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Indian Journal of Pathology &... 2024Shaggy aorta is defined as "very extensive atheromatous disease with diffuse ulcers associated with soft, loosely held debris and a paucity of actual thrombus" and often...
AIMS
Shaggy aorta is defined as "very extensive atheromatous disease with diffuse ulcers associated with soft, loosely held debris and a paucity of actual thrombus" and often results in visceral or peripheral arterial embolization (shaggy aorta syndrome). Most of the studies are clinico-radiological with hardly any assessment of the pathological features. We present an autopsy analysis of shaggy aorta.
MATERIALS AND METHODS
A retrospective study of autopsied cases of shaggy aorta over 15 years was conducted. The involvement of the various segments of the aorta (ascending, transverse, thoracic, and abdominal) was correlated with the clinical manifestations and cardiac/extra-cardiac findings at autopsy. The mortality was categorized as those related to shaggy aorta (Group I), related to cardiac diseases (Group II), and those unrelated to cardiovascular diseases (Group III).
STATISTICAL ANALYSIS
Nil.
RESULTS
In a span of 15 years, there were 76 cases of shaggy aorta affecting predominantly males (85.5%) and patients in the sixth decades of life (mean age of 64.5 years). The important associated cardiovascular risk factors included hypertension, tobacco use, and diabetes mellitus. Predominant involvement of the entire aorta and arch + descending aorta was seen in 39.5% and 35.5% of the cases, respectively. Regardless of extreme severity, only half of the patients (37 cases, 48. 7%) had clinical presentation due to shaggy aorta.
CONCLUSIONS
The occurrence of shaggy aorta may be more common than expected, and it would be important to keep this possibility in mind even in asymptomatic elderly patients with cardiovascular risk factors since aorto-arterial manipulations and anti-coagulant therapy can prove detrimental in such patients.
Topics: Male; Humans; Aged; Middle Aged; Female; Retrospective Studies; Aorta, Thoracic; Autopsy
PubMed: 38358195
DOI: 10.4103/ijpm.ijpm_573_22 -
Virchows Archiv : An International... Dec 2023Autopsy rates are declining, while major discrepancies between autopsies and clinical diagnoses remain. Still, little is known about the impact of suspected underlying...
Autopsy rates are declining, while major discrepancies between autopsies and clinical diagnoses remain. Still, little is known about the impact of suspected underlying diseases, for example, a diagnosis of cancer, on the autopsy rate. The aim of this study was to investigate the relation between the clinical cause of death, a history of cancer, and the medical autopsy rate using data from the Netherlands Cohort Study on Diet and Cancer (NLCS), a large prospective cohort study with a long follow-up. The NLCS is a prospective study initiated in 1986 and includes 120,852 persons (58,279 males and 62,573 females), 55-69 years of age at the time of enrollment. The NLCS was linked with the Dutch Nationwide Pathology Databank (PALGA), the Dutch Population Register (GBA), the Netherlands Cancer Registry, and the causes of death registry (Statistics Netherlands). If applicable, the 95% confidence intervals were calculated. During the follow-up of the NLCS, 59,760 deaths were recorded by linkage with the GBA from 1991 until 2009. Of these, a medical autopsy was performed on 3736 deceased according to linkage with PALGA, resulting in an overall autopsy rate of 6.3%. Major variations in the autopsy rate were observed according to the cause of death. The autopsy rate increased according to the number of contributing causes of death. Lastly, a diagnosis of cancer affected the autopsy rate. The clinical cause of death and a history of cancer both influenced the medical autopsy rate in a large national cohort. The insight this study provides may help clinicians and pathologists counteracting the further downfall of the medical autopsy.
Topics: Male; Female; Humans; Aged; Autopsy; Prospective Studies; Cohort Studies; Cause of Death; Retrospective Studies; Neoplasms
PubMed: 37269366
DOI: 10.1007/s00428-023-03571-0 -
Genes Aug 2023The analysis of genetic material may be the only way to identify an unknown person or solve a criminal case. Often, the conditions in which the genetic material was... (Review)
Review
The analysis of genetic material may be the only way to identify an unknown person or solve a criminal case. Often, the conditions in which the genetic material was found determine the choice of the analytical method. Hence, it is extremely important to understand the influence of various factors, both external and internal, on genetic material. The review presents information on DNA and RNA persistence, depending on the chemical and physical factors affecting the genetic material integrity. One of the factors taken into account is the time elapsing to genetic material recovery. Temperature can both preserve the genetic material or lead to its rapid degradation. Radiation, aquatic environments, and various types of chemical and physical factors also affect the genetic material quality. The substances used during the forensic process, i.e., for biological trace visualization or maceration, are also discussed. Proper analysis of genetic material degradation can help determine the post-mortem interval (PMI) or time since deposition (TsD), which may play a key role in criminal cases.
Topics: Humans; Nucleic Acids; Forensic Genetics; RNA; Autopsy; Physical Examination
PubMed: 37628694
DOI: 10.3390/genes14081643 -
EBioMedicine Oct 2023Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury.... (Review)
Review
BACKGROUND
Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF.
METHODS
This retrospective autopsy study included cases from the São Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers.
FINDINGS
Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test.
INTERPRETATION
Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10.
FUNDING
This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Bill and Melinda Gates Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Topics: Humans; Middle Aged; Yellow Fever; Myocarditis; Chemokine CXCL10; Retrospective Studies; Brazil; Heart Injuries; RNA; Autopsy; Biomarkers; Necrosis
PubMed: 37757571
DOI: 10.1016/j.ebiom.2023.104810 -
Journal of Neurosciences in Rural... 2023The objective of this study is to provide an overview of the psychological autopsy (PA) research method, including its methodology, uses, limitations, and ethical...
OBJECTIVES
The objective of this study is to provide an overview of the psychological autopsy (PA) research method, including its methodology, uses, limitations, and ethical considerations.
MATERIALS AND METHODS
The study conducted a PA investigation on 35 cases of suicide. Information was collected from multiple sources and reliable informants, including family members, friends, medical and mental health professionals, and other relevant individuals. Qualitative and quantitative research methods were used to analyze the collected information.
RESULTS
The results indicated that several factors were associated with suicide, including mental health problems, life stressors, interpersonal conflicts, substance abuse, and history of previous suicide attempts. The findings have important implications for suicide prevention strategies, emphasizing the significance of addressing mental health issues and providing social support.
CONCLUSION
The PA is a valuable research method for investigating and understanding suicide. Despite challenges such as recall biases and methodological limitations, it provides insights into the psychological factors associated with suicide and informs suicide prevention strategies. However, conducting psychological autopsies requires careful consideration of ethical issues. Further research is needed to replicate and extend the findings of this study.
PubMed: 37692808
DOI: 10.25259/JNRP_144_2023 -
The American Journal of Pathology Nov 2023Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease...
Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR-positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.
Topics: Humans; COVID-19; SARS-CoV-2; Autopsy; RNA, Viral; Inflammation
PubMed: 36963628
DOI: 10.1016/j.ajpath.2023.02.016 -
Acta Neuropathologica Dec 2023Understanding age acceleration, the discordance between biological and chronological age, in the brain can reveal mechanistic insights into normal physiology as well as...
Understanding age acceleration, the discordance between biological and chronological age, in the brain can reveal mechanistic insights into normal physiology as well as elucidate pathological determinants of age-related functional decline and identify early disease changes in the context of Alzheimer's and other disorders. Histopathological whole slide images provide a wealth of pathologic data on the cellular level that can be leveraged to build deep learning models to assess age acceleration. Here, we used a collection of digitized human post-mortem hippocampal sections to develop a histological brain age estimation model. Our model predicted brain age within a mean absolute error of 5.45 ± 0.22 years, with attention weights corresponding to neuroanatomical regions vulnerable to age-related changes. We found that histopathologic brain age acceleration had significant associations with clinical and pathologic outcomes that were not found with epigenetic based measures. Our results indicate that histopathologic brain age is a powerful, independent metric for understanding factors that contribute to brain aging.
Topics: Humans; Child, Preschool; Aging; Brain; Epigenomics; Acceleration; Autopsy; Epigenesis, Genetic; DNA Methylation
PubMed: 37815677
DOI: 10.1007/s00401-023-02636-3 -
Acta Neuropathologica Feb 2024Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease...
Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8/perforin/granzyme A/B cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.
Topics: Humans; Animals; Dogs; Glial Fibrillary Acidic Protein; Encephalomyelitis; Astrocytes; Autoimmune Diseases of the Nervous System; Meningoencephalitis; Autoantibodies
PubMed: 38310187
DOI: 10.1007/s00401-023-02678-7 -
Legal Medicine (Tokyo, Japan) Mar 2024Volatile substance abuse is widespread among adolescents due to its easy availability and methods of consumption. Inhalant abuse represents a current problematic issue,... (Review)
Review
Volatile substance abuse is widespread among adolescents due to its easy availability and methods of consumption. Inhalant abuse represents a current problematic issue, causing significant morbidity and mortality due to direct toxicity on several target organs and displacement of gas which results in a lack of oxygen. This review aims to evaluate post-mortem and toxicological investigations in cases of suspected butane intoxication. We performed comprehensive research using the Preferred Reporting Items for Systematic Review (PRISMA) standards. Forty scientific papers fulfilled the inclusion criteria. A total of 58 cases of butane-related deaths were found. Among these, we found 11 cases of suicide (18%), 1 case of homicide (2%), 44 cases of accidental poisoning (76%), and 2 cases of work-related deaths (4%). Autopsy and post-mortem examinations were performed in 54 cases, whereas toxicological analyses were presented in 56 cases. In autopsy, pulmonary edema (51%) and poli-visceral congestion (59%) were the most common findings. When death by butane inhalation is hypothesized, autopsy and histological findings may be nonspecific, therefore toxicological investigations assume a crucial role along with attention to the methods used to collect biological samples.
PubMed: 38579662
DOI: 10.1016/j.legalmed.2024.102442 -
Molecular Neurodegeneration Feb 2024Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated...
BACKGROUND
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated with CTE pathology are unclear. In brain donors with autopsy-confirmed CTE, we investigated the association of CTE p-tau pathology density and location with cognitive, functional, and neuropsychiatric symptoms.
METHODS
In 364 brain donors with autopsy confirmed CTE, semi-quantitative p-tau severity (range: 0-3) was assessed in 10 cortical and subcortical regions. We summed ratings across regions to form a p-tau severity global composite (range: 0-30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF-A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF-A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS-11), aggression (Brown-Goodwin Aggression Scale), depression (Geriatric Depression Scale-15, GDS-15), and apathy (Apathy Evaluation Scale, AES). Ordinary least squares regression models examined associations between global and regional p-tau severity (separate models for each region) with each clinical scale, adjusting for age at death, racial identity, education level, and history of hypertension, obstructive sleep apnea, and substance use treatment. Ridge regression models that incorporated p-tau severity across all regions in the same model assessed which regions showed independent effects.
RESULTS
The sample was predominantly American football players (333; 91.2%); 140 (38.5%) had low CTE and 224 (61.5%) had high CTE. Global p-tau severity was associated with higher (i.e., worse) scores on the cognitive and functional scales: MI ([Formula: see text] = 0.02, 95%CI = 0.01-0.04), CDS ([Formula: see text] = 0.02, 95%CI = 0.01-0.04), and FAQ ([Formula: see text] = 0.03, 95%CI = 0.01-0.04). After false-discovery rate correction, p-tau severity in the frontal, inferior parietal, and superior temporal cortex, and the amygdala was associated with higher CDS ([Formula: see text] s = 0.17-0.29, ps < 0.01) and FAQ ([Formula: see text] s = 0.21-0.26, ps < 0.01); frontal and inferior parietal cortex was associated with higher MI ([Formula: see text] s = 0.21-0.29, ps < 0.05); frontal cortex was associated with higher BRI ([Formula: see text] = 0.21, p < 0.01). Regions with effects independent of other regions included frontal cortex (CDS, MI, FAQ, BRI), inferior parietal cortex (CDS) and amygdala (FAQ). P-tau explained 13-49% of variance in cognitive and functional scales and 6-14% of variance in neuropsychiatric scales.
CONCLUSION
Accumulation of p-tau aggregates, especially in the frontal cortex, are associated with cognitive, functional, and certain neurobehavioral symptoms in CTE.
Topics: Humans; Activities of Daily Living; Autopsy; Brain; Chronic Traumatic Encephalopathy; Cognition; Neurodegenerative Diseases; tau Proteins
PubMed: 38317248
DOI: 10.1186/s13024-023-00697-2