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The reporting of serious adverse events (SAE) and serious adverse reactions (SAR) is an essential part of an effective vigilance and surveillance system (V&S) in organ donation and transplantation. All SAE and SAR reported to the German organ procurement organization (DSO) between 2016 and 2022 were analyzed. In case of a possible transmission of a disease to one or more recipients, an assessment of imputability was done according to the grading system of the US Disease Transmission Advisory Committee (DTAC). 543 SAE and SAR cases were reported to the DSO and analyzed in detail. 53 of the 543 reports (9.8%) were proven or probable (P/P) transmissions of infectious diseases, malignancies or other diseases to 75 recipients. Infections were the most frequently reported P/P disease transmission occurrences (30/53, 57%). In case of disease transmission, the mortality of the recipients was high (17/75, 23%), especially when a malignant disease was transmitted (11/22, 50 %). Donor-Derived disease transmission is a rare event (53/8,519; 0.6 %), but when it occurs can lead to significant morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: In order to achieve short ischemia times between organ donation and transplantation, regional organ allocation has been assigned priority in the development of allocation rules for kidney transplantation. It is unclear whether this leads to differences in regional waiting times in Germany. Methods: A retrospective cohort study over a 24-month observation period was conducted, including all patients who received a kidney-only graft allocated via the standard Eurotransplant Kidney Allocation System (ETKAS) (n = 1487) or the Eurotransplant Senior Program (ESP) (n = 566). Multiple linear regression analyses were performed to investigate differences in waiting times across the regions (ETKAS) or subregions (ESP) as defined by the German Organ Procurement Organization (DSO). Associations between the number of regionally procured kidneys (n = 1444) and regional waiting times were investigated. Results: In ETKAS, the median waiting time was 8.9 years (interquartile range [IQR] 6.7-10.6); in ESP, it was 3.9 (2.4-5.3) years. Compared with the reference region with the shortest waiting time, waiting times in other regions were 0.6 to 1.7 years longer in ETKAS and 1.3 to 4.4 years longer in ESP. The ratio of the number of patients on the waiting list for a particular region to the number of organs donated in that region was associated with the waiting time in ETKAS (R2 = 0.70). In ESP, this association was markedly less pronounced (R2 = 0.45). Conclusion: In Germany, waiting times depend strongly on the region where a patient is listed for kidney transplantation, especially in ESP. These findings call the current allocation algorithms into question and imply a need for suitable modification. [ABSTRACT FROM AUTHOR]

Background: The annual number of post-mortem organ donations in Germany has declined by more than 30% since 2010. The causes of this development have not yet been adequately determined. Methods: All patients hospitalized in Germany between 2010 and 2015 (112 172 869 hospitalizations in total) were included in this nationwide secondary analysis. Among the deceased patients we identified those who had died in the presence of a brain damage and for whom organ donation was not excluded either by a medical contraindication or by the patient's not having been artificially ventilated. The analysis was also conducted separately for six German university hospitals. Results: Over the period 2010-2015, the number of potential organ donors per year in Germany rose by 13.9%, from 23 937 to 27 258. This development was due to an increase in the number of deaths with severe brain damage as well as an increase in the percentage of patients who were treated with invasive ventilation before death. The contact quotient, i.e., the percentage of potential donors for whom contact was made with the German Foundation for Organ Transplantation (Deutsche Stiftung Organtransplantation, DSO) fell over this period from 11.4% to 8.2%. At the same time, the realization quotient (the percentage of potential donors who became actual donors) fell from 5.4% to 3.2%, and the conversion quotient (the percentage of potential donors for whom contact was made who became actual donors) fell from 47% to 39.1%. From 2010 to 2012, the falling realization quotient was accounted for mainly by the falling conversion quotient; from 2012 to 2015, it was accounted for mainly by the falling contact quotient. The contact and realization quotients among the six university hospitals studied differed markedly (by factors of 17.5 and 23.3, respectively), while the conversion quotients differed only minimally (by a factor of 1.3). Conclusion: The decline in post-mortem organ donation is due to a deficiency in the recognition and reporting of potential organ donors in hospital. If this process were better supported on the organizational and political level, far more organs could be transplanted. [ABSTRACT FROM AUTHOR]

Pediatric heart allocation in Eurotransplant (ET) has evolved over the past decades to better serve patients and improve utilization. Pediatric heart transplants (HT) account for 6% of the annual transplant volume in ET. Death rates on the pediatric heart transplant waiting list have decreased over the years, from 25% in 1997 to 18% in 2011. Within the first year after listing, 32% of all infants (<12 months), 20% of all children aged 1-10 years, and 15% of all children aged 11-15 years died without having received a heart transplant. Survival after transplantation improved over the years, and in almost a decade, the 1-year survival went from 83% to 89%, and the 3-year rates increased from 81% to 85%. Improved medical management of heart failure patients and the availability of mechanical support for children have significantly improved the prospects for children on the heart transplant waiting list. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heart-beating deceased ECDs - defined according to the United Network of Organ Sharing definition - were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P = 0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) ( P = 0.04). One-year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P = 0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys. (Current Controlled Trials number: ISRCTN83876362). [ABSTRACT FROM AUTHOR]

This mini-review on European experiences with tackling the problem of organ shortage for transplantation was based on a literature review of predominantly European publications dealing with the issue of organ donation from deceased donors. The authors tried to identify the most significant factors that have demonstrated to impact on donation rates from deceased donors and subsequent transplant successes. These factors include legislative measures (national laws and European Directives), optimization of the donation process, use of expanded criteria donors, innovative preservation and surgical techniques, organizational efforts, and improved allocation algorithms. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Often, organ transplantation is the only option to improve the life expectancy and quality of life of patients with terminal organ failure. Despite improved donor and organ assessment, a residual risk remains for transmitting infection, tumor, or other disease from the donor to recipients. Analysis, reporting, and managing of donor‐derived diseases through a vigilance and surveillance system (V&S) is mandatory in many countries. We report on suspected and proven/probable donor‐derived infections (DDI) in Germany over a period of 8 years (2016–2023).All incoming serious‐adverse‐event and serious‐adverse‐reaction (SAE/SAR) reports from 01.01.2016 to 31.12.2023 were evaluated for suspected DDI. Analysis of imputability followed the definition of the US Disease Transmission Advisory Committee (DTAC). Only probable and proven cases according to DTAC classification were defined as DDI.During the study period, 9771 donors in Germany donated post‐mortem organs to 27 919 recipients. In that period 612 SAE/SAR cases were reported, 377 (62%) involved infections. 41 cases were proven/probable DDI affecting 58 recipients (seven recipients died, 12%). Suspected infections were bacterial (182/377, 48%), fungal (135/377, 36%), viral (55/377, 15%), and parasitic (5/377, 1%). In case of bacterial DDI, no recipient died, but organ loss occurred in six recipients. In case of fungal or viral DDI, 19% (3/16) and 21% (3/14) of the recipients died, respectively.DDI are rare in solid organ transplantation (58/27 919, 0.21%), but when they occur, they are associated with high morbidity and mortality in affected recipients. Careful and detailed donor evaluation and a reliable V&S help improve recipient safety. [ABSTRACT FROM AUTHOR]

We report two cases of pulmonary tuberculosis in heart transplant recipients: a 46-year-old man with pulmonary tuberculosis due to Mycobacterium tuberculosis and a 64-year-old man with nontuberculous mycobacterial infection with pulmonary infiltrates due to Mycobacterium xenopi. The time intervals from transplantation to diagnosis were 3 and 4 years, respectively. The patient with tuberculosis underwent standard treatment with isoniazid, rifampin, ethambutol, and pyrazinamide. The patient with the nontuberculous mycobacterial infection received treatment with clarithromycin and ciprofloxacin for 18 months in addition to rifampin for the first 3 months. Both patients responded well to treatment. No recurrences were observed during follow-up. The interactions between antibiotic treatment and cyclosporine therapy should be observed closely in organ transplant recipients, requiring frequent level determinations and dosing changes. [Copyright &y& Elsevier]

Heart and lung procurements are multiphased processes often accompanied by an array of complex logistics. Approaches to donor evaluation and management, organ procurement, and organ preservation vary among individual procurement teams. Because early graft failure remains a major cause of mortality in contemporary thoracic organ transplant recipients, we sought to establish some standardization in the procurement process. This paper, in this vein, represents an international consensus statement on donor heart and lung procurement and is designed to serve as a guide for physicians, surgeons, and other providers who manage donors to best optimize the clinical status for the procurement of both heart and lungs for transplantation. Donation after brain death (DBD) and donation after circulatory determination death (referred to as donation after circulatory death [DCD] for the remainder of the paper) for both heart and lung transplantation will be discussed in this paper. Although the data available on DCD heart donation are limited, information regarding the surgical technique for procurement is included within this consensus statement. Furthermore, this paper will focus on adult DBD and DCD heart and lung procurement. Currently, no certification, which is either recognized and/or endorsed by the transplant community at large, exists for the training of a cardiothoracic procurement surgeon. Nevertheless, establishing a training curriculum and credentialing requirements are beyond the scope of this paper. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to investigate the impact of the lung allocation score (LAS) on mortality among highly urgent (HU) and urgent (U) lung transplant (LTx) candidates in Eurotransplant (ET) and to identify useful additional parameters (LASplus). Methods: All adult LTx candidates for whom a first request for HU or U status was made in 2008 in ET were included (N = 317). Patients were followed until LTx, death on the waiting list (WL), delisting, or closure date (i.e., January 10, 2010). The relationship between the LAS/LASplus and waiting list, post-transplant, and overall mortality was assessed with a multivariate regression model. The LAS and LASplus were decomposed into their basic waitlist and post-transplant components. Results: Waiting list mortality rate was 22% and 1-year post-transplant mortality rate was 34%. The waitlist component of the LASplus was significantly associated with waiting list mortality (hazard ratio [HR] 1.91, p = 0.021), whereas the LAS was not (p = 0.063). The post-transplant components of both scores were significantly associated with 1-year post-transplant mortality (LAS: HR 2.69, p = 0.005; LASplus: HR 2.55, p = 0.004). Both scores strongly predicted overall mortality (LAS: HR 1.65, p = 0.008; LASplus: HR 1.72, p = 0.005). Conclusion: LAS accurately predicts overall mortality in critically ill transplant candidates and should therefore be considered as the basis for a new lung allocation policy in ET. An adjustment of the original LAS may be indicated to accurately predict waiting list mortality. [ABSTRACT FROM AUTHOR]

Cyclosporin (CsA) or tacrolimus (TRL) is routinely combined with either sirolimus (SRL) or mycophenolate mofetil (MMF) in immunosuppressive regimes in organ transplantation. The aim of our study was to establish a specific human blood assay of lymphocyte function in order to assess interactions of these drug combinations. Different concentrations (106–109 nM) of CsA, TRL, SRL or mycophenolic acid (MPA, the active metabolite of MMF) was added to whole blood of five human volunteers. Drug combinations were studied by adding 250, 500 or 1000 nM of MPA to different concentrations of CsA, TRL, or SRL or by adding 1, 10 or 25 nM of SRL to different concentrations of CsA or TRL. After concanavalin-A stimulation, whole blood cultures were analyzed by flow cytometry detecting lymphocyte proliferation and activation by bivariate expression of proliferating cell nuclear antigen (PCNA)/DNA content and T cell-surface activation antigens (e.g. CD25, CD95, and CD154). We found an order of potency inhibiting lymphocyte function with SRL>TRL>CsA>MPA. In addition, we observed enhanced inhibition of PCNA, CD25, CD95 or CD154, if either CsA or TRL was combined with low concentrations of MPA, or SRL alone or if SRL was combined with low concentrations of MPA. Data analysis revealed an independent functional synergism or partial agonism in most combinations. This human blood assay is able to assess lymphocyte function and to monitor immunosuppressive therapy. The assay also permits pharmacological analysis of drug interactions, which will lead to improved safety and therapeutic efficacy in transplanted patients. [Copyright &y& Elsevier]