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Neck infections are often prone to being underestimated and can manifest insidiously. The spread of infection can lead to translocation into thoracic areas, causing descending necrotizing mediastinitis (DNM). However, the application of the post-mortem approach in such cases is not well-described in the literature. A literature review was carried out according to the PRISMA methods. Nine papers were included in the final review, revealing different levels of involvement of neck layers that can be linked to different causes. Expertise with respect to the anatomy of the fasciae and spaces of the neck enables an understanding of the pathogenesis of DNM. However, a clear autoptic description was not provided in any of the articles. Therefore, we also employed a practical post-mortem approach to cases of death due to DNM. It is fundamental for pathologists to identify the exact head and neck structures involved. Providing dissectors with support from an otolaryngologist could be useful. This paper could help address such difficult cases. [ABSTRACT FROM AUTHOR]

When stroke occurs in pediatric age, it might be mistakenly interpreted as non-accidental head injury (NAHI). In these situations, a multidisciplinary approach is fundamental, including a thorough personal and familial history, along with accurate physical examination and additional investigations. Especially when the clinical picture is uncertain, it is important to remember that certain genetic conditions can cause bleeding inside the brain, which may resemble NAHI. Pediatric strokes occurring around the time of birth can also be an initial sign of undiagnosed genetic disorders. Hence, it is crucial to conduct a thorough evaluation, including genetic testing, when there is a suspicion of NAHI but the symptoms are unclear. In these cases, a characteristic set of symptoms is often observed. This study aims to summarize some of the genetic causes of hemorrhagic stroke in the pediatric population, thus mimicking non-accidental head injury, considering elements that can be useful in characterizing pathologies. A systematic review of genetic disorders that may cause ICH in children was carried out according to the Preferred Reporting Item for Systematic Review (PRISMA) standards. We selected 10 articles regarding the main genetic diseases in stroke; we additionally selected 11 papers concerning patients with pediatric stroke and genetic diseases, or studies outlining the characteristics of stroke in these patients. The disorders we identified were Moyamoya disease (MMD), COL4A1, COL4A2 pathogenic variant, Ehlers–Danlos syndrome (E-D), neurofibromatosis type 1 (Nf1), sickle cell disease (SCD), cerebral cavernous malformations (CCM), hereditary hemorrhagic telangiectasia (HHT) and Marfan syndrome. In conclusion, this paper provides a comprehensive overview of the genetic disorders that could be tested in children when there is a suspicion of NAHI but an unclear picture. [ABSTRACT FROM AUTHOR]

Investigating the causes of Sudden cardiac death (SCD) is always difficult; in fact, genetic cardiac conditions associated with SCD could be "silent" even during autopsy investigation. In these cases, it is important to exclude other aetiology and assist to ask for genetic investigations. Herein, the purpose of this review is to collect the most-implicated genes in SCD and generate a panel with indications for first line and second line investigations. A systematic review of genetic disorders that may cause SCD in the general population was carried out according to the Preferred Reporting Item for Systematic Review (PRISMA) standards. We subsequently listed the genes that may be tested in the case of sudden cardiac death when the autopsy results are negative or with no evidence of acquired cardiac conditions. To make genetic tests more specific and efficient, it is useful and demanded to corroborate autopsy findings with the molecular investigation as evident in the panel proposed. The genes for first line investigations are HCM, MYBPC3, MYH7, TNNT2, TNNI3, while in case of DCM, the most implicated genes are LMNA and TTN, and in second line for these CDM, ACTN2, TPM1, C1QPB could be investigated. In cases of ACM/ARVC, the molecular investigation includes DSP, DSG2, DSC2, RYR2, PKP2. The channelopathies are associated with the following genes: SCN5A, KCNQ1, KCNH2, KCNE1, RYR2. Our work underlines the importance of genetic tests in forensic medicine and clinical pathology; moreover, it could be helpful not only to assist the pathologists to reach a diagnosis, but also to prevent other cases of SCD in the family of the descendant and to standardise the type of analysis performed in similar cases worldwide. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is one of the most well-known causes of neurological impairment and disability in the world. The Forkhead Box class O (FOXO) 3a is a transcription factor that is involved in different molecular processes, such as cell apoptosis regulation, neuroinflammation and the response to oxidative stress. This study is the first to evaluate the post-mortem immunohistochemical (IHC) positivity of FOXO3a expression in human cases of TBI deaths. The autopsy databases of the Legal Medicine and Forensic Institutes of the "Sapienza" University of Roma and the University of Pisa were retrospectively reviewed. After analyzing autopsy reports, 15 cases of TBI deaths were selected as the study group, while the other 15 cases were chosen among non-traumatic brain deaths as the control group. Decomposed bodies and those with initial signs of putrefaction were excluded. Routine histopathological studies were performed using hematoxylin–eosin (H&E) staining. Furthermore, an IHC investigation on cerebral samples was performed. To evaluate FOXO3a expression, anti-FOXO3a antibodies (GTX100277) were utilized. Concerning the IHC analysis, all 15 samples of TBI cases showed positivity for FOXO3a in the cerebral parenchyma. All control cerebral specimens showed FOXO3a negativity. In addition, the longer the survival time, the greater the positivity to the reaction with FOXO3a was. This study shows the important role of FOXO3a in neuronal autophagy and apoptosis regulation and suggests FOXO3a as a possible potential pharmacological target. [ABSTRACT FROM AUTHOR]

One of the most challenging issues in forensic pathology is lesion vitality demonstration, particularly in cases of hanging. Over the past few years, immunohistochemistry has been applied to this field with promising results. In particular, protein and transcription factors involved in the apoptotic process have been studied as vitality markers for the ligature mark. This study represents an implementation of our previous studies on ligature mark vitality demonstration. In this study, we evaluated the FOXO3 expression in post-mortem cervical skin samples through an immunohistochemical analysis. To evaluate FOXO3 expression, anti-FOXO3 antibodies (GTX100277) were used. The study group comprised 21 cases, 8 women and 13 men, whereas the control group consisted of 13 cases of subjects who died due to other causes. Decomposition and no clear circumstantial data were exclusion criteria. We found that FOXO3 is decreased in hanging cases compared with normal skin in other causes of death (p-value < 0.05). No differences were seen concerning the type of hanging material (hard or soft), type of hanging (complete or incomplete), and position of the knot. Our results suggest that FOXO3 depletion could be a valid immunohistochemical marker of ligature mark vitality. [ABSTRACT FROM AUTHOR]

Background and Objectives: Saphenous vein graft (SVG) is a cardiac surgical practice used to create a cardiac bypass in cases of coronary artery obstruction. It consists of a surgical procedure that involves the creation of an aorto-coronary communication by a venous conduit (saphenous vein) to bypass coronary stenosis and allow cardiac revascularization. This practice can be affected by early and late complications. The most feared complication is graft aneurysm or pseudoaneurysm degeneration and rupture which are considered late complications. This paper presents a rare case of SVG aneurysmal rupture that occurred 24 h after surgery and a review of the literature to provide a general look at the state of knowledge. Materials and Methods: The systematic review was carried out using the guidelines according to the PRISMA method. Results: Cases of aneurysmal rupture have never been described prior to one month after surgery. The male sex and subjects under 45 are the most affected by this complication. Death occurs in less than half of the cases, being more frequent in young people. Performing a CT or angio-CT examination led to the diagnosis. Conclusions: It is impossible to estimate the implanted vessel's quality, so postoperative follow-up is fundamental. Transesophageal ultrasound can be useful, and hematochemical tests are valuable early diagnostic tools, whrease CT and angio-CT can be useful even months after surgery. Forensic analysis should always perform an autopsy and graft histological examination. [ABSTRACT FROM AUTHOR]

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6‐diacetyl ester of morphine (diacetylmorphine). The post‐mortem diagnosis of heroin‐related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post‐mortem anti‐6‐MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin‐related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post‐mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications. [ABSTRACT FROM AUTHOR]

Our study aims to demonstrate the experience of analyzing fully or partially charred corpses to offer a proper implementation protocol for determining the cause of death. In this study, we present a total of 103 cases obtained from the University of Rome La Sapienza and the University of Pisa archives. All cases were classified based on the extent and severity of burns using a visual method. We divided all cases into two groups. The first group included grade I–II burns (21 cases) without the need for identification. The second group (82 cases) included injuries worse than grade burns II, so all cases were analyzed using an analytical method. For each case, we have documented which of the following analyses have been used and the corresponding findings: inspection, autopsy examination, imaging examination, genetic and toxicological examinations, and histological examination. The results describe the main diagnostic findings and show that only the application of all the above systematic analyses can provide greater accuracy and reliability in describing the causes of death or solving problems, such as identification. In conclusion, we propose an available protocol that defines the main steps of a complete diagnostic pathway that pathologists should follow daily in studying charred bodies. [ABSTRACT FROM AUTHOR]

Gender-based violence affects one third of women globally with death the ultimate consequence after repeated violence. Government intervention is imperative. This article focuses on recent Italian legislation that provides a framework to assist victims of violence in Italian Emergency Rooms. [ABSTRACT FROM AUTHOR]

In this paper we describe the case of an 81-year-old Caucasian female (142 cm tall, weighing 45 kg) who suffered from a multinodular goiter for approximately 40 years. Following the onset of a clinical condition characterized by acute respiratory failure, she was transported to the emergency room by ambulance, where she died within a few hours after admission. A recent cardiac examination showed the absence of risk factors for cardiovascular disease, sinus tachycardia with a heart rate of 131 bpm, negative objectivity for signs of cardiocirculatory failure, a blood pressure of 120/80 mmHg and modest exertional dyspnea. A recent hemochemical laboratory analysis showed a TSH value of 0.01microUI/mL, FT3 value of 4.76 pg/mL and FT4 value of 2.33 ng/mL, pointing to a pattern of hyperthyroidism, attributable to Basedow's goiter. Autopsy showed some peculiarities, and we came across two extremely rare findings; the thyroid gland had reached a very large size in relation to the patient's body mass (1510 g, in a patient of 142 cm and 45 kg), and the death of the patient was due to the development of a massive intra-thyroid hemorrhage that had caused acute external compression of the trachea. To the best of our knowledge this very rare event has not previously been reported in the international scientific literature. [ABSTRACT FROM AUTHOR]

The histological findings in the heart in cases of fatal sepsis can show myocytolysis, interstitial fibrosis, necrotic contraction band, mononuclear infiltrates, and interstitial edema, which can be used in post mortem diagnosis of sepsis. Septic myocardial calcification is a very rare condition, and only a few cases have been reported in the literature. In general, the pathogenesis of the myocardial calcification has not been well clarified, but two pathogenic mechanisms have been universally recognized: metastatic or dystrophic. We present a rare case of sepsis-related myocardial calcification. Here we report a case involving a 72-year-old white male who was admitted to a hospital for a polytrauma caused by a motorbike accident. On the 110th day of hospitalization, the patient was diagnosed with a septic process and a subsequent transesophageal echocardiogram revealed the presence of a calcification on the right atrial wall. According to the medical history of the patient there were no systemic factors predisposing to calcium crystals deposition in tissues. Patient died due to multi-organ failure in the course of multimicrobial septic shock during the 149th day. The autopsy revealed both the presence of a greenish-brown formation and a greater consistency of the right atrial wall. The histological investigation of the right atrium wall showed a wide calcification area localized at subendocardial level, which contained fibrin deposition and was surrounded by fibrotic tissue. [ABSTRACT FROM AUTHOR]

Sepsis is a severe condition characterized by systemic inflammation. One of the most involved organs in sepsis is the heart. On the other hand, heart failure and dysfunction are some of the most leading causes of death in septic patients. miRNAs are short single-strand non-coding ribonucleic acids involved in the regulation of gene expression on a post-transcriptional phase, which means they are a part of the epigenetic process. Recently, researchers have found that miRNA expression in tissues and blood differs depending on different conditions. Because of this property, their use as serum sepsis biomarkers has also been explored. A narrative review is carried out to gather and summarize what is known about miRNAs' influence on cardiac dysfunction during sepsis. When reviewing the literature, we found at least 77 miRNAs involved in cardiac inflammation and dysfunction during sepsis. In the future, miRNAs may be used as early sepsis-induced cardiac dysfunction biomarkers or as new drug targets. This could help clinicians to early detect, prevent, and treat cardiac damage. The potential role of miRNAs as new diagnostic tools and therapeutic strategies worth deepening the complex network between non-coding RNA and biological pathways. Additional studies are needed to further investigate their role in sepsis-induced myocardium injury. [ABSTRACT FROM AUTHOR]

The FLICE-inhibitory protein (c-FLIPL) (55 kDa) is expressed in numerous tissues and most abundantly in the kidney, skeletal muscles and heart. The c-FLIPL has a region of homology with caspase-8 at the carboxy-terminal end which allows the molecule to assume a tertiary structure similar to that of caspases-8 and -10. Consequently, c-FLIPL acts as a negative inhibitor of caspase-8, preventing the processing and subsequent release of the pro-apoptotic molecule active form. The c-FLIP plays as an inhibitor of apoptosis induced by a variety of agents, such as tumor necrosis factor (TNF), T cell receptor (TCR), TNF-related apoptosis inducing ligand (TRAIL), Fas and death receptor (DR). Increased expression of c-FLIP has been found in many human malignancies and shown to be involved in resistance to CD95/Fas and TRAIL receptor-induced apoptosis. We wanted to verify an investigative protocol using FLIP to make a differential diagnosis between skin sulcus with vitality or non-vital skin sulcus in hanged subjects and those undergoing simulated hanging (suspension of the victim after murder). The study group consisted of 21 cases who died from suicidal hanging. The control group consisted of traumatic or natural deaths, while a third group consisted of simulated hanging cases. The reactions to the Anti-FLIP Antibody (Abcam clone-8421) was scored for each section with a semi-quantitative method by means of microscopic observation carried out with confocal microscopy and three-dimensional reconstruction. The results obtained allow us to state that the skin reaction to the FLIP is extremely clear and precise, allowing a diagnosis of unequivocal vitality and a very objective differentiation with the post-mortal skin sulcus. [ABSTRACT FROM AUTHOR]

Post-traumatic meningitis is a dreadful condition that presents additional challenges, in terms of both diagnosis and management, when compared with community-acquired cases. Post-traumatic meningitis refers to a meningeal infection causally related to a cranio-cerebral trauma, regardless of temporal proximity. The PICO (participants, intervention, control, and outcomes) question was as follows: "Is there an association between traumatic brain injury and post-traumatic meningitis?" The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. Studies examining post-traumatic meningitis, paying particular attention to victims of traumatic brain injury, were included. Post-traumatic meningitis represents a high mortality disease. Diagnosis may be difficult both because clinical signs are nonspecific and blurred and because of the lack of pathognomonic laboratory markers. Moreover, these markers increase with a rather long latency, thus not allowing a prompt diagnosis, which could improve patients' outcome. Among all the detectable clinical signs, the appearance of cranial cerebrospinal fluid (CSF) leakage (manifesting as rhinorrhea or otorrhea) should always arouse suspicion of meningitis. On one hand, microbiological exams on cerebrospinal fluid (CSF), which represent the gold standard for the diagnosis, require days to get reliable results. On the other hand, radiological exams, especially CT of the brain, could represent an alternative for early diagnosis. An update on these issues is certainly of interest to focus on possible predictors of survival and useful tools for prompt diagnosis. [ABSTRACT FROM AUTHOR]

Post-mortem computer tomography (PMCT) is currently an useful procedure that can elucidate patterns of injuries, providing strong medical evidence that is very useful during litigation and at trial. This technique is especially useful in gunshot wounds cases, allowing an easier location and retrieval of the bullet and/or its fragments inside the body. In such cases, the use of 3D rendering can be very useful in order to obtain essential information, such as: accurate depict of the wound track, discerning between entrance and exit wounds, show bone’s fracture and its fragments course inside the body. The authors performed analysis on two cases of death by gunshot wounds, and a PMCT before the postmortem examination was made. The obtained CT scans were evaluated using the open-source software OsiriX on a Mac OS X computer, performing 3D rendering of the DICOM images. The crime scene reconstruction was performed using the software Poser Debut® on a Mac OS X computer. In both cases, PMCT showed multiple advantages: objectivity, reproducibility, ease visualization of the wound paths, easy localization of bullet and their fragments, allowing us to clarify the cause of death before the traditional autopsy. PMCT should became a standard in forensic practice as an aid to the tradition postmortem examination to obtain as much information as possible in order to clarify the cause and manner of death. [ABSTRACT FROM AUTHOR]