Pulmonary arterial hypertension (PAH) from autopsy study: T-cells, B-cells and mastocytes detection as morphological evidence of immunologically mediated pathogenesis.

Background: Pulmonary arterial hypertension (PAH) is characterized by severe vascular remodelling, resulting in increased pulmonary vascular resistance with cardiac hypertrophy and heart failure. However, the diagnosis of PAH is often inaccurate. Many cases of PAH are incorrectly diagnosed or missed, and they are often associated with death. The aim of this study was to verify the morphological and histological criteria of fatal cases of PAH and evaluate the lymphocytic populations associated to lesions with reactive neo-angiogenesis. Methods: Pulmonary lung sections from 10 cases of sudden unexpected death (SUD) in the absence of previously diagnosed diseases and in an apparent state of well-being, with final histological post autopsy diagnosis of PAH were collected. The pathological findings were compared using ten controls from non-pathological lung from deaths from other causes. The autopsies included 4 males (40%) and 6 females (60%) with an average age of 52.1 ± 10.1 years. Sections stained with hematoxylin and eosin (H&E) were revised for a morphological diagnosis. Subsequently, serial sections were performed and stained with immunohistochemistry for anti-CD20 (B-lymphocytes), anti-CD3 (T-lymphocytes), anti-CD4 (T-helper lumphocytes), anti-CD8 (T-cytotoxic lymphocytes) and anti-CD117/C-Kit (mast cells/MCs) to detect inflammatory infiltrate and different ratios of cell-type. Statistical analysis was conducted using a paired t-test looking at 100 cells in 3 different tissue samples representative of vascular lesion and 3 different random normal lung parenchyma fields without lesion (from 10 normal control lungs), to identify specific lymphocyte subpopulations in inflammatory infiltrates. Results: There was a significant percentage increase of CD20 (p < 0.001), CD8 (p = 0.002), CD4 (p < 0.001), and CD117/C-Kit positive (C-Kit+; p < 0.001) cells mainly detected around wall vessels; while increased MCs positivity and C-Kit+ were observed especially in alveolar septa. In addition, reactive angiomatosis was observed. Conclusions: The inflammatory infiltrate should be included for a correct diagnosis of PAH besides the vascular remodelling. The inflammatory infiltrate seems to be implicated as a main factor in the pathogenesis. This finding is important to rule out secondary pulmonary hypertension, to identify SUDs of unknown causes and to add new elements to the literature that can explain the immunologically related pathogenesis of PAH

Relationship between COVID-19 Mortality, Hospital Beds, and Primary Care by Italian Regions: A Lesson for the Future

One of the characteristics of the SARS-CoV-2 infection in Italy is the significant regional difference in terms of lethality and mortality. These geographical variances were clear in the first wave and confirmed in the second one as well. The study aimed to analyze the correlation between regional differences in COVID-19 mortality and different regional care models, by retrospectively analyzing the association between the Italian COVID-19 deaths and the number of hospital beds, long-term care facilities, general practitioners (GPs), and the health expenditure per capita. The period considered was from 1 March 2020 to 1 March 2021. The number of hospital beds (p < 0.0001) and the number of GPs (p = 0.0094) significantly predicted the COVID-19 death rate. The Italian regions with a higher number of hospital beds and a lower number of GPs showed a higher number of deaths. Multivariate analyses confirmed the results. The Italian regions with a higher amount of centralized healthcare, as represented by the number of hospital beds, experienced a higher number of deaths, while the regions with greater community support, as exemplified by the number of the GPs, faced higher survival. These results suggest the need for a change in the current healthcare system organization

Early markers for myocardial ischemia and sudden cardiac death.

The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB

Comparative analysis of bones, mites, soil chemistry, nematodes and soil micro-Eukaryotes from a suspected homicide to estimate the post-mortem interval

Criminal investigations of suspected murder cases require estimating the post-mortem interval (PMI, or time after death) which is challenging for longer periods. Here we present the case of human remains found in a Swiss forest. We have used a multidisciplinary approach involving the analysis of bones, soil chemical characteristics, mites and nematodes (by microscopy) and micro-Eukaryotes (by Illumina high throughput sequencing). We analysed soil samples collected beneath the remains of the head, upper and lower body and “control” samples taken a few meters away. The PMI estimated on hair 14C-data via bomb peak radiocarbon dating gave a time range of 1 to 2 years before the finding of the remains on site. Cluster analyses for chemical constituents, nematodes, mites and micro- Eukaryotes revealed two clusters 1) head and upper body and 2) lower body and controls. From mite evidence, we conclude that the body was likely to have been brought to the site after death. However, chemical analyses, nematode community analyses and the analyses of micro-Eukaryotes indicate that decomposition took place at least partly on site. This study illustrates the usefulness of combining several lines of evidence for the study of homicide cases to better calibrate PMI inference tools

Enhanced Characterization of the Smell of Death by Comprehensive Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry (GCxGC-TOFMS)

Soon after death, the decay process of mammalian soft tissues begins and leads to the release of cadaveric volatile compounds in the surrounding environment. The study of postmortem decomposition products is an emerging field of study in forensic science. However, a better knowledge of the smell of death and its volatile constituents may have many applications in forensic sciences. Domestic pigs are the most widely used human body analogues in forensic experiments, mainly due to ethical restrictions. Indeed, decomposition trials on human corpses are restricted in many countries worldwide. This article reports on the use of comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) for thanatochemistry applications. A total of 832 VOCs released by a decaying pig carcass in terrestrial ecosystem, i.e. a forest biotope, were identified by GCxGC-TOFMS. These postmortem compounds belong to many kinds of chemical class, mainly oxygen compounds (alcohols, acids, ketones, aldehydes, esters), sulfur and nitrogen compounds, aromatic compounds such as phenolic molecules and hydrocarbons. The use of GCxGC-TOFMS in study of postmortem volatile compounds instead of conventional GC-MS was successful

New Specimens of Nemegtomaia from the Baruungoyot and Nemegt Formations (Late Cretaceous) of Mongolia

Two new specimens of the oviraptorid theropod Nemegtomaia barsboldi from the Nemegt Basin of southern Mongolia are described. Specimen MPC-D 107/15 was collected from the upper beds of the Baruungoyot Formation (Campanian-Maastrichtian), and is a nest of eggs with the skeleton of the assumed parent of Nemegtomaia on top in brooding position. Much of the skeleton was damaged by colonies of dermestid coleopterans prior to its complete burial. However, diagnostic characters are recovered from the parts preserved, including the skull, partial forelimbs (including the left hand), legs, and distal portions of both feet. Nemegtomaia represents the fourth known genus of oviraptorid for which individuals have been found on nests of eggs. The second new specimen, MPC-D 107/16, was collected a few kilometers to the east in basal deposits of the Nemegt Formation, and includes both hands and femora of a smaller Nemegtomaia individual. The two formations and their diverse fossil assemblages have been considered to represent sequential time periods and different environments, but data presented here indicate partial overlap across the Baruungoyot-Nemegt transition. All other known oviraptorids from Mongolia and China are known exclusively from xeric or semi-arid environments. However, this study documents that Nemegtomaia is found in both arid/aeolian (Baruungoyot Formation) and more humid/fluvial (Nemegt Formation) facies

Commentary on Letter to the Editor From Jeffrey Wells Reply

We appreciate the opportunity to respond to Dr. Wells' letter, although it appears that he does not take issue with our work (indeed Dr. Wells is a coauthor on Campobasso et al. [2005]). However, as forensic pathologists, we would like to express our point of view on the definitions of terms like postcolonization interval (PCI) and period of insect activity (PIA) concerning the estimation of postmortem interval (PMI) based on the entomological evidence. The letter to the Editor by Dr. Wells follows a previous oral presentation the same author gave in Coimbra at the last annual European Association for Forensic Entomology (EAFE) meeting in April 2013 (http://www.eafe.org/Meeting_Coimbra.htm). Dr. Wells raises several criticisms to the practical implications of PCI and PIA as defined by Tomberlin et al. (2011) to guide basic research. In this regard, we agree with his final suggestion that no forensic entomologist should use those definitions unless she or he has fully explained, in the report, the exact meaning. Although Campobasso et al. (2005) did not provide an explicit definition for PIA, the way in which those authors used the terms makes it clear that the phrase corresponded to the age of the oldest larva collected from the corpse. It was, therefore, a development-based minimum PMI (PMImin), which refers to

Morte improvvisa secondaria a pancreatite acuta necrotico-emorragica. Contributo casistico ed aspetti medico-legali

Gli Autori descrivono un caso di morte improvvisa occorsa ad una donna di 20 anni a seguito di una pancreatica acuta necrotico-emorragica causata da calcoli della colecisti. Il caso si presta a considerazioni di carattere epidemiologico e responsabilità professionali dei sanitari che ebbero in cerca la donna