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Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. Minipig donor lungs with unmodified SLA expression (control group, n = 7) or with modified SLA expression (treatment group, n = 7) were used to evaluate the effects of SLA knockdown on allograft survival and on the nature and strength of immune responses after terminating an initial 4-week period of immunosuppression after LTx. Genetic engineering to down-regulate SLA expression was achieved during ex vivo lung perfusion by lentiviral transduction of short hairpin RNAs targeting mRNAs encoding β2-microglobulin and class II transactivator. Whereas all grafts in the control group were rejected within 3 months, five of seven animals in the treatment group maintained graft survival without immunosuppression during the 2-year monitoring period. Compared with controls, SLA-silenced lung recipients had lower donor-specific antibodies and proinflammatory cytokine concentrations in the serum. Together, these data demonstrate a survival benefit of SLA–down-regulated lung transplants in the absence of immunosuppression. Editor's summary: Solid organ transplants have saved the lives of many with late-stage organ failure. However, the need to match major histocompatibility complex (MHC) molecules reduces the number of donor-recipient pairs and results in long waits for donor organs. A strategy to avoid the need for MHC matching is to knock down MHC expression in the transplanted organ altogether. Here, Figueiredo et al. transplanted lungs that underwent gene engineering to knock down MHC expression in recipient pigs. This approach, which relied on lentiviral vectors carrying shRNAs against B2M and CIITA, effectively hid the donor lungs from the immune system, enabling long-term graft survival. Together, these results suggest that MHC knockdown may be a feasible strategy to improve graft survival after solid organ transplantation. —Courtney Malo [ABSTRACT FROM AUTHOR]

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

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart‐transplanted patients were collected before (pre‐), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4+ or CD8+ T cells and CD56dimCD16+ NK cells immediately after HTx linked to a decrease in naïve CD8+ and CM CD4+ T as well as CD56brightCD16− NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69+CD25− and diminished CD69−CD25−CD4+ or CD8+ T‐cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo‐specific immune responses. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Total ischaemic time (IT) is considered a limiting factor in lung transplantation. In this retrospective study, we investigate effects of IT and disease burden on outcomes after bilateral lung transplantation. METHODS A total of 1298 patients undergoing bilateral lung transplantation between January 2010 and May 2022 (follow-up 100%, median 54 months) were included. Pre-transplant diseases' severity (recipient body mass index, recipient age, previous lung transplantation, Tacrolimus immunosuppression, preoperative recipient extracorporeal membrane oxygenation support, lung volume reduction) for graft failure was individually calculated and—as IT—categorized. Vice versa adjusted Cox models were calculated. Considering competing risks, we assessed cumulative incidences of airway obstructive complications and chronic lung allograft dysfunction with death as competing risk factors for primary graft dysfunction were assessed by binary logistic regression. RESULTS Higher disease burden significantly accelerated chronic lung allograft dysfunction and death occurrence (P  < 0.001); IT did not. IT-adjusted disease burden strata showed 50% graft survival differences at 11 years after transplantation (range 24–74%), disease burden-adjusted IT strata 18% for all and 6% (54–60%) among those above 7 h. All significant primary graft dysfunction risk factors were diagnoses related, IT was not significantly important and odds ratios did not increase with IT. CONCLUSIONS The eventual graft survival disadvantage that results from an IT between 7 and at least 11 h is negligible in contrast to frequent recipients' disease-based risk levels. [ABSTRACT FROM AUTHOR]

Donor shortages have led transplant centers to extend their criteria for lung donors. Accepting lung donors ≥70 years of age has previously shown good short-term outcomes; however, no mid- and long-term outcome data on these extended criteria donors has been published to date. In this study, all patients who underwent lung transplantation between 06/2010 and 12/2019 were included in the analysis, and the outcomes were compared between patients receiving organs from donors <70 years of age and patients transplanted with lungs from donors ≥70 years of age. Among the 1,168 lung-transplanted patients, 62 patients received lungs from donors ≥70 years of age. The recipient age of those receiving older organs was significantly higher, and they were more likely to suffer from obstructive lung disease. Older donors were exposed to significantly shorter periods of mechanical ventilation prior to donation, had higher Horowitz indices, and were less likely to have smoked. The postoperative time on mechanical ventilation, time on ICU, and total hospital stay were comparable. The overall survival as well as CLAD-free survival showed no differences between both groups in the follow-up period. Utilization of lungs from donors ≥70 years of age leads to excellent mid- and long-term results that are similar to organs from younger donors when the organs from older donors are carefully preselected. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Our study shows that the Berlin Heart® EXCOR as a biventricular assist device in adult patients is an effective strategy in heart failure medicine. Our results may increase the use of the EXCOR with acceptable clinical outcomes despite long support times. With ongoing research to implement the EXCOR as a permanent right ventricular assist device, our results highlight possible arising complications. The Berlin Heart® EXCOR is a paracorporeal, pulsatile ventricular assist device used in patients of all age groups. However, adolescent and adult patients on EXCOR support are scarcely explored. Herein, we present a detailed description of infectious complications in this patient cohort. From 2006 to 2020, 58 patients received a biventricular assist device (BiVAD) at our institution and were included in this study. Postoperative infections were assessed after BiVAD implantation and subsequent heart transplantation (HTx). A Berlin Heart® EXCOR BiVAD was implanted as a bridge to transplantation in 58 patients (12–64 years). Most patients were INTERMACS I, and their median age was 49 years. Wound infections (WI) specific to the ventricular assist device (VAD) occurred in 31 (53.4%) patients with a mean time of 113 ± 155 days after BiVAD implantation. HTx was performed in 30 (51.7%) patients and thereof 10 (33.3%) patients developed at least one WI post-HTx. The mean time of WI after HTx was 17 ± 14 days. In four cases, WIs were caused by the same pathogen as before HTx. According to our institutional BiVAD wound classification, the mean wound score was 3. The VAD-specific wound infections were manageable and did not increase mortality nor precluded HTx in Berlin Heart® EXCOR patients. No specific risk factors for VAD-specific wound infections could be identified. [ABSTRACT FROM AUTHOR]

Introduction: For end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed. Passenger cells, derived from donor lungs and migrating into the recipient periphery, are comprised primarily by NK and T cells. Here, we aimed at characterizing the expression of killer cell immunoglobulin-like receptors (KIR) on donor and recipient NK and T cells in recipient blood after DLTx. Furthermore, we investigated the functional status and capacity of donor vs. recipient NK cells. Methods: Peripheral blood samples of 51 DLTx recipients were analyzed pre Tx and at T0, T24 and 3wk post Tx for the presence of HLA-mismatched donor NK and T cells, their KIR repertoire as well as activation status using flow cytometry. Results: Within the first 3 weeks after DLTx, donor NK and T cells were detected in all patients with a peak at T0. An increase of the KIR2DL/S1-positive subset was found within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL/S1-positive cells (p<0.01) 3wk post DLTx compared to recipient NK cells. This effect was also observed in donor KIR+ T cells 3wk after DLTx with higher proportions of KIR2DL/S1 (p<0.05) and KIR3DL/S1 (p<0.01) positive T cells. Higher activation levels of donor NK and T cells (p<0.001) were detected compared to recipient cells via CD25 expression as well as a higher degranulation capacity upon activation by K562 target cells. Conclusion: Higher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as a part of a highly specialized immunocompetent compartment. Despite KIR expression, higher activation levels of donor NK and T cells in the periphery of recipients suggest their pre-activation during the ex situ phase. Taken together, donor NK and T cells are likely to have a regulatory effect in the balance between tolerance and rejection and, hence, graft survival after DLTx. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Lung transplantation from donors with fulminant pulmonary arterial embolism as a cause of death remains controversial. An analysis was performed comparing preoperative characteristics and outcomes of 25 donors with a primary diagnosis of pulmonary arterial embolism to 1085 recipients of donor lungs without pulmonary arterial embolism. No early functional impairment of donor lungs with pulmonary embolism was detectable as depicted by the incidence of primary graft dysfunction immediately after surgery (P = 0.66), 24 (P = 0.79), 48 (P = 0.99) and 72 h (P = 0.99) after transplantation. Pulmonary function testing at 1 year (P = 0.003) and at last outpatient control (P < 0.05) showed superior results in the cohort receiving lungs from donors with pulmonary embolism. Incidence of chronic lung allograft dysfunction (CLAD) showed no difference within the first year after lung transplantation, however, 5 year‐CLAD free survival was superior in recipients (70.4% vs. 55.1%, P = 0.006) of donor lungs with pulmonary embolism. Overall survival was similar in both groups. Lungs from donors with fulminant pulmonary embolism prior to brain death can safely be used for lung transplantation without impairing postoperative outcomes. Lung function testing shows favorable midterm results in recipients of donor lungs with pulmonary embolism. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

View large Download slide View large Download slide OBJECTIVES Combined lung and liver transplantation (Lu-LTx) is an established therapy for patients with cystic fibrosis. The initial sequence has primarily been lung first. We changed the sequence to 'liver first' in 2006. The aim of this study is to present outcomes of this procedure. METHODS The records of combined lung and liver transplant patients treated at our institution between April 1999 and November 2016 were reviewed retrospectively. RESULTS A total of 27 patients received a combined Lu-LTx at our institute. Seventeen patients underwent Lu-LTx beginning with the lung transplantation. In this group, 5 patients had cystic fibrosis (lung first). The other 10 patients received the liver transplant first (liver first). All patients in this group had cystic fibrosis as underlying disease. The lung-first group showed a trend towards longer stays in the intensive care unit (ICU) and in the hospital [median 17 days in the ICU, interquartile range (IQR) 3–47 and 55 in-hospital days, IQR 29–108] than the liver-first group (median 6 days in the ICU, IQR 4–19 and 33 in-hospital days, IQR 26–63). The 90-day, 1- and 5-year survival rates were 80%, 60% and 20% in the lung-first group vs 90%, 79% and 79% in the liver-first group. CONCLUSIONS We present the largest series of patients following combined Lu-LTx according to the liver-first approach. The liver-first sequence results in favourable outcomes in our cohort of combined lung and liver transplants. [ABSTRACT FROM AUTHOR]

Author(s): Marius M. Hoeper [sup.1] [sup.5], Olaf Wiesner [sup.1], Johannes Hadem [sup.2], Oliver Wahl [sup.1], Hendrik Suhling [sup.1], Christoph Duesberg [sup.1], Wiebke Sommer [sup.3], Gregor Warnecke [sup.3] [sup.5], Mark Greer [...]

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. [ABSTRACT FROM AUTHOR]

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 < 0.05). The median of the proximal right ventricular outflow diameter decreased to 25 (23-27) mm after 12 months, compared to 48 (43-51) mm preoperatively (P < 0.05). CONCLUSIONS: The routine application of a prophylactic postoperative veno-arterial ECMO protocol in patients with severe pulmonary hypertension undergoing lung transplantation decreases postoperative mortality and favours achievement of normal cardiac function after 1 year. [ABSTRACT FROM AUTHOR]

Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation ( HTX) was performed in four and left-sided lung transplantation ( LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Since April 2010, extracorporeal membrane oxygenation (ECMO) has replaced cardiopulmonary bypass for intraoperative support during lung transplantation at our institution. The aim of this study was to present our 5-year experience with this technique. Methods Records of patients who underwent transplantation between April 2010 and January 2015 were retrospectively reviewed. Patients who underwent transplantation without ECMO formed Group A. Patients in whom the indication for ECMO support was set a priori before the beginning of the operation formed Group B. The remaining patients in whom the indication for ECMO support was set during transplantation formed Group C. Results Among 595 patients, 425 (71%) patients (Group A) did not require intraoperative ECMO; the remaining 170 (29%) patients did. Among these patients, 95 (56%) patients formed Group B, and the remaining 75 (44%) patients comprised Group C. Pulmonary fibrosis and pre-operative dilated or hypertrophied right ventricle emerged as risk factors for the indication of non–a priori intraoperative ECMO. Patients in Groups B and C showed a higher pre-operative risk profile and higher prevalence of post-operative complications than patients in Group A. Overall survival at 1 year was 93%, 83%, and 82% and at 4 years was 73%, 68%, and 69% in Groups A, B, and C ( p = 0.11). The intraoperative use of ECMO did not emerge as a risk factor for in-hospital mortality or mortality after hospital discharge. Conclusions Intraoperative ECMO filled the gap between pre-operative and post-operative ECMO in lung transplantation. Although complications and in-hospital mortality were higher in patients who received ECMO, survival was similar among patients who underwent transplantation with or without ECMO. [ABSTRACT FROM AUTHOR]

Background Mediocre donation rates and increasing demand for lung transplantation leads transplant centers to consider extended-criteria donor lungs. Arguably, the largest remaining non-utilized lung donor segment is the elderly individual, already considered for visceral organ donation but not thoracic. So far, transplantation of donor lungs aged ≥ 70 years is rarely reported, and recipient outcomes are unknown. Accordingly, we report a single-center series of lung transplantations from donors aged ≥ 70 years and compare outcomes with contemporary lung transplantations from younger donors. Methods All bilateral lung transplantations performed at our center between March 2011 and July 2014 were analyzed, and 2 cohorts were built according to lung donor age. Results A total of 440 bilateral lung transplantations were performed from 413 donors aged <70 years, and 27 donors aged ≥70 years. Donor characteristics did not differ in sex, donor time on mechanical ventilation before retrieval, or donor partial pressure of arterial oxygen/fraction of inspired oxygen ratio. Older donors were significantly less often positive for smoking history (43.7% vs 14.8%, p = 0.003) or for abnormal bronchoscopy results (52.9% vs 15.8%, p = 0.002). Recipients receiving donor lungs aged <70 years were younger than those receiving older donor lungs ≥ 70 (49.8 [range, 35–58] vs 58 [range, 53–62] years, p < 0.0001). Underlying diagnoses did not differ significantly between the groups. Post-operative mechanical ventilation times (15 [range, 10–59] vs 27.5 [range, 10–75.8] hours), intensive care unit stays (3 [range, 1–5] vs 3 [range, 1–8] days), and total hospital lengths of stay (24 [range, 22–40.5] vs 24 [range, 22–40] days) of the recipients did not differ significantly between the two groups. The percentage predicted forced expiratory volume in 1 second was 86.5% ± 26.2% 12 months after transplantation of younger lungs vs 72.2% ± 23.8% ( p = 0.01) after transplantation of older lungs. Differentiating the spirometry findings according to underlying diseases showed significantly lower forced expiratory volume in 1 second values after transplantation of donor lungs aged ≥70 only in idiopathic pulmonary fibrosis recipients but not in emphysema patients. Patient survival up to 36 months was not significantly different, with 1-year survival being 92.9% for younger vs 95.5% for older donor lungs. Conclusion Use of donor lungs aged ≥70 years for transplantation is safe, without compromising survival. However, spirometry findings after transplantation with donors ≥70 years indicate better functional outcomes in emphysema recipients than in idiopathic pulmonary fibrosis recipients. [ABSTRACT FROM AUTHOR]