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1.
Cell ; 184(24): 5932-5949.e15, 2021 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-34798069

RESUMEN

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.


Asunto(s)
Autopsia/métodos , COVID-19/mortalidad , COVID-19/virología , Bulbo Olfatorio/virología , Mucosa Olfatoria/virología , Mucosa Respiratoria/virología , Anciano , Anosmia , COVID-19/fisiopatología , Endoscopía/métodos , Femenino , Glucuronosiltransferasa/biosíntesis , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Trastornos del Olfato , Neuronas Receptoras Olfatorias/metabolismo , Sistema Respiratorio , SARS-CoV-2 , Olfato
2.
Biostatistics ; 25(4): 1233-1253, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38400753

RESUMEN

Determining causes of deaths (CODs) occurred outside of civil registration and vital statistics systems is challenging. A technique called verbal autopsy (VA) is widely adopted to gather information on deaths in practice. A VA consists of interviewing relatives of a deceased person about symptoms of the deceased in the period leading to the death, often resulting in multivariate binary responses. While statistical methods have been devised for estimating the cause-specific mortality fractions (CSMFs) for a study population, continued expansion of VA to new populations (or "domains") necessitates approaches that recognize between-domain differences while capitalizing on potential similarities. In this article, we propose such a domain-adaptive method that integrates external between-domain similarity information encoded by a prespecified rooted weighted tree. Given a cause, we use latent class models to characterize the conditional distributions of the responses that may vary by domain. We specify a logistic stick-breaking Gaussian diffusion process prior along the tree for class mixing weights with node-specific spike-and-slab priors to pool information between the domains in a data-driven way. The posterior inference is conducted via a scalable variational Bayes algorithm. Simulation studies show that the domain adaptation enabled by the proposed method improves CSMF estimation and individual COD assignment. We also illustrate and evaluate the method using a validation dataset. The article concludes with a discussion of limitations and future directions.


Asunto(s)
Autopsia , Teorema de Bayes , Causas de Muerte , Humanos , Autopsia/métodos , Modelos Estadísticos , Bioestadística/métodos
3.
Mol Psychiatry ; 29(4): 1128-1138, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38351171

RESUMEN

Bipolar disorder is a severe neuro-psychiatric condition where genome-wide association and sequencing studies have pointed to dysregulated gene expression as likely to be causal. We observed strong correlation in expression between GWAS-associated genes and hypothesised that healthy function depends on balance in the relative expression levels of the associated genes and that patients display stoichiometric imbalance. We developed a method for quantifying stoichiometric imbalance and used this to predict each sample's diagnosis probability in four cortical brain RNAseq datasets. The percentage of phenotypic variance on the liability-scale explained by these probabilities ranged from 10.0 to 17.4% (AUC: 69.4-76.4%) which is a multiple of the classification performance achieved using absolute expression levels or GWAS-based polygenic risk scores. Most patients display stoichiometric imbalance in three to ten genes, suggesting that dysregulation of only a small fraction of associated genes can trigger the disorder, with the identity of these genes varying between individuals.


Asunto(s)
Trastorno Bipolar , Encéfalo , Estudio de Asociación del Genoma Completo , Humanos , Trastorno Bipolar/genética , Trastorno Bipolar/metabolismo , Estudio de Asociación del Genoma Completo/métodos , Encéfalo/metabolismo , Expresión Génica/genética , Masculino , Femenino , Autopsia/métodos , Herencia Multifactorial/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Fenotipo , Persona de Mediana Edad
4.
Neuroimage ; 296: 120680, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38857819

RESUMEN

Magnetic Resonance Imaging (MRI) can provide the location and signal characteristics of pathological regions within a postmortem tissue block, thereby improving the efficiency of histopathological studies. However, such postmortem-MRI guided histopathological studies have so far only been performed on fixed samples as imaging tissue frozen at the time of extraction, while preserving its integrity, is significantly more challenging. Here we describe the development of cold-postmortem-MRI, which can preserve tissue integrity and help target techniques such as transcriptomics. As a first step, RNA integrity number (RIN) was used to determine the rate of tissue biomolecular degradation in mouse brains placed at various temperatures between -20 °C and +20 °C for up to 24 h. Then, human tissue frozen at the time of autopsy was immersed in 2-methylbutane, sealed in a bio-safe tissue chamber, and cooled in the MRI using a recirculating chiller to determine MRI signal characteristics. The optimal imaging temperature, which did not show significant RIN deterioration for over 12 h, at the same time giving robust MRI signal and contrast between brain tissue types was deemed to be -7 °C. Finally, MRI was performed on human tissue blocks at this optimal imaging temperatures using a magnetization-prepared rapid gradient echo (MPRAGE, isotropic resolution between 0.3-0.4 mm) revealing good gray-white matter contrast and revealing subpial, subcortical, and deep white matter lesions. RINs measured before and after imaging revealed no significant changes (n = 3, p = 0.18, paired t-test). In addition to improving efficiency of downstream processes, imaging tissue at sub-zero temperatures may also improve our understanding of compartment specificity of MRI signal.


Asunto(s)
Autopsia , Encéfalo , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Ratones , Autopsia/métodos , Animales , Congelación , Masculino , Femenino , Ratones Endogámicos C57BL , Neuroimagen/métodos
5.
Malar J ; 23(1): 217, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030612

RESUMEN

BACKGROUND: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. METHODS: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990-March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. RESULTS: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. CONCLUSIONS: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible.


Asunto(s)
Autopsia , Causas de Muerte , Malaria , Autopsia/métodos , Humanos , Malaria/mortalidad
6.
Eur Radiol ; 34(1): 632-642, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37526669

RESUMEN

OBJECTIVES: The acceptance of conventional autopsy (CA), the gold standard method for investigating fetal death, often remains problematic. Post-mortem magnetic resonance imaging (PMMRI) is increasingly advocated, particularly for neurologic malformations. However, PMMRI performances to diagnose non-neurologic malformations remain unclear. We aim to clarify whether a full body CA remains needed after prenatal ultrasound (US) and PMMRI in assessing non-neurologic fetal malformations. METHODS: In this retrospective IRB-approved study, during a 6-year period, all fetuses who underwent PMMRI, prenatal US, and full body CA were included. Body abnormalities were identified in US, PMMRI, and CA reports. US and PMMRI images were all reviewed. All abnormalities were graded as major (2 points) or minor (1 point). Each technique (US, PMMRI, CA) was given a score by adding all grading points. In each fetus, results were compared for both separate and combined US and PMMRI to CA. Sensitivity and specificity were calculated for detecting major abnormalities. RESULTS: Fifty fetuses were included. The score of CA, US, and PMMRI was respectively 53, 37, and 46. Compared with US-PMMRI, CA added information in 2 cases (4%) with major abnormalities and 7 cases (14%) with minor abnormalities. PMMRI and US were concordant in 36/50 (72%) fetuses. Separate US/PMMRI sensitivities and specificities for detecting major body malformations respectively were 80%/80% and 100%/94%. Combined US-PMMRI had a sensitivity of 90% and a specificity of 94%. Two cardiac malformations (2/6) were only described by CA. CONCLUSIONS: After prenatal US and PMMRI, few additional fetal body malformations are discovered with CA. Nevertheless, fetal heart autopsy remains mandatory. CLINICAL RELEVANCE STATEMENT: A cardiac conventional autopsy complemented by prenatal ultrasound and post-mortem MRI allows to detect all major fetal body abnormalities. With this efficient and much less invasive approach, a higher acceptance rate of fetal autopsy can be expected. KEY POINTS: • Excepting cardiac malformations, most major fetal body malformations can reliably be identified by prenatal US combined with post-mortem MRI. • In the post-mortem diagnosis of fetal body malformations, a conventional autopsy limited to the fetal heart might replace a full body autopsy after a well-conducted prenatal US and post-mortem MRI.


Asunto(s)
Muerte Fetal , Feto , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Feto/diagnóstico por imagen , Autopsia/métodos , Imagen por Resonancia Magnética/métodos , Ultrasonografía Prenatal
7.
Eur Radiol ; 34(9): 5561-5569, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38459348

RESUMEN

OBJECTIVES: Corner metaphyseal lesions (CMLs) are specific for child abuse but challenging to detect on radiographs. The accuracy of CT for CML detection is unknown. Our aim was to compare diagnostic accuracy for CML detection on post-mortem skeletal surveys (PMSS, plain radiography) versus post-mortem CT (PMCT). METHODS: A 10-year retrospective review was performed at a children's hospital for patients having PMSS, PMCT and histopathological correlation (reference standard) for suspected CMLs. Twenty-four radiologists independently reported the presence or absence of CMLs in all cases in a blinded randomised cross-over design across two rounds. Logistic regression models were used to compare accuracy between modalities. RESULTS: Twenty CMLs were reviewed for each of the 10 subjects (200 metaphyses in all). Among them, 20 CMLs were confirmed by bone histopathology. Sensitivity for these CMLs was significantly higher for PMSS (69.6%, 95% CI 61.7 to 76.7) than PMCT (60.5%, 95% CI 51.9 to 68.6). Using PMSS for detection of CMLs would yield one extra correct diagnosis for every 11.1 (95% CI 6.6 to 37.0) fractured bones. In contrast, specificity was higher on PMCT (92.7%, 95% CI 90.3 to 94.5) than PMSS (90.5%, 95% CI 87.6 to 92.8) with an absolute difference of 2.2% (95% CI 1.0 to 3.4, p < 0.001). More fractures were reported collectively by readers on PMSS (785) than on PMCT (640). CONCLUSION: PMSS remains preferable to PMCT for CML evaluation. Any investigation of suspected abuse or unexplained deaths should include radiographs of the limbs to exclude CMLs. CLINICAL RELEVANCE STATEMENT: In order to avoid missing evidence that could indicate child abuse as a contributory cause for death in children, radiographs of the limbs should be performed to exclude CMLs, even if a PMCT is being acquired. KEY POINTS: • Corner metaphyseal lesions (CMLs) are indicative for abuse, but challenging to detect. Skeletal surveys (i.e. radiographs) are standard practice; however, accuracy of CT is unknown. • Sensitivity for CML detection on radiographs is significantly higher than CT. • Investigation of unexplained paediatric deaths should include radiographs to exclude CMLs even if CT is also being performed.


Asunto(s)
Autopsia , Maltrato a los Niños , Fracturas Óseas , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Autopsia/métodos , Lactante , Maltrato a los Niños/diagnóstico , Fracturas Óseas/diagnóstico por imagen , Preescolar , Niño , Estudios Cruzados , Imágenes Post Mortem
8.
Int J Legal Med ; 138(5): 1939-1946, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38592482

RESUMEN

Conducting external post-mortem examinations is an essential skill required of physicians in various countries, regardless of their specialization. However, the quality of these examinations has been a subject of continuous debates, and notable errors were reviled. In response to these shortcomings, a virtual reality (VR) application was developed at Halle's medical department in Germany, focusing on the scene of discovery and the completion of death certificates. The initial trial of this VR application in 2020 involved 39 students and 15 early-career professionals. Based on the feedback, the application underwent improvements and was subsequently introduced to the medical department in Dresden, Germany, in 2022. Its primary objective was to showcase the VR training's adaptability and scalability across various educational structures and levels of medical expertise. Out of 73 students who participated, 63 completed the evaluation process. 93.1% (n = 58) of the evaluators reported increased confidence in conducting external post-mortem examinations, and 96.8% (n = 61) felt more assured in filling out death certificates, crediting this progress to the VR training. Additionally, 98.4% (n = 62) believed that repeating forensic medical aspects in their coursework was crucial, and 96.8% (n = 61) viewed the VR examination as a valuable addition to their academic program. Despite these positive responses, 91.6% (n = 55) of participants maintained that training with real corpses remains irreplaceable due to the insufficiency of haptic feedback in VR. Nevertheless, the potential for enhancing the VR content and expanding the training to additional locations or related disciplines warrants further exploration.


Asunto(s)
Autopsia , Realidad Virtual , Humanos , Autopsia/métodos , Alemania , Medicina Legal/métodos , Medicina Legal/educación , Competencia Clínica , Certificado de Defunción , Masculino , Femenino
9.
Int J Legal Med ; 138(2): 431-442, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37837537

RESUMEN

In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Humanos , Autopsia/métodos , SARS-CoV-2 , Pandemias , Causas de Muerte
10.
Int J Legal Med ; 138(4): 1437-1446, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38568229

RESUMEN

Computed tomography angiography (PMCTA) is increasingly used in postmortem cases. Standardized validated protocols permit to compare different PMCTA images and make it more easily to defend a case in court. In addition to the well-known technique by Grabherr et al. (2011) which is using paraffin oil as a carrier substance, water-soluble polyethylene glycol 200 (PEG200) can be used in combination with the contrast agent Accupaque® 300. As to date, there exists no standardized protocol for the use of this contrast agent mixture, the aim of this study was to develop a protocol using it. Between 2012 and 2022, 23 PMCTA with PEG200 and Accupaque®300 were performed at the University Centre of Legal Medicine Lausanne (Switzerland) and the Institute of Forensic Medicine Munich (Germany). The images obtained were evaluated regarding the opacification of the vessels and possible artefacts. The best image quality was obtained with a mixing ratio of 1:15 (Accupaque®300:PEG200) and a perfusion volume of 1000 ml in the arterial, 1400 ml in the venous and 350 ml in the dynamic phase. The infusion rates described by Grabherr et al. were confirmed for the three phases. Overall, the opacification of the vessels was diagnostically sufficient. In 13 cases no opacification of the right coronary artery was observed due to a stratification artefact. By using the PMCTA protocol with PEG200 as a carrier, a good overall image quality can be achieved. This protocol offers the possibility to standardize PMCTA with PEG200.


Asunto(s)
Angiografía por Tomografía Computarizada , Medios de Contraste , Polietilenglicoles , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Autopsia/métodos , Anciano de 80 o más Años , Adulto , Imágenes Post Mortem
11.
Int J Legal Med ; 138(4): 1447-1458, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38386034

RESUMEN

Post-mortem computed tomography (PMCT) enables the creation of subject-specific 3D head models suitable for quantitative analysis such as finite element analysis (FEA). FEA of proposed traumatic events is an objective and repeatable numerical method for assessing whether an event could cause a skull fracture such as seen at autopsy. FEA of blunt force skull fracture in adults with subject-specific 3D models in forensic pathology remains uninvestigated. This study aimed to assess the feasibility of FEA for skull fracture analysis in routine forensic pathology. Five cases with blunt force skull fracture and sufficient information on the kinematics of the traumatic event to enable numerical reconstruction were chosen. Subject-specific finite element (FE) head models were constructed by mesh morphing based on PMCT 3D models and A Detailed and Personalizable Head Model with Axons for Injury Prediction (ADAPT) FE model. Morphing was successful in maintaining subject-specific 3D geometry and quality of the FE mesh in all cases. In three cases, the simulated fracture patterns were comparable in location and pattern to the fractures seen at autopsy/PMCT. In one case, the simulated fracture was in the parietal bone whereas the fracture seen at autopsy/PMCT was in the occipital bone. In another case, the simulated fracture was a spider-web fracture in the frontal bone, whereas a much smaller fracture was seen at autopsy/PMCT; however, the fracture in the early time steps of the simulation was comparable to autopsy/PMCT. FEA might be feasible in forensic pathology in cases with a single blunt force impact and well-described event circumstances.


Asunto(s)
Análisis de Elementos Finitos , Patologia Forense , Imagenología Tridimensional , Fracturas Craneales , Tomografía Computarizada por Rayos X , Humanos , Fracturas Craneales/diagnóstico por imagen , Fracturas Craneales/patología , Masculino , Patologia Forense/métodos , Adulto , Femenino , Persona de Mediana Edad , Autopsia/métodos , Anciano
12.
Int J Legal Med ; 138(4): 1391-1399, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38329584

RESUMEN

During the last years, the detection of different causes of death based on postmortem imaging findings became more and more relevant. Especially postmortem computed tomography (PMCT) as a non-invasive, relatively cheap, and fast technique is progressively used as an important imaging tool for supporting autopsies. Additionally, previous works showed that deep learning applications yielded robust results for in vivo medical imaging interpretation. In this work, we propose a pipeline to identify fatal cerebral haemorrhage on three-dimensional PMCT data. We retrospectively selected 81 PMCT cases from the database of our institute, whereby 36 cases suffered from a fatal cerebral haemorrhage as confirmed by autopsy. The remaining 45 cases were considered as neurologically healthy. Based on these datasets, six machine learning classifiers (k-nearest neighbour, Gaussian naive Bayes, logistic regression, decision tree, linear discriminant analysis, and support vector machine) were executed and two deep learning models, namely a convolutional neural network (CNN) and a densely connected convolutional network (DenseNet), were trained. For all algorithms, 80% of the data was randomly selected for training and 20% for validation purposes and a five-fold cross-validation was executed. The best-performing classification algorithm for fatal cerebral haemorrhage was the artificial neural network CNN, which resulted in an accuracy of 0.94 for all folds. In the future, artificial neural network algorithms may be applied by forensic pathologists as a helpful computer-assisted diagnostics tool supporting PMCT-based evaluation of cause of death.


Asunto(s)
Autopsia , Hemorragia Cerebral , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X , Humanos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Estudios Retrospectivos , Autopsia/métodos , Masculino , Femenino , Persona de Mediana Edad , Aprendizaje Automático , Anciano , Adulto , Algoritmos , Máquina de Vectores de Soporte , Imagenología Tridimensional , Imágenes Post Mortem
13.
Pediatr Dev Pathol ; 27(2): 148-155, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38098260

RESUMEN

While conventional autopsy is the gold-standard for determining cause of demise in the fetal and neonatal population, molecular analysis is increasingly used as an ancillary tool. Testing methods and tissue selection should be optimized to provide informative genetic results. This institutional review compares testing modalities and postmortem tissue type in 53 demises occurring between 20 weeks of gestation and 28 days of life. Testing success, defined as completion of analysis, varies by technique and may require viable cells for culture or extractable nucleic acid. Success was achieved by microarray in 29/30 tests (96.7%), karyotype in 40/54 tests (74.1%), fluorescent in situ hybridization in 5/9 tests (55.6%), and focused gene panels in 2/2 tests (100%). With respect to tissue type, postmortem prepartum amniotic fluid was analyzed to completion in 100% of tests performed; compared to 84.0%, 54.5%, and 80.8% of tests using placenta, fetal only, and mixed fetal-placental tissue collection, respectively. Sampling skin (83.3%, in cases with minimal maceration) and kidney (75.0%) were often successful, compared to lower efficacy of umbilical cord (57.1%) and liver (25.0%). Addition of genetic testing into cases with anomalous clinical and gross findings can increase the utility of the final report for family counseling and future pregnancy planning.


Asunto(s)
Muerte Fetal , Mortinato , Recién Nacido , Embarazo , Femenino , Humanos , Mortinato/epidemiología , Muerte Fetal/etiología , Placenta/patología , Hibridación Fluorescente in Situ , Autopsia/métodos
14.
Clin Radiol ; 79(10): 791-798, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39068113

RESUMEN

AIM: To evaluate the impact of a new, less-invasive micro-computed tomography (CT) service on autopsy service provision. We recorded parental consent, type of autopsy performed, autopsy reporting times and time taken for the body to be released from the mortuary. MATERIALS AND METHODS: A retrospective, single-centre case series was conducted for all perinatal deaths since the introduction of our micro-CT service in 2016, with a detailed review of records extracted from 2019 and 2021. Fetal demographics (gestational age, weight), type of autopsy conducted, and the time taken from receiving the body to releasing the body and issuing a final report were recorded. RESULTS: Micro-CT imaging uptake increased to over two hundred cases/year by 2021. Overall, invasive autopsies reduced from (45.8%, 196/428; 2019) to (32.1%, 125/390; 2021) with an equivalent rise in less-invasive autopsy from 54.2% (232/428;2019) to 67.9% (265/390;2019). Offering a micro-CT service resulted in an increase in consent to imaging-based autopsies from (76.9%, 329/428;2019) to (87.2%, 340/390;2021). Micro-CT has become the most common post-mortem imaging performed in our institution at 54.4% (212/251;2021), although the body preparation time from the tissue staining required has increased the time to provide an autopsy report to 17 days and release of the body to 18 days. CONCLUSION: Our study shows that introducing a micro-CT post-mortem imaging service was associated with reduced use of conventional invasive procedures, despite a slight increase in turnaround times. Understanding these factors and continued improvements in micro-CT service delivery will help make this accessible to a wider population in the future.


Asunto(s)
Autopsia , Microtomografía por Rayos X , Humanos , Autopsia/métodos , Estudios Retrospectivos , Microtomografía por Rayos X/métodos , Femenino , Feto/diagnóstico por imagen , Embarazo
15.
Prenat Diagn ; 44(1): 3-14, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38161284

RESUMEN

OBJECTIVE: This study involved very early post-mortem (PM) examination of human fetal anatomy at 8 weeks of gestation (WG) using whole-body multimodal micro-imaging: micro-CT and high-field MRI (HF-MRI). We discuss the potential place of this imaging in early first-trimester virtual autopsy. METHODS: We performed micro-CT after different contrast-bath protocols including diffusible iodine-based contrast-enhanced (dice) and HF-MRI with a 9.4 T machine with qualitative and quantitative evaluation and obtained histological sections. RESULTS: Nine fetuses were included: the crown-rump length was 10-24 mm and corresponded to 7 and 9 WG according to the Robinson formula. The Carnegie stages were 17-21. Dice micro-CT and HF-MRI presented high signal to noise ratio, >5, according to the Rose criterion, and for allowed anatomical phenotyping in these specimens. Imaging did not alter the histology, allowing immunostaining and pathological examination. CONCLUSION: PM non-destructive whole-body multimodal micro-imaging: dice micro-CT and HF-MRI allows for PM human fetal anatomy study as early as 8 WG. It paves the way to virtual autopsy in the very early first trimester. Obtaining a precision phenotype, even regarding miscarriage products, allows a reverse phenotyping to select variants of interest in genome-wide analysis, offering potential genetic counseling for bereaved parents.


Asunto(s)
Feto , Imagen por Resonancia Magnética , Embarazo , Femenino , Humanos , Microtomografía por Rayos X/métodos , Feto/diagnóstico por imagen , Edad Gestacional , Autopsia/métodos , Imagen por Resonancia Magnética/métodos
16.
Cell Mol Life Sci ; 80(5): 117, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37020120

RESUMEN

Protein expression is a primary area of interest for routine histological diagnostics and tissue-based research projects, but the limitations of its post-mortem applicability remain largely unclear. On the other hand, tissue specimens obtained during autopsies can provide unique insight into advanced disease states, especially in cancer research. Therefore, we aimed to identify the maximum post-mortem interval (PMI) which is still suitable for characterizing protein expression patterns, to explore organ-specific differences in protein degradation, and to investigate whether certain proteins follow specific degradation kinetics. Therefore, the proteome of human tissue samples obtained during routine autopsies of deceased patients with accurate PMI (6, 12, 18, 24, 48, 72, 96 h) and without specific diseases that significantly affect tissue preservation, from lungs, kidneys and livers, was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the kidney and liver, significant protein degradation became apparent at 48 h. For the lung, the proteome composition was rather static for up to 48 h and substantial protein degradation was detected only at 72 h suggesting that degradation kinetics appear to be organ specific. More detailed analyses suggested that proteins with similar post-mortem kinetics are not primarily shared in their biological functions. The overrepresentation of protein families with analogous structural motifs in the kidney indicates that structural features may be a common factor in determining similar postmortem stability. Our study demonstrates that a longer post-mortem period may have a significant impact on proteome composition, but sampling within 24 h may be appropriate, as degradation is within acceptable limits even in organs with faster autolysis.


Asunto(s)
Cambios Post Mortem , Proteoma , Humanos , Autopsia/métodos , Cromatografía Liquida , Espectrometría de Masas en Tándem
17.
J Obstet Gynaecol Can ; 46(9): 102611, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39019327

RESUMEN

The database autopsy method was developed to determine probable causes of maternal deaths in the Canadian Institute for Health Information's hospital discharge abstract database; however, the method has yet to be validated. Using immediate cause of death information from Québec's hospitalization database as the gold standard, this study assessed the validity and reliability of the database autopsy method for pregnancy-associated deaths. The method had high sensitivity and specificity for identifying the most common causes of these deaths, as well as high interobserver agreement. We conclude that the database autopsy method is valid and reliable overall.


Asunto(s)
Autopsia , Bases de Datos Factuales , Humanos , Femenino , Embarazo , Autopsia/estadística & datos numéricos , Autopsia/métodos , Causas de Muerte , Canadá/epidemiología , Reproducibilidad de los Resultados , Complicaciones del Embarazo/mortalidad , Quebec/epidemiología , Adulto , Sensibilidad y Especificidad
18.
Pediatr Radiol ; 54(10): 1713-1719, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39112568

RESUMEN

BACKGROUND: In post-mortem (PM) fetal and neonatal imaging, relevant clinical information is crucial for accurate interpretation and diagnosis; however, it is usually incomplete. OBJECTIVE: To propose a standardized template for PM fetal and neonatal imaging referrals to enhance communication between referring clinicians and reporting radiologists. MATERIALS AND METHODS: A modified Delphi approach was conducted amongst members of the European Society of Paediatric Radiology (ESPR) PM Task Force and other recommended PM imaging specialists worldwide to determine consensus on necessary information. These were based on three pre-existing referral templates already in use across a variety of centers. The study ran for 4 months (December 2023-April 2024). RESULTS: Nineteen specialists from 17 centers worldwide formed our expert panel. The final agreed referral template information includes the patient's identification details (mother and fetus when available), fetal/neonatal information (gestational age, sex, type of demise (including type of termination of pregnancy (i.e., surgical or medical)), date and time of fetal demise (+ delivery) or neonatal death, singleton/multiple pregnancy, clinical information (obstetrical history, prenatal imaging findings, amniocentesis findings, physical external examination findings), provisional clinical diagnosis, and ordering physician's information. CONCLUSION: A comprehensive referral template has been created, representing expert consensus on the minimum data required for the conduct of quality PM fetal and neonatal imaging, with the goal of facilitating accuracy of image interpretation.


Asunto(s)
Autopsia , Técnica Delphi , Derivación y Consulta , Humanos , Recién Nacido , Europa (Continente) , Autopsia/métodos , Femenino , Sociedades Médicas , Comités Consultivos , Embarazo , Pediatría/normas , Feto/diagnóstico por imagen , Muerte Fetal , Imágenes Post Mortem
19.
Pediatr Radiol ; 54(10): 1720-1728, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39115697

RESUMEN

RATIONALE AND OBJECTIVES: Introduction of post-mortem imaging has helped improve sudden unexpected death in infancy (SUDI) management in Europe. French guidelines were issued in 2007 to homogenise SUDI investigations including imaging. The aim of this study was to evaluate current imaging management of SUDI in France. MATERIAL AND METHODS: Between January 2022 and July 2022, all 35 SUDI French referral centres were invited to answer an e-mailed online survey including 29 questions divided into four different sections covering imaging practices for SUDI including radiology department organisation, imaging modalities performed, methods of reading, and current training resources. Partial responses were secondarily completed by a personal call to the SUDI imaging consultant. The current implementation of the 2007 recommendations was compared with a previous evaluation from 2015 and with current North American practices. RESULTS: The participation rate of centres performing SUDI imaging was 100% (35/35). Imaging was systematically performed in 94.3% (33/35) of the centres: 74.3% (26/35) using radiography; 5.7% (2/35) using ultrasound; 94.3% (33/35) using computed tomography (CT), including 89% (31/35) whole-body CT and 5.7% (2/35) brain CT; and 20% (7/35) using magnetic resonance imaging (MRI). Two centres (5.7%, 2/35) did not systematically perform brain imaging. One (2.9%, 1/35) used ultrasound-guided biopsy. In comparison with 2015, rates of brain imaging increased by 25.4% (P=0.008). There was no significant difference in the number of forensic MRIs performed between France and North America (P=0.663). CONCLUSION: Despite improvements since 2015, full compliance with French guidelines for SUDI investigations remains incomplete. The use of imaging, particularly CT and brain imaging, has increased. Further efforts are needed to standardise imaging practices for optimal SUDI investigations.


Asunto(s)
Muerte Súbita del Lactante , Humanos , Francia , Lactante , Recién Nacido , Encuestas y Cuestionarios , Autopsia/métodos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Femenino , Masculino , Diagnóstico por Imagen/métodos , Imagen por Resonancia Magnética/métodos
20.
Am J Forensic Med Pathol ; 45(2): 151-156, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38739896

RESUMEN

ABSTRACT: Autopsy followed by histopathological examination is foundational in clinical and forensic medicine for discovering and understanding pathological changes in disease, their underlying processes, and cause of death. Imaging technology has become increasingly important for advancing clinical research and practice, given its noninvasive, in vivo and ex vivo applicability. Medical and forensic autopsy can benefit greatly from advances in imaging technology that lead toward minimally invasive, whole-brain virtual autopsy. Brain autopsy followed by histopathological examination is still the hallmark for understanding disease and a fundamental modus operandi in forensic pathology and forensic medicine, despite the fact that its practice has become progressively less frequent in medical settings. This situation is especially relevant with respect to new diseases such as COVID-19 caused by the SARS-CoV-2 virus, for which our neuroanatomical knowledge is sparse. In this narrative review, we show that ad hoc clinical autopsies and histopathological analyses combined with neuroimaging of the principal circumventricular organs are critical to gaining insight into the reconstruction of the pathophysiological mechanisms and the explanation of cause of death (ie, atrium mortis) related to the cardiovascular effects of SARS-CoV-2 infection in forensic and clinical medicine.


Asunto(s)
COVID-19 , Humanos , COVID-19/patología , COVID-19/diagnóstico por imagen , Neuroimagen/métodos , Autopsia/métodos , Encéfalo/patología , Encéfalo/diagnóstico por imagen , SARS-CoV-2 , Patologia Forense/métodos , Relevancia Clínica
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