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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]

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]

Background and Objectives: The diagnosis of anaphylaxis comprehensively depends on both situational information and laboratory investigations. For this purpose, serum tryptase concentration is examined as an indicator of systemic mast cell mediator release, linked to an underlying anaphylactic process. Increased levels of tryptase may occur in some events different from anaphylaxis, but usually information from crime scene investigations is lacking and autoptic findings are not specific. For legal reasons, it is required to achieve a definite diagnosis of mast cell degranulation that can lead to a certain diagnosis of death from anaphylaxis. Immunohistochemistry seems to be a relatively simple, reliable, and easily repeatable method that can assist the forensic pathologist in the differential diagnosis of death from anaphylaxis. Materials and Methods: This work provides an overview of the current literature on immunohistochemical methods useful in the determination process of anaphylactic-related deaths. A systematic search, according to the PRISMA statement, was performed in databases to identify studies investigating immunohistochemical targets related to anaphylaxis death. Results: This work underscores the importance of anaphylaxis mediators such as tryptase, CD117, and chymase in the immunohistochemical analysis of anaphylactic deaths. Conclusions: According to the reviewed literature, the diagnosis of death due to anaphylaxis should depend not just on the suspicion of an anaphylactic reaction but also on confirming mast cell degranulation through the identification of IHC positivity for inflammatory mediators, particularly in the respiratory tract. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is the second-most-common childhood vasculitis, and its etiology is still unknown today. Even though the acute illness is usually self-limiting, sometimes, it can generate complications, such as coronary artery aneurysms (CAA), acute myocardial infarction (AMI), heart failure, or arrhythmias, and can rarely cause sudden or unexpected deaths. We present a review of the literature, which collects autoptic and histopathological data relating to many of the cases of these deaths. On the basis of the titles and abstracts, we selected 54 scientific publications for a total of 117 cases. Among them, as expected, the majority of the deaths were due to AMI (41.03%), arrhythmia (8.55%), acute coronary syndrome (8.55%), and CAA rupture (11.97%), involving mostly 20-year-olds or younger individuls (69.23%). This is not surprising since the CAs are the most involved arteries. Gross autoptic and histopathological findings are reported in the paper. Our work revealed that, when compared with the incidence of KD, only a few cases suffered from sudden death, underwent an autoptic examination, and were then described in the literature. We suggest that researchers should perform autopsies to gain a better understanding of the molecular pathways involved in KD so as to propose further innovative therapeutic protocols or implement more appropriate prevention schemes. [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]

Hyperthermia is an internal body temperature increase above 40.5 °C; normally internal body temperature is kept constant through natural homeostatic mechanisms. Heat-related illnesses occur due to exposure to high environmental temperatures in conditions in which an organism is unable to maintain adequate homeostasis. This can happen, for example, when the organism is unable to dissipate heat adequately. Heat dissipation occurs through evaporation, conduction, convection, and radiation. Heat disease exhibits a continuum of signs and symptoms ranging from minor to major clinical pictures. Minor clinical pictures include cramps, syncope, edema, tetany, and exhaustion. Major clinical pictures include heatstroke and life-threatening heat stroke and typically are expressed in the presence of an extremely high body temperature. There are also some categories of people at greater risk of developing these diseases, due to exposure in particular geographic areas (e.g., hot humid environments), to unchangeable predisposing conditions (e.g., advanced age, young age (i.e., children), diabetes, skin disease with reduced sweating), to modifiable risk factors (e.g., alcoholism, excessive exercise, infections), to partially modifiable risk factors (obesity), to certain types of professional activity (e.g., athletes, military personnel, and outdoor laborers) or to the effects of drug treatment (e.g., beta-blockers, anticholinergics, diuretics). Heat-related illness is largely preventable. [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]

Vaccination against coronavirus disease 2019 (COVID-19) is the safest and most effective strategy for controlling the pandemic. However, some cases of acute cardiac events following vaccine administration have been reported, including myocarditis and myocardial infarction (MI). While post-vaccine myocarditis has been widely discussed, information about post-vaccine MI is scarce and heterogenous, often lacking in histopathological and pathophysiological details. We hereby present five cases (four men, mean age 64 years, range 50–76) of sudden death secondary to MI and tightly temporally related to COVID-19 vaccination. In each case, comprehensive macro- and microscopic pathological analyses were performed, including post-mortem cardiac magnetic resonance, to ascertain the cause of death. To investigate the pathophysiological determinants of MI, toxicological and tryptase analyses were performed, yielding negative results, while the absence of anti-platelet factor 4 antibodies ruled out vaccine-induced thrombotic thrombocytopenia. Finally, genetic testing disclosed that all subjects were carriers of at least one pro-thrombotic mutation. Although the presented cases do not allow us to establish any causative relation, they should foster further research to investigate the possible link between COVID-19 vaccination, pro-thrombotic genotypes, and acute cardiovascular events. [ABSTRACT FROM AUTHOR]

The vitality demonstration refers to determining if an injury has been caused ante- or post-mortem, while wound age means to evaluate how long a subject has survived after the infliction of an injury. Histology alone is not enough to prove the vitality of a lesion. Recently, immunohistochemistry, biochemistry, and molecular biology have been introduced in the field of lesions vitality and age demonstration. The study was conducted according to the preferred reporting items for systematic review (PRISMA) protocol. The search terms were "wound", "lesion", "vitality", "evaluation", "immunohistochemistry", "proteins", "electrolytes", "mRNAs", and "miRNAs" in the title, abstract, and keywords. This evaluation left 137 scientific papers. This review aimed to collect all the knowledge on vital wound demonstration and provide a temporal distribution of the methods currently available, in order to determine the age of lesions, thus helping forensic pathologists in finding a way through the tangled jungle of wound vitality evaluation. [ABSTRACT FROM AUTHOR]

SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus responsible for the pandemic disease in the last year, is able to affect the central nervous system (CNS). Compared with its well‐known pulmonary tropism and respiratory complications, little has been studied about SARS‐CoV‐2 neurotropism and pathogenesis of its neurological manifestations, but also about postmortem histopathological findings in the CNS of patients who died from COVID‐19 (coronavirus disease 2019). We present a systematic review, carried out according to the Preferred Reporting Items for Systematic Review standards, of the neuropathological features of COVID‐19. We found 21 scientific papers, the majority of which refer to postmortem examinations; the total amount of cases is 197. Hypoxic changes are the most frequently reported alteration of brain tissue, followed by ischemic and hemorrhagic lesions and reactive astrogliosis and microgliosis. These findings do not seem to be specific to SARS‐CoV‐2 infection, they are more likely because of systemic inflammation and coagulopathy caused by COVID‐19. More studies are needed to confirm this hypothesis and to detect other possible alterations of neural tissue. Brain examination of patients dead from COVID‐19 should be included in a protocol of standardized criteria to perform autopsies on these subjects. [ABSTRACT FROM AUTHOR]

Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements. [ABSTRACT FROM AUTHOR]

Autopsy is a complex and unrepeatable procedure. It is essential to have the possibility of reviewing the autoptic findings, especially when it is done for medico-legal purposes. Traditional photography is not always adequate to record forensic practice since two-dimensional images could lead to distortion and misinterpretation. Three-dimensional (3D) reconstructions of autoptic findings could be a new way to document the autopsy. Besides, nowadays, smartphones and tablets equipped with a LiDAR sensor make it extremely easy to elaborate a 3D model directly in the autopsy room. Herein, a quality and trustworthiness evaluation of 3D models obtained during ten autopsies is made comparing 3D models and conventional autopsy photographic records. Three-dimensional models were realistic and accurate and allowed precise measurements. The review of the autoptic report was facilitated by the 3D model. Conclusions: The LiDAR sensor and 3D models have been demonstrated to be a valid tool to introduce some kind of reproducibility into the autoptic practice. [ABSTRACT FROM AUTHOR]

More than eight billion doses of COVID-19 vaccines have been administered globally so far and 44.29% of people are fully vaccinated. Pre-authorization clinical trials were carried out and the safety of vaccines is still continuously monitored through post-commercialization surveillance. However, some people are afraid of vaccine side effects, claiming they could lead to death, and hesitate to get vaccinated. Herein, a literature review of COVID-19-vaccine-related deaths has been carried out according to the PRISMA standards to understand if there is a causal relationship between vaccination and death and to highlight the real extent of such events. There have been 55 cases of death after COVID-19 vaccination reported and a causal relationship has been excluded in 17 cases. In the remaining cases, the causal link between the vaccine and the death was not specified (8) or considered possible (15), probable (1), or very probable/demonstrated (14). The causes of deaths among these cases were: vaccine-induced immune thrombotic thrombocytopenia (VITT) (32), myocarditis (3), ADEM (1), myocardial infarction (1), and rhabdomyolysis (1). In such cases, the demonstration of a causal relationship is not obvious, and more studies, especially with post-mortem investigations, are needed to deepen understanding of the possible pathophysiological mechanisms of fatal vaccine side effects. In any event, given the scarcity of fatal cases, the benefits of vaccination outweigh the risks and the scientific community needs to be cohesive in asserting that vaccination is fundamental to containing the spread of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease. [ABSTRACT FROM AUTHOR]

Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis in prisoners are higher than the general population and are two public health concerns, especially in low- and middle-income countries. We conducted a cross-sectional study to determine the prevalence and the factors associated with LTBI among the inmate population detained in three Southern Italian penitentiaries. Tuberculin intradermal reaction skin test was performed on the inmates who agreed to participate in the study. In case of positivity, the QuantiFERON-TB test was performed. In those positive to QuantiFERON, chest X-ray films were performed, and treatment initiated. A total of 381 inmates accepted to participate. The prevalence of LTBI was 4.2%. In the analysis, LTBI was associated with no self-reported contact with active tuberculosis patients within the prisons, and 10% of subjects admitted the use of inhaled drugs. No HIV coinfections were found. No cases of active symptomatic tuberculosis were identified during the study period. Our results confirm that incarceration increases the risk of tuberculous infection. Non-EU nationality and a history of drug addiction appear to be major risk factors for tuberculosis infection in the penitentiary setting. Reinforcing tuberculosis control is essential to prevent its transmission in prisons. [ABSTRACT FROM AUTHOR]

Wound vitality demonstration is one of the most challenging fields in forensic pathology. In recent years, researchers focused on the application of histological and immunohistochemical staining in this sphere of study. It is based on the detection of inflammation, red cell infiltration, and tissue alterations at the histological examination, all of which are supposedly present in antemortem rather than post-mortem wounds. Nevertheless, some doubts about the reliability of those markers have arisen. Furthermore, the lack of a standardized protocol and the operator dependency of this approach make the proper interpretation of its results difficult. Moreover, a differential miRNAs expression has been demonstrated in antemortem and post-mortem wounds. Herein, a systematic review concerning the current knowledge about the use of miRNAs in lesion vitality evaluation is carried out, to encourage researchers to deepen this peculiar study area. A compendium about the potential miRNAs that may be further investigated as vitality markers is also provided. The aim is to collect all available data about this topic to direct further studies on this field and highlight the future applications of miRNAs in forensic pathology. We found 20 articles and a total of 51 miRNAs that are involved in inflammation and wound healing. Further studies are certainly needed to deepen the role of miRNAs in inflammatory processes in lesioned skin and to evaluate their reliability in distinguishing between antemortem and post-mortem lesions. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) can potentially affect all organs owing to the ubiquitous diffusion of the angiotensin-converting enzyme II (ACE2) receptor-binding protein. Indeed, the SARS-CoV-2 virus is capable of causing heart disease. This systematic review can offer a new perspective on the potential consequences of COVID-19 through an analysis of the current literature on cardiac involvement. This systematic review, conducted from March 2020 to July 2021, searched the current literature for postmortem findings in patients who were positive for SARS-CoV-2 by combining and meshing the terms "COVID-19", "postmortem", "autopsy", and "heart" in titles, abstracts, and keywords. The PubMed database was searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Sixteen papers met the inclusion criteria (case reports and series, original research, only English-written). A total of 209 patients were found (mean age (interquartile range (IQR)), 60.17 years (IQR, 54.75–70.75 years); 122 men (58.37%, ratio of men to women of 1:0.7%)). Each patient tested positive for SARS-CoV-2. Death was mainly the result of respiratory failure. The second most common cause of death was acute heart failure. Few patients specifically died of myocarditis. Variables such as pathological findings, immunohistochemical data, and previous clinical assessments were analyzed. Main cardiac pathological findings were cardiac dilatation, necrosis, lymphocytic infiltration of the myocardium, and small coronary vessel microthrombosis. Immunohistochemical analyses revealed an inflammatory state dominated by the constant presence of CD3+ and CD8+ cytotoxic lymphocytes and CD68+ macrophages. COVID-19 leads to a systemic inflammatory response and a constant prothrombotic state. The results of our systematic review suggest that SARS-CoV-2 was able to cause irreversible changes in several organs, including the heart; this is reflected by the increased cardiac risk in patients who survive COVID-19. Postmortem analysis (including autopsy, histologic, and immunohistochemical examination) is an indispensable tool to better understand pathological changes caused by emerging diseases such as COVID-19. Our results may provide more information on the involvement of the heart in COVID-19 patients. [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]