Molecular Autopsy in Asphyxia Deaths: Diagnostic Perspectives of miRNAs in the Evaluation of Hypoxia Response.

The forensic investigation of asphyxia deaths still poses a challenge due to the need to demonstrate vital exposure to hypoxic insult according to high levels of evidence. The pulmonary effects of hypoxia are complex and the understanding of the mechanisms underlying the acute pneumotoxicity induced by hypoxia is still incomplete. Redox imbalance has been suggested as the protagonist of the main acute changes in pulmonary function in the hypoxic context. The development of knowledge in biochemistry and molecular biology has allowed research in forensic pathology to identify some markers useful in immunohistochemical diagnostics of asphyxia deaths. Several studies have highlighted the diagnostic potential of markers belonging to the HIF-1α and NF-kB pathways. The central role of some highly specific microRNAs has recently been recognized in the complex molecular mechanisms involved in the hypoxia response; thus, several research activities are currently aimed at identifying miRNAs involved in the regulation of oxygen homeostasis (hypoxamiR). The aim of the manuscript is to identify, the miRNAs involved in the early stages of the cellular response to hypoxia, in order to characterize the possible implications in the forensic field of the determination of expression profiles. At present, more than 60 miRNAs involved in the hypoxia response with different expression profiles (upregulation and downregulation) have been identified. Despite the multiple and different effects on reprogramming following the hypoxic insult, the evaluation of the diagnostic implications of hypoxamiRs in the forensic field presupposes a specific treatment of the influences on HIF-1α regulation, cell cycle progression, DNA repair, and apoptosis.

Identification of 5F-Cumyl-PINACA, a Synthetic Cannabinoid, in the Herbal Material Used for Recreational Purposes in the Province of Trieste: Public Health Implications.

BACKGROUND: In recent years, the phenomenon of the production and trade of synthetic cannabinoids has grown, becoming a public health issue worldwide. The recent access- to the ED of the hospital of Trieste- of people who complained of episodes of hallucinations, sensation of poisoning, tachycardia, and air hunger following the inhalation of "Che Sballo platinum", have highlighted the need to perform further analysis on the contents of the packet sold as an air freshener, produced in Koper (Slovenia). OBJECTIVE: This paper wants to be an alert about the possible consequences on health due to the spreading of "Che Sballo platinum" in the province of Trieste. METHODS: The package contents were analyzed by a multi-target screening method of MRM-IDAEPI experiment. The result was then confirmed, and quantification was achieved via LC-ESI-MS/MS analysis in MRM mode using QTrap 6500 + Sinergy hydro column 100 x 2 mm 1.9 um transitions MRM1 368.3 → 250.0; MRM2 368.3 → 233.0. RESULTS: The initial screening tested negative for THC and showed positive results for 5F-Cumyl- PINACA. Quantitation result reported dose by the package of 8.5 mg of the compound. Formal notification was sent to the Italian Health Authorities (Notification No. 2021110205). CONCLUSION: Consumption of 5F-Cumyl-PINACA results in much more potent effects than marijuana. Lack of information about the actual concentration of the substance on the packaging does not allow drug users to have an adequate dosage, with possible toxic consequences on health. Further investigations must be done to discover the true extent of the phenomenon.

Recreational Cannabis Use: Regulatory Aspects, Public Opinion and Concerns for Public Health.

Cannabis represents the most used substance in the young population after alcohol and tobacco. The consumption of the substance undoubtedly represents an emerging public health issue, and the regulatory aspects are quite heterogeneous. Alternatives to drug prohibition, such as legalization or decriminalization, are a topic of growing debate among researchers, policy makers and the public. Limiting harmful use and combating illicit trafficking are the main objectives of legalization for recreational purposes, although liberalization raises critical issues that have not yet been resolved despite the experience gained in many countries. In the context of legalization, it is essential to allow the lawful production of cannabis, guarantee a supply of controlled quality cannabis, and ensure that the population understands the risks associated with the consumption of the substance. At the same time, it is essential to protect the safety and health of the population by limiting access to cannabis and preventing accidental exposure to fragile categories and children. Incomplete knowledge of law enforcement can create further complications. Incomplete knowledge of the implementation of the laws can create further complications; therefore adequate information must be favored. Scientific evidence helps to understand the potential harms and benefits of cannabis, but the impact of legalization - even in terms of reducing consumption - is not clearly documented. So, far more efforts need to be made in the future to broaden awareness of the general population on the recreational use of cannabis.

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.

Assisted Suicide and Euthanasia in Mental Disorders: Ethical Positions in the Debate between Proportionality, Dignity, and the Right to Die.

The admission of people suffering from psychiatric and neurocognitive disorders to euthanasia and physician-assisted suicide (E/PAS) in some European and non-European countries represents a controversial issue. In some countries, the initial limitation of E/PAS to cases of severe physical illness with poor prognosis in the short term has been overcome, as it was considered discriminatory; thus, E/PAS has also been made available to subjects suffering from mental disorders. This decision has raised significant ethical questions regarding the capacity and freedom of self-determination; the family, social, and economic contexts; the social consideration of the sense of dignity and the pressure on the judgment of one's personal value; the contextual therapeutic possibilities; the identification of figures involved in the validation and application; as well as the epistemological definitions of the clinical conditions in question. To these issues must be added the situation of legislative vacuum peculiar to different countries and the widespread lack of effective evaluation and control systems. Nonetheless, pessimistic indicators on global health status, availability of care and assistance, aging demographics, and socioeconomic levels suggest that there may be further pressure toward the expansion of such requests. The present paper aims to trace an international overview with the aim of providing ethical support to the debate on the matter. Precisely, the goal is the delimitation of foundations for clinical practice in the complex field of psychiatry between the recognition of the irreversibility of the disease, assessment of the state of physical and mental suffering, as well as the possibility of adopting free and informed choices.

Mental health law: a comparison of compulsory hospital admission in Italy and the UK.

In Europe, the mental health law legal framework has had several changes throughout the years to achieve and develop new reforms, better mental health care, and protect the human rights of patients. The UK national data shows rising detention rates and the disproportionate use of the legal framework among people from black and minority ethnic groups. At the national level, compulsory admissions are lower in Italy; it also shows that it has increased in the last few years in both countries. The lack of ethnic national data, especially in Italy, limited the ability to understand compulsory admission, discrimination, and stigma in mental health. The present study aims to compare the legal framework of mental health law and compulsory hospital admission in Italy and the UK. A review of each country's latest amendments to mental health law and the number of compulsory hospital admissions was conducted to understand the impact of changes in mental health care.

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.

Acute Kidney Injury (AKI) in Young Synthetic Cannabinoids Abusers.

Background. Synthetic cannabinoid-related acute kidney injury represents an increasingly important public health issue due to the diagnostic challenges given by low clinical suspicion of the disease and the frequent undetectability in routine drug tests. Methods. A systematic literature search on PubMed was carried out until 31 January 2022. Case reports, case series, retrospective and prospective studies, as well as reviews on acute kidney injury related to the consumption of synthetic cannabinoid were searched. Results. The systematic review process selected 21 studies for a total of 55 subjects with synthetic cannabinoid-induced acute kidney injury. Renal damage was demonstrated by elevated serum creatinine levels in 49 patients (89%). On renal ultrasound, the most frequent finding was an increase in cortical echogenicity. Renal biopsy, performed in 33% of cases, revealed acute tubular damage, acute tubulointerstitial nephritis, and acute interstitial nephritis, in decreasing order of frequency. Conclusion. Prompt identification and treatment of synthetic cannabinoid-related acute kidney injury represent a sensitive public health goal both for the acute management of damage from synthetic cannabinoids and for the prevention of chronic kidney disease.

Mental Health Consequences of COVID-19 Pandemic Period in the European Population: An Institutional Challenge.

The worldwide spread of SARS-CoV-2 has been responsible for an infectious pandemic, with repercussions on socio-economic aspects and on the physical and mental health of the general population. The present systematic review aimed to evaluate the data belonging to the European framework, analyzing the population by age group. Original articles and reviews on the state of mental health of the general European population have been researched starting from 2021. Initially, a total of 1764 studies were found, among which a total of 75 were selected. Youth were the age group most affected by pandemic consequences on mental health, with emotional and behavioral alterations observed from a third to more than a half of children and adolescents examined. Among both adolescents and adults, the female gender had a higher prevalence of psychopathological symptoms. The main risk factors were poor social support, economic difficulties, and, in particular, unemployment or job changes. Additional individual risk factors were the perception of loneliness, the presence of pre-pandemic mental illness/distress, and some personality traits, such as neuroticism, impulsiveness, and the use of maladaptive coping strategies. Unexpectedly, the elderly maintained good resilience towards change, even if a stress factor was represented by the feeling of loneliness and poor social contact. As regards suicidal behaviors, among adolescents, there was an increase in attempts of 25%, with a greater risk for the female gender. This risk increased also among adults, in association with symptoms of anxiety and depression, and poor socio-environmental conditions. In conclusion, some population groups were found to be at greater risk of psychological burden during pandemic waves, thus representing priority targets for socio-health interventions.

Pancreatic transplant surgery and stem cell therapy: Finding the balance between therapeutic advances and ethical principles.

The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments, often characterized by high complexity from a surgical point of view, due to transplantation of multiple organs at the same time or at different times, and from an immunological point of view for stem cell therapy. The fundamental value in the field of organ transplants is, of course, a solidarity principle, namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery, or even of survival. The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems. The general principle of respect for human life, both of the donor and of the recipient, evokes the need not to put oneself and one's neighbor in dangerous conditions. The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person, the respect due to the dead, the voluntary nature of the donation and the consent to the same, the gratuitousness of the donation, the scientific progress and the development of surgical techniques, and the policies of health promotion.

Sodium Nitrite Intoxication and Death: Summarizing Evidence to Facilitate Diagnosis.

BACKGROUND: Over the years, forensic pathology has registered the spread of new methods of suicide, such as the ingestion of sodium nitrite. Sodium nitrite causes increased methemoglobin, resulting in systemic hypoxia, metabolic acidosis, and cyanosis. Since sodium nitrite is a preservative, the ingestion of foods containing an excessive amount of this substance can also cause acute intoxication up to death. The present review is aimed at guiding health professionals in the identification and management of sodium-nitrite-related intoxications and deaths. METHODS: A systematic literature search was carried out on PubMed by following the PRISMA statement's criteria. A total of 35 studies with 132 cases were enrolled, and the data were cataloged in Microsoft Excel. To establish the causal correlation between sodium nitrite ingestion and death, the Naranjo Adverse Drug Reaction Probability Scale was used. RESULTS: In addition to the small number of cases that have currently been published, the study demonstrated that there was a general methodological discrepancy in the diagnostic process. However, some interesting results have emerged, especially in post-mortem diagnostics. CONCLUSION: Sodium-nitrite-related deaths represent a challenge for forensic pathologists; therefore, it is important to promptly recognize the essential features and perform the necessary and unrepeatable examinations for the correct diagnosis of the cause of death.

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.

Shaken Baby Syndrome: Magnetic Resonance Imaging Features in Abusive Head Trauma.

In the context of child abuse spectrum, abusive head trauma (AHT) represents the leading cause of fatal head injuries in children less than 2 years of age. Immature brain is characterized by high water content, partially myelinated neurons, and prominent subarachnoid space, thus being susceptible of devastating damage as consequence of acceleration-deceleration and rotational forces developed by violent shaking mechanism. Diagnosis of AHT is not straightforward and represents a medical, forensic, and social challenge, based on a multidisciplinary approach. Beside a detailed anamnesis, neuroimaging is essential to identify signs suggestive of AHT, often in absence of external detectable lesions. Magnetic resonance imaging (MRI) represents the radiation-free modality of choice to investigate the most typical findings in AHT, such as subdural hematoma, retinal hemorrhage, and hypoxic-ischemic damage and it also allows to detect more subtle signs as parenchymal lacerations, cranio-cervical junction, and spinal injuries. This paper is intended to review the main MRI findings of AHT in the central nervous system of infants, with a specific focus on both hemorrhagic and non-hemorrhagic injuries caused by the pathological mechanisms of shaking. Furthermore, this review provides a brief overview about the most appropriate and feasible MRI protocol to help neuroradiologists identifying AHT in clinical practice.

State-of-Art in the Age Determination of Venous Thromboembolism: A Systematic Review.

Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), requires a forensic age determination to ascertain their causal relationship with recent events, such as trauma or medical treatment. The main objective of this systematic review is to identify the current state-of-the-art immunohistochemical methods for age determination of fatal VTE. A literature search was performed through different databases, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Within the study, we have selected only cases represented by deceased patients for DVT and/or PTE in which thromboembolic material was collected during an autoptic examination and then subjected to a histological and an immunohistochemical investigation. Studies based on animal models were not included. We assessed bias risk. A database-based search produced a total of 19 articles. After excluding duplicate items from the selection, 14 articles were reviewed. Ten articles were excluded because they did not meet the inclusion criteria. The results have pointed out 4 studies that were included in the present analysis for a total of 157 samples of DVT and 171 PTE samples. These were analyzed using traditional histological and immunohistochemical techniques. The results must be interpreted with a critical eye because of their heterogeneity in terms of time, geography, and study design. The present review highlights the importance of associating specific immunohistochemical markers with a histological analysis for the timing of DVT/PTE fatal events. Further future experiences will hopefully endorse actual knowledge on the subject to increase the accuracy in the assessment of thrombus-embolus age.

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.

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.

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.

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").