Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1ß, IL-6, IL-15 and TNF-α.

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1ß, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1ß in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

Medico-legal assessment of personal damage in older people: report from a multidisciplinary consensus conference.

Ageing of the global population represents a challenge for national healthcare systems and healthcare professionals, including medico-legal experts, who assess personal damage in an increasing number of older people. Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. During conference plenary public sessions, 4 pairs of experts reported on each thematic area. After the last session, a multidisciplinary Jury Panel (15 members) drafted the consensus statements. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields.

Neurofibromatosis 1 and massive hemothorax: a fatal combination.

Type 1 neurofibromatosis (NF 1), a rare genetic disease with autosomal dominant transmission, has typical dermatologic manifestations with pathognomonic Lisch nodules, and is rarely known for vascular alterations. Among these, aneurysmal dilatation is the most common form. We report a fatal case of massive hemothorax due to a spontaneous rupture of the left pulmonary artery branch micro-aneurysm in a NF 1 patient. Indeed, spontaneous rupture of these pathologic vessels is very rare in clinical practice and the literature, but, for its potentially life-threatening complications, there is the need for it to be taken into account in differential diagnosis. The origin of bleeding was first confirmed by computed tomography angiography (CTA). The patient's condition worsened suddenly leading to pulmonary hemorrhage and death. A clinical autopsy was required to assess the definitive cause of death.

Is Hospital Autopsy Auditing Suitable for Clinical Risk Manage ment? Actualities and Perspectives of Auditing in the Autopsy Room Following Italian Law 24/2017 on Patient Safety.

BACKGROUND: Autopsy is a valuable tool for understanding the physiopathology of any disease, and it is the gold standard to assess the cause of death. The clinical autopsy is the ultimate medical service for a patient and plays a crucial role in the context of quality control, education of physicians and other medical personnel, as well as mitigation of risk of malpractice claims. OBJECTIVE: This study aims to demonstrate the importance of improving an autopsy service and the relevance of this investigation procedure in daily clinical practice by evaluating the rate of major discrepancies between the assumed cause of death and the ascertained cause of death after a complete post mortem investigation. A further aim is to classify these discrepancies as class I or class II discrepancies according to the Goldman's criteria in order to assess performance quality. METHODS: A retrospective study of the hospital autopsies performed from June 2018 to March 2020 was conducted by considering a diversified dataset, including age and sex of the deceased as well as the clinical and pathological causes of death. RESULTS: 362 cases were taken into consideration. Major discrepancies were found in 71.3% of cases, with a class I error of 22.7% and a class II error of 48.6%. The most frequent misdiagnosis were cardiovascular disorders, embolism, and aneurism rupture. DISCUSSION: The rate of major discrepancies and the rate of class I and class II errors are way above the rate found in the literature. Despite the high rate of a major discrepancy, evidence collected from hospital autopsies (i.e., certainty of the cause of death, unknown comorbidities) has strengthened the legal defense in cases of medical malpractice litigation. In our experience, by accurately determining the cause of death, revealing new or unexpected findings, and any possible diagnostic or technical errors, post-mortem examinations can significantly contribute to the improvement of team performance and quality of care. CONCLUSION: The presence of clinicians during an autopsy and the early sharing of results can be considered a new auditing strategy for hard clinical cases. Finally, by providing a clearer understanding of the nature and cause of the illness, the autopsy results assist in the grieving process by reassuring family members that action or inaction on their part had not contributed to the death.

[Patterns of information and informed consent procedures. Study of the Ethical Commission of the ANMCO]. / Modalità di informazione ed acquisizione del consenso informato. Indiagine della Commissione Etica dell'ANMCO.

A survey on patterns of information and informed consent procedures during daily clinical practice has been performed by the Ethical Commission of ANMCO. A structured questionnaire (38 questions) was sent to the 653 cardiological units of the National Health Service in Italy. Four hundred and eighty (73.5%) were received. The following variables were considered to evaluate differences in the answers from the various cardiological units: geographical site, presence or absence of an in-patient department, a cath-lab, and of cardiac surgery facilities. Independent predictors of returning questionnaires were: geographical site (Northern Italy vs Central and Southern) and the presence of a cath-lab. Informed consent forms were provided in 53% of instances, while in 40% a free comment about the topic of informed consent was sent. Statistically significant differences in the answers were found about physicians' and nurses' role, ways of information, qualitative and quantitative risk estimates, other persons' role, models of consent forms and procedures of obtaining consent. Free comments and informed consent forms did not allow a statistical analysis. However, they still provided sufficient material to identify specific patterns of how cardiologists deal with the informed consent process. The distinction between the two phases of information and consent was rarely clear. Information or educational material was often mixed with consent forms. While some still showed a paternalistic approach, or else considered informed consent as a formal act, others demonstrated a deep understanding of the significance of the concept of informed consent. A widespread need of guidelines and standard patterns resulted.