Background/Objectives: Artificial intelligence (AI), machine-learning (ML), and deep-learning (DL) models are increasingly used for prognostic prediction in intensive care unit (ICU) sepsis, but their clinical readiness remains uncertain. This systematic review aimed to evaluate AI-, ML-, and DL-based models for mortality and clinically relevant outcome prediction in adult ICU patients with sepsis or septic shock. Methods: PubMed/MEDLINE, Scopus, and the Cochrane Library were searched up to April 2026. Eligible studies included adult ICU sepsis or septic shock cohorts evaluating AI/ML/DL-based prognostic models. Screening, full-text assessment, and data extraction were performed independently by two reviewers. Outcomes, model families, validation strategies, discrimination, calibration, clinical utility, explainability, comparative performance versus conventional severity scores, risk of bias, and reporting completeness were synthesized. Risk of bias was assessed using PROBAST domains supplemented by PROBAST + AI considerations, and reporting completeness was evaluated according to TRIPOD/TRIPOD + AI domains. Results: Seventy-five studies were included, comprising 50 PubMed-derived and 25 additional Scopus-derived studies. AUROC or C-statistic was extractable in 64 studies, external validation was reported in 27, prospective evaluation in three, calibration in 38, decision-curve analysis or clinical utility assessment in 37, and explainability in 64. Across 17 directly extractable within-study comparisons from nine studies, AI/ML models usually, but not uniformly, achieved higher discrimination than conventional severity scores, with a median paired ΔAUROC of +0.108 (IQR, +0.082 to +0.148; range, −0.013 to +0.203). Externally validated fixed-horizon models showed clinically relevant but heterogeneous discrimination across sepsis phenotypes, with stronger evidence in selected sepsis-induced coagulopathy cohorts and more variable transportability in respiratory and liver-injury subgroups. However, 45 studies were judged at high risk of bias, mainly because of limitations in the analysis domain. Conclusions: AI/ML models for adult ICU sepsis show a recurrent signal of prognostic discrimination and often perform comparably to or better than conventional severity scores in directly extractable within-study comparisons; however, this signal should be interpreted cautiously given clinical and methodological heterogeneity, limited prospective validation, incomplete calibration, and frequent high risk of bias. The strongest evidence comes from externally validated, phenotype-specific models, although routine clinical implementation remains limited by heterogeneous endpoints, incomplete calibration, insufficient prospective validation, and scarce workflow-level evaluation. Future studies should shift from retrospective AUROC optimization toward calibrated, externally validated, clinically actionable, and workflow-integrated decision-support tools tested in prospective ICU settings.

Sudden cardiac death (SCD) remains a major challenge in forensic medicine, representing a leading cause of natural mortality and frequently occurring in individuals without antecedent symptoms. Although conventional autopsy and histology remain the cornerstones of investigation, up to 10–15% of cases are classified as “autopsy-negative sudden unexplained death,” underscoring the need for complementary diagnostic tools. In recent years, post-mortem biochemistry and molecular approaches have become essential to narrowing this gap. Classical protein markers of myocardial necrosis (cardiac troponins, CK-MB, H-FABP, GPBB) continue to play a fundamental role, though their interpretation is influenced by post-mortem interval and sampling site. Peptide biomarkers reflecting hemodynamic stress (BNP, NT-proBNP, copeptin, sST2) offer additional insight into cardiac dysfunction and ischemic burden, while inflammatory and immunohistochemical markers (CRP, IL-6, fibronectin, desmin, C5b-9, S100A1) assist in detecting early ischemia and myocarditis when routine histology is inconclusive. Beyond these traditional markers, molecular signatures—including cardiac-specific microRNAs, exosomal RNA, proteomic alterations, and metabolomic fingerprints—provide innovative perspectives on metabolic collapse and arrhythmic mechanisms. Molecular autopsy through next-generation sequencing has further expanded diagnostic capability by identifying pathogenic variants associated with channelopathies and cardiomyopathies, enabling both cause-of-death clarification and cascade screening in families. Emerging multi-omics and artificial intelligence frameworks promise to integrate these heterogeneous data into standardized and robust interpretive models. Pre- and post-analytical considerations, together with medico-legal implications ranging from malpractice evaluation to the management of genetic information, remain essential components of this evolving field. Overall, the incorporation of validated biomarkers into harmonized international protocols, increasingly supported by AI, represents the next frontier in forensic cardiology.

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.

MicroRNAs (miRNAs) are small non-coding RNA molecules approximately 20–22 nucleotides in length that regulate gene expression at the post-transcriptional level. By binding to target messenger RNAs (mRNAs), miRNAs inhibit translation or induce degradation, thus influencing a wide array of biological processes including development, inflammation, apoptosis, and tissue remodeling. Owing to their remarkable stability and tissue specificity, miRNAs have emerged as promising biomarkers in both clinical and forensic settings. In recent years, increasing evidence has demonstrated their utility in cardiovascular diseases, where they may serve as diagnostic, prognostic, and therapeutic tools. This systematic review aims to comprehensively summarize the role of miRNAs in cardiovascular pathology, focusing on their diagnostic potential in myocardial infarction, sudden cardiac death (SCD), and cardiomyopathies, and their applicability in post-mortem investigations. Following PRISMA guidelines, we screened PubMed, Scopus, and Web of Science databases for studies up to December 2024. The results highlight several miRNAs—including miR-1, miR-133a, miR-208b, miR-499a, and miR-486-5p—as robust markers for ischemic injury and sudden death, even in degraded or formalin-fixed autopsy samples. The high stability of miRNAs under extreme post-mortem conditions reinforces their potential as molecular tools in forensic pathology. Nevertheless, methodological heterogeneity and limited standardization currently hinder their routine application. Future studies should aim to harmonize analytical protocols and validate diagnostic thresholds across larger, well-characterized cohorts to fully exploit miRNAs as reliable molecular biomarkers in both clinical cardiology and forensic medicine.

Background: Lymphomas account for approximately 10% of cancers diagnosed during pregnancy, with Hodgkin’s lymphoma being the most common. However, non-Hodgkin lymphomas, including primary mediastinal large B-cell lymphoma (PMBCL), also represent a significant proportion. Both mediastinal lymphomas and pregnancy develop a hypercoagulable state, increasing the risk of venous thromboembolism and massive pulmonary embolism (PE), requiring extracorporeal membrane oxygenation (ECMO). Methods: Clinical data, blood test and imagings have been collected by the medical records of the patient. Results: We present a 25-year-old woman, at 32 weeks of gestation, who presented to the emergency department with progressive dyspnea and asthenia. Echocardiography revealed a hemodynamically significant pericardial effusion and severe right ventricular dysfunction. Given the severity of her condition, she underwent an emergency caesarean section and subsequently a pericardial drainage. A chest computed tomography scan revealed an incidental mediastinal mass along with a massive PE. Despite pericardial drainage, she remained hemodynamically unstable. Since thrombolysis was contraindicated for the recent cesarean section, venoarterial ECMO was initiated. Systemic anticoagulation was guaranteed by heparin, which shifted to argatroban for heparin resistance. The mediastinal mass was also biopsied, and the diagnosis of PMBCL carried out. Cytoreductive chemotherapy was initiated with the COMP-R regimen (i.e., cyclophosphamide, vincristine, methotrexate, prednisone, and rituximab), and the patient progressively improved up to ICU and hospital discharge. Conclusions: This case highlights the challenges in managing a complicated patient requiring early multidisciplinary intervention, which was crucial for stabilizing the patient and optimizing fetal and maternal prognosis.

Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in adult critical care, but tracheostomy during ECMO remains controversial because of bleeding risk, anticoagulation exposure, and variability in patient selection. This systematic review evaluated the safety, timing, and clinical outcomes of tracheostomy in adult patients receiving ECMO. Methods: A systematic search of PubMed/MEDLINE was supplemented by additional searches in the Cochrane Library/CENTRAL and Scopus to identify studies evaluating tracheostomy in adult ECMO patients. The review was conducted according to PRISMA 2020 guidelines. After database searching and screening, 13 observational studies were included in the qualitative synthesis. Results: Across 13 studies encompassing 1918 patients, tracheostomy during ECMO was feasible and was not associated with procedure-related mortality. Bleeding was the main procedural complication, with reported rates varying according to study design, ECMO configuration, timing of tracheostomy, anticoagulation management, and bleeding definitions. Tracheostomy performed during active ECMO support was generally associated with a higher burden of bleeding or minor procedure-related complications than tracheostomy performed after decannulation. Tracheostomy was performed using percutaneous, surgical, open, or hybrid techniques, although comparative evidence between approaches remained limited. Early tracheostomy was associated with shorter ECMO duration, shorter mechanical ventilation, or improved clinical outcomes in selected cohorts, but timing definitions and outcome measures were heterogeneous. Conclusions: Tracheostomy during ECMO may support airway management, sedation reduction, and ventilatory progression, particularly in prolonged ECMO courses, but it carries a relevant bleeding and transfusion burden. Timing, anticoagulation management, patient selection, ECMO configuration, and procedural technique are likely to influence the risk-benefit balance. Prospective studies are needed to standardize definitions, compare techniques, and clarify optimal timing strategies.