No metagenomic evidence of tumorigenic viruses in cancers from a selected cohort of immunosuppressed subjects.

The possible existence of yet undiscovered human tumorigenic viruses is still under scrutiny. The development of large-scale sequencing technologies, coupled with bioinformatics techniques for the characterization of metagenomic sequences, have provided an invaluable tool for the detection of unknown, infectious, tumorigenic agents, as demonstrated by several recent studies. However, discoveries of novel viruses possibly associated with tumorigenesis are scarce at best. Here, we apply a rigorous bioinformatics workflow to investigate in depth tumor metagenomes from a small but carefully selected cohort of immunosuppressed patients. While a variegated bacterial microbiome was associated with each tumor, no evidence of the presence of putative oncoviruses was found. These results are consistent with the major findings of several recent papers and suggest that new human tumorigenic viruses are not common even in immunosuppressed populations.

Organ Transplantation From Nonstandard Risk Donors: Midway Between Rigid and Flexible Rules.

In order to bridge the gap between available organs and patients needing transplants, donor selection criteria for donors are increasingly being extended; the possibility of using organs from nonstandard risk donors has been introduced in many countries. This clearly poses considerable ethical issues that should be analyzed and taken into consideration by the competent bodies and institutions. In this article, we illustrate the Italian situation regarding the possibility of using organs from anti-hepatitis C virus (HCV) and HCV RNA-positive donors (anti-HCV+ve) in negative recipients (healthy subjects who have never come into contact with the hepatitis C virus) in light of the availability of new direct-acting antiviral drugs (DAAs) for hepatitis C treatment. We discuss the motivations behind the both favorable opinions of the Ethics Committee of the Italian National Institute of Health (Istituto Superiore di Sanità) and the Italian National Bioethics Committee (Comitato Nazionale per la Bioetica) discussing the main implications from an ethical point of view.

Facial transplantation: from the early trials to ethical and clinical guidelines. Commentary.

Facial transplantation is a complex technique that involves a number of risks. However, although it is not a lifesaving transplant, for individuals in dramatic conditions due to severe facial disfigurements, it constitutes the only possibility of recovering an acceptable quality of life. For this reason, even from an ethical point of view, it is considered an important therapeutic resource, provided it is conducted in rigorously-controlled conditions.

An early start of West Nile virus seasonal transmission: the added value of One Heath surveillance in detecting early circulation and triggering timely response in Italy, June to July 2018.

In Italy, the 2018 West Nile virus transmission season started early with a high number of cases reported. One-Health surveillance, within the Italian West Nile national preparedness and response plan, detected viral circulation 9 days before symptom-onset of the first confirmed human case; triggering timely implementation of blood and transplant safety measures. This is an example of how functional coordination allows health authorities to use early warning triggers from surveillance systems to implement preventive measures.

The "New Charter for Health Care Workers" and the ethics of organ donation and transplantation. Commentary.

Comparison is made between the proposals put forward by the "New Charter for Health Care Workers" in the matter of organ transplants and other models of bioethics. The personalist approach adopted by the New Charter is illustrated and the proposals contained in it are finally placed alongside the reference ethical principles underlying the Italian transplant network: they are found to be fully in agreement.

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

BACKGROUND: Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. METHODS AND FINDINGS: Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. CONCLUSION: The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality.

Physical activity in solid organ transplant recipients: preliminary results of the Italian project.

BACKGROUND/AIMS: The role of physical activity in transplanted patients is often underestimated. We discuss the Italian National Transplant Centre experience, which started in 2008 studying transplanted patients involved in sports activities. The study was then developed through a model of cooperation between surgeons, sports physicians and exercise specialists. METHODS: A multicentre study was realized in 120 transplanted patients of which 60 treated with supervised physical activity (three sessions/week of aerobic and strengthening exercises) and 60 controls. We present the results of the first 26 patients (16 males, 10 females; 47.8 ± 10.0 years; 21 kidney, 5 liver transplanted; time from transplant 2.3 ± 1.4 years) who completed 12 months of supervised physical activity. RESULTS: Data showed an increase of peak aerobic power (t=4.535; P<0.01) and maximum workload (t=4.665; P<0.01) in the incremental cycling test. Maximum strength of knee extensors (t=2.933; P<0.05) and elbow flexors (t=2.450; P<0.05), and the power of lower limb (t=2.303; P<0.05) significantly increases. Health Related Quality of Life showed a significant improvement. Serum creatinine (1.4 ± 0.5 vs 1.3 ± 0.4 mg/dL) and proteinuria (0.10 ± 0.14 vs 0.08 ± 0.08 gr/dL) were stable. CONCLUSION: These preliminary results confirm the positive effects of supervised physical exercise. It can be considered as an input to promote other detailed exercise protocols.

A Bayesian methodology to improve prediction of early graft loss after liver transplantation derived from the liver match study.

BACKGROUND: To generate a robust predictive model of Early (3 months) Graft Loss after liver transplantation, we used a Bayesian approach to combine evidence from a prospective European cohort (Liver-Match) and the United Network for Organ Sharing registry. METHODS: Liver-Match included 1480 consecutive primary liver transplants performed from 2007 to 2009 and the United Network for Organ Sharing a time-matched series of 9740 transplants. There were 173 and 706 Early Graft Loss, respectively. Multivariate analysis identified as significant predictors of Early Graft Loss: donor age, donation after cardiac death, cold ischaemia time, donor body mass index and height, recipient creatinine, bilirubin, disease aetiology, prior upper abdominal surgery and portal thrombosis. RESULTS: A Bayesian Cox model was fitted to Liver-Match data using the United Network for Organ Sharing findings as prior information, allowing to generate an Early Graft Loss-Donor Risk Index and an Early Graft Loss-Recipient Risk Index. A Donor-Recipient Allocation Model, obtained by adding Early Graft Loss-Donor Risk Index to Early Graft Loss-Recipient Risk Index, was then validated in a distinct United Network for Organ Sharing (year 2010) cohort including 2964 transplants. Donor-Recipient Allocation Model updating using the independent Turin Transplant Centre dataset, allowed to predict Early Graft Loss with good accuracy (c-statistic: 0.76). CONCLUSION: Donor-Recipient Allocation Model allows a reliable donor and recipient-based Early Graft Loss prediction. The Bayesian approach permits to adapt the original Donor-Recipient Allocation Model by incorporating evidence from other cohorts, resulting in significantly improved predictive capability.

Skills and requirements of a transplant hepatologist: board certification of the Italian Association for the Study of the Liver (AISF).

Liver transplantation has indeed evolved from an experimental procedure in the early 1980s to the most effective treatment for patients with advanced liver cirrhosis and for selected patients with hepatocellular carcinoma and fulminant hepatic failure. In this new scenario, the transplant hepatologist plays a crucial clinical role, with essential duties and skills to manage the complexities encountered in waitlisted patients or transplant recipients. The clinical tasks of the transplant hepatologist include the management of patients with end-stage liver disease who are candidates for liver transplantation and/or on the waiting list, as well as the care of transplant recipients, in both the in- and outpatient setting. Starting in 2013, the Italian Association of the Study of the Liver, with the endorsement of the National Transplant Centre, will be offering a formal certification process for transplant hepatologists, implemented in accordance to Union Européenne des Médecins Spécialistes-European Board of Transplant Medicine procedures. The Special Article outlines the requirements for board certification of the Italian Association for the Study of the Liver transplant hepatologist.

Incidence and prevalence of cancer in kidney transplantation waiting list patients: an Italian experience.

INTRODUCTION: Evaluation of kidney transplant candidates is based on strict exclusion of major pathologies, such as neoplastic disease. The aim of this study is to evaluate epidemiological and clinical impact of tumor disease in an Italian renal transplant waiting list and to propose a screening schedule for neoplastic detection.
 MATERIALS AND METHODS: We retrospectively observed data of patients enrolled on the Emilia-Romagna kidney transplant waiting list between 1st August 2008 and 31st December 2010, evaluating the different causes of getting out from the list, the histologic type and incidence of cancer and the correlation between cancer onset and clinical features. The ratio of observed to expected cancer numbers (standardized incidence ratio, SIR), was estimated. RESULTS: We observed 2345 patients; 1297 got out from the waiting list; 57 of them (4,4%) got out because the onset of tumor. The overall incidence rate of cancer was 1354.8 (x 100,000 person-year) (1045.9 person-year in patients awaiting for first transplant(FT), 1851.5 person-year in patients awaiting for second transplant(ST)). The overall prevalence of cancer was 2,43% (2.2% in FT, 3.4% in ST) with a SIR of 1.8; In our population the prevalence of cancers related to ESKD was 52.6% with a SIR of 15.8.
 CONCLUSION: Kidney transplant waiting list patients present a higher incidence and prevalence of cancer compared to general population; it could be important to evaluate them for ESKD related malignancies because of their high incidence.

The joint action MODE (Mutual Organ Donation and Transplantation Exchanges): a sound contribution to implementation of health policies in organ donation and transplantation.

BACKGROUND: The main objective of the joint action MODE is the transfer of best-practices in the field of organ donation and transplantation and the creation of positive synergies among participating European (EU) Member States (MS) apt to support authorities in possible decision-making and policy contexts. METHODS: The consortium has chosen to foster the exchange of best-practice through a series of exchange visits followed by the provision of a set of specialized trainings.Each participating MS has presented its strengths and weaknesses through a questionnaire based on the Organ Action Plan. Once the situation was clearer, countries with the strongest program organized and hosted the on-site visits and each country had the opportunity to perform five exchange visits on five selected topics.Specific courses for healthcare staff of organ coordinating and transplantation centres were organized. Based on evaluation of the results of the on-site visits and training needs indicated by the partners, the chosen topics were:• reporting on adverse events and reactions• quality assurance programme of the donation process in Spain• quality assurance of the transplantation process RESULTS AND CONCLUSIONS: The outcome is that within the EU, even among MS with well-developed services, the organ donation and transplantation activity has substantial differences so that all participating countries would benefit from investigating foreign donation and transplant systems. Collaboration at EU level can be beneficial for all systems and the joint action MODE indicated that in some countries the sharing of expertise across the EU Member States has already proved to be useful in starting a virtuous circle in organization and training that would allow to increase organ donor rates and improve overall performance.

Hepatitis B-core antibody positive donors in liver transplantation and their impact on graft survival: evidence from the Liver Match cohort study.

BACKGROUND & AIMS: The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking. METHODS: We evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients. RESULTS: 329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p=0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p=0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p=0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p=0.0002), donor HBcAb positivity (1.56, p=0.0015), recipient HBsAg positivity (0.43, p <0.0001), portal vein thrombosis (1.99, p=0.0156), and DRI (1.41 per unit, p=0.0325). CONCLUSIONS: HBcAb positive donor grafts have better outcomes when transplanted into HBsAg positive than HBsAg negative recipients. These findings suggest that donor HBcAb positivity requires more stringent allocation strategies.

Liver transplantation from hepatitis B surface antigen positive donors: a safe way to expand the donor pool.

BACKGROUND & AIMS: The main limitation of orthotopic liver transplantation (OLT) is the scarcity of available donor organs. A possibility to increase the organ pool is to use grafts from hepatitis B virus surface antigen (HBsAg) positive donors, but few data are currently available in this setting. We assessed the clinical, serovirological, and immunological outcomes of liver transplant from HBsAg positive donors in a single centre study. METHODS: From 2005 to 2009 10 patients underwent OLT from HBsAg positive donors, for HBV-related disease (n=6) or HBV-unrelated disease (n=4). The median follow-up was 42 months (range 12-60). All recipients were HBcAb positive and were given antiviral prophylaxis. RESULTS: Patients transplanted for HBV-related disease never cleared HBsAg. Two HBsAg negative patients never tested positive for HBsAg, whereas the others experienced an HBsAg appearance, followed by spontaneous production of anti-HBs, allowing HBsAg clearance. No patient ever had any sign of HBV hepatitis. HBV replication was effectively controlled by antiviral therapy. The immunologic sub-study showed that a most robust anti-HBV specific T cell response was associated with the control of HBV infection. CONCLUSIONS: OLT from HBsAg positive donors seems to be a safe procedure in the era of highly effective antiviral therapy.

Current situation of donation after circulatory death in European countries.

The aim of the present study was to describe the current situation of donation after circulatory death (DCD) in the Council of Europe, through a dedicated survey. Of 27 participating countries, only 10 confirmed any DCD activity, the highest one being described in Belgium, the Netherlands and the United Kingdom (mainly controlled) and France and Spain (mainly uncontrolled). During 2000-2009, as DCD increased, donation after brain death (DBD) decreased about 20% in the three countries with a predominant controlled DCD activity, while DBD had increased in the majority of European countries. The number of organs recovered and transplanted per DCD increased along time, although it remained substantially lower compared with DBD. During 2000-2008, 5004 organs were transplanted from DCD (4261 kidneys, 505 livers, 157 lungs and 81 pancreas). Short-term outcomes of 2343 kidney recipients from controlled versus 649 from uncontrolled DCD were analyzed: primary non function occurred in 5% vs. 6.4% (P = NS) and delayed graft function in 50.2% vs. 75.7% (P < 0.001). In spite of this, 1 year graft survival was 85.9% vs. 88.9% (P = 0.04), respectively. DCD is increasingly accepted in Europe but still limited to a few countries. Controlled DCD might negatively impact DBD activity. The degree of utilization of DCD is lower compared with DBD. Short-term results of DCD are promising with differences between kidney recipients transplanted from controlled versus uncontrolled DCD, an observation to be further analyzed.

Cord blood stem cell banking: a snapshot of the Italian situation.

BACKGROUND: In Italy, the law does not permit the setting up of private banks to preserve cord blood (CB) stem cells for personal use. However, since 2007 the right to export and preserve them in private laboratories located outside Italy has existed, and an increasing number of women are requesting this collection of umbilical CB at delivery to enable storage of stem cells for autologous use. STUDY DESIGN AND METHODS: Since private banks recruit clients mainly via the Internet, we examined the content of 24 Italian-language websites that offer stem cells storage (from CB or amniotic fluid), to assess what information is available. RESULTS: We found that the majority of private banks give no clear information about the procedures of collection, processing, and banking of CB units and that the standards offered by private CB banks strongly differ in terms of exclusion or acceptance criteria from the public banks. These factors may well influence the overall quality of the CB units stored in private CB banks. Of note, during the period 2007 to 2009, the number collected for autologous use did not create a downward trend on the number of units stored in public CB banks for allogeneic use. CONCLUSION: CB is a valuable community resource but expectant parents should be better informed as to the quality variables necessary for its storage, both by institutions and by professionals. Currently, most of the advertising is insufficient to justify the expense and the hopes pinned on autologous use of CB stem cells.

The critical pathway for deceased donation: reportable uniformity in the approach to deceased donation.

The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification and referral of possible deceased donors.