Postmortem genetic testing in sudden unexplained death: A public health laboratory experience

Sudden unexplained death in the young poses a diagnostically challenging situation for practicing autopsy pathologists, especially in the absence of anatomic and toxicological findings. Postmortem genetic testing may identify pathogenic variants in the deceased of such cases, including those associated with arrhythmogenic channelopathies and cardiomyopathies. The Wisconsin State Laboratory of Hygiene (WSLH) is a state-run public health laboratory which performs postmortem genetic testing at no cost to Wisconsin medical examiners and coroners. The current study examines sequencing data from 18 deceased patients (ages 2 months to 49 years, 5 females) submitted to WSLH, from 2016 to 2021. Panel-based analysis was performed on 10 cases, and whole exome sequencing was performed on the most recent 8 cases. Genetic variants were identified in 14 of 18 decedents (77.8%), including 7 with pathogenic or likely pathogenic variants (38.9%). Whole exome sequencing was more likely to yield a positive result, more variants per decedent, and a larger number of variants of uncertain significance. While panel-based testing may offer definitive pathogenic variants in some cases, less frequent variants may be excluded. Whole exome testing may identify rare variants missed by panels, but increased yield of variants of uncertain significance may be difficult to interpret. Postmortem genetic testing in young decedents of sudden unexplained death can provide invaluable information to autopsy pathologists to establish accurate cause and manner of death and to decedent's relatives to allow appropriate management. A public health laboratory model may be a financially advisable alternative to commercial laboratories for medical examiner's/coroner's offices.     

An unusual blunt force trauma pattern and mechanism to the cranial vault: Investigation of an atypical infant homicide

This case report presents an unusual fracture pattern in the cranium of a four-month-old infant indicative of child abuse. Upon postmortem examination, the infant presented with numerous bilateral linear cranial fractures running perpendicular to the sagittal suture with depressed and curvilinear fractures apparent on the supra-auricular surfaces of the cranium. Histological evidence indicates multiple traumatic events to the cranium. In addition, the stair-step pattern of a parietal fracture may represent multiple contiguous fractures from repeated loading of the head at different times with variation of the focal points of compressive force. Additionally, the left humerus, left radius, and left ulna have healing metaphyseal fractures, and the left ulna also has an antemortem diaphyseal fracture which resulted in the distal metaphysis being rotated 45 degrees medially. Integration of autopsy, anthropological, and neuropathological reports for this case suggest multiple inflicted injury episodes with a repeated atypical mechanism(s) to the cranial vault of the infant. During investigative interviews, the caretaker admitted to squeezing the infant's head and neck on multiple occasions to quiet the child. This reported abusive mechanism is consistent with the pattern of symmetric cranial fractures and soft tissue injuries indicating asphyxiation. This case report provides forensic investigators with a potential trauma mechanism to explore in cases when a similar pattern of cranial trauma is observed and highlights the need for greater research on fracture propagation and fracture healing in the infant cranium.     

Validity and Defeasibility in the Legal Domain

In jurisprudential literature, the adjective ‘defeasible’ appears as a predicate of many terms: concepts, laws, rules, reasoning, justification, proof, and so on. In this paper, we analyze the effects of some versions of the thesis of the defeasibility of legal norms on the reconstruction of the notion of legal validity. We analyze some possible justifications of this thesis considered as a claim concerning validity, and enquire into two possible sets of problems related to the defeasibility of the criteria of identification of a legal system. We also provide a formalization of some options regarding defeasible criteria of identification, which can be used as a tool for meta-jurisprudential analysis. Finally, the thesis according to which defeasibility is better conceived of as a feature of legal application is examined and questioned.     

Histological diagnosis of myocardial sarcoidosis in a fatal fall from a height

The major issues of medico-legal relevance in fatal falls from a height are the manner of death and the reconstruction of the event. We present a peculiar case of a fatal fall from a height of about 9 m, involving a 27-year-old woman. At the death scene investigation, no suicide notes, housebreaking marks, or signs of fight were found, thus weakening both the suicide and homicide hypotheses. Combining circumstantial, autopsy and toxicology data, the kinematic analysis of the jump/fall, and the histological evidence of a myocardial sarcoidosis involving the left ventricle, we hypothesized that the young woman might have accidentally fallen from the window because of a sudden loss of consciousness related to cardiac disease undiagnosed during life. We believe that our brief report is a good example of the powerful additional information that histological investigations can offer for reconstructing the dynamics of the event in falls from a height and other traumatic fatalities.     

Death due to baclofen and dipyrone ingestion.

A fatal suicidal intoxication with unusual drugs is reported. A 56-year-old man was found dead in his house; near by the corpse several empty drugs boxes were found. An autopsy was performed and the biological fluids were submitted to a full toxicological work-up.The analytical results supported the hypothesis of a death due to the acute baclofen (4-amino-3-(p-chlorophenyl)butyric acid) and dipyrone (sodium [N-(1,5-dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-N-methylamino] methanesulfonate) intoxication.     

A Case of Toxic Shock due to Clandestine Abortion by Misoprostol self‐administration

Maternal mortality and morbidity are the leading causes of death and illness, respectively, among women of reproductive age in many countries throughout the world. Of all maternal deaths, those related to unsafe abortions are the most widely underestimated, but they are also the most largely preventable. Medical abortion is a safe and reliable method for termination of a pregnancy in early gestation, although it is important to be aware of signs and symptoms of severe infection and toxic shock syndrome after the medical termination of pregnancy; case studies in literature are rarely fatal events. We report the first case of septic shock syndrome following a clandestine pregnancy termination with a misoprostol‐only regimen (12 tablets 200 μg each). Autopsy findings and histopathological examination proved that the woman died from septic shock. This case suggests to improve the forensic investigations in case of unsafe, often clandestine, abortion is suspected.