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Objectifs En 2019, Salomone et al. [1] publiaient que la 4-anilino N-phenethyl-piperidine (4-ANPP), precurseur et metabolite de nombreux derives du fentanyl pouvait servir de marqueur d’exposition dans les cheveux a cette classe de molecules ultra-actives. Dans le cadre d’une intoxication fatale au fentanyl, les auteurs ont voulu verifier que la 4-ANPP pouvait egalement etre retrouvee dans d’autres matrices biologiques d’interet medicojudiciaire. En France et plus generalement en Europe, le fentanyl est moins frequemment responsable de deces qu’aux Etats-Unis et est principalement utilise comme analgesique chez les patients cancereux. Son usage detourne est surtout limite au personnel hospitalier, mais peut s’observer par diversion de patchs (Durogesic). Pour echapper aux regulations legales, le fentanyl fait partie des molecules les plus copiees et l’on retrouve, dans la grande famille des nouvelles substances psychoactives (NPS), plus d’une cinquantaine d’analogues, dont le carfentanil, le furanylfentanil ou encore l’ocfentanil. Face a cette proliferation et a la quasi-impossibilite pour un laboratoire de disposer de tous les standards de reference, la recherche ciblee de 4-ANPP semble etre un excellent moyen de depistage pour cette classe d’opioides. Methode Un homme de 36 ans est retrouve decede a son domicile, malgre l’intervention des services de secours. D’apres les temoins, l’individu aurait pu utiliser un patch de fentanyl en l’appliquant sous la langue. Il etait connu comme consommateur de produits stupefiants. Aucune cause traumatique de mort n’a pu etre constatee lors de l’autopsie et le Procureur de la Republique a requis une expertise toxicologique de reference a partir des prelevements classiques (sang femoral, sang cardiaque, urine, bile, contenu gastrique, cheveux noirs, de 4–5 cm, en vrac). Une methode analytique par UHPLC-MS/MS (Xevo TQD) permettant de doser le fentanyl et son metabolite primaire, le norfentanyl et d’identifier la 4-ANPP a ete utilisee. Tous les echantillons ont ete analyses apres une extraction par un melange ether diethylique/dichloromethane/hexane/alcool isoamylique (50/30/20/0,5) a pH 9,5, en presence de fentanyl-D5 et de norfentanyl-D5. Chaque compose a ete identifie par 2 transitions ioniques, dont m/z 281 > 188 et 281 > 105 pour le 4-ANPP. Seul le fentanyl et le norfentanyl ont ete quantifies, la caracterisation de la 4-ANPP etant uniquement qualitative au laboratoire (usage pour criblage). Resultats Le fentanyl a ete dose a 44 ng/mL dans le sang cardiaque et a 30 ng/mL dans le sang femoral, ce qui tend a demontrer une possible redistribution post-mortem avec un ratio de 1,5, la litterature retenant 1,6. Le norfentanyl est a 2 ng/mL dans les 2 echantillons de sang. On retrouve egalement le fentanyl et le norfentanyl dans les autres echantillons : urine (20 et 2 ng/mL), bile (112 et 10 ng/mL), contenu gastrique (101 et 1 ng/mL) et enfin cheveux (652 et 92 pg/mg). La 4-ANPP a ete retrouvee dans toutes les matrices biologiques et se revele donc etre un marqueur essentiel pour mettre en evidence une consommation de derives du fentanyl. Conclusion Les concentrations de fentanyl sont tres superieures aux concentrations therapeutiques usuelles et sont potentiellement letales par depression respiratoire, chez un sujet consommateur regulier de cette molecule. A ce jour, la police n’a pas identifiee la source du stupefiant. Les faibles concentrations de norfentanyl sont en faveur d’un deces rapide apres la consommation. Retrouvee dans toutes les matrices biologiques, la 4-ANPP confirme son statut de marqueur d’exposition aux derives du fentanyl. Quelques observations complementaires du laboratoire sur d’autres derives du fentanyl ont confirme cette approche, le concept etant qu’un criblage positif de la 4-ANPP donne lieu a des investigations tres poussees pour identifier la source.

Fire death investigations attempt to determine whether a subject was alive or dead before the fire started. Therefore, it is essential to assess if the bone damage is traumatic or the result of exposure to heat. This observational study aims to expose the specific CT semiology of thermal bone lesions to allow the forensic radiologist to identify and distinguish them from traumatic lesions that would have preceded death. We retrospectively reviewed the CT findings of 25 bodies with thermal bone lesions for which a postmortem computed tomography (PMCT) was performed prior to an autopsy. Imaging findings were correlated to the autopsy data to identify the specific features of thermal bone lesions. Specific signs of thermal injuries to bone were identified on PMCT on all deceased cases. Thermal damages predominated in areas directly exposed to flames (rib cage, distal extremities) with less soft tissue coverage (“soft tissue shielding”). The mottled appearance of bone marrow was a constant sign of burned bones. Heat fractures such as trans-diploic fractures of flat bones and beveled (“flute-mouthpiece”) fractures of extremities seemed specifically related to thermal mechanism. In addition, we provided a better description of superficial cortical fissures of flat bones (“ancient Chinese porcelain”) and observed a “stair step” fracture of a long bone until now undescribed in radiological literature. Thermal bone lesions have specific CT findings, different on several points from traumatic injuries. Their knowledge is essential for radiologists and forensic physicians to provide an accurate report of injury and conclusions.

Self-reflection is an essential component of developing cultural competence. However, there is a paucity of research on how to best accomplish cultural self-reflection in CSD courses. Therefore, the purpose of this research study is to examine the teaching and learning practice of using Photovoice as a means of cultural self-reflection in a foundational, multicultural course in CSD.This qualitative investigation employed a phenomenological approach with emphasis on the scholarship of teaching and learning. Data gathering involved completion of a Photovoice assignment and a prompted reflection of the assignment. The Photovoice assignment entailed the students reflecting and examining their culture. Then, the students submitted two photographs, one that represents a strength of a culture they identify with and one that represents a challenge of a culture they identify with. The students presented their cultural strength and challenges in small and large group discussions. The prompted reflection required the students to address questions in a written or video-recorded response. When the course was completed, the researcher commenced line-by-line focused coding to cluster frequently used terms and common experiences into specific themes.The student participants shared photos of cultural strengths and challenges, discussed these photos in small and large groups, and completed a prompted reflection of the Photovoice assignment. While each student's project and reflection were unique, common themes prevailed. The themes of safety, privilege, and mental health emerged from the Photovoice projects and the themes of learning and formating arose from the reflections on use of the project toward cultural competence.The results of this study suggests that Photovoice is a valuable tool for cultural self-reflection and learning in all courses in CSD programs. In this way cultural self-reflection and the progression toward cultural competence is an on-going process where students are better prepared to provide client-centered, culturally competent care for all people.

Long QT syndrome is one of the most common hereditary channelopathies inducing fatal arrhythmias and sudden cardiac death. We identified in a sudden arrhythmic death syndrome case a C-term KCNH2 mutation (c.3457C &gt, T, p.His1153Tyr) classified as variant of unknown significance and functional impact. Heterologous expression in HEK293 cells combined with western-blot, flow-cytometry, immunocytochemical and microscope analyses shows no modification of channel trafficking to the cell membrane. Electrophysiological studies reveal that the mutation causes a loss of HERG channel function through an alteration of channel biophysical properties that reduces the current density leading to LQT2. These results provide the first functional evidence for H1153Y-KCNH2 mutation-induced abnormal channel properties. They concur with previous biophysical and clinical presentations of a survived patient with another variant that is G1036D. Therefore, the present report importantly highlights the potential severity of variants that may have useful implications for treatment, surveillance, and follow-up of LQT2 patients

Long QT syndrome is one of the most common hereditary channelopathies inducing fatal arrhythmias and sudden cardiac death. We identified in a sudden arrhythmic death syndrome case a C-term KCNH2 mutation (c.3457C > T; p.His1153Tyr) classified as variant of unknown significance and functional impact. Heterologous expression in HEK293 cells combined with western-blot, flow-cytometry, immunocytochemical and microscope analyses shows no modification of channel trafficking to the cell membrane. Electrophysiological studies reveal that the mutation causes a loss of HERG channel function through an alteration of channel biophysical properties that reduces the current density leading to LQT2. These results provide the first functional evidence for H1153Y-KCNH2 mutation-induced abnormal channel properties. They concur with previous biophysical and clinical presentations of a survived patient with another variant that is G1036D. Therefore, the present report importantly highlights the potential severity of variants that may have useful implications for treatment, surveillance, and follow-up of LQT2 patients.

Summary We report the case of a patient who died after falling on the antenna of a radio receiver that was stood on the floor. External examination showed an orificial contuse wound, less than a centimetre in diameter, on the right upper eyelid. There was no ocular lesion. Full-body CT (computed tomography) scan imagery revealed a fracture of the roof of the right orbit and diffuse intra and pericerebral haemorrhages. Those haemorrhages had caused the death of the patient. Penetrating transorbital traumas represent a very small part of cranial traumas and orbital pathologies. They are usually linked to the high-velocity traumas associated with traffic accidents or penetration by firearm projectiles. Low-energy penetrating transorbital traumas are even less frequent; associated prognoses are rarely lethal and generally functional. These traumas cause minimal palpebral or periocular wounds that can seem insignificant upon external forensic examination, especially when the foreign body involved is fully intracranial or absent. Performing a cerebral scan, or even post-mortem angiography, thus appears to be a key-procedure, very useful to the medical examiner.

Hair analysis is very useful for toxicological investigations since, by providing a wider detection window, it gives the possibility to perform a retrospective study on the historical consumption of a substance. Unfortunately, there are no data available for hair concentrations in metformin-related deaths. In this study, the authors present 2 cases of fatal metformin intoxication in which, for the first time, hair analysis was performed using a specific GC–MS/MS method. Metformin was tested positive in femoral blood (112.3 mg/L and 64.7 mg/L respectively) and cardiac blood (226.9 and 203.2 mg/L) of the two subjects. For case 1, other samples were also tested positive, including vitreous humor (31.1 mg/L) and gastric contents (773.5 mg/L). In case 2, metformin was measured at 844.9 mg/L in urine. Metformin hair concentrations were 28.3–44.8 and 22.5 ng/mg for both cases, respectively. The concentrations found in the 2 fatal cases are clearly higher than those obtained in a previous study with subjects under treatment (0.3–3.8 ng/mg) or those found in 3 post-mortem cases where metformin death was excluded (0.6–1.4 ng/mg). Excessive sweating during the agonal phase due to fatal hypoglycemia could explain these elevated concentrations as sweat can have contaminated the hair.

The discovery of exogenous particles in the broncho-pulmonary tree is frequently described in forensic literature, especially in lung samples, in the context of aspirated gastric content during the death agony period or during resuscitation. We report an original observation of a multi-visceral dispersion of exogenous particles detected, in an 8-year-old boy, who allegedly fell from a 2-m high brick-wall. The autopsy found major liver fracture and diaphragm rupture with massive internal hemorrhage without gastric wall rupture. The histological analyses have identified round to oval bodies in the lung bronchi, alveoli, and, rarely, in vascular sections, and also on the surface of several samples. These particles stained strongly pink by the periodic acid Schiff method, evoking dried vegetables. Two hypotheses were invoked: aspirated vegetable particles into the bronchial tree or parasitic infection, like pinworm larva. In order to characterize the nature of these particles, different legumes were cooked, embedded in paraffin wax, and examined under light microscope. Simultaneously, morphological comparison between the gastric content and pinworm larva and lentils was made and a PCR analysis was performed on gastric fluid sample. The DNA sequencing showed a Fabaceae plant family, Lens culinaris. The possibility of a hematogenous dissemination of the starch grains during a perimortem aspiration of gastric content seems unlikely, and a contamination from the gastric content of the organs samples during the autopsy or the pathologic macroscopic and microscopic processes seems to be the principal hypothesis. The formal identification of such particles is important to avoid the misdiagnosis of a potential parasitic infection. The risk of confusion can be detrimental in some circumstances.

Summary Gabapentin, a GABA analogue, is a drug with anticonvulsant properties, used to treat epilepsy in adults and to relieve pain in patients suffering from postherpetic neuralgia. The usual oral daily dose is 300-1800 mg, but may be increased to a maximum of 3600 mg in 1-3 divided doses. The most reported adverse effects of gabapentin are somnolence, dizziness, ataxia, fatigue and impaired vision. The drug is often associated with opiates in the addict population. A 58-year-old man was found dead at his home. He was treated by gabapentin since 3 years for major neuropathic pain and a depressive syndrome. Body examination did not reveal traumatic injury. Following an initial screening of peripheral blood, all the biological specimens collected during autopsy were analysed, using a dedicated liquid chromatography-tandem mass spectrometry method for gabapentin. Analyses revealed intoxication with gabapentin, including cardiac blood concentration at 33800 μg/L, peripheral blood at 42800 μg/L and urine at 854200 μg/L. Hair (2 cm, brown) tested positive at 421 pg/mg. The toxicological significance of the measured concentration was difficult to establish because of the limited identification of gabapentin in human hair. These results appear to be compatible with an overdose of gabapentin and the pathologist attributed the death to a fatal intoxication.

Resume Les patchs Durogesic® sont une bonne alternative pour les patients tolerants aux opioides qui ne peuvent pas prendre des antalgiques par voie orale. Malheureusement, ces patchs sont aussi detournes par les consommateurs de produits stupefiants et utilises comme source massive de fentanyl pour son effet euphorisant. Ils sont souvent consommes en association avec l’alcool et des medicaments psychotropes. Dans ce but, les usagers souvent ignorent la voie d’administration la plus pertinente permettant d’atteindre une plus forte concentration sanguine. Les auteurs rapportent un cas de surdosage au fentanyl, impliquant un patch Durogesic® 100 μg/h trouve dans la bouche de la victime. Le deces est tres probablement survenu suite a une depression respiratoire associant le fentanyl et d’autres psychotropes. L’alcoolemie de la victime etait nulle. L’analyse du sang peripherique a montre une concentration potentiellement letale de fentanyl de 32,9 ng/mL, un usage de cocaine (la benzoylecgonine, metabolite principal est a 342 ng/mL), des concentrations therapeutiques de diazepam (185 ng/mL) et de cyamemazine (43 ng/mL) ainsi qu’une concentration infra-therapeutique de tramadol (44 ng/mL). Une revue de la litterature relative au deces impliquant les patchs transdermiques au fentanyl a confirme le caractere peu frequent de la mastication de cette forme galenique.

Resume Le rocuronium est un curare non depolarisant de la famille des aminosteroides, utilise pour bloquer le passage de l’information neuronale et empecher l’activite musculaire lors d’une anesthesie. Son bref delai d’action, environ 90 secondes, en fait un excellent myorelaxant pour l’intubation des patients. Le rocuronium possede un bon index de securite mais comme tout curare, il est sujet a des accidents therapeutiques, de type choc anaphylactique. En 2016, l’incidence de l’anaphylaxie a ete evaluee en France entre 1:3500 et 1:20 000 anesthesies, responsable d’un deces sur 100 000 interventions. Ces accidents sont non dose-dependants, et le rocuronium apparait comme le curare le plus implique. Nous rapportons le cas d’un homme de 44 ans, hospitalise pour la mise en place d’un bypass gastrique. Dans les suites immediates de l’induction anesthesique avec utilisation de rocuronium, le patient a presente une eruption cutanee, un bronchospasme, suivis d’un arret cardio-respiratoire. Apres 24 heures d’hospitalisation dans le service de reanimation medical, le sujet est decede suite a une defaillance multiviscerale. L’examen externe du corps et l’autopsie medicolegale n’ont pas permis de mettre en evidence la presence de lesion traumatique suspecte, a l’exclusion de stigmates de reanimation, et d’une intense congestion multiviscerale. Les investigations toxicologiques initiales sont sans particularite : alcoolemie nulle, cyanures inferieurs a 80 ng/mL, carboxyhemoglobine a 1,9 %, absence de substances volatiles et pas de stupefiant. Le criblage medicamenteux a mis en evidence la presence de midazolam dose a 356 ng/mL dans le sang peripherique et d’un antibiotique, la levofloxacine (non dosee). A ce stade, le rocuronium, pourtant utilise lors de l’induction anesthesique, n’a pas ete identifie. Une methode specifique a ete developpee par chromatographie liquide ultra performance couplee a la spectrometrie de masse en tandem apres extraction liquide–liquide a pH = 5,4 et appariement d’ions par iodure de potassium. Cette methode a permis l’identification et la quantification du rocuronium dans le sang peripherique a 325 ng/mL et dans la bile a 2219 ng/mL. La presence seule du rocuronium, meme a concentration infra-therapeutique, permet de confirmer l’origine du choc anaphylactique, en accord avec les conclusions thanatologiques et anatomopathologiques.

Resume Le raisonnement clinique est au cœur de la competence des professionnels de sante. L’etape diagnostique est notamment consideree comme cruciale dans la pratique medicale. Pour les superviseurs, il est donc necessaire de pouvoir identifier la demarche diagnostique des etudiants en medecine et de les accompagner dans le developpement de leur raisonnement. La methode SNAPPS, acronyme anglais correspondant aux premieres lettres des six etapes structurant la presentation de cas clinique (Summarize, Narrow, Analyse, Probe, Plan, Select), est une approche centree sur l’apprenant, qui est destinee a structurer la presentation de cas de patients par les etudiants, a faciliter l’expression de leur demarche diagnostique et a les aider a exprimer leur incertitude diagnostique, en respectant les contraintes de temps inherentes a l’activite des cliniciens. L’efficacite de la methode quant a sa capacite a explorer le raisonnement des etudiants en medecine et leur incertitude, et a promouvoir l’apprentissage autodirige a ete demontree par plusieurs travaux. Cette methode s’applique a toutes les specialites, a la fois en milieu liberal et hospitalier. Nous l’avons experimentee avec des etudiants de cinquieme et sixieme annee de medecine, en stage a l’institut de medecine legale de Strasbourg. La methode a ete utilisee dans le cadre des activites de supervision des autopsies, des examens de victimes et des expertises judiciaires. Elle a ete jugee tres utile par les etudiants qui plebiscitent son utilisation dans d’autres stages cliniques.

Resume Les fractures de l’os hyoide s’observent le plus souvent lors d’une pression directe appliquee au niveau de la region cervicale au cours de manœuvres de strangulation (manuelle ou au lien) ou par pendaison. La decouverte de ce type de fracture chez un individu victime d’un traumatisme a haute energie cinetique lors d’une collision ou d’un franchissement par un vehicule automobile souleve, dans certains cas, l’interrogation suivante : la fracture de l’os hyoide peut-elle etre secondaire au polytraumatisme ou a-t-elle ete provoquee par une strangulation ayant precede le polytraumatisme dans un contexte d’homicide maquille en accident ? Les auteurs illustrent cette situation a travers l’expose d’un cas clinique original d’un individu ayant ete franchi par un vehicule automobile et presentant un polytraumatisme gravissime comportant notamment un fracas comminutif de la boite crânienne et du massif facial ainsi qu’un traumatisme thoraco-abdominal. La dissection soigneuse de la region cervicale retrouvait une fracture ecchymotique de la grande corne gauche et une dislocation de la grande corne droite de l’os hyoide associee a une fracture de la mandibule et a une infiltration ecchymotique du muscle sterno-cleido-mastoidien gauche. Apres confrontation des donnees de l’autopsie, des examens complementaires et des donnees de l’enquete avec les donnees bibliographiques, les auteurs discuteront des mecanismes de la fracture de l’os hyoide dont decoulent les causes de la mort.

The abuse of new psychoactive substances (NPS) has been dramatically increasing all around the world since the late 2000s. The availability of hundreds of NPS in the past decade is challenging for both public health and global drug policies. A 39-year-old woman, known as a multidrug addict, was murdered by her partner by ligature strangulation. A comprehensive toxicological screening by gas chromatography and ultra-high performance liquid chromatography with tandem mass spectrometry revealed the simultaneous presence of ethanol (1.37 g/L), diazepam (157 ng/mL) and nordiazepam (204 ng/mL), cocaine (25 ng/mL) and benzoylecgonine (544 ng/mL), and (3-methoxy-(1-(1-phenylcyclohexyl)piperidine) or 3-MeO-PCP, a dissociative hallucinogen anesthetic drug. Concentrations of 3-MeO-PCP were 63, 64, and 94 ng/mL in femoral blood, bile, and urine, respectively. Hair tested also positive for 3-MeO-PCP on 3 × 2-cm segments at 731, 893, and 846 pg/mg, indicating long-term abuse of the drug. This seems to be the first ever reported hair concentrations. Major impairment of the victim, including visual hallucinations and alteration of behavior, was attributed to the mixture of all the drugs, with a major contribution of 3-MeO-PCP. The toxicological findings were compared to the few reports available in the medical literature.

Background The abuse of new psychoactive substances or NPS has been dramatically increasing all around the world since the last half of the year 2000 and has become a serious public health problem. NPS are a challenge for the worldwide forensic community due to the difficulties to accurately document the cases. The N-benzylmethoxy (NBOMe) group is a new class of hallucinogenic designer drugs and has gained importance in recent years. 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)- methyl]ethanamine) is an analog of the 2C series of psychedelic phenethylamine drugs that contain an N-methoxybenzyl substituent, which significantly affects their pharmacological activities. It is a potent agonist of 5-HTA receptors and a severe hallucinogenic drug, with numerous irreversible psychedelic effects which can last from 5 to 10 hours. It is consumed most often in the form of drops or blotters by the transmucosal, sublingual or intranasal routes. The active dosage is very low, supposed to be less than 100 µg. The literature is poor in reporting cases where 25I-NBOMe was identified. Only very few clinical cases of over dosages were published, suggesting a low prevalence of this compound. Methods We present a retrospective demonstration of 25I-NBOMe acute poisoning with dramatic outcome, using hair analysis. Two hair strands, measuring 9.5 cm, were collected 6.5 months after drug consumption during a forensic clinical evaluation of brain dysfunctions after cardiorespiratory arrest and were analyzed by ultra-high performance liquid chromatography system coupled to a tandem mass spectrometry (UPLC-MS/MS) and using two specific transitions: m/z 428.1 > 121.2 (quantification) and 428.1 > 90.6 (confirmation). Hair strands were segmented to determine the historic pattern of drug use and differentiate a single exposure from a chronic exposure. The hair test result for 25I-NBOMe was the following: not detected (0-2 cm), not detected (2-4 cm), 1.0 pg/mg (4-6 cm), 4.9 pg/mg (6-8 cm) and not detected (8-9.5 cm). Result The result of the segment 6-8 cm coincides with the date of consumption (calculated with a hair growth rate at 1 cm/month) and the low concentration detected in the segment 4-6 cm probably corresponds to the contribution of dormant hair. The toxicological significance of the measured concentrations is difficult to determine because this is the first case dealing with hair analysis for 25I-NBOMe. Conclusion The use of hair analysis for NPS is still at the initial stages. In particular, little is known about the incorporation into the keratin matrix after intake and the correlation between dosage frequency of use, and hair concentrations. Under these circumstances, NPS hair analysis should be cautiously interpreted by experienced forensic toxicologist.

The major problem after testing the hair of a child for drugs is the interpretation of the findings. In 2016, the laboratory received several hair specimens with the request to verify if there was any evidence of previous methadone exposure by the donor of the sample. Case 1 was a child admitted to the Emergency Unit for intense sedation and breathing difficulties. Cases 2-4 involved children found dead at home. In all cases, methadone and EDDP, its metabolite, were found in blood. After decontamination, the hair was analysed with LC-MS/MS for methadone and EDDP. The LOQ for both drugs was 10pg/mg. Concentrations were in the range 60-1590 and

BACKGROUND Hair has been suggested since the middle of the 90's to be a suitable matrix to document repetitive exposure to cannabis. Because it is possible to detect Δ9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) in cannabis smoke, the identification of the metabolite, 11-nor-Δ9-tetrahydrocannabinol carboxylic acid (THC-COOH) has been considered to allow the discrimination of active use. OBJECTIVE Although the identification of an active compound in a child's hair shows contamination of the local environment, it is a challenge to discriminate between hair incorporation after ingestion or inhalation and environmental external deposition from dust, smoke, or even contaminated surfaces by hand contact. However, it is particularly important in case of children to correctly interpret the data, particularly for a realistic assessment of the health risk. We present here a series of hair tests for cannabis where the interpretation was almost impossible to establish. METHOD Hair specimens were collected during the autopsy of the 12 children, aged 2 to 24 months, either deceased from shaken baby syndrome (SBS, n=4), mechanic asphyxia (MA, n=1) or sudden infant death (SID, n=7) during January 2015 to April 2017. After decontamination, the hair specimens were tested for THC, CBN and CBD and THC-COOH. The whole length of hair was submitted to analysis. RESULTS The amount of hair from children can be as low as 8 mg. This may affect the limit of quantitation of all drugs, but particularly THC-COOH. Eight from twelve hair tests were positive for cannabis markers, i.e. THC (39 to 1890 pg/mg, n=8), CBN (< 5 to 1300 pg/mg n=8), CBD (10 to 2300 pg/mg, n=8) and THC-COOH (not detected to < 0.5 pg/mg, n=5). In 4 cases from 8 positive findings, it was not possible to test for THC-COOH (not enough material). CONCLUSION Establishing a window of detection when testing for drugs in young children is a very complicated task. Hair from children is finer and more porous in comparison with adult (the risk of contamination from sweat and environmental smoke is higher than in adults). The final interpretation of cannabinoid findings in the children's hair is very complicated as this can result from in utero exposure (although none of the mother admitted cannabis use during pregnancy), oral cannabis administration by the parents to achieve sedation, close contact to cannabis consumers (hands, bedding, dishes) and inhalation of side-stream smoke. Over-interpreting cannabis findings in hair can have very serious legal implication in child protection cases. Practicing scientists have the responsibility to inform the child protection authorities, courts, etc. about these limitations.

Summary A 23 year-old man, health care professional, was found dead in the toilets of a local hospital. Medical supplies for injection (syringe, needles) were found near the body at the scene, in a waste. External body examination revealed a single point of injection located at the left elbow crease and the lack of any traumatic injury. During examination, the pathologist collected cardiac blood and urine. These specimens were tested for ethanol, volatiles, pharmaceuticals and drugs of abuse, using headFspace GC/FID and GC/MS, Elisa, LC-DAD, GC/MS and LC/MS/MS. Ethanol tested positive in blood (0.99 g/L) and urine (0.19 g/L). Using a dedicated LC/MS/MS procedure, alfentanil was identified in both blood (19 ng/mL) and urine (25 ng/mL). Morphine was identified in blood, at 36 ng/mL (free morphine) and 39 ng/mL (total morphine). In urine, total morphine concentration was 81 ng/mL. No other drug was detected. Given the ratio (0.92) free morphine to total morphine in blood and the low concentrations of both alfentanil and morphine in urine, it was considered that the death occurred rapidly after drugs administration. The manner of death was considered as acute intoxication of both alfentanil and morphine, in presence of ethanol.

Contexte : L’implication active des etudiants est un element-cle de la demarche d’evaluation de la qualite des stages hospitaliers. L’exhaustivite des reponses au formulaire d’evaluation des stages hospitaliers par les etudiants du deuxieme cycle de la faculte de medecine de l’Universite de Strasbourg limite la possibilite d’exploiter ces donnees dans une perspective d’amelioration des stages, et amene a se questionner sur la motivation des etudiants a participer a cette evaluation. Buts : Afin d’augmenter la fiabilite de l’evaluation des stages hospitaliers, cette etude cherche a identifier les caracteristiques individuelles et le profil motivationnel des etudiants remplissant le formulaire d’evaluation des stages cliniques, au regard de la theorie de l’autodetermination et du modele de dynamique motivationnelle developpee par Viau. Methode : 223 etudiants en medecine inscrits en troisieme annee du deuxieme cycle des etudes medicales (DCEM3) ont ete soumis a un questionnaire anonyme auto-administre. Resultats : Les caracteristiques individuelles des non-repondants different selon qu’il s’agisse des non-repondants au dernier formulaire ou des non-repondants a tous les formulaires pour l’annee 2008–2009. Par ailleurs, la probabilite de remplir le dernier formulaire en ligne est cinq fois moindre pour un etudiant ayant une activite remuneree et la probabilite de repondre a l’ensemble des formulaires double pour un etudiant assistant aux conferences d’internat. De plus, les motifs d’engagement des etudiants dans l’evaluation des stages cliniques sont faiblement autodetermines. Enfin, l’analyse de la dynamique motivationnelle a permis de souligner la faible perception de la tâche et la faible perception de controle ressentie par les etudiants. Conclusion : Ces resultats permettent de formuler des propositions concretes d’actions afin d’augmenter la motivation des etudiants en medecine a s’engager dans un processus d’evaluation des stages.

High-resolution melting (HRM) analysis is a recently developed molecular technique proved to be applicable for detection of genetic variation, notably in sudden cardiac death. In certain circumstances, especially in postmortem genetic investigations, the formalin-fixed and paraffin-embedded (FFPE) tissues are the only DNA source available. The present study aimed to develop HRM assays, optimized for the analysis of FFPE tissues, to detect sequence variations in KCNQ1 exons in a prospective population-based series of postmortem negative sudden death and to compare the results between the paired freshly frozen and FFPE tissue samples simultaneously obtained from the same case. The analyses were conducted in each case of sudden death involving cases younger than 35 years with no significant morphological anomalies particularly with no cardiac structural disease and with negatives toxicological investigations. HRM analysis was successfully optimized for 13 of the 16 exons of the KCNQ1 gene. All mutated samples were correctly identified by HRM whatever the type of tissue tested. However, for FFPE samples, HRM indicated more positive samples than classical sequencing, used in parallel, due to the degradation of DNA by formalin fixation. This is the first postmortem study of KCNQ1 mutation detection with HRM on DNA extracted from FFPE samples with adapted protocol. Despite the false-positive detection, we concluded that the use of HRM as a screening method with FFPE samples to analyze KCNQ1 mutations can reduce the number of sequencing reactions and, thus, results in substantial time and cost savings.

Ricochet of a bullet in the spinal canal is well known by neurosurgeons but relatively not a common event in usual medico-legal autopsy practice. This article presents a homicide case of a penetrating gunshot injury of the lumbar spine through the T12-L1 intervertebral foramen with active movement of the projectile within the spinal canal to the L5-S1 level. This case illustrates a bullet intradural and intramedullary active movement because of a ricochet of the body of T12 with active redirection of the path. In the current literature, different types of migration in caudal or cranial direction, intradural, or intramedullary are reported. If spontaneous migration of T10 to S1 seems to be more frequent, some authors reported a C1 to S2 migration. Such migration could be asymptomatic or induce neurological impairment. The medico-legal consequences of these migrations within the spinal canal are described.

Formalin-fixed and paraffin-embedded tissue (FF-PET) is an invaluable resource for retrospective molecular genetic studies, but the extraction of high-quality genomic DNA from FF-PET is still a problematic issue. Despite the range of DNA extraction methods currently in use, the association of phenol-chloroform extraction and silica-based purification protocols, reported in ancient DNA studies on archaeological bones, has, to our knowledge, not been used for DNA extraction from FF-PET yet. The present study compared the efficiency of three DNA extraction and purification protocols from two different FF-PET substrates, heart and liver, by using quantitative PCR and multiplex amplification. We showed that the method, using phenol-chloroform and the QIAamp DNA mini Kit (Qiagen), was the most effective DNA extraction and purification method and that the DNA quantity extracted from liver is statistically more important than that extracted from heart. Autosomal STR typing by multiplex amplifications gave partial allelic profiles with only small size products (less than 300 bases) amplified, suggesting that DNA extracted from FF-PET was degraded. In conclusion, the protocol presented here, previously described in studies on ancient bones, should find application in different molecular studies involving FF-PET material.

Genetic testing for cardiac channelopathies in sudden unexplained death (SUD) has developed substantially over the last years. The Next Generation Sequencing (NGS) technology provides an unprecedented opportunity to screen for genetic variations underlying arrhythmogenic genes in a short period of time at a low cost. The present study aimed to perform genetic testing with NGS technologies on the Ion Torrent Personal Genome Machine™ (Ion PGM™) sequencer, in targeting a total of 23 genes reported to be associated with inherited cardiac channelopathies in order to identify the possible cause of death in a cohort of post-mortem cases. The molecular analyses focused on 16 cases of SUD, aged less than 35 years old. In all cases, the cause of death could not be determined after a rigorous autopsy associated with histopathological and toxicological analyses according to the guidelines of the Association for European Cardiovascular Pathology. DNA was extracted from fresh frozen tissue. An average of 200 variants was identified per case. However, after the prioritization process using a new scoring program (VaRank) and after the conjunction of clinical data and molecular findings, four “likely pathogenic” variants (including two undescribed variants), were identified in three cases (18.75%) of our cohort in the genes KCNH2 , ANK2 , SCN5A and RYR2 . One case, who died during psychiatric hospitalization after administration of a QT prolonging drug, showed a double “likely pathogenic” variant in Long QT genes ( ANK2 and SCN5A ) which may have predisposed to drug-induced cardiac arrhythmias. Our study illustrates that the NGS approach based on AmpliSeq™ libraries and Ion Torrent PGM™ sequencing may be an efficient approach, integrated to post-mortem examination. Given the massive amount of information generated by NGS, a rigorous filtration strategy of variants coupled with multidisciplinary collaboration is crucial to determine the potential pathogenic role of identified variants in the cause of death.

Objectif Description d’un cas de deces par choc anaphylactique a la suite d’une injection de rocuronium au decours d’une anesthesie. Introduction Le rocuronium est un curare non depolarisant de la famille des aminosteroides, utilise pour bloquer le passage de l’information neuronale et empecher l’activite musculaire lors d’une anesthesie. Son bref delai d’action, environ 90 secondes, en fait un excellent myorelaxant pour l’intubation des patients. Le rocuronium possede un bon index de securite, mais comme tout curare, il est sujet a des accidents therapeutiques de type choc anaphylactique. L’incidence de l’anaphylaxie aux curares a ete evaluee en France (en 1996) a 1/6500 anesthesies responsables d’un deces sur 100 00 interventions. Ces accidents ne sont pas dose-dependants et le rocuronium apparait comme le curare le plus implique. Description du cas Nous rapportons le cas d’un patient de 44 ans, hospitalise en CHU pour la mise en place d’un bypass gastrique. Dans les suites immediates de l’induction anesthesique avec utilisation de rocuronium, le patient a presente une eruption cutanee et un bronchospasme suivis d’un arret cardiorespiratoire. Apres 24 heures d’hospitalisation dans le service de reanimation medicale, le sujet est decede dans les suites d’une defaillance multiviscerale. L’examen externe du corps a mis en evidence une obesite morbide (indice de masse corporelle superieur a 40), une cyanose ungueale marquee aux membres superieurs et inferieurs et de nombreux stigmates de reanimation. L’autopsie, quant a elle, a revele une congestion multiviscerale non specifique. L’examen radioscopique du corps est sans particularite. Lors de l’autopsie, des prelevements ont ete effectues pour des analyses anatomopathologiques et toxicologiques (sang cardiaque, sang peripherique, humeur vitree, contenu gastrique, bile et cheveux). Methode La recherche de l’alcool ethylique a ete realisee dans les echantillons de sang peripherique et d’humeur vitree par HS-GC-FID. Les cyanures sanguins, les solvants et des substances volatiles ont ete recherches et doses par HS-GC-MS. La teneur en carboxyhemoglobine dans le sang cardiaque a ete determinee par spectrophotometrie a l’aide d’un CO-oxymetre. La recherche des stupefiants usuels et le screening sanguin large ont ete effectues par UPLC-MS/MS (Xevo TQD). Une methode specifique aux curares a ete developpee et effectuee par UPLC-MS/MS (Xevo TQD) apres extraction liquide–liquide a pH 5,4 et appariement d’ions par iodure de potassium. Les ions specifiques du rocuronium sont m/z 530,0 > 111,88 et m/z 530,0 > 99,84. Resultats Les analyses anatomopathologiques ont revele une intense congestion multiviscerale non pathognomonique, une amygdalite aigue et des remaniements inflammatoires cardiaques de la face posterieure du ventricule gauche avec de nombreux polynucleaires eosinophiles, neutrophiles et lymphocytes pouvant faire evoquer le diagnostic de myocardite aigue. La methode specifique aux curares a permis de caracteriser le rocuronium dans le sang peripherique a 325 ng/mL et dans la bile a 2219 ng/mL. La recherche exhaustive des medicaments a mis en evidence du midazolam dose a 356 ng/mL et un antibiotique, la levofloxaxine (non-dosee). Toutes les autres investigations sont negatives. L’identification du rocuronium permet a elle seule de confirmer le choc anaphylactique. Conclusion Les observations thanatologiques, anatomopathologiques et toxicologiques sont compatibles avec un deces dans une situation de choc anaphylactique apres utilisation d’un curare. Cet accident therapeutique est extremement rare et difficile a imputer directement a un curare, d’autant que leur dosage s’avere complique en pratique analytique. L’allergie aux curares reste la premiere cause de reactions allergiques preoperatoires en France. Sans antecedent d’allergie, le choix du curare pourrait etre guide par un bilan allergologique.

International audience; Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification.

Ricochet of a bullet in the spinal canal is well known by neurosurgeons but relatively not a common event in usual medico-legal autopsy practice. This article presents a homicide case of a penetrating gunshot injury of the lumbar spine through the T12-L1 intervertebral foramen with active movement of the projectile within the spinal canal to the L5-S1 level. This case illustrates a bullet intradural and intramedullary active movement because of a ricochet of the body of T12 with active redirection of the path. In the current literature, different types of migration in caudal or cranial direction, intradural, or intramedullary are reported. If spontaneous migration of T10 to S1 seems to be more frequent, some authors reported a C1 to S2 migration. Such migration could be asymptomatic or induce neurological impairment. The medico-legal consequences of these migrations within the spinal canal are described.

International audience; We report a case with an atypical entrance wound as a result of a destabilized full metal jacket bullet penetration. The destabilized bullet by an impact with the dorsal hand experiences a yawing to tumbling motion in flight. The large angle of yaw induces a larger presenting profile upon impact that contributes, associated to a rapid deceleration, to a greater mechanical force on the projectile structure and a fragmentation into core and jacket. Forensic pathologists have to be aware that the metal jacket bullet could tend to break up outside or inside the body particularly after a shooting through a target. This phenomenon induces atypical entrance wounds and atypical X-ray presentation.