Assisted suicide: article 17 of the Italian Code of Medical Ethics follows in the footsteps of the Italian Constitutional Court's landmark ruling

Less than a year ago, on September 25th 2019, the Italian Constitutional Court issued a landmark decision on assistance in dying, thus setting a long-awaited standard in terms of regulating assisted suicide1 . The ruling related to the case of Fabiano Antoniani, also known as DJ Fabo, a man in his forties who had made a pondered, steadfast decision to receive assistance in dying at a Swiss euthanasia clinic in 2017. Fabiano was left blind and tetraplegic in the aftermath of a catastrophic road accident in 2014. His death has since become the subject of heated debate in a country, such as Italy, where euthanasia, whether active (i.e., doctors actively causing the patient’s death) or passive (the self-administration by the patient of lethal drugs to end his or her life, the way Fabiano ended his), is adamantly opposed by the Catholic Church. Italy’s Constitutional Court has made it clear that euthanasia should be permitted by law in certain circumstances, including those in which a patient’s irreversible condition was “causing physical and psychological suffering that he or she considers intolerable”. The court’s ruling was centered around assisted dying and the “legal framework concerning end of life [situations]”. A request had in fact been made by a Milan court to provide a clear interpretation of the law in the trial against pro-euthanasia politician, activist and campaigner Marco Cappato, who had actively helped Antoniani with his journey to a Swiss clinic which provides assisted suicide

Synthetic cathinones related fatalities: an update

Synthetic cathinones, more commonly known as "bath salts", are synthetic drugs chemically related to cathinone, a psychostimulant found in the khat plant. They are the first most consumed products among new psychoactive substances, which cause psychostimulant and hallucinogenic effects determining a number of fatalities worldwide.  In this paper, we have systematically reviewed cases of synthetic cathinones-related fatalities analytically confirmed, which have occurred in the last few years.OBJECTIVE: Synthetic cathinones, more commonly known as “bath salts”, are synthetic drugs chemically related to cathinone, a psychostimulant found in the khat plant. They are the first most consumed products among new psychoactive substances, which cause psychostimulant and hallucinogenic effects determining a number of fatalities worldwide. In this paper, we have systematically reviewed cases of synthetic cathinones-related fatalities analytically confirmed, which have occurred in the last few years. MATERIALS AND METHODS: Relevant scientific articles were identified in Medline, Cochrane Central, Scopus, Web of Science and Institutional/ government websites up to November 2017 using the following keywords: synthetic cathinones, mephedrone, methylenedioxypyrovalerone, MDPV, methylone, ethylone, buthylone, fatal intoxication, fatalities and death. RESULTS: In total, 20 citations met the criteria for inclusion, representing several fatal cases with analytically confirmed synthetic cathinones in biological sample/s of the deceased. The death was attributed to hyperthermia, hypertension, cardiac arrest and more in general to the classic serotonin syndrome. Only rarely did the concentration of the parent drug causing fatality overcome the value of 1 mg/L in post-mortem biological fluids. CONCLUSIONS: Abuse of synthetic cathinones still represents a serious public health issue. Systematic clinical studies on both the animal and human model are lacking; therefore, the only available data are from the users who experience the possible hazardous consequences. Analytical methodologies for the identification of parent compounds and eventual metabolites both in ante-mortem and post-mortem cases need to be developed and validated. Analytical data should be shared through different communication platforms with the aim of stopping this serious health threat for drug users

Hepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature

The available literature assessing Chelidonium majus L. (CM) hepatotoxicity potential, and its risk to benefit assessment has been reviewed in this paper. Identification of significant scientific literature was performed via the following research databases: Cochrane Central, Google Scholar, EMBASE, Medline, Science Direct, Scopus, Web of Science, using the following keywords: "Chelidonium majus", "greater celandine", "Hepatotoxicity", "Liver" "Injury", "Toxicity" individually investigated and then again in association. CM named also greater celandine, swallow-wort, or bai-qu-cai (Chinese), has been used for a long time in traditional Chinese medicine and phytotherapy. Its extracts have been claimed to display a wide variety of biological activities: antimicrobial, anti-inflammatory, spasmolytic, antineoplastic, hepatoprotective, and analgesic. Moreover, herbal medicine suggests this plant have numerous additional effects which have not yet been scientifically evaluated, such as antitussive, diuretic, and eye-regenerative. However, despite its claimed hepatoprotective effects, several hepatotoxicity cases have been reported to be probably or highly probably connected with CM exposure, after their evaluation through liver-targeted causality assessment methods. CM hepatotoxicity has been defined as a distinct form of herb-induced liver injury (HILI), due to an idiosyncratic reaction of the metabolic type. This evidence has to be considered in relationship with the absence of considerable benefits of CM therapy. Therefore, the risk to benefit ratio of the use of herbal products containing greater celandine can actually be considered as negative

The importance of disclosing the conflict of interest (CoI) in the era of open access publishing

In pharmacological and biomedical sciences, most of the principle donators are progressively demanding open access as a condition in economical support, something which has already become common in various other areas1. The expression “open access” has been used since 2002: first in the Budapest Open Access Initiative (February 2002), then in the Bethesda Statement on Open Access Publishing (June 2003) and finally in the Berlin Declaration on Open Access to Knowledge in the Sciences and Humanities (October 2003). Open access was initially intended for scholarly journal manuscripts in order to provide an unrestricted online access to them. However, even though this term first appeared in the 2000s, free on-line access to journal manuscripts had started at least 10 years previousl

Advance healthcare directives: moving towards a universally recognized right

Advance healthcare directives (AD) are still intensively animating debates in Europe and worldwide, leading to the enactment of different laws, according to the diverse legal, sociocultural, religious and philosophical traditions of each society1 . After a long complicated seemingly ever-lasting process, on the 14th of December 2017 the Italian Parliament finally approved the Law on “Informed consent and Advance healthcare directives” putting Italy on the same level as other European countries, which have previously regulated this complicated matter2 . The most controversial point of the law is represented by AD. Section 4 states that everyone able to make a proper judgment, regarding any possible future inability to self-determine, can, through AD, express their beliefs and preferences concerning health treatments, consent or refusal to any diagnostic or therapeutic choice, including artificial nutrition and hydration. One can also indicate a person of trust to represent him/her in the relationships with doctors and hospitals2 . Furthermore, the same provision specifies that the doctor is obliged to respect the AD, unless: a) the patient requests a treatment opposing the law or medical deontology, or b) the AD is clearly incongruous, or c) new and unpredictable therapies have come into force. Therefore, ADs are binding; conscientious objection is not foreseen. The reference of the law to medical deontology finds its rationale in section 38 of the Italian Code of Medical Ethics, updated in May 2014, where the requirements that AD must meet are stated3 . With this new law2 Italy conforms to the orientation of the other main European countries, obliging the respect of ADs, even if the limits are slightly different, France4 , Germany5 , Spain6 and England7 they are binding. We wish to draw the attention of the whole medical scientific community to this matter, advocating for an open dialogue to discuss the ethical and medical issues concerning AD, thereby facilitating the improvement and implementation of guidelines and policies to safeguard patients together with healthcare providers1 . There has been considerable progress in addressing all the ethical issues regarding AD and as a consequence of the constant innovation in medical science and an increase in life expectancy we can demand more research into this topic

Suitability of miRNA assessment in postmortem interval estimation

OBJECTIVE: The aim of this review was to explore recent pieces of evidence focused on the use of miRNAs for PMI estimation both in humans and animal experiments, with particular interest on the best miRNAs to use as reference/target markers in different tissues or biological fluids. MiRNAs are innovative biomarkers used in clinical and research field: they appear very attractive, being introduced in forensic research scenarios even for PMI estimation.MATERIALS AND METHODS: Data from PubMed and Scopus were analyzed from January 2013 to August 2020. Based on inclusion/exclusion criteria, high-quality articles have been selected to become the subject of this review.RESULTS: A total of 737 papers were found but, after titles/abstracts screening for inclusion criteria and a full-text careful selection, 33 papers were deeply studied. After the exclusion of 19 papers, 15 articles remained. Eight papers dealt with animals (mice/rats), two both with animals and humans (for method validation previously built), while 5 exclusively with humans. Myocardium (6/15) and brain (6/15) were the most studied tissues. respectively in mice/rats and humans. PMI considered was up to 7.5 days in mouse studies and less than 3 days in human models.CONCLUSIONS: Because of their significant stability in both early and long PMI, miRNAs are the cleverest reference markers to be used. Temperature and environmental conditions influence mostly mRNA, while miRNAs are less susceptible to them. The best miRNA to choose depends on its tissue specificity, i.e., miR-9 and miR-125 in brain or miR-1 and miR-133 in skeletal muscle/heart

Assessment of the stability of exogenous gamma hydroxybutyric acid (GHB) in stored blood and urine specimens

OBJECTIVE: The aim of this work is to test the stability of exogenous GHB in whole blood and urine samples collected from living and deceased GHB free-users, spiked with known concentrations of GHB and stored at different temperatures (–20°C, 4°C and 20°C) up to 4 weeks. MATERIALS AND METHODS: GHB was added to GHB-free ante-mortem blood and urine samples at the concentration of 5 and 10 mg/L, respectively whereas in post-mortem blood and urine specimens at 50 and 10 mg/L respectively. All samples were stored at three different temperatures: –20°C, 4°C and 20°C and extracted and analyzed at three days, 1 week, 2 weeks, 3 and 4 weeks in duplicate. No preservatives were added. GHB was quantified by GC-MS after LLE according to a previously published method. RESULTS: Post-mortem blood specimens showed a reduction of GHB levels higher than 10% only after a period of 4 weeks of storage for samples kept at +4°C and +20°C, whereas samples stored at –20°C showed a mean reduction of 8.7%. In post-mortem urine samples, there was a mean reduction of GHB levels higher than 20% at all storage temperatures, after 4 weeks of storage. Antemortem blood samples showed a reduction of GHB levels lower than 10% only after 3 days of storage at –20°C and at +4°C (samples stored at +20°C showed a mean reduction of 10.4%). After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 20% at all storage temperatures. Ante-mortem urine samples showed a reduction of GHB levels higher than 10% after just 3 days of storage for samples kept at all tested temperatures. After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 25% at all storage temperatures. CONCLUSIONS: According to our findings, it would be useful to perform GHB analysis both in blood and urine specimens within 3 days of sampling and the specimens should be stored at –20°C or 4°C in order to avoid instability issues

Total tryptase or β-tryptase in post mortem settings: Which is to be preferred?

Dear Editor, We have read with attention and interest the Tsea et al. manuscript [1] entitled “Post mortem tryptase cut-off level for anaphylactic death” where a 5-year retrospective study has compared totaltryptase levels in the femoral blood of 9 anaphylactic deaths and 45 controls. A cut-off of 53.8 mg/L was identified for total post mortem tryptase in femoral blood with a sensitivity of 89% and specificity of 93% through a receiver-operating characteristic (ROC) curve analysis to diagnose anaphylaxis