Identification of furosemide in hair in a post‐mortem case by UHPLC‐MS/MS with guidance on interpretation

Testing for drugs in hair raises several difficulties. Among them is the interpretation of the final concentration(s). In a post‐mortem case, analyses revealed the presence of furosemide (12 ng/mL) in femoral blood, although it was not part of the victim's treatment. The prosecutor requested our laboratory to undertake an additional analysis in hair to obtain information about the use of furosemide. A specific method was therefore developed and validated to identify and quantify furosemide in hair by UHPLC‐MS/MS. After decontamination of 30 mg of hair, incubation in acidic condition, extraction with ethyl acetate, the samples were analyzed by UHPLC‐MS/MS. Furosemide was found in the victim's hair at 225 pg/mg. However, it was not possible to interpret this concentration due to the absence of data in the literature. Therefore, the authors performed a controlled study in two parts. In order to establish the basis of interpretation, several volunteers were tested (four after a single 20 mg administration and twenty‐four under daily treatment). The first part indicated that a single dose is not detectable in hair using our method. The second part demonstrated concentrations ranging from 5 to 1110 pg/mg with no correlation between dosage and hair concentrations. The decedent's hair result was interpreted as repeated exposures. In the case of furosemide analysis, hair can provide information about its presence but cannot give information about dosage or frequency of use.     

Determination of Both Fetus’ and Mother's Blood Type from an Autopsy Case Immersed in Formalin for Over 50 Years

A female fetus which had been immersed in formalin for more than 50 years was found in Japan. Because no liquid blood could be obtained, we tried to use immunohistochemistry (IHC) methods to tissue samples obtained at autopsy to identify both the fetal and mother's blood type. We detected B antigens on endothelial cells in paraffin sections of the fetal organs. Furthermore, we observed both anti‐A‐ and anti‐B‐positive red blood cells in the intervillous space, which is indicative of the mother's blood type. To our knowledge, this is the first case report on determining the blood type of both the fetus and the mother from tissue immersed in formalin for such a long time. The results suggest that IHC is valuable for the determination of ABO blood type in circumstances of long postmortem duration and unfavorable storage conditions.     

Fatal intoxication with 1,4-butanediol: Case report and comprehensive review of the literature

A fatal case of 1,4-butanediol (1,4-BD) oral ingestion is reported here, in which a 51-year-old man was found dead in his bed. According to the police report, the deceased was a known drug user. A glass bottle labeled (and later confirmed to be) “Butandiol 1,4” (1,4-BD) was found in the kitchen. Furthermore, the deceased's friend stated that he consumed 1,4-BD on a regular basis. The autopsy and histological examination of postmortem parenchymatous organ specimens did not revealed a clear cause of death. Chemical-toxicological investigations revealed gammahydroxybutyrat (GHB) in body fluids and tissues in the following quantities: femoral blood 390 mg/L, heart blood 420 mg/L, cerebrospinal fluid 420 mg/L, vitreous humor 640 mg/L, urine 1600 mg/L, and head hair 26.7 ng/mg. In addition, 1,4-BD was qualitatively detected in the head hair, urine, stomach contents, and the bottle. No other substances, including alcohol, were detected at pharmacologically relevant concentrations. 1,4-BD is known as precursor substance that is converted in vivo into GHB. In the synoptic assessment of toxicological findings, the police investigations and having excluded other causes of death, a lethal GHB-intoxication following ingestion of 1,4-BD, can be assumed in this case. Fatal intoxications with 1,4-BD have seldom been reported due to a very rapid conversion to GHB and, among other things, non-specific symptoms after ingestion. This case report aims to give an overview to the published of fatal 1,4-BD-intoxications and to discuss the problems associated with detection of 1,4-BD in (postmortem) specimens.     

The effects of the (fentanyl-fueled) drug overdose epidemic on medicolegal death investigation in the United States

The evolving opioid epidemic in the United States, fueled by illicit fentanyl, has greatly increased deaths from illicit drug use. These nonnatural deaths require formal death investigation. The National Association of Medical Examiners states in its Forensic Autopsy Performance Standards that autopsy remains a necessary component for proper investigation of suspected acute overdose deaths. If a death investigation office lacks adequate resources to investigate all deaths under its jurisdiction while meeting expected standards, then that office may be forced to consider altering its protocols for investigation by changing the types of deaths investigated or the extent of its investigations. Drug death investigations take longer to complete because novel illicit drugs and mixtures of drugs complicate toxicological analyses, prolonging a family's wait for completion of a death certificate and autopsy report. Public health agencies must also wait for results, but some agencies have developed mechanisms for rapid notification of preliminary results to allow timely deployment of public health resources. The increased deaths have strained the resources of medicolegal death investigation systems throughout the United States. Given the significant workforce shortage of forensic pathologists, newly trained forensic pathologists are too few to meet the demand. Nevertheless, forensic pathologists (and all pathologists) must make time to present their work and themselves to medical students and pathology trainees to encourage an understanding of the importance of quality medicolegal death investigation and autopsy pathology and to provide a model that can encourage interest in a career in forensic pathology.     

Development and validation of a LC–MS/MS method for analysis of vortioxetine in postmortem specimens. First data from an authentic case

Vortioxetine is an antidepressant recently licensed in USA and EU for the treatment of major depressive disorder. Neither fatal case due to overdose nor data about postmortem concentrations on blood or other specimens have been reported. The aims of this study were the development and validation of a method for vortioxetine analysis by Liquid Chromatography Tandem Mass Spectrometry (LC–MS/MS) in postmortem samples and its application in an authentic case. The method was validated and applied on blood, vitreous humor, bile, brain, liver, kidney, and gastric content. After protein precipitation, the supernatant was directly injected into LC–MS/MS. Analysis was carried out by Multiple Reaction Monitoring (MRM) mode. The authentic case concerned a 38 years-old woman, affected by depression, who was found hanged at home. The method determined an acceptable sensitivity, selectivity, linearity, precision, and accuracy for all matrices. No interference was shown for all matrices. The matrices do not significantly reduce the peak intensity of vortioxetine. No carryover was shown. Toxicological analysis of the authentic case showed vortioxetine in blood (234 ng/ml), vitreous humor (10.5 ng/ml), brain (490 ng/g), lung (479 ng/g), liver (3751 ng/g), kidney (798 ng/g), bile (2267 ng/ml) and gastric content (253 ng/ml). Our case suggests that even at blood concentrations of vortioxetine equal to 234 ng/ml, the subject was able to stage and carry out the hanging. Vortioxetine concentrations found in the other cadaveric samples (biological fluids, organs, and gastric content) may be helpful to evaluate further similar comparable cases.     

Death by compaction in a robotic dumpster

Robotic waste management automation systems are increasingly utilized around the globe as a user-friendly, ecological and hygienic alternative to waste disposal, simultaneously reducing the volume and frequency of waste collection. The present paper aims to report a case of death by compaction in an automated robotic waste management system and review relevant literature on compactor-related fatalities. The unusual fatal accident involved a 37-year-old male citizen who deliberately entered the robotic dumpster to retrieve his accidentally discarded medication. Upon entering the robotic chamber, the compaction system was automatically activated, although all safety measures were in full operation. This paper highlights the lack of standardized reporting on compactor-related mortality, which however is of importance both in terms of its social impact and public safety. These deaths occur rarely, in scattered areas of the globe, associated with various situations (e.g., occupational fatalities, homeless people, infanticide) and trash compactors of different types, technology, age, maintenance quality, warning signage and safety interlocks. In all previously reported fatalities, the technology involved was considerably older (as in conventional waste containers, garbage compaction trucks, chute-fed compactors in buildings, etc.). The case described in the present report is a rare event in both literature and international news coverage as it encompasses a fully automated technology intended for unsupervised, direct use by the public being located in public spaces where all citizens can interact with it. The aim of this report is to raise awareness and improve knowledge about safety parameters so that similar incidents can be avoided in the future.     

Understanding deliberate indifference to suicide in corrections facilities: A review of recent legal cases

The US corrections system is the largest provider of mental health care in the country. Suicide is a leading cause of death in corrections facilities with rates of inmate suicide being far higher than the national average. Suicide is an event that can lead to legal action against the facility, staff, and treating health-care providers. Some claims are based on medical malpractice. In this setting, claims may also be brought based on violations of the detainee's constitutional rights. Pretrial detainees and prisoners, alike, have a constitutional right to adequate medical and psychiatric care through the Fourteenth Amendment and Eighth Amendment, respectively. But, there is limited information on constitutional claims made against correctional health-care providers for cases of inmate suicide. To help bridge this gap, the authors conducted a search of federal legal case decisions involving claims against health-care providers for deliberate indifference to a detainee's serious illness or injury in the event of attempted suicide or death by suicide over a 5 year period from 2016 to 2021. Fifteen cases were identified. Five themes emerged from the cases, which could serve as bases for claims against health-care professionals: receiving screening, mental health assessment, treatment, documentation, and attention to facility policies. The cases and their clinical significance are summarized in this article. The materials provide an overview of the problems surrounding correctional suicides and can serve as practice pointers in the corporeal setting.     

Deep learning for sex determination: Analyzing over 200,000 panoramic radiographs

The objective of this study is to assess the performance of an innovative AI-powered tool for sex determination using panoramic radiographs (PR) and to explore factors affecting the performance of the convolutional neural network (CNN). The study involved 207,946 panoramic dental X-rays and their corresponding reports from 15 clinical centers in São Paulo, Brazil. The PRs were acquired with four different devices, and 58% of the patients were female. Data preprocessing included anonymizing the exams, extracting pertinent information from the reports, such as sex, age, type of dentition, and number of missing teeth, and organizing the data into a PostgreSQL database. Two neural network architectures, a standard CNN and a ResNet, were utilized for sex classification, with both undergoing hyperparameter tuning and cross-validation to ensure optimal performance. The CNN model achieved 95.02% accuracy in sex estimation, with image resolution being a significant influencing factor. The ResNet model attained over 86% accuracy in subjects older than 6 years and over 96% in those over 16 years. The algorithm performed better on female images, and the area under the curve (AUC) exceeded 96% for most age groups, except the youngest. Accuracy values were also assessed for different dentition types (deciduous, mixed, and permanent) and missing teeth. This study demonstrates the effectiveness of an AI-driven tool for sex determination using PR and emphasizes the role of image resolution, age, and sex in determining the algorithm's performance.