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Healthcare-related homicidal cases are not novel within the medical–legal landscape, but investigations are often made difficult with the scarcity of material evidence related to the crime. For this reason, it is necessary to carefully analyze the clinical documentation and employ ancillary forensic resources such as radiology, histopathology, and toxicology. In the presented scenario, the observation of 14 deaths from abnormal bleeding in a First-Level Italian Hospital revealed the administration of massive doses of heparin by a nurse. On behalf of the Judicial Authority, a multidisciplinary medical team investigated the case through the following steps: a thorough review of the clinical documentation, exhumation of the bodies belonging to the deceased patients, performing PMCT and autopsy, and collecting tissue samples for histopathological, immunohistochemical, and toxicological investigations. All the analyzed cases have been characterized by the observation of fatal hemorrhagic episodes not explained with the clinical conditions of the patients, confirmed using autopsy observations and the histological demonstration of the vitality of the lesions. However, due to the limited availability of biological material for the toxicological analysis, the indirect evidence from hematological analyses in hospitalized patients was crucial in demonstrating heparin overdose and its link to the recorded deaths. The present scenario demonstrates the fundamental importance of a multidisciplinary approach to cases of judicial interest related to the healthcare context. Therefore, the illustrated methodologies can be interpreted as an operational framework for similar future cases. [ABSTRACT FROM AUTHOR]

In recent years, the consumption of energy drinks by young adults and athletes has risen significantly, but concerns have been raised about the potential health risks associated with excessive consumption. These concerns include cardiovascular problems, nervous system disorders, and the potential for addiction. This review aims to examine the reported effects of acute or chronic abuse of energy drinks on human health. The analysis shows a significant prevalence of adverse effects, particularly on the cardiovascular and neurovegetative systems. In particular, the analysis identified nine cases of cardiac arrest, three of which were fatal. The aetiology of these adverse effects is attributed to the inherent neurostimulant properties of these beverages, of which caffeine is the predominant component. A comparison of documented effects in humans with experimental studies in animal models showed an overlap in results. This review highlights the need for greater rigour in the assessment of sudden cardiac death, particularly in young people, as legal substances such as energy drinks may be involved. We propose stricter limits on the consumption of these beverages than for caffeine, based on the evidence found and the data in the literature. This review also calls for the establishment of regulations governing the consumption of these products in view of their potential impact on human health. [ABSTRACT FROM AUTHOR]

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36–42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE. [ABSTRACT FROM AUTHOR]

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

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

As a result of the duty of care, the healthcare professional has an obligation of surveillance towards the patients that are under their treatment. According to that principle, the Italian Criminal Supreme Court declared a guilty sentence in many cases of psychiatric patients' suicide, recognizing the criminal liability of the healthcare personnel. This is true not only for suicides occurred inside the hospital, but also for the suicide of psychiatric outpatients. Only in a few cases, the Italian Supreme Court acquitted the healthcare personnel. This happened when it was recognized that the suicide event was unavoidable. Despite the fact that suicide risk is often unpredictable, this does not exclude medical liability. In this work we examine the judicial aspects of five cases of suicide of psychiatric patients, considering whether different preventive strategies could have been effective in preventing the suicide event. This work aims to understand whether the suicide of psychiatric patient is effectively preventable and - referring to healthcare responsibility under penal judgment - if that could be proven beyond all reasonable doubt. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.10.025 Byline: Vittorio Fineschi (a), Manolis Michalodimitrakis (b), Stefano D'Errico (a), Margherita Neri (a), Cristoforo Pomara (a), Irene Riezzo (a), Emanuela Turillazzi (a) Keywords: Stress-induced cardiomyopathy; Catecholamine systems; Contraction band necrosis; Sudden death Abstract: Emotional, physiological and physical stress is associated with increased rates of cerebrovascular events and sudden deaths. The pathophysiology of stress-induced cardiomyopathy is not well understood. Proposed mechanisms for catecholamine-mediated stunning in stress cardiomyopathy include epicardial vasospasm, microvascular dysfunction, hyperdynamic contractility with midventricular or outflow tract obstruction, and direct effects of catecholamines on cardiomyocytes. Studies show evidence of significant heritable influences on individual responses to adrenergic stimulation. Data from such studies may be of help for a more accurate comprehension of clinical and morphological alterations of the heart. Irrespective of the cause, patients with the classic stress-induced cardiomyopathy morphology deserve special attention because this extensive distribution of wall motion abnormalities has implications for potential associated complications. Cardiac response may be significantly coupled to genetic differences at candidate loci that encode components of catecholamine biosynthesis, storage, and metabolic pathway. Given the role of the sympathetic nervous system in responses to acute stress, it is reasonable to explore whether genetically determined alterations in catecholamine system functions contribute to acute and chronic cardiovascular disorders such as stress-induced cardiomyopathy. Author Affiliation: (a) Department of Forensic Pathology, University of Foggia, Ospedale Colonnello D'Avanzo, Viale degli Aviatori 1, 71100 Foggia, Italy (b) Department of Forensic Sciences, University of Crete, School of Medicine, 71110 Heraklion, Greece Article History: Received 25 April 2009; Revised 25 September 2009; Accepted 20 October 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.01.006 Byline: Vittorio Fineschi, Emanuela Turillazzi, Margherita Neri, Cristoforo Pomara, Irene Riezzo Keywords: Deep venous thrombosis; Pulmonary embolism; Thrombus; Histological age; Immunohistochemistry; Confocal laser scanning microscopy Abstract: The histological age determination of venous thromboses in fatal pulmonary embolism cases is an important task of forensic medicine and requires thorough knowledge of the general and specific pathology of pulmonary thromboembolism (PTE). The aim of our investigation was to carry out a chronological evaluation of the deep venous thrombosis (DVT) phenomenon, to assess the chronological transformation of the thrombus and to determine the causal relationship with PTE as cause of death. The clinical data and the autopsy records of the 2843 autopsies performed over the period 1 November 1998 to 31 December 2007 were retrospectively evaluated, and 140 cases in which PTE was pointed out as cause of death were selected. The dissection of the deep veins of the legs has been performed systematically to search for the starting point of venous embolism. 4.5% of pulmonary embolisms originated in the in iliac veins, 20.7% in the femoral veins, and 74.8% in the deep crural veins. In the venous sites of thrombosis, the histological assessment has been performed in conjunction with the surrounding vascular wall of uncut blood vessel with at least three to six different transverse incisions. Histological assessment of the embolus samples was also performed in conjunction with the venous sites of thrombosis. In our selected 140 cases of PTE, the DVT was classified as phase 1 in 48 cases (34.29%), as phase 2 in 70 cases (50%), and 22 cases (15.71%) were evaluated as older than 2 months (phase 3). The observed transformation of the thrombus by organization is suitable for a forensically utilizable age determination. However, only three chronological stages can be distinguished with any degree of certainty using immunohistochemistry and CLSM. Author Affiliation: Department of Forensic Pathology, University of Foggia, Ospedale Colonnello D'Avanzo, Via degli Aviatori 1, 71100 Foggia, Italy Article History: Received 7 June 2008; Revised 22 November 2008; Accepted 3 January 2009

Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution. [ABSTRACT FROM AUTHOR]

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

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

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2006.12.002 Byline: Emanuela Turillazzi, Sabina Di Donato, Margherita Neri, Irene Riezzo, Vittorio Fineschi Keywords: Acute interstitial pneumonitis; Hamman-Rich syndrome; Adult respiratory distress syndrome; Diffuse alveolar damage; Immunohistochemistry; Anti-surfactant apoprotein (PE-10); Cytokines Abstract: Acute interstitial pneumonitis (AIP), also known as Hamman-Rich syndrome, is a distinct type of idiopathic interstitial pneumonia affecting patients of both genders without pre-existing lung diseases. We describe the case of a fulminant form of AIP and discuss the pathophysiological mechanisms of AIP with reference to the histological pattern. A 15-year-previously-healthy male boy presented to the Hospital with a 6-day history of malaise, fever and cough. The clinical prodromes were followed by the acute onset of increasing shortness of breath rapidly progressing in acute respiratory failure. Chest X-ray demonstrated bilateral diffuse airspace opacification; the high resolution CT confirmed the presence of bilateral, symmetric diffuse ground-glass attenuation. The patient was admitted to the intensive care unit, but died after few hours. An autopsy was performed within 24h. The histological examination of lung specimens showed a pattern of diffuse alveolar damage. immunohistochemical, microbiological and toxicological tests were also carried out. The clinical presentation, the histological findings and the exclusion of infective, traumatic, toxic and metabolic causes of acute respiratory distress syndrome (ARDS) allowed us to conclude that the boy was affected by AIP. In conclusion, AIP is a diagnosis of exclusion. It has a mortality rate ranging about 50%, despite mechanical ventilation. In fatal cases of AIP diagnosis can be based on clinical presentation, radiological, histological and microbiological findings and can be further confirmed by immunohistochemical analysis. Author Affiliation: Department of Forensic Pathology, University of Foggia, Ospedali Riuniti, Via L. Pinto, 1, 71100 Foggia, Italy Article History: Received 27 March 2006; Revised 20 November 2006; Accepted 5 December 2006