It is believed by many that reference data for age estimation purposes must be imaging-modality specific. A study from our department has however proven otherwise. We therefore found it interesting to investigate this further by looking at the level of agreement between different imaging modalities. The aim of this study was to investigate the level of agreement between the three radiological modalities, computed tomography (CT), magnetic resonance imaging (MRI), and digital radiography (DR), in assessing the ossification of the epiphyses of the knee. A total of 34 deceased individuals of 10-25 years of age, brought in for a medicolegal autopsy at our department, were scanned by CT, MRI, and DR. The ossification stages of the three bones of the right knee, distal femoral, proximal tibial, and proximal fibular epiphysis were assessed using the established combined staging method by Schmeling et al. and Kellinghaus et al. Analysis of the results by Cohen\'s weighted kappa showed a good agreement between CT and DR (K = 0.61-0.70), and MRI and DR (K = 0.68-0.79) but only moderate agreement between CT and MRI (K = 0.55-0.57). This leads us to conclude that different radiological images cannot be used interchangeably for age estimation purposes, so reference material needs to be imaging-modality specific. However, to make a more general conclusion research on a larger population is needed.

The development of biomedical soft- or hardware frequently includes testing in animals. However, large efforts have been made to reduce the number of animal experiments, according to the 3Rs principle. Simultaneously, a significant number of surplus animals are euthanized without scientific necessity. The primary aim of this study was to establish a post-mortem rat perfusion model using extracorporeal membrane oxygenation (ECMO) in surplus rat cadavers and generate first post vivo results concerning the oxygenation performance of a recently developed ECMO membrane oxygenator. Four rats were euthanized and connected post-mortem to a venous-arterial ECMO circulation for up to eight hours. Angiographic perfusion proofs, blood gas analyses and blood oxygenation calculations were performed. The mean preparation time for the ECMO system was 791 ± 29 s and sufficient organ perfusion could be maintained for 463 ± 26 min, proofed via angiographic imaging and a mean femoral arterial pressure of 43 ± 17 mmHg. A stable partial oxygen pressure, a 73% rise in arterial oxygen concentration and an exponentially increasing oxygen extraction ratio up to 4.75 times were shown. Considering the 3Rs, the established post-mortal ECMO perfusion rat model using surplus animals represents a promising alternative to models using live animals. Given the preserved organ perfusion, its use could be conceivable for various biomedical device testing.

Sudden and unexpected death (SUD) is a common reason for animals to undergo post-mortem examination. There is limited literature examining the causes of SUD in cats and dogs, and no research specific to Australia. The purpose of this study was to investigate the epidemiology and pathology of SUD in cats and dogs in a multicentric study across Australia. Retrospective post-mortem reports of SUD in cats and dogs were obtained from four veterinary schools in Australia distributed across four states. The frequency of SUD between institutes ranged from 2.1% to 6.5%. Dogs composed the majority of the study population (76%), and males outnumbered females, particularly in the feline subpopulation. After necropsy, 37% of SUD remained cause unknown, the largest category in both cats and dogs. When cause was identified, cardiovascular disease was most common in both species, followed by gastrointestinal disease in dogs, and trauma in cats. In dogs, multinomial logistic regression identified age as a risk factor significantly associated with the four largest categories of SUD. This study identified causes of SUD in Australian cats and dogs, including novel causes not previously reported. Further, this study revealed a higher rate of unsolved SUD in Australia than can be found in the literature from other countries.

The extent of heavy-metal-induced cardiotoxicity is proportional to the levels of metal bioaccumulation, and it was previously assumed that heavy metals accumulate uniformly in the myocardium. Therefore, the aim of this study was to investigate concentrations of metals and metalloids in two distant regions of the left ventricle (LV), the base of the LV, and apex of the LV using inductively coupled plasma mass spectrometry (ICP-MS). We also examined the potential correlation between metal levels and the thickness of the interventricular septum in twenty LV specimens (ten from the base of LV and ten from the apex of LV) from 10 individuals (mean age 75 ± 6 years). We found significantly higher concentrations of arsenic and lead in the LV apex compared to the base of the LV. We also found a positive correlation between the concentrations of arsenic in the myocardium of LV and the thickness of the interventricular septum. Our results indicate that arsenic and lead accumulate to a higher extent in the apex of the LV compared to the base of the LV. Therefore, future studies designed to measure levels of metals in heart muscle should consider non-uniform accumulation of metals in the myocardium.

There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed® between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case-controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of CYP2D6, and to a lower extent, CYP2B6 and CYP3A4/5 genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the CYP2B6*4-allele in our methadone-overdose sample (n = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids.

Aims: There are very few detailed post-mortem studies on idiopathic normal-pressure hydrocephalus (iNPH) and there is a lack of proper neuropathological criteria for iNPH. This study aims to update the knowledge on the neuropathology of iNPH and to develop the neuropathological diagnostic criteria of iNPH. Methods: We evaluated the clinical lifelines and post-mortem findings of 29 patients with possible NPH. Pre-mortem cortical brain biopsies were taken from all patients during an intracranial pressure measurement or a cerebrospinal fluid (CSF) shunt surgery. Results: The mean age at the time of the biopsy was 70±8 SD years and 74±7 SD years at the time of death. At the time of death, 11/29 patients (38%) displayed normal cognition or mild cognitive impairment (MCI), 9/29 (31%) moderate dementia and 9/29 (31%) severe dementia. Two of the demented patients had only scarce neuropathological findings indicating a probable hydrocephalic origin for the dementia. Amyloid-β (Aβ) and hyperphosphorylated τ (HPτ) in the biopsies predicted the neurodegenerative diseases so that there were 4 Aβ positive/low Alzheimer\'s disease neuropathological change (ADNC) cases, 4 Aβ positive/intermediate ADNC cases, 1 Aβ positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HPτ/PSP and primary age-related tauopathy (PART) case, 1 Aβ/HPτ and low ADNC/synucleinopathy case and 1 case with Aβ/HPτ and high ADNC. The most common cause of death was due to cardiovascular diseases (10/29, 34%), followed by cerebrovascular diseases or subdural hematoma (SDH) (8/29, 28%). Three patients died of a postoperative intracerebral hematoma (ICH). Vascular lesions were common (19/29, 65%). Conclusions: We update the suggested neuropathological diagnostic criteria of iNPH, which emphasize the rigorous exclusion of all other known possible neuropathological causes of dementia. Despite the first 2 probable cases reported here, the issue of \"hydrocephalic dementia\" as an independent entity still requires further confirmation. Extensive sampling (with fresh frozen tissue including meninges) with age-matched neurologically healthy controls is highly encouraged.

The aim of this study was to investigate associations between ear, tail, and skin lesions, hernias, bursitis, and rectal prolapses at the abattoir and meat inspection outcomes in slaughter pigs, including carcass condemnations and trimmings, carcass weight, and carcass quality. This was an observational study whereby pigs were managed according to routine practices in a single abattoir. Data were collected from 1816 pigs. The relationship between animal-based welfare and post-mortem outcomes was analyzed using generalized mixed models (Proc Glimmix). Our findings showed that tail lesions were associated with entire carcass condemnations and trimmings (P < 0.001), a reduction in carcass weight (P < 0.05), and a potential to impair carcass quality by reducing muscle pH (P < 0.05), especially in carcasses from male pigs (P < 0.05). Additionally, hernias were associated with viscera condemnation (P < 0.05) and a reduction in carcass weight (P  < 0.05). Therefore, our findings confirm that ante-mortem inspection could be useful to predict post-mortem outcomes in the same pigs, especially in cases of tail lesions and hernia, which might trigger attention of the veterinary inspector in charge of the post-mortem inspection.

Post-mortem imaging has been suggested as an alternative to conventional autopsy in the prenatal and postnatal periods. Noninvasive autopsies do not provide tissue for histological examination, which may limit their clinical value, especially when infection-related morbidity and mortality are suspected.
We performed a prospective, multicentre, cross-sectional study to compare the diagnostic performance of post-mortem magnetic resonance imaging with computed tomography-guided biopsy (Virtopsy®) with that of conventional autopsy in foetuses and infants. Cases referred for conventional autopsy were eligible for enrolment. After post-mortem imaging using a computed tomography scanner and a magnetic resonance imaging unit, computed tomography-guided tissue sampling was performed. Virtopsy results were compared with conventional autopsy in determining the likely final cause of death and major pathologies. The primary outcome was the proportion of cases for which the same cause of death was determined by both methods. Secondary outcomes included the proportion of false positive and false negative major pathological lesions detected by virtopsy and the proportion of computed tomography-guided biopsies that were adequate for histological examination.
Overall, 101 cases (84 fetuses, 17 infants) were included. Virtopsy and autopsy identified the same cause of death in 91 cases (90.1%, 95% CI 82.7 to 94.5). The sensitivity and specificity of virtopsy for determining the cause of death were 96.6% (95% CI 90.6 to 98.8) and 41.7% (95% CI 19.3 to 68.0), respectively. In 32 cases (31.7%, 95% CI 23.4 to 41.3), major pathological findings remained undetected by virtopsy, and in 45 cases (44.6%, 95% CI 35.2 to 54.3), abnormalities were diagnosed by virtopsy but not confirmed by autopsy. Computed tomography-guided tissue sampling was adequate for pathological comments in 506 of 956 biopsies (52.7%) and added important diagnostic value in five of 30 cases (16.1%) with an unclear cause of death before autopsy compared with postmortem imaging alone. In 19 of 20 infective deaths (95%), biopsies revealed infection-related tissue changes. Infection was confirmed by placental examination in all fetal cases.
Virtopsy demonstrated a high concordance with conventional autopsy for the detection of cause of death but was less accurate for the evaluation of major pathologies. Computed tomography-guided biopsy had limited additional diagnostic value.
ClinicalTrials.gov (NCT01888380).

Associations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. Seven hundred forty-one individuals (age at death = 72.2 ± 11.7 years) from the Biobank for Aging Studies were analyzed. a-MDD was present in 54 (7.3%) participants, LLD in 80 (10.8%), and DS in 168 (22.7%). After adjustment for covariates and compared to controls, a-MDD, LDD and DS were associated with small vessel disease (p = 0.039, p = 0.003, and p = 0.003 respectively); LLD, and DS were associated with brain infarcts (p = 0.012, p = 0.018, respectively) and Lewy body disease (p = 0.043, p = 0.002, respectively). DS was associated with beta-amyloid plaque burden (p = 0.027) and cerebral amyloid angiopathy (p = 0.035) in cognitively normal individuals (Clinical Dementia Rating scale = 0). Vascular brain pathology was the strongest correlate of clinical depictions of depression in the absence of dementia, corroborating the vascular hypothesis of depression. Lewy body pathology underlay DS. An older adult with DS or LLD should be monitored for possible cognitive decline or neurodegenerative disorders.

OBJECTIVE: In forensic pathology, wound age evaluation allows to determine if a wound was inflicted before or after death, and to date wounds of different ages. This dating is performed in conventional histopathology by observing inflammatory cells and hemorrhage at the wound site. However, these criteria seem to show low sensitivity and/or specificity. The aim of our study was to compare two models of wound vitality evaluation: a human surgical model, and a porcine experimental model; using these histological criteria.
METHODS: In the two human (n=38) and porcine (n=11) models, three wounds were performed at regular time-lapse before devascularization/sacrifice, and a control wound after devascularization/sacrifice. The main evaluation criteria were the presence of interstitial hemorrhage and the number of interstitial polymorphonuclear neutrophils at 10 high power fields.
RESULTS: In the two models, the number of polymorphonuclears neutrophils was significantly higher in vital wounds compared to the post-devascularization/sacrifice wounds (P<0.001), with a very low sensitivity (human model: 4.3%; porcine: 47%). Hemorrhagic infiltration was more frequent in vital wounds (human: P<0.001; porcine: P=0.01), with a low specificity (human: 48%; porcine: 54%).
CONCLUSIONS: This first study confirms, in the two models, the limitations of conventional histopathology in wound vitality evaluation. The next step will be testing several immunohistochemical markers in the two models.