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.

Data collection, analysis and quality control are fundamental aspects of any program or process. In order to draw scientifically valid and rigorous conclusions, it is imperative to put in place procedures that ensure quality data in terms of completeness, appropriateness, and reliability. Likewise, a fundamental role is played by quality controls, error prevention processes, traceability, and actions to improve performance. The data collection methodology and the quality control processes are essential for guaranteeing scientific quality. Data can be collected and processed at any level, even single transplant centers can create their own database to process statistics and scientific studies, but the reliability of data is only accomplished with large numbers thus requiring sharing information. Through the awareness that nobody really owns the data, the validity of a scientific study can be guaranteed.

The use of extended criteria donors (ECD) became widespread due to the shortage of organs available for transplantation. The use of ex-situ machine perfusion (MP) after organ retrieval is strongly recommended in this field, to improve clinical outcomes following transplantation. Adopting MP strategies requires huge financial resources that can only be optimized if MP is introduced more widely, with evidence of significant benefits. Objective. 1) to evaluate the evolution of MP use in Italy over the time and its potential impact on the organ pool available for transplantation; 2) to measure the quality of the MP program. Methods. The “Methods of organ perfusion in transplantation” was adopted in 2017, including recommendations for implementing a national program; a database was set up to collect the data of ex-situ perfused organs, procured from DCD or DBD donors. Results. The ex-situ MP program started slowly in Italy, but it developed over time thanks to the good results obtained. Most Italian transplant centers currently participate in the program, and most perfused organs (60-95%, depending on the type of organ) undergo transplantation, increasing the use of organs that would otherwise have been discarded. Conclusions. The Italian experience shows the effectiveness of using MP for organ preservation and the potential positive effect of this activity on the health care system. National data recording needs to be better structured to reinforce this evidence so that the competent authority can support transplant centers in obtaining funds or reimbursements from health care institutions.

Purpose In the Italian lung transplant (LTX) allocation system, patients receive national priority (NP) only if on ECMO or mechanical ventilation (MV). We hypothesized that LAS could contribute to identify patients with increased waitlist mortality and who could benefit from NP. Methods We retrospectively reviewed the outcome and calculated the entry list LAS of patients who were listed for LTX in Italy between 2015 and 2021 either with or without NP. Probability of LTX was estimated using a competitive risk survival analysis. Postoperative 1-yr and 3-yr outcome was calculated with the Kaplan-Meier model. Results 1031 patients listed for LTX in the study period (85.3%) had complete data for analysis. 119 (11.5%) were listed with NP and 912 without. Mean LAS was 38.6 in the standard listing group and 50.1 in the NP group (p=0.0001). After stratifying for the value of LAS at the time of listing, more patients (43%) were listed with NP in the 4thquartile (LAS>50) group. The probability of LTX was lower in patients in the LAS>50 quartile who were not placed on NP. The same group had the highest risk of death on the list (20.73%, p<0.001 compared to all other groups). Post-transplant outcomes were available for 481 patients out of 548 who received LTX in the study period (92.5%). 66 patients (13.7%) were transplanted after being on NP. 1-yr KM survival was less favorable in NP patients compared to non-NP patients, although not reaching statistical significance (p=0.08). In the >50 LAS quartile, 36.7% of patients were transplanted on the NP list, and had a worse KM survival compared to other quartiles (p=0.02). Conclusion In a non-LAS allocation context, retrospective analysis shows that high-LAS patients (>50) who do not receive NP allocation display high mortality on the waiting list. NP patients (ECMO/MV) have the worse postoperative outcomes. High LAS (>50) may earlier identify patients who are at higher risk of pre-transplant mortality and need NP, preventing the high postoperative mortality of LTX after ECMO/MV. In the Italian lung transplant (LTX) allocation system, patients receive national priority (NP) only if on ECMO or mechanical ventilation (MV). We hypothesized that LAS could contribute to identify patients with increased waitlist mortality and who could benefit from NP. We retrospectively reviewed the outcome and calculated the entry list LAS of patients who were listed for LTX in Italy between 2015 and 2021 either with or without NP. Probability of LTX was estimated using a competitive risk survival analysis. Postoperative 1-yr and 3-yr outcome was calculated with the Kaplan-Meier model. 1031 patients listed for LTX in the study period (85.3%) had complete data for analysis. 119 (11.5%) were listed with NP and 912 without. Mean LAS was 38.6 in the standard listing group and 50.1 in the NP group (p=0.0001). After stratifying for the value of LAS at the time of listing, more patients (43%) were listed with NP in the 4thquartile (LAS>50) group. The probability of LTX was lower in patients in the LAS>50 quartile who were not placed on NP. The same group had the highest risk of death on the list (20.73%, p<0.001 compared to all other groups). Post-transplant outcomes were available for 481 patients out of 548 who received LTX in the study period (92.5%). 66 patients (13.7%) were transplanted after being on NP. 1-yr KM survival was less favorable in NP patients compared to non-NP patients, although not reaching statistical significance (p=0.08). In the >50 LAS quartile, 36.7% of patients were transplanted on the NP list, and had a worse KM survival compared to other quartiles (p=0.02). In a non-LAS allocation context, retrospective analysis shows that high-LAS patients (>50) who do not receive NP allocation display high mortality on the waiting list. NP patients (ECMO/MV) have the worse postoperative outcomes. High LAS (>50) may earlier identify patients who are at higher risk of pre-transplant mortality and need NP, preventing the high postoperative mortality of LTX after ECMO/MV.

SARS‑CoV‑2 mostly affects the respiratory system with clinical patterns ranging from the common cold to fatal pneumonia. During the first wave of the COVID-19 pandemic, owing to the high number of patients who were infected with SARS‑CoV‑2 and subsequently recovered, it has been shown that some patients with post–COVID-19 terminal respiratory failure need lung transplantation for survival. There is increasing evidence coming from worldwide observations that this procedure can be performed successfully in post–COVID-19 patients. However, owing to the scarcity of organs, there is a need to define the safety and efficacy of lung transplant for post–COVID-19 patients as compared to patients waiting for a lung transplant for other pre-existing conditions, in order to ensure that sound ethical criteria are applied in organ allocation. The Milan's Policlinic Lung Transplant Surgery Unit, with the revision of the National Second Opinion for Infectious Diseases and the contribution of the Italian Lung Transplant Centres and the Italian National Transplant Centre, set up a pivotal observational protocol for the lung transplant of patients infected and successively turned negative for SARS‑CoV‑2, albeit with lung consequences such as acute respiratory distress syndrome or some chronic interstitial lung disease.The protocol was revised and approved by the Italian National Institute of Health Ethics Committee. Description of the protocol and some ethical considerations are reported in this article.

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.

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.

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.

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.

Background. The national protocol for the handling of high-urgency (HU) liver organ procurement for transplant is administered by the Italian National Transplant Center. In recent years, we have witnessed a change in requests to access the program. We have therefore evaluated their temporal trend, the need to change the access criteria, the percentage of transplants performed, the time of request satisfaction, and the follow-up. Methods. We analyzed all the liver requests for the HU program received during the 4-year period of 2014 to 2017 for adult recipients (>= 18 years of age): all the variables linked to the recipient or to the donor and the organ transplants are registered in the Informative Transplant System as established by the law 91/99. In addition, intention to treat (ITT) survival rates were compared among 4 different groups: (1) patients on standard waiting lists vs (2) patients on urgency waiting lists, and (3) patients with a history of transplant in urgency vs (4) patients with a history of transplant not in urgency. Results. Out of the 370 requests included in the study, 291 (78.7%) were satisfied with liver transplantation. Seventy-nine requests (21.3%) have not been processed, but if we consider only the real failures, this percentage falls to 13.1% and the percentage of satisfied requests rises to 86.9%. The average waiting period for liver transplantation (LT) is 1.7 days and most requests (74%) are met in less than 24 hours, if we consider the hours between the registration of the request and the donor reporting . The percentage of late retransplantations is 2.1%. The clinical indication for HU-LT that appears to improve over time is hepatic artery thrombosis (82.5%). The overall 1-year patient survival is 68.3%. The overall 1-year graft survival, performed on all the patients, is 89% and all the indications for HU-LT appear to go well over time with an average survival rate greater than 85%. Conclusions. The indications for HU-LT are changing according to the changes in the hepatologic field in recent years. The centralized management of requests has proven to be successful in optimizing responses. Urgent LT is confirmed to be lifesaving in its timeliness.