First Case of Medically Assisted Suicide in Italy Set New Legal Perspectives.

Abstract: The first act of assisted suicide in Italy was recently carried out. This event is an absolute novelty for the country, affected by recent legislative changes aimed only at introducing the right to interrupt health treatments and, therefore, carry out exclusively omissive end-of-life acts. These normative provisions lay their foundations in a cultural context centered on the protection of the right to life and health; however, the cases that have occurred over time, including the famous story of DJ Fabo, have led the Constitutional Court to re-evaluate these dictates, introducing in 2019 the right to resort to assisted suicide procedures within well-defined areas, including incurability of the condition, the serious suffering of the individual and the retained ability to stand trial. The case addressed concerns a quadriplegic subject who was the victim of a road accident. Following consultation with a specialized institution, the subject made the decision to undergo an assisted sui-cide procedure in Italy. Having obtained the authorization from the competent authorities, he started a fundraiser to finance the devices and drugs required and, finally, he died. The opening by Italy towards the assisted suicide procedure represents a great step towards a broad context, as well as a decisive act for the purpose of protecting the right to self-determination of the individual. However, the current legislative framework presents significant criticalities and shortcomings. In first place, the dissonance between the laws in force and the judicial sentences is likely to generate problems of uneven application of the rules in a country dominated by the principle of Civil Law. Furthermore, the need for the applicant to fully self-finance the procedure clearly clashes with the constitutional principle of free access to care. Then emerges the need for a guideline document regarding the completion of the procedure itself, the times, methods and drugs implied, in order to significantly reduce the decision-making process by the ethics committees that still weighs on each individual case. Finally, conside-ring what has been observed on the subject of voluntary termination of pregnancy, it is necessary to ask what will be the general orientation of the doctors called to perform the act and whether they will be given the opportunity to express their refusal. The case analyzed could represent the beginning of a new era for Italian culture, but the large-scale application of assisted suicide procedures requires the introduction of legislative provisions that definitively eliminate the critical issues that have emerged so far.

Informed consent and compulsory treatment on individuals with severe eating disorders: a bio-ethical and juridical problem.

Background: The problem concerning the activation of the measure of Compulsory Health Treatment (CHT) for subjects suffering from Eating Disorders (ED) represents a legal paradox that places health professionals in the position of frequently doubting the real usefulness of the measure within the hospital context. This issue is mainly related to anorexia nervosa, which puts the subject in a higher life-threatening situation than other EDs. Method and materials: To outline the current state of the art, the most recent national and international scientific publications concerning informed consent and CHT in EDs were searched. In addition, Italian rulings in various degrees of judgement were evaluated with the suggestion of a possible resolution of these issues. Results: The analysis of the literature showed that although a multitude of psychometric instruments has been created to identify the ability to give informed consent, there are still not all the elements necessary to identify the actual degree of disease awareness of ED subjects. An important factor could be the exploration of the person's interception, which has been seen to be very high in individuals with AN who are known not to experience the sensation of hunger. At present, reviews of the bibliography and judgments have shown that the measurement of CHT remains crucial if it is intended as a life-saving treatment. However, it is evident that in terms of BMI, CHT is not a definitive intervention and therefore the adoption of this practice is necessary with extreme caution taking into account the person's actual ability to consent. Conclusions: Future studies will have the task of determining the psychic factors necessary to better understand the state of the person in his or her physical and mental wholeness, giving due weight to these characteristics and orienting knowledge in a practical sense to more profitable direct treatment for individuals with ED.

Attachment behaviours in adults with intellectual disabilities in assisted living facilities: representations from direct-care staff.

BACKGROUND: Studies on individuals with intellectual disabilities (IDs) indicate that primary care staff are potential attachment figures. Therefore, the ability to interpret and respond to attachment behaviours with sensitivity is crucial for professionals working with adults with IDs. However, little is known regarding representations and understanding of these attachment behaviours among professionals. This study investigated the representations of attachment behaviours among adults with IDs, as observed and interpreted by direct-care staff in assisted living facilities. METHODS: Semi-structured interviews were conducted with 19 support workers in seven assisted living facilities in the French community of Belgium. A thematic content analysis was performed. RESULTS: Professional discourse elicited various forms of attachment behaviours that were sometimes considered challenging. Staff reported difficulties in finding a balance between supporting selective attachment and maintaining 'the right distance' to prevent a negative impact on their work conditions. CONCLUSIONS: This study gives insight to how using an attachment-informed framework may provide a new perspective on behaviours of adults with IDs in assisted living facilities, as well as the need to offer professionals the opportunity to reflect upon their practices in relation to this dimension.

Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

PURPOSE: Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. METHODS: All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. RESULTS: Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). CONCLUSION: Autonomic dysfunctions are frequent in subjects with ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Sars-CoV-2 Infection After Lung Transplantation: Is There Professional Liability?

Abstract: For the first time in the literature, a case of Sars-Cov-2 infection after lung Transplantation has been described. This case, particularly rare, brought attention on the in-depth screening for Sars-CoV-2 on lung donor. In addition to infectious problems, it is important to focus attention on medico-legal issues related to this case. In fact, from the point of view of professional responsibility, in theory, there could be criteria for identifying professional responsibility. The author analyzes the possible presence of medical liability in this specific case.

HIV-Dementia Scale as a screening tool for the detection of subcortical cognitive deficits: validation of the Italian version.

Mini-Mental State Examination (MMSE) lacks of sensitivity in detecting cognitive deficits associated with subcortical damage. The HIV-Dementia Scale (HDS), a screening tool originally created for detecting cognitive impairment due to subcortical damage in HIV + patients, has proved to be useful in other neurological diseases. Until now, an Italian version of the HDS is not available. We aimed at: (1) validating the HDS Italian version (HDS-IT) in a cohort of cognitively healthy subjects (CN); (2) exploring the suitability of HDS-IT in detecting cognitive impairment due to subcortical damage (scCI). The psychometric properties of the HDS-IT were assessed in 180 CN (mean age 67.6 ± 8.3, range 41-84) with regard to item-total correlation, test-retest reliability and convergent validity with MMSE. Item-total correlations ranged 0.44-0.72. Test-retest reliability was 0.70 (p < 0.001). The HDS-IT scores were positively associated with MMSE score (rS = 0.49, p < 0.001). Then, both the HDS-IT and the MMSE were administered to 44 scCI subjects (mean age 64.9 ± 10.6, range 41-84). Mean HDS-IT total score was close to the original version and significantly lower in the scCI group compared to CN (8.6 ± 3.6 vs. 12.6 ± 2.5, p < 0.001). ROC analysis yielded an optimal cutoff value of 11, with sensitivity of 0.70 and specificity of 0.82. Patients showed poorer scores on HDS-IT compared to CN (12.6 ± 2.5 vs. 8.6 ± 3.6, p < 0.001). Our results support the use of HDS-IT as a screening tool suitable for detecting cognitive deficits with prevalent subcortical pattern, being complementary to MMSE in clinical practice.

COVID-19 Pandemic and Balance of Constitutional Rights.

ABSTRACT: In 2020 the World Health Organization declared the Covid-19 to be a pandemic. Governments around the world are facing a tough challenge that could jeopardise the national healthcare systems. Safeguarding the rights of Covid patients and all citizens - especially those who are now even more vulnerable than they were before - is part of this challenge. This work aims to examine the issues arising from the current emergency in terms of how individuals' constitutional rights have been balanced and how much people at the highest risk amid this pandemic - the homeless, the inmates in prison, geriatric and psychiatric patients, and doctors on the Covid frontline - have been protected. This analysis focuses mostly on one of the worst-hit countries by the SARS-CoV-2: Italy.

Subcutaneous immunoglobulin for maintenance therapy in stiff-person syndrome: One-year follow-up in two patients.

Stiff person syndrome is a rare condition characterised by prolonged stiffness with superimposed muscle spasms. Immunotherapy relies mainly on intravenous immunoglobulin, steroids and plasma exchange. Azathioprine or rituximab are other possible options. We describe two patients who showed a good clinical response with intravenous immunoglobulin and persistence of the clinical improvement after shifting to equivalent dosage of subcutaneous immunoglobulin. Both patients received a diagnosis of stiff person syndrome based on their clinical symptoms (episodes of stiffness and spasms) and presence of antiglutamic acid decarboxylase. Treatment with intravenous immunoglobulin was started with improvement of symptoms as reported by patients and confirmed also by the spasm frequency scale and modified Ashworth scale. After clinical stabilisation in order to avoid the hospitalisation required for intravenous immunoglobulin treatment a switch to subcutaneous immunoglobulins was made. After one year of follow-up from the switch, the patients show clinical stability. Their scores on the modified Ashworth scale, spasm frequency scale and on the 10 Meter Walking Test were also stable. Subcutaneous formulation of immunoglobulin could be as effective as intravenous immunoglobulin in the maintenance treatment of Stiff person syndrome, although studies involving a larger cohort of patients are needed in order to confirm our anecdotal experience.

Childbirth Injuries: an issue fraught with risks from the health care and medicolegal perspectives.

Birth injuries caused by medical negligence are a real threat for mothers and their children, which can entail catastrophic, life-changing consequences, permanent disability, or even death. Families almost always seek redress from doctors and/or facilities, but in order for a birth injury malpractice claim to be successful, it needs to be proven that the medical care providers owed a duty to the child and that they were derelict in that duty and did not meet the proper standard of care; Furthermore, a causal relationship needs to be established between injury sustained by the child and the physician's or provider's breach of duty to the child. Relevant scientific articles have been collected by drawing upon medical search engines and archives such as Medline, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar, through December 2019, using keywords such as "birth injuries", "malpractice", "claims". Moreover, the Authors have delved into legal databases (Justia, Lexis, De Jure, Leagle), identifying 6 meaningful instances of court cases centered around birth injuries with severe consequences, all stemming from malpractice and negligence. Ultimately, it can be concluded that demonstrable and adequately documented compliance with well-established guidelines and/or best practices are a determining factor in the legal defence of health care operators; that in turn can go a long way towards discouraging meritless claims and frivolous lawsuits, which constitute a challenging issue raising health care costs in many countries.

The Italian Supreme Court Joint Sections set forth the interpretative underpinnings of the "Gelli-Bianco" law: varying degrees of guilt aimed at limiting medical liability, article 2236 c.c. makes a comeback.

The article's author has sought to summarize the regulatory and legal evolution of accidental criminal liability of doctors starting from earliest positions up until the enactment of the Gelli-Bianco law. An in-depth analysis is laid out based on the Italian Supreme Court Joint Sections ruling n. 8770/2018 (so-called Mariotti decision). The author has also elaborated upon the notion of varying degrees of guilt, which was taken out of the law's wording, to be later reintroduced as a concept by judicial interpretation.  It is worth noting that Article 3 of the Balduzzi decree, article 590 sexies of the Italian Criminal Code and the reference to article 2236 of the Civil Code reflect an awareness on the part of legislators that medical liability needs to be limited. Clearly, the approach based on lawfulness alone, which protects from liability physicians that have adhered to guidelines, has been dismissed, superseded by the notion of minor fault. Nonetheless, the new legislation, in the author's estimation, constitutes a standard particularly ill-suited to modern medical practice, which has a high degree of complexity. The author concludes that it might be worth considering a more balanced alternative: getting back to the notion of fault, considering minor fault relevant, rather than major fault.

The health threat of new synthetic opioids as adulterants of classic drugs of abuse.

Extensive scientific evidence shows that there is a broad spectrum of substances used as adulterants, whose effects on the user's health may be extremely harmful. The degree of purity of the drugs most commonly abused is highly variable depending on the region or epidemiological context. Practices of drug adulteration have been substantially evolving over the years: a significant trend has been observed in the last decade indicating a decline in the average purity of most drugs. Although the most frequent adulterants of common street drugs have long been well known, the rise of synthetic opioids has inevitably entailed gaps in knowledge in terms of the substances being used and their composition, which constitutes an even greater threat to public health.

Nootropics use in the workplace: psychiatric and ethical aftermath towards the new frontier of bioengineering.

OBJECTIVE: The authors have sought to expound upon and shed a light on the rise of nootropics, which have gradually taken on a more and more relevant role in workplaces and academic settings. MATERIALS AND METHODS: Multidisciplinary databases have been delved into by entering the following keys: "nootropics", "cognitive enhancement", "workplace", "productivity", "ethics", "bioengineering". In addition, a broad-ranging search has been undertaken on institutional websites in order to identify relevant analysis and recommendations issued by international institutions and agencies. Papers and reports have been independently pored over by each author. This search strategy has led to the identification of 988 sources but only 64 were considered appropriate for the purposes of the paper after being selected by at least 3 of the authors, independently. RESULTS: The notion of an artificially enhanced work performance - carried out by the 'superworker' - is particularly noteworthy and resonates with the conception of contemporary work on so many different levels: the rising need and demands for higher degrees of flexibility and productivity on the job, the implications of a '24/7' society, where more and more services are available at any time, the ever greater emphasis on entrepreneurial spirit, individual self-reliance and self-improvement, and last but not least, the impact of an ageing society on economic standards and performance. CONCLUSIONS: Moreover, it is worth mentioning that human enhancement technologies will predictably and increasingly go hand in hand with gene editing, bioengineering, cybernetics and nanotechnology. Applications are virtually boundless, and may ultimately affect all human traits (physical strength, endurance, vision, intelligence and even personality and mood).

Letter to the editor in response to "Medically-assisted procreation and the rise of off-center, new types of "parenthood": it is incumbent upon lawmakers to intervene".

The present letter is meant as a response to the commentary titled "Medically-assisted procreation and the rise of off-center, new types of "parenthood": it is incumbent upon lawmakers to intervene", which was published in issue 4, 2019, of the La Clinica Terapeutica journal. Newly available reproductive techniques have given rise to new opportunities to fulfill one's wishes for parenthood. Such developments have caused procreation to be perceived as a right, intended as the right to «artificial¼ procreation. Not only do such trends impact those couples who travel abroad in order to have children through heterologous fertilization and surrogacy: singles and same-sex couples pursue those avenues as well in order to become parents. In the article which we are commenting upon, the author has perused the evolving jurisprudence on that subject, pointing out how necessary it is for lawmakers to step in and clearly define the rights of all parties involved, minors in particular.

Analysis of HLA-G expression in renal tissue in lupus nephritis: a pilot study.

BACKGROUND: The study aimed to investigate whether HLA-G antigen is expressed in the kidneys of patients affected by lupus nephritis (LN) and whether its detection in renal biopsies could be adopted as a marker of treatment response and prognosis. METHODS: Thirty renal biopsies from patients with LN were selected and analyzed through immunohistochemistry. Laboratory and clinical data were retrospectively collected at baseline, 6 and 12 months and at the latest clinical appointment. A number of patients (63.3%) were treated with rituximab (RTX) +/- methylprednisolone in the induction phase. The expression of HLA-G in glomeruli, tubules and infiltrating cells was examined and compared between lupus patients who achieved either complete or partial renal response and those who did not respond to treatment. RESULTS: HLA-G staining was observed in the glomeruli of 20 of 30 samples from patients with LN. The expression of the antigen was detected in podocytes, along glomerular capillary walls, on parietal glomerular epithelial cells and within the juxtaglomerular apparatus. Seventy per cent of patients whose glomeruli expressed HLA-G achieved partial or complete response at 6 months and 75% at the latest available follow up compared with 30% and 40%, respectively, of those who did not show any expression. The pattern of staining in tubules and infiltrating cells was highly variable precluding any clinical correlation. CONCLUSION: This study demonstrates that HLA-G is expressed in renal tissue in LN. Our retrospective data suggest that its expression could correlate with response to treatment.

Health in the 21st Century: new rights come to the fore?

Biotechnological advancements have engendered great expectations in patients, changing the very conception of health, which has come to be construed as psycho-physical well-being rather than a mere absence of diseases. The doctor-patient relationship is affected by the dearth of funds allocated for health care. Doctors, however, should make the most out of the meager resources available, while tackling any form of discrimination in access to health care.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy.

BACKGROUND AND PURPOSE: Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. MATERIALS AND METHODS: Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. RESULTS: All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. CONCLUSIONS: Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment.

Cosmetic surgery for children and adolescents. Deontological and bioethical remarks.

The only interventions deemed ethically acceptable are those that serve the "objective interest" of the minors involved from the standpoint of and conducive to sound mental health and balance in a patient's teenage years; by the same token, disproportionate interventions (e.g. overly invasive or pointlessly risky), or all those deemed unsuitable with regards to a poor cost-benefit ratio are viewed as unacceptable. In the process of considering the best interest of the minors involved, a wide array of factors come into play, such as: age, maturity, psychological and emotional conditions, motivations put forth by the underage patient, the opportunity to procrastinate the operation: parents, who are naturally entitled to give consent to the surgical procedures, and physicians are primarily liable to safeguard and act in the minor's best interest. The authors attempt to lay out how medical science has evolved over the past century, and aim to set forth an array of considerations centered on cosmetic surgery for adolescents.

Post-ganglionic autonomic neuropathy associated with anti-glutamic acid decarboxylase antibodies.

PURPOSE: Antibodies to glutamic acid decarboxylase (GAD-Abs) have been associated with several conditions, rarely involving the autonomic nervous system. Here, we describe two patients complaining of autonomic symptoms in whom a post-ganglionic autonomic neuropathy has been demonstrated in association with significantly elevated serum and CSF GAD-Abs levels. METHODS: Patients underwent nerve conduction studies, sympathetic skin response testing, evaluation of autonomic control of the cardiovascular system and skin biopsy. Also, serum screening to exclude predisposing causes of peripheral neuropathy was performed. Anti-GAD65 antibodies were evaluated in serum and CSF. RESULTS: GAD-Abs titer was increased in both serum and CSF in both patients. Sympathetic skin response was absent and skin biopsy revealed a non-length-dependent small-fiber neuropathy with sympathetic cholinergic and adrenergic post-ganglionic damage in both patients. Nerve conduction studies and evaluation of autonomic control of the cardiovascular system were normal in both patients. Both patients were treated with steroids with good, but partial, (patient 2) recovery of the autonomic dysfunctions. CONCLUSIONS: Although the pathophysiological mechanisms involved are not fully defined, GAD-abs positivity in serum and CSF should be searched in patients with autonomic neuropathy when no other acquired causes are evident. This positivity may help to clarify autoimmune etiology and, subsequently, to consider immunomodulatory treatment.

Habitat preference and flowering-time variation contribute to reproductive isolation between diploid and autotetraploid Anacamptis pyramidalis.

Tetraploid lineages are typically reproductively isolated from their diploid ancestors by post-zygotic isolation via triploid sterility. Nevertheless, polyploids often also exhibit ecological divergence that could contribute to reproductive isolation from diploid ancestors. In this study, we disentangled the contribution of different forms of reproductive isolation between sympatric diploid and autotetraploid individuals of the food-deceptive orchid Anacamptis pyramidalis by quantifying the strength of seven reproductive barriers: three prepollination, one post-pollination prezygotic and three post-zygotic. The overall reproductive isolation between the two cytotypes was found very high, with a preponderant contribution of two prepollination barriers, that is phenological and microhabitat differences. Although the contribution of post-zygotic isolation (triploid sterility) is confirmed in our study, these results highlight that prepollination isolation, not necessarily involving pollinator preference, can represent a strong component of reproductive isolation between different cytotypes. Thus, in the context of polyploidy as quantum speciation, that generates reproductive isolation via triploid sterility, ecological divergence can strengthen the reproductive isolation between cytotypes, reducing the waste of gametes in low fitness interploidy crosses and thus favouring the initial establishment of the polyploid lineage. Under this light, speciation by polyploidy involves ecological processes and should not be strictly considered as a nonecological form of speciation.