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International Journal of Molecular... Jun 2024The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to... (Review)
Review
The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to play a significant role. Data from analyses of central nervous system autopsy material from patients diagnosed with multiple sclerosis, as well as from studies in the main experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), suggest the possibility of a role of oxidative stress as well. In this narrative review, we summarize the main data from studies reported on oxidative stress markers in patients diagnosed with MS and in experimental models of MS (mainly EAE), and case-control association studies on the possible association of candidate genes related to oxidative stress with risk for MS. Most studies have shown an increase in markers of oxidative stress, a decrease in antioxidant substances, or both, with cerebrospinal fluid and serum/plasma malonyl-dialdehyde being the most reliable markers. This topic requires further prospective, multicenter studies with a long-term follow-up period involving a large number of patients with MS and controls.
Topics: Humans; Oxidative Stress; Multiple Sclerosis; Biomarkers; Animals; Encephalomyelitis, Autoimmune, Experimental; Antioxidants
PubMed: 38927996
DOI: 10.3390/ijms25126289 -
Journal of Medical Case Reports Jun 2024Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens....
BACKGROUND
Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens. Therefore, we consider it necessary to report our patient's case of testicular metastasis from colon cancer.
CASE PRESENTATION
We report a 61-year-old Han Chinese male patient who presented to our clinic with progressive painless swelling of the right testicle for 2 years. Positron emission tomography-computed tomography scans showed increased 18F-fluorodeoxyglucose metabolism in the right testicle, possibly owing to distant metastasis. His previous medical history suggested that he had undergone laparoscopic-assisted right hemicolectomy for ascending colon cancer 4 years ago. Considering the ascending colon cancer metastasis to the right testicle, we performed a right radical testicular resection through an inguinal approach. Postoperative histological examination showed intestinal metastatic adenocarcinoma.
CONCLUSION
Colon cancer metastasis to the testes is uncommon. The clinical and imaging manifestations of this tumor are nonspecific, so the diagnosis relies on postoperative pathology. If testicular metastasis is found, treatment principles for advanced colon cancer should be followed.
Topics: Humans; Male; Testicular Neoplasms; Colonic Neoplasms; Middle Aged; Adenocarcinoma; Positron Emission Tomography Computed Tomography; Colectomy; Orchiectomy; Colon, Ascending; Fluorodeoxyglucose F18
PubMed: 38926771
DOI: 10.1186/s13256-024-04587-z -
Nature Communications Jun 2024Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples,...
Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.
Topics: Humans; RNA Editing; Adenosine; Adenosine Deaminase; Brain; Inosine; RNA-Binding Proteins; Autopsy; Prefrontal Cortex; Postmortem Changes; Male
PubMed: 38926387
DOI: 10.1038/s41467-024-49268-z -
Molecular Genetics & Genomic Medicine Jun 2024Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It...
BACKGROUND
Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It is a leading cause of heart failure and cardiac death at a young age. Cases with neonatal onset DCM were correlated with severe clinical presentation and poor prognosis. A monogenic molecular etiology accounts for nearly half of cases.
FAMILY DESCRIPTION
Here, we report a family with three deceased offspring at the age of 1 year old. The autopsy of the first deceased infant revealed a DCM. The second infant presented a DCM phenotype with a severely reduced Left Ventricular Ejection Fraction (LVEF) of 10%. Similarly, the third infant showed a severe DCM phenotype with LVEF of 30% as well, in addition to eccentric mitral insufficiency.
RESULTS
Exome sequencing was performed for the trio (the second deceased infant and her parents). Data analysis following the autosomal dominant and recessive patterns of inheritance was carried out along with a mitochondrial pathways-based analysis. We identified a homozygous frameshift variant in the TNNI3 gene (c.204delG; p.(Arg69AlafsTer8)). This variant has been recently reported in the ClinVar database in association with cardiac phenotypes as pathogenic or likely pathogenic and classified as pathogenic according to ACMG.
CONCLUSION
Genetic counseling was provided for the family and a prenatal diagnosis of choronic villus was proposed in the absence of pre-implantation genetic diagnosis possibilities. Our study expands the case series of early-onset DCM patients with a protein-truncating variant in the TNNI3 gene by reporting three affected infant siblings.
Topics: Humans; Cardiomyopathy, Dilated; Frameshift Mutation; Female; Homozygote; Pedigree; Consanguinity; Male; Infant; Phenotype; Troponin I
PubMed: 38924380
DOI: 10.1002/mgg3.2486 -
Cells Jun 2024Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies...
BACKGROUND
Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping.
AIMS
We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS.
METHODS
Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38-98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology.
RESULTS
Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death.
CONCLUSION
Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.
Topics: Humans; Middle Aged; Female; Male; Multiple Sclerosis; Aged; Adult; Biomarkers; Aged, 80 and over; Inflammation; Brain; Microglia; Macrophages
PubMed: 38920650
DOI: 10.3390/cells13121020 -
Archive of Clinical Cases 2024Mediastinal tumors are exceedingly rare during fetal development, presenting significant diagnostic challenges and potentially leading to severe outcomes such as...
Mediastinal tumors are exceedingly rare during fetal development, presenting significant diagnostic challenges and potentially leading to severe outcomes such as stillbirth or metastatic disease if not promptly identified and managed. Pleuropulmonary blastomas are primitive mesenchymal tumors often linked to mutations in the DICER1 gene, indicating a hereditary pattern associated with other common adult neoplasms with dominant inheritance. This report describes a case involving a 20-year-old Caucasian woman whose pregnancy was complicated by a stillbirth in the second trimester. Initial suspicions of a mediastinal tumor arose from blood tests and ultrasound examinations during pregnancy surveillance. However, the definitive diagnosis of a type II pleuropulmonary blastoma was established through a pathological examination at autopsy. This case underscores the complexities of diagnosing fetal mediastinal tumors and contributes to the sparse literature on neonatal pleuropulmonary blastomas. Our comprehensive review of the differential diagnoses and literature emphasizes the unique characteristics of pleuropulmonary blastoma and its similarities to other soft tissue sarcomas, enhancing understanding of their clinical and genetic profiles.
PubMed: 38919847
DOI: 10.22551/2024.43.1102.10286 -
Cureus May 2024Atypical aortic origin of coronary artery (AAOCA) is a rare heart condition that has been identified in only a few autopsy cases and in some patients who have undergone...
Atypical aortic origin of coronary artery (AAOCA) is a rare heart condition that has been identified in only a few autopsy cases and in some patients who have undergone angiographic evaluation. AAOCA is known to be closely linked with aortic valve malformations, with the most common type being the bicuspid aortic valve (BAV). A 77-year-old male with a medical history of hypertension and diabetes presented with dyspnea and orthopnea for three days. During the eventual cardiac catheterization, it was noted that the left coronary artery had an anomalous origin from the right side, coursing between the aorta and pulmonary artery. Contrast-enhanced computerized tomography (CECT) also showed a type 2 BAV and a left main coronary artery arising lower at the level of the pulmonary trunk. The dyspnea in this patient was attributed to diastolic dysfunction, and surgical correction of the coronaries was not done. The patient was managed on an outpatient basis for heart failure. In this case, the patient had an anomalous origin of the left coronary artery and type 2 BAV, which posed significant cardiovascular complications. It is unclear if the presence of the concomitant type 2 BAV led to the origin of the anomalous left coronary artery being at a lower level through its effect on the developmental mechanics. This lower origin may have resulted in lower compressive forces on the coronary artery as the inter-arterial pressures would be lower closer to the heart and farther from the lungs. Our case report aims to highlight this complex presentation where the BAV likely provides a benefit in AAOCA cases.
PubMed: 38919205
DOI: 10.7759/cureus.61136 -
Emerging Infectious Diseases Jul 2024Accurate and timely mortality surveillance is crucial for elucidating risk factors, particularly for emerging diseases. We compared use of COVID-19 keywords on death...
Accurate and timely mortality surveillance is crucial for elucidating risk factors, particularly for emerging diseases. We compared use of COVID-19 keywords on death certificates alone to identify COVID-19 deaths in Minnesota, USA, during 2020-2022, with use of a standardized mortality definition incorporating additional clinical data. For analyses, we used likelihood ratio χ and median 1-way tests. Death certificates alone identified 96% of COVID-19 deaths confirmed by the standardized definition and an additional 3% of deaths that had been classified as non-COVID-19 deaths by the standardized definition. Agreement between methods was >90% for most groups except children, although agreement among adults varied by demographics and location at death. Overall median time from death to filing of death certificate was 3 days; decedent characteristics and whether autopsy was performed varied. Death certificates are an efficient and timely source of COVID-19 mortality data when paired with SARS-CoV-2 testing data.
Topics: Humans; COVID-19; Minnesota; Male; Middle Aged; Female; Death Certificates; Adult; Aged; Child; SARS-CoV-2; Adolescent; Child, Preschool; Young Adult; Infant; Aged, 80 and over; Cause of Death; Autopsy; COVID-19 Testing
PubMed: 38916546
DOI: 10.3201/eid3007.231522 -
International Journal of... Apr 2024Tuberculosis (TB) is the leading infectious cause of mortality in sub-Saharan Africa (SSA); the high prevalence of TB in this region is due to human immunodeficiency... (Meta-Analysis)
Meta-Analysis
Postmortem for Intensified Missed Tuberculosis Case Finding in High Human Immunodeficiency Virus and Tuberculosis-burdened Settings in Sub-Saharan Africa among Adults' Population: Systematic Review and Meta-analysis.
Tuberculosis (TB) is the leading infectious cause of mortality in sub-Saharan Africa (SSA); the high prevalence of TB in this region is due to human immunodeficiency virus (HIV)-coinfection. Despite the advent of modalities to diagnose TB, undiagnosed TB-related deaths among HIV-infected patients remain significantly high. This systematic review aims at characterizing missed TB cases from postmortem studies. This review informs on the burden of TB missed diagnosis and highlights the need of improving TB case-finding strategies, especially among the high-risk groups and early TB therapy initiation to keeping in with the World Health Organization's end TB strategy. We searched PubMed, Cochrane, Web of Science, and African journals online for studies that looked into missed TB cases following postmortem using the following key terms: postmortem, TB diagnosis, and HIV; we included cross-sectional and cohorts from 1980 in the English language that were carried out in SSA among adults' population. Authors used the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reporting, the quality of the included studies was assessed using the Newcastle-Ottawa Scale for observational studies, and STATA 17.0 software was used for analysis. This study was registered in the International Prospective Register of Systematic Reviews with registration number CRD42024507515. The combined prevalence of postmortem missed TB diagnosis among the 6025 participants was 27.13% (95% confidence interval [CI] =14.52-41.89), with a high level of heterogeneity at 98.65% (P < 0.001). The prevalence varied significantly across the included studies, ranging from 1.21% (95% CI = 0.93-1.59) in the general population to 66.67% (95% CI = 50.98-79.37) in people living with HIV (PLWHIV). This current literature suggests that SSA is a region with a high prevalence of missed TB cases but with significant variations between countries. In addition, this study confirms a high number of missed TB infections within the PLWHIV. These results highlight the immediate need for targeted screening and diagnosis strategies and relevant policies.
Topics: Humans; HIV Infections; Africa South of the Sahara; Tuberculosis; Autopsy; Adult; Coinfection; Missed Diagnosis; Prevalence
PubMed: 38916381
DOI: 10.4103/ijmy.ijmy_41_24 -
Journal of Applied Biomedicine Jun 2024In 2020, there were numerous cases in Kazakhstan with clinical symptoms of COVID-19 but negative PCR results in nasopharyngeal and oropharyngeal swabs. The diagnosis was...
In 2020, there were numerous cases in Kazakhstan with clinical symptoms of COVID-19 but negative PCR results in nasopharyngeal and oropharyngeal swabs. The diagnosis was confirmed clinically and by CT scans (computed tomography). The problem with such negative PCR results for SARS-CoV-2 infection confirmation still exists and indicates the need to confirm the diagnosis in the bronchoalveolar lavage in such cases. There is also a lack of information about confirmation of SARS-CoV-2 infection in deceased patients. In this study, various tissue materials, including lungs, bronchi, and trachea, were examined from eight patients who died, presumably from SARS-CoV-2 infection, between 2020 and 2022. Naso/oropharyngeal swabs taken from these patients in hospitals tested PCR negative for SARS-CoV-2. This study presents a modified RNA isolation method based on a comparison of the most used methods for RNA isolation in laboratories: QIAamp Viral RNA Mini Kit and TRIzol-based method. This modified nucleic acid extraction protocol can be used to confirm SARS-CoV-2 infection by RT-qPCR in the tissues of deceased patients in disputed cases. RT-qPCR with RNA of SARS-CoV-2 re-extracted with such method from post-mortem tissues that were stored at -80 °C for more than 32 months still demonstrated high-yielding positive results.
Topics: Humans; COVID-19; SARS-CoV-2; RNA, Viral; Male; Autopsy; Real-Time Polymerase Chain Reaction; Female; Lung; Middle Aged; Aged; COVID-19 Nucleic Acid Testing; Trachea; Adult; Nasopharynx
PubMed: 38912867
DOI: 10.32725/jab.2024.013