Challenges and Complications in the Management of Advanced Oropharyngeal Carcinoma: Role of Post-Mortem Diagnosis and Future Perspectives.

Oropharyngeal squamous-cell carcinoma (OPSCC) poses significant challenges in diagnosis, treatment, and management and has important medico-legal and forensic implications. In particular, the management of OPSCC and its treatment-related complications can often be challenging. In cases with advanced OPSCC, a loco-regional extension of the tumor can contribute to the destruction of oral cavity tissues, while the radiotherapy treatment can induce profound changes in tissue morphology and structure. These changes, which resemble tumor neoplasms and endovascular effects, are related to a higher risk of fatal bleeding, as reported in the case study illustrated, in which a hemorrhage occurred from a lingual artery, originating from an ulcerative, necrotic, hemorrhagic lesion on the tongue. Bleeding complications in OPSCC and prolonged radiotherapy are associated with high mortality and require comprehensive management strategies to improve survival and quality of life. Autopsy investigations, contributing to the definition of post-mortem diagnosis, can provide valuable insights into the pathogenetic mechanisms underlying bleeding and guide therapeutic decisions and preventive measures. The integration of autopsy and histopathological investigation into clinical practice should be considered as a necessary support to optimize the management of complications in advanced OPSCC patients, emphasizing the importance of a patient-centered approach and continued research.

Analysis of miRNA Expression Profiles in Traumatic Brain Injury (TBI) and Their Correlation with Survival and Severity of Injury.

Traumatic brain injury (TBI) is the leading cause of traumatic death worldwide and is a public health problem associated with high mortality and morbidity rates, with a significant socioeconomic burden. The diagnosis of brain injury may be difficult in some cases or may leave diagnostic doubts, especially in mild trauma with insignificant pathological brain changes or in cases where instrumental tests are negative. Therefore, in recent years, an important area of research has been directed towards the study of new biomarkers, such as micro-RNAs (miRNAs), which can assist clinicians in the diagnosis, staging, and prognostic evaluation of TBI, as well as forensic pathologists in the assessment of TBI and in the estimation of additional relevant data, such as survival time. The aim of this study is to investigate the expression profiles (down- and upregulation) of a panel of miRNAs in subjects deceased with TBI in order to assess, verify, and define the role played by non-coding RNA molecules in the different pathophysiological mechanisms of brain damage. This study also aims to correlate the detected expression profiles with survival time, defined as the time elapsed between the traumatic event and death, and with the severity of the trauma. This study was conducted on 40 cases of subjects deceased with TBI (study group) and 10 cases of subjects deceased suddenly from non-traumatic causes (control group). The study group was stratified according to the survival time and the severity of the trauma. The selection of miRNAs to be examined was based on a thorough literature review. Analyses were performed on formalin-fixed, paraffin-embedded (FFPE) brain tissue samples, with a first step of total RNA extraction and a second step of quantification of the selected miRNAs of interest. This study showed higher expression levels in cases compared to controls for miR-16, miR-21, miR-130a, and miR-155. In contrast, lower expression levels were found in cases compared to controls for miR-23a-3p. There were no statistically significant differences in the expression levels between cases and controls for miR-19a. In cases with short survival, the expression levels of miR-16-5p and miR-21-5p were significantly higher. In cases with long survival, miR-21-5p was significantly lower. The expression levels of miR-130a were significantly higher in TBI cases with short and middle survival. In relation to TBI severity, miR-16-5p and miR-21-5p expression levels were significantly higher in the critical-fatal TBI subgroup. Conclusions: This study provides evidence for the potential of the investigated miRNAs as predictive biomarkers to discriminate between TBI cases and controls. These miRNAs could improve the postmortem diagnosis of TBI and also offer the possibility to define the survival time and the severity of the trauma. The analysis of miRNAs could become a key tool in forensic investigations, providing more precise and detailed information on the nature and extent of TBI and helping to define the circumstances of death.

Substance use disorders during the COVID-19 pandemic: looking for new innovative approaches.

BACKGROUND AND AIM: The destructive impact of the still ongoing COVID-19 pandemic on those struggling with substance use disorders (SUD) stems from the daunting challenges which SUD patients experience in terms of coping with their condition and receiving care in a timely fashion. METHODS: Patients struggling with addiction are at particularly high risk, due to the underlying vulnerabilities in their conditions and the stigmatization they often suffer. New Psychoactive Substances stand out as a critical area of concern. The authors have conducted a broad-ranging search to assess the impact of SUDs, along with their related mental, physical, and behavioral symptoms, against the backdrop of the COVID-19, taking into account how drug trafficking and consumption trends have evolved as the emergency draws out, and the cyberspace comes to play an ever-bigger role. RESULTS: Given that roughly 1.5%-5% of the global burden of disease can be ascribed to alcohol abuse and substance addiction, the role of pandemic-related potential contributing factors in the exacerbation and relapse of SUDs and behavioral addiction cannot be discounted and needs targeted measures tailored to the special needs of SUD patients. Escalating environmental stressors stemming from abnormal circumstances can undermine recovery efforts and threaten the very survival of countless SUD patients, increasing the likelihood of relapsing for those in recovery. CONCLUSIONS: Policymakers and legislators have not yet put in place targeted measures and adjustments in the health care delivery mechanisms in order to countervail the pandemic impact on SUD sufferers, and the ever-evolving patterns of use and trafficking.

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.

Medically assisted procreation in times of COVID-19: what impact on health care system organization and the reproductive rights of couples?

BACKGROUND AND AIM: The emergency caused by the spread of COVID-19 has overwhelmed health care facilities and required the reorganization of health systems in many nations worldwide. A year after its appearance, measures aimed at further containing disease transmission through massive vaccination campaigns. In pregnancy, vaccination should be administered with caution, in light of the lack of reliable data, since pregnant women have been excluded from experimentation. The pandemic has had a significant impact on assisted reproduction procedures in Italy. Methods: The authors have set out to analyze the measures issued by the Italian government in order to counter the spread of COVID-19, in addition to the national and international guidelines on assisted reproduction. DISCUSSION: The purpose of these documents is precautionary in nature: such measures are based on the principles of responsibility and solidarity, essential to stave off the saturation of health systems, curb contagion, but also to lay out a set of rules to starting a pregnancy while preserving the health of couples, operators and newborns. The authors also expound upon the rights claimed by couples seeking access to MAP (i.e. the right to become a parent, the couple's right to health, interest in demographic development). Conclusions: The coronavirus disease 2019 (COVID-19) has had a major impact on infertile couples. Since the pandemic broke out, Italy, like most European countries, has interrupted most ordinary activities of the centers operating in the field of assisted fertilization. We believe that access to assisted fertilization techniques by sterile and infertile couples should be part of the right to health rather than of the supposed right to become parents or the increase in the birth rate, also evoked as the COVID-19 pandemic unfolded. The current system of compensation and reimbursements needs to be reconfigured in order to prevent any form of discrimination.

Surrogacy and "Procreative Tourism". What Does the Future Hold from the Ethical and Legal Perspectives?

Background and objectives: To explore the ethical and legal complexities arising from the controversial issue of surrogacy, particularly in terms of how they affect fundamental rights of children and parents. Surrogacy is a form of medically-assisted procreation (MAP) in which a woman "lends" her uterus to carry out a pregnancy on behalf of a third party. There are pathological conditions, such as uterine agenesis or hysterectomy outcomes, that may prevent prospective mothers from becoming pregnant or carry a pregnancy to term; such patients may consider finding a surrogate mother. Many issues relating to surrogacy remain unresolved, with significant disagreements and controversy within the scientific community and public opinion. There are several factors called into play and multiple parties and stakeholders whose objectives and interests need to somehow be reconciled. First and foremost, the authors contend, it is essential to prioritize and uphold the rights of children born through surrogacy and heterologous MAP. Materials and methods: To draw a parallel between Italy and the rest of the world, the legislation in force in twelve European countries was analyzed, eleven of which are part of the European Union (France, Germany, Italy, Spain, Greece, Netherlands, Belgium, Denmark, Lithuania, Czech Republic and Portugal) and three non-members of the same (United Kingdom, Ukraine and Russia), as well as that of twelve non-European countries considered exemplary (United States, Canada, Australia, India, China, Thailand, Israel, Nigeria and South Africa); in particular, legislative sources and legal databases were drawn upon, in order to draw a comparison with the Italian legislation currently in force and map out the evolution of the Italian case law on the basis of the judgments issued by Italian courts, including the Constitutional and Supreme Courts and the European Court of Human Rights (ECHR); search engines such as PubMed and Google Scholar were also used, by entering the keywords "surrogacy" and "surrogate motherhood", to find scientific articles concerning assisted reproduction techniques with a close focus on surrogacy. Results: SM is a prohibited and sanctioned practice in Italy; on the other hand, it is allowed in other countries of the world, which leads Italian couples, or couples from other countries where it is banned, to often contact foreign centers in order to undertake a MAP pathway which includes surrogacy; in addition, challenges may arise from the legal status of children born through surrogacy abroad: to date, in most countries, there is no specific legislation aimed at regulating their legal registration and parental status. Conclusion: With reference to the Italian context, despite the scientific and legal evolution on the subject, a legislative intervention aimed at filling the regulatory gaps in terms of heterologous MAP and surrogacy has not yet come to fruition. Considering the possibility of "fertility tourism", i.e., traveling to countries where the practice is legal, as indeed already happens in a relatively significant number of cases, the current legislation, although integrated by the legal interpretation, does not appear to be effective in avoiding the phenomenon of procreative tourism. Moreover, to overcome some contradictions currently present between law 40 and law 194, it would be appropriate to outline an organic and exhaustive framework of rules, which should take into account the multiplicity of interests at stake, in keeping with a fair and sustainable balance when regulating such practices.