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The Journal of Pediatrics Jan 2024To evaluate in the Netherlands the national outcomes in providing cause of and insights into sudden and unexplained child deaths among children via the Postmortem...
OBJECTIVE
To evaluate in the Netherlands the national outcomes in providing cause of and insights into sudden and unexplained child deaths among children via the Postmortem Evaluation of Sudden Unexplained Death in Youth (PESUDY) procedure.
STUDY DESIGN
Children aged 0-18 years in the Netherlands who died suddenly were included in the PESUDY procedure if their death was unexplained and their parents gave consent. The PESUDY procedure consists of pediatric and forensic examination, biochemical, and microbiological tests; radiologic imaging; autopsy; and multidisciplinary discussion. Data on history, modifiable factors, previous symptoms, performed diagnostics, and cause of death were collected between October 2016 and December 2021.
RESULTS
In total, 212 cases (median age 11 months, 56% boys, 33% comorbidity) were included. Microbiological, toxicological, and metabolic testing was performed in 93%, 34%, and 32% of cases. In 95% a computed tomography scan or magnetic resonance imaging was done and in 62% an autopsy was performed. The cause of death was explained in 58% of cases and a plausible cause was identified in an additional 13%. Most children died from infectious diseases. Noninfectious cardiac causes were the second leading cause of death found. Modifiable factors were identified in 24% of non-sudden infant death syndrome/unclassified sudden infant death cases and mostly involved overlooked alarming symptoms.
CONCLUSIONS
The PESUDY procedure is valuable and effective for determining the cause of death in children with sudden unexplained deaths and for providing answers to grieving parents and involved health care professionals.
Topics: Infant; Male; Adolescent; Child; Humans; Female; Sudden Infant Death; Autopsy; Magnetic Resonance Imaging; Netherlands; Cause of Death
PubMed: 37852434
DOI: 10.1016/j.jpeds.2023.113780 -
Acta Neuropathologica Oct 2023Anti-IgLON5 disease is a rare neurological, probably autoimmune, disorder associated in many cases with a specific tauopathy. Only a few post-mortem neuropathological...
Anti-IgLON5 disease is a rare neurological, probably autoimmune, disorder associated in many cases with a specific tauopathy. Only a few post-mortem neuropathological studies have been reported so far. Little is known about the pathogenic mechanisms that result in neurodegeneration. We investigated the neuropathology of anti-IgLON5 disease and characterized cellular and humoral inflammation. We included nine cases (six of them previously published). Median age of patients was 71 years (53-82 years), the median disease duration was 6 years (0.5-13 years), and the female to male ratio was 5:4. Six cases with a median disease duration of 9 years presented a prominent tauopathy. Five of them had a classical anti-IgLON5-related brainstem tauopathy and another presented a prominent neuronal and glial 4-repeat tauopathy, consistent with progressive supranuclear palsy (PSP). Three cases with short disease duration (median 1.25 years) only showed a primary age-related neurofibrillary pathology. Inflammatory infiltrates of T and B cells were mild to moderate and did not significantly differ between anti-IgLON5 disease cases with or without tauopathy. In contrast, we found an extensive neuropil deposition of IgG4 in the tegmentum of the brainstem, olivary nucleus, and cerebellar cortex that was most prominent in two patients with short disease duration without the typical IgLON5-related tauopathy. The IgG4 deposits were particularly prominent in the cerebellar cortex and in these regions accompanied by mild IgG1 deposits. Activated complement deposition (C9neo) was absent. Our study indicates that IgLON5-related tau pathology occurs in later disease stages and may also present a PSP-phenotype with exclusively 4-repeat neuronal and glial tau pathology. The prominent deposition of anti-IgLON5 IgG4 at predilection sites for tau pathology suggests that anti-IgLON5 antibodies precede the tau pathology. Early start of immunotherapy might prevent irreversible neuronal damage and progression of the disease, at least in a subgroup of patients.
Topics: Aged; Female; Humans; Male; Autopsy; Encephalitis; Hashimoto Disease; Immunoglobulin G; Cell Adhesion Molecules, Neuronal; tau Proteins
PubMed: 37646790
DOI: 10.1007/s00401-023-02625-6 -
Journal of Forensic and Legal Medicine Jan 2024Donepezil is one of the primary treatments options for patients suffering from Alzheimer's Disease. In a review of more than 2200 postmortem donepezil positive blood... (Review)
Review
Donepezil is one of the primary treatments options for patients suffering from Alzheimer's Disease. In a review of more than 2200 postmortem donepezil positive blood specimens, 76% of concentrations were higher than the proposed therapeutic range. Means and medians were similar between central blood specimens and peripheral specimens, indicating minimal postmortem redistribution. Postmortem concentrations may not reflect those circulating antemortem. Mean and median postmortem blood concentrations were approximately 3-fold higher than those in antemortem blood specimens. Additionally, in cases where antemortem blood was available for testing, large increases in donepezil concentrations were reported between antemortem and postmortem specimens without documented administration by medical personnel. Elevated blood donepezil concentrations have been reported in multiple postmortem cases where cause of death was unrelated. The blood concentrations reported in cases where donepezil did not contribute to death overlapped with those in suspected drug overdose cases where other drugs may have been present. In 4 out of 5 suspected donepezil overdose cases, blood concentrations greater than 1000 ng/mL were reported, whereas less than 1% of all postmortem blood samples reviewed achieved these concentrations. Blood concentrations greater than 1000 ng/mL should be considered contributory when a drug overdose is suspected. Postmortem donepezil concentrations should be interpreted with caution in the context of a comprehensive case history.
Topics: Humans; Donepezil; Postmortem Changes; Autopsy; Drug Overdose
PubMed: 38043240
DOI: 10.1016/j.jflm.2023.102625 -
BMC Pulmonary Medicine Oct 2023Risk factors of severe coronavirus disease 2019 (COVID-19) have been previously reported; however, histological risk factors have not been defined thus far. The aim of... (Review)
Review
Risk factors of severe coronavirus disease 2019 (COVID-19) have been previously reported; however, histological risk factors have not been defined thus far. The aim of this study was to clarify subclinical hidden interstitial lung disease (ILD) as a risk factor of severe pneumonia associated with COVID-19. We carefully examined autopsied lungs and chest computed tomography scanning (CT) images from patients with COVID-19 for interstitial lesions and then analyzed their relationship with disease severity. Among the autopsy series, subclinical ILD was found in 13/27 cases (48%) in the COVID-19 group, and in contrast, 8/65 (12%) in the control autopsy group (p = 0.0006; Fisher's exact test). We reviewed CT images from the COVID-19 autopsy cases and verified that subclinical ILD was histologically detectable in the CT images. Then, we retrospectively examined CT images from another series of COVID-19 cases in the Yokohama, Japan area between February-August 2020 for interstitial lesions and analyzed the relationship to the severity of COVID-19 pneumonia. Interstitial lesion was more frequently found in the group with the moderate II/severe disease than in the moderate I/mild disease (severity was evaluated according to the COVID-19 severity classification system of the Ministry of Health, Labor, and Welfare [Japan]) (moderate II/severe, 11/15, 73.3% versus moderate I/mild, 108/245, 44.1%; Fisher exact test, p = 0.0333). In conclusion, it was suggested that subclinical ILD could be an important risk factor for severe COVID-19 pneumonia. A benefit of these findings could be the development of a risk assessment system using high resolution CT images for fatal COVID-19 pneumonia.
Topics: Humans; COVID-19; Autopsy; Retrospective Studies; Lung Diseases, Interstitial; Lung; Risk Factors
PubMed: 37891495
DOI: 10.1186/s12890-023-02692-1 -
The Journal of Pathology Jun 2024While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample...
While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research. Via an extensive questionnaire, we collected information on the study design, enrolment strategy, study conduct, sample and data management, and challenges and opportunities of research autopsy programmes in oncology worldwide. Fourteen programmes participated in this study. Eight programmes operated 24 h/7 days, resulting in a lower median postmortem interval (time between death and start of the autopsy, 4 h) compared with those operating during working hours (9 h). Most programmes (n = 10) succeeded in collecting all samples within a median of 12 h after death. A large number of tumour sites were sampled during each autopsy (median 15.5 per patient). The median number of samples collected per patient was 58, including different processing methods for tumour samples but also non-tumour tissues and liquid biopsies. Unique biological insights derived from these samples included metastatic progression, treatment resistance, disease heterogeneity, tumour dormancy, interactions with the tumour micro-environment, and tumour representation in liquid biopsies. Tumour patient-derived xenograft (PDX) or organoid (PDO) models were additionally established, allowing for drug discovery and treatment sensitivity assays. Apart from the opportunities and achievements, we also present the challenges related with postmortem sample collections and strategies to overcome them, based on the shared experience of these 14 programmes. Through this work, we hope to increase the transparency of postmortem tissue donation, to encourage and aid the creation of new programmes, and to foster collaborations on these unique sample collections. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Humans; Autopsy; Neoplasms; Medical Oncology; Animals; Translational Research, Biomedical
PubMed: 38551513
DOI: 10.1002/path.6271 -
Fa Yi Xue Za Zhi Aug 2023The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been... (Review)
Review
The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been searching for objective, quantifiable and accurate methods of PMI estimation. With the development and combination of high-throughput sequencing technology and artificial intelligence technology, the establishment of PMI model based on the succession of the microbial community on corpses has become a research focus in the field of forensic medicine. This paper reviews the technical methods, research applications and influencing factors of microbial community in PMI estimation explored by using high-throughput sequencing technology, to provide a reference for the related research on the use of microbial community to estimate PMI.
Topics: Humans; Postmortem Changes; Artificial Intelligence; Autopsy; Cadaver; Microbiota
PubMed: 37859480
DOI: 10.12116/j.issn.1004-5619.2022.420606 -
Alzheimer's & Dementia : the Journal of... Oct 2023We examined the progression of extrapyramidal symptoms and signs in autopsy-confirmed dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and...
INTRODUCTION
We examined the progression of extrapyramidal symptoms and signs in autopsy-confirmed dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and Alzheimer's disease dementia (AD).
METHODS
Longitudinal data were obtained from Arizona Study of Aging and Neurodegenerative Disease, with PDD (n = 98), AD (n = 47) and DLB (n = 48) further sub-grouped as with or without parkinsonism (DLB+ and DLB-). Within-group Unified Parkinson's Disease Rating Scale (UPDRS) -II and UPDRS-III trajectories were analyzed using non-linear mixed effects models.
RESULTS
In DLB, 65.6% had parkinsonism. Baseline UPDRS-II and III scores (off-stage) were highest (P < 0.001) for PDD (mean ± SD 14.3 ± 7.8 and 27.4 ± 16.3), followed by DLB+ (6.0 ± 8.8 and 17.2 ± 17.1), DLB- (1.1 ± 1.3 and 3.3 ± 5.5) and AD (3.2 ± 6.1 and 8.2 ± 13.6). Compared to PDD, the DLB+ group had faster UPDRS-III progression over 8-years (Cohen's-d range 0.98 to 2.79, P < 0.001), driven by gait (P < 0.001) and limb bradykinesia (P = 0.02) subscales.
DISCUSSION
Motor deficits progress faster in DLB+ than PDD, providing insights about expected changes in motor function.
HIGHLIGHTS
Dementia with Lewy bodies has faster motor progression than Parkinson's disease dementia Linear and non-linear mixed modeling analysis of longitudinal data was utilized Findings have implications for clinical prognostication and trial design.
Topics: Humans; Alzheimer Disease; Parkinson Disease; Dementia; Lewy Body Disease; Neurodegenerative Diseases; Autopsy
PubMed: 37422286
DOI: 10.1002/alz.13357 -
Nature Communications Mar 2024Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain...
Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.
Topics: Humans; Alzheimer Disease; Neuropathology; Plasma; Neurofibrillary Tangles; Autopsy; tau Proteins; Biomarkers; Amyloid beta-Peptides
PubMed: 38521766
DOI: 10.1038/s41467-024-46876-7 -
The American Journal of Forensic... Dec 2023A key element for diagnosing cardiac enlargement in an autopsy setting is relevant heart weight references. However, most available references are to a large extent not...
A key element for diagnosing cardiac enlargement in an autopsy setting is relevant heart weight references. However, most available references are to a large extent not representative of a medicolegal autopsy population, implying that reference weights are likely lower than those in the relevant population.To establish more applicable heart weight references in a medicolegal autopsy population, we designed a heart weight model that accounts for undiagnosed cardiac enlargement using data from 11,897 nontraumatic Swedish medicolegal autopsy cases autopsied between 2010 and 2019. The model was validated in 296 nonobese young adult suicidal hanging cases.For a decedent of average height (174 cm), the evidence that a heart weight was enlarged reached weak support at approximately 430 g, substantial support at approximately 480 g, and strong support at 520 g. The modeled prevalence of cardiac enlargement was very high among elderly and obese decedents.We believe that our model is more applicable in a medicolegal setting than those previously published. The presented quantification of the degree of uncertainty regarding diagnosis can help the pathologist in diagnosing cardiac enlargement. To facilitate the use of this model, we also made it available through a simple online tool ( https://formedum.shinyapps.io/HeartWeightCalc/ ).
Topics: Young Adult; Humans; Aged; Autopsy; Suicide; Heart; Suicidal Ideation; Cardiomegaly
PubMed: 37819124
DOI: 10.1097/PAF.0000000000000883 -
Forensic Science International Nov 2023Dog bites pose a significant global public health issue and are the most common type of injury caused by animals. While most dog bites result in minor harm, they can... (Review)
Review
Dog bites pose a significant global public health issue and are the most common type of injury caused by animals. While most dog bites result in minor harm, they can also lead to severe or even fatal consequences. In cases involving serious injury or death, forensic pathologists investigate various aspects, including the crime scene, the injuries sustained by the victim, and the characteristics of the dog suspected to have caused the bite. The aim of this study is to provide a systematic review of the literature on the medical-legal implications of dog bites in forensic practice, in order to recognize the dog bite victim features, the injuries and their consequences related to, and to identify the offending dogs. The literature search was performed using PubMed, Scopus and Web of Science from January 1980 to March 2023. Eligible studies have investigated issues of interest to forensic medicine about dog bites to humans. A total of 116 studies met the inclusion criteria and were included in the review and they were organized and discussed by issue of interest (biting dog features, dog bite victim features, anatomical distribution of dog bites, injuries related to dog bites, cause of death, bite features, dog identification and post-mortem dog depredation). The findings of this systematic review highlight the importance of bite mark analysis in reconstructing the events leading to the attack and identifying the dog responsible. In medical forensic evaluations of dog bite cases, a multidisciplinary approach is crucial. This approach involves thorough analysis of the crime scene, identification of risk factors, examination of dog characteristics, and assessment of the victim's injuries. By combining expertise from both human and veterinary forensic fields, a comprehensive understanding can be achieved in dog bite cases.
Topics: Humans; Dogs; Animals; Bites and Stings; Forensic Medicine; Crime; Risk Factors; Autopsy
PubMed: 37783138
DOI: 10.1016/j.forsciint.2023.111849