Search Results (983)

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

In this experiment, we used a late 17th century embalming protocol for the long-term preservation (7.2 years) of an infant-sized piglet in order to evaluate the success of this technique over a period of several years. According to the description of the French anatomist Penicher (published in 1699), an 8.8 kg female piglet corpse was treated with a broad spectrum of herbs, seeds, leaves, flowers and dried berries, along with an alcohol-based fluid following subtotal exenteration and a reduction in peripheral muscle mass. The further process of this dry embalming technique was monitored by visual, tactile and olfactory evaluation of the embalmed body, along with a record of the body weight. Repeatedly taking samples from the skin and soft tissues provided insight into eventual changes on a histomorphological level and two whole-body CT scans complemented the evaluation of the internal changes within the corpse, which was eventually examined at autopsy. On the macroscopic level, we recorded slight signs of autolysis and very mild putrefaction within the first few weeks and a very well preserved and stable body over the subsequent years of evaluation. In parallel, we noted a gradual loss of fluid, as shown by a reduction in the body weight. This occurred faster in the first year (reduction in body weight by ca. 25%) than in the following ca. 4 years (with another ca. 25% loss of body weight). The CT scans showed stable osseous and soft tissue structures, while the few remaining internal organs that had been left inside the body after initial evisceration (such as kidneys and internal genitalia) had already completely disappeared after approx. 1 year. On the histological level, the histoanatomy of skin, subcutis and muscle remained intact over the entire observation period. A loss of epidermal cell nuclei was not noted before day 1772 and there were only slight signs of adipocire formation of fat tissue at the end point of observation (day 2634). In summary, we can confirm that excellent body preservation of external skin and soft tissue was maintained over a considerably long period (in this case, 7.2 years) using the applied protocol of dry embalming, but a complete loss of residual internal organs/structures beyond skin, subcutaneous fat tissue and muscle. Previous observations of the excellent preservation of an infant mummy that underwent the dry embalming procedure are very plausible. 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

Background: Giant cell myocarditis (GCM) is a rare condition with an incompletely understood immune pathogenesis, characterized by inflammatory damage to the myocardium and the presence of multinucleated giant cells on histopathological examination. The frequently fulminant and severe course requires rapid intervention for a correct diagnosis and the initiation of immunosuppressive therapy, which is often life-saving. Materials and methods: This article contains information from observational studies and case reports, systematically collected from prestigious publications such as JACC, NEJN, ESC, JCC, Heliyon, and Cureus found in the PubMed and ClinicalTrials.gov databases. Thus, 25 patients diagnosed with giant cell myocarditis between March 2019 and May 2025 were analyzed, with a focus not only on the initial clinical evolution, mortality incidence, and the need for heart transplantation but also on the incidence of major complications such as cardiogenic shock and malignant rhythm and conduction disorders refractory to drug treatment. These parameters were studied according to certain intrinsic factors that cannot be influenced, such as age at onset, gender, and associated pathology of the patient, as well as extrinsic factors that can be influenced, such as the time of diagnosis and the start of immunosuppressive therapy. The results obtained were compared with those in the literature from previous years, considering the limitations of the current study. Results: The selected patients were 13 women (52%) and 12 men (48%), mostly from the US and Japan, aged between 22 and 76 years, with an average age of 44.92 years. An associated autoimmune pathology was found in 40% of patients in this group, and previous cardiovascular pathology in 28%. Only 8% had a history of GCM. The clinical onset of new-onset heart failure, refractory to usual therapy, with progressive dyspnea as the cardinal symptom was found in 12 patients, representing 48% of cases; palpitations as an expression of rhythm or conduction disorders were found in five patients, representing 20%; precordial discomfort to precordial pain accompanied or not by ST-T segment changes was present in four patients, representing 16%; and general signs and symptoms or those of other organs were present in three (12%) cases. The diagnosis was made by histological examination of the biopsy fragment obtained by endomyocardial biopsy or from the myocardial fragment obtained during the implantation of mechanical cardiovascular support devices and, less frequently, on the explanted heart and at autopsy. In terms of progression, of the 25 patients, four (16%) died, four (16%) required heart transplantation, and 16 (64%) had a severe progression with cardiogenic shock, which required mechanical circulatory support in 11 (44%) cases. The outcome was mainly influenced by the early diagnosis and administration of immunosuppressive medication, but also by the age of the patients and associated chronic diseases. Conclusions: Giant cell myocarditis is a serious condition that, in the absence of rapid diagnosis and appropriate immunosuppressive therapy, has a fulminant, often fatal course. Clinical suspicion of giant cell myocarditis remains important in the initial diagnosis. Raising this suspicion, together with modern and improved paraclinical investigations compared to previous years, has led to faster diagnosis and administration of immunosuppressive therapy in this pathology. Histological examination remains the gold standard for final diagnosis, but it should be noted that it may be non-diagnostic. In the face of a strong suspicion of giant cell myocarditis, the best approach is to start immunosuppressive therapy and monitor the patient’s progress. Immunosuppressive treatment remains decisive in influencing the evolution of this condition, both through prompt administration and through the adaptation of therapeutic regimens to the evolution of patients. A more detailed understanding of the immune-mediated pathogenesis of GCM and the identification of clinical risk factors for unfavorable short- and long-term outcomes may enable earlier risk stratification and the development of more targeted, individualized therapeutic strategies. 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

Background/Objectives: The presence of postmortem pink teeth is a phenomenon occasionally observed during forensic autopsies. This phenomenon has been typically associated with deaths involving drowning, asphyxiation, trauma, or electrocution. However, the recent literature suggests that it is nonspecific. Despite being recognized in forensic literature for decades, its pathophysiology, prevalence, and forensic relevance remain controversial. The existing evidence is scattered and primarily based on case reports, narrative reviews, or isolated observations. This scoping review aims to systematically map the available scientific evidence on the phenomenon of postmortem pink teeth and its potential role in determining the cause of death within the context of forensic medicine. Methods: This review was conducted following the Joanna Briggs Institute (JBI) methodology for scoping reviews and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Results: A comprehensive search was carried out across multiple databases to identify studies addressing the occurrence, mechanisms, and forensic interpretation of pink teeth in postmortem examinations. After application of the inclusion and exclusion criteria, the search allowed for the selection of 12 publications (case reports and observational studies). Conclusions: Collected data from the selected studies allowed us to conclude that PTP is a nonspecific taphonomic artifact, lacking diagnostic value in determining the cause of death. Mapping the current evidence on pink teeth contributed to a better understanding of this phenomenon and its lack of forensic significance, promoting more informed decision-making in postmortem assessments. Full article

Expanding research indicates that oxidative stress, particularly mitochondrial oxidative stress, is one of the key components in the pathogenesis of Alzheimer’s disease (AD). Mitochondrial oxidative stress is largely driven by impaired function of electron transport chain (ETC) complexes and their regulators. This study conducted an immunohistochemical analysis of ETC proteins (α-subunit of complex V, subunits MTCO1 and MTCO2 of complex IV) and mitochondrial complex V inhibitor IF-1 in the neurons of the caudate nucleus head, hippocampus, anterior cingulate gyrus, middle frontal gyrus, and inferior parietal lobule using autopsy material from patients with sporadic AD. Comparisons were made with similar brain regions in autopsy material from age-matched elderly patients and young patients. The results revealed a pattern of ETC impairment in AD fundamentally distinct from that observed in physiological aging. Specifically, a hippocampus-specific failure of the adaptive response was identified: unlike other brain regions, compensatory upregulation of ATP synthase does not occur here despite critical reduction in the protective protein IF-1, directly explaining the heightened vulnerability of hippocampal neurons to damage. Our data deepen the understanding of AD pathogenesis by highlighting region-specific mitochondrial defects as promising targets for tailored therapeutic intervention. Full article

Sudden cardiac death (SCD) is a major global health issue, defined as sudden natural death presumed to be of cardiac cause. While in the elderly SCD is commonly associated with coronary artery disease, in the younger population it is linked to inherited cardiomyopathies or channelopathies, even though SCD can remain unexplained even after a comprehensive autopsy in a substantial proportion of cases. In this context, genetic testing has gained importance, supported by the widespread availability of techniques such as next-generation and whole-exome/genome sequencing and their reduced costs. This state-of-the-art review summarizes the genetic bases of sudden cardiac death among cardiomyopathies, channelopathies and in sudden unexplained death presumed to be of arrhythmic cause. Among the structural causes, inherited cardiomyopathies such as hypertrophic, dilated, non-dilated left ventricular, arrhythmogenic right ventricular and restrictive ones represent major substrates for malignant ventricular arrhythmias mostly arising from variants in sarcomeric or desmosomal genes. Channelopathies (long or short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) are caused by variants in genes encoding cardiac ion channels and/or regulatory proteins, which equally predispose to high risk of life-threatening ventricular arrhythmias. In sudden arrhythmic death syndrome, with a structurally normal heart, post-mortem genetic testing (molecular autopsy) can uncover an underlying inherited condition. However, variants of uncertain significance are detected in more than half of the cases, underscoring the need for a multidisciplinary approach. Genetic testing also plays a key role in cascade screening of first-degree relatives. While monogenic variants drive risk in inherited cardiac disorders, emerging evidence suggests that polygenic contributions may modulate SCD susceptibility, highlighting future roles for polygenic risk scores in risk stratification. Full article

Mimivirus, a giant double-stranded DNA virus ($1.2$ Mbp), possesses unique bacteria-like features, including a Gram-positive staining reaction due to peptidoglycan-containing surface fibers. While detected in the respiratory secretions of pneumonia patients since 2005, its clinical role remains controversial due to high genetic variability and detection challenges. This study aims to clarify the pathological significance of Mimivirus by investigating its presence and replication potential in human lung tissue, specifically exploring its association with fatal respiratory outcomes. A comparative post-mortem analysis was conducted on lung tissue samples from two cohorts: patients who succumbed to lethal viral pneumonia and a control group with no history of pulmonary pathology. Mimivirus is known to productively infect alveolar macrophages, suggesting they may serve as a reservoir for lung inflammation and tissue damage. Current evidence suggests it may act as an opportunistic or commensal agent, particularly in immunocompromised or critically ill patients. By systematically screening autopsy samples, this research seeks to establish whether Mimivirus is a primary causative agent of fatal pneumonia or an incidental inhabitant of the human respiratory tract. 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