Donor selection for allogenic hemopoietic stem cell transplantation: clinical and ethical considerations

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

Ischemia/reperfusion injury following acute myocardial infarction: A critical issue for clinicians and forensic pathologists

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Reperfusion strategies are the current standard therapy for AMI. However, they may result in paradoxical cardiomyocyte dysfunction, known as ischemic reperfusion injury (IRI). Different forms of IRI are recognized, of which only the first two are reversible: reperfusion-induced arrhythmias, myocardial stunning, microvascular obstruction, and lethal myocardial reperfusion injury. Sudden death is the most common pattern for ischemia-induced lethal ventricular arrhythmias during AMI. The exact mechanisms of IRI are not fully known. Molecular, cellular, and tissue alterations such as cell death, inflammation, neurohumoral activation, and oxidative stress are considered to be of paramount importance in IRI. However, comprehension of the exact pathophysiological mechanisms remains a challenge for clinicians. Furthermore, myocardial IRI is a critical issue also for forensic pathologists since sudden death may occur despite timely reperfusion following AMI, that is one of the most frequently litigated areas of cardiology practice. In this paper we explore the literature regarding the pathophysiology of myocardial IRI, focusing on the possible role of the calpain system, oxidative-nitrosative stress, and matrix metalloproteinases and aiming to foster knowledge of IRI pathophysiology also in terms of medicolegal understanding of sudden deaths following AMI

The Long Way to Objectify Organ Damage Related to Cocaine Abuse: Oxidative Stress is the Main Culprit

Cocaine is one of the principal drugs of abuse, it is an illegal psychostimulant, and the chronic consumption of cocaine causes damage in a range of body organs. Cocaine is known to undergo metabolism through multiple enzymatic pathways leading to the formation of several highly reactive species, which have been proposed to exert a direct toxic effect in the organs. All its metabolites may be involved in the activation of redox cycles, the depletion or decrease of antioxidant enzymes and the consequent generation of reactive oxygen species (ROS) leading to oxidative stress (OS) events, the lipid peroxidation and disruption of cellular activity, and consequently cocaine-induced organs damage. However, the exact mechanisms of cocaine-mediated toxicity in all the organs are not fully understood. This review provides extensive evidence in support of the hypothesis that oxidative metabolites play important roles comprising oxidative stress, defined as a disturbance of redox signaling and control that can cause malfunction in organs such as the brain, heart, liver, kidney and skin

DONOR SELECTION FOR ALLOGENIC HAEMOPOIETIC STEM CELL TRANSPLANTATION: CLINICAL AND ETHICAL CONSIDERATIONS

Allogenic haematopoietic 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 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 both for donors and recipients; it carries with it significant clinical, moral and ethical concerns, mostly when donors are minor. 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; 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, are highlighted as well as the need of an adequate insurance protection for all the parties involved

Multi-phase post-mortem CT-angiography: A pathologic correlation study on cardiovascular sudden death

Multi-phase post-mortem CT-angiography (MPMCTA) has the great potential to increase the quality of the post-mortem investigation, especially in the area of sudden death; however, its role as routine complement to the pathology toolbox is still questioned as it needs to be further standardized. The aim of this study is to investigate the contribution of MPMCTA in cases of sudden unexplained death in adults and in particular in sudden cardiovascular death. Sixty-eight sudden unexpected deaths of adults were investigated at our institution between 2012 and 2013. Ten cases underwent MPMCTA and autopsy and were included in the study. Before the angiographic step by complete filling of the vascular system, prior to any manipulation of the body, a non-contrast CT-scan was carried out. Image reconstructions were performed on a CT workstation (Vitrea) and two radiologists experienced with post mortem imaging interpreted the MPMCTA findings. In all 10 cases, we could state a good correlation between combination of post-mortem CT and MPMCTA and autopsy procedures, confirming a high diagnostic sensitivity. With this case series we want to illustrate the advantages offered by performing MPMCTA when facing a sudden death, regardless of specific suspicion for acute coronary syndrome or other vascular or ischemic disease

Multi-phase post-mortem CT-angiography (MPMCTA) is a very significant tool to explain cardiovascular pathologies. A sudden cardiac death case

Multi-Phase Post-Mortem CT-Angiography (MPMCTA) is a standardized technique performed by a protocol that increases the radiological interpretation by decreasing artifacts due to the perfusion and by reaching a complete filling of the vascular system. The quality of the CT angiographies was evaluated radiologically by observing the opacification of the vascular system and assessing the interpretability of the resulting images, and by comparing radiological diagnoses to conventional autopsy conclusions. Here we describe a sudden death case in which Multi-Phase Post-Mortem CT-Angiography was helpful to define the diagnosis. A 72 year-old man that during a violent quarrel with his wife he complained of thoracic pain, and he suddenly died. Multi-Phase Post-Mortem Computed Tomography Angiography was carried out using the standardized protocol and it visualized the blood in pericardial sac and the ruptured wall situated in the posterior part of the left ventricle, as the contrast agent leaked through the rupture. The following autopsy confirmed the hemopericardium; the inspection of the left ventricle showed on the lateral and posterior wall a darkish and stiff area. Axial slices from the apex to the atrioventricular valves revealed a large area of pale myocardium diffused to the lateral and posterior free wall of the left ventricle, and in the forth section the rupture of the ventricular wall was visible. In all sections the marginal and the posterior branches of the left circumflex artery were totally occluded by darkish thrombosis. This catastrophic complication of the extensive myocardial infarction often remains undiagnosed and constitutes an autopsy finding. In this way the post-mortem imaging, in particular the CT-Angiography, is an useful tool to investigate all the vascular system and it enables better visualization of the ruptured ventricular wall

“Freedom and Dignity Are Worth More than Life”: The Dramatic Suicide of an Anti-Vax Man

Since the beginning of the COVID-19 public health emergency, we have witnessed an increase in psychiatric problems and pathologies, such as depression, anxiety, isolation, posttraumatic stress disorder, substance abuse, and burnout. The world’s collective sentiment finally turned toward optimism after authorization was granted for the COVID-19 vaccines’ emergency use by the FDA in December 2020. With the increase in vaccine coverage in Western countries, case counts and deaths gradually plummeted while activity restrictions were progressively lifted. At the same time, however, a new COVID-19-related public health issue has arisen, as a substantial number of eligible individuals refused vaccination. Behaviors assumed by the so-called anti-vax people in manifesting their own opposition towards COVID-19 vaccination are various, and sometimes assume the forms of dramatic gestures with symbolic value, such as suicide. Here, we present the case of a healthy, convinced anti-vax, 58-year-old man, who allowed himself to be run over by a moving train in the presence of eyewitnesses, bringing with him a demonstrative note of his reasons. The present article aims to raise awareness against the social and psychological impact of COVID-19 vaccination refusal and to point out the need of a specific support net to avoid the spread of psychological impairment, social isolation and suicidal behaviors among the “anti-vax community”