SEARCH · PubMed Health

Results for “Autopsy”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Concealed cardiomyopathy in sudden childhood death: translation from molecular autopsy to family assessment.

One of the ongoing challenges in childhood remains the unexplained sudden death. Autopsies identify a subset of cases that harbor rare variants in genes associated with cardiomyopathy in structurally normal hearts, suggesting a concealed cardiomyopathy. Our goal is to interpret all available data in each case to provide answers to unexplained deaths, while also implementing preventative measures for at-risk family members. Our retrospective study included 68 childhood cases of sudden death, classified as inconclusive at autopsy. Molecular autopsy analyzed all genes currently associated with inherited arrhythmogenic syndromes. Variants were reinterpreted according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Seventeen autopsy-inconclusive childhood cases (70.59% males) carried at least one rare variant in any of the cardiomyopathy-susceptibility genes. A definite deleterious variant was identified in seven cases (10.3%), whereas ten (14.7%) carried only variants of uncertain significance. Slight non-diagnostic myocardial alterations were identified in five cases (7.35%), and three of them carried a deleterious variant. Clinical and genetic analyses of all families identified a carrier of deleterious variants with a diagnosis of cardiomyopathy in six of them (8.82%). Our data support the inclusion of a comprehensive analysis of all genes associated with inherited cardiomyopathies in childhood cases of unexpected death. A personalized multidisciplinary interpretation of post-mortem and genetic data, including family assessment, helps to clarify the role of rare variants and determine the most plausible cause of the unexpected death in one-tenth of the childhood individuals.

Journal Article↗

PubMed2026

The brain as an HIV reservoir: Recent findings using autopsy tissues from people with HIV.

HIV persistence within anatomical reservoirs remains the primary barrier to achieving an HIV cure. While antiretroviral therapy effectively suppresses plasma viremia, it does not eliminate integrated proviral genomes that persist in long-lived cellular compartments. The central nervous system (CNS) is a clinically important HIV reservoir, characterized by immune privilege and the persistence of tissue-resident infection despite effective antiretroviral therapy (ART). Evidence from postmortem studies reveals that HIV DNA, RNA, and even intact replication-competent proviruses remain detectable in brain tissue from virally suppressed people with HIV. Evidence derived primarily from in situ approaches and viable-cell studies supports myeloid-lineage reservoirs, particularly microglia and CNS-associated macrophages, as key cellular sources of persistence, while the extent and biological relevance of astrocyte infection remains debated. These reservoirs exhibit transcriptional activity and are associated with chronic neuroinflammation, which may contribute to HIV-associated neurocognitive disorders, despite systemic viral suppression. Here, we synthesize recent findings from autopsy brain studies, including work enabled by major biorepositories, such as the National NeuroHIV Tissue Consortium and rapid-autopsy programs, including the Last Gift, both of which are essential for studying HIV reservoirs in the CNS. We summarize methodologies for detecting and characterizing HIV in brain tissue, highlight heterogeneous patterns of regional distribution and compartmentalization, and review emerging links between CNS persistence and neuroinflammation. We conclude with priorities for harmonized tissue processing, multi-modal single-cell and spatial profiling, and coordinated cross-cohort analyses to clarify the contribution of CNS reservoirs to neuroHIV pathogenesis and systemic rebound.

Humans↗

PubMed2026

First Fatal Case of Adult Meningoencephalitis Caused by Pasteurella canis: An Autopsy Case Report.

Pasteurella canis is a Gram-negative bacterium commonly found as a commensal organism in the oral cavity of dogs and cats. Human infections are rare and typically occur following skin breaches, with bacteremia reported less frequently. To date, fatal central nervous system infections in adults caused by P. canis have not been reported. We report the case of a 25-year-old immunocompetent man with no significant medical history. The patient developed otitis a few days after his dog licked his ear. Twenty days later, he died at home following a febrile illness with headaches. An autopsy revealed purulent meningitis. Bacteriological cultures from the ear and subdural empyema isolated P. canis and Streptococcus anginosus group. To our knowledge, this is the first reported case of fatal adult meningoencephalitis caused by P. canis. The case highlights the pathogen's invasive potential and underscores the importance of prompt evaluation of otitis with neurological involvement.

Humans↗

PubMed2026

Mortality of Individuals With PRNP Variants Associated With Prion Disease in the United States, 1998-2024.

BACKGROUND AND OBJECTIVES: To characterize the survival of individuals with pathogenic PRNP variants-including to estimate annual hazards, to judge the accuracy of previously reported survival data, and to evaluate the utility of public record searches in determining vital status. METHODS: In this single-center cohort study, we gathered data on individuals who received positive antemortem PRNP genetic tests at the US National Prion Disease Pathology Surveillance Center (NPDPSC), including both diagnostic tests in symptomatic individuals, and predictive tests in asymptomatic individuals. Genetic test and autopsy results were queried from the NPDPSC database, and public record searches were conducted using online tools. RESULTS: Four hundred four individuals received positive genetic test results. Of 206 cases symptomatic at the time of genetic testing, 188 are likely now deceased based on typical disease duration for their genetic variants. Combined autopsy and public record searches in combination confirmed 174 of these deaths, for an estimated 92.6% sensitivity. We evaluated the age-dependent penetrance of the reportedly highly penetrance variants D178N and E200K and the reportedly low-penetrance variant V210I. Among 99 initially asymptomatic individuals with the pathogenic E200K variant, more than 936 person-years of follow-up, 18 deaths were observed, significantly fewer than 27.4 expected according to life tables based on retrospective data. The age-dependent penetrance of E200K calculated from these longitudinal data was significantly lower than that from retrospective data, with 69% penetrance by age 80 and a median age at death of 75. For the pathogenic D178N variant, the median age at death was 57, which was numerically later, but not significantly different from, that seen in retrospective data. For V210I, just 2 deaths occurred, both after age 90, consistent with minimal penetrance. DISCUSSION: Our data support high penetrance of PRNP D178N and E200K variants and low penetrance of V210I. For E200K, the age at onset distribution appears to be shifted slightly later, and lifetime risk slightly lower, than previously reported. Autopsy data and public death records in combination were sensitive and concordant for determining long-term outcomes, but additional prospective data should be gathered to support future preventive trials.

Journal Article↗

PubMed2026

Bioepidemiology of cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, primarily due to immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid, is an increasingly recognized cause of heart failure. Modern diagnostic advances suggest that ATTR, particularly in older adults, may be more prevalent than historically reported. METHODS: All Olmsted County decedents aged ≥40 years from 1970 to 1976 were identified. Available ventricular myocardium from retained paraffin blocks was screened histologically for amyloid using sulfated Alcian blue staining; positive cases underwent grading and proteomic typing by laser microdissection coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Beyond prevalence estimation, this analysis characterizes amyloid type, deposition grade and distribution, associated comorbidities, and cause-of-death patterns, comparing amyloid-positive decedents with age- and sex-matched controls. RESULTS: Of 2,566 eligible deaths, 1,028 autopsy cases with evaluable myocardium formed the study cohort (mean age 70.5 years; 61.1% male; 97% White). Cardiac amyloid was present in 52 cases giving an overall prevalence of 5.1% (95% CI: 3.8-6.6, which rose from 0% under age 60 to 37.5% (95% CI: 21.1-56.3) in those ≥90 years (p < 0.001). While prevalence estimates were higher in men above age 80 compared to women, there was no evidence of an interaction of age and sex (p = 0.90). The quantity of amyloid was sufficient for typing in 38 cases: ATTR (84.2%), AL (7.9%), serum amyloid A (5.3%), and apolipoprotein A-IV (2.6%). Adjusted estimates assuming untyped mild cases were ATTR-type increased ATTR prevalence to 4.5% (95% CI: 3.3-5.9) overall. Comorbidity profiles were similar between amyloid-positive and negative groups, though syncope and leg weakness were more common in amyloid-positive decedents. CONCLUSIONS: In an unselected autopsy cohort, cardiac amyloid was common, particularly ATTR in older adults. Prevalence increased steeply after age 80. These findings suggest that ATTR amyloidosis is not rare and is likely underdiagnosed and has similar prevalence in women and men, despite the male predominance reported in the literature.

Humans↗

PubMed2026

Development of a universal primer set for the identification of enterovirus serotypes using next-generation sequencing.

Enteroviruses have been recognized as major etiological agents of viral myocarditis, a significant contributor to sudden cardiac death. However, the causative virus genomes are rarely identified in forensic autopsy specimens, because extensive nucleic acid degradation compromises analysis. The aim of this study was to develop a next-generation sequencing (NGS)-based method for detecting and identifying the serotype of enteroviruses, which are one of the primary viral causes of myocarditis. We developed a primer set using sequences from 21 representative enterovirus serotypes. The sensitivity of the method was assessed using 13 artificial enteroviral DNA constructs. To confirm the clinical performance of our proposed method, a subset of nasal specimens was analyzed independently by a commercial laboratory using the BioFire Respiratory Panel 2.1 microarray-based viral screening assay, and the results were compared with those obtained using our method. Our method was able to detect as few as 10 copies of artificial DNA and successfully identified all 13 evaluated serotypes, even within a mixture sample. Compared with the BioFire Respiratory Panel 2.1 microarray-based assay, our NGS-based method demonstrated concordant results in 12 out of 14 evaluated cases, showing comparable detection sensitivity. In a trial application of the method, we were also able to detect and serotype enteroviruses in frozen myocardial samples from three forensic myocarditis cases. Overall, the findings of this study suggest that the NGS-based method developed here is a promising diagnostic approach for identifying the causative pathogens of viral myocarditis in forensic autopsy cases.

Autopsy myocardial sample↗

PubMed2018

Sex-specific genetic predictors of Alzheimer's disease biomarkers.

Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = - 0.03, p = 4.25 × 10-8; β = 0.03, p = 3.97 × 10-8) than males (β = - 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10-10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

Aged, 80 and over↗

PubMed2026

SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer.

PURPOSE: Treatment intensification with androgen receptor pathway inhibitors (ARPIs) has become the standard of care for patients with metastatic prostate cancer. However, there remains an unmet need to identify biomarkers for treatment resistance. Here, we identify SPEN inactivation as a driver of ARPI resistance. EXPERIMENTAL DESIGN: Pre-clinical studies were performed in LNCaP and VCaP cell lines. Data from a nationwide prostate cancer clinico-genomic database were extracted. Log-rank test and Cox proportional hazards models were used to compare time to next treatment (TTNT) on ARPI with/without SPEN mutations. SPEN immunohistochemistry was performed on a rapid autopsy metastatic tissue microarray. RESULTS: SPEN was identified as a top enzalutamide resistance hit in an unbiased genome-wide loss-of-function screen. SPEN inactivation results in upregulation of cell cycle proliferation and basal/stem cell activity as well as increased translation of pro-oncogenic genes. In a large patient cohort (N=6828), SPEN mutations are enriched following treatment with ARPIs (2.1% to 3.6%, p=0.001) and correlate with shorter TTNT on ARPI in patients with metastatic hormone-sensitive prostate cancer (6.4 vs 29.7 months, HR 2.67, p=0.02). In a metastatic rapid autopsy cohort (N=181), low SPEN H-score is associated with shorter time on abiraterone (5.0 vs 7.9 months, p=0.023) in metastatic castration-resistant prostate cancer. CONCLUSIONS: In real-world cohorts, loss of SPEN function across genomic, transcriptomic, and protein levels is associated with reduced benefit from ARPI therapy in metastatic prostate cancer. These findings identify SPEN inactivation as a clinically relevant biomarker of ARPI resistance that warrants prospective evaluation to guide treatment selection.

Journal Article↗

PubMed2025

Expression of Bovine Meat and Milk Factor in Hepatocellular Carcinoma and Colorectal Liver Metastasis Patients.

Bovine meat and milk factors (BMMFs) are plasmid-like DNA molecules isolated from cow's milk, meat, and human cancer tissues proposed to contribute to the development of specific types of cancer including colorectal cancer (CRC) and breast cancer based on chronic inflammation-associated indirect carcinogenesis. Chronic necro-inflammation of the liver poses a strong risk factor for the induction of hepatocellular carcinoma (HCC), which is associated with high intake of meat. Whether BMMFs contribute to HCC carcinogenesis or the development of colorectal liver metastasis (CRLM) remains unknown. Therefore, in this study, the presence of BMMFs was assessed in the liver of patients with viral and nonviral hepatitis-related HCC (n = 25), CRLM (14) and in healthy liver tissue from autopsy specimens (18) using monoclonal antibodies against the conserved BMMF Rep protein for immunohistochemistry, immunofluorescence detection, and immunoblotting. Rep was expressed in all tumor-distant and peritumor tissue specimens of HCC and CRLM patients and associated with CD68+ macrophages around portal triads. The number of Rep+CD68+cells was increased in HCC and CRLM patients compared to healthy liver tissue, which may indicate a link between BMMFs and tumor-associated chronic inflammation in the liver. Exclusively in viral hepatitis-linked HCC, Rep expression was also detected in the tumor. In addition, specifically in the liver of healthy individuals, we observed a well-defined gradient Rep expression in hepatocytes around the central veins. Altogether, these observations may indicate that the presence of BMMFs in the liver is associated with chronic inflammation and may represent a novel risk factor or surrogate marker for liver cancer.

Humans↗

PubMed2022

An epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2.

Elevated levels of cytokines IL-1β and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1β released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes. SARS-CoV-2-infected HAE supply a second signal, which includes genomic and mitochondrial DNA, to stimulate leukocyte IL-1β release. Nuclease treatment, STING, and caspase-1 inhibition but not NLRP3 inhibition blocked leukocyte IL-1β release. After release, IL-1β stimulates IL-6 secretion from HAE. Therefore, infection alone does not increase IL-1β secretion by either cell type. Rather, bi-directional interactions between the SARS-CoV-2-infected epithelium and immune bystanders stimulates both IL-1β and IL-6, creating a pro-inflammatory cytokine circuit. Consistent with these observations, patient autopsy lungs show elevated myeloid inflammasome gene signatures in severe COVID-19.

Humans↗

PubMed2026

Trop-1/EpCAM Thr115 is a driver of hyperproliferative cell repair and of severe lung damage in COVID-19.

SARS-CoV-2 lung infection triggers an acute reaction that can severely impair oxygen exchange. However, the underlying molecular processes are poorly understood. The TROP1/EPCAM p.M115T polymorphism was found associated with COVID-19 severity. We discovered here that the T115 Trop-1/EpCAM is a driver of cell growth, whereas M115 Trop-1/EpCAM has little, if any, cell growth induction capacity. TROP1/EPCAM knockout mice showed altered proliferation of embryonic stem cells. The Trop-1/EpCAM T115 allele was then found to drive hyperproliferative capacity in murine fibrosarcoma cells. Corresponding growth stimulation was shown in human colon cancer cells, through CRISPR-Cas9 ablation of the endogenous TROP1/EPCAM and comparative transfection of TROP1/EPCAM p.T115 (T-mod) or p.M115 (M-mod) alleles. In COVID-19 patients, T115 Trop-1/EpCAM was shown to cause aberrant, hyperproliferative wound repair in SARS-CoV-2-damaged lung alveoli that led to critical oxygen-exchange impairment. Analysis of COVID-19 patient lungs at autopsy showed hyperproliferation of T115 Trop-1/EpCAM+ epithelial cells over the alveolar epithelium damaged by the infection. This correlated with T115 Trop-1/EpCAM+ inflammatory cells hyperproliferation and alveolar hyaline membrane formation. These multi-layered barriers were computed to reduce oxygen diffusion by up to 100-fold. Our findings indicate an unanticipated mechanism for lung damage by T115 Trop-1/EpCAM, and suggest a potential target for corresponding therapeutic approaches.

COVID-19↗

PubMed2026

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations With Race and Prostate Cancer Outcomes.

Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer, including prostate cancer. In the present study, we report that the prevalence of subclonal genomic loss of CDKN1B, especially among self-reported African-American or Black (AA) individuals, has likely been underestimated in primary prostate cancer. Using immunohistochemistry (IHC) for p27 protein and a large cohort of whole tissue sections from radical prostatectomy (N = 412) from AA and European American (EA) individuals, we discovered an unexpectedly high frequency of regions of intratumoral complete p27 protein loss (IPPL) within larger tumor nodules that otherwise showed intact p27 staining that was more prevalent among prostate cancer in AA individuals (18.1%) than EA individuals (12.2%). Regions of IPPL were tightly associated with loss of CDKN1B messenger RNA by in situ hybridization. Furthermore, these focal regions of IPPL were closely linked to CDKN1B genomic loss as detected by next-generation sequencing panel sequencing of laser-captured regions. The detection of IPPL by IHC was associated with ≥pT3 pathologic stage (extraprostatic extension and seminal vesicle involvement) and pN1 (local lymph node involvement) disease; however, when stratified by race, these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available data sets as well as in our analysis of autopsy specimens via IHC. Overall, subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer and could contribute to worse prostate cancer outcomes, specifically in AA individuals. Our findings warrant further exploration into the clinical utility of using IHC for p27 loss as a prognostic biomarker.

CDKN1B cancer disparities↗

PubMed2026

Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis.

Diabetic polyneuropathy is a common complication of diabetes, yet substantial inter-individual variation in peripheral pain perception suggests underlying genetic influences. This population-based study investigated clinical, metabolic, and genetic determinants of pain threshold using intraepidermal electrical stimulation in 906 participants from the Iwaki Health Promotion Project 2017. Genome-wide association analysis identified 12 loci showing suggestive associations, among which a missense variant in LAMP3 (rs482912) was prioritized as a biologically plausible candidate. Phenotype-stratified analyses showed that individuals carrying the CT or CC genotypes had lower PINT indices than those with the TT genotype, indicating reduced pain thresholds. Notably, the CC genotype retained an association with lower pain threshold using intraepidermal electrical stimulation under conditions of metabolic stress, including impaired glucose tolerance, elevated HbA1c, and obesity, whereas this association was attenuated in the presence of hypertension. Single-cell RNA sequencing analysis of human skin revealed that LAMP3-positive mature dendritic cells, enriched in immunoregulatory molecules, exhibited transcriptional enrichment of inflammatory, antigen-presenting, and nociception-related pathways, including NF-κB, JAK-STAT, cytokine signaling, and neuroimmune sensitization cascades. Autopsy-based skin analysis further demonstrated genotype-associated differences in dermal LAMP3-positive cell infiltration and CD8-positive T-cell abundance, while CD4-positive T-cell abundance and intraepidermal nerve fiber density remained unchanged across genotypes. Taken together, these findings suggest a potential association between LAMP3 variation and individual differences in peripheral pain threshold and provide biological context supporting a role for neuroimmune interactions in early sensory modulation under metabolic stress. Given the suggestive genetic evidence and indirect mechanistic data, these observations should be interpreted as exploratory and hypothesis-generating.

Humans↗

PubMed1991

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.

Alzheimer Disease↗

PubMed2025

Mitochondrial dysfunction in MED13 variant-associated disease: a case of infantile spasms, cardiomyopathy and hepatomegaly.

Here we report a de novo heterozygous MED13 variant (c.2503C>T, p.Pro835Ser) in an infant presenting with infantile spasms, hypertrophic cardiomyopathy and hepatomegaly. Autopsy revealed mitochondrial abnormalities in cardiac and hepatic tissues, with reduced respiratory chain complex activity. This is the first case report linking a MED13 variant to systemic mitochondrial dysfunction, suggesting a novel pathogenic mechanism.

Journal Article↗

PubMed2026

Evolution and heterogeneity of lethal metastatic bladder cancer subtypes.

Histological variation is a prognostic feature of metastatic urothelial cancer1-3, but its evolutionary trajectory remains poorly defined. We developed a metastatic bladder cancer rapid autopsy programme enriched in histological subtypes4 to profile individuals with terminal disease. Here by reconstructing the evolutionary histories of patient tumours, we show that metastasis-to-metastasis seeding is the dominant pattern of cancer spread and that increased polyclonal migration predicts poor prognosis. The burden, heterogeneity and timing of genomic alterations differ markedly among histological subtypes. Plasmacytoid and neuroendocrine variants develop early driver alterations associated with shorter survival. Mutational signature analyses and experimental models demonstrated that plasmacytoid tumours uniquely use the Fanconi anaemia pathway to mitigate chemotherapy-induced genomic scarring. Single-nucleus profiling revealed mixed cell states in histological subtypes and an association between transcriptional heterogeneity and patient survival. Characterization of the tumour microenvironment uncovered distinct immune states across subtypes, with plasmacytoid tumours exhibiting immune-inflamed profiles, whereas squamous tumours are predominantly immunosuppressive. Last, we demonstrate that post-mortem cell-free DNA captures genomic and transcriptional heterogeneity of the subtypes, which provides a potential strategy for noninvasive assessment of tumour identity and aggressiveness. Our results provide new insights into how tumour heterogeneity shapes the evolutionary history of disease progression in bladder cancer histological subtypes.

Journal Article↗

PubMed2026

A profile of deaths in children at the Diepkloof Forensic Pathology Services mortuary in Gauteng, South Africa from 1 January 2019 to 31 December 2020.

This retrospective study was conducted to address the scarcity of knowledge regarding unnatural child deaths in South Africa. This was done by analysing cases admitted to the Diepkloof Forensic Pathology Services mortuary between 1 January 2019 and 31 December 2020. Data from FPS death registers and FPS case files were used to profile: (1) the incidence, causes and manner of death, circumstances of death, and ancillary investigations performed at autopsy; and (2) to assess the impact of the COVID-19 pandemic on trauma-related child deaths. Of 4 704 decedents, 535 (11.4%) were children, predominantly male (55.5%) and Black (94.8%). Accidental deaths were the most common manner of death (42.6%), primarily due to road traffic accidents, burns, and aspiration. Homicides accounted for 6.5% of all deaths in children, most frequently involving sharp force or gunshot injuries. Cranio-cerebral injuries predominated in trauma-related deaths. In 2020, compared to preceding years, with the implementation of the COVID-19 restrictions, there was a decrease in trauma-related child fatalities. These findings suggest that many child deaths are potentially preventable through government implementation of improved safety interventions and community education.

Humans↗

PubMed2026

A profile of firearm-related fatalities admitted to the Diepkloof Forensic Pathology Service Soweto medico-legal mortuary during the COVID-19 and post COVID-19 periods.

This retrospective descriptive study examined firearm-related fatalities during (April-December 2020; n = 241) and after (April-December 2023; n = 299) COVID-19 lockdowns using 540 cases from the Diepkloof Forensic Pathology Service, Soweto, South Africa. Data was obtained from autopsy reports, forensic records, police statements, and death scene documentation. Firearm violence affected young adult Black males (22-43 years), with only minor demographic shifts post-pandemic. The overall burden and core patterns of violence remained stable, with criminal activity - primarily robbery and interpersonal violence - persisting as the leading contexts, and homicide the dominant manner of death. Post-COVID-19 findings demonstrated contextual shifts, including increased incidents in public and social environments, reflecting greater mobility and resumption of social activity. A significant rise in mean blood alcohol concentration (0.09 g/100 mL vs 0.14 g/100 mL; p < 0.0001) suggests increased alcohol involvement following easing of restrictions. Unfortunately, persistent information gaps, noted particularly in circumstantial history, incident location, firearm type, highlighting the need for improved data provision and capture systems. While the epidemiology of firearm-related fatalities remained unchanged, the post-COVID-19 period was characterised by increased alcohol involvement, shifts toward public-space violence, and fewer gunshot wounds per victim, suggesting changes in situational and behavioural dynamics rather than underlying drivers of violence.

Humans↗