discuss the role of investigations after death in children as part of a supplement on "Death and Dying in the PICU." DATA SOURCES: Literature review, personal experience, and expert opinion. DATA SELECTION: Not applicable. DATA EXTRACTION: Moderated by three experts on investigations after death in children. DATA SYNTHESIS: Not relevant. CONCLUSIONS: A multidisciplinary cliniciopathologic conference is important after the death of a child in order to help bring closure to the family and to attempt to address any concerns they may have about the care. It is also an important part of the quality of care process for a tertiary care institution and provides an unique opportunity for ongoing medical education. The model of a multidisciplinary cliniciopathologic conference used by the Ontario Coroner's Office to investigate sudden and unexpected deaths in children under 5 years old, which has been functioning for over 30 years, is described. Reports from this Pediatric Death Review Committee have been influential in improving the care of children in the province of Ontario.

Learning From Investigation After Death.

OBJECTIVES: The acceptability of traditional postmortem examination to bereaved families, coupled with a misguided professional view about their limited utility, has led to decrease in this ultimate investigation. Research recurrently demonstrates that postmortem examination provides clinically relevant information despite ever-improving diagnostic techniques. This review examines postmortem examination for children who die in PICU-whether consented or nonconsented (legally mandated). It explores how such investigations might provide useful information and suggests that PICU and pathology teams work together to provide information for bereaved families to either enable them to consent to postmortem interventions or understand necessary forensic processes. Newer technologies such as postmortem imaging and laparoscope-assisted/ultrasound-guided tissue sampling are reviewed, with the hope that greater acceptability to families may lead to a welcome resurgence in postmortem information for clinicians, tempered by realization that widespread acceptance of their equivalence to standard techniques by most forensic services is awaited. DATA SOURCES: Literature review. STUDY SELECTION: Journal articles describing practices in pediatric and adult postmortem examination. DATA EXTRACTION: Not available. DATA SYNTHESIS: Not available. CONCLUSIONS: The PICU team have a duty to help bereaved parents understand what postmortem investigations are available, or might be mandated, after the death of their child. A thoughtful, unhurried, and compassionate discussion should be arranged with expert pathology teams and any specialists who have cared for the child to explain how investigations can provide information about what is involved-including availability and suitability of newer techniques. This should include information about when a child's body, organs, or tissues will be available for the funeral, necessary legal procedures and how and when results will be explained to them.