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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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Background The role of HLA-sensitization in the absence of detectable DSA in lung re-transplantation is unclear. Antigens of the second donor matching the HLA typing of the first donor are considered ‘unacceptable’, by some tissue typing laboratories, especially in kidney re-transplantation. Methods Thus, we performed a retrospective analysis of all lung re-transplantations focussing on the impact of HLA-homologies between the first and the second donor (‘unacceptable’ antigens; repeated HLA mismatch) on patient and graft survival. Results A total of 132 lung re-transplantations were performed at our centre between 1985 and 2014, of which 120 with complete HLA data were analysed. 55.8% of the recipients received re-transplants with repeated HLA mismatched antigens whereas 43.2% of the re-transplants were transplanted without repeated HLA mismatched antigens. Postoperative survival showed no difference between re-transplant procedures with or without repeated HLA mismatches (p = 0.99). While neither homologies on the HLA-A, -B, -C, or -DR locus, nor the addition of several locus homologies (p = 0.72) had an impact on survival, unexpectedly, repeated HLA mismatching on the HLA-DQ locus was correlated with better survival. Re-transplantations with repeated HLA mismatches did not result in more development of CLAD as compared to recipients without repeated HLA mismatches (p = 0.99). Neither the number of repeated HLA mismatched antigens (p = 0.52) nor the HLA locus (HLA-A(p = 0.34), HLA-B(p = 0.97), HLA-C (p = 0.80), HLA-DR(p = 0.49) and HLA-DQ(p = 0.07)) had an impact on the development of CLAD after re-transplantation. Conclusion Transplantation with repeated HLA mismatches due to sensitization by a previous transplantation in the absence of detectable HLA-antibodies does not have a negative impact on patient or graft survival.

Background At our institution, until April 2013, patients who showed early donor specific anti-HLA antibodies (DSA) after lung transplantation were preemptively treated with therapeutic plasma exchange (tPE) and a single dose of Rituximab. In April 2013, we moved to a therapy based on IgM-enriched human immunoglobulins (IVIG), repeated every 4 weeks, and a single dose of Rituximab. Methods This observational study was designed to evaluate the short-term patient and graft survival in patients who underwent IVIG-based DSA treatment (group A, n = 57) versus contemporary patients transplanted between April 2013 and January 2015 without DSA (group C, n = 180), as well as to evaluate DSA clearance in IVIG-treated patients versus historic patients who had undergone tPE-based treatment (group B, n = 56). Patient records were retrospectively reviewed. Follow-up ended on April 1, 2015. Results At 6 months and 1 year of follow-up, group A had a survival similar to group C (P = 0.81) but better than group B (P = 0.008). Group A showed statistically nonsignificant trends toward improved freedom from pulsed-steroid therapy and biopsy-confirmed rejection over groups B and C. The DSA clearance was better in group A than group B at treatment end (92% vs 64%; P = 0.002) and last DSA control (90% vs 75%; P = 0.04). Conclusions Patients with new early DSA but without graft dysfunction that are treated with IVIG and Rituximab have similarly good early survival as contemporary lung transplant recipients without early DSA. The IVIG yielded increased DSA clearance compared with historic tPE-based treatment, yet spontaneous clearance of new DSA also remains common., Combination treatment of IgM enriched human immunoglobulins (IVIG) and a single dose of rituximab significantly reduced the incidence of de novo DSA production after lung transplantation compared to historical therapeutic plasma exchange and a single dose of rituximab. Supplemental digital content is available in the text.

Hypothermia is a treatment strategy for different clinical conditions and an essential part of cardiopulmonary bypass in complex cardiac procedures. Clinically, cooling patients is achieved via a mattress and heat exchanger integrated into a membrane oxygenator connected to a waterbed using a refrigerator system based on volatile and toxic liquids. Peltier elements are known as environmentally friendly thermoelectric generators that enable rapid warming and cooling. In this paper, we describe the construction of a novel device for rapid and precise control of mouse warming and cooling using thermoelectric Peltier elements. Six male BALB/c mice were subjected to deep hypothermia and were rewarmed under full physiological monitoring. After rewarming, all animals were observed for two hours, and pathology was evaluated in several organs. All animals tolerated the rapid cooling process well and remained active after rewarming. Temperature-relevant changes were seen via electrocardiography, with heart-rate patterns showing a strong linear correlation to body temperature. No myocardial ischaemia was seen. However, two animals experienced bradycardic atrial fibrillation which spontaneously converted to normal sinus rhythm during rewarming. No histological damage was seen in the heart, liver, kidney or lungs. Our device can effectively be used for heat shock and hypothermia studies in mice, and we foresee no obstacles for its application to other small rodents such as hamsters and young rats. In comparison to known experimental and clinical methods of hypothermia, our device is environmentally friendly, cost-effective and easy to handle, allowing precise control and maintenance of body temperatures ranging from 18℃ to 42℃.

Introduction: Lymphangioleiomyomatosis (LAM) is a rare disease in women, leading to progressive deterioration of lung function and respiratory failure. We describe the outcome of patients with end-stage LAM who underwent lung transplantation at our center. Materials and Methods: The records of patients with LAM transplanted at our institution between February 1997 and May 2015 were reviewed retrospectively. Morbidity and mortality were analyzed, and actuarial survival was calculated using Kaplan-Meier methods. The cumulative survival of transplant patients with LAM at our center was compared with survival after transplantation due to different diseases at our center and the results of the International Society for Heart and Lung Transplantation. Quality of life was assessed by a patient self-report at the end of the first postoperative year. Results: During the study period, 25 patients underwent lung transplantation for LAM. All patients were women with a mean age of 50 (9) years. Thirteen patients (52%) had undergone previous thoracotomy. All patients (100%) received bilateral lung transplantation. One (4%) case of in-hospital mortality occurred and 9 (36%) late deaths. Two (8%) cases of late death were due to chronic lung allograft dysfunction. The 1-, 3-, and 5-year survival rates were 92%, 84%, and 76%, respectively. Quality-of-life ratings were above the normal in all eight 36-Item Short Form Health Survey subscales 1 year after transplantation. Conclusions: Lung transplantation offers a valuable therapy for patients with end-stage pulmonary LAM.

In this retrospective study, we analyzed the presence of any association of three CD4

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for acute as well as end-stage lung diseases. With the increase in clinical demand and prolonged use of ECMO, procedural optimization and prevention of multi-organ damage are of critical importance. The aim of this protocol is to present a detailed technique of veno-venous ECMO in a non-intubated, spontaneously breathing mouse. This protocol demonstrates the technical design of the ECMO and surgical steps. This murine ECMO model will facilitate the study of pathophysiology related to ECMO (e.g., inflammation,bleeding and thromboembolic events). Due to the abundance of genetically modified mice, the molecular mechanisms involved in ECMO-related complications can also be dissected.