Uterus Transplantation: A Future Issue for the French Legislator?

Uterus transplantation (UT) is a surgical procedure that seeks to correct absolute uterine infertility. As such, it is coupled with assisted reproductive technologies (ART). Currently performed as an investigational procedure in France, this technique could be subject to a legal framework in the future. Given its specificities, the French legislator will need to state their position on several matters. Regarding the donor, they will need to determine whether the benefits for the infertile woman justify exposure of a living person to the risks of the removal procedure. If necessary, they will have full freedom to set the criteria for selecting the living donor based on age, the existence or not of past pregnancies or the nature of the donor-recipient relationship. On the other side, the conditions for becoming a recipient should be consistent with the existing rules for ART. Other considerations could include age and past pregnancies again. Lastly, the legislator will also need to address the possible desire for UT without the endpoint of pregnancy.

Carbofuran self-poisoning: forensic and analytic investigations in twins and literature review.

Carbofuran is a pesticide widely used in agricultural context to kill insects, mites, and flies by ingestion or contact. Along with literature review, we aimed to (i) present the clinical, autopsy, and toxicological findings of carbofuran self-poisonings in two 69-year-old twins, resulting in the death of one of them and (ii) assess carbofuran metabolite distribution using molecular networking. Quantitative analysis of carbofuran and its main metabolites (3-hydroxycarbofuran and 3-ketocarbofuran) was carried out using an original liquid chromatography-tandem mass spectrometry method on biological samples (cardiac or peripheral blood, urine, bile, and gastric contents). Toxicological analysis of post-mortem samples (twin 1) highlighted high concentrations of carbofuran and its metabolites in cardiac blood, bile, and gastric contents. These compounds were also quantified in blood and/or urine samples of the living brother (twin 2), confirming poisoning. Using molecular networking approach to facilitate visualization of mass spectrometry datasets and sample-to-sample comparisons, we detected two more metabolites (7-phenol-carbofuran and 3-hydroxycarbofuran glucuronide) in bile (twin 1) and urine (twin 2). These results highlight the value of (i) these compounds as carbofuran consumption markers and (ii) bile samples in post-mortem analysis to confirm poisoning. From an analytical point of view, molecular networking allowed the detection and interpretation of carbofuran metabolite ammonium adducts which helped to confirm their identification annotations, as well as their structural data. From a clinical point of view, the different outcomes between the two brothers are discussed. Overall, these cases provide novel information regarding the distribution of carbofuran and its metabolites in poisoning context.

[Health units in prisons]. / Les unités sanitaires en milieu pénitentiaire.

Since the publication of the law of 18 January 1994, health care for detainees has been entrusted to public health establishments, and no longer to the prison administration. This is a real step forward insofar as individuals placed in the hands of justice now benefit from care provided by health professionals, who officiate within health units in prisons. Today, these professionals work in particular to promote preventive and health promotion actions, thereby helping to restore the detainee's place as a subject with a view to reintegrating him or her into the community.

Alcohol and drug consumption among motor vehicle drivers in the Brittany region of France: A 9-year cross-sectional population study.

The primary objective of the present study was to evaluate the frequency of positive tests for alcohol and drugs during roadside testing or after road accidents among drivers in the Brittany region of France. The study's secondary objective was to describe the blood concentrations of the substances found during these tests, in order to provide a scientific basis for the establishment or modification of legislative threshold values for road injuries prevention. We performed a cross-sectional study of a database compiled by Rennes University Hospital's toxicology laboratory in the Brittany region of France between 2010 and 2018. Driver's age, sex, and test status (positive or negative), and blood levels of ethanol, 9-tetrahydrocannabinol (THC), methylene dioxymethamphetamine (MDMA), amphetamine, benzoylecgonine and 6-monoacetylmorphine (6-MAM) were collected. Twelve thousand four hundred and ninety-seven drivers (males: 86.1%; median (range) age: 29 (15-94)) have provided roadside blood samples, giving a total of 25,998 test results. Among the 10,996 drivers with at least one positive test, the median blood concentrations of ethanol, THC, MDMA, amphetamine, benzoylecgonine, and 6-MAM were respectively 1.82 g/L, 2.41 ng/mL, 138.4 ng/mL, 67.7 ng/mL, 173.3 ng/mL, and 0.97 ng/mL. 1159 (10.54%) of the 10,996 drivers tested positive for two or more substances, and 151 (1.4%) tested positive for three or more substances. With the exception of heroin, the currently recommended threshold values appear to be appropriate for road injuries prevention with regard to the concentrations observed in offenders.

Self-inflicted neck wounds under influence of lysergic acid diethylamide: A case report and literature review.

RATIONALE: Lysergic acid diethylamide (LSD) is a highly potent psychedelic drug derived from ergot alkaloids. The available literature data derived from controlled studies or usage in a medical setting seem reassuring; however the literature contains very rare cases of fatal self-inflicted injuries associated with LSD exposure. The behavioral disorder that created the conditions conducive to death is a maladaptive or irrational response to the psychiatric manifestations induced by the substance. PATIENT CONCERN: Here, we report the case of a 26-year-old man found dead with large neck wounds in a locked house. No medical history other than recreational use of alcohol and narcotics was reported as well as any history of psychotic disease. The entirety of the other investigations carried out did not demonstrate the presence of a third party at the place of death and a dropper bottle containing LSD was found near the body. DIAGNOSIS: We report the first case of fatal self-inflicted neck wounds with a cutting instrument in the context of acute exposure to LSD in a patient with no psychiatric history and without suicidal symptoms at the time of the self-aggressive act. INTERVENTION AND OUTCOMES: In the present work, we used a validated method using liquid chromatography coupled with mass spectrometry for simultaneous quantification of LSD and its metabolites (O-H-LSD and Nor-LSD) in whole blood and urine samples. LSD and O-H-LSD were respectively found at 1460 and 182 pg/mL in blood. In the urine, the concentrations of LSD, nor-LSD, O-H-LSD were, respectively, 3670, 201, and 4890 ng/L. LESSONS: This observation is particularly relevant in view of the resurgence of interest in the therapeutic use of LSD, notwithstanding the fact that the literature has not demonstrated a link between suicidal risk and acute or chronic exposure to LSD.

Non-oxidative ethanol metabolism in human hepatic cells in vitro: Involvement of uridine diphospho-glucuronosyltransferase 1A9 in ethylglucuronide production.

Ethanol is the most frequently psychoactive substance used in the world, leading to major public health problems with several millions of deaths attributed to alcohol consumption each year. Metabolism of ethanol occurs mainly in the liver via the predominant oxidative metabolism pathway involving phase I enzymes including alcohol dehydrogenases (ADH), cytochrome P450 (CYP) 2E1 and catalase. In a lesser extent, an alternative non-oxidative pathway also contributes to the metabolism of ethanol, which involves the uridine diphospho-glucuronosyltransferase (UGT) and sulfotransferase (SULT) phase II enzymes. Using liquid chromatography-high resolution mass spectrometry, ethylglucuronide (EtG) and ethylsulfate (EtS) produced respectively by UGT and SULT conjugation and detected in various biological samples are direct markers of alcohol consumption. We report herein the efficient non-oxidative metabolic pathway of ethanol in human differentiated HepaRG cells compared to primary human hepatocytes (HH). We showed dose- and time-dependent production of EtS and EtG after ethanol (25 or 50 mM) treatment in culture media of differentiated HepaRG cells and HH and a significant induction of CYP2E1 mRNA expression upon acute ethanol exposure in HepaRG cells. These differentiated hepatoma cells thus represent a suitable in vitro human liver cell model to explore ethanol metabolism and more particularly EtG and EtS production. In addition, using recombinant HepG2 cells expressing different UGT1A genes, we found that UGT1A9 was the major UGT involved in ethanol glucuronidation.

Fatal acetaminophen poisoning with hepatic microvesicular steatosis in a child after repeated administration of therapeutic doses.

Acetaminophen is the leading cause of acute liver failure worldwide following massive ingestion. We present here a fatal acute liver failure after repeated administration of four therapeutic doses of acetaminophen at 4-h intervals in a previously healthy 9-year-old female who presented dental pain after a facial trauma during sport practice. A diagnosis of paracetamol-induced hepatitis was deduced from the clinical picture of fulminant hepatitis and tubular necrosis, the encephalopathy with oedema and without signs of trauma. Liver biopsy showed typical acetaminophen-induced necrosis and a microvesicular steatosis in periportal hepatocytes. These injuries might have been favored by pre-existing mitochondrial dysfunction related, for instance, to a deficiency in an enzyme of the mitochondrial ß-oxidation pathway, or the respiratory chain. The observation of microvesicular steatosis in the periportal areas suggests an increased vulnerability via pre-existing mitochondrial dysfunction. As the liver status of patients is mostly unknown, the frequency of administration (every six hours) must be respected and the use of pharmaceutical forms allowing to adjust the dose as closely as possible to the child's weight should be promoted.

[Multidisciplinary meetings determining the imputability of xenobiotics in causes of death: What contribution to pharmacovigilance data?] / Réunions pluridisciplinaires déterminant l'imputabilité des xénobiotiques dans les causes de la mort : quel apport aux données de pharmacovigilance ?

PURPOSE: In case of xenobiotics induced toxic deaths analyzed at the university hospital of Rennes, a multidisplinary team of forensic analysts, toxicologists, anatomopathologists and pharmacologists assess xenobiotics' contribution to the death. METHODS: A death contribution score (SCRIM) is collectively established during meetings for each death involving xenobiotic drugs. Graded between 1 and 6, lower was this score, more certain was the imputability. Among deaths with the highest imputability, drug poisonings were isolated. RESULTS: Analysis of 266 deaths presented at meetings over the period 2010-2017 highlight a lot of drug medicine poisonings (60%). The main classes implicated are: opioid substitution treatments (24%) followed by anxiolytics (23%), antidepressants (16%), legal opioids (16%) and antipsychotics (14%). Analysis of these cases by Rennes regional pharmacovigilance center permits to obtain a qualitative signal by establishing a local overview of the main risk classes but also to highlight a specific signal, in particular for oxycodone and antihistamines. CONCLUSIONS: This multidisciplinary approach shows that a majority of toxic deaths are attributed to drugs. Mortality attributed to oxycodone and antihistamines is a specific signal that should be closely monitored.

Lung density measurement in postmortem computed tomography: a new tool to assess immediate neonatal breath in suspected neonaticides.

INTRO: Evidence of breath after birth is one of the main forensic issues in suspected neonaticide. Hydrostatic test (HT) and pathological examination are currently used to assess it, but they are not entirely reliable or immediately available. OBJECTIVE: To determine the performance of postmortem computed tomography (PMCT) to assess neonatal breath in suspected neonaticide, by comparing lung CT attenuation values between live birth and stillbirth cases, in correlation with HT and pathology. METHOD: Cases of suspected neonaticides who underwent a PMCT and complete forensic autopsy with an HT were retrospectively selected from the databases of four French Forensic Medicine Departments. The diagnosis of vitality (i.e., stillbirth or live birth) was based on the pathological examination and/or a combination of arguments, including HT result. Lung density on CT was measured in Hounsfield units (HU) by ROIs drawn in both pulmonary parenchymas. RESULTS: Eleven patients were included, six live birth and five stillbirth cases. The result of HT was concordant with pathological examination when available (seven cases). Mean lung densities in live birth cases (- 173 HU [- 255; - 91 CI 95%]) were significantly lower than in stillbirth cases (40 HU [28; 52 CI 95%]) (p < 0.05), with a very high degree of interobserver reproducibility (ICC = 0.998 (CI 95% 0.991-0.999; p < 0.001). CONCLUSION: PMCT and especially lung CT attenuation measurement is a reliable and easy-to-use method for assessing neonatal breath in suspected neonaticides.

A case of fatal acebutolol poisoning: an illustration of the potential of molecular networking.

Acebutolol is a ß1-selective adrenergic receptor antagonist with moderate membrane-stabilizing activity and intrinsic sympathomimetic activity; accordingly, the drug is indicated in hypertension, angina pectoris, and arrhythmia. However, acebutolol's beta-blocking properties also extend the QRS and QTc intervals, and may predispose the patient to ventricular tachydysrhythmia. Here, we report autopsy and toxicological findings on a fatal case of acebutolol self-poisoning in a 70-year-old woman. Toxicological analyses of post-mortem samples (using a liquid chromatography high-resolution mass spectrometry (LC-HR-MS) method) highlighted high concentrations of acebutolol and its metabolite diacetolol in femoral blood (92.8 mg/L and 21.2 mg/L, respectively) and other matrices (cardiac blood, urine, bile, and gastric contents). A molecular networking approach provided useful information on acebutolol's metabolism and revealed the existence of an unknown phase II metabolite of acebutolol. Molecular networking also facilitated visualization of the complex LC-HR-MS/MS datasets and the sample-to-sample comparisons that confirmed massive acebutolol intoxication by ingestion.

Correction to: A case of fatal acebutolol poisoning: an illustration of the potential of molecular networking.

The published version of this article unfortunately contained a mistake. In Figure 1 on the molecular network of acebutololol, two molecular structures are not displayed ("acebutolol glucuronide "and "impurity J"). The Figure is corrected here.

Intoxication with 3-MeO-PCP alone: A case report and literature review.

RATIONALE: 3-Methoxyphencyclidine (3-MeO-PCP) is a new psychoactive substance derived from phencyclidine. Although it can lead to severe intoxications, the main manifestations and optimal management have not been well characterized. Here, we report 2 cases of 3-MeO-PCP intoxication in the same patient, and summarize the manifestations of this intoxication reported in literature. PATIENT CONCERNS: A 17-year-old male purchased a bag of 3-MeO-PCP on the Internet but took an oral dose (200 mg) that corresponds to the less active isomer 4-MeO-PCP. He developed high blood pressure (158/131 mm Hg), tachycardia (100 bpm), and neurological manifestations (confusion, hypertonia, nystagmus, and then agitation). A maculopapular rash appeared, although this may have been related to the administration of midazolam. Hyperlactatemia (2.6 mmol/L) was the main laboratory finding. Seven days later, he returned to the emergency department after sniffing 50 mg of 3-MeO-PCP. High blood pressure, tachycardia, and neurological manifestations (psychomotor impairment and dysarthria) were present but less severe than after the first intoxication. DIAGNOSIS: In the first intoxication, the blood and urine 3-MeO-PCP concentrations were, respectively, 71.1 ng/mL and 706.9 ng/mL. Conventional toxicity tests were all negative. In the second intoxication, biological samples were not available. INTERVENTIONS: In the first intoxication, treatment consisted of intravenous hydration and midazolam. The patient was transferred to an intensive care unit for monitoring. After the second intoxication, he was monitored for 12 hours. OUTCOMES: The patient's condition improved quickly in both cases. LESSONS: These cases provide additional information on the manifestations of 3-MeO-PCP intoxication. These manifestations are mainly cardiovascular (high blood pressure, tachycardia) and neurological. The fact that second (50 mg) intoxication was less severe than the first (200 mg) is suggestive of a dose-effect relationship for 3-MeO-PCP. The first case also emphasizes the risk of dosing errors caused by the similarity between the names "3-MeO-PCP" and "4-MeO-PCP."

Scientific Uncertainty in Courts. A France-Germany Comparative Perspective on Litigation surrounding Hepatitis B Vaccination.

Litigation concerning hepatitis B vaccination provides a good illustration of the difficulties courts encounter when deciding on compensation claims in which scientific uncertainty, whether real or perceived, is present. Despite the difference in approach to vaccination - an obligation in France and a recommendation in Germany -, their vaccine coverage is comparable, as are their regimes of compensation for damage attributed to vaccination, whether on the basis of producer liability or national solidarity. Confronted with scientific uncertainty, German and French courts choose to make use of presumptions to establish legal causality that is not contingent on scientific causality. German and French case law diverge however, with regard to their relationship to scientific criteria of causality, the volume of court cases, and consideration of claims, highlighting what seems to be a distinctive situation in France.

Death related to consumption of Rauvolfia sp. powder mislabeled as Tabernanthe iboga.

Powdered roots of iboga (Tabernanthe iboga) contain ibogaine, an alkaloid that has been used to treat addictions. We report the case of a 30-year-old woman who died after ingesting a powder labeled as Tabernanthe iboga she had bought online. Analysis of the powder revealed the absence of ibogaine but the presence of toxic alkaloids (ajmaline, yohimbine and reserpine) found in Rauvolfia sp. plant species. An original and specific LC-MS/MS method developed to quantify ajmaline, yohimbine and reserpine showed respective concentrations of 109.1ng/mL, 98.2ng/mL and 30.8ng/mL in blood, and 1528.2ng/mL, 914.2ng/mL and 561.2ng/mL in bile. Moreover, systematic toxicological analyses of biological samples showed the presence of oxazepam at therapeutic concentration and cannabinoids. Death could be attributed to ingestion of a substantial quantity of crushed roots of Rauvolfia in association with concomitant drug withdrawal.

Suicide by self-injection of chlormequat trademark C5SUN(®).

Chlormequat is a quaternary ammonium used as plant growth regulating agent. We report here the first suicide case involving a 45 year-old farmer man who intentionally self-injected C5SUN(®), containing chlormequat and choline. An original liquid chromatography high resolution mass spectrometry method (LC-HR-MS), using a hybrid quadrupole-orbitrap mass spectrometer, was developed for qualitative and quantitative analysis of chlormequat in different biological matrices. Toxicological analyses of post-mortem samples highlighted the presence of chlormequat in the blood (2.25mg/L) and the urine (4.45mg/L), in addition to ethanol impregnation blood (1.15g/L). The route of administration (subcutaneous injection) was confirmed by the detection of chlormequat in the abdominal fat sample (chlormequat: 10.04mg/g) taken from the traumatic injury location, as well as in the syringe found at the death scene, close to the victim's body. Based on the results of these post-mortem investigations, the cause of death was determined to be consecutive to cardiac dysrhythmia and cardiac arrest following chlormequat self-injection.

LEGAL AND ORGANIZATIONAL BARRIERS TO THE DEVELOPMENT OF eHEALTH IN FRANCE.

Although the potential of eHealth in terms of improving quality, safety, efficacy and efficiency of health systems is known, the development of these new tools remains insufficient in Europe and also in France - the focus of the present article - due to the legal status of telemedicine and state involvement. National legislation should be harmonized by directives or standardized by regulations. European unification would considerably reduce the burden of administrative formalities that hold back telemedicine in France, and would lead to the emergence of community-based, non-hospital-dependent eHealth projects, in line with recommendations in the literature. The creation of cooperation protocols and the formal recognition of the patient's role via therapeutic education are valuable tools for achieving this goal. It would be an error to dismiss these tools because of the overly rigid regulations, especially now that financial incentives are shifting from cure to care.

[Medical certificates and the new firearm regulation in France]. / Certificats médicaux et nouvelle réglementation des armes à feu en France.

France has adopted a new firearms regulation. Firearms are now classified into four categories (A, B, C, and D). The administrative procedure for acquisition and possession of firearms of categories B and C requires medical advice. The medical certificate must be dated less than a month, and detail a state of health compatible with the acquisition and possession of a firearm. There are no guidelines mentioning the conditions that can lead to incompatibility. Compatibility does not apply to the handling and use of the firearm. If the applicant is undergoing or has undergone treatment in a psychiatric institution, he must also produce a medical certificate issued by a psychiatrist. The hunting license application requires a medical certificate mentioning a state of physical and mental health compatible with the possession of a firearm. Its validity is acquired for life. The practice of shooting sports or skeet requires an annual medical certificate of non-cons in reference to the rules of sports federations.

Tufted angioma with Kasabach-Merritt syndrome mistaken for child abuse.

We report the case of a 2-month-old infant with a single apparently ecchymotic lesion on the shoulder that raised suspicions of abuse. The medicolegal examination concluded that the appearance of the lesion was only mildly suggestive of an ecchymosis. A second, temporally remote examination confirmed this doubt. The evolution of the lesion, notably an increase in its volume, allowed us to rule out a traumatic lesion and was suggestive of a vascular tumor. The histological type of the tumor was a tufted angioma. There was thrombocytopenia and consumptive coagulopathy. All these data confirmed the diagnosis of Kasabach-Merritt syndrome. In contrast to benign infantile hemangiomas, which are frequent and well-known in clinical practice, vascular tumors complicated by Kasabach-Merritt syndrome are rare. They deserve to be widely known because they mandate rapid medical management and because they are one of the only differential diagnoses of ecchymosis, especially in children. When there is doubt about the traumatic nature of a cutaneous lesion, a temporally remote examination is essential. The evolution of the lesion may then suggest a dermatologic origin.

Whole-body post-mortem computed tomography compared with autopsy in the investigation of unexpected death in infants and children.

OBJECTIVES: To investigate the contribution of whole-body post-mortem computed tomography (PMCT) in sudden unexpected death in infants and children. METHODS: Forty-seven cases of sudden unexpected death in children investigated with radiographic skeletal survey, whole-body PMCT and autopsy were enrolled. For imaging interpretation, non-specific post-mortem modifications and abnormal findings related to the presumed cause of death were considered separately. All findings were correlated with autopsy findings. RESULTS: There were 31 boys and 16 girls. Of these, 44 children (93.6 %) were younger than 2 years. The cause of death was found at autopsy in 18 cases (38.3 %), with 4 confirmed as child abuse, 12 as infectious diseases, 1 as metabolic disease and 1 as bowel volvulus. PMCT results were in accordance with autopsy in all but three of these 18 cases. Death remains unexplained in 29 cases (61.7 %) and was correlated with no abnormal findings on PMCT in 27 cases. Major discrepancies between PMCT and autopsy findings concerned pulmonary analysis. CONCLUSIONS: Whole-body PMCT may detect relevant findings that can help to explain sudden unexpected death and is essential for detecting non-accidental injuries. We found broad concordance between autopsy and PMCT, except in a few cases of pneumonia. It is a non-invasive technique acceptable to relatives. KEY POINTS: • Whole-body post-mortem computed tomography (PMCT) is an effective non-invasive method. • Whole-body PMCT is essential for detecting child abuse in unexpected death. • There is concordance on cause of death between PMCT and autopsy. • Whole-body PMCT could improve autopsy through dissection and sampling guidance. • PMCT shows findings that may be relevant when parents reject autopsy.