A fatal mono-intoxication with 4-fluoroisobutyrylfentanyl: Case report with postmortem concentrations.

We report on a case of a 35-year-old man who died suddenly and unexpectedly due to a 4-fluoroisobutyrylfentanyl (4-FIBF) mono-intoxication. Pathological, toxicological and chemical investigations were conducted at the Netherlands Forensic Institute. A full three-cavity forensic pathological examination was performed according to international guidelines. Biological samples obtained during autopsy were comprehensively investigated for the presence of toxic substances using headspace gas chromatography (GC) with flame ionization detection, liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS), GC-MS, high-performance LC with diode array detection and LC-tandem MS (LC-MS-MS). The seized crystalline substance found next to the body was investigated using a presumptive color test, GC-MS, Fourier-transform infrared spectroscopy and nuclear magnetic resonance. Pathological investigation identified minor lymphocytic infiltrates in the heart, considered irrelevant for the cause of death. Toxicological analysis of the victims' blood indicated the presence of a fluorobutyrylfentanyl (FBF) isomer, with no other compounds detected. The FBF isomer was identified in the seized crystalline substance as 4-FIBF. 4-FIBF concentrations were quantified in femoral blood (0.030 mg/L), heart blood (0.12 mg/L), vitreous humor (0.067 mg/L), brain tissue (>0.081 mg/kg), liver tissue (0.44 mg/kg) and urine (approximately 0.01 mg/L). Based on the outcomes of the pathological, toxicological and chemical investigations, the cause of death of the deceased was attributed to a fatal 4-FIBF mono-intoxication. The presented case underlines the added value of a combined bioanalytical and chemical investigative approach to identify and subsequently quantify fentanyl isomers in postmortem cases. Furthermore, it demonstrates the importance of investigating the postmortem redistribution of novel fentanyl analogs to establish reference values and to subsequently allow for correct interpretation of cause of death analysis in future casework.

Fatal gastric volvulus: forensic pathology considerations and postmortem CT findings.

Gastric volvulus is a rare cause of gastric obstruction, due to the rotation of the stomach by more than 180°. It is a rare but life-threatening medical emergency that is considered difficult to diagnose at the initial clinical presentation. Forensic pathologists may be presented with gastric volvulus in several ways, for instance, as a cause of sudden and unexpected death or in the context of suspected clinical errors. The post-mortem examination of gastric volvulus may be challenging, due to the specific technical issues it presents and the various mechanisms by which volvulus may cause death. We therefore present five cases of gastric volvulus that in combination represent almost the entire spectrum of presentations and post-mortem findings, to discuss how gastric volvulus may come to the attention of a forensic pathologist, the approach and findings at post-mortem examination (including post-mortem CT), and the variety of mechanisms by which gastric volvulus may result in death.

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

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

The histopathological spectrum of myocardial inflammation in relation to circumstance of death: a retrospective cohort study in clinical and forensic autopsies.

Interpreting a myocardial inflammation as causal, contributory or as of no significance at all in the cause of death can be challenging, especially in cases where other pathologic and/or medico-legal findings are also present. To further evaluate the significance of myocardial inflammation as a cause of death we performed a retrospective cohort study of forensic and clinical autopsy cases. We revised the spectrum of histological inflammatory parameters in the myocardium of 79 adult autopsy cases and related these to the reported cause of death. Myocardial slides were reviewed for the distribution and intensity of inflammatory cell infiltrations, the predominant inflammatory cell type, and the presence of inflammation-associated myocyte injury, fibrosis, edema and hemorrhage. Next, the cases were divided over three groups, based on the reported cause of death. Group 1 (n = 27) consisted of all individuals with an obvious unnatural cause of death. Group 2 (n = 29) included all individuals in which myocarditis was interpreted to be one out of more possible causes of death. Group 3 (n = 23) consisted of all individuals in which myocarditis was reported to be the only significant finding at autopsy, and no other cause of death was found. Systematic application of our histological parameters showed that only a diffuse increase of inflammatory cells could discriminate between an incidental presence of inflammation (Group 1) or a potentially significant one (Groups 2 and 3). No other histological parameter showed significant differences between the groups. Our results suggest that generally used histological parameters are often insufficient to differentiate an incidental myocarditis from a (potentially) significant one.

The logic of forensic pathology opinion.

Evaluating evidence and providing opinions are at the heart of forensic science, and forensic experts are expected to provide opinions that are based on logically sound and transparent scientific reasoning, and that honour the boundaries of their area of expertise. In order to meet these objectives, many fields of science explicitly apply Bayes' theorem, which describes the logically correct way to update probabilities on the basis of observations. Making a distinction between 'investigative' and evaluative' modes of operating helps to implement the theorem into daily casework. Use of these principles promotes the logic and transparency of the reasoning that leads to expert's opinion and helps the expert to stay within her remit. Despite these important benefits, forensic pathology seems slow to adopt these principles. In this article, we explore this issue and suggest a way forward. We start with a short introduction to Bayes' theorem and its benefits, followed by a discussion of why its application is actually second nature to medical practitioners. We then discuss the difference between investigative and evaluative opinions, and how they enable the forensic pathologist to reconcile Bayes' theorem with the different phases of a forensic investigation. Throughout the text, practical examples illustrate the various ways in which the logically correct way of evidence interpretation can be implemented, and how it may help the forensic pathologist to provide an appropriate and relevant opinion.

Acute disseminated encephalomyelitis (ADEM) following recent Oxford/AstraZeneca COVID-19 vaccination.

This report describes the clinical context and autopsy findings in the first reported fatal case of acute disseminated encephalomyelitis (ADEM), developed after being vaccinated using the Oxford/AstraZeneca COVID-19 vaccine. ADEM is a rare autoimmune disease, causing demyelination in the brain and spinal cord. A wide variety of precipitating factors can trigger ADEM, and it has long been known to be a rare adverse event following some types of vaccinations. Recently, ADEM has also been associated with COVID-19 infection and (very rarely) with COVID-19 vaccination. The reports of the latter however all pertain to living patients. Our case demonstrates that ADEM should be considered in patients developing neurological symptoms post COVID-19 vaccination, although that this adverse reaction is likely to remain extremely rare. Our report further emphasizes the added value of comprehensive post mortem investigation to confirm ante mortem diagnosis and to determine vaccination safety.

Providing a Forensic Expert Opinion on the "Degree of Force": Evidentiary Considerations.

Forensic pathologists and anthropologists are often asked in court for an opinion about the degree of force required to cause a specific injury. This paper examines and discusses the concept of 'degree of force' and why it is considered a pertinent issue in legal proceedings. This discussion identifies the implicit assumptions that often underpin questions about the 'degree of force'. The current knowledge base for opinions on the degree of force is then provided by means of a literature review. A critical appraisal of this literature shows that much of the results from experimental research is of limited value in routine casework. An alternative approach to addressing the issue is provided through a discussion of the application of Bayes' theorem, also called the likelihood ratio framework. It is argued that the use of this framework makes it possible for an expert to provide relevant and specific evidence, whilst maintaining the boundaries of their field of expertise.

Technical Note: The Forensic Anthropology Society of Europe (FASE) Map of Identified Osteological Collections.

Identified (documented) osteological collections represent an important resource in the development of forensic anthropology standards and methods as well as a precious tool for learning and training of practitioners. Even though the number of papers presenting identified collections worldwide increases, many of the collections have still not been divulged to the scientific community in sufficient detail to ascertain their exact number. The Forensic Anthropology Society of Europe (FASE) therefore developed a tool that goes beyond sporadic publications: the FASE Map of Identified Osteological Collections, which is freely accessible and continuously updated and revised. The online map is available at http://forensicanthropology.eu/osteological-collections/. The map of skeletal collections was created in 2017 and currently displays information on 153 identified osteological collections (43 of them categorized as contemporary) located in 41 different countries. This article offers a short analysis of the type, geographical location and content of the collections included in the map. The aim of this article and the map as such is to provide a useful resource to facilitate research planning and teaching in forensic anthropology and related disciplines.

The radiographic relationship between the cortical overlap view (COV) and the tip of the greater trochanter.

For proximal femoral nailing, choosing the proper entry point with the aid of C-arm imaging is crucial. Therefore, obtaining accurate radiological views that facilitate sound identification of the tip of the greater trochanter (GT) is of utmost importance. The aim of this study was to define a radiological view characterised by reproducible radiographic landmarks which will allow the reliable identification of the tip of the GT in the anteroposterior view. Anatomical and radiographic features of 16 cadaveric femurs were analysed. The cortical overlap view (COV), characterised by the radiological overlap of the density line of the piriform fossa and the intertrochanteric crest, was identified. It marks the rotation of the proximal femur at which the GT can be accurately identified and used to determine the desired entry point for a proximal femoral nail. Trainees and fully qualified orthopedic trauma surgeons were asked to identify the correct COV in radiological imaging series. Mean internal rotation of the femur to achieve a COV was 17.5° (range 12.8°-21.8°). In the COV the tip of the GT is the highest visible point and the mean distance from the cortical overlap line to the tip of the GT is 4.45 mm. Intra- and inter-rater reliability was high with ICC(2,k) = 0.932 and ICC(2,k) = 0.987 respectively. Trainees achieved higher rates of correct COV identification than specialists. There was no significant correlation between the internal rotation of the femur to achieve the COV and femoral antetorsion. In conclusion, the COV is a highly reproducible radiological view that is characterised by radiographic landmarks easy to recognise. It allows for accurate identification of the tip of the GT, which can be used by the surgeon as a reference to determine the desired entry point for an intramedullary nail.

Disaster victim identification operations with fragmented, burnt, or commingled remains: experience-based recommendations.

Human-made and natural disasters can result in severely fragmented, compromised, and commingled human remains. The related disaster victim identification (DVI) operations are invariably challenging, with the state of the remains potentially precluding some identifications. Practitioners involved in these DVI operations will routinely face logistical, practical, and ethical challenges. This review provides information and guidance derived from first-hand experiences to individuals tasked with managing DVI operations with fragmented human remains. We outline several key issues that should be addressed during disaster preparedness planning and at the outset of an operation, when incident-specific strategies are developed. Specific challenges during recovery and examination of fragmented remains are addressed, highlighting the importance of experienced specialists at the scene and in the mortuary. DNA sample selection and sampling techniques are reviewed, as well as downstream effects of commingling and contamination, which can complicate reconciliation and emphasise the need for rigorous quality control. We also touch on issues that may arise during communication with families. While recommendations are provided, they are not intended as proscriptive policy but rather as an addition to the general recommendations given in the International Criminal Police Organization (INTERPOL) DVI Guide, to inform preparative discussions between government officials, judiciary, police, and forensic specialists.Key pointsA DVI operation for an incident characterised by many fragmented and otherwise compromised human remains poses specific challenges that may prolong and complicate identifications.Specialists should be consulted at the outset to address key issues related to the aim and extent of the operation.Specialist expertise in handling compromised human remains is indispensable at the scene, in the mortuary, during reconciliation, and for quality control.Continuous consultation between representatives from government, the judiciary, law enforcement, the media, and various forensic specialists will prevent unnecessary delay and facilitate accurate and timely communication.

Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy. METHODS: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course. FINDINGS: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.. INTERPRETATION: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19. FUNDING: Amsterdam UMC Corona Research Fund.

Strengthening the role of forensic anthropology in personal identification: Position statement by the Board of the Forensic Anthropology Society of Europe (FASE).

In this position statement, the Board members of the Forensic Anthropology Society of Europe (FASE) argue that forensic anthropology methods can be used as means of personal identification, particularly in situations with limited availability of traditional identification methods (i.e. dactyloscopy, odontology, and molecular genetic analysis). This statement has been issued taking into account the international migration crises related to thousands of deaths worldwide, in which the utility of these traditional means of identification has been sporadic to non-existent. The statement is however not limited to deaths related to the migration crises, as similar problems may occur in fatalities en masse such as in natural disasters and armed conflicts, and on a smaller scale in cases of homeless or otherwise socioeconomically disadvantaged persons. The number of reports on personal identification based on sound anthropological methodology is increasing in the scientific literature. However, more research is needed to develop evidence-based standard operating procedures and statistical frameworks. It remains essential to raise awareness among forensic practitioners, law enforcement, and judiciary professionals on the utility of forensic anthropology in cases where it can provide sufficient information for identification.

Histologic Analysis of 2 Alternative Donor Sites of the Ipsilateral Elbow in the Treatment of Capitellar Osteochondritis Dissecans.

PURPOSE: To compare the histologic features of the cartilage from the capitellum with 2 proposed alternative donor sites from the ipsilateral elbow in the treatment of capitellar osteochondritis dissecans (OCD): the nonarticulating part of the radial head and the nonarticulating lateral side of the olecranon tip. METHODS: Ten human cadaveric elbow specimens with macroscopically normal articular surfaces were used to obtain 5-mm osteochondral grafts: 10 from the capitellum (60° anteriorly relative to the humeral shaft), 10 from the radial head (nonarticulating part at 80°), and 4 from the olecranon (lateral side of the olecranon tip). Grafts were fixated in formalin (4% formaldehyde), decalcified, and processed into standard 8-µm-thick hematoxylin and eosin-and Toluidine Blue-stained sections. These were assessed for cartilage thickness, shape of articular surface, and 13 histologic parameters of the International Cartilage Repair Society II. Olecranon scores were excluded from statistical analysis. RESULTS: Mean cartilage thickness was 1.5 ± 0.22 mm at the capitellum; 1.3 ± 0.34 mm at the radial head; and 1.9 ± 1.0 mm at the olecranon. There was no difference in cartilage thickness between the capitellum and radial head (P = .062). All grafts demonstrated a convex articular surface. International Cartilage Repair Society II scores ranged from 82 to 100 for the capitellum, from 81 to 100 for the radial head, and from 67 to 87 for the olecranon tip. There was less chondrocyte clustering at the capitellum (84 ± 14) than in the radial head (94 ± 3.2; P = .019). Mid/deep zone assessment of the capitellum scored higher (97 ± 6.7) than the radial head (91 ± 4.6; P = .038). CONCLUSIONS: This study demonstrates appropriate histologic similarities between the cartilage from the capitellum and 2 alternative donor sites of the ipsilateral elbow in the treatment of capitellar OCD: the nonarticulating part of the radial head and the nonarticulating lateral side of the olecranon tip. CLINICAL RELEVANCE: From an histologic point of view, there seem to be no obstacles to use grafts from these alternative donor sites for reconstruction of the capitellum when performing osteochondral autologous transplantation.

Virtual forensic anthropology: The accuracy of osteometric analysis of 3D bone models derived from clinical computed tomography (CT) scans.

Clinical radiology is increasingly used as a source of data to test or develop forensic anthropological methods, especially in countries where contemporary skeletal collections are not available. Naturally, this requires analysis of the error that is a result of low accuracy of the modality (i.e. accuracy of the segmentation) and the error that arises due to difficulties in landmark recognition in virtual models. The cumulative effect of these errors ultimately determines whether virtual and dry bone measurements can be used interchangeably. To test the interchangeability of virtual and dry bone measurements, 13 male and 14 female intact cadavers from the body donation program of the Amsterdam UMC were CT scanned using a standard patient scanning protocol and processed to obtain the dry os coxae. These were again CT scanned using the same scanning protocol. All CT scans were segmented to create 3D virtual bone models of the os coxae ('dry' CT models and 'clinical' CT models). An Artec Spider 3D optical scanner was used to produce gold standard 'optical 3D models' of ten dry os coxae. The deviation of the surfaces of the 3D virtual bone models compared to the gold standard was used to calculate the accuracy of the CT models, both for the overall os coxae and for selected landmarks. Landmark recognition was studied by comparing the TEM and %TEM of nine traditional inter-landmark distances (ILDs). The percentage difference for the various ILDs between modalities was used to gauge the practical implications of both errors combined. Results showed that 'dry' CT models were 0.36-0.45mm larger than the 'optical 3D models' (deviations -0.27mm to 2.86mm). 'Clinical' CT models were 0.64-0.88mm larger than the 'optical 3D models' (deviations -4.99mm to 5.00mm). The accuracies of the ROIs were variable and larger for 'clinical' CT models than for 'dry' CT models. TEM and %TEM were generally in the acceptable ranges for all ILDs whilst no single modality was obviously more or less reliable than the others. For almost all ILDs, the average percentage difference between modalities was substantially larger than the average percentage difference between observers in 'dry bone' measurements only. Our results show that the combined error of segmentation- and landmark recognition error can be substantial, which may preclude the usage of 'clinical' CT scans as an alternative source for forensic anthropological reference data.

Histologic and radiological analysis on bone fractures: Estimation of posttraumatic survival time in skeletal trauma.

In antemortem fractures, the estimation of the amount of time that has lapsed between the traumatic event and eventual death (the socalled 'posttraumatic survival time' or PTST) can have substantial implications in legal proceedings. It might for instance help to corroborate witness testimonies, to reconstruct the chain of events leading to eventual death or to establish a sequence when multiple traumata in a single individual are encountered. However, PTST estimation of bone trauma is impeded by a myriad of theoretical and practical issues, and is therefore almost invariably considered challenging. A few years ago, a method that combines radiological and histological analysis of fractures to estimate the minimum amount of lapsed PTST in skeletonized remains was proposed. This study aims to test its accuracy on a set of five rib fractures and four skull lesions fractures with known and varying amounts of posttraumatic survival time. In addition, it explores the differences between the assessment on ribs and skull bones and it expands on the proposed method by including computed tomography (CT) scanning. Using conventional radiology and histology, the minimum amount of PTST was accurately estimated in 8 out of 9 of the cases (89%). The one discrepancy between the estimated and known PTST was minimal, being just one day. The precision of the method diminishes as healing advances. It was noted that skull lesions showed less advanced and less well-developed healing features than the lapsed PTST would suggest. Of the three used modalities, conventional radiology proved to be the least accurate. CT scanning proved to be a valuable, sometimes even superior alternative to conventional radiology. Histology was superior to both conventional radiology and CT scanning. The results of our study illustrate the potential of the combined application of radiology and histology to estimate the PSTS in skeletonized human fractures.

The Status of Forensic Anthropology in Europe and South Africa: Results of the 2016 FASE Questionnaire on Forensic Anthropology.

One of the goals of the Forensic Anthropology Society of Europe (FASE) is to map the existing education and practice opportunities in the field of forensic anthropology in order to support the development of the discipline and to optimize the training courses provided by the Society. To address this goal, an online questionnaire was sent to European and South African practitioners of forensic anthropology and related disciplines in 2016. The results of the questionnaire showed that the status and roles of forensic anthropologists vary depending on the national legal systems, education, and employment status of the practitioners. Despite the fact that the expertise of forensic anthropologists has been increasingly requested in a variety of investigations and the spectrum of tasks has become broader, including identification of living persons, specialized education in forensic anthropology is still restricted to a few graduate and postgraduate programs in European countries and to annual FASE courses.

The accuracy of 3D virtual bone models of the pelvis for morphological sex estimation.

It is currently unknown whether morphological sex estimation traits are accurately portrayed on virtual bone models, and this hampers the use of virtual bone models as an alternative source of contemporary skeletal reference data. This study determines whether commonly used morphological sex estimation traits can be accurately scored on virtual 3D pelvic bone elements. Twenty-seven intact cadavers from the body donation program of the Amsterdam UMC, University of Amsterdam, were CT scanned; this data was used to produce virtual bone models. Thereafter, the dry bones were obtained. Three traits by Klales (2012) and five traits from the Workshop of European Anthropologists (WEA) (1980) were scored on the virtual bone models and their dry skeletal counterparts. Intra- and inter-observer agreement and the agreement between the scores for each virtual bone model-dry bone pair were calculated using weighted Cohen's kappa (K). For all Klales (2012) traits, intra- and inter-observer agreement was substantial to almost perfect for the virtual- and dry bones (K = 0.62-0.90). The agreement in scores in the virtual-dry bone pairs ranged from moderate to almost perfect (K = 0.58-0.82). For the WEA (1980) traits, intra-observer agreement was substantial to almost perfect (K = 0.64-0.91), but results were less unambiguous for inter-observer agreement (K = 0.24-0.88). Comparison of the scores between the virtual bone models and the dry bones yielded kappa values of 0.42-0.87. On one hand, clinical CT data is a promising source for contemporary forensic anthropological reference data, but the interchangeability of forensic anthropological methods between virtual bone models and dry skeletal elements needs to be tested further.