Sudden Death due to Diseases of the Adrenal Glands and Paraganglia

Coroners and pathologists commonly evaluate unexpected deaths due to diseases of the adrenal glands and paraganglia, which are, unfortunately, not rare in their totality. Although cardiac causes are the main cause of sudden death, endocrine conditions can produce sudden, unexpected deaths that need further investigation, especially in younger patients. This chapter focuses on the issue of sudden death due to diseases involving adrenal glands and paraganglia. The main causes of sudden death due to adrenal gland pathology will be examined, paying particular attention to the pathophysiology of sudden death, macroscopic and microscopic characteristics and their correlation with clinical features. These issues are of great interest, especially considering the clinical impact of sudden death and its rarity among patients with adrenal gland diseases. The forensic pathologist’s examination is extremely important in determining the cause of death and findings not clinically observable and can contribute to the improvement of the clinical and surgical approach in treating such patients

Vaccination policy in Italy: An update

The effective control of vaccine-preventable diseases generally requires indefinite maintenance of extremely high rates of timely vaccination. Therefore, vaccine hesitancy is of paramount importance and needs to be addressed. In Italy, regulations about vaccinations are controversial and, to some extent, inconsistent. Even though the childhood vaccinations are mandatory by law (Italian Law n. 891/1939, n. 292/1963, n.51/1966 and n. 165/1991), the limited deterrent effectiveness of the sanctioning system, and the changes introduced by the Italian Constitutional Law n. 3/2001 (devolution of almost all the competences and responsibilities in health matters to the Regions and the Autonomous Provinces), were the fertile ground in which new vaccine policies were generated and developed, radically different from the existing ones: many Regions, based on what was decided in 2005 - on an experimental basis - by the State-Regions Conference, decided to abolish the vaccination obligation and/or to stop the imposition of administrative sanctions on non-compliant parents. In addition, since then, there is a worrying tendency to decline vaccinations due to the parents’ mistrust in pharmaceutical companies and health policies. Therefore, recently, the Italian government decided to deploy an emergency ordinance (Italian Decree Law n. 73/2017). In this article, the authors are going to illustrate the current situation in Italy concerning vaccination policy, from a legislative and social point of view

Diagnosis of sudden cardiac death due to early myocardial ischemia: An ultrastructural and immunohistochemical study

The aim of this post-mortem ultrastructural and immunohistochemical study is to explore the characteristics of acute myocardial ischemia in the context of sudden death, using the combination of two different methods, both more insightful than ordinary histology. Transmission electron microscope and immunohistochemistry, in addition to the traditional histology, were applied to study human heart specimens collected during forensic autopsies. The whole series was sub-grouped into cases (n=17) and controls (n=10). The control group consisted of unnatural death with a short agonal period (immediately lethal injuries). Heart samples of the two cohorts of subjects were prepared for electron microscopy. On the other hand, each specimen, formalin fixed and paraffin embedded, was stained with haematoxylin and eosin and immunoreacted with the following primary antibodies: antiFibronectin, antiConnexin-43, anti npCx43 (dephosphorylated form of Connexin43), antiZonula occludens-1. Immunopositivity of each marker in the myocardium was semi-quantitatively graded. Electron microscopy revealed a number of interesting differences between acute myocardial ischemia and controls, regarding the morphology of nucleus, mitochondria and intercellular junctions. By immunohistochemistry, fibronectin was found to be markedly increased in the extracellular matrix of the acute myocardial ischemia cases, with a remarkable difference in respect of controls. Connexin 43 staining disclosed a slightly increase in the cytoplasm of acute myocardial ischemia cases with respect to the controls, whereas no relevant differences were seen between cases and controls at intercellular junctions. Dephosphorylated form of Cx43 showed an evident difference of staining in cases compared to controls and overall this difference more evident in the cytoplasm. Zonula occludens 1, described as an important marker for functional modification of cardiac muscle fibers, resulted negative or very weak in the vast majority of both cases and controls. The present study attempts to simultaneously apply electron microscopy and immunohistochemistry, in order to figure out the morphological changes that might lead to pathological processes underlying the sudden, unexpected death due to acute myocardial ischemia, and consequently to find useful diagnostic markers of very early ischemic injury. Both methods showed significant differences between acute myocardial ischemia and controls, regarding, overall nuclei, mitochondria, and intercellular junctions.

The transcriptional profile of adipose-derived stromal cells (ASC) mirrors the whitening of adipose tissue with age

Multipotent stem cells persist within the stromal vascular fraction (SVF) of adipose tissue during adulthood. These cells, commonly referred to as adipose-derived stromal cells (ASC), have been extensively investigated over the past years as a promising therapeutic tool based on their regenerative and immunomodulatory properties. However, how ASC might mirror the age-related alteration of the fat they reside in remains unclear. Herein, we show that inguinal adipose tissue in mice turns from brown/beige- to white-like with age and resident ASC readily mirror these changes both at mRNA and microRNA transcriptional level. Mechanistically, our data suggest that these brown/age-related changes in ASC transcription rely on changes in the activity of E2F1 and NFkB transcription factors

Impact of asbestos on public health: a retrospective study on a series of subjects with occupational and non-occupational exposure to asbestos during the activity of Fibronit plant (Broni, Italy)

The goal of this study is to understand more about the role of asbestos in causing human diseases, first of all mesothelioma, by investigating a large series of deaths due to asbestos-related diseases (ARDs). The main aim is to clarify if even very low amounts of asbestos can cause mesothelioma and other ARDs, as well as to find out if a different individual vulnerability can be important. This retrospective study included 188 subjects who died from asbestos related diseases in 2000-2017 in the area around Broni, Italy, where an important asbestos cement factory had been active from 1932 until 1993. In each case, a forensic autopsy has been performed. In order to perform the present study, the records were retrieved, including the clinical files, the autopsy, and the histological report. The statistical analysis performed showed that there was a significant relation between the cause of death (mesothelioma, lung cancer or asbestosis) and the kind of exposure (occupational, neighborhood or household), showing that all the subjects not exposed occupationally (and, therefore, exposed to lower amounts of asbestos) died from mesothelioma, whereas the individuals who used to work at the plant died also from other caused (asbestosis, lung cancer). Significant differences were highlighted examining the distribution of the causes of death according to the smoking habits. Moreover, among the mesothelioma patients, the survival time was shorter in the subjects with a neighborhood or household exposure than in the occupationally exposed individuals. The study provided meaningful data about the role of asbestos in causing human pathologies. In particular, the present data appear to support the hypothesis that even an exposure to a very little amount of asbestos can cause mesothelioma in hypersusceptible subjects (probably, on a genetic basis)

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Asbestos exposure and malignant mesothelioma: the role of inorganic fiber burden and disruption of iron homeostasis in lung microenvironment. A postmortem study on human lungs

Asbestos-related diseases still represents a major public health problem all over the world. Among them, malignant mesothelioma (MM) is a highly aggressive, poor-prognosis cancer, arising from the serosal lining of pleura, pericardium and peritoneum, triggered by asbestos exposure. Asbestos is the collective name of six kinds of naturally occurring minerals, namely chrysotile (the only serpentine asbestos), and the amphiboles crocidolite, amosite, tremolite asbestos, actinolite asbestos, anthophyllite asbestos. The response of human lungs to asbestos inhalation and the molecular mechanisms which lead to MM development several decades after exposure are still largely unknown. One of the most debated issues is the formation of asbestos bodies, that are asbestos fibers covered by an iron-rich amorphous substance. Literature data suggest the key role of iron metabolism in the coating process leading to the formation of asbestos bodies, that has been regarded as both protective and harmful. This study aims to understand more about the reaction of the human organisms to asbestos inhalation and the individual susceptibility to MM. First, the lung inorganic fiber burden has been characterized in lungs of individuals who were previously exposed to asbestos (occupationally or environmentally) using electron scanning microscopy with energy dispersive spectroscopy (SEM-EDS). All the subjects used to work at an asbestos-cement industry, which was active between 1932 and 1993 in Broni, a small town in Lombardy. Unexpectedly, a significantly lower concentration of asbestos fibers has been found in MM compared to asbestosis patients. Chrysotile was not detected at all in any of the examined samples, despite it was largely used at the plant, suggesting a complete clearance of this type of asbestos from lungs. Crocidolite was the most represented asbestos, followed by amosite, tremolite/actinolite asbestos and anthophyllite asbestos, consistently with the data about the industry production. The ratio between asbestos fibers and asbestos bodies was widely different from subject to subject. Based on the well-known role of iron in asbestos-induced pulmonary toxicity, the second part of the study investigated the frequency of a group of single nucleotide polymorphisms (SNPs) in genes involved in iron homeostasis in individuals who died from MM compared to controls. Despite the successful DNA extraction from formalin-fixed paraffin-embedded samples (FFPE), we failed to identify any genotype associated with a protective or predisposing effect in relation to MM development as a consequence of asbestos exposure. Finally, on the basis of the established role of BAP1 in MM pathogenesis and its association with ferroptosis impairment observed in various kinds of cancers, the expression of BAP1, transferrin receptor 1 (TRF1), ferritin heavy chain 1 (FTH1) and ferroportin (FPN) has been investigated using immunohistochemistry and rtPCR, finding that asbestos affects the expression of the mentioned proteins in lungs differently in MM patients compared to subjects exposed to asbestos but died of other causes. These findings suggest that a different biological response to asbestos inhalation and to the consequent iron overload in lungs may play an important role in cancer initiation. The formation of asbestos bodies appears to be a key mechanism in the formation of a pro-neoplastic microenvironment, as well as ferroptosis impairment. These results are important from a prevention point of view, as iron metabolism, as well as the consequent oxidative stress, chronic inflammation and cancerogenic stimuli might be targets for therapeutic strategies aiming to delay or prevent MM onset in individuals previously exposed to asbestos. Moreover, knowing the mechanism that can make an individual vulnerable to asbestos can be of crucial importance for prevention