Hangings: Lessons Learned from the Coroner's Office.

BACKGROUND: Hangings are an infrequent wounding mechanism among patients arriving alive to hospital but are frequently encountered by the Coroner's Office. It is unclear if classically described hanging injuries, such as the Hangman's fracture, are common among contemporary hangings patients who typically do not suspend from height. This study was undertaken to define patient and injury characteristics after hangings causing death. METHODS: All patients presenting to the Los Angeles County Medical Examiner/Coroner's Office (January 2016 - May 2020) who died by hanging were included. Demographics, psychiatric history, hanging details, autopsy type, and sustained injuries were collected. Data variables were summarized with descriptive statistics and the diagnostic yield of a ligature mark in the diagnosis/exclusion of cervical injuries was calculated. RESULTS: Over the study, 1,401 patients died by hanging. Patients underwent external exam alone (n = 1,282, 92%), traditional neck autopsy (n = 114, 8%), or traditional neck autopsy plus postmortem computed tomography scan (n = 5, <1%). Home was the most frequent hanging setting (n = 1,028, 73%) followed by public spaces (n = 80, 6%) and jail (n = 28, 2%). The manner of death was almost exclusively suicide (n = 1,395, >99%) and psychiatric disease was common (n = 968, 69%). Of the patients undergoing traditional autopsy, most had a ligature mark (n = 109, 92%) and only 9 (8%) had a cervical injury (hyoid fractures, n = 6, 5%; thyroid cartilage fractures, n = 4, 3%). None had a vertebral fracture/dislocation. Sensitivity, specificity, positive predictive value, and negative predictive value of a ligature mark were 100%, 5%, 8%, and 100%. CONCLUSIONS: Hangings are a frequent cause of death in Los Angeles County. Patients typically have a psychiatric history and die almost exclusively from suicide. Hangings commonly occur at home, in public places, and in jail. Injuries were exceedingly rare and no patient sustained a Hangman's fracture, which may be related to the lack of significant suspension with modern hangings.

Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases.

BACKGROUND: Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis. METHODS: Of the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem "molecular autopsy" cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest. RESULTS: Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively. CONCLUSIONS: The basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.

Molecular Autopsy for Sudden Death in the Young: Is Data Aggregation the Key?

The Scripps molecular autopsy study seeks to incorporate genetic testing into the postmortem examination of cases of sudden death in the young (<45 years old). Here, we describe the results from the first 2 years of the study, which consisted of whole exome sequencing (WES) of a cohort of 50 cases predominantly from San Diego County. Apart from the individual description of cases, we analyzed the data at the cohort-level, which brought new perspectives on the genetic causes of sudden death. We investigated the advantages and disadvantages of using WES compared to a gene panel for cardiac disease (usually the first genetic test used by medical examiners). In an attempt to connect complex clinical phenotypes with genotypes, we classified samples by their genetic fingerprint. Finally, we studied the benefits of analyzing the mitochondrial DNA genome. In this regard, we found that half of the cases clinically diagnosed as sudden infant death syndrome had an increased ratio of heteroplasmic variants, and that the variants were also present in the mothers. We believe that community-based data aggregation and sharing will eventually lead to an improved classification of variants. Allele frequencies for the all cases can be accessed via our genomics browser at https://genomics.scripps.edu/browser.

Corrigendum: Molecular Autopsy for Sudden Death in the Young: Is Data Aggregation the Key?

[This corrects the article on p. 72 in vol. 4, PMID: 29181379.].

An Acute Acetyl Fentanyl Fatality: A Case Report With Postmortem Concentrations.

In this case report, we present an evaluation of the distribution of postmortem concentrations of acetyl fentanyl in a fatality attributed to the drug. A young man who had a history of heroin abuse was found deceased at his parents' home. Toxicology testing, which initially screened positive for fentanyl by ELISA, subsequently confirmed acetyl fentanyl by gas chromatography-mass spectrometry specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. No other drugs or medications, including fentanyl, were detected. The acetyl fentanyl peripheral blood concentration was quantified at 260 ng/mL compared with the central blood concentration of 250 ng/mL. The liver concentration was 1,000 ng/kg, the vitreous was 240 ng/mL and the urine was 2,600 ng/mL. The cause of death was certified due to acute acetyl fentanyl intoxication, and the manner of death was certified as an accident.

Sudden death in a toddler with laryngotracheitis caused by human parainfluenza virus-1.

Laryngotracheitis caused by human parainfluenza virus (HPIV) and not complicated by bacterial superinfection rarely causes sudden unexpected death in infants and toddlers, especially in the absence of stridor and a barking cough. We therefore describe a 15-month-old white male who died suddenly and unexpectedly with clinical and pathological features of laryngotracheitis caused by culture-proven HPIV-1 infection. Given the presence of mucosal inflammation extending into the vocalis muscle of the larynx without associated significant narrowing of the laryngotracheal airway lumen, we propose his death was a result of a laryngospasm, perhaps mediated by immune responses.

The analysis of an intracerebral hematoma for drugs of abuse.

Toxicological investigations were performed on an intracerebral hematoma, antemortem blood, and postmortem blood of an individual who was found unresponsive in his home. The hematoma was found to have ethanol at a concentration of 0.05% (w/v), and benzoylecgonine (a cocaine metabolite) was also confirmed at a concentration of 0.43 mg/L by specific analysis using gas chromatography/mass spectrometry (GC/MS). These results enabled the pathologist to record the cause of death as intracerebral hemorrhage due to acute cocaine intoxication.