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Background: Malignancy is a significant, life-limiting complication after lung transplantation (LuTx) and the second common long-term cause of death. We aimed to investigate its incidence and effect on the outcome. Methods: This is a retrospective observational study. Between 1996 and 2022, n = 627 lung transplantations (LuTx) were performed in our department. We used our institutional database to identify recipients with malignancies after LuTx and examined the malignancies’ incidence and mortality. Results: N = 59 malignancies occurred in n = 55 (8.8%) LuTx recipients. The post-LTx malignancies incidence was 9.4% (59/627). We report the following rates based on their location: n = 17/55 (28,8% of all recipients diagnosed with malignancies) skin, n = 10/55 (16,95%) gastrointestinal, n = 9/55 (15,3%) respiratory, n = 5/55 (8,48%) lymphatic, n = 13/55 (23,6%) other, n = 5 (8,48%) multiple synchronous.During this study period, a total of n = 328 deaths after LuTx was determined. N = 29 (8,84% of all deaths) were malignancy induced, corresponding to a total malignancy-induced mortality of 4.6% (n = 29/627). The majority of deaths were attributed to GI adenocarcinoma and PTLD. Malignancies’ origin, primary COPD diagnosis, type, and specific age group were significantly survival-related (p-values colorectal > PTLD. Post-LTx malignancy was the second commonest cause of death. Further studies are needed, while post-LuTx malignomas remain a serious impairment of long-term LuTx survival.

BackgroundEx vivo lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, specifically for marginal donor lungs after the donation after circulatory death. Despite major efforts, the optimal perfusion protocol and the composition of the perfusate in clinical lung transplantation have not been identified. Our study aims to compare the concentration levels of cytokine/chemokine in different perfusion solutions during EVLP, after 1 and 9 h of cold static preservation (CSP) in a porcine cardiac arrest model, and to correlate inflammatory parameters to oxygenation capacities.MethodsFollowing cardiac arrest, the lungs were harvested and were categorized into two groups: immediate (I-EVLP) and delayed EVLP (D-EVLP), after 1 and 9 h of CSP, respectively. The D-EVLP lungs were perfused with either Steen or modified Custodiol-N solution containing only dextran (CD) or dextran and albumin (CDA). The cytokine/chemokine levels were analyzed at baseline (0 h) and after 1 and 4 h of EVLP using Luminex-based multiplex assays.ResultsWithin 4 h of EVLP, the concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α, and IL-1β increased significantly (P

Introduction: Organ shortage, subsequent use of extended donor criteria organs and high-risk recipients needing redo-surgery are increasing the complexity of heart transplantation. Donor organ machine perfusion (MP) is an emerging technology allowing reduction of ischemia time as well as standardized evaluation of the organ. The aim of this study was to review the introduction of MP and analyze the results of heart transplantation after MP in our center. Methods: In a retrospective single-center study, data from a prospectively collected database were analysed. From July 2018 to August 2021, fourteen hearts were retrieved and perfused using the Organ Care System (OCS), 12 hearts were transplanted. Criteria to use the OCS were based on donor/recipient characteristics. Primary objective was 30-day survival, secondary objectives were major cardiac adverse events, graft function, rejection episodes as well as overall survival in the follow-up and assessment of MP technical reliability. Results: All patients survived the procedure and the postoperative 30-day interval. No MP related complications were noted. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsy showed excellent results with no or mild rejection. Two donor hearts were rejected after OCS perfusion and evaluation. Conclusion: Ex vivo normothermic MP during organ procurement is a safe and promising technique to expand the donor pool. Reduction of cold ischemic time while providing additional donor heart assessment and reconditioning options increased the number of acceptable donor hearts. Additional clinical trials are necessary to develop guidelines regarding the application of MP.

Background: Extra Corporeal Life Support (ECLS) is an evolving therapy in therapy-resistant cardiogenic shock (CS). Vascular cannulation in emergency situations can be accomplished through puncture of the femoral vessels by specialised teams. Since lower limb ischemia constitutes one of the major complications following cannulation, a distal perfusion cannula (DPC) has emerged as standard of care. We here aimed to analyse the impact of the DPC on limb perfusion and 6-month survival rate. Methods: In a retrospective study from January 2012 to December 2018, 98 patients with cardiogenic shock and peripheral (v-a) ECLS implantation with documented limb perfusion status were identified and analysed. Demographic data, laboratory parameters, cause of CS, comorbidities, limb perfusion complications and complication management were analysed. Results: 53 patients (54%) received ECLS therapy in referral centers by our mobile ECLS team, while in 45 patients (46%) the cannulation occured in our center. 71 patients (72%) received a DPC (group A) at the time of ECLS implantation, whereas 27 (28%) (group B) did not or received later (14 patients owing to limb ischemia). 44 patients (45%) developed limb ischemia as a complication of ECLS therapy (31% in group A and 81% in group B- p

Abstract Ex-vivo lung perfusion (EVLP) systems like XVIVO are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial cultures (46–89%) which leads to a donor-to-recipient transmission and after a higher risk of lung infection with reduced posttransplant outcome. We have previously shown that sphingosine very efficiently kills a variety of pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and epidermidis, Escherichia coli or Haemophilus influenzae. Thus, sphingosine could be a new treatment option with broadspectrum antiinfective potential, which may improve outcome after lung transplantation when administered prior to lung re-implantation. Here, we tested whether sphingosine has any adverse effects in the respiratory tract when applied into isolated ventilated and perfused lungs. A 4-h EVLP run using minipig lungs was performed. Functional parameters as well as perfusate measurements where obtained. Biopsies were obtained 30 min and 150 min after inhalation of sphingosine. Tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Hemalaun, TUNEL as well as stainings with Cy3-coupled anti-sphingosine or anti-ceramide antibodies were implemented. We demonstrate that tube-inhalation of sphingosine into ex-vivo perfused and ventilated minipig lungs results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea without morphological side effects up to very high doses of sphingosine. Sphingosine also did not affect functional lung performance. In summary, the inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated minipig lungs.

BackgroundEx-vivo lung perfusion (EVLP) is a save way to verify performance of donor lungs prior to implantation. A major problem of lung transplantation is a donor-to-recipient-transmission of bacterial cultures. Thus, a broadspectrum anti-infective treatment with sphingosine in EVLP might be a novel way to prevent such infections. Sphingosine inhalation might provide a reliable anti-infective treatment option in EVLP. Here, antimicrobial potency of inhalative sphingosine in an infection EVLP model was tested.MethodsA 3-hour EVLP run using pig lungs was performed. Bacterial infection was initiated 1-hour before sphingosine inhalation. Biopsies were obtained 60 and 120 min after infection with Pseudomonas aeruginosa. Aliquots of broncho-alveolar lavage (BAL) before and after inhalation of sphingosine were plated and counted, tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Immunostainings were performed.ResultsSphingosine inhalation in the setting of EVLP rapidly resulted in a 6-fold decrease of P. aeruginosa CFU in the lung (p = 0.016). We did not observe any negative side effects of sphingosine.ConclusionInhalation of sphingosine induced a significant decrease of Pseudomonas aeruginosa at the epithelial layer of tracheal and bronchial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated pig lungs.

Background The majority of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection present mild symptoms. However, some patients develop severe acute respiratory distress syndrome (ARDS) and subsequent irreversible lung damage despite extracorporeal membrane oxygenation, leaving lung transplantation the ultimate therapeutically option. Case Description Here, we report a case of lung transplantation in a 31-year-old male recipient suffering from post-coronavirus disease 2019 respiratory failure with irreversible ARDS after prolonged extracorporeal membrane oxygenation therapy. Conclusion Patient selection criteria are elucidated. One relevant mechanism for susceptibility to SARS-CoV-2 in the respiratory system, the acid sphingomyelinase/ceramide system might be altered during infection with SARS-CoV-2.

Abstract Background Resternotomy in cardiac surgery is considered a risk factor for postoperative complications. Previous studies have demonstrated an ambiguous relationship between resternotomy and clinical outcomes. Registry data from a mixed population of durable circulatory support devices suggest that history of cardiac surgery is a risk factor for mortality. Our study investigates the prognostic significance of resternotomy in a homogenous cohort of left ventricular assist device (LVAD) recipients. Methods The study included adult patients receiving a continuous-flow LVAD at our institution during the period 2010–2016. Postoperative adverse events and length of stay were analyzed. Survival was assessed at 6 months and by the end of the study. Multivariate risk factor analysis was conducted for independent predictors of death. Results One hundred twelve patients, who received an intrapericardial LVAD (HVAD, HeartWare), were included in our analysis. Twenty-four patients (21.4%) had a history of previous sternotomy. These patients were older and non-eligible for bridging, and had more frequently coronary heart disease. Univariate analysis demonstrated no differences in the observed complications postoperatively. Survival was similar among groups. Destination therapy was the only predictor of mortality in our analysis (p = 0.02). Conclusions Resternotomy was not associated with worse outcomes after LVAD implantation in our cohort.

Background and Objectives: The understanding of high body mass index (BMI) and outcomes after Left Ventricular Assist Device (LVAD) implantation continues to evolve and the relationship has not been established yet. In this study, we investigated the effects of obesity (BMI > 30 kg/m2) on post–LVAD implantation outcomes. HeartWare LVAD and Heart Mate III LVAD were implanted. The primary outcome that was measured was mortality (in-hospital and on follow-up). The secondary outcomes that were measured were major adverse events. Materials and Methods: At our institution, the West German Heart and Vascular Center (Essen, Germany), from August 2010 to January 2020, a total of 210 patients received a long-term LVAD. Patients were stratified according to BMI ≥ 30 kg/m2 representing the obesity threshold. The first group (n = 162) had an average BMI of 24.2 kg/m2 (±2.9), and the second group (n = 48) had an average BMI of 33.9 kg/m2 (±3.2). Baseline demographics were analysed alongside comorbidities per group. Results: Overall mortality was not significantly different between the obese group (51.1% n = 24) and the nonobese group (55.2%, n = 85) (p = 0.619). The difference between the mean duration of survival of patients who expired after hospital discharge was insignificant (2.1 years ± 1.6, group 1; 2.6 years ± 1.5, group 2; p = 0.29). In-hospital mortality was unvaried between the two groups: group 1: n = 34 (44% out of overall group 1 deaths); group 2: n = 11 (45.8% out of overall group 2 deaths) (p > 0.05). Postoperative complications were unvaried between the obese and the non-obese group (all with p > 0.05). However, a significant difference was found with regards to follow-up neurological complications (18.5% vs. 37.8%, p = 0.01) and LVAD thrombosis (14.7% vs. 33.3%, p = 0.01), as both were higher in the obese population. Conclusion: Obesity does not form a barrier for LVAD implantation in terms of mortality (in-hospital and on follow up). However, a significantly higher incidence of follow-up LVAD thrombosis and neurological complications has been found in the obese group of patients.