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Heart transplantation across preformed donor-specific HLA-antibody barriers is associated with impaired short- and long-term survival. Therefore, in recipients with preformed anti-HLA antibodies, waiting for crossmatch-negative donors is standard practice. As an alternative strategy, recipients with preformed anti-HLA donor specific antibodies have been managed at our institutions with a perioperative desensitization regimen. A retrospective analysis was performed comparing heart transplant recipients with preformed donor-specific HLA-antibodies to recipients without donor-specific antibodies. Recipients with a positive virtual crossmatch received a perioperative desensitization protocol including tocilizumab intraoperatively, plasma exchange and rituximab followed by a six-month course of IgGAM. Among the 117 heart-transplanted patients, 19 (16%) patients underwent perioperative desensitization, and the remaining 98 (84%) patients did not. Cold ischemic time, posttransplant extracorporeal life support for primary graft dysfunction, and intensive care unit stay time did not differ between groups. At 1-year follow-up, freedom from pulsed steroid therapy for presumed rejection and biopsy-confirmed acute cellular or humoral rejection did not differ between groups. One-year survival amounted to 94.7% in the treated patients and 81.4% in the control group. Therefore, heart transplantation in sensitized recipients undergoing a perioperative desensitization appears safe with comparable postoperative outcomes as patients with a negative crossmatch.

Aims: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX. Methods: We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus. Results: A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications (p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage (p = 0.011) compared to patients with VKAs after HTX in the Kaplan–Meier estimator. Conclusions: DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients.

Objectives Total ischemic time is considered a limiting factor in lung transplantation. In this retrospective study we investigate effects of ischemic time and disease burden on outcomes after bilateral lung transplantation. Methods 1,298 patients undergoing bilateral lung transplantation between January 2010 and May 2022 (Follow-up 100%, median 54 months) were included. Pre-transplant diseases ‘severity (recipient body mass index, recipient age, previous lung transplantation, Tacrolimus immunosuppression, preoperative recipient extracorporeal membrane oxygenation support, lung volume reduction) for graft failure was individually calculated and- as ischemic time- categorised. Vice-versa adjusted Cox models were calculated. Considering competing risks, we assessed cumulative incidences of airway obstructive complications and chronic lung allograft dysfunction with death as competing risk factors for primary graft dysfunction were assessed by binary logistic regression. Results Higher disease burden significantly accelerated chronic lung allograft dysfunction and death occurrence (p Conclusion The eventual graft survival disadvantage that results from an ischemic time between 7 and at least 11 hours is negligible in contrast to frequent recipients’ disease-based risk levels.

Donor shortages have led transplant centers to extend their criteria for lung donors. Accepting lung donors ≥70 years of age has previously shown good short-term outcomes; however, no mid- and long-term outcome data on these extended criteria donors has been published to date. In this study, all patients who underwent lung transplantation between 06/2010 and 12/2019 were included in the analysis, and the outcomes were compared between patients receiving organs from donors

OBJECTIVESLack of organ donors demands transplantation of older lung allografts for recipients between 0 and 50 years. So far, it has not yet been investigated whether donor–recipient age mismatch affects long-term outcome.METHODSRecords of patients aged between 0 and 50 years were retrospectively reviewed. Donor–recipient age mismatch was calculated subtracting recipient age from donor age. Multivariable Cox regression analyses was performed to assess donor–recipient age mismatch regarding the end points’ overall patient mortality, mortality conditioned to hospital discharge, biopsy-confirmed rejection and chronic lung allograft dysfunction. Furthermore, we performed competing risk analysis to analyse if age mismatch affects biopsy-confirmed rejection and CLAD while death being a competing risk.RESULTSBetween January 2010 and September 2021, out of 1363 patients who underwent lung transplantation at our institution, 409 patients fulfilled the eligibility criteria and were included. Age mismatch ranged between 0 and 56 years. Multivariable analysis revealed that donor–recipient age mismatch does not affect overall patient mortality (P = 0.19), biopsy-confirmed rejection (P = 0.68) and chronic lung allograft dysfunction (P = 0.42). There was no difference seen in CLAD (P = 0.166) and biopsy-confirmed rejection (P = 0.944) with the competing risk death (P = 0.765 and P = 0.851; respectively).CONCLUSIONSAge mismatch between recipients and donors of lung allografts does not affect long-term outcomes after lung transplantation.

OBJECTIVE Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children

Background The benefit of revascularizing chronically occluded coronary arteries remains debatable, and available long-term outcome reports are sparse. Current guidelines recommend revascularization of chronically occluded arteries only in patients with myocardial ischemia and/or symptoms associated with angina. We investigated outcome of patients with total chronic occlusion of the right coronary artery (RCA) receiving coronary artery bypass grafting (CABG) surgery with and without revascularization of the RCA. Methods We retrospectively analyzed all patients with chronically occluded RCAs receiving CABG with (group 1 = RCA-CABG; n = 487) and without (group 2 = No-RCA-CABG; n = 100) revascularization of the RCA. In total, 587 patients with complete follow-up of a minimum of 6 years were included (92%). Results In total, 82% in group 1 versus 86% in group 2 were male (P = .38). European System for Cardiac Operative Risk Evaluation II was comparable between both groups (4.35 ± 7.09% vs 4.80 ± 5.77%, P = .56) with no major differences regarding preoperative characteristics between groups. Patients in group 1 received 3.24 ± 0.79 distal anastomoses, whereas group 2 received 2.45 ± 0.83 distal anastomoses (P Conclusions Patients with a chronically occluded RCA undergoing CABG who did not receive an RCA graft showed a significantly reduced long-term survival. Given the herein presented data, revascularization of chronically occluded right arteries during CABG should be recommended whenever technically feasible.

Venous-arterial extracorporeal membrane oxygenation (ECMO) is an established technique for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Patients with pulmonary fibrosis have a higher risk to require it. The aim of this study was to identify risk factors for the need of intraoperative ECMO use.Records of patients undergoing lung transplantation for pulmonary fibrosis at our institution between January 2010 and May 2018 were retrospectively reviewed. Univariate logistic regression analysis was used for statistical identification of risk factors.There were 105 patients (34%) who required intraoperative ECMO support (ECMO+ group), and 203 (66%) did not (ECMO- group). Preoperative proof of pulmonary hypertension was identified as a risk factor for intraoperative ECMO support (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.2-6.5; P.01). Revealed mean pulmonary arterial pressure values exceeding 50 mm Hg and pulmonary vascular resistance values exceeding 9.4 Wood units were identified as risk factors for the need of intraoperative ECMO use with a prediction probability of 70%. Increased recipient body surface area (OR, 0.2; 95% CI, 0.1-0.5; P.01) emerged as a protective factor against intraoperative ECMO (Hosmer-Lemeshow statistic, P = .71) as well as higher cardiac output (OR, 0.7; 95% CI, 0.6-0.9; P.01). The postoperative course was more complicated in the ECMO+ group, whereas survival at 5 years did not differ among groups (70% vs 69%, P = .79).Pulmonary hypertension with elevated pulmonary vascular resistance values predicts the need of intraoperative ECMO in patients receiving lung transplantation for pulmonary fibrosis. Although the postoperative course was more complicated in the ECMO+ group, long-term survival did not differ significantly.

OBJECTIVES Our goal was to analyse adverse events in adolescent and adult patients with the Berlin Heart EXCOR and to assess the outcome of a subsequent heart transplant (HTX). METHODS From 2006 to 2020, a total of 58 patients (12–64 years old) received a biventricular assist device (BIVAD) at our institution and were included in this study. RESULTS The causes of biventricular heart failure were nonischaemic cardiomyopathy (62.1%), ischaemic cardiomyopathy (22.4%) and myocarditis (15.5%). The median INTERMACS score was I (I—III). The median age was 49 years (interquartile range, 34–55 years), and 82.8% were male. Causes of death were multiorgan failure (25.0%), septic shock (17.9%), cerebral haemorrhage (14.3%), bleeding (14.3%) and embolic events (14.3%). Major bleeding was more frequent in the patients who died while on BIVADs (60.7 vs 6.7%, P CONCLUSIONS Pump thrombosis, infections and bleeding after receiving a BIVAD did not preclude a successful HTX. Although only 50% of patients with BIVADs were successfully given a transplant, long-term survival after an HTX in patients with BIVAD was noninferior compared to that of other recipients.

Lung retransplantation remains the standard treatment of irreversible lung allograft failure. The most common indications for lung retransplantation are acute graft failure, chronic lung allograft dysfunction, and postoperative airway complications. Careful patient selection with regards to indications, anatomy, extrapulmonary organ dysfunction (specifically renal dysfunction), and immunologic consideration are of utmost importance. The conduct of the lung retransplantation operation is arduous with special considerations given to operative approach, type of surgery (single vs bilateral), use of extracorporeal circulatory support, and hematological management. Outcomes have improved significantly for most patients, nearing short and midterm outcomes of primary lung recipients in select cases.

Over the past decade, extracorporeal membrane oxygenation (ECMO) has replaced cardiopulmonary bypass (CPB) for cardiopulmonary support during lung transplantation at our institution. In this study, we present our experience using intraoperative ECMO in isolated lung transplantation and evaluate its impact on long-term graft function and survival.All patients undergoing isolated lung transplantation with or without ECMO support between January 2010 and June 2019 were evaluated. Patients transplanted using CPB were excluded. Peri-operative and follow-up results from our database and patient charts were analyzed. Follow-up continued until September 1, 2019 (median, 3.34 years).In total, 311 of 1,161 lung transplant recipients (27%) received intraoperative ECMO, with 24 (2%) patients further requiring CPB. None of the remaining 826 (71%) patients required intraoperative cardiopulmonary support. ECMO patients exhibited higher pre-transplant surgical risk profiles and endured more complicated early post-operative courses than those without ECMO (in-hospital mortality, 10.9% vs 2.3%; p0.001). Inevitably, this resulted in poorer overall graft survival among ECMO recipients (p = 0.0025). However, correcting for patients surviving to hospital discharge, no difference in survival between groups was observed (5-year survival, 71% vs 72%; p = 0.56). Similarly, freedom from chronic lung allograft dysfunction, biopsy-confirmed cellular rejection, or need for pulsed-steroid therapy did not differ between the groups (p = 0.99, p = 0.78, and p = 0.93, respectively).Compared with patients not requiring cardiopulmonary support, ECMO recipients endured a more complicated peri-operative and early post-operative course. However, among those surviving to hospital discharge, no differences in long-term complications or outcomes were observed.

Heart retransplantation remains a controversial issue, due to the overall shortage of donor organs. Many patients put on the waiting list for retransplantation, decompensate rapidly, and do not survive. The use of veno-arterial extracorporeal life support remains an option in such emergency situations as bridge-to-recovery or bridge-to-transplantation therapy. In peripheral femoral configuration, veno-arterial extracorporeal life support improves the patient’s condition by relieving low-cardiac output but immobilizes him or her for an uncertain period of time. The upper-body cannulation is an alternative approach, which allows to maintain the patient awake and mobile. We present two cases of midterm circulatory support as a bridge to heart retransplantation, using upper-body cannulation veno-arterial extracorporeal life support. Two male patients, presenting with progressive cardiac decompensation due to severe graft rejection, were placed on upper-body veno-arterial extracorporeal life support. The stabilization of hemodynamics and improvement of end-organ perfusion could be achieved after extracorporeal life support initiation. After 48 and 40 days, respectively, on extracorporeal life support with active physical therapy and no major adverse events, both patients received a cardiac retransplantation and were eventually discharged home. The presented cases are the first reported where a successful cardiac retransplant was performed following prolonged upper-body extracorporeal life support.

In this retrospective study, we analyzed the presence of any association of three CD4+ CD25high regulatory T-cell subpopulations at 3 weeks after lung transplantation with the later incidence of chronic lung allograft dysfunction and graft survival. Among lung-transplanted patients between January 2009 and April 2018, only patients with sufficient T-cell measurements at 3 weeks after transplantation were included into the study. Putative regulatory T cells were defined as CD4+ CD25high T cells, detected in peripheral blood and further analyzed for CD127low , FoxP3+ , and CD152+ using fluorescence-activated cell sorting (FACS) analysis. Associations of regulatory T cells with chronic lung allograft dysfunction (CLAD) and graft survival were evaluated using Cox analysis. During the study period, 724 (71%) patients were included into the study. Freedom from chronic lung allograft dysfunction (CLAD) and graft survival amounted to 66% and 68% at 5 years. At the multivariable analysis, increasing frequencies of CD127low were associated with better freedom from CLAD (hazard ratio for each 1% increase of %CD127low , HR = 0.989, 95% CI = 0.981-0.996, P = 0.003) and better graft survival (HR = 0.991, 95% CI = 0.984-0.999, P = 0.026). A higher frequency of CD127low regulatory T cells in peripheral blood early after lung transplantation estimated a protective effect against chronic lung allograft dysfunction, mortality, and re-transplantation.

OBJECTIVES Experience with the treatment of early donor-specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, we have treated patients with eDSA since 2013 with successive infusions of intravenous human immunoglobulins (IVIG), combined in some cases with a single dose of Rituximab and plasmapheresis (therapeutic plasma exchange [tPE]) or immunoabsorption. The aim of this study was to present the 6-year results of IVIG-based therapy in pediatric lung recipients. METHODS Records of pediatric (

OBJECTIVES The management of severe coronary artery disease at the time of a lung transplant remains a challenge. We analysed the short- and long-term outcomes of lung transplant recipients with severe coronary artery disease. METHODS Records of adult patients who received transplants at our institution between April 2010 and February 2021 were reviewed retrospectively. Severe coronary artery disease was defined as coronary stenosis ≥70% (main stem ≥50%) seen on the coronary angiographic scans performed before or at the time of listing. Patient characteristics, perioperative and long-term outcomes were compared between patients with and without severe coronary artery disease. RESULTS Among 896 patients who received lung transplants who had undergone coronary angiography before the transplant, 77 (8.5%) had severe coronary artery disease; the remaining 819 (91.5%) did not. Patients with severe coronary artery disease were older (p CONCLUSIONS Severe coronary artery disease was not associated with decreased survival after a lung transplant. Concomitant coronary artery bypass graft surgery and pretransplant percutaneous transluminal coronary angioplasty can be used for revascularization.

In children with pulmonary arterial hypertension, lung transplantation illustrates a feasible treatment option once pharmacological therapy is exhausted. Timing of listing for lung transplantation in children remains difficult since hemodynamic deterioration often occurs abruptly and the time on the waiting list is usually hard to predict. Clear contraindications for lung transplantation are recent history of malignancies as well as irreversible end-organ failure. Generally, patients with pulmonary arterial hypertension in the absence of structural cardiac defects can safely undergo bilateral lung transplantation, combined heart-lung transplantation remains a procedure with a higher perioperative risk and should only be performed in selected cases with irreversible structural defects. Donor selection in recent years shows donors with extended criteria as well as lobar transplantation with good outcome, having the positive effect of broadening of the donor pool. Bridging to lung transplantation with veno-arterial ECMO treatment is feasible and has a good outcome in experienced transplant centers. Surgical considerations should include the risk of hemodynamic decompensation upon anesthesia induction and the need for extracorporeal support pre-, intra- and postoperative. Lung transplantation should be performed on veno-arterial ECMO support with either peripheral (>20 kg) or central cannulation (

Disparities at the major histocompatibility complex (MHC) antigens and associated minor antigens trigger harmful immune responses, leading to graft rejection after transplantation. We showed that MHC-silenced cells and tissues are efficiently protected against rejection. In complex vascularized organs, the endothelium is the major interface between donor and recipient. This study therefore aimed to reduce the immunogenicity of the lung by silencing MHC expression on the endothelium. In porcine lungs, short-hairpin RNAs targeting beta-2-microglobulin and class II-transactivator transcripts were delivered by lentiviral vectors during normothermic ex vivo perfusion to silence swine leukocyte antigen (SLA) I and II expression permanently. The results demonstrated the feasibility of genetically engineering all lung regions, achieving a targeted silencing effect for SLA I and II of 67% and 52%, respectively, without affecting cell viability or tissue integrity. This decrease in immunogenicity carries the potential to generate immunologically invisible organs to counteract the burden of rejection and immunosuppression.

Background: Venoarterial extracorporeal membrane oxygenation support is a well-established tool in the care of severe refractory cardiac and respiratory failure. The application of this support may serve as a bridge to transplant, recovery or to implantation of a ventricular assist device. Venoarterial extracorporeal membrane oxygenation support can be administered through an open surgical access via the common femoral or axillary artery or a percutaneous approach using Seldinger technique. Both techniques may obstruct the blood flow to the lower limb and may cause a significant ischemia with possible limb loss. Malperfusion of the distal limb can be avoided using an ipsilateral distal limb perfusion, which may be established by adding a single-lumen catheter during venoarterial extracorporeal membrane oxygenation treatment to overcome the obstruction. The aim of this study is to distinguish the presence or absence of a distal limb perfusion regarding the incidence of distal limb ischemia. Furthermore, expected risk factors of open and percutaneous femoral venoarterial extracorporeal membrane oxygenation installation were evaluated for the development of distal limb ischemia. Methods: Between January 2012 and September 2015, 489 patients received venoarterial extracorporeal membrane oxygenation support at our institution. In total, 307 patients (204 male, 103 female) with femoral cannulation were included in the analysis. The cohort was distinguished by the presence (group A; n = 237) or absence (group B; n = 70) of a distal limb perfusion during peripheral venoarterial extracorporeal membrane oxygenation treatment. Furthermore, a risk factor analysis for the development of distal limb ischemia was performed. Results: The main indications for venoarterial extracorporeal membrane oxygenation therapy were a low cardiac output syndrome (LCOS) (53%) and failed weaning of extracorporeal circulation (23%). A total of 23 patients (7.49%) under venoarterial extracorporeal membrane oxygenation support developed severe distal limb malperfusion (3.38% in group A vs 21.42% in group B). Preemptive installation of distal limb perfusion extended the intervention-free intervals to 7.8 ± 19.3 days in group A and 6.3 ± 12.5 in group B. A missing distal limb perfusion (p = 0.001) was identified as a main risk factor for critical limb ischemia. Other comorbidities such as arterial occlusion disease (p = 0.738) were not statistically significantly associated. Surgical intervention due to vascular complications after extracorporeal membrane oxygenation explantation was needed in 14 cases (4.22% in group A and 5.71% in group B). Conclusion: We were able to identify the absence of distal limb perfusion as an independent risk factor for the development of critical distal limb ischemia during femoral venoarterial extracorporeal membrane oxygenation treatment. The application of a distal limb perfusion should be considered as a mandatory approach in the context of femoral venoarterial extracorporeal membrane oxygenation treatment regardless of the implantation technique.

This study evaluated the impact of unilateral diaphragm elevation following bilateral lung transplantation on postoperative course. Patient data for all lung transplantations performed at our institution between 01/2010 and 12/2019 were reviewed. Presence of right or left diaphragm elevation was retrospectively evaluated using serial chest X-rays performed while patients were standing and breathing spontaneously. Right elevation was defined by a > 40 mm difference between right and left diaphragmatic height. Left elevation was present if the left diaphragm was at the same height or higher than the right diaphragm. In total, 1093/1213 (90%) lung transplant recipients were included. Of these, 255 (23%) patients exhibited radiologic evidence of diaphragm elevation (right, 55%; left 45%; permanent, 62%). Postoperative course did not differ between groups. Forced expiratory volume in 1 second, forced vital capacity and total lung capacity were lower at 1-year follow-up in patients with permanent than in patients with transient or absent diaphragmatic elevation (P = 0.038, P < 0.001, P = 0.002, respectively). Graft survival did not differ between these groups (P = 0.597). Radiologic evidence of diaphragm elevation was found in 23% of our lung transplant recipients. While lung function tests were worse in patients with permanent elevation, diaphragm elevation did not have any relevant impact on outcomes.

Background Ischemia/reperfusion injury (IRI) is associated with inflammatory responses contributing to the development of primary graft dysfunction (PGD) and rejection. Here, we investigated the pathophysiology of IRI and the early phase after heart transplantation (HTx) regarding its cytokine/chemokine and endothelial networks. Methods Using multiplex technology, we assessed protein concentrations in plasma samples of HTx recipients (n = 11) pre-, postoperatively, 24 h and 3 weeks after HTx. The same proteins were quantified in organ storage solutions at the end of heart storage (n = 10). Unsupervised cluster, principal component analysis (PCA), K-nearest neighbor (KNN) network classifier analysis, ANOVA and Spearman correlation analyses were performed to identify specific patterns for IRI and individual kinetics of important soluble factors in HTx. Results Unique patterns of soluble factors were identified in plasma of HTx patients. KNN analysis defined IL-10, IL-6, sIL-6Rα, IL-1RA, IL-16, sVEGFR-1, IGFBP-1, HGF and sHer-2 as strongest signals directly post-Tx declining 24 hrs after HTx. By contrast, MIF, osteopontin (OPN), sVCAM-1 and sICAM-1, IGFBP-1, SCGF-s, HGF were highly enriched in organ storage solutions, reflecting distinct ischemic (storage solution) vs. reperfusion (plasma) signatures. Conclusions We identified specific inflammatory signatures for ischemic vs. reperfusion phases of HTx, associated with pro- as well as anti-inflammatory and endothelial biomarker candidates for IRI. These signatures might help to identify potential danger factors and their networks at both the ex situ (ischemic) as well as the reperfusion phase in the recipient after implantation.

Purpose Pediatric lung transplantation poses unique challenges, from donor shortage to surgical access, intraoperative cardiopulmonary support and postoperative management. Moreover, experience with pediatric lung transplantation is scarce, especially in patients younger than 12 years old. In this study, we present our 15-year experience with lung transplantation in pediatric patients younger than 12 years old. Methods Records of pediatric (≤18 years old) patients transplanted at our institution between 01/2005 and 10/2020 were retrospectively reviewed. Outcomes were compared between pediatric patients Results During the study period, among the 1,741 lung-transplanted patients, 125 (7%) patients were pediatric, being 43 (34%) patients Conclusion Lung transplantation in patients

We previously induced long-term allograft acceptance in an allogeneic lung transplantation (LTx) model in miniature swine using perioperative non-myeloablative irradiation (IRR) combined with infusion of donor specific alloantigen. In order to improve clinical applicability, we delayed induction with irradiation in this study. Left sided single LTx was performed in minipigs. Group 1 received non-myeloablative irradiation (7Gy thymus and 1.5Gy whole body IRR) before LTx and a perioperative donor specific splenocyte infusion (SpTx). Group 2 received perioperative SpTx but delayed IRR three days after LTx. Group 3 was exposed to delayed IRR without SpTx. Whereas 4 out of 7 animals from the non-delayed group never rejected their grafts and were electively sacrificed on postoperative day (POD) +500, all animals from group 2 rejected their grafts before POD 108. In group 3, 3 out of 8 animals developed long-term allograft acceptance. In all groups, donor leukocyte chimerism peaked up to 20% in peripheral blood one hour after reperfusion of the lung. Group 1 maintained prolonged chimerism beyond POD 7, whereas chimerism levels in groups 2 and 3 decreased continuously thereafter. Delayed irradiation has the potential to improve long-term graft survival, yet not as efficient as a perioperative conditioning protocol.

Purpose Everolimus is a proliferation signal inhibitor used for triple immunosuppressive therapy following solid organ transplantation. Its positive benefits, such as reduction of acute rejection episodes and reduced nephrotoxicity have been shown in kidney- as well as heart transplantation. However the role of everolimus is less well defined in lung transplantation. We thus wished to study the effect of primary immunosuppression with everolimus in a preclinical large animal lung transplantation model. Methods Left-sided single lung transplantation from MHC-mismatched donors was performed in 11 adult minipigs. Intravenous pharmacologic immunosuppression was maintained for 28 days with 1.5 mg/kg/d methylprednisolone, 1.0 mg/kg/d azathioprine and cyclosporine A (blood levels 300-500 ng/ml; CsA group; n = 5). A further group (CsA + Ev; n = 6) received methylprednisolone, CsA (200–300 ng/ml) and Everolimus (5–10 ng/ml). Immunosuppression was discontinued on postoperative day (POD) 28. Graft survival was monitored by sequential chest X-rays, bronchoscopies and transbronchial biopsy histology. Results All animals survived the 28 day course of immunosuppressive therapy and showed healthy grafts on POD 28. Median allograft survival in the CsA group was 55 ± 15 days. CsA + Ev grafts showed median survival of 49 ± 86 days (p = 0.37). Conclusion Whereas everolimus might be advantageous as maintenance immunosuppressive agent, this data does not support an important role for everolimus in the immunosuppressive induction phase following lung transplantation.

This retrospective study presents our 4‐year experience of preemptive treatment of early anti‐HLA donor specific antibodies with IgA‐ and IgM‐enriched immunoglobulins. We compared outcomes between patients with antibodies and treatment (case patients) and patients without antibodies (control patients). Records of patients transplanted at our institution between March 2013 and November 2017 were reviewed. The treatment protocol included one single 2 g/kg immunoglobulin infusion followed by successive 0.5 g/kg infusions for a maximum of 6 months, usually combined with a single dose of anti‐CD20 antibody and, in case of clinical rejection or positive crossmatch, with plasmapheresis or immunoabsorption. Among the 598 transplanted patients, 128 (21%) patients formed the case group and 452 (76%) the control group. In 116 (91%) patients who completed treatment, 106 (91%) showed no antibodies at treatment end. Fourteen (13%) patients showed antibody recurrence thereafter. In case versus control patients and at 4‐year follow‐up, respectively, graft survival (%) was 79 versus 81 (P = .59), freedom (%) from biopsy‐confirmed rejection 57 versus 53 (P = .34), and from chronic lung allograft dysfunction 82 versus 78 (P = .83). After lung transplantation, patients with early donor‐specific antibodies and treated with IgA‐ and IgM‐enriched immunoglobulins had 4‐year graft survival similar to patients without antibodies and showed high antibody clearance., Lung‐transplanted patients who develop early anti‐HLA donor‐specific antibodies and are treated with a protocol based on successive infusion of IgA‐ and IgM‐enriched intravenous immunoglobulins show good antibody clearance and graft survival, similar to the survival of patients without early donor‐specific antibodies.

Background Lung retransplantation is a demanding procedure with outcomes lagging primary transplantation. We implemented less invasive surgical techniques aiming at improving early outcomes. Here, we wish to describe these techniques and analyze the clinical outcomes. Methods Since April 2010, a protocol of less invasive techniques was applied to all lung retransplantations. This protocol comprises bilateral lung retransplantation via sternum-sparing anterolateral thoracotomies, off-pump surgery, and empiric administration of 2 g fibrinogen and 2 platelet concentrates. Patient charts were retrospectively reviewed starting in April 2010 until May 2016 for this study and compared with a cohort of patients undergoing lung retransplantation between January 2005 and March 2010. Results From April 2010 through March 2016, 774 total lung transplantations were performed at our center, 49 were retransplantations. In the era January 2005 to March 2010, a total of 480 lung transplantations were performed, 38 of those being retransplantations. Mean operation time in the era April 2010 to May 2016 was significantly longer as compared with the era January 2005 to March 2010, median time until extubation was significantly shorter in the era April 2010 to May 2016 (1 [1-2] days vs 11.5 [1-24] days; P = 0.0009). Similarly, median intensive care unit stay time was shorter in the era April 2010 to May 2016 (4 [2-5.5] days vs 12.5 [3-30.5] days; P = 0.003). Patient survival was significantly better in the era starting in April 2010 at 30 days (98% vs 76.3%, P = 0.002) as well as at 1 year (80.6% vs 63.2%; P = 0.01). Conclusions Less invasive retransplantation of the lung via sternum-sparing anterolateral thoracotomies and off-pump is a safe procedure with low associated morbidity and favorable midterm survival.

OBJECTIVES Extracorporeal membrane oxygenation (ECMO) has an important role in bridging patients to lung transplantation. In this study, we present our experience with pretransplant ECMO during the last 7 years and investigate its impact on graft outcomes. METHODS Records of all lung-transplanted patients at our institution between January 2010 and April 2017 were retrospectively reviewed. Graft survival was compared between patients who required pretransplant ECMO (pre-Tx ECMO+) and patients who did not (pre-Tx ECMO-). Risk factors for in-hospital mortality and graft survival were identified using a binary logistic regression and the Cox regression analyses, respectively. RESULTS Among the 917 patients transplanted during the study period, 68 (7%) required ECMO as a bridge to transplantation [awake strategy, n = 57 (84%) patients]. Median bridging time was 9 days. Among pre-Tx ECMO+ patients, the need for haemodialysis at any point during bridging emerged as an independent risk factor for in-hospital mortality (odds ratio 7.79, 95% confidence interval 1.21-50.24; P = 0.031). Although in-hospital mortality was significantly higher in pre-Tx ECMO+ versus pre-Tx ECMO- patients (15% vs 5%, P = 0.003), overall graft survival did not differ between groups (79% vs 90% and 61% vs 68% at 1 and 5 years, respectively, P = 0.13). Pretransplant ECMO did not emerge as a risk factor for graft survival in the multivariable analysis. CONCLUSIONS If applied in selected patients in a high-volume centre, pretransplant ECMO as a bridge to transplantation results in impaired, but still high in-hospital, survival and does not impact graft survival.