Acute myocardial infarction (AMI) remains the leading cause of death worldwide, with myocardial ischemia/reperfusion injury (MIRI) emerging as a significant factor influencing patient outcomes despite timely reperfusion therapy. MIRI refers to paradoxical myocardial damage that occurs upon restoration of coronary blood flow and is driven by complex inflammatory, oxidative, and metabolic mechanisms, which can exacerbate infarct size (IS), contributing to adverse outcomes. This review explores the molecular and cellular pathophysiology of MIRI, emphasizing both its clinical and forensic relevance. The principal mechanisms discussed include oxidative stress and mitochondrial dysfunction, calcium overload and ion homeostasis imbalance, inflammatory responses, with particular focus on the NLRP3 inflammasome and cytokine pathways, and multiple forms of cell death (apoptosis, necroptosis, pyroptosis, and autophagy). Additionally, the authors present original immunohistochemical findings from autopsy cases of patients who suffered ST-segment elevation myocardial infarction (STEMI) and underwent percutaneous coronary intervention (PCI), but subsequently died. These findings underscore that successful reperfusion does not completely prevent delayed complications, like arrhythmias, ventricular fibrillation (VF), and sudden cardiac death (SCD), often caused by secondary MIRI-related mechanisms. Moreover, the case series highlight the diagnostic value of inflammatory markers for pathologists in identifying MIRI as a contributing factor in such fatalities. Finally, immunotherapeutic strategies—including IL-1 and IL-6 inhibitors such as Canakinumab and Tocilizumab—are reviewed for their potential to reduce cardiovascular events and mitigate the effects of MIRI. The review advocates for continued multidisciplinary research aimed at improving our understanding of MIRI, developing effective treatments, and informing forensic investigations of reperfusion-related deaths.

Ostarine (enobasarm) is a selective androgen receptor modulator with great therapeutic potential. However, it is also used by athletes to promote muscle growth and enhance performances without the typical adverse effects of anabolic steroids. Ostarine popularity increased in recent years, and it is currently the most abused “other anabolic agent” (subclass S1.2. of the “anabolic agents” class S1) from the World Anti-Doping Agency’s (WADA) prohibited list. Several cases of liver toxicity were recently reported in regular users. Detecting ostarine or markers of intake in biological matrices is essential to document ostarine use in doping. Therefore, we sought to investigate ostarine metabolism to identify optimal markers of consumption. The substance was incubated with human hepatocytes, and urine samples from six ostarine-positive cases were screened. Analyses were performed via liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-assisted data mining, with in silico metabolite predictions. Ten metabolites were identified with hydroxylation, ether cleavage, dealkylation, O-glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C₂₅H₂₂O₉N₃F₃, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C₂₅H₂₂O₁₀N₃F₃, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C₁₉H₁₄O₄N₃F₃, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.

Background: Digital pathology (DP) combined with fluorescence confocal microscopy (FCM) allows rapid tissue assessment while preserving specimens. Artificial intelligence (AI) and large language models (LLMs) may enhance diagnostic workflows, but their role in pediatric surgical pathology is largely unexplored. Methods: We conducted a prospective, single-center study including 20 pediatric surgical cases with ex vivo FCM images acquired intraoperatively. Two commercially available LLMs, GPT-4V (AnPathology-Gpt) and Claude 3.7 Sonnet (AnPathology Project), were tested using structured prompts to generate diagnostic reports with and without immunohistochemistry (IHC) data, when available. Outputs were compared against the gold standard diagnosis by an experienced pediatric pathologist. Diagnostic performance was evaluated through accuracy, sensitivity, specificity, and Cohen’s kappa. A paired sub-analysis was performed for cases with IHC (n = 5), and a sensitivity analysis excluding IHC cases (n = 15) was conducted. Results: Across all 20 cases, AnPathology-Gpt achieved 85% accuracy, 100% sensitivity, 86% specificity, and κ = 0.78, while AnPathology Project reached 80% accuracy, 100% sensitivity, 57% specificity, and κ = 0.63. Both models correctly identified all 13 neoplastic cases, with errors limited to non-neoplastic lesions mimicking tumors. In the IHC sub-analysis, accuracy improved from 40% to 80% and sensitivity from 50% to 100% for both models, resolving two false negatives observed in the FCM-only evaluation. Sensitivity analysis excluding IHC confirmed consistency of the results. Conclusions: This pilot study demonstrates that multimodal LLMs can support accurate and rapid diagnosis in pediatric digital pathology. The addition of IHC improves performance in diagnostically complex cases. Larger multicenter studies are needed to validate these findings and to define the role of AI-assisted workflows in pediatric surgical pathology.

N , N -Dimethyltryptamine (DMT) is a naturally occurring substituted tryptamine used as a psychedelic drug for ritual purposes by various cultures. Derivatives were already found on the drug of abuse market, such as N ¹ - tert -butoxycarbonyl- N , N -dimethyltryptamine (DMT-Boc). The aim of the current study was to investigate the toxicokinetics of DMT-Boc and three related DMT derivatives, by name DMT-isopropylcarbamate, DMT-pivaloylamide, and DMT-THP ( N , N -dimethyl-2-[1-(oxan-2-yl)indol-3-yl]ethanamine). In vitro and in vivo metabolism studies with pooled human liver S9 incubations and zebrafish embryos were performed, respectively. Monooxygenase and monoamine oxidase (MAO) isozymes involved in the phase I metabolism were identified. In vitro metabolic stability and plasma protein binding (PPB) were evaluated. A total of 11 metabolites for DMT-Boc, 13 for DMT-isopropylcarbamate, eight for DMT-pivaloylamide and 16 for DMT-THP were identified using high-resolution tandem mass spectrometry. N -Demethylation and hydroxylation were the most relevant metabolic reactions. CYP1A2, CYP2D6, and FMO3 were identified as most active phase I isozymes and MAO-A contributed to DMT-THP metabolism. The in vitro half-lives of DMT-Boc, DMT-isopropylcarbamate, and DMT-pivaloylamide were calculated to be between 74 and 79 min, while that of DMT-THP was found to be > 180 min. All compounds showed high PPB (> 99%) indicating that co-consumption with other drugs might increase the DMT derivatives’ toxicity. Combined in vitro and in vivo approaches provided a comprehensive metabolism overview. N , N-bis -Demethylated, N -demethylated and N -oxygenated metabolites along with parent compound were proposed as consumption markers in order to support clinical and forensic toxicologists to identify these substances in biosamples in case of suspected abuse.