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We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome. From January 1, 2010 to June 30, 2012 all donors after brain death managed by the NITp (n = 1100) were prospectively included in this study. CXCL10 and IL-6 were measured on serum collected for the crossmatch at the beginning of the observation period. Graft outcome in recipients who received kidney (n = 1325, follow-up 4.9 years), liver (n = 815, follow-up 4.3 years) and heart (n = 272, follow-up 5 years) was evaluated. Both CXCL-10 and IL-6 showed increased concentration in donors after brain death. The intensive care unit stay, the hemodynamic instability, the cause of death, the presence of risk factors for cardiovascular disease and the presence of ongoing infection resulted as significant determinants of IL-6 and CXCL10 donor concentrations. Both cytokines resulted as independent predictors of Immediate Graft Function. Donor IL-6 or CXCL10 were associated with graft failure after liver transplant, and acted as predictors of recipient survival after kidney, liver and heart transplantation. Serum donor IL-6 and CXCL10 concentration can provide independent incremental prediction of graft outcome among recipients followed according to standard clinical practice.

Summary Background Medico-legal conflicts arise when it is difficult to prove the cause of nosocomial infections. Aim To report an outbreak of patient-to-patient transmission of hepatitis C virus (HCV) through the repeated use of a multi-dose saline flask during the rinsing of central venous catheters. Methods Blood samples were taken from each patient for the comparative analysis of their HCV RNA strains. No samples were available for one patient who died before the investigation started. Despite the known lability of HCV RNA, the body was exhumed four months after burial and postmortem samples were collected. HCV RNA was extracted successfully from liver and spleen samples. Genotyping of all the HCV strains was performed by sequence analysis of the 5′NC untranslated region, the E1 core conserved region and the E1/E2 hypervariable region. Findings Forensic investigators retraced the route used by two ward nurses, when saline catheter flushes were given to 14 patients with each nurse administering to seven patients. The comparative phylogenetic analysis of all case strains identified the deceased patient as the source of contamination to five patients. Conclusions This study highlights the value of sequence analysis as a tool for solving medico-legal conflicts. The High Court of Justice found that a health worker's re-use of a contaminated needle resulted in the nosocomial transmission of HCV.

Background To limit the chimerism typical of transplanted organs, which constantly reveals mixed profiles, laser microdissection (LCM) has been hypothesized as a valid tool in comparison with manual dissection. Case report A 42-year-old man with end-stage HBV/HDV liver cirrhosis and single hepatocellular carcinoma (HCC) underwent liver transplantation. Four months later hepatic nodules were diagnosed. The histological investigation showed an HCC. Despite therapy, the man died as a result of metastatic carcinoma 9 months later. On behalf of the public prosecutor, we performed short tandem repeat analysis on the hepatic nodules to determine whether the carcinoma had originated from the transplanted liver. Conclusions The manually dissected samples revealed a high degree of chimerism that did not allow a clear diagnosis. Instead, the detected chimerism was very low in the microdissected samples, where the tumor origin was clearly diagnosable as a recurrence of the recipient's primitive HCC. Accordingly, the application of LCM improved the quality of the results leading to an exclusion of medical liability profiles, confirming the high quality safety procedure of the Italian system in solid organ transplantation, and showing at the same time how useful this technique may be in selected forensic cases.

Background. The shortage of available organs, has increasingly prompted the use of elderly donors, with a consequent growth of possible risk factors. In this context the risk of donor-recipient transmission of infectious or neoplastic pathologies may be considered as a major issue; in each case for each organ potentially available, acceptable quality must be provided and unacceptable risks must be avoided. Methods. We are presenting here the process of risk management followed by the Italian centers. In 2001, the Italian National Transplant Centre created a national commission of experts, with the mission of defining guidelines for the evaluation process of the potential organ donor. As a supplement to these measures, the Italian National Transplant Centre has supported transplant network health workers through ad hoc developed information tools and an expert task force (second opinion) for evaluation of doubtful cases. Results. Starting from the date of guidelines application and second opinion start up, 9519 potential cadaveric donors were reported in Italy. Of these, 1611 presented a neoplastic or infectious risk. Over this period, 4861 donors were used for transplantation, equal to 48.5% of reported donors. Among the 1611 donors, who had been diagnosed at risk, 674 were neoplastic-disease affected donors and 937 infection-disease affected donors. Conclusions. At the European level, several new activities have been recently implemented to increase organ safety. In Italy, new guidelines and actions to ensure organ safety have been implemented. The evaluation of the impact of these actions will be performed in the near future.

The increasing number of clinical indications for liver transplantation has forced physicians to use livers procured from elderly cadaveric donors to expand the graft pool. However, the degree of ischemia/reperfusion damage in elderly livers remains poorly investigated. In this study, the outcomes of livers procured from a group (I) of young donors (n=12; 38 +/- 12 years; range: 21-58) were compared with a group (II) from elderly donors (n=7; 68 +/- 7 years; range: 62-84) for changes in reduced glutathione, the main hepatic free radical scavenger. Reduced and oxidized glutathione were assayed by high performance liquid chromatography in liver biopsies performed just before cold ischemia and during early reperfusion. A significant decrease in reduced glutathione was observed at the time of reperfusion in both groups I (P=.0195) and II (P=.002). Before cold ischemia and during early reperfusion, no differences between young versus elderly donors were noted in the oxidized/reduced glutathione ratio, in conventional graft function markers or in liver-related hemostatic parameters. Comparable glutathione contents were measured at the time of early reperfusion in livers obtained from young and elderly cadaveric donors, suggesting that livers procured from elderly donors might be adequately protected against ischemia/reperfusion damage.

The shortage of available organs, has increasingly prompted the use of elderly donors, with a consequent growth of possible risk factors. In this context the risk of donor-recipient transmission of infectious or neoplastic pathologies may be considered as a major issue; in each case for each organ potentially available, acceptable quality must be provided and unacceptable risks must be avoided. METHODS: We are presenting here the process of risk management followed by the Italian centers. In 2001, the Italian National Transplant Centre created a national commission of experts, with the mission of defining guidelines for the evaluation process of the potential organ donor. As a supplement to these measures, the Italian National Transplant Centre has supported transplant network health workers through ad hoc developed information tools and an expert task force (second opinion) for evaluation of doubtful cases. RESULTS: Starting from the date of guidelines application and second opinion start up, 9519 potential cadaveric donors were reported in Italy. Of these, 1611 presented a neoplastic or infectious risk. Over this period, 4861 donors were used for transplantation, equal to 48.5% of reported donors. Among the 1611 donors, who had been diagnosed at risk, 674 were neoplastic-disease affected donors and 937 infection-disease affected donors. CONCLUSIONS: At the European level, several new activities have been recently implemented to increase organ safety. In Italy, new guidelines and actions to ensure organ safety have been implemented. The evaluation of the impact of these actions will be performed in the near future.

Dai tempi della redazione dei criteri di Harvard [1] fino alla Legge 644/1975 [2], che regolava le attivita di prelievo e trapianto in Italia, tutti i Paesi del mondo hanno gradualmente adottato la metodologia di accertamento della morte con criteri neurologici.

Limited access to scarce resources, such as organs for transplantation, has increasingly prompted the use of elderly donors, with a consequent growth of possible risk factors linked to their particular features. Acceptable organ quality must therefore be guaranteed, without exposing recipients to unacceptable risks. For this reason, a set of guidelines for assessing donor suitability has been drawn up. This document standardizes the operative steps in the donor evaluation process and provides precise instructions for center staff. A pool of experts is available round the clock to offer advice on doubtful clinical cases. Such measures have allowed more effective use of available donors for transplantation.

L’autore parte da un breve resoconto del suo coinvolgimento nella questione, concentrandosi sugli incontri dei filosofi morali/teologi, medici, giuristi e infermieri che presiedette nel 1986 per discutere l’argomento in profondità, dopo la dichiarazione della Pontificia Accademia delle Scienze del 1985 che affermava che il trattamento delle persone in uno stato di incoscienza permanente non è obbligatorio ma che tutta l’assistenza, compresa la nutrizione, dovrebbe essere loro profusa. Questi incontri portarono l’autore stesso e alcuni altri a cambiare le loro precedenti opinioni, secondo cui non era obbligatoria la nutrizione, e a scrivere un documento, pubblicato nella rivista Issues in Law and Medicine nel 1987 e firmato da più di 90 studiosi, in cui vengono fornite le ragioni per cui tale nutrizione è moralmente necessaria in modo ordinario. Egli analizza quindi i punti di vista delle diverse fonti sull’argomento, compresi i vescovi cattolici e gli studiosi, dai primi anni ‘80 fino al pronunciamento di Giovanni Paolo II del 20 marzo 2004. In particolare egli presenta l’argomento assai influente presentato da Kevin O’Rourke, O.P., che afferma che un’adeguata lettura del discorso del 1957 di Papa Pio XII sosterrebbe l’opinione secondo cui tale somministrazione di cibo/acqua è straordinaria perché non permette al soggetto in stato di incoscienza permanente di perseguire il fine spirituale della vita. L’autore mostra che questa interpretazione di Pio XII è grossolanamente imprecisa. L’autore, quindi, riassume il discorso di Giovanni Paolo II del 20 marzo affermando che la nutrizione di tali persone è una questione di assistenza ordinaria ed è obbligatoria. Egli poi esamina l’accoglienza estremamente ostile che questo discorso ha avuto da parte di molti teologi, che hanno affermato che esso non è compatibile con l’insegnamento della tradizione Cattolica, o che impone gravi pesi non necessari a coloro che forniscono le cure, o che non era ben ragionato, ecc. L’autore conclude con la difesa del discorso di Giovanni Paolo II, rispondendo alle obiezioni sollevategli contro. ---------- The Author begins with a brief account of his own involvement in the question, focusing on the meeting of moral philosophers/theologians, doctors, lawyers and nurses he chaired in 1986 to discuss the issue in depth after the 1985 declaration by the Pontifical Academy of Sciences that treatment of permanently unconscious person is not required but that all care, including feeding, should be lavished on them. These meeting led him and some others to change their carlier views that considered such feeding not obligatory and to prepare a paper, published in Issues in Law and Medicine in 1987 and signed by more than 90 scholars, proving the reasons why such feeding is ordinarily morally required. He then reviews the views of different sources, including both Catholic bishops and scholars, over this issue from early 1980s until John Paul II’s statement of March 20, 2004. He in particular presents the highly influential argument advanced by Kevin O’Rourke, O.P., claiming that a proper reading of a 1957 address by Pope Pius XII support the view that such provision of food/hydration is extraordinary because it does not enable the permanently unconscious to pursue the spiritual goal of life and shows that this interpretation of Pius XII is grossly inaccurate. He then summarizes John Paul II’s March 20 address affirming that feeding such persons is ordinarily a matter of ordinary care and is obligatory. He next surveys the extremely hostile reception this address received from may theologians, who declared that it was not compatible with traditional Catholic teaching, that it imposed unnecessarily grave burdens on care givers, that it was not well reasoned etc. He concludes by defending John Paul II’s address and responding to objections leveled against it.

The Model for End-stage Liver Disease (MELD) provides a score able to predict short-term mortality in patients awaiting liver transplantation (LT). In the early 2002, United Network for Organ Sharing (UNOS) has proposed to replace the conventional statuses 3, 2B, and 2A with a modified MELD score. However, the accuracy of the MELD model to predict post-transplantation outcome is fairly elusive. In the present study we investigated the predictive value of the MELD score for short-term patient and graft mortality in comparison with conventional UNOS status. Sixty-nine patients listed at UNOS status 3 (n = 5), 2B (n = 55) or 2A (n = 9) who underwent LT were enrolled according to strict criteria. No donor-related parameters affected 3-month patient survival. Through univariate Cox regression, pretransplantation international normalized ratio (P = 0.049) and activated partial thromboplastin time (P = 0.032) were significantly associated with 3-month patient survival, although not in the subsequent multivariate analysis. The overall MELD score was 17 +/- 6.63 (median: 16, range: 4-34), increasing from UNOS Status 3 to 2A (r(2) = 0.171, P = 0.0001). No significant difference occurred in the median MELD score between patients who underwent a second LT and those who did not (P =0.458). The inter-rate agreement between UNOS status and MELD score after categorization for clinical urgency showed a fair agreement (kappa = 0.244). The 3-month patient and graft mortality was 15.94% and 20.29% respectively. The concordance statistic did not find significance between UNOS status and MELD score for 3-month patient (P = 0.283) or graft mortality (P = 0.957), although the MELD score revealed a major sensitivity for short-term patient mortality (0.637; 95%CI: 0.513-0.75). These findings suggest the need to implement MELD model accuracy for both inter-rate agreement with UNOS Status and patient outcome.

The increase in the number of patients awaiting liver transplantation (OLT) has forced the use of cadaveric donors (CD) with suboptimal characteristics. Of these, donor age is perhaps the most investigated parameter. Although excellent outcomes were observed for OLT using CD aged over 60 years, the European Liver Transplant Registry (ELTR) Group found an increased risk by using CD of more than 55 years. The Italian National Transplant Center has recently assumed that CD age more than 60 years is a potential risk factor for OLT. In this study, a single-center analysis was performed by stratifying CD by three age cut-offs (or =55 or55,or =60 or60, andor =65 or65 years) to evaluate effects on OLT outcome. Although no significant difference in 6-month and 1-year patient or graft survival occurred after stratification for each donor age cut-off, a better survival was observed with OLT performed using livers procured from CD55 years. A significant increase in cold ischemia time (CIT) was observed among OLT performed with grafts procured from CDor =55 andor =65 years (P = .007), and there was an inverse correlation between overall CIT and donor age (R = -0.300; P = .0022). However, no impact on 1-year patient survival was observed by introducing CIT in univariate logistic regression models as well as donor age, recipient age, donor/recipient age ratio, donor/recipient sex mismatch, ELTR diagnostic categories, and UNOS status. The results of this study suggest the suitability of CD of more than 55 years for OLT and the need to further investigate the cut-off value for CIT-related risk.

Gli Autori intendono con questo lavoro proporre un contributo nell’analisi delle difficili problematiche etiche che derivano dagli allotrapianti di mano. Nell’articolo si descrive brevemente la storia del primo trapiantato e l’iter che ha condotto, nel settembre del 1998, a Lione, a questo tipo d’intervento. Ci si è soffermati altresì sulle complicazioni nate di seguito e che hanno alfine obbligato all’amputazione dell’arto trapiantato, imputandone le cause ad una superficiale valutazione psichiatrica del ricevente. Questo recente tipo d’intervento obbliga a riflettere, a causa della novità e della particolarità dell’organo da trapiantare, sull’opportunità di quei trapianti cosiddetti “non-salvavita” in base ai rischi conosciuti cui conduce una terapia imunosoppressiva a lungo termine. Ciò porta a riconsiderare anche il concetto di salute e i principi di libertà e autodeterminazione. Ci si è altresì interrogati sulle modalità di scelta dei riceventi e sull’approccio più opportuno da tenersi nei loro riguardi soprattutto a livello psicologico prima e dopo l’operazione. Tutte le recenti acquisizioni sono state valutate in rapporto a ciò che la legislazione italiana e la deontologia medica impongono. Si è detto anche dei vizi di un consenso per lo meno scarsamente informato, derivante dalla carenza di dati sperimentali. Nel prosieguo dell’articolo gli Autori hanno evidenziato come possano sollevarsi numerosi interrogativi e remore culturali e inconsce oltre che morali circa l’acquisizione da parte del ricevente di un organo che più di altri appare visibile e intimamente legato alla propria identità e personalità, la qual cosa rende possibile che venga ancor più percepito come estraneo e intollerabile da alcuni. In conclusione gli Autori ritengono che i candidati ideali dovrebbero essere giovani che hanno perduto di recente entrambe le mani, soprattutto se è stata compromessa anche la loro vista, mentre poco ragionevole appare il trapianto di mano in un amputato unilaterale. ---------- The bioethical issues arising from hand transplantation are discussed in this paper. We briefly recall the first case ever performed of hand transplant, in France in the year 1998. Unfortunately a superficial evaluation of the recipient caused the failure of the transplant with the consequent explant of the graft. The peculiarity of hand transplant poses serious doubts on the opportunity of the non life-saving transplant especially for the controversial costs–benefits relationship of such interventions and the lifelong immunodepressant therapy needed. Most important is therefore the clinical and psychological evaluation of the recipients and the correct communication before and after the intervention. We also underline the limits of the “informed” consent due to the lack of scientifical data on the outcome of such transplant, in respect to the Italian legal framework. In addiction we examine the possible psychological difficulties of the patients to adapt to an organ coming from a dead donor due to the high visibility and strong symbolic meaning of the hand. Our conclusion is for a selection of the recipients limited to strongly motivated, psychologically stable and refusing the protesis application patients such as to get a real improvement to their “health” according to WHO definition.

Current Italian statutes concern the safety of organ donors. The law of April 1, 1999 (no. 91), established the fundamental principles for a new structure for organ transplants in Italy and, therefore, for the quality of transplanted organs. The Ministry of Health decree of February 8, 2002, defined organ conditions that preclude the utilization of an organ and identified conditions for suitability of non-optimal organs for some types of transplants or for some recipients. Guidelines from the National Transplant Center establish risk levels, criteria for absolute exclusion, and standard procedures for the evaluation of donor risk and organ suitability for transplant. This article also examines the levels of responsibility of various professionals involved in the harvesting-transplant process.

Expert-opinion elicitation (EOE) is a heuristic process for gathering evidence and data or answering questions on issues/problems of concern. The Delphi method (DM) is the most frequent technique used to obtain structured elicitation of expert opinions. It has been increasingly applied in medicine to produce guidelines and to evaluate the appropriateness of diagnostic procedures. In this study, a DM has been used as structured EOE process to assess the appropriateness and clinical priority of a data set-based informative system in the context of the Liguria-Trento Transplant Network (LTTN) Project, funded by Italian Ministry of Health. The original data set was obtained by using an interdisciplinary pool of regional experts (n = 60). This data set held 1506 items stratified in 21 categories at various surgical phases (preoperative, intraoperative, and postoperative) and transplantation types (liver, kidney, and kidney/pancreas) in adult and pediatric recipients. Some categories included cadaveric donor management, organ allocation, and acute liver failure. In the second DM round, the data set was subjected to a panel of extraregional, independent experts (n = 9) to assess scores ranging from 1 to 9 on each item, based on increasing appropriateness/priority, according to RAND/UCLA Appropriateness Method. The overall agreement between experts was 95.88%, whereas disagreement and uncertainty were 0.13% and 3.98%, respectively. A major uncertainty occurred for the data set concerning the multiorgan cadaveric donor, for liver transplantation, and for kidney transplantation in adult recipients. The use of a structured EOE process may represent an effective strategy to define the appropriateness and prioritization criteria of a large data set in the field of solid organ transplantation.