A European Multi-Center Analysis of Extracorporeal Photopheresis as Therapy for Chronic Lung Allograft Dysfunction.

Extracorporeal photopheresis (ECP) is used by few lung transplant centers to treat chronic lung allograft dysfunction (CLAD). Although reported results suggest a beneficial effect on CLAD progression, evidence is limited to single center experiences. The aim of this study is to analyze outcomes of ECP in a large multicenter European cohort. The primary endpoint was patient survival after initiation of ECP. This study included 631 patients, 87% suffered from bronchiolitis obliterans syndrome (BOS), and 13% had restrictive allograft syndrome (RAS). Long-term stabilization was achieved in 42%, improvement in 9%, and no response in 26%. Within the first 12 months of therapy, 23% of patients died. Patients' survival after initiation of ECP at 5 years was 56% in stable, 70% in responders, and 35% in non-responders (p = 0.001). In multivariable Cox regression, both stabilization (HR: 0.48, CI: 0.27-0.86, p = 0.013) and response (HR: 0.11, CI: 0.04-0.35, p < 0.001) to ECP were associated with survival. Absolute FEV1 at baseline was also protective (HR: 0.09, CI: 0.01-0.94, p = 0.046). RAS phenotype was the only risk factor for mortality (HR: 2.11, 1.16-3.83, p = 0.006). This study provides long-term outcomes of ECP use in CLAD patients in the largest published cohort to date. Two-thirds of the cohort had a sustained response to ECP with excellent long-term results.

Bilateral lung transplantation during pregnancy after ECMO for influenza-A caused ARDS.

Pregnant women with influenza-A have an increased risk of developing acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can be used as salvage therapy, with lung transplantation as a therapeutic option. However, successful bilateral lung transplantation during pregnancy has never been reported before. We herein report the case of a 34-year-old primipara, who was diagnosed with ARDS caused by influenza-A-induced pneumonia at early gestation. After considering all possible therapeutic options and being fully dependent on VV-ECMO support, she underwent bilateral lung transplantation. The transplantation with intraoperative central VA-ECMO support was successfully performed with good recovery after an initial primary graft dysfunction. The pregnancy was prolonged until 29+5  gestational weeks. The newborn exhibited growth retardation and was initially stabilized, but later died due to severe, hypoxic respiratory failure and pulmonary hypertension. In conclusion, lung transplantation is a possible salvage therapy for patients with severe lung failure following ARDS during pregnancy. However, it places the mother and unborn child at risk. A multi-professional approach is warranted to diagnose and treat complications at an early stage.

Comparison of donor scores in bilateral lung transplantation-A large single-center analysis.

Objectifying donor lung quality is difficult and currently there is no consensus. Several donor scoring systems have been proposed in recent years. They all lack large-scale external validation and widespread acceptance. A retrospective evaluation of 2201 donor lungs offered to the lung transplant program at the Medical University of Vienna between January 2010 and June 2018 was performed. Five different lung donor scores were calculated for each offer (Oto, ET, MALT, UMN-DLQI, and ODSS). Prediction of organ utilization, 1-year graft survival, and long-term outcome were analyzed for each score. 1049 organs were rejected at the initial offer (group I), 209 lungs declined after procurement (group II), and 841 lungs accepted and transplanted (group III). The Oto score was superior in predicting acceptance of the initial offer (AUC: 0.795; CI: 0.776-0.815) and actual donor utilization (AUC: 0.660; CI: 0.618-0.701). Prediction of 1-year graft survival was best using the MALT score, Oto score, and UMN-DLQI. Stratification of early outcome by MALT was significant for length of mechanical ventilation (LMV), PGD3 rates, ICU stay and hospital stay, and in-hospital-mortality, respectively. To the best of our knowledge, this study is the largest validation analysis comparing currently available donor scores. The Oto score was superior in predicting organ utilization, and MALT score and UMN-DLQI for predicting outcome after lung transplantation.

Simultaneous pectus excavatum correction and lung transplantation-A case series.

Severe chest wall deformities are considered an absolute contraindication for lung transplantation. The significantly impaired chest compliance associated with pectus excavatum is thought to result in a high risk of postoperative respiratory complications and significant morbidity and mortality. We herein report our pooled institutional experience consisting of 3 patients who underwent bilateral lung transplantation and simultaneous correction of a pectus excavatum. Two of the patients were children and 1 patient had severe asymmetric pectus. All patients received a size-reduced double lung transplant and the deformity was corrected by a Nuss or modified Ravitch procedure. The perioperative course was complicated by prolonged weaning requiring tracheostomy in 2 of the 3 patients. However, long-term results were good and all 3 patients are alive in excellent clinical condition 72, 60, and 12 months after the transplantation. This case series demonstrates that patients with severe chest wall deformities should not a priori be excluded from lung transplantation, and a combined approach is feasible for selected patients.

MiR-21 in Lung Transplant Recipients With Chronic Lung Allograft Dysfunction.

Background: Micro-RNA-21 (miR-21) is a post-translational regulator involved in epithelial-to-mesenchymal transition (EMT). Since EMT is thought to contribute to chronic lung allograft dysfunction (CLAD), we aimed to characterize miR-21 expression and distinct EMT markers in CLAD. Methods: Expression of miR-21, vimentin, Notch intracellular domain (NICD) and SMAD 2/3 was investigated in explanted CLAD lungs of patients who underwent retransplantation. Circulating miR-21 was determined in collected serum samples of CLAD and matched stable recipients. Results: The frequency of miR-21 expression was higher in restrictive allograft syndrome (RAS) than in bronchiolitis obliterans syndrome (BOS) specimens (86 vs 30%, p = 0.01); Vimentin, NICD and p-SMAD 2/3 were positive in 17 (100%), 12 (71%), and 7 (42%) BOS patients and in 7 (100%), 4 (57%) and 4 (57%) RAS cases, respectively. All four markers were negative in control tissue from donor lungs. RAS patients showed a significant increase in serum concentration of miR-21 over time as compared to stable recipients (p = 0.040). Conclusion: To the best of our knowledge this is the first study highlighting the role miR-21 in CLAD. Further studies are necessary to investigate the involvement of miR-21 in the pathogenesis of CLAD and its potential as a therapeutic target.

Outcomes with alemtuzumab induction therapy in lung transplantation: a comprehensive large-scale single-center analysis.

Alemtuzumab is a monoclonal antibody targeting CD52, increasingly used as induction therapy after transplantation. The aim of this study was to analyze the outcomes of alemtuzumab induction therapy followed by a low-dose maintenance immunosuppression in a large single-center cohort of lung transplant recipients. All patients, who received alemtuzumab induction followed by a low-dose maintenance immunosuppression were included in the analysis. Short- and long-term outcomes were analyzed. 721 lung transplant recipients, transplanted between January 2008 and June 2019, were included in this retrospective study. Freedom from higher-grade ACR at 1, 5, and 10 years was 98%, 96%, and 96%, respectively. Thirty-nine patients (5%) developed clinical AMR. Twenty-one percent of patients developed high-grade CKD. A total of 1488 infections were recorded. Sixteen percent were diagnosed within the first 3 months. Sixty-two patients (9%) developed a malignancy during follow-up. Freedom from CLAD at 1, 5, and 10 years was 94%, 72%, and 53%, respectively. Overall survival rates at 1, 5, and 10 years were 85%, 71%, and 61%, respectively. Alemtuzumab induction combined with a low-dose tacrolimus protocol is safe and associated with low rates of acute and chronic rejection, as well as an excellent long-term survival.

Cardiopulmonary response to high-altitude mountaineering in lung transplant recipients-The Jebel Toubkal experience.

OBJECTIVES: Only a small proportion of lung transplant recipients achieve a physical status comparable to healthy individuals in the long term. It is reasonable to hypothesize that the necessary cardiopulmonary adaptation required for strenuous physical exercise may be impaired. Exposure to high altitude provides an optimal platform to study the physiological cardiopulmonary adaptation in lung transplant recipients under aerobic conditions. To gain a deeper understanding, 14 healthy lung transplant recipients and healthcare professionals climbed the highest peak in North Africa (Mount Jebel Toubkal; 4167 m) in September 2019. METHODS: Monitoring included daily assessment of vital signs, repeated transthoracic echocardiography, pulmonary function tests, and capillary blood sampling throughout the expedition. RESULTS: Eleven out of fourteen lung transplant recipients reached the summit. All recipients showed a stable lung function and vital parameters and physiological adaptation of blood gases. Similar results were found in healthy controls. Lung transplant recipients showed worse results in the 6-minute walk test at low and high altitude compared to controls (day 1: 662 m vs. 725 m, p < 0.001, day 5: 656 m vs. 700 m, p = 0.033) and a lack of contractile adaptation of right ventricular function with increasing altitude as measured by tricuspid plane systolic excursion on echocardiography (day 2: 22 mm vs. 24 mm, p = 0.202, day 5: 23 mm vs. 26 mm, p = 0.035). CONCLUSIONS: Strenuous exercise in healthy lung transplant recipients is safe. However, the poorer cardiopulmonary performance in the 6-minute walk test and the lack of right ventricular cardiac adaptation may indicate underlying autonomic dysregulation.

Outcome of Extracorporeal Photopheresis as an Add-On Therapy for Antibody-Mediated Rejection in Lung Transplant Recipients.

INTRODUCTION: The diagnosis and treatment of antibody-mediated rejection (AMR) after lung transplantation has recently gained recognition within the transplant community. Extracorporeal photopheresis (ECP), currently used to treat chronic lung allograft dysfunction, modulates various pathways of the immune system known to be involved in AMR. We hypothesize that adding ECP to established AMR treatments could prevent the rebound of donor-specific antibodies (DSA). OBJECTIVES: This study aimed to analyze the role of ECP as an add-on therapy to prevent the rebound of DSA. METHODS: Lung transplant recipients who received ECP as an add-on therapy for pulmonary AMR between January 2010 and January 2019 were included in this single-center retrospective analysis. Baseline demographics of the patients, as well as their immunological characteristics and long-term transplant outcomes, were analyzed. RESULTS: A total of 41 patients developed clinical AMR during the study period. Sixteen patients received ECP as an add-on therapy after first-line AMR treatment. Among the 16 patients, 2 (13%) had pretransplant DSA, both against human leukocyte antigen (HLA) class I (B38, B13, and C06). Fifteen patients (94%) developed de novo DSA (dnDSA), i.e., 10 (63%) against class I and 14 (88%) against class II. The median time to dnDSA after lung transplantation was 361 days (range 25-2,548). According to the most recent International Society of Heart and Lung Transplantation (ISHLT) consensus report, 2 (13%) patients had definite clinical AMR, 6 (38%) had probable AMR, and 7 (44%) had possible AMR. The median mean fluorescence intensity (MFI) of dnDSA at the time of clinical diagnosis was 4,220 (range 1,319-10,552) for anti-HLA class I and 10,953 (range 1,969-27,501) for anti-HLA class II antibodies. ECP was performed for a median of 14 cycles (range 1-64). MFI values of dnDSA against HLA classes I and II were significantly reduced over the treatment period (for anti-class I: 752; range 70-2,066; for anti-class II: 5,612; range 1,689-21,858). The 1-year survival rate was 55%. No adverse events related to ECP were reported in any of the patients. CONCLUSIONS: ECP is associated with a reduction of dnDSA in lung transplant recipients affected by AMR. Prospective studies are warranted to confirm the beneficial effects of ECP in the setting of AMR.

Tissue Engineered Esophageal Patch by Mesenchymal Stromal Cells: Optimization of Electrospun Patch Engineering.

Aim of work was to locate a simple, reproducible protocol for uniform seeding and optimal cellularization of biodegradable patch minimizing the risk of structural damages of patch and its contamination in long-term culture. Two seeding procedures are exploited, namely static seeding procedures on biodegradable and biocompatible patches incubated as free floating (floating conditions) or supported by CellCrownTM insert (fixed conditions) and engineered by porcine bone marrow MSCs (p-MSCs). Scaffold prototypes having specific structural features with regard to pore size, pore orientation, porosity, and pore distribution were produced using two different techniques, such as temperature-induced precipitation method and electrospinning technology. The investigation on different prototypes allowed achieving several implementations in terms of cell distribution uniformity, seeding efficiency, and cellularization timing. The cell seeding protocol in stating conditions demonstrated to be the most suitable method, as these conditions successfully improved the cellularization of polymeric patches. Furthermore, the investigation provided interesting information on patches' stability in physiological simulating experimental conditions. Considering the in vitro results, it can be stated that the in vitro protocol proposed for patches cellularization is suitable to achieve homogeneous and complete cellularizations of patch. Moreover, the protocol turned out to be simple, repeatable, and reproducible.

Torque Teno Virus as a Novel Biomarker Targeting the Efficacy of Immunosuppression After Lung Transplantation.

Torque teno viruses (TTV) are small DNA-viruses, of the genus Alphatorquevirus, whose replication is linked to immune status. TTV load may be an indicator for efficacy of IS in lung transplant recipients (LTRs). In a prospective single-center-study 143 LTRs were followed up and tested by quantitative TTV-DNA PCR. Using multivariate Cox-regression contribution of TTV-load to the occurrence of severe infections, chronic lung allograft dysfunction (CLAD), acute cellular rejection (ACR), and death was assessed. During follow-up 28 (20%) patients developed infections with a rate of 7.7 per 100 patient-years (PY). The hazard-ratio (HR) associated with a one-log10 increase of TTV-load before the event was 5.05. CLAD occurred with a rate of 6.0%-PY. HR for a 1 log10 increase of the lowest TTV level before the event was 0.71 (CI: 0.54-0.93). TTV-load predicts clinical events and may be useful to optimize IS during the first years of follow-up of LTRs.

Case Report: Recurrence of Acute Respiratory Distress Syndrome After Bilateral Lung Transplantation.

BACKGROUND: The main causes of early respiratory failure after lung transplantation include primary graft dysfunction (PGD), acute rejection, and infection. This report describes a case of unclear early respiratory failure after bilateral lung transplantation for extensive COVID-19-induced acute respiratory distress syndrome (ARDS). METHODS: We reviewed the patient file to investigate the course of the functional decline and evaluate reasons for early graft failure. Analyzed data included crossmatching results, biopsy results, HLA antibodies testing, bronchoalveolar lavages, respiratory parameters, and medications. RESULTS: After an initial excellent early postoperative course, the patient developed progressive respiratory failure, making re-implantation of extracorporeal membrane oxygenation (ECMO) support necessary. An extensive diagnostic workup revealed no signs of infection or rejection. Because the patient showed no signs of improvement with any treatment, lung-protective ventilation with the intermittent prone position was initiated. The patient's respiratory situation and bilateral opacities slowly improved over the next few weeks, and ECMO support was eventually discontinued. CONCLUSION: With no evidence of PGD, rejection, or infection, recurrent ARDS caused by a systemic immunologic process was seen as the only plausible cause for the patient's respiratory failure after lung transplantation. The fact that ARDS can develop extrapulmonarily, without direct viral or bacterial damage, makes us conclude that the preceding systemic activation and recruitment of immune cells by the primarily injured lung could potentially lead to the recurrence of ARDS even if the injured organ is removed.

The Effect of Prone Positioning After Lung Transplantation.

BACKGROUND: Prone positioning has become a standard therapy in acute respiratory distress syndrome to improve oxygenation and decrease mortality. However, little is known about prone positioning in lung transplant recipients. This large, singe-center analysis investigated whether prone positioning improves gas exchange after lung transplantation. METHODS: Clinical data of 583 patients were analyzed. Prone position was considered in case of impaired gas exchange Pao2/fraction of oxygen in inhaled air (<250), signs of edema after lung transplantation, and/or evidence of reperfusion injury. Patients with hemodynamic instability or active bleeding were not proned. Impact of prone positioning (n = 165) on gas exchange, early outcome and survival were determined and compared with patients in supine positioning (n = 418). RESULTS: Patients in prone position were younger, more likely to have interstitial lung disease, and had a higher lung allocation score. Patients were proned for a median of 19 hours (interquartile range,15-26) hours). They had significantly lower Pao2/fraction of oxygen in inhaled air (227 ± 96 vs 303 ± 127 mm Hg, P = .004), and lower lung compliance (24.8 ± 9.1 mL/mbar vs 29.8 ± 9.7 mL/mbar, P < .001) immediately after lung transplantation. Both values significantly improved after prone positioning for 24 hours (Pao2/fraction of oxygen ratio: 331 ± 91 mm Hg; lung compliance: 31.7 ± 20.2 mL/mbar). Survival at 90 days was similar between the 2 groups (93% vs 96%, P = .105). CONCLUSIONS: Prone positioning led to a significant improvement in lung compliance and oxygenation after lung transplantation. Prospective studies are needed to confirm the benefit of prone positioning in lung transplantation.

Completion Pneumonectomy for Second Primary/Primary Lung Cancer and Local Recurrence Lung Cancer.

BACKGROUND: Completion pneumonectomy (CP) for second primary/primary lung cancer (SPLC) and local recurrence lung cancer (LRLC) is still controversial. Although several case series on such a practice exist, the oncological benefit is under debate. The purpose of this study was to review available literatures on CP for SPLC and LRLC and evaluate postoperative and long-term outcomes. METHODS: MEDLINE, SCOPUS, and Web of Science were reviewed for eligible studies in January 2021. Studies were included if they indicated outcomes of patients with lung cancer undergoing CP. Overall survival (OS) was defined as the primary endpoint; secondary endpoints included operative morbidity and 30-day mortality. Random-effects meta-analysis based on a binomial distribution was used to create pooled estimates. RESULTS: Thirty-two eligible studies including 1157 patients were identified. These studies were uniformly retrospective reports. Pooled estimates for 3-year and 5-year OS were 50.6% (95% confidence interval [CI], 34.7%-66.5%) and 38.9% (95% CI, 32.2%-46.1%) in SPLC patients. When the SPLC was a stage I tumor, pooled 5-year OS was favorable with 60.7% (95% CI, 43.2%-75.9%). In LRLC, pooled 3-year and 5-year OS were 47.6% (95% CI, 36.1%-59.4%) and 33.8% (95% CI, 26.8%-41.5%), respectively. Pooled morbidity and 30-day mortality was reported in 38.2% (95% CI, 32.0%-44.9%), and 10.0% (95% CI, 8.1%-12.3%), respectively. CONCLUSIONS: CP for SPLC and LRLC is a challenging procedure with significant perioperative morbimortality. However, published evidence indicates good long-term survival for selected patients. Further studies are needed to identify patient subgroups which benefit most from CP.

Lungs from polytrauma donors with significant chest trauma can be safely used for transplantation.

BACKGROUND: The use of organs from polytrauma donors for lung transplantation is controversial in the literature. For many centers, the radiologic manifestation of lung contusions is a clear reason to reject an organ offer. This results in the loss of potentially viable organs for the donor pool. METHODS: We analyzed 1152 donor lungs procured by our transplant center between January 2010 and June 2018. These included 118 lungs with a history of polytrauma involving the chest. Sixteen polytrauma donor lungs were rejected after procurement. A total of 102 lungs were transplanted, divided into 2 groups: the polytrauma contusion group (n = 44), comprising polytrauma donors with radiologic signs of lung contusion at the time of offer, and the polytrauma clear group (n = 58), comprising polytrauma donors without lung contusion. Nontrauma donor lungs transplanted during the study period were assigned to a polytrauma control group (n = 650). Short- and long-term outcomes of the 3 groups were compared. RESULTS: Basic demographic data and preoperative factors were similar in the 3 groups. Rates of primary graft dysfunction grade 3 at 72 hours did not differ among the 3 groups (0.0% vs 3.4% vs 3.9%; P = .409). The duration of ventilation was similar the 3 groups: 45 hours (interquartile range [IQR], 28-94 hours), 37 hours (IQR, 22-71 hours), and 42 hours (IQR, 22-96 hours), respectively (P = .674). Long-term graft survival was not impaired in the trauma groups compared with controls. One-year survival rates were 84.1% for the polytrauma contusion group, 93.1% for the polytrauma clear group, and 83.1% for the no polytrauma group. Five-year graft survival in the 3 groups was 74.7%, 87.2%, and 70.0%, respectively. CONCLUSIONS: Lung transplantation using organs from polytrauma donors is associated with similar short- and long-term results as transplantation from nontrauma donors. The presence or absence of radiologic signs of lung contusion at the time of offer has no impact on primary graft function and long-term survival.

Early implementation of renal replacement therapy after lung transplantation does not impair long-term kidney function in patients with idiopathic pulmonary arterial hypertension.

OBJECTIVES: In patients with idiopathic pulmonary arterial hypertension, cardiac function can be impaired in the early postoperative phase after lung transplantation because the chronically untrained left ventricle is prone to fail. Thus, restrictive fluid management is pivotal to unload the left heart. In our institution, continuous renal replacement therapy is implemented liberally whenever a patient cannot be balanced negatively. It remains unclear whether such strategy impairs long-term kidney function. METHODS: We retrospectively reviewed our institutional database for patients with idiopathic pulmonary arterial hypertension who underwent transplantation between 2000 and 2018. The impact of postoperative continuous renal replacement therapy on long-term outcomes was investigated using a linear mixed model and multivariable Cox regression. RESULTS: A total of 87 idiopathic pulmonary arterial hypertension lung transplant recipients were included in this analysis. In 38 patients (43%), continuous renal replacement therapy was started in the early postoperative period for a median of 16 days (10-22). In this group, urine production significantly decreased and patients began to acquire a positive fluid balance; however, homeostatic functions of the kidney were still preserved at the time of continuous renal replacement therapy initiation. All patients were successfully weaned from continuous renal replacement therapy and fully recovered their kidney function at the time of hospital discharge. No difference in kidney function was found between continuous renal replacement therapy and noncontinuous renal replacement therapy in patients within 5 years. CONCLUSIONS: Early implementation of continuous renal replacement therapy for perioperative volume management does not impair long-term kidney function in idiopathic pulmonary arterial hypertension lung transplant recipients. Our data suggest that such a strategy leads to excellent long-term outcomes.

Duration of extracorporeal life support bridging delineates differences in the outcome between awake and sedated bridge-to-transplant patients.

OBJECTIVES: Traditionally, patients on bridge-to-transplant extracorporeal membrane oxygenation were kept sedated and intubated. However, awake bridging strategies have evolved during recent years. This study aims to elaborate differences in physical activity and postoperative outcomes after lung transplantation (LTx), depending on bridging strategy and duration. METHODS: Bridged patients receiving LTx between March 2013 and April 2021 were analysed. Awake bridging was defined as a Richmond Agitation-Sedation Scale score of ≥-1 until 24 h before transplantation. Patients were grouped in awake and sedated cohorts. RESULTS: A total of 88 patients (35 awake, 53 sedated bridging) were included. After LTx, mobilization to standing position was achieved earlier in awake bridged patients (7 vs 15 days, P < 0.001). Postoperative ventilation time (247 vs 88 h, P = 0.005) and intensive care unit stay (30 vs 16 days, P = 0.004) were longer in the sedated cohort. Awake patients with bridging duration >6 days showed shorter postoperative ventilation time (108 vs 383 h, P = 0.003), less intensive care unit days (23 vs 36, P = 0.003) and earlier mobilization to standing position (9 vs 17 days, P < 0.001). In contrast, postoperative ventilation time and days in intensive care unit in patients with bridge-to-transplant duration ≤6 days were comparable between cohorts. Mobilization to standing position was achieved faster in the awake (≤6 days) bridged cohort (5 vs 9 days, P = 0.024). CONCLUSIONS: Despite the complex management of bridged patients, excellent survival rates after LTx can be achieved. Especially in patients with more than 1 week on extracorporeal membrane oxygenation, awake bridging concepts are associated with significantly faster recovery.

A Dual-Lumen Extracorporeal Membrane Oxygenation Cannulation Technique Using a Mobile X-Ray Device.

PURPOSE: Dual-lumen extracorporeal membrane oxygenation (ECMO) cannulation is considered technically challenging and harbors the risk of potential life-threatening complications during cannulation. Dual-lumen cannula insertion is performed under either ultrasound or fluoroscopy guidance. Both techniques have significant disadvantages, such as examiner dependence or the necessity for transportation of the patient from the intensive care unit to the operating room. DESCRIPTION: Digital, mobile x-ray devices provide a novel, examiner-independent imaging modality for bedside dual-lumen ECMO cannulation. EVALUATION: From November 2019 to November 2021, 23 dual-lumen cannulations were performed in 20 patients at the Department of Thoracic Surgery, Medical University of Vienna. Twelve of 23 (52.2%) were inserted in the intensive care unit using a mobile x-ray device. The remaining patients (47.8%) were cannulated in the operating room with conventional fluoroscopy guidance. In none of the procedures did cardiovascular injuries occur. Insertion site bleeding was the most common ECMO-related complication (n = 2). CONCLUSIONS: Dual-lumen cannulation using sequential x-rays can be performed safely. Especially for infectious patients or patients who require an awake ECMO, this technique overcomes disadvantages of established imaging modalities.

Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs.

Clinical evidence suggests an improvement or stabilization of lung function in a fraction of patients with bronchiolitis obliterans syndrome (BOS) treated by extracorporeal photopheresis (ECP); however, few studies have explored the epigenetic and molecular regulation of this therapy. The aim of present study was to evaluate whether a specific set of miRNAs were significantly regulated by ECP. Total RNA was isolated from serum of patients with established BOS grade 1-2 prior to the start and after 6 months of ECP treatment. We observed a significant downregulation of circulating hsa-miR-155-5p, hsa-miR-146a-5p and hsa-miR-31-5p in BOS patients at the start of ECP when compared to healthy subjects. In responders, increased miR-155-5p and decreased miR-23b-3p expression levels at 6 months were found. SMAD4 mRNA was found to be a common target of these two miRNAs in prediction pathways analysis, and a significant downregulation was found at 6 months in PBMCs of a subgroup of ECP-treated patients. According to previous evidence, the upregulation of miR-155 might be correlated with a pro-tolerogenic modulation of the immune system. Our analysis also suggests that SMAD4 might be a possible target for miR-155-5p. Further longitudinal studies are needed to address the possible role of miR-155 and its downstream targets.

Prioritizing direct heart procurement in organ donors after circulatory death does not jeopardize lung transplant outcomes.

Background: Controlled donation after circulatory death (cDCD) has become a standard in liver, kidney, and lung transplantation (LTx). Based on recent innovations in ex vivo heart preservation, heart transplant centers have started to accept cDCD heart allografts. Because the heart has very limited tolerance to warm ischemia, changes to the cDCD organ procurement procedures are needed. These changes entail delayed ventilation and prolonged warm ischemia for the lungs. Whether this negatively impacts lung allograft function is unclear. Methods: A retrospective analysis of cDCD lungs transplanted between 2012 and February 2022 at the Medical University of Vienna was performed. The heart + lung group consisted of cases in which the heart was procured by a cardiac team for subsequent normothermic ex vivo perfusion. A control group (lung group) was formed by cases where only the lungs were explanted. In heart + lung group cases, the heart procurement team placed cannulas after circulatory death and a hands-off time, collected donor blood for ex vivo perfusion, and performed rapid organ perfusion with Custodiol solution, after which the heart was explanted. Up to this point, the lung procurement team did not interfere. No concurrent lung ventilation or pulmonary artery perfusion was performed. After the cardiac procurement team left the table, ventilation was initiated, and lung perfusion was performed directly through both stumps of the pulmonary arteries using 2 large-bore Foley catheters. This study analyzed procedural explant times, postoperative outcomes, primary graft dysfunction (PGD), duration of mechanical ventilation, length of intensive care unit (ICU) stay, and early survival after LTx. Results: A total of 56 cDCD lungs were transplanted during the study period. In 7 cases (12.5%), the heart was also procured (heart + lung group); in 49 cases (87.5%), only the lungs were explanted (lung group). Basic donor parameters were comparable in the 2 groups. The median times from circulatory arrest to lung perfusion (24 minutes vs 13.5 minutes; P = .002) and from skin incision to lung perfusion (14 minutes vs 5 minutes; P = .005) were significantly longer for the heart + lung procedures. However, this did not affect post-transplantation PGD grade at 0 hours (P = .851), 24 hours (P = .856), 48 hours (P = .929), and 72 hours (P = .874). At 72 hours after transplantation, none of the lungs in the heart + lung group but 1 lung (2.2%) in lung group was in PGD 3. The median duration of mechanical ventilation (50 hours vs 41 hours; P = .801), length of ICU stay (8 days vs 6 days; P = .951), and total length of hospital stay (27 days vs 25 days; P = .814) were also comparable in the 2 groups. In-hospital mortality occurred in only 1 patient of the lung group (2.2%). Conclusions: Although prioritized cDCD heart explantation is associated with delayed ventilation and significantly longer warm ischemic time to the lungs, post-LTx outcomes within the first year are unchanged. Prioritizing heart perfusion and explantation in the setting of cDCD procurement can be considered acceptable.

Immune Response after mRNA COVID-19 Vaccination in Lung Transplant Recipients: A 6-Month Follow-Up.

BACKGROUND AND OBJECTIVE: This prospective cohort study analyzed the immune response to COVID-19 mRNA vaccines in lung transplant recipients (LuTRs) compared to healthy controls (HCs) at a 6-month follow-up. METHODS: After the first two doses of either BNT162b2 or mRNA-1273, SARS-CoV-2 antibodies were measured in LuTRs (n = 57) and sex- and age-matched HCs (n = 57). Antibody kinetics during a 6-month follow-up and the effect of a third vaccine dose were evaluated. Humoral responses were assessed using the Elecsys® Anti-SARS-CoV-2 S immunoassay. In 16 LuTRs, SARS-CoV-2-specific T cell responses were quantified using IFN-γ ELISpot assays. RESULTS: Seroconversion rates were 94% and 100% after the first and second vaccine dose, respectively, in HCs, while only 19% and 56% of LuTRs developed antibodies. Furthermore, 22 of 24 LuTRs who received the third vaccine dose showed seroconversion (five of seven primary non-responders and 17 of 17 primary responders). A T cell response against SARS-CoV-2-spike S1 and/or S2 was detected in 100% (16/16) of HCs and 50% (8/16) of LuTRs. CONCLUSIONS: The data suggest that LuTRs have reduced humoral and cellular immune responses after two doses of COVID-19 mRNA vaccination when compared to HCs. A third dose may be of substantial benefit.