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Medical autopsies have been in considerable decline for several decades, in France and worldwide. We aimed to determine whether a medical autopsy still currently has a role to play in diagnosis, by analyzing its performance and diagnostic limitations. This dual-centre retrospective descriptive study included all medical autopsies performed in the university hospitals of Lille and Marseille, France, between January 2007 and December 2012. Autopsies of fetuses or stillborn infants, or those related to sudden infant deaths and research protocols were excluded. 412 medical autopsies were included. The male:female ratio was 1.5:1 and mean age was 27.3 years. Half of all autopsies were pediatric. Regarding anatomical region and/or injury mechanism, a clinical diagnosis was suggested in 52.2% of cases, an autopsy diagnosis in 55.6% and a microscopic diagnosis in 81.8%. There was very low agreement between the clinician's suggested diagnosis and the final diagnosis, both for organ specific diseases and cause of death. Agreement was moderate between autopsy diagnoses and microscopic diagnoses for organ specific diseases and low for cause of death. From our findings we concluded that an autopsy associated with microscopic examination was still valuable in diagnosing cause of death. Microscopic examination was indispensable to determine certain causes of death.

Background: Dating the traumatic event is usually done on subdural hematoma (SDH). After infant deaths due to Abusive head trauma (AHT) without SDH available, the magistrates still ask experts to date the traumatic event. To do so, the expert only has tools based on adult series of AHT. We aimed to develop a subarachnoid hemorrhage (SAH) and retinal hemorrhage (RH) dating system applicable to infants aged under 3 years., Methods and Results: We studied a retrospective multicenter collection of 235 infants who died between the ages of 0 and 36 months, diagnosed with SAH and/or RH by forensic pathological examination and with known posttraumatic interval (PTI). Two pathologists assessed blindly and independently 12histomorphological features in 83 infants (35 girls, 48 boys) whose median age was 3.8 months. For SAH, histopathological changes were significantly correlated with PTI for the appearance of red blood cells, of fibrino-plaquetted organization, the quantity of lymphocytes and macrophages and the presence or absence of siderophages, collagen and fibroblast formation and presence or absence of neovascularization. For RH, histopathological changes were significantly correlated with PTI for the appearance of red blood cells, the presence or absence of siderophages and sclerosis of the retina., Conclusion: Our HAS dating system improves the precision and reliability of forensic pathological expert examination of AHT, when SDH are not available, for age estimation in infants. The study of RH histomorphological changes does not allow for reliable dating., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Activation of indirect pathway medium spiny neurons (MSNs) via promotion of cAMP production is the principal mechanism of action of current antipsychotics with dopamine D 2 receptor antagonism. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a novel phosphodiesterase 10A inhibitor that activates both direct and indirect pathway MSNs through increasing both cAMP and cGMP levels by inhibition of their degradation. The activation of indirect pathway MSNs through the distinct mechanism of action of these drugs raises the possibility of augmented pharmacological effects by combination therapy. In this study, we evaluated the potential of combination therapy with TAK-063 and current antipsychotics, such as haloperidol or olanzapine after oral administration. Combined treatment with TAK-063 and either haloperidol or olanzapine produced a significant increase in phosphorylation of glutamate receptor subunit 1 in the rat striatum. An electrophysiological study using rat corticostriatal slices showed that TAK-063 enhanced N-methyl- D -aspartic acid receptor-mediated synaptic responses in both direct and indirect pathway MSNs to a similar extent. Further evaluation using pathway-specific markers revealed that coadministration of TAK-063 with haloperidol or olanzapine additively activated the indirect pathway, but not the direct pathway. Combined treatment with TAK-063 and either haloperidol or olanzapine at subeffective doses produced significant effects on methamphetamine- or MK-801-induced hyperactivity in rats and MK-801-induced deficits in prepulse inhibition in mice. TAK-063 at 0.1 mg/kg did not affect plasma prolactin levels and cataleptic response from antipsychotics in rats. Thus, TAK-063 may produce augmented antipsychotic-like activities in combination with antipsychotics without effects on plasma prolactin levels and cataleptic responses in rodents., (© 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

The aim of postmortem medicolegal examination in pediatric death is primarily to establish the circumstances and causes of death and to exclude child abuse. In France, pediatric death is systematically documented by medicolegal or medical autopsy. In case of medicolegal autopsy, the complementary examinations, requested and financed by justice, are rarely limited to a histopathological examination. However in medical autopsies other tools are available to the pathologist as toxicology, biochemistry and molecular biology. The purpose of this article is to evaluate the efficacy of forensic histopathology in pediatric forensic autopsies. We analyze the main causes of pediatric death in a forensic context. Between 2004 and 2015, 157 infant deaths were identified in Marseille university hospital. The forensic histopathology and autopsy reports of all 157 cases were available for systematic review. Medical or surgical causes represented 41,3% of deaths in our center, accidental causes 8.1% and child abuse 28,8%. The definitive diagnosis was made at autopsy in 30% of cases and at histopathological examination in 70% highlighting that forensic histopathology is an indispensable tool in pediatric medicolegal autopsies. Significant histological abnormalities may be detected in selected organs such as the brain, lungs, heart, liver, adrenal glands and kidneys in spite of macroscopically normal appearances. This justifies systematic sampling of all organs. Despite the implementation of the French sudden infant death protocol which recommends medical autopsies, too many pediatric autopsies are carried out in a medicolegal context. 30% of the cases remain without diagnosis at the end of the autopsy and histological examination. This number could be reduced by the contribution of others laboratory investigation., (Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

In France, sudden death is responsible every year for 40,000 deaths. The most frequent etiology is cardiac disease. Atheromatous-related pathology is the most common etiology beyond 35, but cardiomyopathies and channelopathies are responsible for a significant number of deaths in young adults. Some acquired disorders can also cause sudden cardiac death. We report the case of a 17-year-old man who died suddenly after sport. Autopsy and pathological study found multiple giant coronary aneurysms. Thrombosis and fibrous scar of myocardial ischemic events were observed. These lesions were in favor of late sequelae of Kawasaki disease. Kawasaki disease is a rare but not exceptional cause of sudden cardiac death in young adults. In the lack of known clinical history, some aspects, even not specific, should evoke this diagnosis. Even in front of apparent good clinical tolerance, these sequelae require appropriate follow-up because of a significant risk of sudden death., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 2: FHM2) is caused by loss-of-function mutations in α2 Na(+),K(+) ATPase (α2 NKA), an isoform almost exclusively expressed in astrocytes in adult brain. Cortical spreading depression (CSD), the phenomenon that underlies migraine aura and activates migraine headache mechanisms, is facilitated in heterozygous FHM2-knockin mice with reduced expression of α2 NKA The mechanisms underlying an increased susceptibility to CSD in FHM2 are unknown. Here, we show reduced rates of glutamate and K(+) clearance by cortical astrocytes during neuronal activity and reduced density of GLT-1a glutamate transporters in cortical perisynaptic astrocytic processes in heterozygous FHM2-knockin mice, demonstrating key physiological roles of α2 NKA and supporting tight coupling with GLT-1a. Using ceftriaxone treatment of FHM2 mutants and partial inhibition of glutamate transporters in wild-type mice, we obtain evidence that defective glutamate clearance can account for most of the facilitation of CSD initiation in FHM2-knockin mice, pointing to excessive glutamatergic transmission as a key mechanism underlying the vulnerability to CSD ignition in migraine., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)

Characteristics of sharp bone trauma can be extremely useful to determine the origin of cut marks and to provide information regarding the context of death. Using human ribs and clavicle bones, this study analyzes the characteristics of bone kerfs made by different bladed implements, thanks to epifluorescence macroscopy. This technique, which is a nondestructive tool that uses autofluorescence of bones, documents bone damage precisely with high resolution. Both qualitative and quantitative criteria are analyzed. Our results identify unique class characteristics on bone lesions, allowing modeling kerf depending on the weapon, regardless of the type of bone that is wounded. Moreover, we demonstrate for the first time microscopic criteria of directionality, using fluorescence excitation. Orientation of cracks, flakes, and lateral pushing back especially helps in determining the tip and the end of the lesion, leading to the position of the aggressor. Kerf wall characteristics and striation location are also very useful. Epifluorescence macroscopy could be a new tool of choice in anthropology through cut mark analysis in establishing how the blade was used and providing details about the blow.

A 27-year-old man suddenly died in hospital of acute respiratory distress syndrome secondary to severe systemic vasculitis. Multi-phase post-mortem computed tomography angiography followed by scientific autopsy of the thoracic and abdominal cavity and histology was performed, illustrating the advantages and drawbacks of such techniques. Imaging enabled us to examine the cranium, as the family refused cerebral dissection. MPMCTA revealed absence of opacification of the left middle cerebral artery. But parenchymal findings of thoracic and abdominal organs were still difficult to interpret after both imaging and macroscopic examination during the autopsy. Microscopic examination provided the definitive diagnosis of cause of death. Analysis revealed systemic vasculitis of the lung complicated by diffuse alveolar, mediastinal, splenic and retroperitoneal lesions. We were unable to determine the type of vasculitis, whether polyarteritis nodosa or microscopic polyangiitis, because of artifactual glomerular collapse. We observed some structural changes in tissue secondary to contrast agent injection, affecting the vascular system and renal parenchyma in particular. Such artifacts must be known in order to avoid misinterpreting them as pathological findings. MPMCTA and conventional autopsy are two complementary techniques showing both their specific advantages and limits which have to be known in order to choose the appropriate technique. One limit of both techniques is the detection of microscopic findings which can only be obtained by additional histological examination. This case report underlines this fact and demonstrates that caution is required in some cases if microscopic analyses are carried out after contrast agent injection., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Analysis of dismemberment trauma aims at identifying characteristics of false starts and complete sections in order to identify the class of saw. Nevertheless, determination of the individual weapon remains a challenging task. We attempted to determine the unique characteristics of different blades within the same class of saws using epifluorescence macroscopy, a non-invasive technique, in order to establish an individual injury profile. Two hacksaw blades of identical characteristics (size, set and shape of the teeth) were used to create false starts and complete sections on partially defleshed pig bones. These wounds were then analyzed using epifluorescence macroscopy. Bone lesion analysis determined characteristics that were common to both blades, corresponding to size, raker set and ripcut shape. The data collected made it possible to reconstruct the trauma. Furthermore, we highlighted specific characteristics of each blade in both false starts and complete sections. These characteristics mainly related to the shape and profile of the kerf, the consistency of cut and type of fluorescent wall striations. The sum of the information collected in examination of dismemberment wounds can identify, through comparative analysis, the individual weapon responsible for the imprints observed on the bones., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We report two cases of spine injury following a low-energy trauma in persons with ankylosing spondylitis (AS) and discuss the forensic considerations. A 60-year-old man presented with a wide anterior fracture of the superior endplate of T8 after an accidental fall down three wooden steps. A 93-year-old man presented with disjunction between C6 and C7 and 90-degree spinal angulation after a fall from a standing height or a fall from a bed. Post-mortem multislice computed tomography (MSCT) was performed before autopsy in both the cases. MSCT and autopsy findings were in agreement with a past medical history of AS. A spine injury occurring after a low-energy trauma is unusual and could be suspicious. In the forensic literature we found only a single case, which concerned multiple spinal fractures after a fall from a bicycle at low speed. Such specific mechanisms must be studied and known to the forensic expert. In this context, MSCT is a useful tool to investigate the spine and knowledge of the victim's entire past medical history is essential., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Belatacept has been found to be efficient at preserving good kidney function in maintenance kidney-transplant patients. Herein, we report on the use of belatacept as a rescue therapy for two kidney-transplant patients presenting with severe adverse events after treatment with calcineurin inhibitors (CNIs) and mammalian target-of-rapamycin (mTOR) inhibitors. Two kidney-transplant patients developed severely impaired kidney function after receiving CNIs. The use of everolimus was associated with severe angioedema. Belatacept was then successfully used to improve kidney function in both cases, even though estimated glomerular-filtration rate before conversion was <20 mL/min. These case reports show that belatacept can be used as a rescue therapy, even if kidney function is very low in kidney-transplant patients who cannot tolerate CNIs and/or mTOR inhibitors.

Unlabelled: Despite its progressive decline, clinical autopsy remains a useful diagnostic tool. In the French Toulouse University Hospital, a pathologist in collaboration with a forensic scientist performs theses autopsies since macroscopic time., Aim: Our purpose is to present a retrospective study of theses autopsies since the beginning of this collaboration., Patients and Method: We reviewed the demands of medical autopsies between January 2006 and June 2010. We have then analyzed different data such as epidemiological data, gross and microscopic findings and the different causes of death., Results: Thirty-eight medical autopsies were performed during this period. The average age of patients was 45.7 years and the sex ratio M/F 1.5. We distinguished two different populations in this sample: hospitalized patients with numerous associated diseases and non-hospitalized patients who died in a context of sudden unexpected death. A diagnosis was established in 73.7% of the observations. Most of them suffered from infections. Discrepancies between clinical and autopsy diagnoses reached 50% of all cases. Histological examination allowed to establish a complete diagnosis in 47.3% of cases. Histological analysis has a major impact on necropsy diagnosis especially in the lungs, heart or brain., Conclusion: Medical autopsy is still the most accurate method of determining the cause of death. Gross and microscopic examinations are fundamental to achieve this aim. Two experts, one pathologist and one forensic scientist, perform these autopsies in Toulouse, in order to improve both experiences and performance in the diagnosis of death., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Characterization of sharp-force trauma on human bones can be extremely useful in providing information regarding the nature and context of death. Nevertheless, in the identification of weapons used to cause sharp-force trauma and analysis of bone wounds, challenging tasks still remain. Current analysis attempting to dissect bone wound characteristics varied quite a lot and mixed different criteria, thus leading sometimes to conflicting results. In this context, the aim of our study is to clarify qualitative aspects of cut marks induced by sharp weapons on human bones. For that purpose, we analyzed bone samples via an original approach based on bone autofluorescence with an epifluorescence macroscope and compared it to previous existing methods. In this study, we used bone sections from human clavicles on which three different kinds of lesions were manually implemented, using different weapons. The bone wounds were analyzed by three different methodologies, light microscopy, scanning electron microscopy (SEM), and micro-computed tomography, and were compared with epifluorescence macroscopy. We paid attention more significantly to the aspect of walls and floor of the kerf, so as to conclude on the nature and distinguish between weapons used. Among all technologies used in this study, the most precise and efficient methods were epifluorescence macroscopy and SEM. Nonetheless, epifluorescence macroscopy is faster, cheaper, and more accessible than SEM. More significantly, this technique, which has the potential to accurately document the nature of the damage, is nondestructive, and could thus be highly useful in forensic science as anthropology.

An 18-year-old patient presented with a solitary limbal tumor on his left eye that had appeared and increased in size for 3 weeks. This mass did not display any extension into the anterior chamber on gonioscopy. Excisional biopsy by lamellar sclerokeratectomy was carried out and the lesion was sent for histologic examination. The pathologic diagnosis showed the characteristic picture of juvenile xanthogranuloma with numerous Touton giant cells. There was no recurrence after a 9-month follow-up. The diagnosis of isolated ocular juvenile xanthogranuloma may be difficult and histologic examination of ocular lesions is often necessary. When juvenile xanthogranuloma affects the uvea, treatment is medical. When it appears as a limbal mass, treatment is surgical. Juvenile xanthogranuloma should always be considered a differential diagnosis of a limbal mass, especially in children.

Context: Primary sellar melanocytic tumors are extremely rare, and they can mimic hormonally inactive pituitary macroadenoma both clinically and radiologically., Objectives: The aim of this study was to describe a new case of primary sellar melanocytic tumor, and place it in the context of published literature., Design: This is a case report., Patient: The case of a 61-year-old woman presenting with a 2-month history of fatigue and progressive bitemporal hemianopia is described. Endocrine investigation revealed anterior pituitary insufficiency and hyperprolactinemia without diabetes insipidus. Magnetic resonance imaging demonstrated a sellar tumor mass with suprasellar extension compressing the optic chiasm, and intense gadolinium enhancement. Transsphenoidal surgical excision of the pituitary tumor was undertaken. Histological examination showed a melanocytic tumor. An extensive search failed to find evidence of any other primary or secondary site. Due to the presence of significant tumor residue at 3-month follow-up, another surgical resection was done followed by post-operative stereotactic radiotherapy of the sellar region., Conclusion: Primary sellar melanocytic tumors are exceptional lesions presenting most often as a tumor syndrome and/or anterior pituitary insufficiency mimicking a non-secreting pituitary macroadenoma. The management of these tumors consists of surgical removal of the tumor. However, surgery is often incomplete and stereotactic fractionated radiotherapy is frequently indicated.

A 17-month-old male infant died at home. The infant's right arm was immobilized because of a humeral fracture 1 month earlier. The circumstances of death appeared unclear to the police investigators and a medicolegal autopsy was carried out. External examination revealed diffuse ecchymoses of varying color. Postmortem imaging was performed prior to autopsy (X-rays, multislice computed tomography [MSCT], and focused brain magnetic resonance imaging [MRI]). These investigations revealed four rib fractures of varying ages, one of which was posterior. Cerebral and pericerebral traumatic lesions were also diagnosed: bilateral subdural hematomas, intraventricular, meningeal, and interpedoncular hemorrhages. In the abdomen, fresh blood was visible within the anterior abdominal wall and the mesenteric root. Autopsy and microscopic study confirmed these lesions. This case report illustrates the valuable assistance rendered by MSCT and MRI to diagnose abuse when a child has died in unclear circumstances.