Search Results (323)

Background/Objectives: Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive lysosomal storage disorder caused by deficiencies in enzymes required for heparan sulfate degradation. While primarily recognized for its devastating neurodegenerative course, the systemic extent of glycosaminoglycan (GAG) accumulation remains under-characterized. This study aims to provide a detailed multisystemic pathological mapping of MPS III to challenge the traditional “brain-only” disease paradigm and highlight the clinical relevance of extracerebral involvement. Methods: We present a comprehensive clinicopathological analysis of a 15-year-old female patient with a history of profound neuropsychomotor delay, refractory epilepsy, and spastic tetraplegia. Following her death due to terminal bronchopneumonia during palliative care, a complete forensic and pathological autopsy was conducted. Tissue samples from all major organ systems were processed using routine Hematoxylin–Eosin (HE) staining, immunohistochemical staining for CD68, and specialized histochemical stains to identify intracellular storage products. Results: Macroscopic evaluation revealed significant diffuse cerebral atrophy, meningoencephalic edema, cardiac valvulopathy with compensatory myocardial remodeling, and hepatosplenomegaly. Furthermore, erosive gastrointestinal lesions and degenerative renal changes were identified. Histopathological examination confirmed widespread cytoplasmic vacuolization across diverse cell populations, including neurons, hepatocytes, renal tubular cells, and the reticuloendothelial system. These findings demonstrate that GAG deposition is a generalized process affecting nearly every parenchymal structure. Conclusions: Although neurological decline dominates the clinical phenotype, our findings underscore that MPS III is a true systemic storage disorder. Significant involvement of the cardiovascular and visceral systems contributes to the disease’s complexity and mortality. This case reinforces the critical diagnostic value of a comprehensive autopsy in delineating the full morphological spectrum of Sanfilippo syndrome, providing essential insights for multidisciplinary management. Full article

Background and Objectives: Pancreas divisum (PD) is the most common congenital anomaly of the pancreatic ductal system and has been suggested to contribute to pancreatic pathology. However, its true prevalence and relationship with pancreatic diseases remain debated. This systematic review and meta-analysis aimed to estimate the global prevalence of PD and evaluate its association with pancreatic disease. Materials and Methods: A comprehensive search of Google Scholar, Scopus, and PubMed was conducted to identify studies reporting the prevalence of PD across all populations and diagnostic modalities. Pooled prevalence estimates were calculated using a random-effects model. Between-study heterogeneity was assessed using the I² statistic, and publication bias was evaluated using Egger’s test. Results: A total of 117 studies comprising 193,672 subjects were included. The pooled global prevalence of PD was 11.1% (95% CI: 8.0–14.2%) with substantial heterogeneity (I² = 99.96%). PD prevalence was higher among individuals with pancreatic disease (18.7%) compared with cadaveric/autopsy studies (8.8%), healthy individuals (5.6%), and consecutive patients (4.7%). Both complete and incomplete PD were more common in subjects with pancreatic diseases. Among PD subtypes, type I was the most prevalent. Egger’s test demonstrated significant publication bias (p < 0.01). Conclusions: PD affects approximately one in ten individuals worldwide and appears more prevalent in patients with pancreatic diseases. However, this finding should be interpreted with caution due to potential selection bias from predominantly ERCP-based studies. Full article

Background: Severe neurocognitive decline is often seen in elderly glioblastoma patients after treatment with radiation and chemotherapy. But the mechanism behind their deterioration is unclear. We describe one such patient with concomitant primary age-related tauopathy (PART) in bilateral hippocampi. Case presentation: An 88-year-old woman experienced unsteadiness, memory loss, and slurred speech that was caused by an epithelioid glioblastoma with wild-type isocitrate dehydrogenase-1 and methylated promoter of O⁶-methylguanine-DNA methyltransferase. She was treated with gross total resection, followed by intensity-modulated radiotherapy and daily temozolomide. Shortly after starting treatment, she developed fatigue, anorexia, and neurocognitive impairment, which were refractory to corticosteroids. After two cycles of adjuvant temozolomide, she experienced impulsivity, disorientation, hallucinations, somnolence, and incontinence despite stable neuroimaging findings. Treatment was subsequently discontinued, and she died 20 months from the time of her glioblastoma diagnosis. Autopsy revealed tau-positive neurofibrillary tangles, but rare Aβ plaques, in the trans-entorhinal and entorhinal cortices of both hippocampi. These findings are consistent with a diagnosis of PART. Conclusions: Undiagnosed tauopathy could be a negative modifier of glioblastoma treatment. The identification of PART and other tauopathies as risk factors in the elderly population may be important to guide treatment decision. Full article

Background/Objectives: Left ventricular free wall rupture is a rare but catastrophic complication of acute myocardial infarction with extremely high mortality. Deaths occurring in water environments present unique forensic challenges requiring systematic evaluation of drowning, intoxication, trauma, and natural disease. This case report describes a fatal left ventricular free wall rupture occurring shortly after successful percutaneous coronary intervention (PCI), emphasizing the medicolegal differential diagnosis and the importance of comprehensive postmortem evaluation. Results: A 58-year-old man with non-ST-elevation myocardial infarction underwent successful PCI with three drug-eluting stents and was discharged home. Six hours later, he developed severe back pain and was found unresponsive in a bathtub. Autopsy demonstrated a 2.6 cm transmural rupture of the anterolateral left ventricular free wall with 150 mL of hemopericardium. Postmortem computed tomography (PMCT), performed as part of routine forensic evaluation, had identified hemopericardium prior to autopsy. Histology showed coagulative necrosis with neutrophilic infiltration. The rupture site was remote from stented vessels with no procedural injury. Toxicology revealed therapeutic medication levels. Pulmonary and scene findings did not support drowning as a cause of death. Conclusions: Ventricular free wall rupture remains a relevant cause of sudden death following myocardial infarction despite successful revascularization. Comprehensive forensic evaluation integrating scene investigation, macroscopic autopsy findings, histopathology, and toxicology is essential to distinguish natural disease progression from accidental or iatrogenic causes in deaths occurring in water environments. This case highlights that ventricular free wall rupture can occur shortly after apparently successful PCI and underscores the importance of comprehensive forensic evaluation in water-associated deaths. Full article

Background and Objectives: Primary progressive aphasia (PPA) and its variants—logopenic (lvPPA), semantic (svPPA), and nonfluent/agrammatic (nfvPPA)—are progressive neurocognitive syndromes characterized by predominant language impairment and associated with heterogeneous underlying neuropathologies. Accurate diagnosis remains challenging due to overlapping clinical features and complex pathobiological mechanisms. Fluorodeoxyglucose positron emission tomography (FDG-PET), which reflects regional cerebral glucose metabolism, may provide valuable insights into both the diagnosis and pathophysiological characterization of PPA. Materials and Methods: We reviewed the current literature and identified 48 original research articles that utilized FDG-PET in the evaluation of at least one PPA variant. Eight studies focused exclusively on lvPPA, six on svPPA, and two on nfvPPA, either alone or in comparison with other neurodegenerative diseases. Eighteen studies evaluated at least two PPA variants, while thirteen compared multiple PPA variants with other neurodegenerative disorders. Results: Most studies identified characteristic hypometabolic patterns for each PPA variant: left temporoparietal regions in lvPPA, bilateral anterior temporal regions with left predominance in svPPA, and left posterior frontal regions in nfvPPA. These variant-specific metabolic signatures may support differential diagnosis. Additionally, FDG-PET provided important insights into disease progression, including associations with worsening language impairment, evolution toward broader neurodegenerative syndromes, and correlations with specific neurocognitive deficits. These findings are largely consistent with other neuroimaging modalities and disease-specific biomarkers. However, limitations such as small sample sizes and the lack of autopsy confirmation in most studies limit the robustness of the results. Conclusions: FDG-PET appears to be a valuable tool for the diagnosis, differential diagnosis, and pathophysiological understanding of PPA. Nevertheless, large-scale, multicenter investigations incorporating pathologically confirmed cases to further validate its clinical utility are needed. Full article

Background/Objectives: Determining the cardiovascular cause of death, particularly distinguishing ischemic from congestive mechanisms, remains challenging in forensic practice, especially in early ischemia without definitive histological findings. Proteomic techniques and molecular profiling may provide complementary diagnostic information beyond conventional autopsy. Methods: We applied an untargeted high-resolution proteomic approach to postmortem cardiac tissue samples from cardiovascular (ischemic and congestive) and non-cardiovascular deaths. Identified proteins were analyzed using bioinformatic and differential expression workflows. Selected candidates were evaluated in peripheral blood samples for translational validation using statistical modeling, including regression analyses and receiver operating characteristic (ROC) curve assessment. Results: A total of 572 proteins were identified. Although no proteins fulfilled strict exclusivity criteria for a single cause-of-death group, differential expression analysis revealed distinct molecular patterns distinguishing ischemic, congestive, and non-cardiovascular deaths. Thirty-one proteins were differentially expressed between ischemic and congestive cases, including α-1 antitrypsin (AAT), plasma levels did not demonstrate statistically significant discrimination. In contrast, plasma Apolipoprotein A-IV (ApoA-IV) levels were significantly associated with ischemic death in regression models, and ROC analysis yielded a cutoff point with complete separation between ischemic and selected non-cardiovascular cases. However, the limited sample size warrants cautious interpretation due to potential overfitting. Conclusions: Postmortem cardiac proteomic profiling reveals biologically coherent molecular signatures associated with different cardiovascular causes of death. Although further validation in larger independent cohorts is required, ApoA-IV emerges as a promising candidate biomarker for ischemic cardiac death. Multimarker proteomic strategies may complement traditional autopsy to enhance diagnostic accuracy in forensic investigations, particularly in cases with equivocal morphological findings. Full article

The use of postmortem (autopsy) material in fundamental and applied biomedical research significantly facilitates the collection of biomaterial for statistically robust sample cohorts. However, natural adaptive processes to developing cellular stress in the early postmortem period, caused by oxygen and nutrient deprivation, trigger the activation of numerous genes promoting cell survival under stress. Many of these activated pathways are also crucial for tumor cell survival in vivo, as evidenced by various transcriptomic studies. This study aimed to investigate the potential influence of postmortem interval (PMI) duration on gene expression in normal and tumor tissues. Using a model of chemically induced hepatocellular carcinoma in mouse liver, we comparatively analyzed the dynamics of transcript levels for several genes (BRCA1, BRCA2, CHEK1, CHEK2, ATM, CDK12) in paired samples of normal and tumor tissue over a 24-h PMI using RT-qPCR. In normal tissue, gene expression increased significantly, while tumor tissue demonstrated relative transcriptional stability, with no substantial changes in the studied transcript levels. A critical finding was the observed convergence of expression profiles: initial differences between the tissues were completely eliminated by 24 h PMI. This pattern developed despite formally adequate RNA quality (RQN) and the absence of clear signs of progressive autolysis in histology, indicating the insufficiency of standard quality criteria for detecting postmortem changes. These findings collectively underscore the critical importance of minimizing and controlling PMI during the biobanking of oncological samples for reliable transcriptomic research. Full article

Membrane distillation (MD) is an attractive technology for desalination driven by renewable energy and low-grade heat sources. However, specific practical guidelines for intermittent operations, typical of such alternative energy sources, are still limited—particularly with respect to established shutdown measures to mitigate adverse effects on the overall system performance. The present study compares continuous and intermittent air-gap MD desalination at a lab-scale by evaluating performance parameters and scaling development. Apart from a slightly lower distillate productivity and a similar distillate quality under intermittent conditions, no direct difference in MD performance between continuous and intermittent experiments was detected. Nevertheless, online monitoring by image analysis with optical coherence tomography revealed more advanced scaling development during intermittent operation, with larger scaling volumes and cover ratios, particularly after implementing a membrane rinsing and preservation protocol with demineralized water. Membrane autopsies revealed that intermittency led to alterations in the development of the crystal morphology of predominantly CaCO₃ scaling. These changes were attributed to enhanced nucleation and modified growth kinetics triggered by recurring shutdown and start-up phases. Overall, the findings showed that intermittency had an adverse effect in terms of scaling behavior, highlighting the need for operating protocols tailored to each specific MD application. Full article

Fatal intraspecific aggression in brown bears (Ursus arctos) remains poorly documented, yet elucidating its dynamics is critical in order to understand species’ physiology, informing management strategies, and advancing wildlife forensic science applications, which are useful in cases where a natural or illegal cause of death needs to be discerned. In this study, we reported four confirmed cases of lethal aggression (two yearlings and two adults) in the Italian Alps. Comprehensive autopsies were performed to characterize lesion patterns and infer the aggressor identity. Claw-induced lacerations, bite marks and the aspect of hemorrhages suggested the attack sequence. Aggressor identity was investigated by using forensic odontology through inter-canine distance (I-CD) and genetic analysis of peri-lesional saliva. I-CD allowed us to plausibly hypothesize the aggressor’s species and, in the cases where it was possible, to classify the sex and/or age group of the aggressors. While genetic analysis allowed the identification of the four brown bear victims, it did not provide informative results on the aggressors. The cause and manner of death were coded according to international criteria (International Classification of Diseases 11th Revision [ICD-11], WHO). Adult fatalities, supported by gastric content analysis, reflect trophic competition regardless of the mating context and highlight the role of anthropogenic food sources in conflict emergence. These findings underscore the value of integrated approaches in wildlife investigations and provide new insights into ecophysiological factors driving lethal intraspecific aggression. Full article

Background/Objectives: Placental vascular malperfusion, on both the maternal (MVM) and fetal (FVM) side, is a key mechanism linking hypertensive disorders of pregnancy, fetal growth restriction (FGR), stillbirth, preterm neonatal death and neonatal encephalopathy. Nevertheless, clinical use and medico-legal interpretation of placental findings remain inconsistent. To summarize recent evidence on the relationship between placental vascular malperfusion, perinatal mortality and neonatal brain injury, integrating standardized placental pathology with Doppler and angiogenic biomarkers, and to outline the main medico-legal implications. Methods: A PubMed search using the string “((placenta OR placental pathology) AND (stillbirth OR fetal death) AND (maternal vascular malperfusion OR fetal vascular malperfusion))” yielded 118 records. After excluding reviews, meta-analyses, case reports (except one illustrative SARS-CoV-2 placentitis case), non-human studies and papers without original histopathology, 33 studies were included: observational cohorts and case–control studies with standardized placental assessment, autopsy series, biomarker/Doppler cohorts, mechanistic work, one randomized trial protocol and a small number of focused clinical commentaries. Results: Across these studies, MVM emerges as the dominant placental lesion in pre-eclampsia, FGR and a large proportion of stillbirths, especially in early-onset disease and in association with maternal hypertension. FVM is strongly linked to stillbirth and term neonatal encephalopathy, and specific combinations of MVM, FVM and inflammatory lesions correspond to distinct patterns of brain injury. Large population-based cohorts confirm that maternal hypertensive disorders and placental malperfusion are major upstream causes of intrauterine hypoxia and preterm neonatal death. Doppler velocimetry and angiogenic biomarkers (PlGF, sFlt-1 and their ratio) are strongly associated with an increased likelihood of underlying MVM and adverse neonatal outcomes, although their predictive performance remains probabilistic and context-dependent rather than diagnostic. Mechanistic studies suggest roles for placental genomic instability and altered decidual immunity in defective placentation. Conclusions: Maternal and fetal vascular malperfusion represent converging pathways to FGR, stillbirth, preterm neonatal death and neonatal encephalopathy. Routine, standardized placental examination, interpreted together with Doppler and biomarker data, substantially improves causal attribution and timing of injury, with direct consequences for counselling, prevention and medico-legal assessment. Full article

In high-income countries, humans are continuously exposed to indoor and outdoor air pollution. Chronic exposure to these airborne solids and gases from natural or artificial sources is related to higher mortality. The objective of this work is to critically assess whether the association between indoor air pollution and death can support robust causal inference from a strict medico-legal perspective. We conducted a narrative review of existing literature on reported health consequences, autopsy and histopathological findings potentially linked to indoor air pollution exposure, and dose–response relationships and examined their role in criminal liability in Western countries. Despite prevention measures and regulations, establishing criminal liability for indoor air pollution remains arduous beyond a reasonable doubt given associative epidemiological evidence, translational biases, and non-specific autopsy findings. Further research on non-linear models and targeted forensic investigations is warranted. Full article

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy, for which population-level evidence regarding prognostic factors and survival conditions is limited. The available data mostly represent single-institution series, limiting their applicability. This study, therefore, assesses clinicopathological features and determines independent predictive variables of overall survival (OS) in patients with ACC using a population-based cohort. Methods: This retrospective observational cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) Program between 2000 and 2022, initially identifying 1176 patients with ACC. Adult patients (≥18 years) with histologically confirmed ACC were identified using ICD-O-3 histology code 8370/3 and primary site code C74.0. Cases with zero-month survival, missing survival data, or identified only through autopsy or death certificate were excluded. To ensure dataset harmonization, patients with missing or indeterminate tumor grade and unknown stage were also excluded. After applying these inclusion and exclusion criteria, the final analytic cohort consisted of 267 patients. Data on demographic factors, stage of the disease, and treatment (surgery, chemotherapy, radiotherapy) were extracted. OS was evaluated using the Kaplan–Meier method, and independent prognostic factors were identified using Cox proportional hazards regression analysis. Results: The median OS was 54 months [95% confidence intervals (CI): 36–85]. The estimated 1-, 3-, and 5-year OS rates were 77%, 57%, and 48%, respectively. Survival differed significantly according to tumor grade, stage, and surgical treatment. In multivariable Cox regression analysis, increasing age [Hazard ratio (HR): 1.03, 95% CI: 1.02–1.04; p < 0.001], high tumor grade (HR: 2.21, 95% CI: 1.43–3.41; p < 0.001), and distant-stage disease (HR: 3.24, 95% CI: 1.95–5.38; p < 0.001) were independently associated with an increased risk of mortality, whereas surgical treatment was associated with improved survival (HR 0.53, 95% CI 0.30–0.93; p = 0.028). Chemotherapy and radiotherapy were not significantly associated with mortality. Conclusions: In this SEER-based cohort of patients with adrenocortical carcinoma, older age, high tumor grade, and distant-stage disease were independently associated with worse OS, whereas documented receipt of surgery was associated with longer OS. Treatment-related associations should be interpreted cautiously in view of the inherent limitations of registry-based data. Further prospective multicenter studies are needed to confirm these findings. Full article

Escherichia coli, Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans are microorganisms capable of causing severe infections, particularly in patients with underlying comorbidities or immune dysfunction. We report a rare clinical case of a 65-year-old man with advanced cardiac and hepatic disease who developed severe diarrheal syndrome followed by septic shock, rapid clinical deterioration, and death. Microbiological examination of autopsy specimens from the intestinal wall and spleen identified Escherichia coli O128 with an enterotoxigenic profile (lt+, st+, eae−), together with Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans. Histopathological analysis demonstrated catarrhal enteritis with fibrinous deposits, mucosal edema, vascular congestion, and inflammatory infiltration. Although the microbiological findings were partly derived from autopsy material and postmortem bacterial translocation cannot be completely excluded, the concordance between clinical presentation, laboratory findings, and morphological changes supports the presence of a clinically significant infectious process. To our knowledge, this is the first reported human case of fatal polymicrobial infection involving these four pathogens. The case highlights the potential severity of polymicrobial infections in patients with cirrhosis-associated immune dysfunction and underscores the importance of integrated microbiological and molecular diagnostics for accurate etiological assessment. Full article

Hemorrhagic fever with renal syndrome (HFRS) is the most common zoonotic disease in Russia, with about a 98% abundance of Puumala virus in all HFRS cases. We report clinical manifestations and genomic characteristics of the Puumala virus strain that caused an unconventional course of HFRS with sudden death. The patient was admitted to the hospital on the third day from fever onset with hyperthermia, cough, shortness of breath, and severe weakness, and died 28 h after hospitalization despite intensive care. Further analyses of autopsy samples led to Puumala virus detection. The viral genome was sequenced, followed by phylogenetic and similarity plot analyses. The genomic sequences of three viral segments were identified as endemic for the Moscow region strain. Phylogenetic and similarity plot analysis revealed the reassortant origin of the strain via M segment exchange. This finding increases the explored molecular diversity of Puumala virus in the Central Federal District and underscores the need for heightened awareness of HFRS manifestations that deviate from regular clinical presentation. Full article

Chronic exposure to heavy metals poses significant health risks. This study analyzed the concentrations of toxic (Cr, Pb, Cd, Ni) and essential (Cu, Zn, Se, Mn) elements in autopsy samples (the frontal pole area of the brain, the 6th intercostal space of the liver, and lungs (average of left and right lung samples) from 45 residents of South-Eastern Poland using ICP-MS. The aim was to determine the average body burden and organ-specific accumulation in a moderately industrialized region. HDBSCAN clustering revealed highly homogeneous elemental profiles, suggesting a unifying influence of local environmental factors. The liver acted as a metabolic hub, showing preferential sequestration (p < 0.0001) of essential elements (Zn, Se, Mn, Cu) regulated by homeostatic mechanisms. Toxic metals exhibited ‘metabolic trap’ patterns, particularly Cd and Pb in the liver and Cr in the lungs, due to their long biological half-lives. Strong positive correlations (Se–Zn, Se–Cu) indicated integrated antioxidant responses, while toxic pairs (Cr–Ni, Pb–Cd) suggested shared exposure pathways and molecular mimicry via transporters such as DMT1. Results confirmed long-term bioaccumulation, with toxic elements in the brain remaining below 0.25 µg/g. In the lungs, the accumulation hierarchy (Pb > Mn > Cd > Cr) reflected inhalation exposure. These findings emphasize the role of organ-specific sequestration in assessing long-term environmental exposure. Full article