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PubMed displayed almost 37,000 hits for the search term “cardiac surgery AND 2022.” As before, we used the PRISMA approach and selected relevant publications for a results-oriented summary. We focused on coronary and conventional valve surgery, their overlap with interventional alternatives, and briefly assessed surgery for aorta or terminal heart failure. In the field of coronary artery disease (CAD), key manuscripts addressed prognostic implications of invasive treatment options, classically compared modern interventions (percutaneous coronary intervention [PCI]) with surgery (coronary artery bypass grafting [CABG]), and addressed technical aspects of CABG. The general direction in 2022 confirms the superiority of CABG over PCI in patients with anatomically complex chronic CAD and supports an infarct-preventative effect as underlying mechanism. In addition, the relevance of proper surgical technique to achieve durable graft patency and the need for optimal medical treatment in CABG patients was impressively illustrated. In structural heart disease, the comparisons of interventional and surgical techniques have been characterized by prognostic and mechanistic investigations underscoring the need for durable treatment effects and reductions of valve-related complications. Early surgery for most valve pathologies appears to provide significant survival advantages, and two publications on the Ross operation prototypically illustrate an inverse association between long-term survival and valve-related complications. For surgical treatment of heart failure, the first xenotransplantation was certainly dominant, and in the aortic surgery field, innovations in arch surgery prevailed. This article summarizes publications perceived as important by us. It cannot be complete nor free of individual interpretation, but provides up-to-date information for decision-making and patient information.

PubMed displayed more than 35,000 hits for the search term “cardiac surgery AND 2021.” We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) approach and selected relevant publications for a results-oriented summary. As in recent years, we reviewed the fields of coronary and conventional valve surgery and their overlap with their interventional alternatives. COVID reduced cardiac surgical activity around the world. In the coronary field, the FAME 3 trial dominated publications by practically repeating SYNTAX, but with modern stents and fractional flow reserve (FFR)-guided percutaneous coronary interventions (PCIs). PCI was again unable to achieve non-inferiority compared with coronary artery bypass graft surgery (CABG) in patients with triple-vessel disease. Survival advantages of CABG over PCI could be linked to a reduction in myocardial infarctions and current terminology was criticized because the term “myocardial revascularization” is not precise and does not reflect the infarct-preventing collateralization effect of CABG. In structural heart disease, new guidelines were published, providing upgrades of interventional treatments of both aortic and mitral valve disease. While for aortic stenosis, transcatheter aortic valve implantation (TAVI) received a primary recommendation in older and high-risk patients; recommendations for transcatheter mitral edge-to-edge treatment were upgraded for patients considered inappropriate for surgery. For heart team discussions it is important to know that classic aortic valve replacement currently provides strong signals (from registry and randomized evidence) for a survival advantage over TAVI after 5 years. This article summarizes publications perceived as important by us. It can neither be complete nor free of individual interpretation, but provides up-to-date information for decision-making and patient information.

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.

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.

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.

INTRODUCTION AND OBJECTIVES Malnutrition has been shown to affect clinical outcomes in patients with heart failure. The aim of this study was to analyze the impact of preoperative nutritional status assessed by the nutritional risk index (NRI) on the prognosis of patients with a continuous-flow left ventricular assist device (cf-LVAD). METHODS We performed a retrospective study of 279 patients who underwent cf-LVAD implantation between 2009 and 2015 in our center. Preoperative NRI was calculated and the patients were followed-up for 1 year. The association between preoperative NRI and postoperative clinical events was analyzed using multivariable logistic regression. RESULTS The prevalence of severe (NRI

Resumen Introduccion y objetivos La desnutricion influye en la evolucion clinica de los pacientes con insuficiencia cardiaca. El objetivo es analizar el impacto del estado nutricional preoperatorio evaluado mediante el indice de riesgo nutricional (IRN) en el pronostico de los pacientes que recibieron dispositivos de asistencia ventricular izquierda de flujo continuo (DAVI-fc). Metodos Estudio retrospectivo de 279 pacientes tratados con implante de DAVI-fc entre 2009 y 2015 en el centro. Se calculo el IRN preoperatorio y se realizo un seguimiento del primer ano tras el implante. Se analizo mediante regresion la asociacion entre el IRN preoperatorio y los eventos clinicos posoperatorios. Resultados Las prevalencias de riesgo nutricional grave (IRN Conclusiones Los pacientes desnutridos tienen mayor riesgo de complicaciones posoperatorias y muerte despues del implante de un DAVI-fc. La evaluacion del riesgo nutricional puede contribuir a mejorar la seleccion de pacientes e iniciar un apoyo nutricional precoz.

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.

OBJECTIVES A combined lung and liver transplant in patients with cystic fibrosis (CF) is an uncommon procedure. The goal of this study was to compare long-term outcomes between patients with CF who underwent either a combined lung-liver or a lung-only transplant. METHODS This is a retrospective single-centre study of patients with CF who underwent a lung transplant between January 2005 and May 2020. Since 2006, our preference for a combined lung-liver transplant was to transplant the liver first and then the lung. Outcomes were compared using the Kaplan–Meier analysis and the log-rank test. Median follow-up was 53 (23–97) months. RESULTS During the study period, among 357 patients with CF who underwent a lung transplant, 14 (4%) required a lung-liver transplant whereas 343 (96%) had a lung-only transplant. Lung cold ischaemic time was longer in the lung-liver transplant group, but no patient in this group showed primary graft dysfunction at 72 h after the transplant. Prevalence of anti-human leucocyte antigen donor-specific antibodies was 7.1% vs 13.7% in the lung-liver versus the lung-only transplant group (P = 0.42). At 5 years, lung graft survival (78% vs 69%) and freedom from chronic lung allograft dysfunction (79% vs 62%) did not differ between the lung-liver versus the lung-only groups (P = 0.45 and P = 0.55, respectively). Freedom from lung biopsy-confirmed rejection was significantly higher in patients undergoing a lung-liver transplant (91% vs 50%; P = 0.027). CONCLUSIONS A lung-liver transplant did not impair lung graft function. The lower prevalence of donor-specific antibodies and the better freedom from lung biopsy-confirmed rejection suggest tolerogenic effects of the liver graft.

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.

Purpose Lack of organ donors demands transplantation of older lungs into younger recipients. Providing that other general organ donor selection criteria are fulfilled; it still remains questionable whether high age mismatch negatively affects short- and long-term outcomes. Here we investigate outcomes of lung recipients aged between 0 and 50 years whose donors had a high or low age mismatch compared to their respective recipients. Methods Records of patients aged between 0 and 50 years (33±12 years) and transplanted between 2005 and 2020 were retrospectively reviewed. Two groups were formed, one including recipients who received organs from donors at least 20 years older (high-mismatch group) and the other group including recipients whose donors were not older than 10 years (low-mismatch group) compared to their corresponding recipients. Donor smoking status, pO2-pressure and ventilation time (days) were evaluated. Incidence of Primary Graft Dysfunction grade 3 (PGD 3), ICU stay, ventilation time, perioperative hospital stay, chronic lung allograft dysfunction (CLAD) and graft survival were compared using Chi-Square test, Mann-Whitney-U test and Kaplan-Meier analysis, respectively. Results During the study period, among the 1722 patients transplanted at our institution, 172 (9.9 %) patients form the high-mismatch group and 212 (12.3%) patients the low mismatch group. Prevalence of donor smoking history was higher in low-mismatch recipients (34% vs. 46%; p=0.024). PO2-pressure (390 vs. 405 mmHg; p=0.39) and median ventilation time (4 vs. 4 days; p=0.898) prior organ procurement did not differ between groups. Incidence of PGD Grade 3 after 48 (11% vs. 6%; p=0.078) and 72 (11% vs. 6%; p=0.078) hours was not significantly different. Median mechanical ventilation (14 vs. 14 hours; p=0.76), ICU stay (4 vs. 4 days; p=0.6) and postoperative hospital stay times (25 vs. 24 days; p=0.17) did not differ between groups. At 5- and 10-year follow-up, overall graft survival (66.3% vs. 67.3%, 54% vs. 48%, p=0.956), patient survival conditioned to hospital discharge (75.7% vs. 79.2%, 62.9% vs. 64.1%, p=0.541) and freedom from CLAD (57.6% vs. 62.9%, 47% vs. 38%, p=0.944) was comparable between the groups. Conclusion Age mismatch alone is not a limiting factor for accepting donor lungs. Long term survival and incidence of CLAD are not affected providing general donor organ selection criteria are considered.

OBJECTIVES In severe pulmonary hypertension, diastolic dysfunction of the left ventricle causes significant morbidity and mortality after lung transplantation, which may be successfully reversed using a protocol based on perioperative veno-arterial extracorporeal membrane oxygenation (ECMO) and early extubation. Here, we present echocardiographic data and mid-term outcomes. METHODS The records of lung transplanted patients at our institution between May 2010 and January 2016 were retrospectively reviewed. Echocardiography data were collected preoperatively, at discharge, 3 and 12 months after transplantation. RESULTS During the study period, 717 patients underwent lung transplantation at our institution, 38 (5%) patients being transplanted for severe pulmonary hypertension. All patients underwent bilateral lung transplantation on veno-arterial ECMO cannulated in the groin, through a sternum sparing thoracotomy in 36 (95%) patients. Extubation was performed early, after a median of 2 days, and awake ECMO was extended for at least 5 days after transplantation. The survival at 3 months, 1 year and 5 years was not different in comparison to patients transplanted for other underlying diseases ( P = 0.45). At 1 year, tricuspid valve regurgitation had disappeared in all patients. The median of the left ventricular end-diastolic dimension improved from 40 (32-44) mm preoperatively to 45 (44-47) mm at 12 months after lung transplantation ( P

Purpose Chronic lung allograft dysfunction (CLAD) is the most important complication after lung transplantation (LTx), which is classified bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Acute rejection (AR) is a high potential risk factor for BOS. Therefore, we have analyzed our clinical database to search the missing link between AR and BOS. Methods From January 2015 to March 2020, 746 patients underwent LTx in our institute. In this cohort, 88 patients suffered from AR (11.8%). These patients were divided in patients with BOS and without BOS. Results Our AR incident was also a risk factor of BOS (p=0.003). Mean age AR patients amounted to 47.1 years old. Forty-five patients were male (51.1%). Transplant indication was lung fibrosis (n=32, 36.4%), COPD (n=27, 30.7%), cystic fibrosis (n=13, 14.8%), bronchiectasis (n=4, 4.5%), pulmonary hypertension (n=3, 3.4%), sarcoidosis (n=2, 2.3%), re-transplantation (n=4, 4.5%) and others (n=3). Nine (10.2%) patients showed primary graft dysfunction (PGD) Grade 2-3. At follow-up, 29 (33%) patients developed BOS. Transplant indications did not differ between BOS patients and BOS-free patients. Similarly, age, gender, and PGD Grade 2-3 did not differ between groups. Incidence of infection was significantly higher in BOS than BOS-free patients (p=0.0002). The infections occurred before the AR (n=12) after AR (n=12) and after BOS episode (n=7) in BOS patients (There were repeated infection episodes in 6 patients). Moreover, the first episode of AR occurred earlier in BOS-free patients than that of BOS patients (5.5 months vs. 14.6 months, respectively: p=0.003) Conclusion In our cohort, infection is a risk factor for BOS in patients with AR. However, the infection episode occurred not only after AR but also before AR and after BOS. That means, it could not be related between AR and BOS. The most significant difference was in the first AR phase.

Purpose At our institution, since early 2010, patients with severe pulmonary hypertension have been transplanted using a protocol based on postoperative extension of intraoperatively-started veno-arterial extracorporeal membrane oxygenation (vaECMO) support. Here we present our 10-year experience with bilateral lung transplantation using vaECMO support in patients with severe pulmonary hypertension. Methods Records of patients transplanted at our institution between January 2010 and October 2020 were retrospectively reviewed. Prevalence of primary graft dysfunction (PGD) and ventilation time were compared between patients transplanted for severe pulmonary hypertension vs. patients transplanted for other indications (control group), using Chi-Square test and Mann-Whitney U test, respectively. Graft survival and freedom from chronic lung allograft dysfunction (CLAD), were compared between groups using Kaplan-Meyer analysis with the log-rank test. Results During the study period, among the 1288 lung transplanted patients at our institution, 85 (6.2%) patients were transplanted for sPAH and 1201 (93.8%) patients for other indications. Patients with severe pulmonary hypertension were younger than control patients (31 vs. 47 years, p Conclusion A protocol based on postoperatively-extended intraoperative ECMO support allows safe transplantation of sPHT patients. Despite increased morbidity in the early postoperative period, long-term survival and freedom from CLAD do not differ compared to patients who were transplanted for other indications.

Purpose Development of anti-HLA donor specific antibodies early after lung transplantation (eDSA) has been associated with antibody-mediated rejection (AMR) and poor graft survival. Since 2013, our institution has employed successive infusions of IgA- and IgM-enriched intravenous immunoglobulins (IgGAM, first infusion: 2gr/kg, then 0.5gr/kg once every 4 weeks for a maximum of 6 months) as 1st line treatment in such cases. Asymptomatic eDSA development (possible subclinical AMR) was treated with IgGAM only. Patients with concomitant graft dysfunction (possible clinical AMR) or positive crossmatch additionally receive 5 sessions of plasmapheresis pre-IgGAM, and a single dose of anti-CD20 antibody (Rituximab) afterwards. This study was presents 7-year results of this IgGAM-based protocol. Methods Records of patients transplanted between 02/2013 and 10/2020 were reviewed. Outcomes were compared between patients with eDSA and treated with IgGAM (IgGAM group) and those without eDSA (control group). Median follow-up was 41 (18-64) months. Results he 913 transplanted recipients, 224 (25%) patients were included in the IgGAM group and 667 (73%) the control group. The remaining 22 (2%) patients (13 patients with eDSA but not treated, and 9 patients treated only with tPE and Rituximab) were excluded. Forty-one (18%) IgGAM patients exhibited pre-formed eDSA and 16 (7%) patients showed a positive retrospective crossmatch. Thirty-six (16%) patients showed concomitant graft dysfunction (possible clinical AMR). Median time to eDSA detection was 14 days post-transplant. At follow-up end, treatment was completed in 204 (91%) patients (ongoing treatment, n=7; in-hospital deaths, n=4; treatment prematurely interrupted, n=9). In these 204 patients, IgGAM treatment cleared eDSA in 184 (90%) patients. Twenty-five (12%) patients developed eDSA recurrence at a median of 9 months after completing treatment. Clearance was less effective in patients with preformed eDSA (p Conclusion In lung recipients, treatment of eDSA with IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM-treatment have good 7-year graft survival similar to control patients.

Purpose Although use of extended-criteria donor organs (ECD) has increased in lung transplantation, their impact on outcomes remains unclear. The Eurotransplant (ET) lung donor score (ELDS) was designed to classify lung donor quality, taking into account donor history, tobacco exposure, age, arterial blood gases, chest x-ray and bronchoscopic findings. This retrospective single-center study evaluates the impact of ECD on graft function and survival. Methods Records of lung allograft recipients transplanted at our institution between 01/2010 and 10/2020 were reviewed. Individual ELDS were calculated from the corresponding ET donor reports. Outcomes were compared between recipients of ideal donors (ELDS 6, Group 1), of intermediate-risk donors (ELDS 7-8, Group 2), and of extended-criteria donors (ELDS 9-15, Group 3). Median (IQR) follow-up was 46 (20-77) months. Results In total, 238/1,283 (19%) patients received Group 1 donor organs, 651 (51%) patients Group 2 donor organs, and 394 (30%) patients Group 3 donor organs. Group 2 and 3 recipients were older than group 1 recipients (median age, 52 and 54 vs. 43 years, p Conclusion ECD lungs constituted one third of our donor pool. Their use did not negatively impact the recipient survival, but CLAD-free survival was worse in ECD recipients.

Purpose After lung transplantation (LuTx), the development of early donor HLA-specific antibodies (eDSA) has been shown to be associated with antibody-mediated rejection (AMR) and poor graft survival. Since 2013, patients with eDSA within the first month after LuTx in our center are treated with IgA/IgM enriched intravenous immunoglobulins (IgGAM), combined with anti-CD20 antibody (Rituximab). We addressed the hypothesis that naive vs. memory B cell subsets differ between eDSA-positive and negative patients already early after LuTx before onset of the treatment regimen. Methods In a pilot study of 31 out of 97 LuTx recipients in our immune monitoring cohort, B cell subsets were analysed pre, post (T0), 24h (T24) and 3 wks after LuTx. B cells were phenotyped using flow cytometry with CD19, CD27, IgD, CD24 mab. The kinetics of B cell subsets were compared between eDSA-positive (n=7) and -negative (n=24) patients. Results During the first 24h, relative B cell frequencies increased and returned to baseline at 3 wks without differences between eDSA-positive and negative LuTx patients. In eDSA-positive patients, higher frequencies of IgD+CD27-CD24hi naive and lower frequencies of IgD-CD27-CD24lo memory B cell subsets were observed constantly pre, at T0, T24 and 3wks. In contrast, a transient decrease in IgG+CD27+ switch memory B cells was detected at T0 in both groups, returning to baseline levels already at T24. Conclusion In the context of lung transplantation, the ratio between naive and memory B cells even before and directly after LuTx may be associated with the development of de novo DSA. Therefore, a refined B cell monitoring may be able to identify patients with a higher risk for eDSA development. The impact of the treatment regimen on these B cell subsets is currently further investigated in terms of differential effects on their depletion and reconstitution, respectively.

Purpose In lung transplantation, intraoperative extracorporeal membrane oxygenation (ECMO) allows transplanting high-risk patients, such as those with idiopathic pulmonary arterial hypertension (iPAH). However, early postoperative course is more complicated in patients with than without ECMO, with higher prevalence of severe primary graft dysfunction (PGD), a risk factor for chronic lung allograft dysfunction (CLAD). Aim of this retrospective study was to test the hypothesis if the worse early postoperative course in ECMO patients translates in a worse long-term graft function too. Methods Our institutional lung database was searched for patients who were transplanted with intraoperative ECMO between January 2010 and September 2019. Perioperative and follow-up results were compared between patients transplanted with ECMO and without ECMO. Follow-up amounted to a median of 41 (19-71) months. Results During the study period, among the 1,189 lung-transplanted patients, 316 (27%) patients required ECMO and the remaining 848 (71%) patients did not. Twenty-four (2%) patients requiring intraoperative cardiopulmonary bypass (CPB) support were excluded. ECMO patients showed a higher pre-transplant surgical risk profile (iPAH, 23% vs 0%, p Conclusion The worse graft survival in ECMO patients was driven by a higher in-hospital mortality, but graft function at follow-up did not differ in discharged patients transplanted with and without ECMO.

Purpose Ex vivo heart perfusion is an innovative preservation technique, that permits graft assessment and extended out-of-body intervals. In times of high-risk recipients and donors with extended criteria, we hypothesized that its properties for prolonged heart preservation might be especially beneficial. Methods We reviewed the outcome of 76 end-stage heart failure patients that underwent heart transplantation using the Organ Care System (OCS Heart, Transmedics, USA) in our institutions since 2015. Data was collected from prospective institutional databases. All recipients were potentially considered eligible, but an effort was made to apply OCS Heart particularly in challenging cases with previous cardiac surgery. Results Baseline characteristics. Mean age: 45,4±16,9 y, male gender: 77,6%, time on waiting list: 610±999 d, high-urgency (HU) status: 88,2%, previous cardiac surgery: 86,7%, previous VAD: 72,4%, previous BIVAD: 8,9%, previous VAD exchange: 20,0%. Donor characteristics. Mean age: 41,9±12,5 y, presence of CAD: 2,7%, presence of LV-hypertrophy: 17,3%, previous cardiac arrest: 34,7%. Operative results. Total ex situ time: 382,1±72,4 min, mean OCS run time: 268,2±54,2 min, total length of surgery: 488,8±101,7 min, ventilation time: 10,2±19,9 d, ICU stay: 19,8±24,3 d, postoperative ECMO (all types): 23,7%, incidence of bleeding: 19,7%, permanent dialysis 4%, stroke 4%. Follow-up. 30-day survival: 92,1%, 1-year-survival: 82,9%. Causes of death: Multi organ failure: 30,8%, pancreatitis 23,1%, acute graft rejection: 7,7%. Conclusion OCS Heart allowed safe transplantation of surgically complex recipients with excellent outcomes, despite extended donor criteria and prolonged preservation times. In the context of reduced organ availability and increasing recipient complexity, ex vivo heart perfusion is a novel technology that enables otherwise infeasible allocations and contributes to increase surgical safety.

Purpose Diaphragmatic dysfunction after bilateral lung transplantation is often unrecognized and its impact on outcomes has not been evaluated yet. Here, we aimed to study the prevalence of diaphragmatic dysfunction after lung transplantation and its impact on the postoperative course. Methods The records of patients transplanted at our institution between January 2010 and August 2019 were reviewed. Presence of post-transplant unilateral diaphragmatic dysfunction was retrospectively evaluated using two-projection chest X-rays performed at hospital discharge, and was defined, according to our radiologists, by a >40mm difference between right and left diaphragmatic height, measured in an anterior-posterior projection while patients were standing upright and spontaneously breathing. Patients without a chest X-ray while spontaneously breathing and patients undergoing single lung transplantation were excluded from the study. Post-transplant outcomes were compared between patients with and without diaphragmatic dysfunction. Results During the study period, among the 1,181 lung-transplanted patients, 1,124 (95%) patients were included. One hundred (9%) patients showed a >40mm difference between right and left diaphragmatic height (median, 47.3mm) and the remaining 1,024 (91%) patients did not, at the chest X-ray performed at a median of 21 days after lung transplantation. Patients with diaphragmatic dysfunction were transplanted more often for pulmonary fibrosis (41% vs. 29%, p=0.011). Postoperatively, patients with diaphragmatic dysfunction required longer invasive ventilation (median, 24 vs. 13 hours, p=0.001), ICU (median, 3 vs. 2 days, p Conclusion Unilateral diaphragmatic dysfunction prolonged the early postoperative course after lung transplantation, but did not impair long-term graft survival.

Purpose Regulatory T cells (Treg) may counteract chronic lung allograft dysfunction (CLAD). In the present study, we analyzed Treg in peripheral blood before lung transplantation and at 3 weeks and at 3, 6, 12 and 24 months after transplantation and correlated the percentages of 3 Treg subpopulations at 3 weeks with the later incidence of CLAD and graft survival. Methods Among lung-transplanted patients between January 2009 and September 2019, only adult patients with Treg measurements were included into the study. Treg were detected in peripheral blood and defined as % of CD4+CD25highT cells and further analyzed for CD127low, FoxP3+and CD152+ using FACS analysis. Associations of Treg with CLAD and graft survival, defined as patient survival and freedom from re-transplantation, were evaluated using Cox analysis. Results Among the 1,189 lung-transplanted adult patients at our institution, 918 (77%) patients had Treg measurements after transplantation. Frequencies (%) of CD4+CD25highCD127low, but not of FoxP3+ and CD152+ Treg were significantly higher in patients without CLAD than in patients with CLAD at each time point after transplantation (Figure 1). Similar results were found for graft survival. Treg frequencies were higher in patients treated with tacrolimus vs. cyclosporine. Follow-up was 47±31 months. Freedom from CLAD was 66% at 5 years. At the Cox analysis, increasing frequencies of CD127low at 3 weeks (HR=0.989, p=0.001), but not of FoxP3+ (HR=0.994, p=0.22) and of CD152+ (HR=0.999, p=0.75) Treg were protective against CLAD. Graft survival amounted to 71% at 5 years. Only increasing frequencies of CD127low Treg (HR=0.992, p=0.024) were protective against mortality or retransplantation. Conclusion A higher frequency of CD127low Treg in peripheral blood early after lung transplantation is protective against CLAD and associated with better survival. The effect of tacrolimus on Treg deserves further investigation.

Purpose The development of early detectable anti-HLA donor specific antibodies after lung transplantation (eDSA) has been associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, eDSA patients were treated with successive infusions (first infusion: 2g/kg, then 0.5g/kg once every 4 weeks for a maximum of 6 months) of IgA- and IgM-enriched human intravenous immunoglobulins (IgGAM), usually combined with a single dose of anti-CD20 antibody (Rituximab) since 2013. In some cases, plasmapheresis (PE) or immunoabsorption were added before the first IgGAM dose. Aims of this study were to present the 6-year results of the IgGAM-based therapy. Methods Records of patients transplanted at our institution between 02/2013 and 09/2019 were reviewed. Outcomes were compared between patients with eDSA and treated with IgGAM and patients without eDSA (control group). Median follow-up was 35 (16-56) months. Results During the study period, among the 816 transplanted patients, 186 (23%) patients formed the IgGAM group and 609 (75%) the control group. The remaining 21 (2%) patients (12 patients with eDSA but not treated, and 9 patients treated only with PE and Rituximab) were excluded. eDSA developed at a median of 14 days after transplantation. Thirty-four (18%) IgGAM patients showed graft dysfunction at the same time with eDSA detection (possible clinical AMR). Immunoabsorption/PE were performed in 71 (38%) patients and Rituximab was given to 132 (71%) patients. Treatment was completed in 167 (90%) patients (still on treatment, n=8; in-hospital deaths, n=4; treatment interrupted earlier as per protocol, n=7). In these 167 patients, IgGAM treatment cleared eDSA in 150 (90%) patients, 23 (15%) patients showing eDSA recurrence at a median 9months after treatment end. Clearance was worse in patients with preformed eDSA (p Conclusion After lung transplantation, a treatment based on IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM treatment have good 6-year graft survival similar to control patients.

Purpose Chronic lung allograft dysfunction (CLAD) is the leading cause of long-term mortality after LuTX. We studied correlations between CLAD five years after clinical LuTX and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. Methods The pericardiophrenic artery was procured from surplus tissue of 25 donor lungs transplanted in our clinical program and each was implanted into the abdominal aorta of cohorts of at least four immune deficient mice. The mice from each experiment were then divided into four groups. Negative control mice received no human leukocyte reconstitution (neg. co). PBMC group mice received 5 × 106 allogeneic human peripheral blood mononuclear cells (PBMC) from the respective lung recipients. A further group of animals was reconstituted with the respective PBMC additionally enriched with autologous CD4+CD25high cells (putative regulatory T cells, Treg). Human leukocyte engraftment was monitored by FACS and development of TA was histologically assessed 28 days after PBMC reconstitution. The 25 lung recipients were divided into two groups at least 5 years post LTX according to their development of chronic rejection. Sixteen patients (64%) developed CLAD 74.5± 7.01 months after LuTX. The remaining nine patients (36%) did not develop CLAD within 67.81± 2.24 months after LuTX Results The neg. co group showed only mild thickening of the intima (7.78±4.60%). In the PBMC CLAD+ group, intimal thickening obliterating the vessel lumen was significantly more severe than in the PBMC CLAD- group (41.91 ± 6.12% vs. 15.45 ± 3.22%, p= 0.001). Then, intimal thickening was significantly inhibited in the PBMC+Treg CLAD+ group as compared to the PBMC CLAD+ group (0.29 ± 2.99% vs 41.91 ± 6.12%, p=0.012). In the experiments using PBMC from lung recipients without CLAD, enriching Treg also further suppressed the development of TA (12.77 ± 2.59% PBMC CLAD- vs. 0.39 ± 4.11% PBMC+Treg CLAD-, p=0.012). Conclusion Lung transplant recipients, who later developed CLAD, had peripheral leukocytes already at the time of LTX that transferred pro-inflammatory properties leading to TA into a humanized mouse model. TA remained sensitive to inhibition by autologous regulatory T cells, suggesting a cell therapy-based approach for the prevention and treatment of CLAD after LuTX.

Purpose After lung transplantation (LuTx), the development of early donor HLA-specific antibodies (eDSA) has been shown to be associated with antibody-mediated rejection (AMR) and poor graft survival. Since 2013, patients with eDSA within the first month after LuTx in our center are treated with IgA/IgM enriched intravenous immunoglobulins (IgGAM), combined with anti-CD20 antibody (Rituximab). We addressed the hypothesis that naive vs. memory B cell subsets differ between eDSA-positive and negative patients already early after LuTx before onset of the treatment regimen. Methods In a pilot study of 31 out of 97 LuTx recipients in our immune monitoring cohort, B cell subsets were analysed pre, post (T0), 24h (T24) and 3 wks after LuTx. B cells were phenotyped using flow cytometry with CD19, CD27, IgD, CD24 mab. The kinetics of B cell subsets were compared between eDSA-positive (n=7) and -negative (n=24) patients. Results During the first 24h, relative B cell frequencies increased and returned to baseline at 3 wks without differences between eDSA-positive and negative LuTx patients. In eDSA-positive patients, higher frequencies of IgD+CD27−CD24hi naive and lower frequencies of IgD−CD27−CD24lo memory B cell subsets were observed constantly pre, at T0, T24 and 3wks. In contrast, a transient decrease in IgG+CD27+ switch memory B cells was detected at T0 in both groups, returning to baseline levels already at T24. Conclusion In the context of lung transplantation, the ratio between naive and memory B cells even before and directly after LuTx may be associated with the development of de novo DSA. Therefore, a refined B cell monitoring may be able to identify patients with a higher risk for eDSA development. The impact of the treatment regimen on these B cell subsets is currently further investigated in terms of differential effects on their depletion and reconstitution, respectively.

BACKGROUND Pediatric lung transplantation remains the only curative treatment option for some end-stage lung diseases in childhood. Recipient numbers outnumber potential donor organs, and therefore a broader group of donor organs must be considered for pediatric lung transplantation. Herein we describe the outcome of utilizing extended criteria donor organs in pediatric lung transplantation. METHODS A retrospective analysis was performed on all pediatric lung transplantations performed at the Hannover Medical School between April 2010 and December 2016. Donors were assigned to a group fulfilling standard donor criteria (International Society for Heart and Lung Transplantation [ISHLT] 2003) or not. Recipients’ early- and mid-term morbidity and mortality were recorded. RESULTS A total of 57 pediatric lung transplantations were performed: 27 donors fulfilled standard donor criteria (standard criteria donor [SCD] group) and 30 donors were extended criteria donors not fulfilling standard donor criteria (extended criteria donor [ECD] group). Pre-operative recipient characteristics, including age (median [IQR]: 14 [10‒15] vs 13 [10.8‒15] years, p = 0.71), underlying disease, admission to intensive care unit (37.0% vs 50%, p = 0.42), mechanical ventilation (14.8% vs 10.0%, p = 0.70), and extracorporeal membrane oxygenation (ECMO) support (11.1% vs 23.3%, p = 0.30) of both groups were similar. In the ECD group, more atypical volume reductions of the allograft were performed (0% vs 16.7%, p = 0.05), yet incidence of post-operative ECMO support was similar for the 2 groups. ECD recipients spent significantly less time on mechanical ventilation (median [IQR]: 2 [1‒2] vs 1 [1‒2] days, p = 0.04)] after surgery, but total intensive care unit stay and total hospital stay were similar between groups. Pulmonaryfunction testing results at discharge from initial hospital stay, after 1 year, and at last assessment were also similar. Freedom from chronic lung allograft dysfunction at 1 and 5years after transplantation showed no significant differences between groups. Survival rates up to 5years (67.9% vs 90.5%, p = 0.35) after transplantation were comparable between groups, yet, counterintuitively, long-term survival in the ECD group showed superior trends compared with the SCD group. CONCLUSIONS ECD lungs can be used safely for pediatric lung transplantation without compromising short- and mid-term results.

Purpose Chronic lung allograft dysfunction (CLAD) is a severe complication of lung transplantation (LTX) limiting long term survival. Here, we studied correlations between CLAD after clinical LTX and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. Methods The pericardiophrenic artery was procured from surplus tissue of 27 donor lungs transplanted in our clinical program and was implanted into the abdominal aorta of immune deficient mice. The experimental mice were then divided into four groups. Negative control mice received no human leukocyte reconstitution (neg. co). PBMC group mice received 5 × 106 allogeneic human peripheral blood mononuclear cells (PBMC) from the respective lung recipients (LR). A further group of animals was reconstituted with the respective PBMC additionally enriched with autologous CD4+CD25high cells (putative regulatory T cells, Treg). Human leukocyte engraftment was monitored by FACS and development of TA was histologically assessed 28 days after PBMC reconstitution. The 27 LR were divided into two groups at least 3 years post transplantation according to their development of chronic rejection. Nine patients (33.3%) developed CLAD 36.2± 4.16 month after LTX. The remaining eighteen patients (66,6%) did not develop CLAD within 35.9± 5.1 month after LTX. Results The neg. co group showed only mild thickening of the intima (6.38±5.70%). In the PBMC CLAD+ group, intimal thickening obliterating the vessel lumen was significantly more severe than in the PBMC CLAD- group (33.19 ± 7.02% vs. 13.37 ± 2.99%, p= 0.011). Then, intimal thickening was significantly inhibited in the PBMC+Treg CLAD+ group as compared to the PBMC CLAD+ group (0.39 ± 3.69% vs 33.19 ± 7.02%, p=0.012). In the experiments using PBMC from lung recipients without CLAD, enriching Treg also further suppressed the development of transplant arteriosclerosis (13.37 ± 2.99% PBMC CLAD- vs. 0.69 ± 5.88% PBMC+Treg CLAD-, p=0.007). Conclusion Lung transplant recipients, who later developed CLAD, had peripheral leukocytes already at the time of transplant that transfered pro-inflammatory properties leading to TA into a humanized mouse model. TA remained sensitive to inhibition by autologous regulatory T cells, suggesting a cell therapy-based approach for the prevention and treatment of CLAD after LTX.

Purpose An important cause of early morbidity and mortality after lung transplantation is primary graft dysfunction (PGD). Natural killer (NK) cells are important components of the innate immunity and activated B cells could regulate the activity of innate cells. The involvement of B and NK cells in the immune reaction after lung transplantation remains incompletely understood. Neither the involvement of the innate immune reaction to the development of PGD after lung transplantation has not yet been thoroughly investigated. In this study, we aimed to investigate the correlation between early peripheral B and NK cell frequencies and the development of CLAD and PGD 24h. Methods We performed a retrospective study in 178 lung transplant recipients. The frequencies of circulating peripheral cell subsets were detected by flow cytometry at 3 weeks after transplantation. We analyzed B cells by CD19, CD27, IgM and IgG expressions, as well as the main NK cell subsets, CD56dimCD16+ vs. CD56bright CD16-. And correlated all measured cell types with CLAD development and PGD 24h. Results The cohort was divided into two groups based on CLAD development at 2 years after lung transplant and without CLAD development. Three weeks after lung transplantation, the B cell population in the CLAD-group was significantly more frequent (8.06±5.8% vs. 4.05±4.6; p=0.0009) compared to the non-CLAD-group. The patients in the non-CLAD group showed 3 weeks after lung transplantation higher proportions of CD56+CD16+ NK cells (73.09±20.4% vs. 63.78±22.3) compared to the CLAD group. In PGD24h, the B cell populations were similar (3.62±3.9% vs. 4.34±4.7). The patients in the PGD2/3 at 24h group showed 3 weeks after lung transplantation significantly higher proportions of CD56+CD16+ NK cells (5.33±4.6% vs. 3.19±2.4) compared to the PGD0/1 at 24h group. Conclusion At three weeks after lung transplantation, non-CLAD patients showed increased frequencies of CD56dimCD16+ NK cells and decreased frequencies of CD19+ B cells, indicating that a stable NK cell composition may contribute to protection from CLAD while upregulation of B cells could be an initiator of CLAD development. But it seems like that primary graft dysfunction is correlated with the activation of innate immunity, specifically CD56bright CD16- NK cells in the periphery.

Purpose Regulatory T cells (Treg) may counteract chronic lung allograft dysfunction (CLAD). In the present study, we analyzed Treg in peripheral blood at 3 weeks and at 3, 6, 12 and 24 months after lung transplantation and correlated the percentages of 3 Treg subpopulations at 3 weeks with the later incidence of CLAD and graft survival . Methods Among lung-transplanted patients between January 2009 and October 2018, only adult patients with Treg measurements after transplantation were included into the study. Tregs were detected in peripheral blood and defined as CD4+CD25highT cells and further analyzed for CD127lowand FoxP3+ using FACS analysis . CD4 +CD25highIL2+ T cells were also evaluated. Associations of Treg with CLAD and graft survival, defined as patient survival and freedom from re-transplantation , were evaluated using Cox analysis. Results Among the 1,089 lung-transplanted adult patients at our institution, 830 (76%) patients had Treg measurements after transplantation. Frequencies (%) of CD127low and IL2+ but not of FoxP3+ cells were significantly higher in patients without CLAD than in patients with CLAD at each time point after transplantation (Figure 1). Similar results were found for graft survival. Treg frequencies were higher in patients treated with tacrolimus vs. cyclosporine . Follow-up was 42±29 months. Freedom (%) from CLAD was 66 at 5 years. At the Cox analysis, increasing frequencies of CD127 low (HR=0.988, p Conclusion A higher frequency of CD127low Tregs early after lung transplantation is protective against CLAD and associated with better survival. The role of CD4+CD25highIL2+ T cells and the effect of tacrolimus on Treg deserve further investigation.

Objective De novo donor-specific anti-human leukocyte antigen antibodies develop in a high proportion of lung transplant recipients early after lung transplantation. We recently showed that de novo donor-specific antibodies (DSA) occurrence is associated with significantly increased mortality. Here, we studied the efficacy of a preemptive treatment protocol. Methods A retrospective observational study was conducted on all lung transplantations at Hanover Medical School between January 2009 and May 2013. Results Among the 500 transplant recipients, early DSA developed in 86 (17%). Of these, 56 patients (65%; Group A) received therapeutic plasma exchange, and 30 patients (35%; Group B) did not. Among Group A patients, 51 also received rituximab. Between groups, there was no statistically significant difference in mortality, incidence of pulsed steroid therapies, rejections diagnosed by biopsy specimen, incidence of bronchitis obliterans syndrome (BOS), or infections requiring hospitalization at 1 year and 3 years. Also, there were no statistically significant differences after matching 21 Group A with 21 Group B patients through propensity score analysis. Significantly more Group A patients (65%) than Group B patients (34%) cleared DSA at hospital discharge ( p = 0.01). At the last control after transplantation (median, 14 months; interquartile range, 5–24 months), 11 Group A (22%) and 9 Group B patients (33%) still showed DSA ( p = 0.28). Conclusions Preemptive treatment with therapeutic plasma exchange and rituximab led to improved elimination of DSA early after lung transplantation ( p = 0.01). However, spontaneous elimination in untreated Group B patients also occurred frequently. This treatment protocol was not associated with significantly improved outcome.

Purpose The development of anti-HLA donor specific antibodies early after lung transplantation (eDSA) is associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, since 2013, we have treated patients with eDSA with successive infusions (first infusion: 2gr/kg, then 0.5gr/kg every 4 weeks for a maximum of 6 months) of IgA and IgM-enriched human intravenous immunoglobulins G (Pentaglobin®, IgGAM), combined in some cases with a single dose of anti-CD20 antibody (Rituximab) and plasmapheresis (PE) or immunoabsorption. Aims of this study were to present the 5-year results of the IgGAM-based therapy and its impact on graft survival. Methods Records of patients transplanted at our institution between 03/2013 and 10/2018 were reviewed. Outcomes of patients with eDSA and treated with IgGAM (IgGAM group) and without eDSA(control group) were compared using the product-limit method of Kaplan-Meier and the log-rank test. Median (IQR) follow-up amounted to 29 (14, 48) months. Results During the study period, among the 705 transplanted patients, 158 (22%) patients formed the IgGAM group and 530 (75%) the control group. Among the remaining 17 (3%) patients, 10 patients developed eDSA but were not treated and 7 were treated only with PE and Rituximab, and thus were not considered in the study. Among the 158 IgGAM patients, 132 (84%) showed only eDSA (possible subclinical AMR) and were pre-emptively treated. The remaining 26 (16%) patients showed graft dysfunction concomitant with eDSA (possible clinical AMR). Median time to eDSA detection was 14 (11, 20) days after transplantation. As of October 2018, treatment was completed in 138 (87%) patients. IgGAM treatment cleared eDSA in 126 (91%) patients (median time 3 months), 15 (12%) patients showing eDSA recurrence at a median of 9 months after treatment end. During treatment time, freedom from biopsy-confirmed rejection (%) was 72 vs. 65 in IgGAM vs. control patients. At 5 years, graft survival (%) was 71 vs. 75 (p=0.74) and freedom from CLAD 84 vs. 70 (p=0.28) in IgGAM vs. control patients, respectively. Conclusion After lung transplantation, a IgGAM-based treatment for eDSA yielded high eDSA clearance. IgGAM patients showed improved 5-year CLAD-free survival in comparison to control patients. Graft survival was similar between groups.

Purpose V-a extracorporeal membrane oxygenation (ECMO) has been successfully used for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Especially patients with lung fibrosis are at risk to require intraoperative v-a ECMO. Aim of this study was to identify predisposing risk factors for intraoperative ECMO support and postoperative outcomes in this cohort of patients. Methods Patients transplanted for lung fibrosis between January 2010 and May 2018 were included into the study. Patients transplanted on v-a ECMO formed group A, the remaining, group B. Follow-up amounted to a mean of 37±27 months. Multivariate forward and backward logistic regression analysis was used to identify risk factors for ECMO. Results Among the 1042 lung-transplanted patients, 313 (30%) patients underwent bilateral transplantation for lung fibrosis. Five patients were excluded as they received conventional cardiopulmonary support due to different resaons. Among the remaining 308 patients, 109 (35%) patients formed group A, 199 (65%), group B. Presence of pulmonary hypertension (OR 3.1; 95%CI 1.8-5.3, p Conclusion Smaller recipient BSA, pulmonary hypertension with high PVR values and evidence of a dilated and hypertrophic right ventricle can predict the need for intraoperative ECMO in patients transplanted for lung fibrosis. Although the postoperative course was more complicated in group A than B, long-term survival did not differ between groups.

Purpose Ex vivo organ perfusion is an advanced preservation technique that allows graft assessment and extended ex situ intervals. We hypothesized that its properties for prolonged heart preservation might be especially beneficial for high risk recipients. Methods We reviewed the 1-year-outcome of 126 end-stage heart failure patients that underwent cardiac transplantation in two German institutions between 01/2015 and 09/2018. Data was collected from prospective institutional databases. Patients were divided into two groups: group A (OCS) vs. group B (conventional). Ex vivo organ perfusion was performed using Organ Care System (OCS Heart, Transmedics, USA). All recipients were potentially considered eligible, but an effort was made to apply the OCS Heart particularly in challenging cases with previous cardiac surgery. Results A total of 44 patients were transplanted using the OCS. Baseline characteristics in both groups: age (y) (A:46,4±16,2 vs. B:32,1±22,9; p 30-d-survival (%) (A:99,6 vs. B:91,2, p=0,263), 1-y-survival (%) (A:88,6 vs. B:78,2, p=0.222). Conclusion OCS Heart allowed safe transplantation of surgically complex recipients with excellent 1-year outcomes, despite mean preservation times of almost 7 hours. Furthermore, we observed trends to decreased ventilation times, fewer ECMO treatments and shorter ICU stays in the OCS group. In times of reduced organ availability and increasing recipient complexity, OCS heart is a strong instrument that enables otherwise infeasible allocations and contributes to increase surgical safety.

Purpose An important cause of early mortality after lung transplantation is primary graft dysfunction (PGD). In a humanized mouse model, we studied the impact of the baseline condition of the endothelium of lung donors in combination with recipient PBMC with or without PGD on the development of luminal occlusion. Methods Segments of arteries were implanted into the aorta of immunodeficient mice. Mice were divided into six treatment groups: group A mice with aortic vessels from PGD grade ≥ 2 (PGD+) patients were reconstituted with the respective allogeneic recipient PBMC, group B mice additionally received recipient CD4+CD25high Treg cells. Group C mice with aortic vessels from PGD grade ≤ 1 (PGD-) patients received recipient PBMC and group D mice additionally CD4+CD25high Treg cells. Control group E mice received arteries from PGD+, group F mice from PGD- patients, both without PBMC reconstitution. Luminal occlusion was quantified histologically and systemic immune responses by quantification of plasma cytokine and chemokines etc. Results Luminal occlusion of aortic vessels as sign of TA was significantly more severe in PGD+ group E compared to those from PGD- group F control mice in the absence of PBMC which was paralleled by higher IFN-γ (p Conclusion We conclude that a pre-existing Th1 response of the donor endothelial system contributes to PGD development, which is further enhanced by alloreactive T cells.