Matteo Gulino

The Evolution of Legislation in the Field of Medically Assisted Reproduction and Embryo Stem Cell Research in European Union Members

Medically Assisted Reproduction (MAR), involving in vitro fertilisation (IVF), and research on embryos have created expectation to many people affected by infertility; at the same time it has generated a surplus of laws and ethical and social debates. Undoubtedly, MAR represents a rather new medical field and constant developments in medicine and new opportunities continue to defy the attempt to respond to those questions. In this paper, the authors reviewed the current legislation in the 28 EU member states trying to evaluate the different legislation paths adopted over the last 15 years and highlighting those EU countries with no specific legislation in place and MAR is covered by a general health Law and those countries in which there are no laws in this field but only “guidelines.” The second aim of this work has been to compare MAR legislation and embryo research in EU countries, which derive from different origins ranging from an extremely prohibitive approach versus a liberal one, going through a cautious regulatory approach.

The effects of giving patients verbal or written pre-operative information in gynecologic oncology surgery: a randomized study and the medical-legal point of view

OBJECTIVES To evaluate the verbal and written preoperative information in patients undergoing surgery for malignant gynaecologic disease, in terms of satisfaction about preoperative received informations, hospitalization days, postoperative pain experienced using visual analogue scale (VAS) and number of pain drugs used daily. STUDY DESIGN From January 2008 to December 2012, consecutive patients with diagnosis of endometrial cancer, referred to the Division of Gynecology of University Campus Bio-Medico of Rome, were enrolled. Eligible subjects were randomized into two groups: Group V (Verbal information ward) consisted of patients who had verbal preoperative information about surgical procedure and postoperative management and Group W (Written Information ward) consisted of patients who had written preoperative information. All preoperative and postoperative data were recorded. Concerning satisfaction about preoperative received informations, patients were asked to complete the QLQ-C30 and the EORTC INFO25. RESULTS 190 patients were considered in this study. Group W (n=92) has a better info satisfaction (p=0.0008, statistically significant), a mean VAS value lower (p=0.02, statistically significant) and also a lower number of hospitalization days (p=0.0265, statistically significant) and pain medications used daily, (p=0.0120, statistically significant), comparing with group V (n=98). CONCLUSIONS We support the use of preoperative information leaflet to better prepare patients for a surgical procedure, showing a faster recovery, low medications use and a better quality of life outcome.

Is age the limit for human-assisted reproduction techniques? ‘Yes’, said an Italian judge

Although use of assisted reproduction techniques was examined by an ad hoc act in 2004 in Italy, there are many opposing views about ethical and economic implications of the technologies dealing with infertility and sterility problems. In this paper, the authors examine a recent judges decision that ordered the removal and subsequent adoption of a 1-year-old child because her parents were considered too old to be parents. The couple had had recourse to heterologous artificial insemination abroad and decided to give birth in Italy. The judgement deals with and discusses the complex issue of the right to procreate in order to balance the opportunities offered by scientific progress with the unborn childs condition.

Vemurafenib and panitumumab combination tailored therapy in BRAF-mutated metastatic colorectal cancer: A case report

As the knowledge on cancer genetic alterations progresses, it fosters the need for more personalized therapeutic intervention in modern cancer management. Recently, mutations in KRAS, BRAF, and PIK3CA genes have emerged as important mechanisms of resistance to EGFR-targeted therapy in metastatic colorectal cancer (mCRC). Here we report the first case of a mCRC patient whose disease had progressed on standard lines of treatment and for which we devised a personalized therapeutic approach consisting of vemurafenib (ZelborafTM) and panitumumab (VectibixTM), based on the following molecular profile: BRAFV600E-mutant, amplified EGFR (double positive) and WT KRAS, WT PIK3CA, not-amplified HER2 (triple negative). This new combination therapy was well tolerated and resulted in a strong control of the disease. In particular, the vemurafenib-panitumumab combination appears to limit the typical toxicity of single agents, since no cutaneous toxic effects typically associated with vemurafenib were observed. Here we report the first clinical evidence that the combination of an anti-EGFR (panitumumab) and an inhibitor of BRAFV600E (vemurafenib) is well tolerated and results in a strong disease control in an extensively pretreated mCRC patient.

Stem cell therapy: from evidence-based medicine to emotion-based medicine? The long Italian way for a scientific regulation

On 23 May 2013, the Italian health minister decided to endorse a law regarding controversial stem cell-based therapies in 32 young terminally ill patients, shocking many scientists. According to the international scientific community, these therapies could be dangerous because they were not rigorously tested in humans. This decision was made after many days of media and judiciary pressure. Several lawsuits regarding stem cell-based therapies were brought before the judiciary districts of different Italian regions. We analyzed the Italian legal context regarding the field of pharmaceutical and medical devices, including the European Union trend. A national database - commonly used to manage legal materials for professional or educational purposes or both - was used to find relevant legal cases involving stem cell-based therapies. Stem cell-based therapies endorsed by the new Italian law have been the subject of an important discussion not only in the scientific community but also in various courts. We found several legal actions filed by parents in order to make stem cells available to their young children, who had serious neurodegenerative diseases. The majority of the analyzed legal disputes were settled in favor of the applicants, whereas only two decisions (Courts of Justice of Rome and Florence) rejected the complaint because of the absence of sufficient scientific data regarding stem cell-based therapies. The present Italian situation is influencing the destiny of future young patients and strongly impacting public and institutional opinion. It is a practical example of the complexity of the decision of not providing unapproved scientific stem cell-based therapies when medicine does not have any other alternative therapies.

Ethical and Legal Implications of Elective Ventilation and Organ Transplantation: “Medicalization” of Dying versus Medical Mission

A critical controversy surrounds the type of allowable interventions to be carried out in patients who are potential organ donors, in an attempt to improve organ perfusion and successful transplantation. The main goal is to transplant an organ in conditions as close as possible to its physiological live state. “Elective ventilation” (EV), that is, the use of ventilation for the sole purpose of retrieving the organs of patients close to death, is an option which offsets the shortage of organ donation. We have analyzed the legal context of the dying process of the organ donor and the feasibility of EV in the Italian context. There is no legal framework regulating the practice of EV, neither is any real information given to the general public. A public debate has yet to be initiated. In the Italian cultural and legislative scenario, we believe that, under some circumstances (i.e., the expressed wishes of the patient, even in the form of advance directives), the use of EV does not violate the principle of beneficence. We believe that the crux of the matter lies in the need to explore the real determination and will of the patient and his/her orientation towards the specific aim of organ donation.

Not Only a Clinical Nightmare: Amniotic Fluid Embolism in Court

Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving usually women in labour or in the early post-partum period. Clinical consequences of this unpredictable and unpreventable pathology may be extremely serious with high morbidity and mortality rates. Data obtained from the US Amniotic Fluid Embolism Registry show that the process is more similar to anaphylaxis than to embolism, and the term anaphylactoid syndrome of pregnancy has been suggested because foetal tissue or amniotic fluid components are not universally found in women who present signs and symptoms related to AFE. The first aim of this paper has been to focus on the medico-legal aspects concerning the misdiagnosis and the treatment of the AFE and the Authors, with this purpose in mind, reviewed the main national law cases on medical malpractice claims involving both physicians and hospitals. The second aim has been to highlight the need to introduce a National register as a useful tool to raise the awareness of this disease among physicians and to improve the quality of care, which can be achieved through a proper identification and reporting of AFE cases. The application of a national register may limit the number of medico-legal litigations, which according to the national and foreign Jurisprudence are not currently based in favour of the predictability of AFE, but they focus their discussion on the importance of a prompt medical assistance when the effects of this disorder occur.

The European Court legitimates access of Italian couples to assisted reproductive techniques and to pre-implantation genetic diagnosis

On 28 August 2012, the European Court of Human Rights (ECHR) issued a judgment regarding the requirements for the legitimate access of couples to assisted reproductive techniques (ART) and to pre-implantation genetic diagnosis (PGD). This judgment concerns the case of an Italian couple who found out after their first child was born with cystic fibrosis that they were healthy carriers of the disease. When the woman became pregnant again in 2010 and underwent fetal screening, it was found that the unborn child also had cystic fibrosis, whereupon she had the pregnancy terminated on medical grounds. In order to have the embryo genetically screened prior to implantation under the procedure of PGD, the couple sought to use in vitro fertilisation to have another child. Since article 1 of the Italian law strictly limits access to ART to sterile/infertile couples or those in which the man has a sexually transmissible disease, the couple appealed to the European court, raising the question of the violation of articles 8 and 14 of the European Convention on Human Rights. The applicants lodged a complaint that they were not allowed legitimate access to ART and to PGD to select an embryo not affected by the disease. The European Court affirmed that the prohibition imposed by Italian law violated article 8 of the European Convention on Human Rights. Focusing on important regulatory and legal differences among EU Nations in providing ART treatments and PGD, we derived some important similarities and differences.

Does defensive medicine change the behaviors of vascular surgeons? A qualitative review.

Although in literature few successful claims have been shown in comparison with other medical specialties such as gynaecology and orthopaedics, vascular surgery is included among high-risk specialties. The high-risk of receiving medical claims may lead vascular surgeons to practice defensive medicine, as is normal in several other areas of clinical practice. No studies are available to our knowledge of the incidence of defensive medicine in the field of vascular surgery. Taking into consideration the scarce amount of information, the authors provide a critical discussion regarding the application of defensive medicine behaviour among vascular surgeons.

The physician's breach of the duty to inform the parent of deformities and abnormalities in the foetus: "wrongful life" actions, a new frontier of medical responsibility.

Abstract A recent decision of the Italian Highest Court for the first time legitimized wrongful life suits. The Court stated the following principles: (a) the contract between the mother and the doctor has also protective effects in favour of third parties (father, siblings and the disabled child) who have the right to be compensated; (b) the right to compensation is neither based on the right not to be born nor on the right to be born healthy, but rather it is based on the breach of duty of care which coincides with the child’s disabled status; (c) siblings may suffer the reduced availability of their parents; (d) the doctor is held responsible for not providing full information to the mother about the foetal deformity. The Supreme Court once again emphasized the importance of information on the matter of very personal choices, such as termination of pregnancy in case of foetal malformations. In the present case, the gynaecologist breached the duty to inform, especially after the patient requested diagnostic tests designed to highlight any foetal malformations and informed the doctor of the possibility of an eventual subsequent termination of pregnancy if foetal malformations were found.