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Background: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) recipients is challenging. The aim of this study was to assess the diagnostic and prognostic value of longitudinal lung function tests in SLTX recipients with CLAD., Methods: A total of 295 SLTX recipients were analyzed and stratified according to native lung physiology. In addition to spirometry, measurements of static lung volumes and lung capacities were used to phenotype patients and to assess their prognostic value. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n = 71)., Results: Of 224 lung transplant recipients, 105 (46.9%) developed CLAD. Time to CLAD onset (hazard ratio [HR]: 0.82, 95% CI: 0.74-0.90; p < 0.001), severity of CLAD at onset (HR: 0.97, 95% CI: 0.94-0.99; p = 0.009), and progression after onset of CLAD (HR: 1.03, 95% CI: 1.00-1.05; p = 0.023) were associated with outcome. Phenotypes at onset were bronchiolitis obliterans syndrome (BOS) (59.1%), restrictive allograft syndrome (RAS) (12.4%), mixed phenotype (6.7%), and undefined phenotype (21.9%). Survival estimates differed significantly between phenotypes (p = 0.004), with RAS and mixed phenotype being associated with the worst survival, followed by BOS and undefined phenotype. Finally, a higher hazard for mortality was noticed for RAS (HR: 2.34, 95% CI: 0.99-5.52; p = 0.054) and mixed phenotype (HR: 3.30, 95% CI: 1.20-9.11; p = 0.021) while controlling for time to CLAD onset and severity of CLAD at onset., Conclusions: Phenotyping CLAD in SLTX remains challenging with a high number of patients with an undefined phenotype despite comprehensive lung function testing. However, phenotyping is of prognostic value. Furthermore, early, severe, and progressive CLADs are associated with worse survival., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: This retrospective single-center study aimed to analyze transfusion requirements, coagulation parameters, and outcome parameters in patients undergoing lung transplantation (LuTx) with intraoperative extracorporeal circulatory support, comparing cardiopulmonary bypass (CPB), and extracorporeal membrane oxygenation (ECMO)., Methods: Over a 3-year period, 49 of a total of 188 LuTx recipients were identified being set intraoperatively on either conventional CPB (n = 22) or ECMO (n = 27). Intra- and postoperative transfusion and coagulation factor requirements as well as early outcome parameters were analyzed., Results: LuTx patients on CPB had significantly higher intraoperative transfusion requirements when compared with ECMO patients, that is, packed red cells (9 units [5-18] vs. 6 units [4-8], p = 0.011), platelets (3.5 units [2-4] vs. 2 units [0-3], p = 0.034), fibrinogen (5 g [4-6] vs. 0 g [0-4], p = 0.013), prothrombin complex concentrate (3 iU [2-5] vs. 0 iU [0-2], p = 0.001), and tranexamic acid (2.5 mg [2-5] vs. 2.0 mg [1-3], p = 0.002). Also, ventilator support requirements (21 days [7-31] vs. 5 days [3-21], p = 0.013) and lengths of ICU stays (36 days [14-62] vs. 15 days [6-44], p = 0.030) were markedly longer in CPB patients. There were no differences in 30-day and 1-year mortality rates., Conclusion: These data indicate a perioperative advantage of ECMO usage with low-dose heparinization over conventional CPB for extracorporeal circulatory support during LuTx. Long-term outcome is not affected., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Current guidelines advocate administration of inotropic agents to stabilize potential deceased heart-beating donors. A consensus on the specific agent or combination therapy is lacking. We thus initiated a retrospective analysis of patients being transplanted at our center in a matched-pair study design focusing on survival after donor pre-treatment either with norepinephrine or dopamine., Material and Methods: 936 patients (759 male; 177 female; mean age: 47.5 ± 15.4 years) were transplanted at our center between 8/1981 and 12/2010. An overall of 22 patient pairs (all male; mean age 55.4 ± 7.5 years; range 23-67 years) were matched according to our strict criteria. During follow-up (5037 ± 1791 days) 11 deaths occurred. Overall survival in both groups was not different (p=0.1438)., Results: In a sub-population analysis of all patient-pairs that completed 5-year follow-up (n=19), Kaplan-Meier analysis revealed significant superior survival of recipients that received hearts pre-treated with norepinephrine vs. dopamine pre-treatment (p=0.0368)., Conclusions: Neither norepinephrine nor dopamine pre-treatment of potential heart donors showed superior overall survival. In a sub-population of long-term survivors norepinephrine pre-treatment was associated with better survival in a rather small cohort of heart transplant recipients. These findings underscore the urgent need of further prospective multicenter randomized trials to recommend a preferable adrenergic therapy.

Purpose: The purpose of this study was to assess the impact of surgical training and surgeon's experience on surgical quality and early outcome parameters., Methods: The outcomes of 184 deceased donor kidney transplant procedures were retrospectively reviewed. Intraoperative quality parameters, complication rates, and early outcome parameters were analyzed with respect to surgeon's experience. Surgeons were grouped according to their level of experience: trainees (n = 5), who were senior residents in their transplant rotation; low-experience surgeons (n = 4), who had an individual caseload of at least 30 supervised procedures; medium-experience surgeons (n = 5), who had an individual caseload of a minimum of 30 unsupervised (+30 supervised) procedures; and high-experience surgeons (n = 2), who had an individual caseload of more than 200 procedures., Results: Surgical training was offered in 20 % of all cases. Surgeons with a high experience in kidney transplantation had a significantly lower warm ischemic time (30 versus 35 min, p = 0.01) and total operation time (135 versus 155 min, p = 0.43) as compared to the other study groups. However, this did not translate into a better outcome after transplantation. The complication rate and early outcome parameters such as length of hospital stay, serum creatinine at discharge, and graft and patient survival at 3 months post TX did not show any significant difference between the groups., Conclusion: We conclude that hands-on training of residents in kidney transplantation is feasible and surgical experience can be safely gained within a staged surgical training program.

Objectives: Gender differences between donors and recipients might have an effect on outcome after heart transplantation. Literature and registries reveal controversial results. We reviewed 1000 heart transplantations at our center focusing on the influence of gender differences on short- and long-term outcome after heart transplantation., Materials and Methods: We performed a retrospective analysis of 1000 (960 primary and 40 redo-heart transplantations) between August 1981 and July 2008. In contrast to other studies, the data for gender differences (donor gender and recipient gender) were evaluated for recipient survival and survival conditional to early mortality., Results: Female donors are significantly older than male donors (females, 36.5 ± 14.5 years; males, 31.2 ± 13.8 years). One-year survival was significantly inferior in male recipients receiving female donor hearts (mR/fD: 73.7%) compared to females receiving male donor organs (fR/mD: 90.9%) (P = .045). Univariate analysis revealed that, for recipients who survived > 1 year, survival at 10 years was significantly greater for female donors and female recipients (90%) than it was for male donors and male recipients (72%; P = .034). Multivariate analysis showed that the gender combination with female donors and female recipients was an independent indicator for greater long-term survival (P = .04)., Conclusions: The gender combination of female donors and male recipients had a greater risk for early mortality after heart transplantation, and the combination of male donors and female recipients resulted in favorable short-term outcomes. In long-term follow-up, recipients of hearts from female donors had better survival, especially female recipients.

Background: For short-term ventricular and pulmonary support the extracorporeal membrane oxygenation (ECMO) system using the Bio-Medicus centrifugal pump (Medtronic®, Minneapolis, MN, USA) was applied in 108 patients with cardiac low-output., Methods: From December 1996 to July 2006 the ECMO was implanted in 108 patients (73 adult, mean age: 49.3±18.0 yrs and 35 children, mean age: 1.3 ± 2.7 yrs) with mostly postcardiotomy cardiac low output. The surgical procedures included congenital heart surgery (n=35), heart transplantation (HTx) (n=21), coronary artery bypass operation (CABG) and/or valvular operation (n=33), other operations (n=6) and 13 patients with ECMO support for bridge to recovery., Results: The mean supporting time was 5.1±5.6 days. Overall, 30-day-survival was 40.2%. Best survival rates were seen after congenital heart surgery (24/35, 65.7%) and after HTx (9/21, 42.9%); the worst rates were in the group of CABG and/or valvular operations (5/33, 15.2%), only ECMO support (3/13, 23.1%) and other operations (1/6, 16.7%). Fifty-four patients died while supported by ECMO, 15 were weaned from ECMO but died in hospital, 39 patients were weaned and survived. Causes of death were multi-organ failure (40.6%), bleeding (23.2%), persistent cardiac low output (21.7%), thrombembolic events (8.7%), and graft failure (5.8%). Markers for adverse outcome were identified as older age, high body weight, increased AST/GOT levels, and lower thrombocyte count in adults; and as higher levels of serum creatinine in pediatric patients., Conclusions: ECMO support showed best results in pediatric patients after congenital heart surgery and in patients after HTx in contrast to multimorbid, older patients with often irreversible myocardial damage.

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., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

Background: Elevated donor serum sodium is a phenomenon often encountered in the management of brain dead donors. The clinical relevance on recipient outcome is less examined. We investigated the impact of elevated donor serum sodium levels (DSL) on outcome after heart transplantation in 1800 heart transplantations., Methods: Data was conducted in a retrospective analysis from 1989 until 2005. The transplantations were performed at three German heart transplant centers. The joined database included DSL at the time of organ procurement, recipient and donor age, ischemia time, primary graft failure and survival data., Results: Mean DSL was 147.7 +/- 10.3 l/l (range 111 - 208 l/l). Recipients were divided into 4 groups with percentiles of 141, 147, and 154 l/l resulting in DSL of A: 135.8 +/- 4.4, B: 143.6 +/- 1.7, C: 149.7 +/- 1.9, and D: 161.3 +/- 7.7 l/l for the four quartiles. Primary graft failure occurred in 2.6 % of the patients with A: 2.8 %, B: 2.8 %, C: 3.7% and D: 1.4 % ( P = n.s.). Mean 5- and 10-year-survival rates were 70.9 % (57.6 %) with A: 71.1 % (53.86 %), B: 69.3 % (53.9 %), C: 72.7 % (61.0 %), D: 71.2 % (62.4 %), respectively ( P = n. s.). In a multivariate analysis a significant impact on postoperative results could be revealed for recipient age ( P = 0.002), ischemia time ( P = 0.002) and donor age ( P = 0.009). DSL were no individual risk factor in the multivariate analysis., Conclusion: There was no impact of donor serum sodium levels neither on early postoperative results, nor on long-term outcome indicating that cardiac allografts from donors with elevated sodium levels might be transplanted successfully, achieving favourable results.

Background and Purpose: Prospective randomized trials have demonstrated that early and continuous use of statins in heart transplant recipients significantly decreases cholesterol and also significantly lowers mortality and the development of transplant vasculopathy. This evaluation presents the authors' 11-year experience using simvastatin in heart transplant patients., Patients and Methods: In 1991, a prospective randomized study was initiated comparing the efficacy of simvastatin, beginning on postoperative day 4 (n = 35), with that of a dietary therapy alone (n = 37) in heart transplant patients receiving standard triple immunosuppression. After 4 years most of the patients in both groups received statins due to a significantly improved survival and a lower incidence of transplant vasculopathy., Results: After 11 years Kaplan-Meier survival rates were 77% in the simvastatin group versus 56.8% in the control group (p < 0.05). The incidence of graft coronary vasculopathy confirmed by angiography was 34.6% in the simvastatin group versus 73.9% in the control group (p < 0.01). There was no difference in organ function between the two groups., Conclusion: Statin therapy initiated in heart transplant patients early in the postoperative period plays an important role for better survival and lower incidence of transplant vasculopathy. The 11-year results of this study implicate that each heart transplant patient should receive early treatment with a statin as a matter of routine.

Objective: Allocation criteria changed in 2000 as a result of Germany's new transplantation law. Before, thoracic organs were primarily allocated electively within the donor region (according to urgency and waiting time). Afterwards, all patients in Germany eligible for heart transplants were registered in a national waiting list. With the exception of high-urgency patients that are approved by an audit committee, waiting time has become the major criteria for allocation. In this study, we investigated the impact of the new allocation system on economic aspects as on clinical results., Methods: One year in the new allocation system (NA) was compared to the previous year in the old allocation system (OA) regarding explantation/transportation distance, costs, ischemia time and clinical outcome. All explantations performed by our institution within Germany were evaluated., Results: The number of transplantations and the spectrum was similar between the two time periods (NA vs. OA: 61 vs. 57 overall). Eighty-two percent of these explanted organs were transplanted within the donor region in the OA time period, but only 37 % in the NA period. This resulted in higher transportation distances (NA: 441 +/- 177 km vs. OA: 179 +/- 118 km), higher transportation cost (NA: EUR 4,472 +/- 2,858 per explantation vs. OA: EUR 1,858 +/- 2,293 explantation, p = 0.001), and therefore longer ischemia times in the NA period (NA: 264 +/- 56 min: OA: 208 + 61 min, p = 0.001). Perioperative results and survival after a mean clinical follow-up of 21 +/- 8 (OA) and 11 +/- 5 (NA) months were comparable (86 % vs. 87 % (p = 0.93)., Conclusion: Transportation distance, costs for explantation and ischemia time increased significantly with the NA period. While the clinical short-term outcome proved to be comparable, we cannot yet judge the long-term impact of the prolonged ischemia time on the development of chronic rejection.

Study Objective: To evaluate whether transfusion of platelet-rich plasma from the organ donor during cardiac transplantation can influence the amount of the needed homologous blood products., Design: Randomized, controlled study., Setting: University hospital., Patients: 16 ASA physical status III patients undergoing orthotopic cardiac transplantation., Interventions: Eight patients received donor plasma, while another 8 patients served as a control group. Blood from the organ donor was acquired during cardiac explantation. Thereafter platelet-rich plasma was separated by plasmapheresis (2400 turns per minute). The plasma was then transfused to the organ recipient at the end of the cardiac transplantation. The control group received a similar amount of albumin 5%., Measurements and Main Results: In the patients who received donor plasma, the platelet count increased significantly from 98,000 +/- 49,000 mm-3 to 123,000 +/- 55,000 mm-3, the postoperative requirement of packed red blood cells (PRBCs) was 5.8 +/- 4.5 units, which was significantly lower as compared to the control group (10.8 +/- 5.9 units)., Conclusions: Transfusion of platelet-rich plasma from the organ donor to the recipient was confirmed to be feasible, the number of postoperatively transfused PRBCs was reduced.