Utilization of livers donated after circulatory death for transplantation - An international comparison.

BACKGROUND & AIMS: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. METHODS: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. RESULTS: A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS: Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. IMPACT AND IMPLICATIONS: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.

Importance and Potential of European Cross-Border Deceased Donor Organ Allocation Through FOEDUS-EOEO Platform.

The FOEDUS-EOEO platform was relaunched in 2015 to allocate deceased donor organs across European borders when there are no suitable recipients in the donor's country. We analyzed organ offers from 01.06.2015-31.12.2021 and present the number of offers and transplants, and utilization as percentage of transplanted organs. 1,483 organs were offered, 287 were transplanted (19.4% utilization). Yearly number of offers and transplants increased from 2017 to 2021, while utilization stabilized after 2018. Utilization was highest for organs offered by Slovakia (47.2%), followed for organs offered by Lithuania, France, Greece, and Czechia (19.3%-22.9%). The most frequently offered organ was the heart (n = 405; 27.3%), followed by the lungs (n = 369; 24.9%) and the liver (n = 345; 23.3%). Utilization differed significantly by organ type (highest for liver, 35.7%; followed by heart, 18.8%; and kidney, 18.3%) and by donor age (highest for 1 to 5 year-old donors (25.0%)). FOEDUS-EOEO allowed for many European patients receiving a long-awaited transplant, especially for very young pediatric patients waiting for a liver, a heart, or a kidney. The increasing number of participating countries has increased both the number of offered organs and, to a lesser extent, the number of transplanted organs.

Deceased organ donation activity and efficiency in Switzerland between 2008 and 2017: achievements and future challenges.

BACKGROUND: Various actions have been taken during the last decade to increase the number of organs from deceased donors available for transplantation in Switzerland. This study provides an overview on key figures of the Swiss deceased organ donation and transplant activity between 2008 and 2017. In addition, it puts the evolution of the Swiss donation program's efficiency in relation to the situation in the neighboring countries. METHODS: This study is an analysis of prospective registry data, covering the period from 1 January 2008 to 31 December 2017. It includes all actual deceased organ donors (ADD) in Switzerland. Donor data were extracted from the Swiss Organ Allocation System. The "donor conversion index" (DCI) methodology and data was used for the comparison of donation program efficiency in Switzerland, Germany, Austria, Italy and France. RESULTS: During the study period there were 1116 ADD in Switzerland. The number of ADD per year increased from 91 in 2008 to 145 in 2017 (+ 59%). The reintroduction of the donation after cardiocirculatory death (DCD) program in 2011 resulted in the growth of annual percentages of DCD donors, reaching a maximum of 27% in 2017. The total number of organs transplanted from ADD was 3763 (3.4 ± 1.5 transplants per donor on average). Of these, 48% were kidneys (n = 1814), 24% livers (n = 903), 12% lungs (n = 445), 9% hearts (n = 352) and 7% pancreata or pancreatic islets (n = 249). The donation program efficiency assessment showed an increase of the Swiss DCI from 1.6% in 2008 to 2.7% in 2017 (+ 69%). The most prominent efficiency growth was observed between 2012 and 2017. Even though Swiss donation efficiency increased during the study period, it remained below the DCI of the French and Austrian donation programs. CONCLUSION: Swiss donation activity and efficiency grew during the last decade. The increased donation efficiency suggests that measures implemented so far were effective. The lower efficiency of the Swiss donation program, compared to the French and Austrian programs, may likely be explained by the lower consent rate in Switzerland. This issue should be addressed in order to achieve the goal of more organs available for transplantation.

Clinical prediction model for prognosis in kidney transplant recipients (KIDMO): study protocol.

BACKGROUND: Many potential prognostic factors for predicting kidney transplantation outcomes have been identified. However, in Switzerland, no widely accepted prognostic model or risk score for transplantation outcomes is being routinely used in clinical practice yet. We aim to develop three prediction models for the prognosis of graft survival, quality of life, and graft function following transplantation in Switzerland. METHODS: The clinical kidney prediction models (KIDMO) are developed with data from a national multi-center cohort study (Swiss Transplant Cohort Study; STCS) and the Swiss Organ Allocation System (SOAS). The primary outcome is the kidney graft survival (with death of recipient as competing risk); the secondary outcomes are the quality of life (patient-reported health status) at 12 months and estimated glomerular filtration rate (eGFR) slope. Organ donor, transplantation, and recipient-related clinical information will be used as predictors at the time of organ allocation. We will use a Fine & Gray subdistribution model and linear mixed-effects models for the primary and the two secondary outcomes, respectively. Model optimism, calibration, discrimination, and heterogeneity between transplant centres will be assessed using bootstrapping, internal-external cross-validation, and methods from meta-analysis. DISCUSSION: Thorough evaluation of the existing risk scores for the kidney graft survival or patient-reported outcomes has been lacking in the Swiss transplant setting. In order to be useful in clinical practice, a prognostic score needs to be valid, reliable, clinically relevant, and preferably integrated into the decision-making process to improve long-term patient outcomes and support informed decisions for clinicians and their patients. The state-of-the-art methodology by taking into account competing risks and variable selection using expert knowledge is applied to data from a nationwide prospective multi-center cohort study. Ideally, healthcare providers together with patients can predetermine the risk they are willing to accept from a deceased-donor kidney, with graft survival, quality of life, and graft function estimates available for their consideration. STUDY REGISTRATION: Open Science Framework ID: z6mvj.

Screening for mitochondrial function before use-routine liver assessment during hypothermic oxygenated perfusion impacts liver utilization.

BACKGROUND: To report on a concept of liver assessment during ex situ hypothermic oxygenated perfusion (HOPE) and its significant impact on liver utilization. METHODS: An analysis of prospectively collected data on donation after circulatory death (DCD) livers, treated by HOPE at our institution, during a 11-year period between January 2012 and December 2022. FINDINGS: Four hundred and fifteen DCD Maastricht III livers were offered during the study period in Switzerland, resulting in 249 liver transplants. Of those, we performed 158 DCD III liver transplants at our institution, with 1-year patient survival and death censored graft survival (death with functioning graft) of 87 and 89%, respectively, thus comparable to benchmark graft survivals of ideal DBD and DCD liver transplants (89% and 86%). Correspondingly, graft loss for primary non-function or cholangiopathy was overall low, i.e., 7/158 (4.4%) and 11/158 (6.9%), despite more than 82% of DCD liver grafts ranked high (6-10 points) or futile risk (>10 points) according to the UK-DCD score. Consistently, death censored graft survival was not different between low-, high-risk or futile DCD III livers. The key behind these achievements was the careful development and implementation of a routine perfusate assessment of mitochondrial biomarkers for injury and function, i.e., release of flavin mononucleotide from complex I, perfusate NADH, and mitochondrial CO2 production during HOPE, allowing a more objective interpretation of liver quality on a subcellular level, compared to donor derived data. INTERPRETATION: HOPE after cold storage is a highly suitable and easy to perform perfusion approach, which allows reliable liver graft assessment, enabling surgeons to make a fact based decision on whether or not to implant the organ. HOPE-treatment should be combined with viability assessment particularly when used for high-risk organs, including DCD livers or organs with relevant steatosis. FUNDING: This study was supported by the Swiss National Foundation (SNF) grant 320030_189055/1 to PD.

Organ donation after circulatory death as compared with organ donation after brain death in Switzerland - an observational study.

AIMS OF THE STUDY: Organ donation after circulatory death (DCD) was reintroduced in Switzerland in 2011 and accounts for a third of deceased organ donors today. Controversy persists if DCD transplants are of similar quality to transplants following donation after brain death (DBD), mainly due to warm ischaemia time DCD organs are exposed to. We compared DCD with DBD in Switzerland. METHODS: Data on deceased adults who were referred to and approved for organ donation from 1 September 2011 to 31 December 2019 were retrospectively analysed (217 DCD, 840 DBD donors). We compared DCD and DBD donor/organ characteristics, transplant rates of lungs, liver, kidneys, and pancreas, and early liver and kidney graft function in the recipient. The effect of DCD/DBD on transplant rates (organ transplanted or not) and 72-hour recipient graft function (moderate/good vs delayed graft function / organ loss) was analysed using multivariable logistic regression. Among utilised DCD donors, we analysed the effect of functional warm ischaemia time (FWIT) and donor age on 72-hour post-transplant liver and kidney graft function, also using multivariable logistic regression. RESULTS: DCD donors were more often male (64.5% vs 56.8% p = 0.039), presented with heart disease (36.4% vs 25.5%, p <0.001), were resuscitated before hospital admission (41.9% vs 30.7%, p = 0.006), and died from anoxia (41.9% vs 23.9%). Kidney function before transplantation was comparable, lung, liver and pancreas function were poorer in DCD than DBD. Eighty-one and 91% of approved DCD and DBD donors were utilised (p <0.001). Median FWIT in DCD was 29 minutes (interquartile range 25-35). DCD transplant rates ranged from 4% (pancreas) to 73% (left kidney) and were all lower compared with DBD. Seventy-two-hour liver graft function was comparable between DCD and DBD (94.2% vs 96.6% moderate/good, p = 0.199). DCD kidney transplants showed increased risk of delayed graft function or early organ loss (odds ratios 8.32 and 5.05; 95% confidence intervals CI 5.28-13.28 and 3.22-7.95; both p <0.001, for left and right kidney transplants, respectively). No negative effect of prolonged FWIT or higher donor age was detected. CONCLUSION: Despite less favourable donor/organ characteristics compared with donation after brain death, donation after circulatory death donors are increasingly referred and today provide an important source for scarce transplants in Switzerland. We identified a higher risk for delayed graft function or early organ loss for DCD kidney transplants, but not for DCD liver transplants. When carefully selected and allowed for other risk factors in organ allocation, prolonged functional warm ischaemia time or higher age in donation after circulatory death does not seem to be associated with impaired graft function early after transplantation.

Impact of cardiopulmonary resuscitation on organ donation in Switzerland.

AIMS OF THE STUDY: The lack of suitable donor organs limits the number of solid organ transplants. Patients who underwent cardiopulmonary resuscitation (CPR) after cardiac arrest may represent a sizeable subgroup of deceased organ donors, as they often progress to brain death or have life-sustaining therapy withdrawn. We aimed to quantify deceased organ donation after CPR in Switzerland for the first time by analysing the characteristics of potential and utilised organ donors after CPR. METHODS: Data on deceased adult and paediatric patients who were reported to and approved by Swisstransplant for organ donation were analysed, including both donation after brain death (DBD) and donation after controlled cardiocirculatory death (cDCD) from 2016 to 2018. We analysed baseline characteristics of potential donors who underwent CPR in the context of their hospitalisation, as compared with donors without prior CPR. Considering the varying characteristics between these two donor groups, we assessed the effect of CPR on different allocation outcomes (donor and organ utilisation, organ yield per utilised donor) using multivariable regression. Additionally, we present selected CPR circumstances and compared different subgroups of CPR donors according to duration of CPR and duration of no-flow time. RESULTS: Of the 461 deceased potential organ donors included in the analysis, 173 (37.5%) underwent CPR. CPR donors were, on average, younger (median age 53 vs 62, p <0.001), had different causes of death (p <0.001), and were more often of the cDCD type (30.1% vs 18.4%, p = 0.004) as compared with non-CPR donors. Of the 173 CPR donors, 152 (87.9%) could be utilised (minimum one organ transplanted), and in the multivariable analysis, utilisation rate was higher in the CPR donor group than in the non-CPR donor group (odds ratio 3.3, 95% confidence interval 1.1–11.5; p = 0.046). Organ specific utilisation of heart, liver, and kidney, and total organ yield per donor, did not differ significantly between CPR and non-CPR donors. CONCLUSION: Our study reveals that a substantial proprotion of deceased organ donors in Switzerland underwent CPR in context of their hospitalisation. CPR donors are different from non-CPR donors with respect to age, cause of death and donation type. However, when carefully selected according to their haemodynamic condition, CPR donors are comparable to non-CPR donors in terms of donor and organ utilisation, as well as the average organ yield. Thus, all patients who are resuscitated from cardiac arrest but who subsequently progress to death should be evaluated for organ donation. How CPR donors compare with non-CPR donors regarding transplant outcomes should be studied further.

In the eye of the hurricane: the Swiss COVID-19 pandemic stepwise shutdown approach in organ donation and transplantation.

The Swiss stepwise shutdown approach in organ donation and transplantation helped to maintain a limited national organ procurement and vital organ transplant activity, avoiding a complete nationwide shutdown of organ donation and transplant activity. .

Extended-criteria donors in lung transplantation in Switzerland: an evaluation of two adapted lung donor scores.

AIM: Various scoring systems aim to assess the quality of organs donated for transplantation on the basis of patient characteristics, clinical examination and laboratory results. How well such scoring systems reflect the practice in lung transplantation in Switzerland has never been studied. Therefore, we evaluated two scoring systems for their ability to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. METHODS: We retrospectively analysed patient data of adult deceased organ donors in Switzerland between 1 July 2007 and 30 June 2014. Included were all donors from whom at least one organ was transplanted. We evaluated two lung donor quality scores, the multicentre-developed Eurotransplant donor score (EDS), and the single-centre-developed Zurich donor score (ZDS). Both scores were slightly adapted to be applicable to Swiss deceased organ donor data. We evaluated whether these scores can predict whether lungs were transplanted or refused by Swiss transplant centres, using univariate logistic regression. We further assessed their discriminative power by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 635 donors included in our analysis, 295 (46%) were accepted as lung donors by one of the two lung transplant centres in Switzerland. Our analysis showed that both scores can predict whether or not a donor lung is likely to be accepted for transplantation in Switzerland. As the score value of a donor increases, the odds of the lung being transplanted significantly decreases (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.51-0.65 for the adapted EDS; OR 0.35, 95% CI 0.28-0.43 for the adapted ZDS). This effect is slightly more pronounced in the adapted ZDS than in the adapted EDS. The discriminatory power of the scores from the AUC was 0.719 (95% CI 0.680-0.758) for the adapted EDS, and 0.723 (95% CI 0.681-0.760) for the adapted ZDS, which for both was deemed fair discrimination. CONCLUSIONS: Both scoring systems are able to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. As an alternative to adapting an established scoring system, a national lung quality score could be derived de novo. This could be based on a logistic regression analysis including the most relevant donor characteristics. However, such a new score would need to be validated on an independent sample and ideally tested for its predictive value in terms of post-transplantation outcome.

Evolution of Deceased Organ Donation Activity Versus Efficiency Over a 15-year Period: An International Comparison.

BACKGROUND: The donation rate (DR) per million population is not ideal for an efficiency comparison of national deceased organ donation programs. The DR does not account for variabilities in the potential for deceased donation which mainly depends on fatalities from causes leading to brain death. In this study, the donation activity was put into relation to the mortality from selected causes. Based on that metric, this study assesses the efficiency of different donation programs. METHODS: This is a retrospective analysis of 2001 to 2015 deceased organ donation and mortality registry data. Included are 27 Council of Europe countries, as well as the United States. A donor conversion index (DCI) was calculated for assessing donation program efficiency over time and in international comparisons. RESULTS: According to the DCI and of the countries included in the study, Spain, France, and the United States had the most efficient donation programs in 2015. Even though mortality from the selected causes decreased in most countries during the study period, differences in international comparisons persist. This indicates that the potential for deceased organ donation and its conversion into actual donation is far from being similar internationally. CONCLUSIONS: Compared with the DR, the DCI takes into account the potential for deceased organ donation, and therefore is a more accurate metric of performance. National donation programs could optimize performance by identifying the areas where most potential is lost, and by implementing measures to tackle these issues.

Dynamic Measurement of Tumor Vascular Permeability and Perfusion using a Hybrid System for Simultaneous Magnetic Resonance and Fluorescence Imaging.

PURPOSE: Assessing tumor vascular features including permeability and perfusion is essential for diagnostic and therapeutic purposes. The aim of this study was to compare fluorescence and magnetic resonance imaging (MRI)-based vascular readouts in subcutaneously implanted tumors in mice by simultaneous dynamic measurement of tracer uptake using a hybrid fluorescence molecular tomography (FMT)/MRI system. PROCEDURE: Vascular permeability was measured using a mixture of extravascular imaging agents, GdDOTA and the dye Cy5.5, and perfusion using a mixture of intravascular agents, Endorem and a fluorescent probe (Angiosense). Dynamic fluorescence reflectance imaging (dFRI) was integrated into the hybrid system for high temporal resolution. RESULTS: Excellent correspondence between uptake curves of Cy5.5/GdDOTA and Endorem/Angiosense has been found with correlation coefficients R > 0.98. The two modalities revealed good agreement regarding permeability coefficients and centers-of-gravity of the imaging agent distribution. CONCLUSION: The FMT/dFRI protocol presented is able to accurately map physiological processes and poses an attractive alternative to MRI for characterizing tumor neoangiogenesis.