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Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS.

A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged researchers to extend these studies to ACD and compare the changes of the microvasculature. Lung tissue samples of children with ACD (n= 12), adults with non-specific interstitial pneumonia (n= 12), and controls (n= 20) were studied using transmission electron microscopy, single-gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1, PTK2B, and FN1and decreased VITexpression, confirmed by immunohistochemistry. In contrast, non-specific interstitial pneumonia samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1+vessels. This study provides insight into the ultrastructure and pathophysiology of ACD. The lack of normally developed lung capillaries appeared to cause a replacement by COL15A1+vessels, a mechanism recently described in interstitial lung disease. The VITloss and FN1overexpression might contribute to the unique appearance of basement membranes in ACD. Future studies are needed to explore the therapeutic potential of down-regulating the expression of FN1and balancing VIT deficiency.

Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B-cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain. As proof-of-concept, CORA receptors based on HLA-A*02 were developed. In co-cultures with anti-HLA-A*02 B-cell lines, CORA-Ts were specifically activated, released pro-inflammatory mediators, and exhibited strong cytotoxicity resulting in an effective reduction of anti-HLA-A*02 antibody release. Significant reduction of growth of an anti-HLA-A*02 B-cell line could be confirmed using an in vivomouse model. Modification of the CORA receptor effectively abrogated T-cell binding, thereby avoiding T-cell sensitization. Additionally, using CRISPR/Cas9-mediated knockout of the FKBP12gene, CORA-Ts were able to resist immunosuppressive treatment with tacrolimus, thereby allowing high efficiency in transplant patients. Our results demonstrate that CORA-Ts are able to specifically eliminate alloreactive, anti-HLA B cells, thus selectively preventing anti-HLA antibody release even under immunosuppressive conditions. This suggests CORA-Ts as potent approach to combat AMR and improve long-term graft survival in SOT patients while preserving their overall B-cell immunity.

Die Transplantationsmedizin in Deutschland ist klar strukturiert und verbindlich geregelt. Zur Stärkung der Organspende wurden die rechtlichen Rahmenbedingungen in den letzten Jahren mehrfach angepasst. Dennoch bleibt die eingeschränkte Organverfügbarkeit die Hauptlimitation dieser Therapie, auch im Bereich der Herz- und Lungentransplantation. Beide Verfahren sind mittlerweile etablierte Therapieoptionen für selektierte Patienten mit terminalem Organversagen. Ziel ist die Verbesserung der Lebensqualität und des Überlebens. Der Erfolg der Therapie hängt maßgeblich von der Selektion geeigneter Empfänger sowie dem optimalen peri- und postoperativen Management ab, einschließlich einer lebenslangen spezialisierten Nachsorge. Die Komplexität der Therapie erfordert ein hohes Maß an speziellen Kenntnissen und Fertigkeiten. Der vorliegende Beitrag fasst den aktuellen Stand der Transplantationsmedizin thorakaler Organe mit dem Fokus auf den Inhalt der neuen Zusatzweiterbildung Transplantationsmedizin zusammen.

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

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

Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo‐immune responses. Ex vivolung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long‐term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non‐ischemic, perfused, and ventilated status. In this work, we review potential mechanisms of EVLP that may attenuate IRI and improve organ quality. Moreover, we dissect experimental treatment approaches during EVLP that may further attenuate inflammatory events deriving from tissue ischemia, shear forces or allograft rejection associated with LuTx. This minireview examines the impact on ischemia reperfusion injury derived inflammation of ex vivo lung perfusion and other promising experimental approaches to improve donor lung quality.

Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivolung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non-ischemic, perfused, and ventilated status.

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

La desnutrición influye en la evolución clínica de los pacientes con insuficiencia cardiaca. El objetivo es analizar el impacto del estado nutricional preoperatorio evaluado mediante el índice de riesgo nutricional (IRN) en el pronóstico de los pacientes que recibieron dispositivos de asistencia ventricular izquierda de flujo continuo (DAVI-fc).

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.

This retrospective study presents our 4‐year experience of preemptive treatment of early anti‐HLAdonor 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.

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 retransplantation is a demanding procedure with outcomes lagging primary transplantation and less invasive retransplantation of the lung via sternum-sparing anterolateral thoracotomies and off-pump is a safe procedure with low associated morbidity and favorable mid-term survival.

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.

Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient’s waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA. Records of patients transplanted between February 2013 and May 2022 were reviewed. Outcomes were compared between patients with pfDSA and those without any de novo donor-specific antiHLA antibodies. The median follow-up time was 50 months. Of the 1,043 patients who had undergone lung transplantation, 758 (72.7%) did not develop any early donor-specific antiHLA antibodies, and 62 (5.9%) patients exhibited pfDSA. Among the 52 (84%) patients who completed treatment, pfDSA was cleared in 38 (73%). In pfDSA vs control patients and at 8-year follow-up, respectively, graft survival (%) was 75 vs 65 (P= .493) and freedom from chronic lung allograft dysfunction (%) was 63 vs 65 (P= .525). In lung transplantation, crossing the preformed HLA-antibody barrier is safe using a treatment protocol based on IgGAM. Patients with pfDSA have a good 8-year graft survival rate and freedom from chronic lung allograft dysfunction, similar to control patients.

Bilateral lung transplantation (BLTx) is an established treatment for end-stage pulmonary hypertension (PH). Ventilator weaning failure and death are more common as in BLTx for other indications. We hypothesized that left ventricular (LV) dysfunction is the main cause of early postoperative morbidity or mortality and investigated a weaning strategy using awake venoarterial extracorporeal membrane oxygenation (ECMO).

Primary graft dysfunction (PGD) is the most important cause of early morbidity and mortality in lung transplantation (LTX) with an incidence of 8 to 20. We hypothesized that application of C1-esterase-inhibitor (C1-INH) in LTX-recipients showing early signs of severe PGD would attenuate the condition.

Cold flush and static cold storage is the standard preservation technique for donor lungs before transplantations. Several research groups have assessed normothermic perfusion of donor lungs but all devices investigated were non-portable. We report first-in-man experience of the portable Organ Care System (OCS) Lung device for concomitant preservation, assessment, and transport of donor lungs.

Objective This study was carried out with the aim of presenting our experience with minimally invasive mitral surgery and compare the endoaortic clamp with the external aortic clamp (EAC) techniques.Methods Between December 2002 and May 2009, 139 patients (75 men, aged 63 ± 11 years) underwent video-assisted mitral valve surgery through right thoracotomy. Twelve (9%) patients were operated without clamping the aorta, 32 (23%) patients (group A) were operated on by using the endoaortic clamp, and 95 (68%) patients were operated on by using the EAC (group B). There was no significant difference between groups A and B regarding preoperative variables.Results Intraoperative procedure-associated problems were experienced in three group A patients (9.3%, two aortic dissections with conversion to sternotomy; one conversion due to bad exposure) and in two group B patients (2%, one conversion to sternotomy for bleeding and one for ascending aorta hematoma). At a mean follow-up of 32 months, 121 patients (97%) were in New York Heart Association class I–II, with satisfactory echocardiographic results. There was one in-hospital and six late deaths (three noncardiac, two cardiac, and one valve related). Five-year actuarial survival was 88% ± 8%. There were three reoperations, one early (<30 days) after complex mitral valve repair, with a 5-year freedom from reoperation of 97% ± 2%. Postoperative levels of myocardial cytonecrosis enzymes as well as the extracorporeal circulation time were significantly lower in group B patients (P < 0.05).Conclusions Intraoperative procedure-associated complications with endoclamping combined with an apparently better myocardial protection forced us to change our practice to the more simple and economic EAC technique.

Objective This study was carried out with the aim of presenting our experience with minimally invasive mitral surgery and compare the endoaortic clamp with the external aortic clamp (EAC) techniques.Methods Between December 2002 and May 2009, 139 patients (75 men, aged 63 ± 11 years) underwent video-assisted mitral valve surgery through right thoracotomy. Twelve (9%) patients were operated without clamping the aorta, 32 (23%) patients (group A) were operated on by using the endoaortic clamp, and 95 (68%) patients were operated on by using the EAC (group B). There was no significant difference between groups A and B regarding preoperative variables.Results Intraoperative procedure-associated problems were experienced in three group A patients (9.3%, two aortic dissections with conversion to sternotomy; one conversion due to bad exposure) and in two group B patients (2%, one conversion to sternotomy for bleeding and one for ascending aorta hematoma). At a mean follow-up of 32 months, 121 patients (97%) were in New York Heart Association class I–II, with satisfactory echocardiographic results. There was one in-hospital and six late deaths (three noncardiac, two cardiac, and one valve related). Five-year actuarial survival was 88% ± 8%. There were three reoperations, one early (<30 days) after complex mitral valve repair, with a 5-year freedom from reoperation of 97% ± 2%. Postoperative levels of myocardial cytonecrosis enzymes as well as the extracorporeal circulation time were significantly lower in group B patients (P < 0.05).Conclusions Intraoperative procedure-associated complications with endoclamping combined with an apparently better myocardial protection forced us to change our practice to the more simple and economic EAC technique.

Introduction:The optimal pulmonary revascularization strategy in acute high-risk pulmonary embolism (PE) requiring the implantation of extra corporeal membrane oxygenation (ECMO) remains controversial.Methods:We conducted a systematic review and meta-analysis of available evidence comparing mechanical reperfusion and other strategies, including systemic or catheter-directed thrombolysis and ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes.Results:The literature search identified 835 studies, 17 of which were included, totaling 321 PE patients with ECMO. Overall, 31.1% were treated with mechanical pulmonary reperfusion, while 78.9% received other strategies. The mortality rate was 23.0% in the mechanical reperfusion group and 43.1% in the other strategy group. The pooled OR for mortality with mechanical reperfusion was 0.46 (95%CI, 0.213-0.997; I2= 28.3%) versus other reperfusion strategies (Figure). The rate of bleeding in PE patients under ECMO was 29.1% in the mechanical reperfusion group and 26.0% in the other reperfusion group (OR, 1.09; 95% CI, 0.46-2.54; I2, 0.0%) among 10 eligible studies with available bleeding data. The meta-regression model did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy” and “ECMO implantation before pulmonary reperfusion therapy”, and outcomes.Conclusions:The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, yields the best results, regardless of the timing of ECMO implantation in the reperfusion timeline, and regardless of whether thrombolysis has been administered or not.