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Chest trauma is the leading cause of death in people under 40. It is estimated to cause around 140,000 deaths each year. The key aims are to reduce mortality and the impact of associated complications to expedite recovery and to restore patient’s conditions. The recognition of lesions through appropriate imaging and early treatment already in the emergency department are fundamental. The majority can be managed in a non-surgical way, but especially after traumatic cardiac arrest, a surgical approach is required. One of the most important surgical procedures is the Emergency Department Thoracotomy (EDT). The aim of this review is to provide a comprehensive synthesis about the management of thoracic trauma, the surgical procedures, accepted indications, and technical details adopted during the most important surgical procedures for different thoracic trauma injuries. Literature from 1990 to 2023 was retrieved from multiple databases and reviewed. It is also important to emphasize the medico-legal implications of this type of trauma, both from the point of view of collaboration with the judicial authority and in the prevention of any litigation.

Objective Osteoarthritis (OA), particularly knee OA, is a leading cause of disability and poses significant challenges in healthcare management. Mobile applications (apps) have emerged as potential tools to support therapeutic exercise by providing tailored programs, instructional content, and progress tracking. This systematic review evaluates the efficacy of mobile apps in enhancing therapeutic exercise for knee OA management. Methods A systematic review was conducted, analyzing randomized controlled trials (RCTs) to assess the impact of mobile apps on pain and knee function in patients with OA. The review followed the Cochrane Handbook guidelines and was registered with PROSPERO. Inclusion criteria focused on RCTs involving adults aged 40 and above with knee OA, and outcomes were measured based on pain intensity and knee function. Results Five RCTs met the inclusion criteria. The results varied: while some studies demonstrated minor improvements in pain and function with app-based interventions, others showed comparable effectiveness to traditional methods. The review highlights the potential of mobile apps to offer benefits in managing knee OA, though outcomes were inconsistent due to intervention and population heterogeneity. Conclusion Despite the low certainty of evidence, mobile app-based interventions appear to have a positive impact on reducing pain and improving physical function in patients with knee OA. Continued research is essential to better understand the effectiveness and long-term impact of mobile technology in OA management, underscoring the value of digital health interventions in enhancing patient care.

Gender incongruence is a current issue with implications in the legislative, social, and healthcare fields. In this context, misinformation is, at present, the main enemy of transgender rights equity. Over time, the scientific community has worked to reclassify this condition, removing it from psychiatric diagnoses. The method of our work involved investigating and comparing the different social and legislative measures adopted by various countries to ensure the rights and equality of individuals with gender incongruence. The result showed that there are various international approaches allowing adult and minor patients to access medical and administrative procedures for gender transition. In conclusion, there appears to be a need for international bioethical and legislative guidance in order to reduce and eventually eliminate the social inequalities faced by individuals with gender incongruence.

Background: COVID-19 caused by SARS-CoV-2 virus is characterized by respiratory compromise and immune system involvement, even leading to serious disorders, such as cytokine storm. Methods: We then conducted a literature review on the topic of sepsis and covid-19, and in parallel conducted an experimental study on the histological finding of patients who died from SARS-Covid 19 infection and a control group. Results: Sepsis associated with covid-19 infection has some similarities and differences from that from other causes. Conclusion: In this paper the complex interplay between the 2 disorders was discussed, focusing on the similarities and on the effect that one could have on the other. A preliminary experimental section that demonstrates the multisystemic involvement in subjects who die from SARS-CoV-2 is also proposed.

Carbon dioxide (CO2) is an endogenous molecule produced by cellular respiration and therefore present in our body and in the atmosphere. It is known that, at high levels, CO2 causes fatal toxic effects. The production of CO2 can prove particularly dangerous in closed and unventilated environments. Although some cases of death due to CO2 are described in forensic literature, today this diagnosis of CO2 intoxication on cadaver is still a challenge as it is a volatile endogenous molecule and strongly increased after death due to anoxia. In this paper, we describe six cases of simultaneous CO2 intoxications which was caused by a fermentation of grape must in a closed environment. Four people died while the other two were rescued. Scene investigation with measurement of environmental gas levels using sensors was performed. Autopsies were carried out with toxicological investigations and histopathological analyses. Finally, a review of the scientific literature on deaths related to fermenting grape gas was carried out. The results demonstrated toxic levels of CO2 at the scene. The corpses showed initial transformative phenomena such as skin discoloration and slippage, while toxicological investigations demonstrated a peak of HbCO2 (carbaminohemoglobin) with alcohol positivity in the blood of the deceased subjects. Histopathological investigations showed must yeasts (Saccharomyces) in the pulmonary alveoli. The paper reports the procedures performed proposing the introduction of new experimental investigations for the post-mortem diagnosis of CO2 intoxication with a forensic diagnostic protocol.

BackgroundCAR-T-related deaths observed worldwide are rare. The underlying pathogenetic mechanisms are the subject of study, as are the findings that enable diagnosis. A systematic literature search of the PubMed database and a critical review of the collected studies were conducted from the inception of this database until January 2023. The aim of the study is to determine when death is related to CAR-T cell therapy and to develop a shareable diagnostic algorithm.MethodsThe database was searched by combining and meshing the terms (“CAR-t” OR “CART”) AND (“Pathology” OR “Histology” OR “Histological” OR “Autopsy”) AND (“Heart” OR “Cardiac” OR “Nervous System” OR “Kidney” OR “Liver”) with 34 results and also the terms: [(Lethal effect) OR (Death)] AND (CAR-T therapy) with 52 results in titles, abstracts, and keywords [all fields]. One hundred scientific articles were examined, 14 of which were additional records identified through other sources. Fifteen records were included in the review.ResultsNeuronal death, neuronal edema, perivascular edema, perivascular and intraparenchymal hemorrhagic extravasation, as well as perivascular plasmatodendrosis, have been observed in cases with fatal cerebral edema. A cross-reactivity of CAR-T cells in cases of fatal encephalopathy can be hypothesized when, in addition to the increased vascular permeability, there is also a perivascular lymphocyte infiltrate, which appears to be a common factor among most authors.ConclusionMost CAR-T-related deaths are associated with blood–brain barrier breakdown, central nervous system cell damage, and infiltrated T cells. Further autopsies and microscopic investigations would shed more light on the lethal toxicity related to CAR-T cells. A differential diagnosis of CAR-T-related death is crucial to identifying adverse events. In this article, we propose an algorithm that could facilitate the comparison of findings through a systematic approach. Despite toxicity cases, CAR-T therapy continues to stand out as the most innovative treatment within the field of oncology, and emerging strategies hold the promise of delivering safer therapies in future.

In Europe, the mental health law legal framework has had several changes throughout the years to achieve and develop new reforms, better mental health care, and protect the human rights of patients. The UK national data shows rising detention rates and the disproportionate use of the legal framework among people from black and minority ethnic groups. At the national level, compulsory admissions are lower in Italy; it also shows that it has increased in the last few years in both countries. The lack of ethnic national data, especially in Italy, limited the ability to understand compulsory admission, discrimination, and stigma in mental health. The present study aims to compare the legal framework of mental health law and compulsory hospital admission in Italy and the UK. A review of each country’s latest amendments to mental health law and the number of compulsory hospital admissions was conducted to understand the impact of changes in mental health care.

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.

Point-of-Care Ultrasound (POCUS) is a rapid and valuable diagnostic tool available in emergency and intensive care units. In the context of cardiac arrest, POCUS application can help assess cardiac activity, identify causes of arrest that could be reversible (such as pericardial effusion or pneumothorax), guide interventions like central line placement or pericardiocentesis, and provide real-time feedback on the effectiveness of resuscitation efforts, among other critical applications. Its use, in addition to cardiovascular life support maneuvers, is advocated by all resuscitation guidelines. The purpose of this narrative review is to summarize the key applications of POCUS in cardiac arrest, highlighting, among others, its prognostic, diagnostic, and forensic potential. We conducted an extensive literature review utilizing PubMed by employing key search terms regarding ultrasound and its use in cardiac arrest. Apart from its numerous advantages, its limitations and challenges such as the potential for interruption of chest compressions during image acquisition and operator proficiency should be considered as well and are discussed herein.

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.

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.

Haemodialysis (HD) is one of the methods for renal replacement therapy in the management of advanced chronic kidney disease through an osmosis process that allows purification of blood in the dialysis machine. The complexity of the dialytic procedure often requires the presence of a multi-specialist, multi-disciplinary team. The dialysis process is an important target for clinical risk management. Failure Mode and Effect Analysis (FMEA) is a proactive technique, considered a purposeful and dynamic tool for clinical risk management. FMEA is noted in five phases that allow a preliminary assessment of a definite process through identification and classification of risk priorities. This study represents the first of a two-phase project where FMEA is applied to HD in the setting of San Feliciano Hospital. The dialysis center performs ~12,000 dialysis sessions per year. The dialysis process is divided into different stages. A total of 31 failure modes were identified in the whole dialysis stages; more than 2/3 of the failure modes were related to the only connecting of the patient to the dialysis machine. The first phase of the study clearly remarked that the most critical step of the dialytic process is represented by the connection between the patient and the machine, as expected. Indeed, in order to have the dialysis set up, an arteriovenous fistula must be surgically created prior to the procedure and it is one of the most important issues in the HD process because of the necessity of a constant revision of it. FMEA application to HD is a useful tool, easy to be implemented and it is likely to nimbly reveal the practical and potential solutions to the critical steps of the procedure.

In forensic practice, the pathologist is often asked to determine whether a hanging was committed as suicide or as a simulated hanging (when a dead body is suspended after death). When exterior evidence of violence is absent and the crime scene investigation fails to identify useful proof, it is nearly impossible to tell whether the dead body was suspended or not. As a result, determining whether the ligature mark was created during life or not should rely on the research and demonstration of vital reactions on the ligature mark. The main purpose of this review article is to provide a summary of current knowledge about the histological and immunohistochemical characteristics of vitality in hanging. The authors also aim to identify the most significant vitality markers on ligature marks for further scientific validation and to propose a standardized diagnostic protocol for hanging. The study was conducted according to the Preferred Reporting Items for Systematic Review (PRISMA) Protocol. Relevant scientific papers were found from PubMed up to April 2021, using the following keywords: hanging AND skin AND vitality. Three main points were studied: ligature mark dehydration, immunological response to mechanical injury, and apoptosis induction as a result of the previous points. An increase in apoptosis is evident in the ligature mark (due to physical and chemical processes involved), as demonstrated by FLICE-inhibitory protein (FLIP) depletion. Immunohistochemical detection of Aquaporin 3 (AQP3) and increase in the concentration of different electrolytes rely solely on ligature mark dehydration. Also, microRNAs (MiRNAs) could become reliable forensic biomarkers for ligature mark vitality diagnosis in the near future. To ensure high reliability in court cases, forensic investigation in hanging should rely on modern and proven markers, even a mix of several markers.

Background:The timing of wounds production is a significant issue in forensic pathology. Although various methods have been evaluated, obtaining an accurate dating of lesions is still a challenge. The pathologist uses many parameters to value wound age, such as histological and immunohistochemical. In recent years, there have been many studies regarding the use of miRNAs in wound-age estimation; indeed, miRNAs have multiple potential uses in forensic pathology.Scope:This review aims to verify the efficacy and feasibility of miRNAs as a tool for determining the timing of lesions.Materials and Methods:The authors conducted the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was used as a search engine to find articles published between January, 1st 2016 and October, 1st 2021, to evaluate the current state of the art regarding wound-age estimation.Results:A total of 256 articles were collected; after screening according to PRISMA guidelines, the systematic review included 8 articles. The studies included in this review were all Original articles evaluating the use of biomarkers for wound-age determination.Discussion and Conclusion:The literature review showed that analysis of miRNA is an innovative field of study with significant potentiality in forensic pathology. There are few studies, and almost all of them are at an early stage. The challenge is to understand how to standardize the samples' selection to obtain reliable experimental data. This observation represents a necessary prerequisite to planning further clinical trials.

WHO identifies vaccine hesitancy (VH) as one of the ten threats to global health. The authors bring to the international scientific community an Italian episode that offers the opportunity to renew the discussion on the extent of the VH matter. The purpose of this systematic review is to analyze the factors determining vaccine hesitancy in the Italian population, to understand its roots, and suggest potential strategies to mitigate it. A systematic review of the literature according to the PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, using the following strategy: (COVID-19 vaccines) AND (vaccination hesitancy) AND (Italy). After the selection process, 36 articles were included in this systematic review. The most frequently detected factors associated with VH in the Italian population can be grouped as vaccine-related factors, socio-cultural factors, and demographic factors. Currently, we are facing a gap between the population and science, governments, and institutions. To heal this breach, it is necessary to strengthen the trust of the population through the implementation of health communication and public education strategies, while scientific literacy must continue to support families and individuals in discerning evidence from opinions to recognize the real risks and balance them with the benefits.

Acute idiopathic pulmonary hemorrhage in infants (AIPHI) is a rare and quite low-described entity. Nowadays, pathophysiological mechanisms are poorly understood, although the lethality remains high. We present an autopsy case report of a 2-day-old male who developed respiratory distress and blood leakage from the endotracheal tube (ET) and suddenly died because of acute pulmonary hemorrhage. A postmortem examination and histological analysis were performed and are reported in this paper. Alveolar spaces were filled with red blood cells and hyaline membranes in all the examined samples. The absence of other findings led us to select a post-mortem diagnosis of AIPHI. To support our diagnosis, we conducted a systematic review of the updated scientific literature and found that only 61 cases have been reported. Most of them presented acute respiratory distress and bleeding from the upper airways with blood leakage from ET (9.83%), hemoptysis (52.45%), epistaxis (8.2%), and hematemesis (3.27%). The autopsy data revealed hemorrhages of the lower airways and hemosiderin-laden macrophages. The data from the scientific publications and our findings are essential to achieving a correct diagnosis. On these bases, we suggest autoptic criteria to achieve a post-mortem diagnosis of AIPHI.

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.

Background: The question about wound vitality and the estimation of wound age of production are two of the classic investigation fields of forensic sciences. To answer this, the techniques most frequently used in research studies are immunohistochemistry (IHC), molecular biology, and biochemistry. Despite the great data on the literature about the usefulness of IHC in forensic pathology, there is always a request for further studies, especially on tissues altered by putrefactive phenomena. In fact, the degradation of the tissues is intended as the main limiting factor to the use of this technique.Scope: The aim of this pilot study was to evaluate the immunohistochemical behavior of samples collected from decomposed bodies (in different putrefaction phases) and to relate these findings to wound vitality and postmortem interval.Materials and Methods: Samples of skin and soft tissues were collected during autopsies, which were executed on decomposed bodies, whose cause of death was concluded to be traumatic. An immunohistochemical study was performed using antibodies against CD15, CD45, IL-15, tryptase, and glycophorin-A MMPs (endopeptidases involved in degrading extracellular matrix proteins: MMP-9 and MMP-2). An immunohistochemistry (IHC) reaction was evaluated according to a qualitative method as the following legend: (0): not expressed, (+): isolated and disseminated expression, (++): expression in groups or widespread foci, and (+++): widespread expression.Results: Most of the tested markers (tryptase, glycophorin, IL15, CD 15, CD 45, and MMP9) showed to be highly expressed in the tissue of putrefied skin for 15 days.Discussion and Conclusion: Although certainly inconclusive, this experimental application demonstrated that a nonexclusive but combined use of multiple antibodies is appropriate to verify wound vitality in decomposed bodies. Among them, GPA exhibited major reliability.

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.

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.

Background: Suicide is a significant cause of mortality affecting each age, gender, and country. In 2018, the Italian National Institute of Statistics (ISTAT) estimated that 3820 people committed suicide, with the highest incidence in males between 35 and 64 years old. The present study aims to report and analyze the data relating to suicides collected by the Institute of Forensic Medicine of Foggia compared to the data presented in the literature. Methods: The present study represents a retrospective analysis of crime scene investigations and autopsies records relating to all suicides from January 2015 to December 2021 referred to the archives of the Institute of Forensic Medicine of Foggia. The analyzed features were: the sex of the victim, method of suicide, age, the season of death, and presence of psychiatric or addiction history. Results: We selected 226 cases of suicide during the period from January 2015 to December 2021, from a total of 1184 deceases. 78% of the victims are men of average age; the most common methods of suicide are hanging and precipitation. Conclusions: The results of this study highlight the importance of personalized and gender-specific interventions and can inform policy-makers in the development of provincial suicide prevention plans and public health interventions. Studying suicidality in a well-defined population can help implement targeted interventions.

Intravascular large B-cell lymphoma (IVLBCL) is a rare (

Limb fractures are the most common injuries in pediatric orthopedics. Early and late complications are often not preventable, even when providing the best treatment; furthermore, these injuries are largely implicated in medico-legal claims. The development of evidence-based guidelines is one of the main goals of medical research. Approved guidelines for diagnosis, treatment, and follow up are fundamental to obtain the best results in medical practice. Guidelines in pediatric traumatology have been developed, even though specific conditions, like obesity, could influence their drafting. The cast and fixation systems usually applied in pediatric fractures provide a growth plate sparing, a satisfying reduction, and good stress resistance, mostly because of a lower bodyweight compared to adults. Several studies suggest that obesity influences the bone quality, the management, and the outcomes in cases of fracture. High body weight increases the risk of trauma, modifies fracture characteristics, and increases the risk of incomplete reduction. Fractures in obese children have a higher rate of complications, regardless of conservative or surgical treatment. In obese children, surgical treatment is often used more frequently than with non-obese children. Such considerations are valid both for lower and upper limb fractures. The aim of this paper is to discuss recent scientific literature and provide a perspective on the benefits of a dedicated approach in the management of obese children. Guideline updates could improve healthcare quality in a pediatric setting, and also reduce medico-legal implications.

Background: The purpose of this manuscript is to provide a comparative overview of the two global pandemics: the first on June 11th 2009 due to influenza A H1N1 (H1N1-09); the second and current pandemic caused by coronavirus 2019 (COVID-19) on March 11th 2020, focusing on how autopsy can contribute to the definition of cellular pathology, to clinical pathology and, more generally, to public health. Methods: A systematic literature search selection was conducted on PubMed database on June 5, 2021, with this search strategy: (COVID-19) AND (H1N1 influenza) showing 101 results. The following inclusion criteria were selected: English language; published in a scholarly peer-reviewed journal; full-length articles were further elected. To further refine the research was to focus on the type of manuscript: review, systematic review, and meta-analysis. A critical appraisal of the collected studies was conducted, analyzing titles and abstracts, excluding the following topics: treatment, public health measures and perception of the general population or healthcare personnel about their quality of life. According to these procedures, 54 eligible studies were included in the present review. Results: Histopathological findings play a key role in understanding the pathophysiological mechanisms of diseases and, thus possible therapeutic approaches. The evidence on the thrombo-inflammatory mechanism underlying COVID-19 is growing to a much greater magnitude than the diffuse alveolar damage in common with H1N1-09; our study appears to be in line with these results. The prevailing scientific thinking to explain the morbidity and mortality of COVID-19 patients is that it elicits an exuberant immune reaction characterized by dysregulated cytokine production, known as a “cytokine storm”. Conclusions: The histological and immunohistochemical pattern demonstrated similarities and differences between the infectious manifestations of the two pathogens, which justify empirical therapeutic approaches, in the first phase of the COVID-19 pandemic. Therefore, the previous pandemic should have taught us to promote a culture of clinical and forensic autopsies in order to provide timely evidence from integration among autopsy and clinical data for early adopting adequate therapies.

Traumatic abdominal injuries are life-threatening emergencies frequently seen in the Emergency Department (ED). The most common is liver trauma, which accounts for approximately 5% of all ED admissions for trauma. The management of blunt liver trauma has evolved significantly over the past few decades and, according to the injury’s severity, it may require massive resuscitation, radiological procedures, endoscopy, or surgery. Patients admitted to the ED with blunt abdominal trauma require a multidisciplinary evaluation, including emergency physicians, surgeons, radiologists, and anesthetists, who must promptly identify the extent of the injury to prevent serious complications. In case of a patient’s death, the execution of a forensic examination carried out with a multidisciplinary approach (radiological, macroscopic, and histological) is essential to understand the cause of death and to correlate the extent of the injuries to the possibility of survival to be able to manage any medico-legal disputes. This manuscript aims to collect the most up-to-date evidence regarding the management of hepatic trauma in the emergency room and to explore radiological findings and medico-legal implications.

Background: Cervical spine manipulations (CSM) have been performed for centuries and are a widely practiced intervention to manage cervical spine musculoskeletal disorders. We aimed to perform an overview of the literature concerning the effects and the adverse events of CSM in the Physical and Rehabilitation Medicine (PRM) field with a forensic medicine perspective. Methods: A search in the scientific literature (PubMed, Google Scholar, PEDro and Cochrane) was carried out from inception until October 2020. Results: Fourteen articles were included in this narrative summary. The possible development of side effects requires a careful mandatory balance of benefits and risks even when there is an indication for this approach. Moreover, a qualified professional is essential to perform CSM–a non-invasive therapeutic procedure that can be potentially harmful. Conclusions: In conclusion, it is essential to perform the diagnosis, to treat, and to manage complications within the PRM field, both for the reduction of malpractice claims and, most importantly, for the safety of the patient.

Italy, like other European countries, has produced a series of regulations during the COVID-19 pandemic. Compulsory vaccination has been introduced for the Italian population. Meanwhile, the Decree-Law 27 January 2022 n. 4 provided for the compensation mechanism for those who have received damage of the psycho-physical integrity due to the anti-SARS-CoV-2 vaccination recommended by the Italian Health Authority. Law 1992 no. 210 already provided for the indemnity system for persons damaged by irreversible complications due to compulsory vaccinations, transfusions, and the administration of blood products. The legislator intended to attribute the right to an indemnity that is not compensatory in order to repair a wrong connected to some hypothesis of liability, but it rather has a welfare character in the broad sense, being attributable to Constitutional fundamentals. In the Italian panorama, although the vaccination damages have been fully included in the already existing law no. 210/1992, to date, no precise indications have been provided regarding the ascertainment of the causal link and the extent of the compensable damage. In the near future, the interest of the scientific community will focus on the evaluation of applications for access to the benefit.

Background: Traumatic brain injury (TBI) during birth constitutes one of the most relevant causes of mortality and morbidity in newborns worldwide. Although improvements in obstetrical management and better indications for caesarean section have led to a consistent decrease in the incidence of perinatal mechanical injury, vacuum extraction is still associated with a high complications rate leading to several forensic issues in the evaluation of healthcare professional management. Methods: Vacuum-associated lesions may be topographically distinguished as extracranial or intracranial injuries. In order to achieve a correct assessment, diagnostic procedure should include post-mortem computed tomography and magnetic resonance imaging, autopsy examination, brain sampling and histological/immunohistochemical examination. Results: Post-mortem imaging represents a valid aid to guarantee preliminary evidence and direct subsequent investigations. An appropriate autopsy sampling must include several areas of cortex and underlying white matter; moreover, any visceral hemorrhages or other lesions should be sampled for the histological and immunohistochemical assessment of vitality and timing. Conclusions: This study aimed to promote a validated step-by-step procedure to be adopted in order to standardize and to make easier the post-mortem framing and timing of vacuum-associated pediatric brain injuries.

During the last years, post-mortem imaging has gradually been assumed within research in the field of forensic pathology. This role appears to be clearly and simply applied in the trauma field with the use of conventional radiography or Post Mortem Computed Tomography (PMCT). Recently, particular attention was paid to cardiovascular imaging using Post Mortem Magnetic Resonance Imaging (PMMRI). The present experimental study aims to: (i) confirm the efficacy of a Post Mortem Cardiac Resonance Imaging (PMCRI) study protocol for the study of human hearts collected during the autopsy; (ii) apply the defined protocol on subjects who died of “SCD (sudden cardiac death)”, to identify alterations that could guide subsequent sampling. Two hearts of healthy subjects (A: male 22 years; B: female 26 years), who died from causes other than SCD were collected and compared to hearts that belonged to SCD individuals (C: male, 47 years old; D: female, 44 years old; E: male; 72 years old). The exams were performed on a 1.5 T scanner (Philips Intera Achieva, Best, the Netherlands) on hearts collected during autopsy and after a 30-day formalin fixation. Two readers analyzed the obtained images blindly and after randomization. From the comparison between the data from imaging and the macroscopic and histological investigations carried out, the present study proved the effectiveness of a PMMRI protocol to study ex-situ hearts. Moreover, it suggested the following semeiology in post-mortem SCD cases: the hyperintense area with indistinct margins in the Short Tau Inversion Recovery (STIR) sequence was linked to edema or area of pathological fibers, whereas the hypointense area in the T2-FFE sequences was linked to fibrosis. PMMRI can provide a valuable benefit to post-mortem investigations, helping to distinctly improve the success rate of histological sampling and investigations, which remains the gold standard in the diagnosis of sudden death.

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.

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.

The European Convention on Human Rights (ECHR) judgement no. 116(2021) of 8 April 2021 establishes the principle of mandatory vaccination, indicating the criteria that national legislation must comply with, following the principle of non-interference in the private life of the individual. Vaccination for the prevention of SARS-CoV-2 infection appears to be an essential requirement for providing healthcare assistance. The European experience with compulsory vaccinations, offers a composite panorama, as the strategy of some European countries is to make vaccinations compulsory, including financial penalties for non-compliance. As in other countries, there is a clear need for Italy to impose compulsory vaccination for healthcare workers, in response to a pressing social need to protect individual and public health, and above all as a defense for vulnerable subjects or patients, for whom health workers have a specific position of guarantee and trust. The Italian Republic provided for mandatory vaccinations for health professionals by Decree-Law of 1 April 2021 no. 44, to guarantee public health and adequate safety conditions. As stated by ECHR, the Italian State, despite having initially opted for recommendation as regards to SARS-CoV-2 vaccination, had to adopt the mandatory system to achieve the highest possible degree of vaccination coverage among health professionals to guarantee the safety of treatments and protection of patients’ health. We present the Italian situation on vaccine hesitation in healthcare workers, with updated epidemiological data as well as the doctrinaire, social, and political debate that is raging in Italy and Europe.

Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic “neutropenic enterocolitis and sepsis” appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.

Estimating the time of death remains the most challenging question in forensic medicine, because post-mortem interval (PMI) estimation can be a remarkably difficult goal to achieve. The aim of this review is to analyze the potential of microRNAs (miRNAs) to evaluate PMI. MiRNAs have been studied as hallmarks and biomarkers in several pathologies and have also showed interesting applications in forensic science, such as high sensible biomarkers in body fluid and tissue, for wound age determination and PMI evaluation due to their low molecular weight and tissue-specific expression. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. We performed an electronic search of PubMed, Science Direct Scopus, and Excerpta Medica Database (EMBASE) from the inception of these databases to 12 August 2020. The search terms were (“PMI miRNA” or “PMI micro RNA”) and (“miRNA” and “time of death”) in the title, abstract and keywords. Through analysis of scientific literature regarding forensic uses of miRNAs, has emerged that the intrinsic characteristics of such molecules, and their subsequent resistance to degradation, make them suitable as endogenous markers in order to determine PMI. However, further and larger studies with human samples and standardized protocols are still needed.

Perinatal hypoxic-ischemic brain injury, as a result of chronic, subacute, and acute insults, represents the pathological consequence of fetal distress and birth or perinatal asphyxia, that is, “nonreassuring fetal status.” Hypoxic-ischemic injury (HII) is typically characterized by an early phase of damage, followed by a delayed inflammatory local response, in an apoptosis-necrosis continuum. In the early phase, the cytotoxic edema and eventual acute lysis take place; with reperfusion, additional damage should be assigned to excitotoxicity and oxidative stress. Finally, a later phase involves all the inflammatory activity and long-term neural tissue repairing and remodeling. In this model mechanism, loss of mitochondrial function is supposed to be the hallmark of secondary injury progression, and autophagy which is lysosome-mediated play a role in enhancing brain injury. Early-induced molecules driven by hypoxia, as chaperonins HSPs and ORP150, besides common markers for inflammatory responses, have predictive value in timing the onset of neonatal HII; on the other hand, clinical biomarkers for HII diagnosis, as CK-BB, LDH, S-100beta, and NSE, could be useful to predict outcomes.

Adult cardiac progenitor cells (CPCs), isolated as cardiosphere-derived cells (CDCs), represent promising candidates for cardiac regenerative therapy. CDCs can be expanded in vitro manyfolds without losing their differentiation potential, reaching numbers that are appropriate for clinical applications. Since mechanisms of successful CDC survival and engraftment in the damaged myocardium are still critical and unresolved issues, we aimed at deciphering possible key factors capable of bolstering CDC function. In particular, the response and the phenotype of CDCs exposed to low concentrations of the multifunctional cytokine tumor necrosis factor α (TNF-α), known to be capable of activating cell survival pathways, have been investigated. Furthermore, differential biological responses of CDCs from male and female donors, in terms of cell cycle progression and cell spreading, have also been assessed. The results obtained indicate that (i) the intracellular signaling activated in our experimental conditions is most likely due to the prosurvival and proliferative signaling of TNF-α receptor 2 and that (ii) cells from female patients appear more responsive to TNF-α treatment in terms of cell cycle progression and migration ability. In conclusion, the present report highlights the hypothesis that TNF-stimulated CDCs isolated from females may represent a promising candidate for cardiac regenerative therapy applications.

Hematopoietic stem cell transplantation (HSCT) is one of a range of therapeutic options available to patients suffering from various diseases. HSCT procedure involves important ethical and legal aspects that can occur at every phase of the procedure: the clinical choice of whether to perform the procedure, pretransplantation preparation regimens, donor selection, stem cell harvest procedure, transplantation phase, and short-term and long-term follow-up care. In this discussion paper, we outline the ethical issue-facing physicians involved in HSCT. Currently, HSCT is a widely accepted treatment for many life-threatening diseases. It thus represents a real therapeutic hope for many patients. It does, however, carry a burden of possible morbidity and mortality. Consequently, there are substantial information and communication issues involved in the consent process for HSCT. In the final decision, the judgements of different parties, such as patients, family members, and healthcare professionals, intersect and overlap and this is particularly true when the patient is a minor. Finally, HSCT is a very expensive procedure. The social and economic concerns of HSCT are discussed within the actual contextual framework of the dramatic increase in healthcare costs and inequalities in healthcare in relation to socioeconomic status, educational status, and ethnicity.

Allogenic hematopoietic progenitor cell transplantation (allo-HSCT) is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA-) identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.