Two single lung transplantations from one donor: lung twinning in the LAS era.

OBJECTIVES: The implementation of the Lung Allocation Score (LAS) in the Eurotransplant international collaborative framework decreased waiting list mortality, but organ shortage remains a significant problem. Transplantation of two single lungs from one donor into two recipients (lung twinning) may decrease waiting list mortality. We sought to analyze if this strategy can lead to an acceptable intermediate-term outcome. METHODS: Since the LAS-implementation we performed 32 paired single-lung transplantations from 16 postmortal donors. Data and outcome were analyzed retrospectively comparing recipients receiving the first lung (first twins) with recipients receiving the second lung (second twins), left versus right transplantation and restrictive versus obstructive disease. RESULTS: Survival at one year was 81% and 54% at five years. Veno-venous ECMO had been successfully used as bridge-to-transplant in three patients with ECMO-explantation immediately after surgery. Bronchial anastomotic complications were not observed in any patient. First twins and second twins exhibited similar survival (p = 0.82) despite higher LAS in first twins (median 45 versus 34, p < 0.001) and longer cold ischemic time in second twins (280 ± 83 vs. 478 ± 125 min, p < 0.001). Survival of left and right transplantation was similar (p = 0.45) with similar best post-transplant FEV1 (68 ± 15% versus 62 ± 14%, p = 0.26). Survival was similar in restrictive and obstructive disease (p = 0.28) with better post-transplant FEV1 (70 ± 15% versus 57 ± 11%, p = 0.02) in restrictive disease. CONCLUSIONS: Performing two single-lung transplantations from one donor can be performed safely with encouraging intermediate-term outcome and good functional capacity. Lung twinning maximizes the donor pool and may help to overcome severe organ shortage. CLINICAL TRIALS: This research is not a clinical trial. Thus no registration details will be provided.

THSD7A Positivity Predicts Poor Survival and Is Linked to High FAK Expression and FGFR1-Wildtype in Female Patients with Squamous Cell Carcinoma of the Lung.

Lung cancer is the leading cause of cancer-related deaths in the western world, with squamous cell carcinoma being one of the most common histological subtypes. Prognostic and predictive markers are still largely missing for squamous cell carcinoma of the lung (LSCC). Several studies indicate that THSD7A might at least play a role in the prognosis of different tumors. FAK seems to play an important role in lung cancer and is discussed as a potential therapeutic target. In addition, there is evidence that FAK-dependent signaling pathways might be affected by THSD7A. For that reason, we investigated the role of THSD7A as a potential tumor marker in LSCC and whether THSD7A expression has an impact on the expression level of FAK. A total of 101 LSCCs were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity was associated with poor overall survival in female patients and showed a relation to high FAK expression in this subgroup. To our knowledge, we are the first to report these correlations in lung cancer. The results might be proof of the assumed activation of FAK-dependent signaling pathways by THSD7A and that as a membrane-associated protein, THSD7A might serve as a putative therapeutic target in LSCC.

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial.

BACKGROUND: Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes. METHODS: In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration. RESULTS: In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation. CONCLUSION: During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation. REGISTRATION OF CLINICAL TRIAL: DRKS-ID DRKS00014788 (www.drks.de).

COVID-19: a catalyst for the digitization of surgical teaching at a German University Hospital.

BACKGROUND: The summer semester 2020, had to be restructured due to the SARS-CoV-2 pandemic and the associated contact restrictions. Here, for the first time, the established lectures in lecture halls and small group seminars could not be conducted in presence as usual. A possible tool for the implementation of medical teaching, offers the use of eLearning, online webinars and learning platforms. At present it is unclear how the SARS-CoV-2 pandemic will affect surgical teaching, how digitization will be accepted by students, and how virtual teaching can be expanded in the future. METHODS: The teaching, which was previously delivered purely through face-to-face lectures, was completely converted to digital media. For this purpose, all lectures were recorded and were available to students on demand. The seminars were held as a twice a week occurring online webinar. The block internship was also conducted as a daily online webinar and concluded with an online exam at the end. At the end of the semester, a survey of the students was carried out, which was answered by n = 192 students with an anonymized questionnaire. The questionnaire inquires about the previous and current experience with eLearning, as well as the possibility of a further development towards a purely digital university. RESULTS: There were n = 192 students in the study population. For 88%, the conversion of classes to web-based lectures represented their first eLearning experience. For 77% of all students, the digitization of teaching led to a change in the way they prepare for class. 73% of the participating students are of the opinion that eLearning lectures should continue to be offered. 54% of the students felt that eLearning lectures made more sense than face-to-face lectures. A purely virtual university could be imagined by 41% of the students. CONCLUSION: The conversion of teaching represented the first contact with eLearning for most students. Overall, the eLearning offering was experienced as positive. Due to the new teaching structure, the way of learning had already changed during the semester. Based on the new eLearning content, the already existing formats can be further expanded in the future. Nevertheless, it turned out that the practical-surgical contents and skills cannot be adequately represented by purely online offers; for this, the development of hybrid practice-oriented teaching concepts is necessary.

Survival analysis for AdVerse events with VarYing follow-up times (SAVVY)-estimation of adverse event risks.

BACKGROUND: The SAVVY project aims to improve the analyses of adverse events (AEs), whether prespecified or emerging, in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). Although statistical methodologies have advanced, in AE analyses, often the incidence proportion, the incidence density, or a non-parametric Kaplan-Meier estimator are used, which ignore either censoring or CEs. In an empirical study including randomized clinical trials from several sponsor organizations, these potential sources of bias are investigated. The main purpose is to compare the estimators that are typically used to quantify AE risk within trial arms to the non-parametric Aalen-Johansen estimator as the gold-standard for estimating cumulative AE probabilities. A follow-up paper will consider consequences when comparing safety between treatment groups. METHODS: Estimators are compared with descriptive statistics, graphical displays, and a more formal assessment using a random effects meta-analysis. The influence of different factors on the size of deviations from the gold-standard is investigated in a meta-regression. Comparisons are conducted at the maximum follow-up time and at earlier evaluation times. CEs definition does not only include death before AE but also end of follow-up for AEs due to events related to the disease course or safety of the treatment. RESULTS: Ten sponsor organizations provided 17 clinical trials including 186 types of investigated AEs. The one minus Kaplan-Meier estimator was on average about 1.2-fold larger than the Aalen-Johansen estimator and the probability transform of the incidence density ignoring CEs was even 2-fold larger. The average bias using the incidence proportion was less than 5%. Assuming constant hazards using incidence densities was hardly an issue provided that CEs were accounted for. The meta-regression showed that the bias depended mainly on the amount of censoring and on the amount of CEs. CONCLUSIONS: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. We recommend using the Aalen-Johansen estimator with an appropriate definition of CEs whenever the risk for AEs is to be quantified and to change the guidelines accordingly.

Endoscopic lung volume reduction coils for patients with severe emphysema-a single-centre retrospective analysis.

OBJECTIVES: Patients with chronic obstructive pulmonary disease and lung emphysema may benefit from surgical or endoscopic lung volume reduction (ELVR). Previously reported outcomes of nitinol coil-based ELVR techniques have been ambiguous. The analysis was done to analyse outcomes of ELVR with nitinol coils in patients with severe pulmonary emphysema. METHODS: From September 2013 to November 2014, our centre performed a total of 41 coil implantations on 29 patients with severe emphysema. Coils were bronchoscopically placed during general anaesthesia. Twelve out of 29 patients received staged contralateral treatments up to 112 days later to avoid bilateral pneumothorax. Lung function and 6-min walking distance were assessed 1 week prior, 1 week after as well as 6-12 months after the procedure. Patients were followed up to 48 months after ELVR and overall mortality was compared to a historic cohort. RESULTS: While coil-based ELVR led to significant short-term improvement of vital capacity (VC, +0.14 ± 0.39 l, P = 0.032) and hyperinflation (Δ residual volume/total lung capacity -2.32% ± 6.24%, P = 0.022), no significant changes were observed in 6-min walking distance or forced expiratory volume in 1 s. Benefits were short-lived, with only 15.4% and 14.3% of patients showing sustained improvements in forced expiratory volume in 1 s or residual volume after 6 months. Adverse events included haemoptysis (40%) and pneumothorax (3.4%), major complications occurred in 6.9% of cases. Overall survival without lung transplant was 63.8% after 48 months following ELVR, differing insignificantly from what BODE indices of patients would have predicted as median 4-year survival (57%) at the time of ELVR treatment. CONCLUSIONS: ELVR with coils can achieve small and short-lived benefits in lung function at the cost of major complications in a highly morbid cohort. Treatment failed to improve 4-year overall survival. ELVR coils are not worthwhile the risk for most patients with severe emphysema.

Long-term Outcomes After Pulmonary Endarterectomy in 499 Patients Over a 20-Year Period.

BACKGROUND: Pulmonary endarterectomy (PEA) is a curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). Pulmonary hypertension (PH) after PEA is not uncommon, and its impact on long-term outcomes is poorly understood. We investigated the effects of residual PH on current long-term survival and on postoperative status. METHODS: Data of 499 consecutive patients who underwent PEA between December 1995 and December 2014 were analyzed retrospectively. Kaplan-Meier survival analysis was used to estimate the survival rates with the 95% confidence interval. RESULTS: Overall survival at 5, 10, and 15 years postoperatively was 84.8% ± 1.9%, 77.1% ± 2.7%, and 59.2% ± 5.3%, respectively. Survival after discharge at 5, 10, and 15 years was 93.9% ± 1.5%, 85.4% ± 2.6%, and 65.6% ± 5.8%, respectively. Of all, 166 patients had residual PH immediately after PEA and a poorer prognosis regarding freedom from CTEPH-related death. CTEPH-related survival at 10 years in patients with normal pulmonary artery pressure vs residual PH was 89.0% ± 2.7% vs 67.9% ± 4.7%, respectively (P < .001). There was a trend to CTEPH-related survival after discharge being affected by residual PH (P = .092). At follow-up, patients with residual PH had worse exercise tolerance (P < .001) and symptoms (P < .001) compared with those with normal pulmonary artery pressure. The probability of developing PH over time was 41.9% at 15 years. CONCLUSIONS: Survival after hospital discharge is excellent for patients undergoing PEA. Postoperative PH is associated with more symptoms and poorer functional capacity. Patients who have clinically relevant postoperative PH should be monitored closely and may be candidates for additional medical therapy.

An Evaluation of the Learning Curve in Pulmonary Endarterectomy Using Propensity Score Matching.

OBJECTIVE: Pulmonary endarterectomy (PEA) is the only causative, but demanding treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). We analyzed our results with PEA to evaluate the learning curve. METHODS: Consecutive 499 patients who underwent PEA between 1995 and 2014 were divided into two groups according to the temporal order: early cohort (n = 200, December 1995-March 2006), and late cohort (n = 299, March 2006-December 2014). We assessed perioperative outcomes after PEA as compared between the early and the late cohort also in propensity-score-matched cohorts. RESULTS: Age at the surgery was older in the late cohort (p = 0.042). Preoperative mean pulmonary artery pressure (mPAP) was 46.8 ± 11.0 mm Hg in the early cohort and 43.5 ± 112.7 mm Hg in the late cohort (p = 0.0035). The in-hospital mortality in the early and late cohorts was 14.0% (28/200) and 4.7% (14/299), respectively (p = 0.00030). The duration of circulatory arrest (CA) became much shorter in the late cohort (42.0 ± 20.5 min in the early and 24.2 ± 11.6 min in the late cohort, respectively, p < .0001). In matched cohorts, the in-hospital mortality showed no significant difference (8.7% in the early cohort and 5.2% in the late cohort, < 0.0001). The CA duration, however, was still shorter in the late cohort (p <0.0001). CONCLUSIONS: Over time, older patients have been accepted for surgery, more patients were operated for lesser severity of CTEPH. Duration of CA and mortality decreased even beyond the first 200 patients, indicating a long learning curve.

Management of lung transplantation in the COVID-19 era-An international survey.

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.

A 71-Year-Old Man With Chest Pain and a Solitary Pulmonary Mass.

CASE PRESENTATION: A 71-year-old man was admitted to our hospital because of diffuse chest pain and a mass on routine chest radiography. He did not report cough, dyspnea, fever, night sweats, or weight loss. His medical history was remarkable for chronic lymphocytic leukemia diagnosed 13 years before presentation, and secondary myelodysplastic syndrome diagnosed 2 years before the onset of the current symptoms. As a curative approach, he had received a matched unrelated stem cell transplantation 16 months earlier, and he had been in complete remission since. He developed chronic graft-vs-host disease, presenting mainly as oral ulceration (grade 1, according to National Institute of Health consensus criteria), which had been treated with oral cyclosporine and extracorporeal photopheresis. The immunosuppression had been tapered 6 months before presentation. Routine medication included co-trimoxazole prophylaxis twice per week. He had no known allergies, and he denied recent travels and sick contacts.

Flagellin shifts 3D bronchospheres towards mucus hyperproduction.

Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are associated with acute and chronic bacterial infections of the lung. Excessive differentiation of basal cells to mucus-producing goblet cells can result in mucus hyperproduction and loss of mucociliary clearance in the airways of CF and COPD patients. Here, we aimed to investigate the effect of pathogen-associated molecular patterns (PAMPs) on the differentiation of human 3D bronchospheres. Primary human bronchial epithelial cells (HBECs) were differentiated to bronchospheres in the presence of bacterial flagellin and LPS and the synthetic Toll-like receptor (TLR) ligands Pam3CSK4 (TLR-2) and polyinosinic:polycytidylic acid (pIC, TLR-3). Electron and fluorescence microscopy showed that the differentiation of bronchospheres associated with the formation of lumina and appearance of cilia within 30 days after seeding. Incubation with flagellin resulted in a decreased formation of lumina and loss of cilia formation. Incubation with Pam3CSK, pIC, and LPS did not significantly affect formation of lumina and ciliation. Mucus production was strongly increased in response to flagellin and, to a lesser degree, in response to Pam3CSK4. Our results indicate that bacterial factors, such as flagellin, drive the differentiation of the respiratory epithelium towards mucus hyperproduction.

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant - a historical prospective study.

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2 /FiO2  ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.

Bilateral papillary muscle repositioning: successful repair of functional mitral regurgitation in dilative cardiomyopathy.

OBJECTIVES: Functional mitral regurgitation (FMR) in patients with non-ischaemic dilative cardiomyopathy (DCM) is associated with heart failure and poor outcome. Aggressively undersized annuloplasty as an annular solution for a ventricular problem ameliorates heart failure but may be associated with recurrent FMR and does not improve survival. We sought to analyse if moderately undersized annuloplasty with repositioning of both papillary muscles can lead to improved valve stability and outcome in patients with DCM and FMR. METHODS: In 66 patients with DCM-associated FMR (age 66 ± 12 years, ejection fraction 29 ± 6% and mean pulmonary artery pressure 35 ± 11 mmHg) and severe leaflet tethering (tenting height ≥10 mm) bilateral papillary muscle repositioning was added to moderately undersized ring annuloplasty (median size 30 mm). Concomitant surgery included tricuspid valve repair in 86% of patients and atrial ablation in 44%. RESULTS: The early mortality rate was 9%. Overall 5-year freedom from all-cause death, left ventricular assist device implantation or heart transplant was 58% (95% confidence interval 45-71%). Six patients underwent reoperation (redo repair n = 4). Reverse remodelling was observed during follow-up in 66% of patients with decreasing left ventricular end-diastolic diameters (66 ± 5 to 61 ± 12 mm; P < 0.001) and left ventricular end-systolic diameters (56 ± 9 to 51 ± 14 mm; P = 0.001). Subgroup analyses (partial versus complete ring, preoperative left ventricular end-diastolic diameters <65 mm vs left ventricular end-diastolic diameter ≥65 mm) documented similar survival rates. A competing risks regression analysis identified cerebral vascular disease (P = 0.01), use of a partial ring (P = 0.03) and absence of tricuspid valve repair (P = 0.03) as independent predictors of death. CONCLUSIONS: The combination of bilateral papillary muscle repositioning and moderately undersized ring annuloplasty leads to stable mid-term repair results and reverse remodelling in patients with DCM and FMR and severe leaflet tethering.

On estimands and the analysis of adverse events in the presence of varying follow-up times within the benefit assessment of therapies.

The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The statistical analysis of AEs is complicated by the fact that the follow-up times can vary between the patients included in a clinical trial. This paper takes as its focus the analysis of AE data in the presence of varying follow-up times within the benefit assessment of therapeutic interventions. Instead of approaching this issue directly and solely from an analysis point of view, we first discuss what should be estimated in the context of safety data, leading to the concept of estimands. Although the current discussion on estimands is mainly related to efficacy evaluation, the concept is applicable to safety endpoints as well. Within the framework of estimands, we present statistical methods for analysing AEs with the focus being on the time to the occurrence of the first AE of a specific type. We give recommendations which estimators should be used for the estimands described. Furthermore, we state practical implications of the analysis of AEs in clinical trials and give an overview of examples across different indications. We also provide a review of current practices of health technology assessment (HTA) agencies with respect to the evaluation of safety data. Finally, we describe problems with meta-analyses of AE data and sketch possible solutions.

Improving Outcomes in Bridge-to-Transplant: Extended Extracorporeal Membrane Oxygenation Support to Obtain Optimal Donor Lungs for Marginal Recipients.

The use of extracorporeal membrane oxygenation (ECMO) as bridge-to-lung transplantation has been discussed controversially because of discouraging results. We report our experience with this challenging strategy. This retrospective investigation includes all consecutive lung transplantations in our center between January 2012 and July 2017 (n = 88, median Lung Allocation Score 66). Data of patients on ECMO bridge-to-transplant (n = 34) were compared with patients without such support (n = 54). Patients requiring ECMO support underwent lung transplantation after median bridging time of 29 days (range, 0-129 days). Survival was superior if transplantation was performed within 29 days of ECMO (p = 0.04). Donor age and oxygenation (pO2/FiO2) were similar in recipients with ECMO (42.3 ± 15.2 years, 444.5 ± 68.9 mm·Hg) or without ECMO (43.1 ± 13.9 years, 454.5 ± 73.4 mm·Hg). Four patients required postoperative ECMO support >1 day. Survival at 1 year and 3 years was similar in recipients with ECMO support (79%, 63%) or without ECMO support (86%, 71%). Successful lung transplantation after ECMO as bridge-to-transplant can be achieved, even in patients with prolonged support times. Bridging time of less than 30 days, however, is crucial for success. Extracorporeal membrane oxygenation expertise and donor organ quality may be important factors for favorable outcome.

Lung allocation score: the Eurotransplant model versus the revised US model - a cross-sectional study.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

Percutaneous Mechanical Circulation Support Combined with Extracorporeal Membrane Oxygenation (oxyRVAD) in Secondary Right Heart Failure.

Right heart failure (RHF) because of pulmonary hypertension (PH) is a frequently encountered clinical problem with high mortality. The last resort, if pharmacological therapy fails, is mechanical circulatory support. There is a lack of percutaneous systems to support the right ventricle (RV). Venoarterial extracorporeal membrane oxygenation is widely used as a bailout in acute RHF in non-left ventricular assist device patients. Venoarterial extracorporeal membrane oxygenation does not unload the left ventricle and may cause failure of the left ventricle if used for a longer period of time. We report the long-term use of an ECMO-based percutaneous right ventricular assist system (oxyRVAD) capable to deliver up to 6 L/min of blood flow with a returning cannula placed in the main pulmonary artery used in RHF originating from PH with poor oxygenation. We present a series of four patients on oxyRVAD (mean treatment duration 15 ± 7.6 days). Patients benefited from the system clinically; however, two patients eventually died while on oxyRVAD. Nevertheless, we provide a proof-of-concept of this system in PH patients, which is feasible and might provide a useful "bridge-to-recovery" or "bridge-to-transplant" option in the management of patients with severe RHF because of PH.

High Serum Bilirubin Levels, NT-pro-BNP, and Lactate Predict Mortality in Long-Term, Severely Ill Respiratory ECMO Patients.

Mortality in patients treated with extracorporeal membrane oxygenation (ECMO) is high. Therefore, it is crucial to better understand conditions that are associated with mortality in ECMO patients. In this retrospective analysis, we observed 51 patients treated with high-flow ECMO in 2013 and 2014 at our center. We recorded laboratory values and intensive care procedures. The hypothesis of bilirubin being a predictor of mortality during ECMO treatment was initially addressed. Therefore, laboratory values were obtained before initiation and at the time of highest bilirubin throughout the procedure. Receiver operating characteristic (ROC) curves and survival analysis were conducted. Our cohort consisted of patients with advanced age (median: 55 years; range: 22-76) and high mortality (26/51; 51%). Lactate, bilirubin, and NT-pro-BNP were significantly (p < 0.05) associated with mortality in univariable analyses. The cut-off values with highest Youden's index were bilirubin ≥10 mg/dl, lactate ≥2.25 mmol/L, and NT-pro-BNP ≥11,500 pg/ml. A multivariable analysis, revealed an area under the curve (AUC) of 0.85 (95% confidence interval [CI]: 0.74-0.97), sensitivity of 0.79, and specificity of 0.91. Bilirubin, lactate, and NT-pro-BNP were associated with mortality during ECMO treatment. However, laboratory values were only evaluated at the time of peak bilirubin.