Postmortem interval (PMI) estimation is a challenge of utmost importance in forensic daily practice. Traditional methods face limitations in accuracy and reliability, particularly for advanced decomposition stages. Recent advances in “omics” sciences, providing a holistic view of postmortem biochemical changes, offer promising avenues for overcoming these challenges. This systematic review aims at investigating the role of mass-spectrometry-based “omics” approaches in PMI estimation to elucidate molecular mechanisms underlying predictable time-dependent biochemical alterations occurring after death. A systematic search was performed, adhering to PRISMA guidelines, through “free-text” protocols in the databases PubMed, SCOPUS and Web of Science. The inclusion criteria were as follows: experimental studies analyzing, as investigated samples, animal or human corpses in toto or in parts and estimating PMI through MS-based untargeted omics approaches, with full texts in the English language. Quality assessment was performed using STROBE and ARRIVE critical appraisal checklists. A total of 1152 papers were screened and 26 included. Seventeen papers adopted a proteomic approach (65.4%), nine focused on metabolomics (34.6%) and two on lipidomics (7.7%). Most papers (57.7%) focused on short PMIs (120 days) (15.4%). Muscle tissue was the most frequently analyzed substrate (34.6% of papers), followed by liver (19.2%), bones (15.4%), cardiac blood and leaking fluids (11.5%), lung, kidney and serum (7.7%), and spleen, vitreous humor and heart (3.8%). Predictable time-dependent degradation patterns of macromolecules in different biological substrates have been discussed, with special attention to molecular insights into postmortem biochemical changes.

West Nile virus (WNV) is an arthropod-borne flavivirus first identified in 1937. Over time, WNV has spread globally and is now endemic in Italy. Although most human WNV infections are asymptomatic (80%), less than 1% progress to a neuroinvasive disease with high mortality rates. This case involves a 45-year-old woman with post-surgical hypoparathyroidism and Sjögren’s syndrome who developed severe encephalomyelitis linked to WNV, leading to ventilator-associated pneumonia and death. Neuropathological findings revealed a bilaterally cribriform thalamus and reddish punctate lesions near the dentate nucleus of the cerebellum. The trachea and bronchial hilum branches contained whitish foamy liquid. The left lung showed multiple brownish-violet areas, with whitish regions at dissection. The heart appeared unremarkable. A detailed neuropathological examination focused on areas involved in motor control pathways. Tissue samples were stained with hematoxylin and eosin and trichrome techniques, and immunohistochemistry was performed using CD68, CD3, and CD20. A significant damage was observed in the lenticular nucleus and motor thalamus, with prominent concentric vascular calcifications. The cerebellar cortex showed near-total depletion of Purkinje cells. In the spinal cord, CD68 and CD3 positivity was noted in the lateral funiculi, anterior horns, and Clarke’s column. Lung findings showed pulmonary edema, chronic emphysema, and bronchopneumonia. The observed CD3 and CD68 positivity confirms that WNV spreads trans-synaptically along motor control pathways. We speculate on the potential molecular mechanisms by which hypoparathyroidism and Sjögren’s syndrome may have played a role in the neuroinvasive progression of the disease.

Acute chorioamnionitis is a placental inflammatory condition often implicated in adverse pregnancy outcomes, including intrauterine death. The histopathological identification of maternal and fetal inflammatory responses (MIR and FIR) is critical for diagnosis and understanding potential causal mechanisms. Chorioamnionitis frequently warrants medico-legal investigation, particularly for suspected medical malpractice. Two forensic cases of intrauterine fetal death with histological finding of acute chorioamnionitis are presented. Each case has been investigated with a complete autopsy with histological examination of fetal organs and placenta. The investigations were conducted following the Royal College of Pathologists' Guidelines on autopsy practice for fetal death and the European Guidelines for forensic investigations involving suspected healthcare professional liability. In Case 1, histopathology revealed acute necrotizing chorioamnionitis associated with chorionic vasculitis, funisitis and fetal organ involvement (stage 3/grade 2 MIR; stage 2/grade 1 FIR), supporting a causal role in fetal death. In Case 2, only focal chorioamnionitis with minimal fetal inflammatory response (stage 2/grade 1 MIR; stage 1/grade 1 FIR) was detected. A definitive and certain causal relationship with the death cannot be established due to the absence of systemic fetal involvement. No substandard medical care was identified in either case. These cases underscore the importance of integrating clinical and histological data to determine the pathophysiological significance of chorioamnionitis in fetal death. The evaluation of FIR and organ involvement are critical for distinguishing between causal and incidental findings. Thorough histopathological evaluation is essential for accurate cause of death determination and medicolegal assessment.