Outcomes of controlled DCDD lung transplantation after thoraco-abdominal vs abdominal normothermic regional perfusion: The Spanish experience.

BACKGROUND: Thoraco-abdominal normothermic regional perfusion (TA-NRP) has emerged as a strategy for evaluating and recovering the heart in controlled donation after the circulatory determination of death (cDCDD). However, its impact on lung grafts remains largely unknown. We aimed to assess the impact of TA-NRP on the outcomes of recipients of cDCDD lungs. METHODS: This is a retrospective, multicenter, nationwide study describing the outcomes of cDCDD lung transplants (LTs) performed in Spain from January 2021 to November 2023. Patients were divided in 2 groups based on the recovery technique: TA-NRP with the simultaneous recovery of the heart vs abdominal NRP (A-NRP) without simultaneous heart recovery. The primary endpoint was the incidence of Primary Graft Dysfunction (PGD) grade 3 at 72 hours. Secondary endpoints included the overall incidence of PGD, days on mechanical ventilation, intensive care unit (ICU) and hospital length of stay, early survival rates, and mid-term outcomes. RESULTS: Two hundred and eighty three cDCDD LTs were performed during the study period, 28 (10%) using TA-NRP and 255 (90%) using A-NRP. No differences were observed in the incidence of PGD grade 3 at 72 hours between the TA-NRP and the A-NRP group (0% vs 7.6%; p = 0.231), though the overall incidence of PGD was significantly lower with TA-NRP (14.3% vs 41.5%; p = 0.005). We found no significant differences between the groups regarding other post-transplant outcome variables. CONCLUSIONS: TA-NRP allows the simultaneous recovery of both the heart and the lungs in the cDCDD scenario with appropriate LT outcomes comparable to those observed with the A-NRP approach.

Reinforcing Global Oversight of Organ Transplantation: Activity and Outcome Monitoring Through the Development of Registries.

Establishing transparency and oversight of organ transplantation by regulatory agencies is of paramount importance to assure ethical, legal, and clinically robust transplantation practices. Registries reporting activity and outcome data of the donor and recipient, including donor source (living or deceased), must be developed for each transplant and should be a mandatory requirement to achieve accreditation to perform transplant surgeries. Collected data for the living organ donor must include the nationality, the nature of their relationship with the recipient, and the complications encountered by living donors that result in prolonged morbidity or mortality. Long-term patient and graft survival must be reported for the recipient with the underlying reasons for mortality or graft loss. To retain the authorization to perform organ transplantation, a facility must ensure that it reports this required information regarding every organ transplant.

Promoting Equitable and Affordable Patient Access to Safe and Effective Innovations in Donation and Transplantation of Substances of Human Origin and Derived Therapies.

Innovation is a hallmark of organ, tissue, and cell transplantation. The development of new treatments derived from these substances of human origin (SoHO) has rapidly evolved in recent years. Despite the great benefits that these innovative therapies could bring to patients, significant difficulties have arisen in making them equitably and widely accessible. Herein, we identify and address 4 challenges to promote innovation in this field in a collaborative, sustainable, and transparent manner and propose some concrete solutions applicable to SoHO-derived treatments, ranging from cell therapies to solid organ transplantation. Regulators, health policymakers, and government officials are recommended to incorporate specific elements into the regulatory frameworks of their respective jurisdictions, although regulatory convergence and equivalent quality and safety standards applicable to SoHO at a global level would be needed. An innovation-driven regulatory environment, respectful with the human origin and in accordance with the altruistic donation of SoHO, should be encouraged to improve the safety, effectiveness, accessibility, and affordability of SoHO and to promote collaboration between countries and between public and private sectors. This overview is the outcome of a working group focused on "Innovation in the donation and clinical application of SoHO" as part of the international Summit "Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight" convened by the Organización Nacional de Trasplantes under the Spanish Presidency of the Council of the European Union in November 2023 and cosponsored by the Council of Europe, the World Health Organization, the Transplantation Society, and the European Society for Organ Transplantation.

Expanding Opportunities for Living Donation: Recommendations From the 2023 Santander Summit to Ensure Donor Protections, Informed Decision Making, and Equitable Access.

A strategic vision toward global convergence in transplantation must encourage and remove barriers to living organ donation and transplantation. Here, we discuss deliberations of a working group of the 2023 Santander Summit charged with formulating recommendations for the safe expansion of living donor kidney transplantation and living donor liver transplantation worldwide. Living donor kidney transplantation has grown to be the preferred treatment for advanced kidney failure. Living donor liver transplantation emerged more recently as a strategy to reduce waitlist mortality, with adoption influenced by cultural factors, regional policies, clinical team experience, and the maturity of regional deceased donor transplant systems. Barriers to living donor transplantation span domains of education, infrastructure, risk assessment/risk communication, and financial burden to donors. Paired donor exchange is a growing option for overcoming incompatibilities to transplantation but is variably used across and within countries. Effectively expanding access to living donor transplantation requires multifaceted strategies, including improved education and outreach, and measures to enhance efficiency, transparency, and shared decision making in donor candidate evaluation. Efforts toward global dissemination and vigilant oversight of best practices and international standards for the assessment, informed consent, approval, and monitoring of living donors are needed. Fostering greater participation in paired exchange requires eliminating disincentives and logistical obstacles for transplant programs and patients, and establishing an ethical and legal framework grounded in World Health Organization Guiding Principles. Sharing of best practices from successful countries and programs to jurisdictions with emerging practices is vital to safely expand the practice of living donation worldwide and bring the field together globally.

Developing and Expanding Deceased Organ Donation to its Maximum Therapeutic Potential: An Actionable Global Challenge From the 2023 Santander Summit.

On November 9 and 10, 2023, the Organización Nacional de Trasplantes (ONT), under the Spanish Presidency of the Council of the European Union, convened in Santander a Global Summit entitled "Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight." This article summarizes two distinct but related challenges elaborated at the Santander Summit by Working Group 2 that must be overcome if we are to develop and expand deceased donation worldwide and achieve the goal of self-sufficiency in organ donation and transplantation. Challenge 1: the need for a unified concept of death based on the permanent cessation of brain function. Working group 2 proposed that challenge 1 requires the global community to work toward a uniform, worldwide definition of human death, conceptually unifying circulatory and neurological criteria of death around the cessation of brain function and accepting that permanent cessation of brain function is a valid criterion to determine death. Challenge 2: reducing disparities in deceased donation and increasing organ utilization through donation after the circulatory determination of death (DCDD). Working group 2 proposed that challenge 2 requires the global community to work toward increasing organ utilization through DCDD, expanding DCDD through in situ normothermic regional perfusion, and expanding DCDD through ex situ machine organ perfusion technology. Recommendations for implementation are described.

Transplantation: A Priority in the Healthcare Agenda.

BACKGROUND: In November 2023, in the context of the Spanish Presidency of the Council of the European Union, the Organization National de Transplante organized a global summit discussing global action in transplantation for the next decade. This article reports the recommendations supporting the need to prioritize transplantation in healthcare systems. METHODS: The working group investigated how transplantation addresses noncommunicable disease mortality, particularly related to kidney and liver disease. They also investigated how transplantation can contribute to the achievement of several of the United Nations Sustainable Development Goals, especially Goal 3 (good health and well-being), Goal 8 (sustained, inclusive, and sustainable economic growth and employment for all), and Goal 13 (combat climate change and its impact). RESULTS: By prioritizing transplantation, the increased availability and accessibility of life-saving organs and tissues to the public will not only lead to saving more lives and improving health outcomes for individual patients but also contribute to the development of a resilient health system in general in that country as a consequence of developing the infrastructure required for transplantation. CONCLUSIONS: The ethical principles associated with transplantation promote the principles of solidarity in society by fostering the donation process and equity in access to therapy. This article aims to advocate for the widespread availability of solid organ, tissue, and cell transplantation for all patients.

The value of organ and tissue biovigilance: a cross-sectional analysis.

Introduction: Biovigilance (BV) systems aim to improve the quality and safety of tissues and organs for transplantation. This study describes the Catalan BV system and analyzes its utility. Methods: It is a retrospective analysis of notifications on serious adverse events (SAEs) and reactions (SARs) since the implementation of the BV system (2008 for tissues and 2016 for organs) until 2020. Variables are presented to describe the most common critical steps of the pathway and complications associated with the quality and safety of tissues and organs. Results: A total of 154 and 125 notifications were reported to the Tissue and the Organ BV systems, respectively. Most SAEs were related to unexpected donor diseases and implemented actions were assured on those deemed preventable. Regarding SARs, donor-transmitted infections and malignancies (only organs) were the most common, followed by graft failure (tissues) and process-related (organs). The incidence of SAEs and SARs related to tissue was 3.44‰ and 0.22‰, respectively. The corresponding figures for organs were 31.48‰ and 8.8‰, respectively. Discussion: The analysis of the notifications to the Catalan BV systems has provided useful information about existing risks associated with the quality and safety of tissues and organs, and enabled the implementation of actions targeted to diminish risks and mitigate damage.

Normothermic Regional Perfusion in Controlled Donation After the Circulatory Determination of Death: Understanding Where the Benefit Lies.

Controlled donation after the circulatory determination of death (cDCDD) has emerged as a strategy to increase the availability of organs for clinical use. Traditionally, organs from cDCDD donors have been subject to standard rapid recovery (SRR) with poor posttransplant outcomes of abdominal organs, particularly the liver, and limited organ utilization. Normothermic regional perfusion (NRP), based on the use of extracorporeal membrane oxygenation devices, consists of the in situ perfusion of organs that will be subject to transplantation with oxygenated blood under normothermic conditions after the declaration of death and before organ recovery. NRP is a potential solution to address the limitations of traditional recovery methods. It has become normal practice in several European countries and has been recently introduced in the United States. The increased use of NRP in cDCDD has occurred as a result of a growing body of evidence on its association with improved posttransplant outcomes and organ utilization compared with SRR. However, the expansion of NRP is precluded by obstacles of an organizational, legal, and ethical nature. This article details the technique of both abdominal and thoracoabdominal NRP. Based on the available evidence, it describes its benefits in terms of posttransplant outcomes of abdominal and thoracic organs and organ utilization. It addresses cost-effectiveness aspects of NRP, as well as logistical and ethical obstacles that limit the implementation of this innovative preservation strategy.

Organ Donation and Transplantation Registries Across the Globe: A Review of the Current State.

BACKGROUND: The current landscape of organ donation and transplantation (ODT) registries is not well established. This narrative review sought to identify and characterize the coverage, structure, and data capture of ODT registries globally. METHODS: We conducted a literature search using Ovid Medline and web searches to identify ODT registries from 2000 to 2023. A list of ODT registries was compiled based on publications of registry design, studies, and reports. Extracted data elements included operational features of registries and the types of donor and recipient data captured. RESULTS: We identified 129 registries encompassing patients from all continents except Antarctica. Most registries were active, received funding from government or professional societies, were national in scope, included both adult and pediatric patients, and reported patient-level data. Registries included kidney (n = 99), pancreas (n = 32), liver (n = 44), heart (n = 35), lung (n = 30), intestine (n = 15), and islet cell (n = 5) transplants. Most registries captured donor data (including living versus deceased) and recipient features (including demographics, cause of organ failure, and posttransplant outcomes) but there was underreporting of other domains (eg, donor comorbidities, deceased donor referral rates, waitlist statistics). CONCLUSIONS: This review highlights existing ODT registries globally and serves as a call for increased visibility and transparency in data management and reporting practices. We propose that standards for ODT registries, a common data model, and technical platforms for collaboration, will enable a high-functioning global ODT system responsive to the needs of transplant candidates, recipients, and donors.

Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study.

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.

Transplantation in the Context of Migration and Refugees: A Summary of the DICG and TTS Ethics Committee Workshop, Buenos Aires, Argentina, September 2022.

Global conflicts and humanitarian crises have resulted in an unprecedented number of refugees and migrants. This challenges the limited resources of health care systems and jeopardizes the availability of transplant care for these deserving migrants and refugees. This was the basis for a workshop held during the Congress of the Transplantation Society (Buenos Aires, 2022). We elaborate on the proceedings of the workshop entitled "Transplantation in the Context of Migration and Refugees," organized by the Ethics Committee of The Transplantation Society and Declaration of Istanbul Custodian Group. Transplant providers from around the world shared strategies of how each region has responded to providing access to care for refugees and migrants in need of transplant services. The potential exploitation of this vulnerable group leading to illicit organ removal was addressed for each region. The Transplantation Society, Declaration of Istanbul Custodian Group, and global transplant community should continue to focus on the status of refugees and migrants and collaborate on strategies to provide access to transplant care for this deserving population. Global cooperation will be essential to provide vigilant oversight to prevent exploitation of this vulnerable population.

Improving the Access of Highly Sensitized Patients to Kidney Transplantation From Deceased Donors: The Spanish PATHI Program With Allocation Based on the Virtual Crossmatch.

BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection. RESULTS: One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies. CONCLUSIONS: A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.

Maintaining the permanence principle of death during normothermic regional perfusion in controlled donation after the circulatory determination of death: Results of a prospective clinical study.

One concern about the use of normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is that the brain may be perfused. We aimed to demonstrate that certain technical maneuvers preclude such brain perfusion. A nonrandomized trial was performed on cDCD donors. In abdominal normothermic regional perfusion (A-NRP), the thoracic aorta was blocked with an intra-aortic occlusion balloon. In thoracoabdominal normothermic regional perfusion (TA-NRP), the arch vessels were clamped and the cephalad ends vented to the atmosphere. The mean intracranial arterial blood pressure (ICBP) was invasively measured at the circle of Willis. Ten cDCD donors subject to A-NRP or TA-NRP were included. Mean ICBP and mean blood pressure at the thoracic and the abdominal aorta during the circulatory arrest were 17 (standard deviation [SD], 3), 17 (SD, 3), and 18 (SD, 4) mmHg, respectively. When A-NRP started, pressure at the abdominal aorta increased to 50 (SD, 13) mmHg, while the ICBP remained unchanged. When TA-NRP was initiated, thoracic aorta pressure increased to 71 (SD, 18) mmHg, but the ICBP remained unmodified. Recorded values of ICBP during NRP were 10 mmHg. In conclusion, appropriate technical measures applied during NRP preclude perfusion of the brain in cDCD. This study might help to expand NRP and increase the number of organs available for transplantation.

Review of the allocation criteria for heart transplant in Spain in 2023. SEC-Heart Failure Association/ONT/SECCE consensus document.

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain.

Approaching the Families of Potential Deceased Organ Donors: An Overview of Regulations and Practices in Council of Europe Member States.

The primary aim of this study was to describe regulations and practices concerning the family approach to discuss donation, specifically after the neurological determination of death, one of the most challenging steps in the donation pathway. A secondary objective was to assess the impact of legislation on consent rates for organ donation. The Council of Europe surveyed 39 member states about national regulations, practices, and consent rates; 34 replied. Opt-out legislation is present in 19, opt-in in 9 and a mixed system in six countries. An opt-out register is kept by 24 countries and an opt-in register by 18 countries, some keeping both. The mean consent rate was 81.2% of all family approaches. Most countries regulate how death using neurological criteria is confirmed (85.3%), while regulation of other aspects of the deceased donation pathway varies: the timing of informing the family about brain death (47.1%) and organ donation (58.8%), the profile of professional who discusses both topics with the family (52.9% and 64.7%, respectively) and the withdrawal of treatment after brain death (47.1%). We also noted a mismatch between what regulations state and what is done in practice in most countries. We suggest possible reasons for this disparity.