An atypical case of fatal 'esophageal apoplexy': post-mortem findings and differential diagnosis.

Forensic pathologists need to have comprehensive knowledge of a large variety of causes of sudden natural death. We describe a case of sudden and unexpected death in woman in her sixties due to rupture of a large paraesophageal hematoma. The post-mortem examination and differential diagnosis are discussed. The combined findings of whole-body post-mortem CT imaging (PMCT), targeted PMCT angiography, autopsy, and histology are most in keeping with 'esophageal apoplexy'; a rare cause of hemorrhage in the esophageal wall. A review of the literature indicates that most cases of esophageal apoplexy are self-limiting and that fatal complications are exceedingly rare. Our case demonstrates that esophageal apoplexy can present as sudden unexpected death.

Suspension-associated dislocation of the jaw in hanging.

Hanging is a common type of death, and the role of the medical investigation of such deaths by a forensic pathologist not only requires the determination of the cause of death but providing information to assist in the determination of the manner of death. The forensic pathologist should be well versed in the spectrum of injuries known to be associated with neck compression, to document injuries known to be associated with hanging, but also to identify those that are inconsistent with self-inflicted hanging or that may suggest the involvement of a third party in the death. Comprehensive identification and correct interpretation of external and internal injury are crucial for the appropriate degree of police and coroner/medical examiner investigation. We present two cases of deaths believed to be caused by self-inflicted hanging that were observed to have unexpected unilateral dislocation of the temporomandibular joint identified on routine post-mortem computed tomography, without any evidence of involvement of a third party. This injury was unexplained and had not been previously observed at our Forensic Institute nor was it identified after a review of the published biomedical research literature. Issues regarding the cause of this abnormality, possible mechanisms, and the medicolegal significance of this finding will be discussed.

Extensive subcutaneous needle fragment retention due to injecting drug use.

Deaths in those with a history of injecting drug use commonly come to the attention of forensic pathologists, and therefore, one must have knowledge of possible findings and hazards of performing autopsies in these cases. This case demonstrates the finding of extensive retained broken needles in the subcutis of the arms and femoral region in a man with a long history of injecting drug use. While few or single broken needles are not uncommonly encountered, the multiplicity of needles in this case is noteworthy. We have demonstrated the findings both radiologically with PMCT and by conventional autopsy.

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.

Lethal hemorrhage from iliac vein rupture complicating inferior vena cava thrombosis demonstrated by post-mortem CT angiography.

Spontaneous iliac vein rupture is a rare cause of retroperitoneal hemorrhage that may present to the forensic pathologist. It has been reported in association with venous thrombosis, anatomical variants such as May-Thurner syndrome, and as a complication of a long-term indwelling IVC filter. It has a female predominance and most often occurs due to rupture of the left iliac vein. This is the first report of the use of post-mortem computed tomography (PMCT) and post-mortem computed tomography angiography (PMCTA) as an adjunct to a conventional autopsy to diagnose rupture of the left iliac vein causing retroperitoneal hemorrhage arising as a complication of an inferior vena cava (IVC) thrombus. We discuss the use of PMCTA as a useful tool in the diagnosis of vascular injury and how it can be used to assist the forensic pathologist. The use of PMCT with PMCTA is an invaluable adjunct to conventional autopsy to diagnose the site of vascular rupture.

Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE, we conducted a genome-wide association study (GWAS) of VTE and a transcriptome-wide association study (TWAS) based on imputed gene expression from whole blood and liver. We meta-analyzed GWAS data from 18 studies for 30 234 VTE cases and 172 122 controls and assessed the association between 12 923 718 genetic variants and VTE. We generated variant prediction scores of gene expression from whole blood and liver tissue and assessed them for association with VTE. Mendelian randomization analyses were conducted for traits genetically associated with novel VTE loci. We identified 34 independent genetic signals for VTE risk from GWAS meta-analysis, of which 14 are newly reported associations. This included 11 newly associated genetic loci (C1orf198, PLEK, OSMR-AS1, NUGGC/SCARA5, GRK5, MPHOSPH9, ARID4A, PLCG2, SMG6, EIF5A, and STX10) of which 6 replicated, and 3 new independent signals in 3 known genes. Further, TWAS identified 5 additional genetic loci with imputed gene expression levels differing between cases and controls in whole blood (SH2B3, SPSB1, RP11-747H7.3, RP4-737E23.2) and in liver (ERAP1). At some GWAS loci, we found suggestive evidence that the VTE association signal for novel and previously known regions colocalized with expression quantitative trait locus signals. Mendelian randomization analyses suggested that blood traits may contribute to the underlying risk of VTE. To conclude, we identified 16 novel susceptibility loci for VTE; for some loci, the association signals are likely mediated through gene expression of nearby genes.

Post-mortem CT lung findings at a medicolegal institute in SARS-CoV-2 RT-PCR positive cases with autopsy correlation.

CoVID-19 is a novel viral infection with now well-established clinical radiological findings. There is limited data on post-mortem imaging. We explore the proposition that PMCT could be used as screening test. In an 11-week period, 39 deceased persons were referred for medicolegal investigation with pre-existing or subsequent nasopharyngeal swabs showing positivity on SARS-CoV-2 RT-PCR testing. All 39 had routine whole-body CT scans on admission and 12 underwent medicolegal autopsy. These cases were contrasted with 4 others which were negative on nasopharyngeal swabs despite PMCT findings suggestive of CoVID-19 pneumonia (designated false positive). Nine of the 12 autopsies showed lung histology consistent with those reported in CoVID-19 pneumonia. Typical clinical CoVID-19 lung findings on PMCT were only detected in 5 (42%). In 3 of the 4 false positive cases, lung findings showed non-COVID-19 histology but in 1, findings were identical. PMCT CoVID-19 findings in the lungs are therefore not specific and may not be detected in all cases due to obscuration by expected agonal CT findings or other pathologies that pre-dated SARS-CoV-2 infection. PMCT findings may otherwise be subtle. Although PMCT may hint at CoVID-19, we believe that nasopharyngeal swabs are still required for definitive diagnosis. Even with positive swabs, clinical CoVID-19 lung findings on PMCT are often not detected. PMCT findings can be subtle, extreme or obscured by agonal changes. Given this range of PMCT changes, the challenge for pathologists is to determine whether death has been caused by, or merely associated with, SARS-CoV-2 infection.

Weed seed spread and its prevention: The role of roadside wash down.

Vehicles are one of the major vectors of long-distance weed seed spread. Viable seed removed from vehicles at roadside wash down facilities was studied at five locations in central Queensland, Australia over a 3-year period. Seed from 145 plant species, belonging to 34 different families, were identified in the sludge samples obtained from the wet particulate matter collection pit of the wash down facilities. Most of the species were annual forbs (50%) with small or very small seed size (<2 mm in diameter). A significant amount of seed from the highly invasive, parthenium weed was observed in these samples. More parthenium weed seed were found in the Rolleston facility and in the spring, but its seed was present in all facilities and in all seasons. The average number of viable seed found within every ton of dry particulate matter removed from vehicles was ca. 68,000. Thus, a typical wash down facility was removing up to ca. 335,000 viable seed from vehicles per week, of which ca. 6700 were parthenium weed seed. Furthermore, 61% of these seed (ca. 200,000) were from introduced species, and about half of these (35% of total) were from species considered to be weeds. Therefore, the roadside wash down facilities found throughout Queensland can remove a substantial amount of viable weed seed from vehicles, including the invasive parthenium weed, and the use of such facilities should be strongly encouraged.

Death from pulmonary embolism of cyanoacrylate glue following gastric varix endoscopic injection.

We present the case of a 25 year old woman with a complex past medical history including Crigler-Najjar syndrome (Type 1) with a liver transplant in 1993 and subsequent development of cirrhosis with portal hypertension in the transplanted liver. The deceased presented to hospital with hematemesis and investigations showed a large gastric varix. The varix was injected with cyanoacrylate glue. Within 30 min of injection the patient became acutely hypoxic. Urgent chest X-ray demonstrated radio opaque glue within the pulmonary arteries. It was evident that future treatment was futile and supportive treatment was withdrawn. The deceased was referred for medico legal post mortem examination. The post mortem CT scan performed prior to autopsy showed widespread radio-opaque material within the pulmonary arteries. At autopsy, rubbery grey/tan "clot" occluded the major proximal and segmental pulmonary arteries. Microscopic examination of the "clot" showed clumps of erythrocytes surrounded by foreign material. We discuss this relatively uncommon but well recognized complication of variceal injection with cyanoacrylate glue.

The effect of post-mortem computed tomography angiography (PMCTA) using water-soluble, iodine-based radiographic contrast on histological analysis of the liver, kidneys and left ventricle of the heart.

The purpose of this study was to investigate the impact of post-mortem computed-tomography angiography (PMCTA) on the histology of the liver, kidneys and heart. Multiple tissue cores were collected from the liver, left and right kidneys and left ventricle utilizing CT-guided biopsy. Subsequent whole body PMCTA was performed using a solution of polyethylene glycol and iodinated radiographic contrast, and an embalming pump. Corresponding biopsy cores were collected at autopsy, and blinded histology analysis assessing for PMCTA-induced histology artefact was performed. The blinded analysis of pre-PMCTA and post-PMCTA biopsy samples demonstrated that whole body PMCTA had no effect on the histological analyses of the liver (0%, CI = 0-13.7%), left ventricle of the heart (0%, CI = 0-36.9%) and right kidney (0%, CI = 13.2%), however likely caused increased Bowman's capsule spaces in the left kidney of one case (4%, CI = 0.01-20.4%). Other artefactual histological changes identified included eosinophilic material in the liver, whiter interstitium and dilated tubules in kidney samples, and autolysis-related changes, however these could not be categorically attributed to the PMCTA procedure. PMCTA causes zero or minimal effect to the histological examination of the liver, left kidney, right kidney and left ventricle, and as such performing PMCTA prior to autopsy is unlikely to impact autopsy histological results in these organs.

The use of computed tomography in determining development, anomalies, and trauma of the hyoid bone.

PURPOSE: Recognition of injury to the hyoid bone is intrinsic to post-mortem examination. Given its superficial location in the neck hyoid fractures are generally associated with some form of compressive neck force although they are well recognized in the peri-mortem period, in the context of manual handling and resuscitation. Hyoid fractures are variably reported to occur in manual strangulation and during hanging. METHODS: In this study Computer Tomography (CT) scans of the head and neck of 431 deceased persons (235 males and 196 females) between the ages of 1 day and 100 years of age (mean age 35.93 ± 24.15) and including 25 victims of hangings were examined to reveal the pattern of age-related change and the types of injury that occurred. Hyoid variants were also documented. RESULTS: The synchondroses between greater cornua and body were found to progressively fuse with age although in the current sample 20% non-fusion was observed beyond 65 years of age. Sex differences were evident in adult hyoid bones and discriminant function analysis correctly confirmed sex in 74.7% of cases. CONCLUSIONS: The greatest age-related changes occurred from puberty to post-adolescence and a linear regression equation successfully assessed age into three general categories in 87.7% of cases. Hyoid fractures were documented in 24% of victims of hangings and while previous reports indicate these are more likely in older age, when synchondroses are fused, in this study the average age of victims with fracture was 27 ± 10 years. In the majority of cases the site of ligature was below the hyoid bone and in only one on the hyoid body.

Post-mortem CT findings in a case of necrotizing cellulitis of the floor of the mouth (Ludwig angina).

Ludwig angina is a rare but potentially lethal infection of the submandibular space that can cause significant upper airway obstruction. We report a case of undiagnosed Ludwig angina that progressed rapidly to death. Ludwig angina was suspected after post-mortem computed tomography (PMCT) found swollen mylohyoid muscle with stranding in subcutaneous fat, thickening of deep fascia, and local lymphadenopathy. Subsequently, an autopsy revealed woody induration of the submental region and liquefactive necrosis of the mylohyoid muscle, confirming the diagnosis. It is likely that the dental abscess identified on PMCT was the source of infection. Multiple invasive medical procedures were performed on the subject by the ambulance crew prior to his death. PMCT assisted further in determining procedural success.

Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis.

BACKGROUND AND PURPOSE: A novel association between a single nucleotide polymorphism on chromosome 7p21.1 and large-vessel ischemic stroke was recently identified. The most likely underlying gene is histone deacetylase 9 (HDAC9). The mechanism by which HDAC9 increases stroke risk is not clear; both vascular and neuronal mechanisms have been proposed. METHODS: We determined whether the lead single nucleotide polymorphisms were associated with asymptomatic carotid plaque (N=25 179) and carotid intima-media thickness (N=31 210) detected by carotid ultrasound in a meta-analysis of population-based and community cohorts. Immunohistochemistry was used to determine whether HDAC9 was expressed in healthy human cerebral and systemic arteries. In the Tampere Vascular Study, we determined whether HDAC9 mRNA expression was altered in carotid (N=29), abdominal aortic (N=15), and femoral (N=24) atherosclerotic plaques compared with control (left internal thoracic, N=28) arteries. RESULTS: Both single nucleotide polymorphisms (rs11984041 and rs2107595) were associated with common carotid intima-media thickness (rs2107595; P=0.0018) and with presence of carotid plaque (rs2107595; P=0.0022). In both cerebral and systemic arteries, HDAC9 labeling was seen in nuclei and cytoplasm of vascular smooth muscle cells, and in endothelial cells. HDAC9 expression was upregulated in carotid plaques compared with left internal thoracic controls (P=0.00000103). It was also upregulated in aortic and femoral plaques compared with controls, with mRNA expression increased in carotid compared with femoral plaques (P=0.0038). CONCLUSIONS: Our results are consistent with the 7p21.1 association acting via promoting atherosclerosis, and consistent with alterations in HDAC9 expression mediating this increased risk. Further studies in experimental models are required to confirm this link.

Non-invasive visualisation and volume estimation of maggot masses using computed tomography scanning.

There is limited understanding of the actual temperatures that maggots experience during growth. The impact of maggot mass heating on their growth rates cannot be properly factored into maggot growth rate models, thus limiting the accuracy of forensic entomology estimates. One of the major factors contributing to mass heating is the mass size; however, measuring mass volume is problematic as masses quickly become disturbed when probing them to measure their depth and width. Furthermore, many masses are deep within the body cavity and are inaccessible. This study examined the development of a non-invasive means for measuring mass volume using computed tomography(CT) scanning. It was found that CT can be used to visualise and measure the volume of maggot masses, and a series of rules for doing so were established. The level of agreement between mass measurements made by four 'judges' using CT volumetric analysis tools produced excellent reliability (ICC > 0.95). This high level of reliability was maintained when applied to masses of different sizes in experimental cups of meat and natural masses of mixed species on human bodies. Entomological features of mortuary CT scans are now routinely reported in forensic entomology casework in Victoria, Australia, as a result of our work.

The use of computed tomography in determining developmental changes, anomalies, and trauma of the thyroid cartilage.

Recognition of injury to the hyoid bone and thyroid and cricoid cartilages is intrinsic to post-mortem examination. Due to its increasing brittleness with age the thyroid cartilage is particularly susceptible to injury following neck trauma, although there is inconsistency in the patterns of injury reported. In this study computed tomography scans of the head and neck of 431 deceased persons (235 males and 196 females) between the ages of 1 day and 100 years (mean age 35.93 ± 24.15), and including 25 victims of hangings, were examined to reveal the pattern of age-related change and the types of injury that occurred. Thyroid cartilage anomalies likely to cause confusion and be misinterpreted as trauma-related are documented. Angulation of the thyroid cartilage horns was found to change with age, and it is suggested this may be a significant factor in traumatic neck injury. Unlike in previous reports, the average age of hanging victims with fractures to the thyroid cartilage was 34 years. The base of the superior horn was the most common fracture site and in 50 % of hanging cases was associated with a ligature positioned on the thyrohyoid membrane or thyroid lamina. Although an age-related relationship exists it was not possible to establish narrow age-prediction ranges from calcification of the thyroid cartilage.

Social exclusion and its impact on health over the life course: A realist review protocol.

Background: Social exclusion is a process whereby certain individuals are born into or pushed to the margins of society and prevented from participating in social, cultural, economic, and political life. People who experience social exclusion are not afforded the same rights and privileges as other population groups. Socially excluded people often experience poorer outcomes in a variety of domains including health, education, employment, and housing than people with socio-economic privilege. People experiencing social exclusion frequently have higher and more complex health needs and poorer access to healthcare than the general population. The aim of this study is to better understand and explain how social exclusion occurs and how it impacts health over the life course. Methods: A realist review will be undertaken. Data will be collected via a systematic search of databases of peer-reviewed literature and further iterative searches of peer-reviewed and other literatures as needed. The following data bases will be searched: MEDLINE, Embase, CINAHL, and ASSIA, using both indexed subject headings in each database and relevant key words. Grey literature will be searched via Google Scholar and relevant websites of organisations that work with populations affected by social exclusion. Conclusion: A realist review will be conducted to explain the underlying societal mechanisms which produce social exclusion and related health outcomes in particular contexts affecting excluded population groups across the life course. The study has the potential to inform policy makers and service managers of how and why social exclusion occurs and potential key intervention points to prevent exclusion from happening.

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.

Demonstration of liver metastases on postmortem whole body CT angiography following inadvertent systemic venous infusion of the contrast medium.

An 86-year-old woman was hospitalized for breathlessness and a large right-sided pleural effusion. Approximately 1 h after thoracentesis, she developed a hemothorax resulting in hypotension and death. Routine postmortem CT scanning showed a large volume right hemothorax and a markedly enlarged liver. In an attempt to determine the origin of bleeding prior to autopsy, a postmortem CT angiogram was performed. Following inadvertent cannulation of the left long saphenous vein and infusion of ∼1,700 mL of a polyethylene glycol 200 and iodine-based radiographic contrast solution into systemic veins using a mechanical pump, CT scanning revealed a dense hepatic "parenchogram" containing multiple large, filling defects indicative of metastases. These were confirmed at autopsy. Microscopic evaluation of the liver using hematoxylin and eosin staining showed marked histological artifact characterized by centrilobular sinusoidal expansion although histology of the adenocarcinoma metastases was typical and apparently unaffected by the contrast solution. Postmortem CT angiography using an aqueous radiographic contrast agent in the so-called venous phase seems to be useful for the identification of hepatic parenchymal metastatic disease although it does cause histological artifact.