The choice of gadolinium-based contrast agents: a radiologist’s responsibility between pharmaceutical equivalence and bioethical issues

Contrast Agents (CA) are among the most commonly prescribed drugs worldwide, and are used, with a variety of techniques, to increase and intensify the differences between body tissues and to help radiologist make diagnoses in a fast and precise way. In recent decades, advancements in research have resulted in significant improvements in their composition, and have made them safer and better-tolerated by patients; this notwithstanding, although the currently available CA are generally considered to be safe, their use is not completely without risk. The use of CA faces the radiologist with economic considerations, bioethical dilemmas, and possible profiles of professional responsibility. In fact, to achieve the best results in diagnostic imaging, radiologists have to focus on making an appropriate choice of CA, in consideration of efficacy, safety and appropriateness. Moreover, besides by cost/benefit models widely introduced in health management, radiologists are also influenced by their responsibility of appropriate use for the various diagnostic tests and, finally, the choice of best CA to utilise for each individual patient. Thus, the dilemma of choosing between the best and the most cost-effective tests and procedures is occurring more frequently every day. Different variables, such as the patient, examinations, and technology available, can affect the choice of CA in terms of obtaining the highest diagnostic quality, minimum impact on higher-risk patients, and optimisation of used volumes and injection flow

A technical report from the Italian SARS-CoV-2 outbreak. Postmortem sampling and autopsy investigation in cases of suspected or probable COVID-19

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a coronavirus responsible for COVID-19 (coronavirus disease 2019) which resulted in a cluster of cases of pneumonia that originated in China around 31 December 2019 and has subsequently spread across the globe. Currently, COVID-19 represents a health emergency worldwide, leading, in severe cases, to pneumonia, severe acute respiratory syndrome, multiorgan dysfunction or failure, and death. In the context of limited scientific knowledge and evidence of SARS-CoV-2 infection, guidance is becoming increasingly necessary for pathologists who have to perform postmortem investigations on COVID-19 cases. The aim of the present report is to share a procedure applicable to cases of COVID-19-related death, particularly in cases of death without medical intervention and in the absence of an ascertained SARSCoV-2 infection and/or COVID-19 diagnosis, therefore providing support for diagnostic activity in the present COVID-19 pandemic. For this purpose, a standard operating procedure for correct swab collection, autopsy investigation and tissue sampling is provided

New frontiers in thermal analysis: A TG/Chemometrics approach for postmortem interval estimation in vitreous humor

The coupling of thermogravimetric analysis (TG) associated with chemometrics is proposed as an innovative approach in thanatochemistry in order to develop a new analytical tool using thermal analysis for the characterization of vitreous humor. Vitreous samples were selected from the medicolegal deaths which occurred in casualty and where the death interval is known. Only hospital deaths with no metabolic disorders were taken, and the precise time of death was certified by the treating physician. Samples were analyzed by TG7 thermobalance, and principal component analysis was used to evaluate the results. The TG/Chemometrics outcomes show a clearly distinct behavior according to the postmortem interval, concluding that TG and Chemometrics are capable of predicting the time since death using only a few microliters of vitreous, without any pretreatment and with an hour of analysis tim

Clinical applications of personalized medicine: a new paradigm and challenge

The personalized medicine is an emergent and rapidly developing method of clinical practice that uses new technologies to provide decisions in regard to the prediction, prevention, diagnosis and treatment of disease. The continue evolution of technology and the developments in molecular diagnostics and genomic analysis increased the possibility of an even more understanding and interpretation of the human genome and exome, allowing a "personalized" approach to clinical care, so that the concepts of "Systems Medicine" and "System Biology" are increasingly actual. The purpose of this study is to evaluate the personalized medicine about its indications and benefits, actual clinical applications and future perspectives as well as its issues and health care implications. It was made a careful review of the scientific literature on this field that highlighted the applicability and usefulness of this new medical approach as well as the fact that personalized medicine strategy is even more increasing in numerous fields of applications

Widespread septic embolization in injection drug use mitro-aortic infective endocarditis as a remote cause of death

Injection drug use-related infective endocarditis (IDU-IE) assumes peculiar epidemiological, pathogenetic, and prognostic characteristics that allow to consider it a distinct nosological entity, as well as a current problem of considerable social weight. Incidence is reasonably underestimated because diagnosis is often accidental in postmortem examination when drug-related death is suspected. In many cases, postmortem toxicological examinations are negative for acute drug abuse, and findings of infective endocarditis became relevant in the explanation of the mechanism of death. Extracardiac involvement of infective endocarditis is rarely reported as fatal. Fragmentation and embolization of bacterial vegetations can be associated with parenchymal infarcts, systemic spread of the infectious process by formation of an abscess. A case of septic shock as a consequence of the constant bacteremia determined by the continuous proliferation and release of bacteria into the circulation is presented in an injection drug user with left-sided endocarditis and widespread septic embolization. Authors reviewed forensic and medical literature and promote epidemiological value of medical and forensic autopsy. Extracardiac involvement of infective endocarditis may represent a remote and alternative cause of death in injection drug users, and an early diagnosis can be relevant for prognosis. Postmortem examination still represents a valuable opportunity of learning for clinicians and improving diagnostic accuracy with injection drug users. A call for changing of attitudes and practice toward autopsy is finally demanded

La consulenza tecnica d’Ufficio in tema di transessualismo alla luce del D.Lgs n. 150 del 2011: il contributo non sempre richiesto della medicina legale

A seguito delle modifiche apportate alla Legge n. 164/1982 dal Decreto Legislativo n. 150/2011, che non prevede più espressamente il richiamo alla possibilità di espletare una consulenza tecnica d’ufficio per lo studio delle condizioni psico-sessuali del soggetto transessuale, parte della dottrina medico-legale ha sollevato obiezioni circa il possibile restringimento delle indagini tecnico-peritali e quindi dell’apporto della disciplina medico-legale e psichiatrico-forense nei casi di rettificazione di attribuzione anagrafica del sesso. Partendo da tale assunto, gli autori hanno affrontato la tematica relativa alla consulenza tecnica di ufficio in tema di transessualismo, analizzando in particolare le professionalità richieste e la metodologia peritale da adottare nell’ambito della c.t.u. Al fine di tutelare maggiormente la salute psico-fisica del soggetto transessuale, è stata sottolineata l’importanza di un approccio multidisciplinare e, quindi, la necessità della nomina di un collegio peritale costituito da: uno specialista in Medicina Legale ed uno in Psichiatria. Al tempo stesso, è emerso come in realtà in alcuni Tribunali Italiani già prima della modifica legislativa fosse consuetudine basare il giudizio anche soltanto sulla documentazione allegata dall’istante e rilasciata dai vari centri autorizzati.Following the amendments made to the Law no. 164/1982, Legislative Decree no. 150/2011, which no longer expressly provides the possibility of carrying out a technical consultancy for the study of psycho-sexual conditions of the transsexual subject, part of Legal-Medicine interpretation has questioned the possible narrowing of technical-expert surveys and therefore the contribution of Legal Medicine and Mental-Forensic disciplines in cases of rectification of sex registry attribution. Starting from this assumption, the authors addressed the issue concerning the technical consultancy on the subject of transsexualism, focusing on the skills required and on the expert's methodology to be adopted in the c.t.u. field. In order to better protect the mental and physical health of transsexual subject, the importance of a multidisciplinary approach, and so the need of the appointment of an expert panel composed by one specialist in Forensic Medicine and one in Psychiatry have been stressed. At the same time, it emerged that in fact in some Italian Courts, already before the legislative amendment, was customary to base the judgment even only on the documentation attached by the applicant and released from various authorized centers

Immunohistochemical evaluation of aquaporin-4 and its correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 expressions in fatal traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance

Diffuse axonal injury and oxidative stress: A comprehensive review

Traumatic brain injury (TBI) is one of the worldâ\u80\u99s leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)-mediated axonal degeneration is mainly caused by extracellular Ca2+. Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure

Post-mortem computed tomography (PMCT) radiological findings and assessment in advanced decomposed bodies.

PURPOSE: The aim of the study is to report radiological findings and features in advanced decomposed bodies obtained by post-mortem computed tomography (PMCT) with autopsy correlation. MATERIALS AND METHODS: This retrospective descriptive multicentric study included 41 forensic cases examined between May 2013 and November 2016. All the bodies were PMCT-scanned prior to autopsy, and internal putrefactive state was determined using the radiological alteration index (RAI) by a radiologist with expertise in forensic radiology and a forensic pathologist trained in forensic imaging. After PMCT scans, grade of external putrefaction (GEP) was assigned during the external examination and the complete autopsy was performed by forensic pathologists. RESULTS: The PMCT images evaluation revealed that the RAI index was > 61 in all bodies, corresponding to a moderate-massive presence of putrefactive gas. The gas grade was > II in correspondence of the major vessels, heart cavities, liver parenchyma, vertebra L3 and subcutaneous pectoral tissues, and varied from I to III in correspondence of the kidney. Cadaveric external examination revealed the presence of advanced transformative phenomena, with a GEP3 and GEP4 in most of the cases, with body swelling, eyes and tongue protrusion, body fluids expulsion and fat liquefaction. CONCLUSION: Radiological imaging by PMCT as an adjunct to autopsy in advanced decomposed bodies represents a useful tool in detecting post-mortem gas, even in very small amounts. A correct interpretation process of the PMCT data is essential to avoid images pitfalls, due to natural decomposition that can be mistaken for pathologic processes