Fourteen Deaths from Suspected Heparin Overdose in an Italian Primary-Level Hospital.

Healthcare-related homicidal cases are not novel within the medical-legal landscape, but investigations are often made difficult with the scarcity of material evidence related to the crime. For this reason, it is necessary to carefully analyze the clinical documentation and employ ancillary forensic resources such as radiology, histopathology, and toxicology. In the presented scenario, the observation of 14 deaths from abnormal bleeding in a First-Level Italian Hospital revealed the administration of massive doses of heparin by a nurse. On behalf of the Judicial Authority, a multidisciplinary medical team investigated the case through the following steps: a thorough review of the clinical documentation, exhumation of the bodies belonging to the deceased patients, performing PMCT and autopsy, and collecting tissue samples for histopathological, immunohistochemical, and toxicological investigations. All the analyzed cases have been characterized by the observation of fatal hemorrhagic episodes not explained with the clinical conditions of the patients, confirmed using autopsy observations and the histological demonstration of the vitality of the lesions. However, due to the limited availability of biological material for the toxicological analysis, the indirect evidence from hematological analyses in hospitalized patients was crucial in demonstrating heparin overdose and its link to the recorded deaths. The present scenario demonstrates the fundamental importance of a multidisciplinary approach to cases of judicial interest related to the healthcare context. Therefore, the illustrated methodologies can be interpreted as an operational framework for similar future cases.

Cannabis regulatory system in European Union countries, forensic concept of "doping dose" and medico-legal implications.

Cannabis is the most widely used illicit psychoactive substance in the world. In recent years, in many European Union countries, there has been a decriminalisation of the use and personal possession of cannabis for recreational purposes. There has been a spread of medical cannabis, as well as marketing of cannabis products at low concentrations of delta-9-tetrahydrocannabinol (Delta-9-THC), the major chemical to which cannabis owes its psychotropic effect. The percentage limit of this substance, only recently set by the European Court of Justice, must be distinguished from the "doping dose" of Delta-9-THC, namely, the dose which causes psychotropic effect in the consumer. Our study analyses and summarises the regulations in the countries of the European Union on the penalisation of recreational cannabis, the legalisation of medical cannabis and limits on percentage of THC imposed locally. Based on the analysis of a recent judgment of the Italian Supreme Court of Cassation, we discuss the importance of the role of the forensic toxicologist in the scientific definition of "doping dose". The distinction between the doping dose of THC and the percentage of THC contained in the marketed cannabis product is vital when establishing fair punishment in the event of a crime.

Correction: Aquaro et al. Post-Mortem Cardiac Magnetic Resonance in Explanted Heart of Patients with Sudden Death. Int. J. Environ. Res. Public Health 2022, 19, 13395.

The authors wish to make the following corrections to this paper [...].

The Importance of the International Community in Protecting the Right to Abortion: The Cases of Malta and of the US Supreme Court.

According to the World Health Organization (WHO), abortion is often necessary and is not a criminalizable medical act. Unfortunately, despite the global trend in recent years tending towards liberalization of abortion as a fundamental right of women in certain circumstances, it is still not guaranteed in all countries of the world in the same way. Moreover, the abortion debate is often characterized by unscientific opinions based on political and/or religious ideologies. Recently, a European episode has rekindled the debate on abortion: in Malta, a tourist was unable to have an abortion, with consequent risks, even serious ones, on her health. In addition, even in the United States a Supreme Court ruling created a considerable stir: the Roe v. Wade (1973) ruling that had legalized abortion at the federal level was revoked. After the ruling of the Supreme Court, each state of the USA can decide for itself whether and how to legalize abortion. These recent international developments are particularly worrying and make even more evident the need for abortion to be protected at an international level as an inalienable and fundamental human right, and therefore not to be limited.

Cannabinoids and Brain Damage: A Systematic Review on a Frequently Overlooked Issue.

BACKGROUND: Although cannabinoid consumption represents a current social and health problem, especially in a historical context characterized by an open orientation for recreational and therapeutic purposes, risks regarding the neurotoxicity of such substances are frequently overlooked. OBJECTIVE: The present systematic review aims to summarize the available evidence regarding the mechanism of cannabinoids-induced brain damage as a substrate of neurological, psychiatric, and behavioral effects. Another objective is to provide support for future investigations and legislative choices. METHODS: The systematic literature search through PubMed and Scopus and a critical appraisal of the collected studies were conducted. Search terms were "(("Cannabinoids" OR "THC" OR "CBD") AND "Brain" AND ("Damage" OR "Toxicity"))" in the title and abstracts. Studies were included examining toxic effects on the brain potentially induced by cannabinoids on human subjects. RESULTS: At the end of the literature selection process, 30 papers were considered for the present review. The consumption of cannabinoids is associated with the development of psychiatric, neurocognitive, neurological disorders and, in some cases of acute consumption, even death. In this sense, the greatest risks have been related to the consumption of high-potency synthetic cannabinoids, although the consumption of phytocannabinoids is not devoid of risks. CONCLUSION: The research carried out has allowed to highlight some critical points to focus on, such as the need to reinforce the toxic-epidemiologic monitor of new substances market and the importance of information for both medical personnel and general population, with particular attention to the mostly involved age groups.

Cannabis and Driving: Developing Guidelines for Safety Policies.

INTRODUCTION: The dynamism in the regulatory frameworks concerning the consumption of cannabinoids has placed their effects on cognitive and psychomotor skills at the center of the scientific debate. In consideration of the potential repercussions on public safety, particular attention has been focused on the impairment of driving skills, opening up the need to specifically regulate driving under the effects of cannabinoids. PHARMACOKINETICS: Both native cannabinoids and metabolites show a long positivity at low concentrations in the biological fluids, especially in the case of chronic consumption. Qualitative positivity to cannabinoids does not itself prove the presence of detrimental effects, which require the presence of active substances at relevant concentrations. Driving Skill Impairment: Multiple studies highlight a tetrahydrocannabinol (THC) concentration- based alteration of driving skills mainly affecting automatisms, whereas skills subjected to cognitive control are preserved up to higher dosages. The evidence relating to associations with other substances, chronic consumption and other cannabinoids, on the other hand, is still burdened by a high degree of uncertainty. Regulation Policies: Different models can be adopted in the regulation of driving under the effects of cannabinoids: sanctions can be applied in case of qualitative positivity, cannabinoids concentration above a defined threshold, or in presence of a demonstrated state of cognitive alteration. CONCLUSION: "Per se limit" with a quantitative THC cut-off between 3.5 and 5 ng/ml can currently be considered the most balanced choice. Finally, the analysis carried out allowed to identify pitfalls in both scientific and legislative fields for the improvement of safety policies.

Post-Mortem Cardiac Magnetic Resonance in Explanted Heart of Patients with Sudden Death.

BACKGROUND: We sought to evaluate the diagnostic accuracy of post-mortem cardiac magnetic resonance (PMCMR) of explanted hearts to detect the cardiac causes of sudden death. METHODS: PMCMR was performed in formalin-fixed explanted hearts of 115 cases of sudden death. Histological sampling of myocardium was performed using two different approaches: (1) guideline-based sampling; (2) guideline-based plus PMCMR-driven sampling. RESULTS: Forensic diagnosis of cardiac cause of death was ascertained in 72 (63%) patients. When the guideline-driven histological sampling was used, the PMCMR interpretation matched with final forensic diagnosis in 93 out of 115 cases (81%) with sensitivity of 88% (79-95%), specificity of 65% (47-80%), PPV of 84% (78-90%), NPV of 73% (58-84%), accuracy of 81% (72-88%), and AUC of 0.77 (0.68-0.84). When a PMCMR-driven approach was added to the guideline-based one, the matching increased to 102 (89%) cases with a PMCMR sensitivity of 89% (80-94%), a specificity of 86% (67-96%), PPV of 95% (89-98%), NPV of 73% (59-83%), accuracy of 89% (81-93%), and AUC of 0.88 (0.80-0.93). CONCLUSIONS: PMCMR has high accuracy to identify the cardiac cause of sudden death and may be considered a valid auxilium for forensic diagnosis. PMCMR could improve histological diagnosis in conditions with focal myocardial involvement or demonstrating signs of myocardial ischemia.

Mapping complications in thyroid surgery: statistical data are useful for medico-legal management of a recurrent safety issue.

Quality of care assessment is a crucial tool for patient safety implementation. Litigation relating to thyroid surgery is one of the most represented sectors also due to the continuous increase in the number of thyroid interventions. Given the incidence of the problem, the present study aims to outline an operational methodology for risk mapping and litigation management in thyroid surgery. The study was conducted through the analysis of data collected at Umberto I General Hospital in Rome from 2007 to 2018. All thyroid surgery claims were included and, subsequently, a descriptive statistical analysis of the categorical variables was performed with the representation of frequencies in absolute terms and as a percentage. The results obtained show that in 94% of cases (44 cases) the reported event consists of incorrect treatment. The most frequent adverse events were identified in unilateral or bilateral recurrent nerve lesions (31; 70%); incomplete removal of the thyroid gland (6; 14%), post-surgical hypoparathyroidism (4; 9%), aesthetic damage secondary to surgical scars (2; 5%), dental avulsion during intubation maneuvers (1; 2%). The experience derived from the risk mapping through management of thyroid claims proved it to be a reactive tool of considerable importance in clinical governance. The promotion of measures aimed at improving the satisfaction of some critical parameters identified in the litigation management activity such as adherence to the indications for surgery, the preoperative diagnostic path, and the adequacy of the surgical report allows to further implement the quality of care in the surgical treatment of thyroid pathology.

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.

Atypical Fentanyl Transdermal Patch Consumption and Fatalities: Case Report and Literature Review.

Fentanyl is a synthetic L-opioid receptor agonist, approximately 100 times more potent than morphine, that is experiencing an upward trend in the field of abuse. Fentanyl patches' abusive consumption can occur either by transdermal absorption or through other atypical and ingenious routes. In the present case, a 29-year-old man with a history of illicit drug use was found dead in a suburban neighborhood of an Italian city. At autopsy, lungs appeared increased in weight and showed minute subpleural hemorrhages. Airways contained abundant reddish foamy material; in addition, a fentanyl patch protective film was found inside the left main bronchus. Toxicological analysis revealed the presence of morphine, fentanyl, BEG and ethyl alcohol in peripheric blood; 6-MAM was also revealed in urine. Findings collected during post-mortem investigations allowed us to identify fentanyl consumption as the cause of death. Fentanyl consumption presumably took place by chewing of a transdermal patch, with subsequent aspiration of the protective film. The pathophysiology of death can be identified as combined respiratory failure-both central suppression and a fentanyl-induced increase in muscular stiffness; a further minor contribution may be identified in the mechanical airflow obstruction caused by the presence of the protective film at the bronchial level.

Supporting Decision Making in Intensive Care: Ethical Principles for Managing Access to Care During the COVID-19 Pandemic.

The pandemic from COVID-19 causes a health threat for many countries and requires an internationally coordinated response due to the high spread of the infection. The current local and international situation gives rise to logistical and ethical considerations regarding the imbalance between needs for assistance and availability of health resources in the continuation of the emergency. A shortage condition will require healthcare professionals to choose between patients who will have access to respiratory support and those who will have to continue without. The sharing of criteria for the introduction of patients to the different therapeutic paths is fundamental to prevent the onset of ethical issues. The present paper analyzes the critical issues related to the scarcity of healthcare resources and the limitation of access to intensive care with the aim of proposing ethically sustainable principles for the management of the current pandemic situation.

Atypical antipsychotics and oxidative cardiotoxicity: review of literature and future perspectives to prevent sudden cardiac death.

Oxidative stress is considered the principal mediator of myocardial injury under pathological conditions. It is well known that reactive oxygen (ROS) or nitrogen species (RNS) are involved in myocardial injury and repair at the same time and that cellular damage is generally due to an unbalance between generation and elimination of the free radicals due to an inadequate mechanism of antioxidant defense or to an increase in ROS and RNS. Major adverse cardiovascular events are often associated with drugs with associated findings such as fibrosis or inflammation of the myocardium. Despite efforts in the preclinical phase of the development of drugs, cardiotoxicity still remains a great concern. Cardiac toxicity due to second-generation antipsychotics (clozapine, olanzapine, quetiapine) has been observed in preclinical studies and described in patients affected with mental disorders. A role of oxidative stress has been hypothesized but more evidence is needed to confirm a causal relationship. A better knowledge of cardiotoxicity mechanisms should address in the future to establish the right dose and length of treatment without impacting the physical health of the patients.

Key Performance Indicators in Claims Management: Definition of a Set of Indicators for the Evaluation of the Medico-Legal Activity.

BACKGROUND: In recent decades, in the field of healthcare, awareness of the problems inherent to the quality has steadily increased. Currently, the evaluation of healthcare activities is one of the ways in which health systems regulate internal relationships and define strategic decisions. OBJECTIVE: The study aims to describe in detail the entire process of developing a group of Key Performance Indicators for monitoring and implementing the management of litigation due to medical liability. Particularly, the objective is to centralize and standardize the indicators to provide scientifically reliable data on claims management to hospital professionals responsible for strategic choices. METHODS: The study was conducted to analyze data relating to the claims management at Umberto I General Hospital in Rome from 2012 to 2018. All claims reported were classified according to a selection of the categories coded in the International Classification for Patient Safety system, the economic features, and the chronological references of the main management extrajudicial and judicial phases. The Process Analysis Method was followed to develop significant indicators for measuring the performance and the quality of claims management. RESULTS AND CONCLUSION: The results obtained demonstrate how the assessment of performance in claims management can potentially lead to greater risk control with significant repercussions in terms of reduction of disputes, speed in settling claims, reduction of management times, planning of loss prevention measures, and implementation of quality of care.

Mors Gaudet Succurrere Vitae. The Role of Clinical Autopsy in Preventing Litigation Related to the Management of Liver and Digestive Disorders.

Over the last 50 years, the number of clinical autopsies has decreased, but their role in assessing cause of death and clinical performance is still acknowledged. Few publications have studied their role in malpractice claim prevention. The paper aims to highlight the role of clinical autopsy in preventing errors and improve healthcare quality. A retrospective study was conducted on 28 clinical autopsies performed between 2015 and 2021 on patients dead unexpectedly after procedures for the diagnosis and treatment of digestive and hepatic diseases. After an accurate analysis of medical records and consultation with healthcare professionals, all cases were subjected to autopsy and histopathology. The data obtained were analyzed and shared with the risk-management team to identify pitfalls and preventive strategies. Post-mortem evaluations confirmed the clinical diagnosis only in six cases (21.4%). Discordances were observed in 10 cases (35.7%). In the remaining 12 cases (42.9%) the clinical diagnosis was labeled as "unknown" and post-mortem examinations made it possible to document the cause of death. Post-mortem examinations can concretely enrich hospital prevention systems and improve patient safety. The methodological approach outlined certainly demonstrates that, even in the risk-management field, "mors gaudet succurrere vitae" ("death delights in helping life").

Role of induced pluripotent stem cells in diagnostic cardiology.

Ethical concerns about stem cell-based research have delayed important advances in many areas of medicine, including cardiology. The introduction of induced pluripotent stem cells (iPSCs) has supplanted the need to use human stem cells for most purposes, thus eliminating all ethical controversies. Since then, many new avenues have been opened in cardiology research, not only in approaches to tissue replacement but also in the design and testing of antiarrhythmic drugs. This methodology has advanced to the point where induced human cardiomyocyte cell lines can now also be obtained from commercial sources or tissue banks. Initial studies with readily available iPSCs have generally confirmed that their behavioral characteristics accurately predict the behavior of beating cardiomyocytes in vivo. As a result, iPSCs can provide new ways to study arrhythmias and heart disease in general, accelerating the development of new, more effective antiarrhythmic drugs, clinical diagnoses, and personalized medical care. The focus on producing cardiomyocytes that can be used to replace damaged heart tissue has somewhat diverted interest in a host of other applications. This manuscript is intended to provide non-specialists with a brief introduction and overview of the research carried out in the field of heart rhythm disorders.

Bioethical issues and legal frameworks of surrogacy: A global perspective about the right to health and dignity.

Modern advances in assisted reproduction technology (ART) have disrupted the traditional concept of parenthood. Every year, thousands of people travel abroad from their home countries in order to circumvent restrictive legislation or to benefit from lower fees. In a similar context, surrogacy raises many bioethical and legal issues. The present paper will address the main questions arising from the debate prompted by surrogacy, focusing on international legislation, and looking critically at the different legislative models. As a result of worldwide heterogeneity in policies, legal approaches, and access to ART throughout the world, a growing number of would-be parents are seeking treatment abroad. The lack of regulation on cross-border surrogacy in low income countries can undermine the dignity and rights of women as even modest economic compensation determines a significant purchasing power. The international effort should be aimed at creating an international regulatory framework from which guidelines useful to national governments derive. An international agreement would provide a solid legal basis for the protection of surrogate women. In order to limit the economic interests linked to procreative tourism, so as to truly protect global health and women's rights, legislative uniformity is therefore necessary between the various states.

Expanding frontiers of risk management: care safety in nursing home during COVID-19 pandemic.

BACKGROUND: Nursing homes provide long-term care and have residential-oriented hospitalizations characterized by medical, nursing and social-care treatments for a typically geriatric population. In the current emergency phase, the problem of infections in residential structures for the elderly is taking on considerable importance in relation to the significant prevalence rates of coronavirus disease 2019 (COVID-19). SAFETY IMPROVEMENT STRATEGIES: Prevention and control measures for severe acute respiratory syndrome coronavirus 2 infection in nursing homes should be planned before a possible outbreak of COVID-19 occurs and should be intensified during any exacerbation of the same. Each facility should identify a properly trained contact person-also external-for the prevention and control of infections, who can refer to a multidisciplinary support committee and who is in close contact with the local health authorities. The contact person should collaborate with professionals in order to prepare a prevention and intervention plan that considers national provisions and scientific evidence, the requirements for reporting patients with symptoms compatible with COVID-19 and the indications for the management of suspected, probable or confirmed cases of COVID-19. DISCUSSION: Adequate risk management in residential structures implies the establishment of a coordination committee with dedicated staff, the implementation of a surveillance program for the rapid recognition of the outbreaks, the identification of suitable premises and equipment, the application of universal precautions, the adaptation of care plans to reduce the possibility of contagion among residents and the protection of operators and staff training initiatives.

Medication Errors in Pediatrics: Proposals to Improve the Quality and Safety of Care Through Clinical Risk Management.

Medication errors represent one of the most common causes of adverse events in pediatrics and are widely reported in the literature. Despite the awareness that children are at increased risk for medication errors, little is known about the real incidence of the phenomenon. Most studies have focused on prescription, although medication errors also include transcription, dispensing, dosage, administration, and certification errors. Known risk factors for therapeutic errors include parenteral infusions, oral fluid administration, and tablet splitting, as well as the off-label use of drugs with dosages taken from adult literature. Emergency Departments and Intensive Care Units constitute the care areas mainly affected by the phenomenon in the hospital setting. The present paper aims to identify the risk profiles in pediatric therapy to outline adequate preventive strategies. Precisely, through the analysis of the available evidence, solutions such as standardization of recommended doses for children, electronic prescribing, targeted training of healthcare professionals, and implementation of reporting systems will be indicated for the prevention of medication errors.