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Background: Growing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA). Methods: The Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA. Results: Overall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58-75) vs. 90 (85-95); p = <0.001], role limitations due to physical health [25 (0-50) vs. 62 (50-75); p = 0.004], bodily pain [47.5 (41.1-61.3) vs. 55.5 (55-96); p = 0.001], general health [40 (30-60) vs. 70 (50-80); p = 0.0003] and social functioning [50 (37.5-62.5) vs. 62.5 (54.9-75); p = 0.007] while higher scores for depressive symptoms [14 (11-15.4) vs. (9.5 (6-15.4); p = 0.05)] compared to HVA patients (n = 43). All the dimensions of SF-36 were negatively correlated with anxiety (r from -0.26 to -0.66; p all < 0.01) and depressive symptoms (r from -0.44 to -0.73; p all < 0.001). Alexithymia was negatively correlated with vitality (r = -0.28; p = 0.02) and mental health (r = -027; p = 0.03). Additionally, patients with alexithymia (38% of participants) showed higher levels of depressive symptoms [9.5 (10-19) vs. 14 (6-13.9); p = 0.005] and anxiety levels [31 (27.9-35) vs. 24 (16-33.9); p = 0.02]; they also showed less vitality [40 (39.9-50) vs. 55 (50-60) p = 0.01], social functioning [50 (37.5-62.5) vs. 62.5 (50 vs. 75); p = 0.01] and mental health [48 (44-60) vs. 68 (56-76); p = 0.004]. Conclusion: Clinical psychological features due to severe hypersensitive reactions may contribute to the patient's perceived HR-QoL. Focused clinical psychological interventions should be promoted to improve the clinical management of such conditions.

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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.

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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.

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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.

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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.

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Kounis Syndrome (KS) is a clinical entity triggered by allergic or hypersensitivity reactions capable of inducing acute coronary events. Several causes can induce KS, including drugs and insect stings. Here, a rare case of post mortem assessment of fatal KS related to fluorescein retinal angiography has been reported. An 80-year-old man in follow-up for a retinal vein thrombosis underwent a retinal fluoroangiography. Approximately 30 min later, the patient complained of sweating and dizziness, and suddenly lost consciousness due to a cardiac arrest. Despite the immediate cardiopulmonary resuscitation, he died. The autopsy revealed foamy yellowish edema in the respiratory tract and coronary atherosclerosis with eccentric plaques partially obstructing the lumen. The routine histology highlighted lung emphysema and myocyte break-up with foci of contraction band necrosis at the myocardial tissue. Biochemistry showed increased serum tryptase, troponin, and p-BNP. Activated and degranulated (tryptase) mast cells were detected, using immunohistochemistry, in the larynx, lungs, spleen, and heart. Acute myocardial ischemia due to allergic coronary vasospasm related to fluorescein hypersensitivity has been assessed as cause of death. KS-related deaths are considered rare events, and the post mortem assessment of KS quite difficult. The integration of several investigations (gross and microscopic examination, biochemistry, immunohistochemistry) can provide useful findings to support the diagnosis, helping to reduce the unrecognized cases as much as possible.

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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.

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Sigma-1 receptor (σ-1R) modulates cellular signaling pathways, probably acting as a ligand operated chaperone. When activated, the receptor translocates from the interface mitochondrion associated membrane of the endoplasmic reticulum to the cell membrane. σ-1R was demonstrated in some brain regions, including the pineal gland, and was proposed to be involved in several cerebral processes, including neuroprotective responses against homeostasis alterations. On this basis, the immunohistochemical expression of σ-1R in human pineal glands was evaluated, with particular regard to the different causes of death. Thirty-eight pineal glands obtained from forensic autopsies were divided into five groups according to the cause of death: sudden death, drowning, fire fatality, hanging, and hemorrhagic shock, and examined with hematoxylin-eosin stain and immunohistochemistry for σ-1R. Both pinealocytes and perivascular spaces were evaluated. The pineal glands from sudden death were only mildly positive for σ-1R, while a more evident immunopositivity was observed in hanging, fire fatality, hemorrhagic shock, and drowning. These results were confirmed in a two-by-two comparison between the sudden death group and other groups. Our data demonstrate for the first time with immunohistochemical techniques the presence of σ-1R expression in the human pineal gland and propose a direct correlation between σ-1R expression and duration of the death process, in particular when hypoxic conditions and/or excessive psychological stress are present.

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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.

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Kounis syndrome (KS) is an acute coronary syndrome triggered by allergic or hypersensitivity reactions. Incidence rates vary, with studies reporting 19.4 per 100.000 among all admissions and 3.4% among allergy patients. This review explores the expanding understanding of KS, encompassing various manifestations, and focusing on both clinical data and forensic findings useful in performing a diagnosis. The pathophysiology of this syndrome involves a complex interplay between allergic reactions and the cardiovascular system. Mast cell activation, histamine release, leukotrienes, cytokines, and platelet activation can contribute to coronary events. Three types of classification systems (allergic angina, allergic myocardial infarction, allergic stent thrombosis) aid in categorizing presentations. The diagnosis of KS relies on clinical presentation, laboratory findings, and imaging. Postmortem assessment of KS is based on the integration of circumstantial data, autopsy, and histological findings. Biochemical and immunohistochemical analyses also contribute to postmortem diagnosis. In conclusion, a combined, multidisciplinary approach should be used to ease the diagnostic process, which is crucial for forensic practitioners in confirming KS occurrence.

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Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.

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Background: Several diagnostic and therapeutic processes are regulated by guidelines and recommendations provided by International and National Societies which offer standardized indications for health-care practitioners, including the treatment of pathologies that may affect the thyroid gland. These documents are very important for patient health promotion and, also, for preventing adverse events associated with patient injuries and related malpractice litigations. Particularly, thyroid surgery can be a cause of professional liability due to complications from surgical errors. Even if the most frequent complications are hypocalcemia and recurrent laryngeal nerve injury, this surgical specialty can be also burdened by other rare and serious adverse events such as esophagus lesions. Case Description: Here a case of alleged medical malpractice involving a 22-year-old woman reporting a complete esophagus section during thyroidectomy was described. The case analysis highlighted that the surgical treatment was performed for an unconfirmed Graves-Basedow disease which was then assessed as Hashimoto thyroiditis by histological exam of the removed gland. The esophagus section was treated by termino-terminal pharyngo-jejunal anastomosis and termino-terminal jejuno-esophagus anastomosis. The medico-legal analysis of the case revealed two different profiles of medical malpractice related, respectively, to the misdiagnosis of the pathology due to an inappropriate diagnostic-therapeutic procedure and the production of the complete section of the esophagus, representing an extremely rare complication of thyroidectomy. Conclusions: Clinicians should ensure an adequate diagnostic-therapeutic path based on guidelines, operational procedures, and evidence-based publications. The non-observance of the "required rules" for diagnosis and treatment of thyroid disease can be associated with a very rare and severe complication that strongly compromises the patient quality of life.

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The recovery of severely altered cadavers (i.e., extensively decomposed, mummified, charred or dismembered) can be a challenge for forensic pathologists due to the difficulties in identification, PMI estimation and manner and cause of death determination. In such cases, integrating routine approaches (autopsy, histology, toxicology) to more specific forensic branches can be fundamental to improving the investigative process. In this paper a systematic review using PubMed, Scopus and Web of Science databases has been performed. The aim was to evaluate the forensic approaches implemented in the management of severely altered bodies due to decomposition, mummification, skeletonization, charring or dismemberment (to which we refer to as "complex"), and the role of each approach in the solution of a case. Then, the literature revision results were used to propose a schematic flowchart summarizing the post mortem activities that can be performed in forensic practice, adaptable in relation to each case.

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OBJECTIVE: Age estimation of living or dead individuals has a strategic importance in medicine, anthropology, and forensic science, in the context of mass disasters and in civil or criminal matters such as adoption or asylum. Teeth play a major role in this context in particular, the third molars are useful for determining whether an individual has reached the legal age of 18 years because they are still in development from the age of 14. MATERIALS AND METHODS: In this study, a sample of 307 panoramic radiographs performed on healthy subjects aged between 13 and 23 was analyzed to consider the correlation between the maturity index of the third molar (I3M) and age to verify the reliability of the cutoff 0.08 indicated by Cameriere et al in a sample of Italian subjects living in the Province of Messina (Sicily, South Italy) to discern the adult subjects from the minors. STATISTICAL ANALYSIS: The analysis of 307 panoramic radiographs resulted in a sensitivity of 89.2% with a confidence interval of 95%, a specificity of 96.5% with a confidence interval of 95%, and a positive predictive value of 96.7%. RESULTS: The method proved itself reliable in estimating adulthood in the population of the Messina- Sicily, but the I3M should not be used as the sole indicator to determine whether a person is younger or older than 18 years because age estimation based on dental methods alone has limitations as the third molars suffer from many variations related to their morphology, their location, and their development. CONCLUSION: We recommend a combination of several methods that are available to increase accuracy of age estimation, depending on the different legal requirements in civil or criminal cases.

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Complex suicides are rare events pursued by the victims by means of two or more different fatal methods and can be further classified in planned or unplanned depending on the simultaneous or sequential application of the methods, respectively. The multiplicity of the injuries detected can frequently lead to misinterpretations, thus making a multidisciplinary approach of utmost importance. Here an unusual unplanned complex suicide was described discussing the post-mortem data leading to the forensic diagnosis; moreover, a focus on the depression cause was reported. The case regarded a 48-year-old man with a recent diagnosis of depression who self-stabbed his neck and, subsequentially, fallen from height. Data obtained from autopsy, histology, radiology and toxicology were described, highlighting the main findings for achieving the differential diagnosis between suicide and homicide. Moreover, microscopic findings compatible with an unrecognized thyroiditis led to consider the thyroid dysfunction as a possible substrate of depression, suggesting it potential effect on suicidal behaviour.

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The need of a minimally invasive approach, especially in cases of cultural or religious oppositions to the internal examination of the body, has led over the years to the introduction of postmortem CT (PMCT) methodologies within forensic investigations for the comprehension of the cause of death in selected cases (e.g., traumatic deaths, acute hemorrhages, etc.), as well as for personal identification. The impossibility to yield clear information concerning the coronary arteries due to the lack of an active circulation to adequately distribute contrast agents has been subsequently overcome by the introduction of coronary-targeted PMCT Angiography (PMCTA), which has revealed useful in the detection of stenoses related to calcifications and/or atherosclerotic plaques, as well as in the suspicion of thrombosis. In parallel, due to the best ability to study the soft tissues, cardiac postmortem MR (PMMR) methodologies have been further implemented, which proved suitable for the detection and aging of infarcted areas, and for cardiomyopathies. Hence, the purpose of the present work to shed light on the state of the art concerning the value of both coronary-targeted PMCTA and PMMR in the diagnosis of coronary artery disease and/or myocardial infarction as causes of death, further evaluating their suitability as alternatives or complementary approaches to standard autopsy and histologic investigations.

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In this report, the authors provide a contribution of PMCT in assessing the cause of death due to natural disasters. Here, the PMCT findings of 43 subjects who died during both landslide and flood were described. The post-mortem imaging revealed, clearly, traumatic injuries and/or the presence of foreign material in airways allowing to assess the cause of death of each subject, together with external inspection and the collected circumstantial data. Particularly, the PMCT has been helpful for characterization and localization of the clogging substance in airways providing findings on bronchial branches involvement. Moreover, the investigation offered detailed data on skeletal injuries in all anatomic districts and put in evidence both the precise fracturing site and the characteristics of fracture stubs for each bone fracture. This report supports the recommendation of the virtual autopsy in a case with several victims, as in natural disasters, and its role as an alternative diagnostic investigation when the standard autopsy is not feasible.

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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

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The presented study evaluated the expression of dystrophin and MMP-9 in cases of sudden cardiac death (SCD) due to coronary atherosclerotic disease (CAD) in order to analyze the characteristics and the chronology of their expression, providing evidence on the possible role in post-mortem diagnosis of myocardial ischemia. The expression of these proteins was also compared to C5b-9 complex and fibronectin expression to evaluate any differences. Two groups of CAD-related SCD, respectively group 1 with gross and/or histological evidence and group 2 with no specific histological signs of myocardial ischemia, were used. A third group formed by cases of acute mechanical asphyxiation was used as a control. The immunohistochemical staining by dystrophin, MMP-9, C5b-9, and fibronectin antibodies was performed. The study revealed that dystrophin and MMP-9 showed different expression in group 1 and group 2 as, respectively, different degree of sarcolemmal staining depletion and increasing of interstitial and granulocytes immunopositivity. Moreover, loss of dystrophin staining and C5b-9 immunopositivity were more significant when compared to MMP-9 increasing. Dystrophin and MMP-9 seemed to be useful immunohistochemical markers for the detection of myocardial ischemic damage. However, the comparison of the four markers suggested that loss of dystrophin could be considered as an earlier marker.

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The patient's security and safety represent a topic of great importance for public health that led several healthcare organizations in many Countries to share documents to promote risk management and preventing adverse events. Surgical Fire (SF) is an infrequent adverse event generally occurring in the operating room (OR) and consisting of a fire that occurs in, on, or around a patient undergoing a medical or surgical procedure. Here a medico-legal case involving a 65-year-old woman reporting burns to the neck due to an SF during a thyroidectomy was described. A literature review was performed using Pubmed and Scopus databases, focusing on epidemiology, causes, prevention activities associated with the SF, and the related best practices recommendations. The medico-legal analysis of the case led to admit the professional liability because the suggested time (3 min) to use the electrocautery after CHG application was not respected. The case analysis and the literature review suggest the importance of implementing National and Local procedures to promote the management of SF risk. Finally, it is necessary to highlight the role of incident reporting and root causes analysis in understanding the cause of the adverse events and thus enforce their prevention.

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