Perspective on donor-derived infections in Italy.

BACKGROUND: Expected and unexpected donor-derived infections (DDI) are a rare event in solid organ transplant (SOT) recipients but are potentially associated with significant morbidity and mortality. To assure the microbial safety of transplantation, both national guidelines and the current, regional, and local epidemiology of infectious diseases must be considered. METHODS: In the present paper the strategies adopted by the Italian National Center for Transplantation (CNT) since 2003 and their evolution to guarantee the safety of organ transplantation are reported. Starting in 2012 mandatory reporting to the CNT of all adverse reactions was started. The number and type of DDI reported to the CNT are currently being analyzed. RESULTS: The infectious diseases second opinion has written and updated the guidelines on the safety of organs for transplantation and supported the Italian transplant network for the use of organs from donors with suspected or documented potentially transmissible infections. CONCLUSION: A transplant safety network was developed in Italy in 2003 and has been updated according to the evolving knowledge and the changing epidemiology. This is an evolving field, and a continuous update of the recommendation is needed.

Organ donation from patients with a rare disease is often safe: the italian guidelines.

Although a disease is defined as rare when it has a prevalence of less than 1:2000, the overall prevalence of rare diseases in the population is greater than 1%. Among potential organ donors, a similar frequency is observed. To date, guidelines have not been established, and operational decisions have been made empirically, case- by-case, based on the experience and expertise of clinicians. For this reason, the Italian Superior Health Council (CSS) has appointed a working Group to address "patients with a rare disease as potential organ donors," with the aim of devising recommendations for the management of transplant cases in which the donors have a rare disease. This group evaluated 493 diseases (10% of all rare diseases, including over 95% of patients with a rare disease) to deliver a technical report dealing with the suitability of organ donation and transplantation, with a focus on the organs most frequently used, including kidney, liver, heart, lung, and pancreas. This work has made it clear that a rare disease "per se" does not contraindicate organ donation at all. Indeed, in donors affected by a rare disease, almost 80% of the organs are suitable for transplantation, approximately 7% are unsuitable, and approximately 14% are suitable as non-standard with an acceptable risk.

The frequency of rare and monogenic diseases in pediatric organ transplant recipients in Italy.

BACKGROUND: Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. For most of them, clinical symptoms and signs can be observed at birth or childhood. Approximately 80% of all rare diseases have a genetic background and most of them are monogenic conditions. In addition, while the majority of these diseases is still incurable, early diagnosis and specific treatment can improve patients' quality of life. Transplantation is among the therapeutic options and represents the definitive treatment for end-stage organ failure, both in children and adults. The aim of this paper was to analyze, in a large cohort of Italian patients, the main rare genetic diseases that led to organ transplantation, specifically pointing the attention on the pediatric cohort. RESULTS: To the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002-2019 timeframe. Overall, 49,404 recipients were enrolled in the cohort, 5.1% of whom in the pediatric age. For 40,909 (82.8%) transplant recipients, a disease diagnosis was available, of which 38,615 in the adult cohort, while 8,495 patients (17.2%) were undiagnosed. There were 128 disease categories, and of these, 117 were listed in the main rare disease databases. In the pediatric cohort, 2,294 (5.6%) patients had a disease diagnosis: of the 2,126 (92.7%) patients affected by a rare disease, 1,402 (61.1%) presented with a monogenic condition. As expected, the frequencies of pathologies leading to organ failure were different between the pediatric and the adult cohort. Moreover, the pediatric group was characterized, compared to the adult one, by an overall better survival of the graft at ten years after transplant, with the only exception of lung transplants. When comparing survival considering rare vs non-rare diseases or rare and monogenic vs rare non-monogenic conditions, no differences were highlighted for kidney and lung transplants, while rare diseases had a better survival in liver as opposed to heart transplants. CONCLUSIONS: This work represents the first national survey analyzing the main genetic causes and frequencies of rare and/or monogenic diseases leading to organ failure and requiring transplantation both in adults and children.

Rare Disease Patients as Potential Organ Donors.

BACKGROUND: Rare diseases (RDs) are a heterogeneous group of pathologies, which, when present in a donor, with their anatomic or functional deficiencies, may put the recipient at risk. The aim of our work is to analyze the incidence of RDs in our donors to support transplant experts in the evaluation of these organs. METHODS: We retrospectively assessed the incidence of RDs in donors from July 2017 to June 2019, along with the risk attributed, the number of transplanted organs, and the follow-up results of the recipients. RESULTS: Over a 24-month period, we had 19 donors with RDs. Of those, the organs of 4 donors were rejected before the risk assessment, the organs of 4 other donors were deemed an unacceptable risk, the organs of 4 more donors were rejected by transplant centers, and the organs of 7 donors were accepted with 16 organs ultimately transplanted (2 hearts, 3 livers, and 11 kidneys). Three of the recipients died of causes not related to the RDs. Thirteen of the recipients are still alive with a functioning organ with an average follow-up of 9 months. CONCLUSIONS: Although the evaluation of the results is influenced by the limited follow-up period, the use of donors with RDs has proved safe. One of the critical issues encountered in the evaluation process was the impossibility of carrying out genetic and histologic investigations for each organ in urgency. Moreover, the heterogeneity of RDs and the lack of solid literature data require, for the purpose of assessing the level of risk, a specific assessment of individual cases. To overcome these limitations, a group of experts was set up at the Superior Health Council, who drafted a reference document, which allowed for the assessment of the suitability and risk level of donors with the most frequent RDs.

Evaluation on the Use of Italian High-Speed Rail to Support Transportation Network for Transplantation Activities.

BACKGROUND: One of the main activities connected with transplantation is the rapid and timely transportation of patients, medical teams, and human organs from donation to transplantation centers under the compliance of national guidelines and principles of quality, performance, and safety. High-speed transportation on a railway network is becoming relevant both in terms of performance and extensiveness of the service. METHODS AND OBJECTIVES: Our study explores the feasibility of adopting a high-speed rail network for the transportation of those organs with large cold ischemia time and those less influenced by transportation-related perturbations (ie, temperature, speed, vibrations), assessing savings and relative performance improvement. In this study, only kidneys have been considered; the transplantation database has been integrated with the national high-speed railway network and timetables. A function is implemented that allocates to air transportations those records with 1 of the 2 ends situated on islands, remote regions, and abroad, while rail transportation is preferred where constraints on capacity and compliance with cold ischemia time are met. Road transportation is still feasible for those records involving 2 adjacent regions and for intraregional transportation. RESULTS: The opportunity of integrated road-rail transportation in place of air or all-road transportation allows users to lower generalized costs and reduce driven distance for personnel and vehicles allocated to a regional transplantation center's fleet and staff. Savings in fleet and staff usage can serve to improve the performances at the local level. CONCLUSIONS: The knowledge and analysis of transportation alternatives for human organs with less stringent safety and preservation criteria allow a more efficient allocation of resources both at the local and national level-without compromising quality and reliability of the system.