Implementation of Endoscopic Minimally Invasive Mitral Valve Replacement Surgery With Automated Suturing Technology.

In the evolving landscape of cardiac surgery, this article explores the potential of minimally invasive mitral valve replacement procedures as a viable alternative to conventional surgical techniques. Leveraging advancements in automated suturing devices and video endoscopy, our work aims to demonstrate that minimally invasive approaches can be applied across a broad spectrum of surgical scenarios. Herein we highlight preoperative diagnostics and operative techniques, with a focus on infra-axillary anterolateral minithoracotomy as the access point. Our technique utilizes technology from LSI SOLUTIONS® (Victor, NY, USA), including the RAM® Device for automated suturing, which has an ergonomic design and safety features. The device's capabilities are further enhanced by the SEW-EASY® Device, the RAM® RING, and the COR-KNOT MINI® Device, which streamline suture management and securement. This work outlines how these technological advancements can mitigate concerns about technical complexity and learning curves, thereby encouraging wider adoption of minimally invasive techniques. Clinical benefits may include reduced surgical trauma, quicker recovery, and cost-effectiveness, making it a compelling option in an era of aggressively promoted transcatheter interventions.

Hypoxic perfusion of pulmonary arterial vasa vasorum increases pulmonary arterial pressure.

The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasorum of the pulmonary arterial (PA) wall causes PH. Young adult pig lungs were explanted and placed into a modified ex vivo lung perfusion unit (Organ care system, OCS) allowing the separate adjustment of parameters for mechanical ventilation, as well as PA perfusion and bronchial arterial (BA) perfusion. PA vasa vasorum are branches of the BA. The lungs were used either as control (n=3) or intervention group (n=8). The protocol of the intervention group was as follows: normoxic ventilation and perfusion (steady state) -hypoxic BA perfusion -steady state -hypoxic BA perfusion. During hypoxic BA perfusion, ventilation and PA perfusion maintained normal. Control lungs were kept under steady state conditions for 105 minutes. During the experiments, PA pressure (PAP) and blood gas analysis was frequently monitored. Hypoxic perfusion of the BA resulted in an increase in systolic and mean PAP, a reaction that was reversible upon normoxic BA perfusion. The PAP increase was reproducible in the second hypoxic BA perfusion. Under control conditions the PAP stayed constant until about 80 minutes of the experiment. In conclusion, the results of the current study prove that hypoxic perfusion of the vasa vasorum of the PA directly increases PAP in an ex situ lung perfusion setup suggesting that PA vasa vasorum function and wall ischemia may contribute to the development of PH.

Risk factors, prevention, and therapy of intraluminal stent thrombosis in frozen elephant trunk prostheses-what we know so far.

Intraluminal thrombus formation (ILT) is a recently discovered and highly clinically relevant complication after frozen elephant trunk implantation in cardiovascular surgery. In this phenomenon, a thrombus forms within the lumen of the stent graft component of the frozen elephant trunk prosthesis and puts the patient at risk for downstream embolization with visceral or lower limb ischemia. Incidence of ILT reported in the currently available studies ranges from 6% to 17% of patients after frozen elephant trunk implantation. Adverse thromboembolic events include acute occlusion of the celiac and superior mesenteric arteries, both renal arteries as well as acute lower limb ischemia due to iliac or femoral artery embolization that not infrequently require interventional or open embolectomy. Therefore, the presence of ILT is associated with increased short-term mortality and morbidity. Currently proposed strategies to avoid ILT formation include a more aggressive anticoagulation management, minimization of postoperative coagulation factor application, and even technical optimizations of the stent graft portion itself. If ILT is manifested, the therapeutic strategies tested to date are long-term escalation of anticoagulation and early endovascular extension of the FET stent graft with overstenting of the intraluminal thrombus. The long-term efficiency of these prophylactic and therapeutic measures has yet to be proven. Nonetheless, all surgeons performing the frozen elephant trunk procedure must be aware of the risk of ILT formation to facilitate a timely diagnosis and therapy.

Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia.

Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo-horseradish peroxidase-based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger-protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery.

Heart Transplantation in High-Risk Recipients Employing Donor Marginal Grafts Preserved With Ex-Vivo Perfusion.

Extending selection criteria to face donor organ shortage in heart transplantation (HTx) may increase the risk of mortality. Ex-vivo normothermic perfusion (EVP) limits ischemic time allowing assessment of graft function. We investigated the outcome of HTx in 80 high-risk recipients transplanted with marginal donor and EVP-preserved grafts, from 2016 to 2021. The recipients median age was 57 years (range, 13-75), with chronic renal failure in 61%, impaired liver function in 11% and previous cardiac surgery in 90%; 80% were mechanically supported. Median RADIAL score was 3. Mean graft ischemic time was 118 ± 25 min, "out-of-body" time 420 ± 66 min and median cardiopulmonary bypass (CPB) time 228 min (126-416). In-hospital mortality was 11% and ≥moderate primary graft dysfunction 16%. At univariable analysis, CPB time and high central venous pressure were risk factors for mortality. Actuarial survival at 1 and 3 years was 83% ± 4%, and 72% ± 7%, with a median follow-up of 16 months (range 2-43). Recipient and donor ages, pre-HTx extracorporeal life support and intra-aortic balloon pump were risk factors for late mortality. In conclusion, the use of EVP allows extension of the graft pool by recruitment of marginal donors to successfully perform HTx even in high-risk recipients.

Impact of total ischaemic time and disease severity class on graft function after bilateral lung transplantation.

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.

Minimally Invasive Mitral Valve Surgery in the Elderly.

BACKGROUND: The minimally invasive mitral valve procedure warrants minimal surgical trauma and might influence the postoperative course positively, especially in old patients. In this retrospective study, we reviewed our experience in minimally invasive mitral valve surgery (miMVS) in patients aged ≥ 75 years. METHODS: In this retrospective cohort study, based on propensity score matching, we compared patients aged ≥75 years with patients aged <75 years who underwent miMVS. The primary endpoint was 30-day mortality. Secondary endpoints were myocardial infarction, stroke, and renal failure. RESULTS: Between January 2011 and February 2021, 761 patients underwent miMVS at our institution. After propensity score matching, a study group (≥75 years, n = 189) and a control group (<75 years, n = 189) were formed. Preoperatively patients ≥75 years more often suffered from NYHA III heart failure (60 vs. 46%; p = 0.013). Their valves were more often frequently replaced (48 vs. 32%; p < 0.001), and their postoperative ventilation time was longer (13 hours vs. 11 hours; p < 0.001). There were no statistically significant differences regarding postoperative stroke (3 vs. 0.6%; p = 0.16), myocardial infarction (0 vs. 1%; p = 0.32), renal insufficiency with new dialysis (5 vs. 4%; p = 0.62), and 30-day mortality (4 vs. 2%; p = 0.56). CONCLUSION: miMVS results in satisfactory early postoperative outcomes in elderly patients.

Does donor-recipient age mismatch have an influence on outcome after lung transplantation? A single-centre experience.

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.

Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia/Reperfusion.

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.

Lung transplant and severe coronary artery disease: results from a single-centre experience.

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 < 0.0001), more often male (p < 0.0001) and received transplants more often for pulmonary fibrosis (p = 0.0007). The median (interquartile range) follow-up was 46 (20-76) months. At the Cox multivariable analysis, severe coronary artery disease was not associated with death. Patients with pretransplant percutaneous transluminal coronary angioplasty and patients with coronary artery bypass graft surgery concomitant to a transplant had survival equivalent to that of patients without severe coronary artery disease (p = 0.513; p = 0.556). 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.

Heart transplantation across preformed donor-specific antibody barriers using a perioperative desensitization protocol.

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.

Donor NK and T Cells in the Periphery of Lung Transplant Recipients Contain High Frequencies of Killer Cell Immunoglobulin-Like Receptor-Positive Subsets.

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.

ECLS supported transport of ICU patients: does out-of -house implantation impact survival?

BACKGROUND: Extracorporeal life support (ECLS) is an established tool to stabilize severely ill patients with therapy-refractory hemodynamic or respiratory failure. Recently, we established a mobile ECLS retrieval service at our institution. However, data on the outcome of patients receiving ECLS at outside hospitals for transportation into tertiary hospitals is still sparse. METHODS: We have analyzed all patients receiving ECLS in outside hospitals (Transport group, TG) prior to transportation to our institution and compared the outcome to our in-house ECLS experience (Home Group, HG). RESULTS: Between 2012 and 2018, we performed 978 ECLS implantations, 243 of which were performed on-site in tertiary hospitals for ECLS supported transportation. Significantly more veno-venous systems were implanted in TG (n = 129 (53%) vs. n = 327 (45%), p = 0.012). Indication for ECLS support differed between the groups, with more pneumonia; acute respiratory distress syndromes in the TG group and of course, more postcardiotomy patients in HG. Mean age was 47 (± 20) (HG) vs. 48 (± 18) (TG) years, p = 0.477 with no change over time. No differences were seen in ECLS support time (8.03 days ±8.19 days HG vs 7.81 days ±6.71 days TG, p = 0.675). 30-day mortality (n = 379 (52%) (HG) vs. n = 119 (49%) (TG) p = 0.265) and death on ECLS support (n = 322 (44%) (HG) vs. n = 97 (40%) TG, p = 0.162) were comparable between the two groups, despite a more severe SAVE score in the v-a TG (HG: - 1.56 (± 4.73) vs. TG -3.93 (± 4.22) p < 0.001). Mortality rates did not change significantly over the years. Multivariate risk analysis revealed Influenza, Peak Insp. Pressure at implantation, pO2/FiO2 ratio and ECLS Score (SAVE/RESP) as well as ECLS support time to be independent risk factors for mortality. CONCLUSION: Mobile ECLS support is a tremendous challenge. However, it is justified to offer 24 h/7d ECLS standby for secondary and primary hospitals as a tertiary hospital. Increasing indications and total numbers for ECLS support raise the need for further studies to evaluate outcome in these patients.

Liver-first strategy for a combined lung and liver transplant in patients with cystic fibrosis.

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.

Intraoperative Extracorporeal Circulatory Support in Lung Transplantation for Pulmonary Fibrosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Delayed non-myeloablative irradiation to induce long-term allograft acceptance in a large animal lung transplantation model.

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.

Long-term outcomes after intraoperative extracorporeal membrane oxygenation during lung transplantation.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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%; p < 0.001). 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). CONCLUSIONS: 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.

Long-Term Results of Bilateral Lung Transplantation in Patients With End-Stage Pulmonary Lymphangioleiomyomatosis.

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.

Transplant arteriosclerosis in humanized mice reflects chronic lung allograft dysfunction and is controlled by regulatory T cells.

OBJECTIVE: Chronic lung allograft dysfunction (CLAD) is a severe complication of lung transplantation limiting long-term survival. We studied correlations between CLAD after clinical lung transplantation and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. The pericardiophrenic artery was procured from surplus tissue of donor lungs (n = 22) transplanted in our clinical program and was implanted into the abdominal aorta of immune-deficient mice. METHODS: Allogeneic human peripheral blood mononuclear cells (PBMCs) had been procured 1 day after lung transplantation from the respective recipients with or without enriching for CD4+CD25high T cells were used. TA was assessed in mice 28 days later by histology. The respective clinical lung recipients were later divided into 2 groups. Eight patients (36.3%) had developed CLAD 23 ± 5 months after lung transplantation, whereas the remaining 14 (63.6%) did not develop CLAD within 25 ± 5 months. RESULTS: In the PBMC CLAD+ group of mouse experiments, TA was significantly more severe than in the PBMC CLAD- group (39.9% ± 13% vs 14.9% ± 4% intimal thickening; P = .0081). Then, intimal thickening was significantly inhibited in the PBMC+ regulatory T cells CLAD+ group compared with the PBMC CLAD+ group (0.4% ± 4% vs 39.9% ± 13%; P = .003). In the experiments using PBMCs from lung recipients without CLAD, enriching regulatory T cells also suppressed the development of TA (0.9% ± 3% PBMC CLAD- vs 14.9% ± 4% PBMC+ regulatory T cells CLAD-; P = .001). CONCLUSIONS: Lung transplant recipients who later develop CLAD have peripheral leukocytes already at the time of transplant that transfer proinflammatory properties leading to TA in a humanized mouse model. TA remains sensitive to inhibition by autologous regulatory T cells, suggesting a cell therapy-based approach for the prevention of CLAD after lung transplantation.

Extended criteria donor lungs do not impact recipient outcomes in pediatric transplantation.

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