Oxidative Stress in Sepsis: A Focus on Cardiac Pathology.

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.

Is It Still Time for Safety Walkaround? Pilot Project Proposing a New Model and a Review of the Methodology.

Background and Objectives: Healthcare facilities are complex systems due to the interaction between different factors (human, environmental, management, and technological). As complexity increases, it is known that the possibility of error increases; therefore, it becomes essential to be able to analyze the processes that occur within these contexts to prevent their occurrence, which is the task of risk management. For this purpose, in this feasibility study, we chose to evaluate the application of a new safety walkaround (SWA) model. Materials and Methods: A multidisciplinary working group made up of experts was established and then the subsequent phases of the activity were divided into three stages, namely the initial meeting, the operational phase, and the final meeting, to investigate knowledge regarding patient safety before and subsequently through visits to the department: the correct compilation of the medical record, adherence to evidence-based medicine (EBM) practices, the overall health and the degree of burnout of the various healthcare professionals, as well as the perception of empathy of staff by patients. Results: This working group chose to start this pilot project in the vascular surgery ward, demonstrating the ability of the tool used to capture the different aspects it set out to collect. In detail, the new version of SWA proposed in this work has made it possible to identify risk situations and system vulnerabilities that have allowed the introduction of corrective tools; detect adherence to existing company procedures, reschedule training on these specific topics after reviewing, and possibly update the same procedures; record the patient experience about the doctor-patient relationship and communication to hypothesize thematic courses on the subject; evaluate workers' perception of their health conditions about work, and above all reassure operators that their well-being is in the interest of the management of the healthcare company, which is maintained. Conclusions: Therefore, the outcome of the present study demonstrates the versatility and ever-present usefulness of the SWA tool.

Cervical spine injury: clinical and medico-legal overview.

Spinal trauma is an important cause of disability worldwide. Injury to the cervical spine (CS) occurs frequently after major trauma. 5-10% of patients with blunt trauma have a cervical spine injury. The cervical spine accounts for ~ 50% of all spinal injuries. Determination of CS stability is a common challenge in the acute care setting of patients with trauma. Several issues, indeed, are of particular concern: who needs CS imaging; what imaging should be obtained; when should computed tomography (CT), magnetic resonance imaging (MRI), or flexion/extension (F/E) radiographs be obtained; and how is significant ligamentous injury excluded in the comatose patient. CT and MRI both have roles to play. This article aims to present the different imaging to frame techniques to be used with greater precision in the acute event also for the purpose of planning the next therapeutic process. An overview of the applicability of the same methods in forensic pathology is also provided highlighting possible future biomarker to ease in diagnosis of acute TBI.

Glymphatic System a Window on TBI Pathophysiology: A Systematic Review.

BACKGROUND: In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its similarity to the lymphatic system in peripheral tissue and the relevant role of the AQP4 glial channels and described for the first time in 2012. Consequently, numerous studies focused on its role in organ damage in cases of neuropathologies, including TBI. METHODS: To evaluate the role that the glymphatic system has in the pathogenesis of TBI, on 23 March 2022, a systematic review of the literature according to PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, resulting in 12 articles after the selection process. DISCUSSION AND CONCLUSION: The present review demonstrated that an alteration of AQP4 is associated with the accumulation of substances S100b, GFAP, and NSE, known markers of TBI in the forensic field. In addition, the alteration of the functionality of AQP4 favors edema, which, as already described, constitutes alterations of secondary brain injuries. Moreover, specific areas of the brain were demonstrated to be prone to alterations of the glymphatic pathway, suggesting their involvement in post-TBI damage. Therefore, further studies are mandatory. In this regard, a study protocol on cadavers is also proposed, based on the analyzed evidence.

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy.

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.

Traumatic Epidural and Subdural Hematoma: Epidemiology, Outcome, and Dating.

Epidural hematomas (EDHs) and subdural hematomas (SDHs), or so-called extra-axial bleedings, are common clinical entities after a traumatic brain injury (TBI). A forensic pathologist often analyzes cases of traumatic EDHs or SDHs due to road accidents, suicides, homicides, assaults, domestic or on-the-job accidents, and even in a medical responsibility scenario. The aim of this review is to give an overview of the published data in the medical literature, useful to forensic pathologists. We mainly focused on the data from the last 15 years, and considered the most updated protocols and diagnostic-therapeutic tools. This study reviews the epidemiology, outcome, and dating of extra-axial hematomas in the adult population; studies on the controversial interdural hematoma are also included.

Neutropenic Enterocolitis and Sepsis: Towards the Definition of a Pathologic Profile.

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.

Fatal Rupture of Brachial Pseudoaneurysm in a Drug Abuser: Case Report and Review of the Literature.

The injection of drugs of abuse causes many millions of deaths each year; deaths are mostly due to fatal overdose and the trauma and infection caused by repeated injections. The scientific literature widely reports cases of infected pseudoaneurysm in injecting drug abusers; however, most of these autopsy cases deal with the rupture of pseudoaneurysm of the femoral artery. We present fatal hemorrhagic shock in a heroin-cocaine abuser subsequent to rupture of pseudoaneurysm of the brachial artery; the man collapsed just before injecting himself with a dose of heroin-cocaine (speedball).

Human Brain Injury and miRNAs: An Experimental Study.

Brain damage is a complex dysfunction that involves a variety of conditions whose pathogenesis involves a number of mediators that lead to clinical sequelae. For this reason, the identification of specific circulating and/or tissue biomarkers which could indicate brain injury is challenging. This experimental study focused on microRNAs (miRNAs), a well-known diagnostic tool both in the clinical setting and in medico-legal investigation. Previous studies demonstrated that specific miRNAs (miR-21, miR-34, miR-124, miR-132, and miR-200b) control important target genes involved in neuronal apoptosis and neuronal stress-induced adaptation. Thus, in this experimental setting, their expression was evaluated in three selected groups of cadavers: drug abusers (cocaine), ischemic-stroke-related deaths, and aging damage in elder people who died from other neurological causes. The results demonstrated that the drug abuser group showed a higher expression of miR-132 and miR-34, suggesting a specific pathway in consumption-induced neurodegeneration. Instead, miR-200b and miR-21 dysregulation was linked to age-related cognitive impairment, and finally, stroke events and consequences were associated with an alteration in miR-200b, miR-21, and miR-124; significantly higher levels of this last expression are strongly sensitive for ischemic damage. Moreover, these results suggest that these expression patterns could be studied in other biological samples (plasma, urine) in subjects with brain injury linked to aging, drug abuse, and stroke to identify reliable biomarkers that could be applied in clinical practice. Further studies with larger samples are needed to confirm these interesting findings.

Neuropsychiatric and Behavioral Involvement in AAS Abusers. A Literature Review.

Background and Objectives: Anabolic androgenic steroids (AASs) are a complex group of molecules that include both steroidal androgens and synthetic compounds, derived from testosterone. AASs are commonly used to support pharmacological therapy in cases of primary or secondary hypogonadism, major burns, and neoplastic cachexia. Their prolonged and supra-physiological consumption can provoke several adverse effects on various organs and systems. Among these, the physiopathological mechanisms that induce neuropsychiatric disorders related to AAS abuse are poorly known. For this reason, the proposed review aims to retrace the pathway of action of testosterone to focus on the effects on the central nervous system and specifically highlight the effects of AASs on neuropsychiatric and behavioral functions, as well as on lifestyle. Materials and Methods: This review was conducted using PubMed and Google Scholar databases. On these database websites, we searched for articles from 1 January 1980 to March 2019 using the key terms: "AAS," "Anabolic Androgenic Steroids," "brain," and "neurology." Results: The use of AASs through self-administration yields circulating androgens levels, inducing neuron apoptosis, which is linked to thinner cortex and, in general, less cortical volume. The same alterations affect the putamen. These differences were more evident when correlated with longer use. From a functional point of view, prolonged AAS consumption seemed to be related to lower connectivity between amygdala and frontal, striatal, limbic, hippocampal and visual cortical areas. On the other hand, AAS use seems to negatively condition the positive effects of the sport exercise, reducing its important anti-apoptotic and pro-proliferative functions on the hippocampus, implicated in anxiolytic control. Conclusion: This review clarifies the major aspects of the side effects related to AAS use/abuse highlighting the complex mechanisms on neuropsychiatric and cognitive pathological alterations and also the emotional and behavioral dysfunctions.

Immunodeficiency as a side effect of anabolic androgenic steroid abuse: a case of necrotizing myofasciitis.

Even if there are well-known consequences of anabolic androgenic steroid (AAS) abuse, their full pathway of action is still being investigated. In this context, the presented case report aims to discuss and provide evidence of unusual adverse effects linked to immunodeficiency in an AAS abuser. In fact, this kind of chronic complication, even if not usually considered, may lead sudden death. In this case a 31-year-old aesthetic weightlifter, who presented to the emergency department due to an accidental fall that resulted in left thigh trauma. This subsequently developed into left thigh necrotizing myofasciitis in the following few days. Although surgery and hyperbaric therapy were carried out, the man died. An autopsy with complete biological sampling for toxicological studies was performed. This case highlights the close relationship between AAS abuse and immunodeficiency and highlights it's importance for further studies. However, it should be considered that of all the dangerous effects produced by AAS use, necrotizing fasciitis is not such an unusual consequence.

Risk Management and Patient Safety in the Artificial Intelligence Era: A Systematic Review.

BACKGROUND: Healthcare systems represent complex organizations within which multiple factors (physical environment, human factor, technological devices, quality of care) interconnect to form a dense network whose imbalance is potentially able to compromise patient safety. In this scenario, the need for hospitals to expand reactive and proactive clinical risk management programs is easily understood, and artificial intelligence fits well in this context. This systematic review aims to investigate the state of the art regarding the impact of AI on clinical risk management processes. To simplify the analysis of the review outcomes and to motivate future standardized comparisons with any subsequent studies, the findings of the present review will be grouped according to the possibility of applying AI in the prevention of the different incident type groups as defined by the ICPS. MATERIALS AND METHODS: On 3 November 2023, a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out using the SCOPUS and Medline (via PubMed) databases. A total of 297 articles were identified. After the selection process, 36 articles were included in the present systematic review. RESULTS AND DISCUSSION: The studies included in this review allowed for the identification of three main "incident type" domains: clinical process, healthcare-associated infection, and medication. Another relevant application of AI in clinical risk management concerns the topic of incident reporting. CONCLUSIONS: This review highlighted that AI can be applied transversely in various clinical contexts to enhance patient safety and facilitate the identification of errors. It appears to be a promising tool to improve clinical risk management, although its use requires human supervision and cannot completely replace human skills. To facilitate the analysis of the present review outcome and to enable comparison with future systematic reviews, it was deemed useful to refer to a pre-existing taxonomy for the identification of adverse events. However, the results of the present study highlighted the usefulness of AI not only for risk prevention in clinical practice, but also in improving the use of an essential risk identification tool, which is incident reporting. For this reason, the taxonomy of the areas of application of AI to clinical risk processes should include an additional class relating to risk identification and analysis tools. For this purpose, it was considered convenient to use ICPS classification.

Learning from the Past to Improve the Future-Vaccine Hesitancy Determinants in the Italian Population: A Systematic Review.

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.

The role of SARS-COV-2 infection in promoting abnormal immune response and sepsis: A comparison between SARS-COV-2-related sepsis and sepsis from other causes.

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.

Unusual suicide with an electric Jigsaw: A case report and literature review.

Fatal injuries caused by power saws are rare. In most cases, they are accidental and non-voluntary. Even rarer are suicides carried out using power saws, with no previously reported cases of suicide by electric jigsaw. We report a case of suicide by electric jigsaw of a young obese woman suffering from major depression with psychotic features. The peculiarity of our case - compared to those known in the scientific literature - concerns not only the means used for suicide, but also the results of psychological autopsy and the characteristics of the fatal injury. In fact, the autopsy showed a large wound on the anterior and lateral region of the neck with preservation of the integrity of the large vessels of the neck. The cause of death was attributed to haemorrhagic shock due to slow bleeding of small and medium calibre neck vessels, with blood aspiration.

SARS-CoV2 Vaccination Adverse Events Trend in Italy: A Retrospective Interpretation of the Last Year (December 2020-September 2021).

At the end of 2020, a vaccination campaign against COVID-19 was launched. In 2021, legal obligations for health workers, as well as specific regulations for all workers, were introduced. The global SARS-CoV-2 pandemic was followed by epochal changes in life, school, and work habits in Italy. Therefore, the pharmacovigilance work currently being conducted in Italy by the AIFA concerning the recording and analysing of adverse reactions related to the use of vaccines has proved to be very important. The latest report, including a period of 10 months from December 2020 to September 2021, has allowed us to combine the results received so far, and to compare the safety of all vaccines currently available in Italy. The results of this analysis are highly encouraging and reveal the statistical reliability of the safety of the COVID-19 vaccines currently used in Italy. The dissemination of these findings could increase the public's awareness of vaccines and their ability to make free and informed choices concerning vaccination. The potential increase in the Italian population's adherence to the vaccination campaign could ultimately be a decisive factor in achieving herd immunity and the final resolution of the pandemic.

Penetrating cardiac injuries: literature review and analysis of the forensic approach.

Penetrating cardiac injuries represent an increasingly frequent type of trauma in clinical and autopsy practice. The present study aims to review the specialist literature of the last decade (2010-2020) to assess whether the main features of these lesions have changed compared to previous years. The following characteristics were considered: sex, age, cardiac structure involved, execution or not of surgery and postoperative survival, hemodynamic stability, circumstances and mechanism of production, injury and cause of death. Furthermore, the authors propose a practical appraisal of penetrating heart injury in which death was due to a delay in rescue. In line with the data obtained from the practical case, the review showed that compared to the past, the differences concern especially the mortality rate. This paper highlights that the forensic pathologist who approaches a case of transcardiac injury must consider that the circumstances of death are not always attributable to accidental events, attacks or suicides, but may also be due to clinical malpractice or failure to rescue.

Proactive Risk Assessment through Failure Mode and Effect Analysis (FMEA) for Perioperative Management Model of Oral Anticoagulant Therapy: A Pilot Project.

INTRODUCTION: Correct perioperative management of anticoagulant therapy is essential to prevent thromboembolic events and reduce the risk of bleeding. The lack of universally accepted guidelines makes perioperative anticoagulant therapy management difficult. The present study aims to identify the perioperative risks of oral anticoagulant therapy and to reduce adverse events through Failure Mode and Effect Analysis (FMEA). MATERIALS AND METHODS: A multidisciplinary working group was set up, and four main phases of the process were identified. Each of these phases was divided into micro-activities to identify the related possible failure modes and their potential consequences. The Risk Priority Number was calculated for each failure mode. RESULTS AND DISCUSSION: Seventeen failure modes were identified in the entire perioperative period; those with a higher priority of intervention concern the incorrect timing between therapy suspension and surgery, and the incorrect assessment of the bleeding risk related to the invasive procedure. CONCLUSION: The FMEA method can help identify anticoagulant therapy perioperative failures and implement the management and patient safety of surgical procedures.

Liver Trauma: Management in the Emergency Setting and Medico-Legal Implications.

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.

COVID-19 and H1N1-09: A Systematic Review of Two Pandemics with a Focus on the Lung at Autopsy.

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.