microRNAs as New Biomolecular Markers to Estimate Time since Death: A Systematic Review.

Estimating the post-mortem interval is still one of the most complex challenges in forensics. In fact, the main tools currently used are burdened by numerous limitations, which sometimes allow the time of death to be placed only within too large time intervals. In recent years, researchers have tried to identify new tools to try to narrow down the interval within which to place the time of death; among these, the analysis of microRNAs seems to be promising. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of knowledge, focusing on the potential correlation between miRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed, Scopus, and WOS. The results allowed us to highlight the usefulness of miRNAs both as markers for PMI estimation and for normalization, especially due to their stability. In fact, some miRNAs remain particularly stable for long periods and in different tissues, while others degrade faster. Furthermore, there are numerous factors capable of influencing the behavior of these molecules, among which the type of tissue, the cause of death, and the circadian rhythm appear to be the most relevant. Despite the promising results of the few articles present in the literature, because of the numerous limitations they are burdened by, further research is still necessary to achieve more solid and shareable results.

Potential Role of mRNA in Estimating Postmortem Interval: A Systematic Review.

Although the postmortem interval estimation still represents one of the main goals of forensic medicine, there are still several limitations that weigh on the methods most used for its determination: for this reason, even today, precisely estimating the postmortem interval remains one of the most important challenges in the forensic pathology field. To try to overcome these limitations, in recent years, numerous studies have been conducted on the potential use of the mRNA degradation time for reaching a more precise post mortem interval (PMI) estimation. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of the knowledge focusing on the potential correlation between mRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed and Scopus. The analysis conducted made it possible to confirm the potential applicability of mRNA for reaching a more precise PMI estimation. The analysis of the results highlighted the usefulness of some mRNAs, such as ß-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, especially in short time frames, within a few hours or days of death. The matrices on which these analyses were conducted were also analyzed, resulting in less exposure to the external environment, including the heart, brain, and dental pulp. The major limitations were also reported, including the short time intervals analyzed in most of the articles, the lack of mathematical models, and the failure to report the error rate between the mRNA degradation time and PMI. Given the still small number of published articles, the lack of globally recognized standardized methods, and the numerous techniques used to evaluate the mRNA degradation times, numerous and larger studies are still necessary to reach more solid and shared evidence.

Arrhythmogenic Right Ventricular Cardiomyopathy Post-Mortem Assessment: A Systematic Review.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular myocardium, leading to myocardial atrophy. Although the structural changes usually affect the right ventricle, the pathology may also manifest with either isolated left ventricular myocardium or biventricular involvement. As ARVC shows an autosomal dominant pattern of inheritance with variable penetrance, the clinical presentation of the disease is highly heterogeneous, with different degrees of severity and patterns of myocardial involvement even in patients of the same familiar group with the same gene mutation: the pathology spectrum ranges from the absence of symptoms to sudden cardiac death (SCD) sustained by ventricular arrhythmias, which may, in some cases, be the first manifestation of an otherwise silent pathology. An evidence-based systematic review of the literature was conducted to evaluate the state of the art of the diagnostic techniques for the correct post-mortem identification of ARVC. The research was performed using the electronic databases PubMed and Scopus. A methodological approach to reach a correct post-mortem diagnosis of ARVC was described, analyzing the main post-mortem peculiar macroscopic, microscopic and radiological alterations. In addition, the importance of performing post-mortem genetic tests has been underlined, which may lead to the correct identification and characterization of the disease, especially in those ARVC forms where anatomopathological investigation does not show evident morphostructural damage. Furthermore, the usefulness of genetic testing is not exclusively limited to the correct diagnosis of the pathology, but is essential for promoting targeted screening programs to the deceased's family members. Nowadays, the post-mortem diagnosis of ARVC performed by forensic pathologist remains very challenging: therefore, the identification of a clear methodological approach may lead to both a reduction in under-diagnoses and to the improvement of knowledge on the disease.

Hyoid Bone Fracture Pattern Assessment in the Forensic Field: The Importance of Post Mortem Radiological Imaging.

Post mortem hyoid bone fracture findings may be attributable to various factors, including both the onset of acute mechanical asphyxia as it happens in manual strangulation and in charred corpses. In forensic practice, the discovery of corpses burned after death to hide their real cause of death is not uncommon: in these cases, the diagnostic challenge is even greater, as the action of flames is capable of both masking previously generated lesions and/or generating new ones, as occurs for hyoid bone fractures. The case concerns a 76-year-old man found charred in his bedroom. Almost complete body charring made it impossible to evaluate any external damage. Post mortem computed tomography (PMCT) was performed, and an evident bilateral fracture of the greater horn of the hyoid bone was detected. Although the absence of typical charring signs had steered the diagnosis towards post mortem exposure to flames, PMCT proved to be very useful in increasing the accuracy in correctly determining the cause of death. In particular, making use of Maximum Intensity Projection (MIP) hyoid bone reconstructions, it was possible to measure the medial dislocation angle of the fracture fragments and then to establish the applied direction of force, which acted in a lateral-medial way. A manual strangulation diagnosis was confirmed. The increasing importance of performing post mortem radiological exams as a corollary for conventional autopsy has been further confirmed.

Postmortem Detection of "Clinically Undiagnosed" Diffuse Large B-Cell Lymphoma: Gross and Microscopic Findings.

Diffuse large B-cell lymphoma is considered the most found non-Hodgkin lymphoma in adults. Diffuse large B-cell lymphoma, which also occurs in sporadic forms, is associated with some pathological conditions, including human immunodeficiency virus infection, especially if it progresses to AIDS. The authors report the case of a 45-year-old man with AIDS in whom a postmortem diagnosis of diffuse large B-cell lymphoma was performed. The proposed images document extensive pluri-visceral involvement, already visible macroscopically, and subsequently confirmed through histological examination.

Epidemiological Changes in Transthyretin Cardiac Amyloidosis: Evidence from In Vivo Data and Autoptic Series.

Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice.