Antonio Gioacchino Spagnolo

Male fertility and reduction in semen parameters: A single tertiary-care center experience

Background. Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice. Objective. To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009. Results. Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients. Conclusion. Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues.

Outlining ethical issues in nanotechnologies

Nanotechnologies are an expression of the human ability to control and manipulate matter on a very small scale. Their use will enable an even and constant monitoring of human organisms, in a new and perhaps less invasive way. Debates at all levels--national, European and international--have pointed out the common difficulty of giving a complete, clear definition of nanotechnologies. This is primarily due to the variety of their components, to the fact that there is not just one technology but several. The most significant medical applications of nanotechnologies are in the diagnostic and the therapeutic fields, eg biosensors and molecular imaging, providing diagnosis and drug delivery with no invasive methods involved. Like any other emerging field, such technologies imply new possibilities for improving health but, on the other hand, they are still at an experimental stage and therefore should be implemented under rigorous safety testing before going on general release. For this purpose, the ethical, legal and social implications (ELSI) of nanotechnologies have been elaborated by study groups, in order to develop solutions before the results of the tests are diffused into medical practice. The aim of this paper is to define some of the ethical issues concerning biomedical applications and to evaluate whether there is a need for new or additional guidelines and regulations.

Conservative (non dialytic) management of end-stage renal disease and withdrawal of dialysis

Abstract Several key questions help to clarify the evolving debate concerning management of end-stage renal disease and withdrawal of dialysis. First, what is the evidence about survival, quality of life, and course of illness, following conservative management or dialysis withdrawal? Second, what criteria are used for deciding on conservative management or withdrawing dialysis, and how are these criteria justified? Third, who should make the decision and how should it be reached, particularly when there is cognitive impairment and the patient cannot make the decision for themselves? Decision criteria, the evidence, and who decides are each considered in this review.

A colloquium on the congress "A gift for life. Considerations on organ donation".

Alessandro Nanni Costa, J. M. Simon i Castellvi, Antonio G. Spagnolo, Nunziata Comoretto, Jean Laffitte, Hakan Gabel, Francis L. Delmonico, Ferdinand Muehlbacher, Walter Schaupp, Alexandra K. Glazier, Valter D. Garcia, Mario Abbud-Filho, Jose O. Medina-Pestana, Mariangela Gritta Grainer, Pier Paolo Donadio, Anna Guermani, Riccardo Bosco, Francesco Giordano, Blanca Martinez Lopez de Arroyabe, Marco Brunetti, Marti Manyalich, Gloria Paez, Ricardo Valero, Rafael Matesanz, Elisabeth Coll, Beatriz Dominguez-Gil, Beatriz Mahillo, Eduardo Martin Escobar, Gregorio Garrido, and Felix Cantarovich

Ventricular Parasystole: A Chronobiologic Study

Previous works have reported circadian rhythms for several cardiovascular parameters. A chronobiologic rhythm is characterized by: mesor (a rhythm‐determined average), amplitude (half difference between the highest and lowest values), and acrophase (timing of high point in degrees and/or in hours) along with 95% confidence limits. We performed 24‐hour ECG Holler monitoring in seven patients (mean age, 50.6 years) with ventricular parasystole (VP) in order to determine whether the chronotropic activity of parasystolic foci has a circadian rhythm similar to that of the sinus node. For each Holter recording parasystolic rates (PRs) and heart rates (HRs) were calculated every hour. Furthermore, a mean hourly PR and a mean hourly HR were calculated from the hourly PRs and HRs of the patients. The statistic chronobiologic analysis was done by single and mean cosinor methods. Correlation between mean hourly PR and HR was evaluated by Pearsons V coefficient. A statistically significant rhythm (P < 0.05) was found for the single and mean rhythms both of HR and PR. In our patients, HR had acrophase at 1.27 P.M., mesor at 73.28 beats/min, and amplitude at 9.53 beats/min, whereas PR had acrophase at 1.42 P.M., mesor al 38.31 beats/min, and amplitude at 3.64 beats/ min. Chronobiological data and the high direct correlation between mean hourly HRs and mean hourly PRs (r = 0.96, P < 0.001) indicate a similar circadian variability of the chronotropic activity of sinus nodes and parasystolic foci. Although several hypotheses can be made, responsiveness of parasystolic foci to circadian variations of the autonomic nervous system tone (sympathetic and/or vagal) and/or circulating substances (particularly catecholamines) seems the more probable one for explaining our findings.

Ethical considerations regarding head transplantation

Dear Editor, We read with interest and some perplexity the article by the Italian surgeon, Sergio Canavero, on the subject of head transplantation commonly known as HEAVEN surgery shorthand for its more full name, “head anastomosis venture” and GEMINI spinal cord fusion (SCF) procedure.[2] We find it essential to address some crucial ethical questions that might even clarify the real need for the HEAVEN and GEMINI SCF procedures. Recently he drew much attention with his procedure. Well known bioethicist Arthur Caplan stated in Forbes that “it is both rotten scientifically and lousy ethically.”[3] In his previous article,[1] Canavero emphasized that he didn’t address the ethical aspects, but we find it essential to address some of the ethical issues in order to bring to light the real necessity for this procedure. Although the technical feasibility of the GEMINI SCF procedure is not entirely clear, even for neurologists, the question to ask is how can the axons in the spinal cord be properly connected or glued with each other, even with a most precise cut. Despite the uncertainty regarding the technical feasibility of this procedure, for the sake of argument, we will assume that the procedure is possible and feasible to perform. Before entering into the sphere of human head transplantation, the first ethical problem that the HEAVEN and GEMINI SCF procedures will encounter is its approval by the Animal Welfare and Ethics Research Committee to perform pre-clinical experimentation on animals. Previous experiments of Robert J. White and Vladimir Demikhov affirmed that these kinds of experiments were lethal for animals and even the final outcome of the experimentation was more for the sake of experimentation. The HEAVEN procedure, seen in its finality, is not a therapeutic procedure but one for prolonging life, that could even play an essential role in the decision to accept it. Even if the procedure is accepted in years to come, the subject will be exposed to far greater and unknown risks than the benefits of the procedure. First of all, assuming that the spinal cord connection succeeds, the patient will need to take a large amount of immunosupressive drugs and it is not even clear if the rejection problem will be solved by taking such drugs. Starting with a presupposition that transplanting the head with a brain would automatically transplant the whole person with its mind, personality and consciousness, Canavero brings forth a mechanistic framework of the human person. Despite his vision, modern cognitive science shows that our cognition is an embodied cognition, in which the body is a real part in the formation of human self. Therefore, the person will encounter huge difficulties to incorporate the new body in its already existing body schema and body image that would have strong implications on human identity. Even memories of the role the former body played in the creation of the subjects identity would encounter possible conflict with a new donor given body, because the identity would reflect itself in the corporeality that does not exist anymore. Similar issues were also seen in cases of face and hand transplants. This confusion to the persons psychological state could possibly lead to serious psychological problems, namely insanity and finally death. Another ethical issue that could emerge in this procedure, that Canavaro himself addresses, is the problem of the donors gonads and the transmission of genetic inheritance to the offsprings. As a matter of fact, these organs are related to each other, because they are human identity organs, and therefore they are by some legislations forbidden for transplantation (e.g. the Italian law).[4] Moreover, this procedure encounters some social and ethical problems facing organ donations: on one hand because of uncertainty of the procedure, the donor body with its organs would be wracking the organs that could be useful to someone else that needs a heart or liver that could save his/her life. Finally, the same idea of the head transplant and the donation procedure could provoke strong side-effects in the form of a “yuck factor”[5] toward organ donation, in general, among the people.

Health Technology Assessment of pathogen reduction technologies applied to plasma for clinical use.

Although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. Pathogen reduction technologies may offer a new approach to increase blood safety. The study is the output of collaboration between the Italian National Blood Centre and the Post-Graduate School of Health Economics and Management, Catholic University of the Sacred Heart, Rome, Italy. A large, multidisciplinary team was created and divided into six groups, each of which addressed one or more HTA domains.Plasma treated with amotosalen + UV light, riboflavin + UV light, methylene blue or a solvent/detergent process was compared to fresh-frozen plasma with regards to current use, technical features, effectiveness, safety, economic and organisational impact, and ethical, social and legal implications. The available evidence is not sufficient to state which of the techniques compared is superior in terms of efficacy, safety and cost-effectiveness. Evidence on efficacy is only available for the solvent/detergent method, which proved to be non-inferior to untreated fresh-frozen plasma in the treatment of a wide range of congenital and acquired bleeding disorders. With regards to safety, the solvent/detergent technique apparently has the most favourable risk-benefit profile. Further research is needed to provide a comprehensive overview of the cost-effectiveness profile of the different pathogen-reduction techniques. The wide heterogeneity of results and the lack of comparative evidence are reasons why more comparative studies need to be performed.

Ethical and deontological issues in Transfusion Medicine

Recent developments in Transfusion Medicine Since the second half of the 1980s, Transfusion Medicine has gradually taken on an increasing autonomous place in the world of medical specialties, continuing its evolution from its initial, mainly immunohaematological role, towards new diagnostic, clinical-therapeutic and research activities. Currently, in addition to direct care activities for patients and support of specific highly specialised care processes, Transfusion Medicine ranges from the collection and banking of haematopoietic stem cells to the banking of tissues and cell therapy. In parallel to the growth of the activities mentioned above, there has been constant progress in research activities, as evidenced by the exponential increase in randomised controlled trials and meta-analyses1. Despite this gradual transformation, blood collection and the production of sufficient amounts of blood components to reach and/or maintain local and national self-sufficiency continue to be priority aims and the object of planning the activities of the whole national transfusion network2. Blood donation and Transfusion Medicine now constitute an essential component of the integrated care processes that are typical of the current, modern vision of health, oriented in a logic of disease management. Operational coordination and management, including administrative area, of the many activities that are part of the transfusion process have a fundamental role in the clinical governance of all the procedures pertaining to the field of transfusion3. Blood and blood components are in fact “the final result of various processes (clinical, laboratory, social), which are linked together and intertwine, involving different professional skills and responsibilities”4. The transfusion process can be defined as a “supply chain” because, ultimately, the patients’ demands condition the supply, that is, the need for blood donations. A lack of blood occurs when the supply is not sufficient to meet the demand and the transfusion needs of the patients cannot be met quantitatively and/or qualitatively, or waiting times are imposed, particularly for elective surgery. The supply chain in the transfusion field begins with the donor and the donor procedures and continues through the processing, qualification and biological validation, reception of transfusion requests, evaluation of the appropriateness of the requests, determination of the immunological compatibility, allocation of blood components to individual patients, delivery to the requesting clinical unit, transfusion to the recipient patient and recording and reporting of any side effects and adverse events possibly associated with the transfusion5. The correct management of the processes that make up the transfusion supply chain affects the safety of the whole process, the monitoring of which is a specific aim of haemovigilance systems. A good haemovigilance system includes appropriate management of patients’ transfusion requirements as well as safe fulfilment of these needs. Transfusion safety goes beyond the intrinsic safety of the transfused therapeutic products, depending on a series of closely interconnected processes which start with the donor and finish with the recipient. The systematic recording of transfusion outcomes and adverse events associated with transfusion therapy constitutes the afferent branch of every haemovigilance system and plays a fundamental role in the search for and the identification of possible strategies for improvement. In contrast, the purpose of the efferent branch of these systems is to achieve a constant, global improvement in the transfusion process through an analysis of the data collected and their possible changes over time, to identify possible corrective or preventive strategies based on objective evidence. Therefore, it seems clear that the multifaceted and complex transfusion process, with its unique global organisational and management framework, is not possible without a systematic approach aimed at raising quality and, therefore, at continuous improvement4. Since 2002, and in particular in the 3-year period from 2005 to 2007, national and European community law-making in the field of blood transfusion, and related activities, has been more intense and important than ever before6–18. The regulatory scenario that has developed is, therefore, very complex in terms of relations between European and national legislations, in particular because of the need to harmonise the acts implementing the European Directives with existing national laws. The European regulatory provisions concerning transfusions and associated activities are strongly inspired by the social and ethical concepts of solidarity, voluntariness and periodic repetition of donations, as well as the fundamental principle of protecting public health, in terms of fairness, transparency and right of access to safe and systematically controlled services19. Great emphasis is also given to the principles of management and control of the specific care processes, in order that these are aimed at ensuring high organisational and professional standards as well as safeguarding the appropriateness of the clinical use of blood products. Finally, specific regulations concerning the cord blood banking have been introduced20. The aim of this review is to focus on the ethical and deontological issues of the macro-processes of the transfusion chain, extending the considerations to the most recent, innovate area of development of Transfusion Medicine, biobanking, and outlining possible additional areas of practical ethical reflection related to it, such as health technology assessment and the organisational ethics of services. The reason for this is the paucity of specific contributions on the subject. The ethical issues related to the donation of cord blood will not be dealt with here: the reader is referred to the recent, but still limited literature21–22.

Deliberate termination of life of newborns with spina bifida

The decision to make medical treatment on newborns with severe pathologies represents one of the most controversial aspects of the current neonatal and pediatric medical practice because, in spite of medical progress in this field, it is not possible to gain always a complete recovery of these little patients. In this context, physicians as well as parents are worried about a possible prolongation of suffering without a real perspective of benefits. The de Jong article gives us another occasion to make a critical evaluation of the Dutch practice to deliberately terminate life of newborns with spina bifida according to the so-called Groningen Protocol, adopted by the Dutch Association of Paediatrics in 2005. The use of selection criteria to decide treatments, along with the Groningen Protocol, was anticipated in the 1970s by the so-called “Lorber selection criteria”, based on the concept of foreseen quality of life. However, the nature of such criteria is essentially psycho-social, and therefore they are not “sensu stricto” proper medical criteria. Moreover, the use of such criteria brought warring “errors” of evaluation as shown, for example, by the ethical debate in the USA on the Baby Jane Doe case, followed to the prospect physicians made about the future life of handicapped children. The interesting historical overview about the treatments of newborns with spina bifida presented by de Jong suggests to us that, although the selection criteria have been introduced since the 1970s, it is only recently that in Netherlands those criteria have been put into practice for an active termination of newborns with severe pathologies. Should we consider the novel decision to terminate life of these infants a medical “progress”, a human “advancement” in medicine? Should we consider such decision a medical progress instead of an active and devote caring of these patients? The Groningen Protocol states that the decision to terminate life of these fragile patients would be more “human” than letting them live. In our view, an effective medical human progress includes a sympathetic attitude towards the most fragile and needy, and it demands to take care of them, not to make an easier termination of life. In this case, the founding value of the medical act would be overwhelmed and, according to de Jong, a fundamental requirement for a civil sharing would be lost. The author underlines that the choice operated within the Groningen Protocol is in contrast with the recognition of the dignity inherent to humans and with the promise of a more incisive protection of the fundamental human rights that rise from that dignity. Such commitment belongs much more to the physician who makes a public promise that he will place the interests of his patients above his own interests [1]. Groningen Protocol is just one of the examples that show how in medical practice new ways of discrimination are gaining place. The progressive shift from the choice of not to treat to the decision of a deliberate termination of life of newborns with spina bifida, together with the arguments held to this aim, evidently shows how the problematical aspect cannot be sought in the “adequacy” (efficacy, burdensome) of the measures needed to preserve life, but it consists of the “adequacy” (utility, burdensome) of the life of the patient in terms of present and future quality of life. In other words, the question seems to be the existence of life in itself, but how is it possible to consider life as a problem which needs to be terminated? It is evident that the base of such perspective is a distortion of the concept of human dignity, together with an outrage to the essence of the medical profession. Childs Nerv Syst (2008) 24:37–38 DOI 10.1007/s00381-007-0482-7

Research Ethics Committee Auditing: The Experience of a University Hospital.

The authors report the first Italian experience of a research ethics committee (REC) audit focused on the evaluation of the REC’s compliance with standard operating procedures, requirements in insurance coverage, informed consent, protection of privacy and confidentiality, predictable risks/harms, selection of subjects, withdrawal criteria and other issues, such as advertisement details and justification of placebo. The internal audit was conducted over a two-year period (March 2009–February 2011) divided into quarters to better value the influence of the new insurance coverage regulation that came into effect in March 2010 (Ministerial Decree of 14 July, 2009) and expand the requirements to safeguard participants in clinical drug trials including other critical items as information and consent and the risks to benefits ratio. Out of a total of 639 REC’s opinions and research studies, 316 were reviewed. Regarding the insurance policy requirements, Auditor/REC non-compliance occurred only in one case. The highest number of Auditor/REC non-compliance was in regard to information and consent, which should have incurred a suspended decision rather than a favorable opinion. This internal audit shows the importance and the difficulty of the review process. For this reason, specific courses for members of the research ethics committee and for those who aspire to become auditors will be provided. There may also be efforts to improve the standard operating procedures already in place.