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Circulation Dec 2023
Topics: Humans; Pandemics; COVID-19; Death, Sudden, Cardiac; Autopsy; Vaccination; Cause of Death
PubMed: 38109343
DOI: 10.1161/CIRCULATIONAHA.123.066270 -
Acta Neuropathologica Communications Dec 2023Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other... (Review)
Review
BACKGROUND
Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample.
METHODS
Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43).
RESULTS
We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (β = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (β = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition.
CONCLUSION
The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Alleles; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Arteriosclerosis; Autopsy; Cerebral Amyloid Angiopathy; Cognition; DNA-Binding Proteins; Genotype; Lewy Body Disease; Stroke, Lacunar
PubMed: 38115150
DOI: 10.1186/s40478-023-01681-z -
BMC Pregnancy and Childbirth Dec 2023Reduction of Tanzania's neonatal mortality rate has lagged behind that for all under-fives, and perinatal mortality has remained stagnant over the past two decades. We...
BACKGROUND
Reduction of Tanzania's neonatal mortality rate has lagged behind that for all under-fives, and perinatal mortality has remained stagnant over the past two decades. We conducted a national verbal and social autopsy (VASA) study to estimate the causes and social determinants of stillbirths and neonatal deaths with the aim of identifying relevant health care and social interventions.
METHODS
A VASA interview was conducted of all stillbirths and neonatal deaths in the prior 5 years identified by the 2015-16 Tanzania Demographic and Health Survey. We evaluated associations of maternal complications with antepartum and intrapartum stillbirth and leading causes of neonatal death; conducted descriptive analyses of antenatal (ANC) and delivery care and mothers' careseeking for complications; and developed logistic regression models to examine factors associated with delivery place and mode.
RESULTS
There were 204 stillbirths, with 185 able to be classified as antepartum (88 [47.5%]) or intrapartum (97 [52.5%]), and 228 neonatal deaths. Women with an intrapartum stillbirth were 6.5% (adjusted odds ratio (aOR) = 1.065, 95% confidence interval (CI) 1.002, 1.132) more likely to have a C-section for every additional hour before delivery after reaching the birth attendant. Antepartum hemorrhage (APH), maternal anemia, and premature rupture of membranes (PROM) were significantly positively associated with early neonatal mortality due to preterm delivery, intrapartum-related events and serious infection, respectively. While half to two-thirds of mothers made four or more ANC visits (ANC4+), a third or fewer received quality ANC (Q-ANC). Women with a complication were more likely to deliver at hospital only if they received Q-ANC (neonates: aOR = 4.5, 95% CI 1.6, 12.3) or ANC4+ (stillbirths: aOR = 11.8, 95% CI 3.6, 38.0). Nevertheless, urban residence was the strongest predictor of hospital delivery.
CONCLUSIONS
While Q-ANC and ANC4 + boosted hospital delivery among women with a complication, attendance was low and the quality of care is critical. Quality improvement efforts in urban and rural areas should focus on early detection and management of APH, maternal anemia, PROM, and prolonged labor, and on newborn resuscitation.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Stillbirth; Perinatal Death; Tanzania; Cross-Sectional Studies; Infant Mortality; Obstetric Labor Complications; Uterine Hemorrhage; Autopsy; Anemia
PubMed: 38082404
DOI: 10.1186/s12884-023-06099-y -
Forensic Science International Jun 2024Cardiac implantable electronic devices (CIED) are a heterogeneous group of medical devices with increasingly sophisticated diagnostic capabilities, which could be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiac implantable electronic devices (CIED) are a heterogeneous group of medical devices with increasingly sophisticated diagnostic capabilities, which could be exploited in forensic investigations. However, current guidelines are lacking clear recommendations on the topic. The first aim of this systematic review is to provide an updated assessment of the role of postmortem CIED interrogation, and to give practical recommendations, which can be used in daily practice. Secondly, the authors aim to determine the rates of postmortem CIED interrogation and autopsy investigations, the type of final rhythm detected close to death (with a focus on the significance of documented arrhythmias), as well as the role of postmortem CIED interrogation in the determination of final cause/time of death, and any potentially fatal device malfunctions.
METHODS
A systematic search in MEDLINE and Scopus aiming to identify reports concerning postmortem human CIED interrogation was performed, including a systematic screening of reference lists. Case reports, letters to the editors, commentaries, review articles or guidelines were excluded, along with studies related to cardiac devices other than CIED. All data were pooled and analyzed using fixed-effects meta-analysis models, and the I statistic was used to assess heterogeneity.
RESULTS
A total of 25 articles were included in the systematic review, enrolling 3194 decedent CIED carriers. Ten studies (40%) had a 100% autopsy rate, whereas in further 6 studies autopsy findings were variably reported; CIED interrogation was available from 22 studies (88%), and it was never performed prior to autopsy. The overall rate of successful postmortem CIED interrogation was 89%, with high heterogeneity among studies, mainly due to device deactivation/battery discharge. Twenty-four percent of CIED carriers experienced sudden cardiac death (SCD), whereas non-sudden cardiac and non-cardiac death (NSCD, NCD) were reported in 37% and 30% of decedents, respectively. Ventricular tachyarrhythmias were recorded in 34% of overall successfully interrogated CIED, and in 62% of decedents who experienced a SCD; of all ventricular tachyarrhythmias recorded, 40% was found in NSCD or NCD. A clear interpretation of the etiological role of recorded arrhythmias in the causation of death required integration with autopsy findings. Overall, potentially fatal device malfunctions were detected in 12% of cases.
CONCLUSIONS
Postmortem CIED interrogation is a valuable tool for the determination of the cause of death, and may complement autopsy. Forensic pathologists need to know the potential utility, pitfalls, and limitations of this diagnostic examination to make this tool as much reliable as possible.
Topics: Humans; Arrhythmias, Cardiac; Defibrillators, Implantable; Equipment Failure; Pacemaker, Artificial; Cause of Death; Guidelines as Topic; Autopsy
PubMed: 38714107
DOI: 10.1016/j.forsciint.2024.112001 -
Europace : European Pacing,... Feb 2024Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic... (Review)
Review
AIMS
Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic testing, molecular autopsy (MA), in elucidating the cause of SCD in athletes.
METHODS AND RESULTS
We reviewed a database of 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre. All cases underwent detailed cardiac autopsy, and 748 were deemed to be athletes. Of these, 42 (6%) were investigated with MA (28 using a targeted sequencing, 14 exome sequencing). Variants were classified as pathogenic, likely pathogenic, or variant of unknown significance using international guidelines. Clinical information was obtained from referring coroners who completed a detailed health questionnaire. Out of the 42 decedents (average age 35 years old, 98% males) who were investigated with MA, the autopsy was in keeping with a structurally normal heart [sudden arrhythmic death syndrome (SADS)] in n = 33 (78%) cases, followed by arrhythmogenic cardiomyopathy (ACM) in eight (19%) individuals and idiopathic left ventricular fibrosis in one (2%). Death occurred during exercise and at rest in 26 (62%) and 16 (38%) individuals, respectively. Variants that were adjudicated clinically actionable were present in seven cases (17%). There was concordance between the genetic and phenotypic findings in two cases of ACM (in FLNC and TMEM43 genes). None of the variants identified in SADS cases were previously linked to channelopathies. Clinically actionable variants in cardiomyopathy-associated genes were found in five cases of SADS.
CONCLUSION
The yield of MA in athletes who died suddenly is 17%. In SADS cases, clinically actionable variants were found in cardiomyopathy-associated genes and not in channelopathy-associated genes. Arrhythmogenic cardiomyopathy is a common cause of SCD in athletes, and one in four decedents with this condition had a clinically actionable variant in FLNC and TMEM43 genes.
Topics: Male; Humans; Adult; Female; Death, Sudden, Cardiac; Cardiomyopathies; Autopsy; Athletes; Registries; United Kingdom
PubMed: 38289717
DOI: 10.1093/europace/euae029 -
Current Opinion in Microbiology Jun 2024Hepatic sequelae are frequently reported in coronavirus disease 2019 cases and are correlated with increased disease severity. Therefore, a detailed exploration of host... (Review)
Review
Hepatic sequelae are frequently reported in coronavirus disease 2019 cases and are correlated with increased disease severity. Therefore, a detailed exploration of host factors contributing to hepatic impairment and ultimately infection outcomes in patients is essential for improved clinical management. The causes of hepatic injury are not limited to drug-mediated toxicity or aberrant host inflammatory responses. Indeed, multiple studies report the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver autopsies and the susceptibility of explanted human hepatocytes to infection. In this review, we confirm that hepatic cells express an extensive range of factors implicated in SARS-CoV-2 entry. We also provide an overview of studies reporting evidence for direct infection of liver cell types and the infection-induced cell-intrinsic processes that likely contribute to hepatic impairment.
Topics: Humans; SARS-CoV-2; COVID-19; Liver; Viral Tropism; Hepatocytes; Virus Internalization; Host-Pathogen Interactions; Animals
PubMed: 38522265
DOI: 10.1016/j.mib.2024.102455 -
Forensic Science International Feb 2024Autopsy rates are declining worldwide, resulting in increasing selectivity in referral for forensic autopsy and increased uncertainty about the validity of assigned...
INTRODUCTION
Autopsy rates are declining worldwide, resulting in increasing selectivity in referral for forensic autopsy and increased uncertainty about the validity of assigned causes of death. Persons with psychiatric disorders have high rates of premature death but not all are referred for forensic autopsies. Knowledge is needed on which decedents with psychiatric disorders are chosen for forensic autopsy to determine whether causes of death are at risk of being misclassified among certain subgroups of decedents.
METHODS
We conducted a nationwide register-based case-control study including all decedents with psychiatric disorders in Denmark in the period 1998-2015. Using multivariate logistic regression, we examined associations between demographic and socioeconomic factors, comorbidities, healthcare utilization, and referral for forensic autopsy, overall and stratified by age at death (<45, 45-64, ≥65 years).
RESULTS
Of the 152,799 decedents in the study population, 7043 (4.61 %) had a forensic autopsy. Decedents referred for forensic autopsy were more likely to be young, have a history of substance use, and have schizophrenia or an affective disorder (factors listed in diminishing order of strength of association). Increasing severity of comorbidities as measured by the Charlson comorbidity index was associated with decreasing likelihood of being autopsied. Patterns of association with sex, alcohol use, habitation and education did not vary by age at death. Schizophrenia and drug use were most strongly associated with forensic autopsy in decedents < 45 years of age, whereas death early in the study period was more strongly associated with autopsy in the oldest age groups.
DISCUSSION
The decision to refer a decedent for forensic autopsy was predominantly based on the decedent's age, history of drug use, and the absence of non-psychiatric comorbidities. Causes of death in decedents with comorbidities or recent contact with the healthcare system and decedents > 65 years may be more likely to be inaccurate, particularly in drug users.
Topics: Humans; Aged; Case-Control Studies; Autopsy; Mental Disorders; Substance-Related Disorders; Schizophrenia; Cause of Death
PubMed: 38290227
DOI: 10.1016/j.forsciint.2024.111940 -
International Journal of Legal Medicine May 2024The possibility of using epigenetics in forensic investigation has gradually risen over the last few years. Epigenetic changes with their dynamic nature can either be... (Review)
Review
The possibility of using epigenetics in forensic investigation has gradually risen over the last few years. Epigenetic changes with their dynamic nature can either be inherited or accumulated throughout a lifetime and be reversible, prompting investigation of their use across various fields. In forensic sciences, multiple applications have been proposed, such as the discrimination of monozygotic twins, identifying the source of a biological trace left at a crime scene, age prediction, determination of body fluids and tissues, human behavior association, wound healing progression, and determination of the post-mortem interval (PMI). Despite all these applications, not all the studies considered the impact of PMI and post-sampling effects on the epigenetic modifications and the tissue-specificity of the epigenetic marks.This review aims to highlight the substantial forensic significance that epigenetics could support in various forensic investigations. First, basic concepts in epigenetics, describing the main epigenetic modifications and their functions, in particular, DNA methylation, histone modifications, and non-coding RNA, with a particular focus on forensic applications, were covered. For each epigenetic marker, post-mortem stability and tissue-specificity, factors that should be carefully considered in the study of epigenetic biomarkers in the forensic context, have been discussed. The advantages and limitations of using post-mortem tissues have been also addressed, proposing directions for these innovative strategies to analyze forensic specimens.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Body Fluids; Biomarkers; Autopsy; Forensic Medicine
PubMed: 38242965
DOI: 10.1007/s00414-024-03165-8 -
PloS One 2023The majority (40%) of the world's under-five mortality burden is concentrated in nations like Nigeria (16.5%), India (16%), Pakistan (8%), and the Democratic Republic of...
The majority (40%) of the world's under-five mortality burden is concentrated in nations like Nigeria (16.5%), India (16%), Pakistan (8%), and the Democratic Republic of the Congo (6%), where an undetermined number of under-five deaths go unrecorded. In low-resource settings throughout the world, the Verbal Autopsy-Social Autopsy (VASA) technique may assist assess under-five mortality estimates, assigning medical and social causes of death, and identifying relevant determinants. Uncertainty regarding missing data in high-burden nations like Pakistan necessitates a valid and reliable VASA instrument. This is the first study to validate Child Health Epidemiology Reference Group-CHERG's VASA tool globally. In Pakistan, data from such a valid and reliable tool is vital for policy. This paper reports on the VASA tool in Karachi, Pakistan. Validity and reliability of the CHERG VASA tool were tested using face, content, discriminant validation, and reliability tests on one hundred randomly selected mothers who had recently experienced an under-five child death event. Data were computed on SPSS (version-21) and R software. Testing revealed high Item-content Validity Index (I-CVI) (>81.43%); high Cronbach's Alpha (0.843); the accuracy of between 75-100% of the discriminants classifying births to live and stillbirths; and I-CVI (>82.07% and 88.98% respectively) with high accuracy (92% and 97% respectively) for assigning biological and social causes of child deaths, respectively. The CHERG VASA questionnaire was found relevant to the conceptual framework and valid in Pakistan. This valid tool can assign accurate medical and non-medical causes of child mortality cases occurring in Pakistan.
Topics: Female; Humans; Autopsy; Cause of Death; Child Mortality; Pakistan; Reproducibility of Results; Stillbirth; Infant, Newborn; Infant; Child, Preschool
PubMed: 38109305
DOI: 10.1371/journal.pone.0278149 -
Frontiers in Endocrinology 2023The number of patients with prolonged critical illness (PCI) has been increasing in many countries, and the adrenal gland plays an important role in maintaining...
BACKGROUND
The number of patients with prolonged critical illness (PCI) has been increasing in many countries, and the adrenal gland plays an important role in maintaining homeostasis during PCI. Chronic disease burden is reportedly associated with shorter telomere lengths in human tissues. Telomere shortening in human somatic cells is largely dependent on cell divisions, and critically short telomeres lead to cellular dysfunction and aging. However, the association between PCI and telomere lengths in human adrenal cells is poorly understood. In this study, we investigated this association to assess whether the burden of PCI could accelerate the aging process in adrenal cells.
METHODS
Adrenocortical tissues from patients who died after PCI usually show a diffuse pattern of intracellular cholesterol ester depletion (i.e., lipid depletion). This study examined near-normal adrenal glands obtained from autopsied patients who died suddenly (control group) and lipid-depleted adrenal glands obtained from autopsied patients who died after PCI (PCI group). The control group included 7 men aged 80 to 94 years (mean age: 85.3 years) and 7 women aged 84 to 94 years (mean age: 87.7 years). The PCI group included 10 men aged 71 to 88 years (mean age: 78.8 years) and 8 women aged 77 to 95 years (mean age: 85.6 years). By using quantitative fluorescence hybridization, relative telomere lengths (RTLs) were determined in the parenchymal cells of the three adrenocortical zones (zona glomerulosa, zona fasciculata, and zona reticularis [ZR]) and in the chromaffin cells of the medulla. The number of adrenal parenchymal cells was determined by immunohistochemistry and digital image analysis.
RESULTS
RTLs in ZR cells were significantly shorter in the PCI group than in the control group for both men and women ( = 0.0001 for men and = 0.0012 for women). However, RTLs in the remaining three types of adrenal cells did not differ between the control and PCI groups for both men and women. The number of ZR cells was higher in the PCI group than in the control group for both men and women ( < 0.0001 for both men and women). The proportion of the number of ZR cells to the total number of adrenocortical parenchymal cells was also higher in the PCI group than in the control group ( < 0.0001 for both men and women). The Ki-67 proliferation index in ZR cells was higher in the PCI group than in the control group ( = 0.0039 for men and = 0.0063 for women).
CONCLUSIONS
This study demonstrated ZR cell-specific telomere shortening in patients with adrenal lipid depletion who died after PCI. Our results suggest that the reactive proliferation of ZR cells accelerates the telomere shortening and aging process in ZR cells in these patients. The results of our study may contribute to the understanding of adrenal aging during PCI.
Topics: Male; Humans; Female; Aged, 80 and over; Aged; Zona Reticularis; Critical Illness; In Situ Hybridization, Fluorescence; Telomere Shortening; Cholesterol Esters
PubMed: 37745694
DOI: 10.3389/fendo.2023.1244553