Pharmacobezoar-Related Fatalities: A Case Report and a Review of the Literature.

ABSTRACT: Pharmacobezoars develop after an acute overdose or during routine drug administration. Here, the authors present a case of fatal multidrug overdose involving a 62-year-old woman. Her usual treatment included tramadol extended-release, citalopram, and mirtazapine. Furthermore, she self-medicated and misused her husband's medications. The autopsy revealed the presence of a voluminous medication bezoar in the stomach. No mechanical complication was noted. Toxicologic analyses were performed using gas chromatography with flame ionization detection, liquid chromatography with diode array detection, gas chromatography with mass spectrometry detection, and liquid chromatography coupled to tandem mass spectrometry. Tramadol (34,000 mcg/L), O-desmethyltramadol (2200 mcg/L), propranolol (6000 mcg/L), bromazepam (2500 mcg/L), zopiclone (1200 mcg/L), and citalopram (700 mcg/L) were identified in femoral blood at toxic concentrations. Interestingly, the femoral blood and vitreous humor concentration ratio was approximately 0.7. Furthermore, an English exhaustive literature search was performed using several different electronic databases without any limiting period to identify published pharmacobezoar-related fatalities. Seventeen publications were identified reporting a total of 19 cases. Decedents' mean age was 47.6 years [0.8-79] and a clear female predominance emerged. Several drugs were involved in pharmacobezoar formation. Death was attributed to drug toxicity in 13 cases, and to mechanical complications and/or sepsis in 4 cases. A mixed cause of death was reported in 2 cases. Although rare, pharmacobezoars remain potentially lethal and raise challenges in therapeutic management.

A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation.

INTRODUCTION: Hypothermia is a potentially lethal condition whose postmortem diagnosis is often complex to perform due to the absence of pathognomonic lesions and biomarkers. Our first study of human serum and urinary metabolome in hypothermia fatalities sought novel biomarkers with better diagnostic performances than those already existing. MATERIAL AND METHOD: Thirty-two cases of hypothermia deaths and 16 cases excluding known antemortem exposure to cold or postmortem elements suggesting hypothermia were selected. A targeted metabolomic study allowing the detection and quantitation of 188 metabolites was performed on collected serum and urine using direct flow injection (FIA) and liquid chromatography (LC) separation, both coupled to tandem mass spectrometry (MS/MS). Amino acid quantification was also carried on using an in-house LC-MS/MS method in order to replicate the results obtained with the metabolomic study. RESULTS: A discriminant metabolic signature allowing a clear separation between hypothermia and control groups was obtained in the serum. This signature was characterized by increased arginase activity and fatty acid unsaturation along with decreased levels of tryptophan in hypothermia fatalities compared to controls. By contrast, no discriminant metabolic signature separating hypothermia from control fatalities was found in urines. DISCUSSION: The serum metabolic signature of hypothermia fatalities herein observed pointed toward metabolic adaptations that likely aimed at heat production enhancement, endothelial function, and cell membrane fluidity preservation. Novel biomarkers potentially useful in a hypothermia diagnosis were also identified.

A diabetic ketoacidosis in a context of hyperglycemia addiction.

We herein present a case of a 20-year-old woman who suffered from type I diabetes mellitus and died from a diabetic ketoacidosis in a context of addiction to hyperglycemia. Diabetic ketoacidosis is a lethal complication of insulin-dependent diabetes mellitus, which can result from insulin therapy stoppage. This can occur voluntarily with suicidal intent or involuntarily due to treatment inaccessibility, forgotten injections, or material deficiency. A new possibility is investigated in our case study: hyperglycemia addiction. The patient was treated by insulin glargine and insulin aspartate. She regularly stopped insulin glargine injections seeking the asthenia sensation produced by hyperglycemia, keeping the insulin aspartate injections to treat the disabling symptom related to hyperketonemia.

Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses.

Hypothermia is defined as a core body temperature below 35°C and can be caused by environmental exposure, drug intoxication, metabolic or nervous system dysfunction. This lethal pathology with medico-legal implications is complex to diagnose because macroscopic and microscopic lesions observed at the autopsy and the histological analysis are suggestive but not pathognomonic. Postmortem biochemical explorations have been progressively developed through the study of several biomarkers to improve the diagnosis decision cluster. Here, we present an updated review with novel biomarkers (such as catecholamines O-methylated metabolites, thrombomodulin and the cardiac oxyhemoglobin ratio) as well as some propositional interpretative postmortem thresholds and, to the best of our knowledge, for the first time, we present the most adapted strategy of sampling and analyses to identify biomarkers of hypothermia. For our consideration, the most relevant identified biomarkers are urinary catecholamines and their O-methylated metabolites, urinary free cortisol, blood cortisol, as well as blood, vitreous humor and pericardial fluid for ketone bodies and blood free fatty acids. These biomarkers are increased in response either to cold-mediated stress or to bioenergetics ketogenesis crisis and significantly contribute to the diagnosis by exclusion of death by hypothermia.

Organ Procurement in Forensic Deaths: Specific Features of Nonheart-Beating Donors.

The need for organs has increased in the recent years, and this shortage will only worsen. In addition to the organs procured from brain-dead donors, a procedure for non-heart-beating donors was therefore developed. When deaths involve legal proceedings, the medical examiner makes the decision of whether or not to remove organs. To assist medical examiner in their decision-making, a number of forensic scientific societies aimed to develop recommendations, and legal adjustments were adopted. Nevertheless, these do present certain limits in special cases of procurement: Maastricht class I and II non-heart-beating donors. The peculiarity of this procedure stems from the urgency of the process. Compliance with temporal criteria would require that the deceased subject be removed from the crime scene even before the arrival of the authorities. This is extremely problematic legally and technically because forensic teams must collect evidence at crime scenes. Developments will have to be made to further minimize the restrictions on donations in forensic deaths.

The interest of using vitreous humor for γ-hydroxybutyrate (GHB) quantification in related fatalities: Stability evaluation, case report and literature review.

Analysis and interpretation of the findings for γ-hydroxybutyrate (GHB) in related fatalities remains problematic. Indeed, GHB is a naturally occurring compound present in both the mammalian central nervous system and peripheral tissue. Moreover, a postmortem increase in endogenous GHB concentration has been observed, especially in blood. Facing this issue, the use of an alternative matrix such as vitreous humor (VH) can thus be particularly interesting for GHB testing and quantification. VH is considered to be less prone to postmortem redistribution, is easy to collect, and has relatively few interfering compounds for the analytical process. In this context, the authors report the case of a GHB-related fatality involving 22-year-old male. In this case, GHB femoral blood (FB) (790 mg/L) and vitreous (750 mg/L) concentrations appeared similar with a FB to VH (FB/VH) ratio of 1.05. In addition, other similar cases with both GHB blood and vitreous concentrations were reviewed. Five cases were identified. The blood to VH ratios ranging from 0.13 to 2.58. Finally, GHB stability was documented in postmortem blood and VH, in order to address the reliability of VH as an alternative matrix for GHB quantitation at postmortem. GHB appeared relatively stable in postmortem blood specimens (at 50 mg/L) over a period of 28 days when stored at +4 °C or -20 °C. The same results were observed in VH specimens.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among sexual assault victims referred to three French clinical forensic units.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are the most common bacterial sexually transmitted infections (STIs) worldwide. These STIs are frequently asymptomatic, which often delays diagnosis and treatment with the risk of serious long-term complications. Current French recommendations call for targeted screening of populations considered to be at risk, including victims of sexual assault. However, no recent data on the prevalence of these STIs in this population are available in France. The aim of this study was therefore to determine the prevalence of CT/NG infections among victims of sexual assault attending three Clinical Forensic Units (CFUs). METHODS: We retrospectively reviewed the forensic records of patients aged over 12 years reporting a sexual assault and referred between January 1, 2020 and December 31, 2021 to the CFU of Montpellier, Angers or Saint-Denis de La Réunion. Patients who had been screened for CT and NG infections were included. RESULTS: 341 alleged victims of sexual assault (324 women, 17 men, median age = 23 years) were screened for CT/NG STIs during the inclusion period (Montpellier, n=196; Angers, n=63; Saint-Denis, n=82). The median time between the sexual assault and the examination was 1 day. CT and NG were detected in 28 patients (8.2 %) and 8 patients (2.3 %) respectively, with no men tested positive. Positive results concerned genital samples, except for two CT-positive anorectal samples and one NG-positive oropharyngeal sample. Two patients (0.6 %) were co-infected with CT/NG. The overall prevalence of CT/NG STIs was 10.0 % and was higher in the 18-24 age group, reaching 13.2 % for CT. CONCLUSIONS: This multicenter study confirms the high prevalence of CT/NG STIs in victims of sexual assault, and the vulnerability of the youngest age groups to these infections. Systematic screening for CT/NG STIs at the time of the forensic examination is the key to early diagnosis and effective treatment to prevent transmission and subsequent complications in these patients.

Sudden death due to black esophagus: a case report.

Black esophagus, also known as acute esophageal necrosis syndrome, is a rare but often fatal pathology. It can be identified during autopsy examination and should be diagnosed by the forensic examiner via simple macroscopic examination. We report the case of an elderly man who was found dead, presenting with this pathology. A microscopic examination was carried out that confirmed the diagnosis. We consider that all forensic examiners should be made aware of this pathology to make the diagnosis quickly, in turn allowing the deceased to be returned promptly to their loved ones.

Lethal self-administration of propofol and atracurium.

Acute propofol intoxications appear rare and remain primarily related to the acquisition of the material from the hospital. In this study, two cases of suicide following self-administration of a propofol-atracurium combination are presented as well as other propofol-related fatalities, in order to investigate propofol postmortem blood concentrations and circumstances surrounding death. The two case studies involved a 48-years-old male and a 61-year-old female, both anesthesiologists, who were found unresponsive with drugs (propofol, atracurium for both, and cisatracurium for one of them) discovered at the scene. Toxicological analyses were performed using validated chromatographic methods and highlighted the presence of propofol (1.0 µg/ml), laudanosine (0.2 µg/ml), paroxetine (3.4 µg/ml), and ethanol (12 mg/dl) for the first case and propofol (1.9 µg/ml), laudanosine (1.2 µg/ml), and hydroxyzine (0.03 µg/ml) for the second case. In the literature, 14 publications describing 27 cases of propofol-related lethal intoxications were identified. Except for two cases, all these fatalities involved healthcare professionals. Accidental overdose was the most frequently reported manner of death and the reported propofol blood concentrations ranged from 0.026 to 223.8 µg/ml. These cases, in agreement with other reported cases, highlight the concerns related to the misuse of hospital-based medicines, especially by health-care professionals, and so, the need for a much more stringent internal control of such drugs.

Difficulties interpreting concentrations in fatal cases: example of 2,5-dimethoxy-4-chloroamphetamine.

PURPOSE: Death related to the use of drugs is evident when drugs are detected in biological matrices within toxic levels, but sometimes it can be less obvious. Intoxications after 2,5-dimethoxy-4-chloroamphetamine (DOC) use are occurring but up to date, only one fatality has been reported. Here we present the case of a young woman admitted to hospital as she presented vomiting, convulsions and cardiorespiratory arrest. METHODS: Blood ethanol concentration was determined using gas chromatography with flame ionization detection and toxicological screenings (blood, gastric content and hair samples) were performed using liquid chromatography with diode array detection, gas chromatography or liquid chromatography with mass spectrometry detection. RESULTS: Her health state declined with cardiac troubles, organs failure and cerebral edema till death occurring 4 days later. The autopsy revealed the presence of hemorrhagic infiltration inside the left ventricle, pulmonary edema and hemorrhagic infiltration of the terminal ileum. The analysis of biological fluids confirmed the presence of DOC (< 10 ng/mL in cardiac blood sample), buprenorphine, cocaine and cannabis metabolites. The analysis of hair highlighted a history of drugs abuse. CONCLUSION: In the absence of evident identified cause, the hypothesis of a death due to acute drugs use within a history of chronic consumption of drugs has been put forward. The concentration of some substances such as new psychoactive substances can be low in biological matrices but the toxic effects can be additive and lead to death even within young people, hence the importance of the knowledge of consumption history.

Suicide by skull stab wounds: a case of drug-induced psychosis.

Suicide by stabbing to the head and/or driving sharp objects into the skull is of extreme rarity. This article reports the case of a 27-year-old man, who committed suicide by multiple knife stabs and cuts to the head, the torso, one shoulder and the forearms. Autopsy showed a perforating wound of the skull and the 10-cm long broken blade of the knife being still embedded in the right temporal lobe of the brain. The deceased had no history of psychiatric illness but was currently treated by mefloquine, a quinine derivative associated with a high rate of psychiatric adverse effects. Toxicological examination confirmed a recent intake of mefloquine together with chloroquine, another antimalarial drug. To our knowledge, this is the first report of a completed suicide with very strong evidence of mefloquine implication. Discussion focuses upon mefloquine-induced psychiatric disorders and highlights the importance of performing toxicological investigations in cases of unusual suicides.

Organ donation in France: legislation, epidemiology and ethical comments.

The Bioethics Laws revised in 2004 have defined rules concerning organ donation and transplantation. They have also permitted the creation of the French Biomedicine Agency which guarantees the right of enforcement. In France there are three situations in which organs may be harvested: from cadaveric donors, from living donors and, since 2005, from non heart beating donors. Organ harvesting from cadaveric donors is permissible if the deceased did not make known his refusal during his lifetime (this may be recorded in the national registry set up for this purpose). The rule of presumed consent also applies in the case of organs taken after cardiac arrest. With regard to organ harvesting from living persons, a panel of experts is required to give approval. The recipient's spouse, brothers or sisters, sons or daughters, grandparents, uncles or aunts and first cousins may be authorised to donate organs, as well as the spouse of the recipient's father or mother. The donor may be any person who provides proof of having lived with the recipient for at least two years. Some ethical questions will need to be resolved; for example the relevance of maintaining the EEG for brain death diagnosis, enforcement of the law on presumed consent, the real nature of the will of living donors and the definition of death.

Practitioner sex abuse: occurrence, prevention and disciplinary sanction.

Studies put forward figures for male practitioner sex abuse of around ten per cent. This practice, which is contrary to medical ethics, is highly reprehensible in ethical terms. The assaults range from uninvited meddling in patients' sexual lives to proven rape and inappropriate touching. The majority of this type of abuse is perpetrated by psychiatrists, but in more recent times a growing number of cases have been uncovered involving general practitioners or obstetric gynaecologists. For the most part, the abusers are men, aged between 45 and 64, who are insufficiently trained in terms of the 'practitioner-patient' relationship, or who are suffering from a mental pathology or who are in a situation of personal or professional crisis. Raising awareness of this issue is the driving force behind the implementation of prevention strategies, based on initial and ongoing training for practitioners in France, whistle-blowing on fellow practitioners in the United States and professional help in Canada. Disciplinary sanctions are more severe than those given within the framework of non-sexual misconduct in the United States. In France, the Order of Practitioners does not appear to be taking its role of defending patients seriously, since it seldom issues anything more substantial than minor penalties.

[Thanatobiochemistry: post mortem study of the vitreous humor for the diagnosis of diabetic ketoacidosis death]. / Biochimie thanatologique : intérêt de l'étude post mortem de l'humeur vitrée pour le diagnostic de décès par acidocétose diabétique.

Thanatobiochemistry refers to a post mortem study of biochemical parameters enabling to shed light on a cause of death. This discipline shines when suspected lethal pathology doesn't have any noticeable macroscopic or microscopic features such as diabetic ketoacidosis. We relate the case of fourty-five years old patient followed-up for type I diabetes mellitus, discovered dead at home, for which only post mortem biochemical exploration of vitreous humor allowed to determine the cause of death by diabetic ketoacidosis.

[Spectacular suicide associated with mefloquine]. / Suicide spectaculaire lié à une prise de méfloquine.

INTRODUCTION: We present a case in which suicide was a severe neuropsychiatric reaction to treatment with mefloquine. Physicians must be aware of these serious psychiatric complications and bear them in mind when faced with atypical behavior or suspected suicide. CASE REPORT: The body of a 27-year-old man was discovered at his home, covered with multiple knife wounds. The autopsy report concluded that death was due to a craniocerebral wound from a violent blow. Homicide was initially suspected. Suicide during acute psychosis associated with mefloquine was suggested, and toxicologic analyses confirmed this hypothesis. DISCUSSION: Serious neurologic and psychiatric adverse events associated with mefloquine (Lariam) have been reported since its introduction in 1985. Mefloquine prophylaxis is recommended for travelers to high-risk areas of chloroquine-resistant plasmodium falciparum. The risk of malarial infection and the proven efficacy of mefloquine to prevent malaria should be weighed against the risk of drug-associated adverse events. Physicians must nonetheless be aware of these serious psychiatric complications, especially when faced with atypical behavior and atypical suicides. The patient's' family and friends should be asked about a possible trips abroad that might have entailed antimalaria treatment, even several months earlier. Testing for mefloquine during toxicological examinations is then essential. The World Health Organization recommendations and contraindications must be followed in prescribing mefloquine.

Specific Characteristics of Injuries Inflicted by Claw Hammer.

Claw hammers have the specific characteristic of having two distinct ends: one a flat head of variable form, the other bifurcated. So the use of this tool as a blunt instrument will cause varying injuries. The authors present two clinical cases of assault with a claw hammer. Examinations revealed two types of wound. A first injury composed of integumentary lacerations and underlying bone injuries in terms of "shape" suggested the use of a blunt instrument. A second injury made up of damage showing two parallel wounds or two wounds located one in the extension of the other suggested the use of an object with a bifurcated end. The combination of both types of injury should alert examiners to the possibility of the use of a claw hammer in causing the injuries in order to help direct investigators in their investigations and in the search for the weapon used.

Organ procurement in forensic deaths: French developments.

Organ procurement and transplantation have grown steadily, and the need for organs will only rise in the future. Increasing the number of potential donors is therefore paramount. However, transplant coordination teams face refusals that can be linked to the contexts of the deaths, especially when they involve legal issues. In France, deaths involving legal proceedings are not uncommon (7-10%). In these cases, the prosecutor is immediately contacted, and makes the decision of whether to remove the involved organs. Refusals of this type represent 4% (approximately 30 cases per year) of obstacles to organ removals, and are governed by specific legislation. Thus, the prosecutor must arrange contact with a forensic pathologist and with the organ transplant teams to assemble all of the necessary elements for him to take the decision. To assist prosecutors in their decision making and to ensure them scientific rigour, the French Society of Forensic Medicine sought to develop a national recommendation to harmonise practices; it emerged in early 2013. The guideline makes practical recommendations, including among others: nominating local referents; writing regional protocols between judicial authorities, forensic pathologists and transplant teams; establishing terms for the forensic pathologist's intervention on the donor's body before and after a procurement. This recommendation by the French Society of Forensic Medicine aimed to combine two interests: addressing the shortage of organs, and fulfilling the requisites of a criminal investigation by standardising practices and encouraging communication.

Left Diaphragm Laceration Due to Cardiopulmonary Resuscitation.

External cardiac massage is the essential life-saving gesture for the management of any cardiac arrest. Since the 1960s, many recommendations have been published to improve the effectiveness of chest compressions alongside the development of automated systems intended to maximize the chances of survival. The use of these manual and/or instrumental techniques can cause secondary injuries, of which rib fractures are the most commonly observed by forensic pathologists. However, a comprehensive review of the literature seldom highlights reports of injuries to the abdomen, even less so to the diaphragm. In this observation, an iatrogenic left diaphragmatic laceration for the first time is described, as a result of manual and instrumental cardiopulmonary resuscitation, in a victim from an intrathoracic wound caused by a bladed weapon.