Introduction of the lung allocation score in Germany.

The aim of this study was to assess performance of the new lung allocation system in Germany based on lung allocation score (LAS). Retrospective analysis of waitlist (WL) outflow, lung transplantation (LTx) activity and 3-month outcomes comparing 1-year pre- and post-LAS introduction on December 10, 2011 was performed. Following LAS introduction, WL registrations remained constant, while WL mortality fell by 23% (p = 0.04). Reductions in WL mortality occurred in patients with cystic fibrosis (CF; -52%), emphysema (chronic obstructive pulmonary disease [COPD]; -49%) and pulmonary hypertension (PH; -67%), but not idiopathic pulmonary fibrosis (IPF; +48%). LTx activity increased by 9% (p = 0.146). Compared to pre-LAS, more patients with IPF (32% vs. 29%) and CF (20% vs. 18%) underwent transplantation and comparatively fewer with COPD (30% vs. 39%). Median LAS among transplant recipients was highest in PH (53) and IPF (49) and lowest in COPD (34). Transplantation under invasive respiratory support increased to 13% (in CF 28%, +85%, p = 0.017). Three-month survival remained unchanged (pre: 96.1% and post: 94.9%, p = 0.94). Following LAS implementation in Germany, reductions in waiting list size and WL mortality were observed. Composition of transplant recipients changed, with fewer COPD and more IPF recipients. Transplantation under invasive respiratory support increased. Reductions in WL mortality were most pronounced among CF and PH patients.

Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation.

Static cold storage (CS) is the most widely used organ preservation method for deceased donor kidney grafts but there is increasing evidence that hypothermic machine perfusion (MP) may result in better outcome after transplantation. We performed an economic evaluation of MP versus CS alongside a multicenter RCT investigating short- and long-term cost-effectiveness. Three hundred thirty-six consecutive kidney pairs were included, one of which was assigned to MP and one to CS. The economic evaluation combined the short-term results based on the empirical data from the study with a Markov model with a 10-year time horizon. Direct medical costs of hospital stay, dialysis treatment, and complications were included. Data regarding long-term survival, quality of life, and long-term costs were derived from literature. The short-term evaluation showed that MP reduced the risk of delayed graft function and graft failure at lower costs than CS. The Markov model revealed cost savings of $86,750 per life-year gained in favor of MP. The corresponding incremental cost-utility ratio was minus $496,223 per quality-adjusted life-year (QALY) gained. We conclude that life-years and QALYs can be gained while reducing costs at the same time, when kidneys are preserved by MP instead of CS.

The influence of laboratory-induced MELD score differences on liver allocation: more reality than myth.

BACKGROUND: Liver allocation in Eurotransplant (ET) is based on the MELD score. Interlaboratory MELD score differences in INR and creatinine determination have been reported. The clinical implication of this observation has not been demonstrated. METHODS: MELD scores were calculated in 66 patients with liver cirrhosis using bilirubin, creatinine, and INR analyzed in six liver transplant centers. Based on allocation results of ET, patients transplanted from December 2006 to June 2007 were divided according to MELD score in four groups. For each group, the influence of the match MELD on the probability of receiving a transplant was studied (Cox proportional hazards model). RESULTS: Laboratory-dependent significant differences in MELD score were demonstrated. Cox proportional hazards model showed a significant association between MELD score and the probability of organ allocation. The unadjusted hazard ratio for receiving a liver transplant was significantly different between group 2 and group 4 (group 2: MELD 19-24; group 4: MELD > 30). CONCLUSION: Laboratory-dependent significant differences in MELD score were observed between the six transplant centers. We demonstrated a significant association between the MELD score and the probability of organ allocation. The observed interlaboratory variation might yield a significant difference in organ allocation in patients with high MELD scores.

The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys.

Vascular renal resistance (RR) during hypothermic machine perfusion (HMP) is frequently used in kidney graft quality assessment. However, the association between RR and outcome has never been prospectively validated. Prospectively collected RR values of 302 machine-perfused deceased donor kidneys of all types (standard and extended criteria donor kidneys and kidneys donated after cardiac death), transplanted without prior knowledge of these RR values, were studied. In this cohort, we determined the association between RR and delayed graft function (DGF) and 1-year graft survival. The RR (mmHg/mL/min) at the end of HMP was an independent risk factor for DGF (odds ratio 38.1 [1.56-934]; p = 0.026) [corrected] but the predictive value of RR was low, reflected by a c-statistic of the receiver operator characteristic curve of 0.58. The RR was also found to be an independent risk factor for 1-year graft failure (hazard ratio 12.33 [1.11-136.85]; p = 0.004). Determinants of transplant outcome are multifactorial in nature and this study identifies RR as an additional parameter to take into account when evaluating graft quality and estimating the likelihood of successful outcome. However, RR as a stand-alone quality assessment tool cannot be used to predict outcome with sufficient precision.

Considerations for patients awaiting heart transplantation.

The aim of this study is to provide a description of patients on the waiting list for heart transplants in Germany; the focus is on comparing the era after implementation of the new transplant law with the former era. This study used data from the Eurotransplant registry. The population consisted of all patients who registered for heart transplantation in Germany between January 1990 and May 2009. Patients were followed up to the earliest of the following events: heart transplantation, death, or end of the observation period. The actual mortality rates were calculated using a competing risk methodology. The proportion of patients on the waiting list aged 65 years or older has increased from 1.9 % in 1990 to 8.3 % in 1997, 7.8 % in 2000 and 12.6 % on December 31, 2008. The 1-year waiting list mortality rate, expressed as the proportion of patients who die within 1 year after being listed for heart transplantation decreased in the period 2001-2009 compared to the period 1991-2000. Patients registered in the period from 1991-2000 had a 25.9 % chance of dying prior to heart transplantation compared to 18.9 % for patients who were registered in the years 2001-2009. In the registration period 1981-1990, a transplant candidate had a 64.3 % chance of undergoing heart transplantation within the first year after being listed, while for patients who were registered in the period 2001-2009 this probability has been reduced to 40.2 %. Despite the fact that patient profiles have worsened and access to transplantation decreased, mortality rates of patients on the heart transplant waiting list have decreased. These data show that treatment of patients with advanced heart disease has improved in Germany.

How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors.

INTRODUCTION: Because of the increasing demand for pancreas transplantation, more marginal donors are offered to Eurotransplant. The aim of this study was to validate a donor quality score that would facilitate recognition of a suitable pancreas donor among all reported donors. MATERIALS AND METHODS: We analyzed all 3180 consecutively reported pancreas donors for the period between January 1, 2002 and June 30, 2005 and determined the influence of the preprocurement pancreas suitability score (P-PASS) on the acceptance of a pancreas. We defined a range and point weight for each variable based on clinical expertise and known literature. RESULTS: Multiple regression analysis using pancreas acceptance as an outcome variable identified P-PASS > or = 17 as a significant cutoff point (P < .001). Pancreata from donors with P-PASS > or = 17 were three times more likely to be refused. CONCLUSION: The donor score can help in screening for potential pancreas donors, where an ideal donor has a P-PASS < 17. Our data demonstrate that consideration of a combination of preprocurement factors can help identify a suitable pancreas donor. Therefore, we recommend that a pancreas donor score be calculated for each potential pancreas donor, and all donors with a P-PASS < 17 should be considered for pancreas donation.

Kidney transplantation without prior dialysis in children: the Eurotransplant experience.

Kidney transplantation without prior dialysis may prevent dialysis-associated morbidity. We analyzed the outcome of 1113 first kidney transplants in children performed between 1990 and 2000 in the Eurotransplant community. Enlistment for a deceased donor kidney before start of dialysis (127/895, 14%) made dialysis redundant in 55% of cases. Mean residual creatinine clearance at transplantation of these patients was 8 mL/min/1.73 m(2). Pre-emptive transplantations of deceased donor kidneys showed less acute rejections (52% vs. 37% rejection-free at 3 years, p = 0.039), compared to transplantations following dialysis. The difference in graft survival between non-dialyzed and dialyzed patients (82% vs. 69% at 6 year) did not reach statistical significance (p = 0.055). No differences were noted after living donor transplantation. Multivariate analysis showed that the period of transplantation was the strongest predictor of graft survival (p < 0.001). Congenital structural abnormalities such as primary kidney disease predominated in nondialyzed patients as compared to dialyzed patients (p < 0.001); this factor did not influence graft survival. Based on our conclusion that pre-emptive transplantation is at least as good as post-dialysis transplantation, as well as on quality of life arguments, we recommend to consider pre-emptive transplantation in children with end-stage renal failure.

Predictors of lung transplant survival in eurotransplant.

This study was undertaken to assess the influence of patient/donor and center factors on lung transplantation outcome. Outcomes of all consecutive first cadaveric lung transplants performed at 21 Eurotransplant centers in 1997-99 were analyzed. The risk-adjusted center effect on mortality was estimated. A Cox model was built including donor and recipient age and gender, primary disease, HLA mismatches, patient's residence, cold ischemic time, donor's cause of death, serum creatinine, type of lung transplant, respiratory support status, clinical condition and percentage predicted FEV1. The center effect was calculated (expressed as the standardized difference between the observed and expected survival rates), and empirical and full Bayes methods were applied to evaluate between-center differences. A total of 590 adults underwent lung transplantation. The primary disease (p=0.01), HLA-mismatches (p = 0.02), clinical condition(p < 0.0001) and the patient's respiratory support status (p = 0.05) were significantly associated with survival. After adjusting for case-mix, no between-center differences could be found. An in-depth empirical Bayes analysis showed the between-center variation to be zero. Similar results were obtained from the full Bayes analysis. Based on these data, there is no scientific basis to support a hypothesis of possible association between center volume and lung survival rates.

[Risk factors of contamination of pig farms in the Netherlands with pig diseases and agents thereof: a review of the literature]. / Risicofactoren voor insleep van varkensziekten/-ziekteverwekkers op varkensbedrijven in Nederland: een literatuuroverzicht.

Part of the project 'Clean pigs' an extensive study of literature was made of the risk factors related to the introduction of pathogenic micro-organisms in pigfarms in the Netherlands. On the basis of this study of literature and in close cooperation with the experts of the steering group of the project 'Clean pigs' a number of risk factors relevant for the Dutch pig farming were estimated. The impact of these risk factors on the introduction of the most important pig diseases/-agents in Dutch pig farming was quantified for three different levels of preventive measures. It is shown that many risks can be reduced or even be neglected by the biosecurity measures already applied on pig farms. For most diseases, including list A and B diseases of the OIE list, introduction of new animals is regarded as the main risk factor, but this risk can be reduced in several ways. Besides this, aerogenic transmission and introduction by rodents and pet animals need the most attention. Through specific actions and measures several important risk factors can be diminished or even eliminated.

Mortality rates after heart transplantation: how to compare center-specific outcome data?

BACKGROUND: Studies of outcome in cardiac transplantation have focused primarily on identifying patient- and donor-related factors associated with patient mortality. Less consideration has been given to the impact of the transplant center. This study was undertaken to assess variability in heart transplantation outcome in Eurotransplant centers to provide a framework for auditing. METHODS AND RESULTS: In a 2-year period, 1,401 adult patients underwent heart transplantation in 45 centers. The 1-year patient survival rate was 76% (95% CI, 74%-78%) with a range of 0% to 100% at the center level. The risk-adjusted center effect on mortality was estimated by calculating a standardized difference between the observed number of deaths 1 year after transplantation and the expected number of deaths based on the case mix. By assessing within- and between-center variations with empirical Bayes (EB) methods, after adjustment for all registered prognostic factors, an improved estimate of the true center effect was obtained. Compared with the standard risk-adjusted center effect method, fewer outlying centers were identified with the EB method. CONCLUSION: EB methods, because they are known to incorporate more information from the data, enable a more precise and realistic portrayal of heart transplant centers' performances, compared with other risk-adjusted center effect methods. In the context of auditing procedures, EB methods should preferably be used for the identification of centers that deviate significantly from quality standards.

Selecting patients for heart transplantation: which patients are too well for transplant?

In the context of contemporary medical and surgical therapy, the revolutionary procedure of cardiac transplantation should be redefined in its relative role. Based on the assumption that its goal is to prolong life while improving its quality, and in the absence of randomized clinical trial data testing its benefit, data from early breakthrough studies, more recent observational cohort studies, and studies testing other therapies in advanced heart failure must be analyzed to characterize clinical profiles of patients who should be considered too well for cardiac transplantation at specific stages of their disease processes. These profiles likely include advanced heart failure with (1) low risk according to the Heart Failure Survival Score, (2) peak oxygen consumption greater than 14 to 18 mL/kg/min without other indications, (3) left ventricular ejection fraction less than 20% alone, (4) history of New York Heart Association class III to IV symptoms alone, (5) history of ventricular arrhythmias alone, (6) no previous attempt at comprehensive neurohormonal blockade, and (7) no structured cardiac transplantation evaluation in a designated cardiac transplantation center. The evaluation may identify the potential transplant candidate, who could be placed on a national potential transplant candidate list, combining the psychologic benefit of acceptance by the program with an ongoing openness to the diversity of advanced heart failure treatment modalities.

[Improved pig health with farm management systems. Project 'Beautiful stream of pigs' 21]. / Gezondheidsverbetering in de varkenshouderij door toepassing van bedrijfssystemen. Project 'Schone varkensstromen' 21.

As part of the project 'Clean pigs', an inventory was made of the different pig farm management systems described in the literature. These systems were evaluated for their potential use in improving animal health, focusing on the pathogens important in the Netherlands. The most promising systems for the control and/or eradication of pig pathogens in the Netherlands can be divided into two groups (with decreasing effect): I. Eradication from an existing positive population. The best systems for this are Embryo Transplantation (ET), Specific-Pathogen Free pigs (SPF), Piglet Snatching and Segregated Weaning (SW). II. Strategic veterinary and breeding strategies. The best systems for this are Freeze infection, test and removal, Test and removal, Vaccination, Medical elimination, Strategic medication and Genetic resistance. Farm systems can be a big help when trying to improve animal health, but the 'biosecurity' measures on the farm are at least of equal importance.

Transplanting horseshoe kidneys: a worldwide survey.

PURPOSE: Horseshoe kidney is the most common anatomical renal variation. It represents a fusion anomaly, usually of the lower poles. Horseshoe kidneys can be transplanted en bloc or after division of the renal isthmus. We constructed a decision cascade for horseshoe kidney transplantation. MATERIALS AND METHODS: A worldwide survey of transplantation clinics and foundations was performed to discover cases of horseshoe kidney transplantation. In each case data were collected on horseshoe kidney anatomy and post-transplantation results. The number of renal arteries and veins was correlated with primary nonfunction due to technical failure. RESULTS: From 1975 to 2000, 23 horseshoe kidneys were transplanted en bloc, while 57 were split and transplanted into 97 recipients. Primary nonfunction was observed in 4.3% and 13.4% of en bloc and divided transplanted kidneys, respectively. Postoperatively a urinary fistula formed after renal isthmus division in 2 cases. An increased number of renal vessels was not associated with an increased risk of primary nonfunction. CONCLUSIONS: Horseshoe kidney anatomy should be closely inspected after explantation. The decision to split a horseshoe kidney should be based on urinary collecting system anatomy in the renal isthmus and on the number as well as the position of the renal vessels. Horseshoe kidneys can and should always be considered for transplantation.

Iso-risk curves as a tool for clinical decision-making: donor factors and medical urgency in cardiac transplantation.

UNLABELLED: BACKGROUND; No significant improvement of overall graft survival in cardiac transplantation has occurred during the past decade, notwithstanding the identification of several prognostic donor and recipient risk factors. By translating multivariate results into iso-risk curves plots, stratified for medical urgency, we attempt to present results in a more practical manner, to be used as guidelines at the time of donor heart offer and of allocation. METHODS: We analyzed all first heart-only transplants performed in adults and carried out between January 1, 1997, and June 30, 1998 (N = 1120). Before transplant, 687 patients were at home, 233 on hospital wards, and 200 on the intensive care unit. The overall Cox model yielded 5 independent factors associated with 1-year graft outcome: donor age, donor:recipient weight ratio, medical urgency, end-stage heart disease, and transplant country. We used the significant donor variables of donor age and donor:recipient weight ratio for the iso-risk curves; we calculated relative risks for all combinations of donor age and donor:recipient weight ratio. We obtained iso-risk curves by linking equal relative risks. RESULTS: All iso-risk curves showed that with older donor age, the donor:recipient weight ratio must be higher to obtain the same relative risk for all 3 medical urgency groups. The more urgent the heart transplant candidate, the higher the course of the iso-risk curve for all donor ages. CONCLUSIONS: Iso-risk curve is an elegant tool for presenting multivariate analyses in a more practical and patient-oriented manner. The more understandable prognostic factors become the more likely we are to achieve better results in cardiac transplantation and to use more optimally donor hearts. As an example, we have demonstrated the interaction between donor age, donor:recipient size ratio, and medical urgency.

Renal retransplantation of children: is a policy 'first cadaver donor, then live donor' an acceptable option?

Retransplantation is often a necessity for children with end-stage renal disease (ESRD), as kidney graft survival is still not infinite. If a suitable live donor is present, the current policy is to use the live donor first, in order to obtain excellent long-term outcome and to prevent human leucocyte antigen (HLA) sensitization. Data from the Eurotransplant International Foundation were analyzed to determine whether the sequence, first a cadaveric donor then a live donor, is acceptable. Between January 1 1983 and December 31 1995, 1305 children received a first renal transplant; 269 of them had a second transplant during the same period. Follow-up of at least 1 yr was available. Categories were made according to the sequence of renal donor source: 217 patients were classified as first cadaver and second cadaver (1cad-2cad) transplant, 26 as first cadaver and second live (1cad-2liv) donor transplant, 23 as first live donor and second cadaver (1liv-2cad) transplant and three patients had two subsequent live donor transplants (1liv-2liv). When a live donor transplant was carried out, either first or second, the donor age was always higher, and the chance of a pre-emptive transplantation or short stay on dialysis was higher, compared with a cadaver transplant. The re-graft survival rate of the '1cad-2liv' was better than the '1cad-2cad' and '1liv-2cad' transplants. At 5 yr, the survival was 76%, 49%, and 61%, respectively. These data suggest that, when a suitable live donor is not available for a first transplantation owing to medical and/or familial reservations, a policy of 'first a cadaver donor then a live donor' transplantation is a viable option and should even be promoted. The pre-emptive stage of the second transplant, probably with a live donor, is additionally advantageous.

Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience.

BACKGROUND: Increased referral for lung transplantation, persistent shortage of donor lungs, and moderate transplant outcome call not only for adequate listing criteria, but also for an optimal allocation scheme. We used global cohort survival after listing and survival benefit from transplantation to study the effect of a lung allocation scheme, primarily driven by waiting time, on the different types of end-stage lung disease. METHODS: We followed all adult patients consecutively listed for first, lung-only transplantation between 1990 and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up after transplantation (n = 744). We used the competing risk method, the Kaplan-Meier method, and a time-dependent non-proportional hazards model to analyze waiting-list outcome and global mortality after listing, post-transplant survival, and transplant effect, respectively. Each analysis was stratified for type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had received lung transplants, whereas 25% had died on the waiting list. The 2-year survival post-transplant was 55%. The global mortality of the cohort, since listing, amounted to 46% at 2 years. Compared with continued waiting, patients experienced benefit from transplantation by Day 100, which lasted until the end of the 2-year analysis period. We noticed the highest global mortality rates for patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%); emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days, respectively. Transplantation also benefited emphysema patients by Day 260. CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western European cohort of adults, in particular for patients with pulmonary fibrosis and cystic fibrosis, but also for patients with emphysema. The global survival rate, reflecting the real life expectancy for a newly listed transplant candidate, is poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation algorithms that lessen the impact of waiting time and take into account the type of end-stage lung disease should be developed.