Publications by authors named "Peter Jaksch"

118 Publications

Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries.

Lancet Respir Med 2021 05 31;9(5):487-497. Epub 2021 Mar 31.

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Background: Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.

Methods: We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.

Findings: Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.

Interpretation: The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.

Funding: National Institutes of Health. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/S2213-2600(21)00077-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012035PMC
May 2021

Potential novel biomarkers for chronic lung allograft dysfunction and azithromycin responsive allograft dysfunction.

Sci Rep 2021 Mar 24;11(1):6799. Epub 2021 Mar 24.

Division of Surgery, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Chronic Lung Allograft Dysfunction (CLAD), manifesting as Bronchiolitis Obliterans Syndrome (BOS) or Restrictive Allograft Syndrome (RAS), is the main reason for adverse long-term outcome after Lung Transplantation (LTX). Until now, no specific biomarkers exist to differentiate between CLAD phenotypes. Therefore, we sought to find suitable cytokines to distinguish between BOS, RAS and Azithromycin Responsive Allograft Dysfunction (ARAD); and reveal potential similarities or differences to end-stage fibrotic diseases. We observed significantly increased Lipocalin-2 serum concentrations in RAS compared to BOS patients. In addition, in RAS patients immunohistochemistry revealed Lipocalin-2 expression in bronchial epithelium and alveolar walls. Patients with ARAD showed significantly lower Activin-A serum concentrations compared to Stable-LTX and BOS patients. Further, increased serum concentrations of Lipocalin-2 and Activin-A were predictors of worse freedom-from-CLAD in Stable-LTX patients. These biomarkers serve as promising serum biomarkers for CLAD prediction and seem suitable for implementation in clinical practice.
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http://dx.doi.org/10.1038/s41598-021-85949-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990920PMC
March 2021

Extent of Cytomegalovirus Replication in the Human Host Depends on Variations of the HLA-E/UL40 Axis.

mBio 2021 03 16;12(2). Epub 2021 Mar 16.

Center for Virology, Medical University of Vienna, Vienna, Austria

Human cytomegalovirus (HCMV) may cause severe infections in lung transplant recipients (LTRs). In response to HCMV infections, a subset of NKG2C NK cells expands, which limits HCMV replication and is characterized by high expression of the activating NKG2C/CD94 and absence of the inhibitory NKG2A/CD94 receptor. Both receptors bind to HLA-E, which is stabilized by HCMV-encoded UL40 peptides. HLA-E and UL40 occur as different genetic variants. In this study, we investigated the interplay between the human NK cell response and the infecting HCMV-UL40 strain, and we assessed the impact of HCMV-UL40 and of donor- and recipient-encoded HLA-E*0101/0103 variants on HCMV replication after lung transplantation. We included 137 LTRs displaying either no or low- or high-level (>1,000 copies/ml plasma) viremia. HCMV-UL40 and HLA-E*0101/0103 variants were determined. UL40 diversity was investigated by next-generation sequencing. UL40 peptide-dependent NK cell cytotoxicity was assessed by flow cytometry. Donor-encoded HLA-E*0101/0103 was significantly associated with development of high-level viremia after transplantation ( = 0.007). The HCMV-UL40 variant VMAPRTLIL occurred significantly more frequently in highly viremic LTRs, and the variant VMTPRTLIL occurred significantly more frequently in low-viremic LTRs ( = 0.004). This difference was associated with a better inhibition of NKG2A NKG2C NK cells by VMAPRTLIL ( < 0.001). In LTRs with repeated high-level viremic episodes, HCMV strains with UL40 variants displaying low affinity to the patients' HLA-E variant emerged over time. The HLA-E-UL40 axis has a substantial impact on the level of HCMV replication in LTRs. The interplay between UL40 peptide variants, the recipient HLA-E status, and the activation of inhibitory NKG2A NKG2C cells is of major importance for development of high-level viremia after lung transplantation. Infection with human cytomegalovirus (HCMV) is associated with substantial morbidity in immunosuppressed patients and after congenital infections. Therefore, development of a vaccine against HCMV is a main public health priority. Revealing the complex interaction between HCMV and host responses, is of utmost importance for understanding viral pathogenesis and for vaccine design. The present data contribute to the understanding of HCMV-specific host immune responses and reveal specifically the interaction between HLA-E and the virus-encoded UL40 peptide, which further leads to a potent NK cell response. We demonstrate that this interaction is a key factor for reduction of virus replication in immunosuppressed patients. We further show that distinct naturally occurring HCMV-UL40 variants reduce the activation of a specific subpopulation of host NK cells and thereby are associated with high-level viremia in the patients. These findings will allow the characterization of patients at risk for severe HCMV infection and contribute to strategies for HCMV vaccine development.
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http://dx.doi.org/10.1128/mBio.02996-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092275PMC
March 2021

Initial Postoperative Hemoglobin Values Are Independently Associated With One-Year Mortality in Patients Undergoing Double-Lung Transplantation Requiring Intraoperative Transfusion.

J Cardiothorac Vasc Anesth 2020 Dec 29. Epub 2020 Dec 29.

Division of Cardiothoracic and Vascular Anesthesia and Intensive Care Medicine, Department of Anesthesia, Intensive Care Medicine and Pain Medicine, General Hospital Vienna, Medical University of Vienna, Wien, Austria. Electronic address:

Objective: To evaluate the association of postoperative hemoglobin values and mortality in patients undergoing double- lung transplantation with intraoperative transfusion.

Design: Retrospective cohort study.

Setting: University hospital.

Participants: Adult patients who underwent double-lung transplantation at the authors' institution, with intraoperative transfusion of packed red blood cells between 2009 and 2015.

Interventions: None.

Measurements And Main Results: Intraoperative transfusion requirements and general characteristics of 554 patients were collected. A generalized additive model, controlling for postoperative hemoglobin levels, number of transfused units of packed red blood cells, perioperative change in hemoglobin levels, disease leading to lung transplantation, and postoperative extracorporeal membrane oxygenation, was created to predict one-year mortality. A postoperative hemoglobin level of 11.3 g/dL was calculated as an optimal cutoff point. The patients were stratified according to this level. The end -point was all-cause one-year mortality after double-lung transplantation, assessed using the Kaplan-Meier analysis with log-rank test. All-cause mortality of the 554 patients was 17%. Postoperatively, 171 patients (31%) were categorized as being below the cutoff point. Improved survival was observed in the group with higher postoperative hemoglobin values (p = 0.002).

Conclusion: Lower postoperative hemoglobin levels in double-lung transplantation recipients were associated with increased mortality during the first year after surgery. Confirmation of these findings in additional investigations could alter patient blood management for double-lung transplantation.
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http://dx.doi.org/10.1053/j.jvca.2020.12.040DOI Listing
December 2020

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

J Thorac Cardiovasc Surg 2020 Nov 27. Epub 2020 Nov 27.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jtcvs.2020.10.150DOI Listing
November 2020

Viral load-guided immunosuppression after lung transplantation (VIGILung)-study protocol for a randomized controlled trial.

Trials 2021 Jan 11;22(1):48. Epub 2021 Jan 11.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Background: Immunosuppression including high-dose calcineurin inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with a risk of graft injury. Adaptation of CNI-based immunosuppression by monitoring of torque teno virus (TTV), a latent nonpathogenic DNA virus, measured in the whole blood in addition to conventional therapeutic drug monitoring may reduce the toxicity of immunosuppression with similar efficacy.

Methods/design: An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as an add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 to 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (arm 1: immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements of renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss, and infections.

Discussion: The results of this randomized controlled trial may reduce the toxicity of immunosuppression after lung transplantation while maintaining the efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.

Trial Registration: ClinicalTrials.gov NCT04198506 . Registered on 12 December 2019.
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http://dx.doi.org/10.1186/s13063-020-04985-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798016PMC
January 2021

Combined low-dose everolimus and low-dose tacrolimus after Alemtuzumab induction therapy: a randomized prospective trial in lung transplantation.

Trials 2021 Jan 4;22(1). Epub 2021 Jan 4.

Medizinische Universitat Wien, Vienna, Austria.

Background: Long-term outcomes of lung transplantation are severely affected by comorbidities and development of chronic rejection. Among the comorbidities, kidney insufficiency is one of the most frequent and it is mainly caused by the cumulative effect of calcineurin inhibitors (CNIs). Currently, the most used immunosuppression protocols worldwide include induction therapy and a triple-drug maintenance immunosuppression, with one calcineurin inhibitor, one anti-proliferative drug, and steroids. Our center has pioneered the use of alemtuzumab as induction therapy, showing promising results in terms of short- and long-term outcomes. The use of alemtuzumab followed by a low-dose double drug maintenance immunosuppression, in fact, led to better kidney function along with excellent results in terms of acute rejection, chronic lung allograft dysfunction, and survival (Benazzo et al., PLoS One 14(1):e0210443, 2019). The hypothesis driving the proposed clinical trial is that de novo introduction of low-dose everolimus early after transplantation could further improve kidney function via a further reduction of tacrolimus. Based on evidences from kidney transplantation, moreover, alemtuzumab induction therapy followed by a low-dose everolimus and low-dose tacrolimus may have a permissive action on regulatory immune cells thus stimulating allograft acceptance.

Methods: A randomized prospective clinical trial has been set up to answer the research hypothesis. One hundred ten patients will be randomized in two groups. Treatment group will receive the new maintenance immunosuppression protocol based on low-dose tacrolimus and low-dose everolimus and the control group will receive our standard immunosuppression protocol. Both groups will receive alemtuzumab induction therapy. The primary endpoint of the study is to analyze the effect of the new low-dose immunosuppression protocol on kidney function in terms of eGFR change. The study will have a duration of 24 months from the time of randomization. Immunomodulatory status of the patients will be assessed with flow cytometry and gene expression analysis.

Discussion: For the first time in the field of lung transplantation, this trial proposes the combined use of significantly reduced tacrolimus and everolimus after alemtuzumab induction. The new protocol may have a twofold advantage: (1) further reduction of nephrotoxic tacrolimus and (2) permissive influence on regulatory cells development with further reduction of rejection episodes.

Trial Registration: EUDRACT Nr 2018-001680-24. Registered on 15 May 2018.
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http://dx.doi.org/10.1186/s13063-020-04843-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783986PMC
January 2021

Update on Respiratory Fungal Infections in Cystic Fibrosis Lung Disease and after Lung Transplantation.

J Fungi (Basel) 2020 Dec 21;6(4). Epub 2020 Dec 21.

Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Associated National Center in the European Reference Network on Rare Respiratory Diseases ERN-LUNG and the European Reference Network on Transplantation in Children, ERN TRANSPLANT-CHILD, Medical University of Vienna, 1090 Vienna, Austria.

Cystic fibrosis is the most common autosomal-recessive metabolic disease in the Western world. Impaired trans-membrane chloride transport via the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes thickened body fluids. In the respiratory system, this leads to chronic suppurative cough and recurrent pulmonary infective exacerbations, resulting in progressive lung damage and respiratory failure. Whilst the impact of bacterial infections on CF lung disease has long been recognized, our understanding of pulmonary mycosis is less clear. The range and detection rates of fungal taxa isolated from CF airway samples are expanding, however, in the absence of consensus criteria and univocal treatment protocols for most respiratory fungal conditions, interpretation of laboratory reports and the decision to treat remain challenging. In this review, we give an overview on fungal airway infections in CF and CF-lung transplant recipients and focus on the most common fungal taxa detected in CF, , spp., , species, and , their clinical presentations, common treatments and prophylactic strategies, and clinical challenges from a physician's point of view.
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http://dx.doi.org/10.3390/jof6040381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766476PMC
December 2020

Commentary: Selection criteria for lung transplantation-is there room for individualization?

J Thorac Cardiovasc Surg 2020 Nov 9. Epub 2020 Nov 9.

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.10.119DOI Listing
November 2020

Donor ventilation parameters as predictors for length of mechanical ventilation after lung transplantation: Results of a prospective multicenter study.

J Heart Lung Transplant 2021 Jan 28;40(1):33-41. Epub 2020 Oct 28.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: The evaluation of donor lungs heavily depends on the subjective judgment of the retrieval surgeon. As a consequence, acceptance rates vary significantly among transplant centers. We aimed to determine donor ventilation parameters in a prospective study and test if they could be used as objective quality criteria during organ retrieval.

Methods: A prospective evaluation of lung donors was performed in 3 transplant centers. Ventilation parameters were collected at the time of retrieval using a standardized ventilation protocol. Recipient length of mechanical ventilation (LMV) was defined as the primary end point, and collected data was used to build linear models predicting LMV.

Results: In total, 166 donors were included in this study. Median LMV after transplantation was 32 hours (interquartile range: 20-63 hours). Peak inspiratory pressure and dynamic compliance (C) at the time of retrieval, but not the partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio, correlated with recipient LMV in Spearman correlations (r = 0.280, p = 0.002; r = -0.245, p = 0.003; and r = 0.064, p = 0.432, respectively). Linear models were built to further evaluate the impact of donor ventilation parameters on LMV. The first model was based on donor P/F ratio, donor age, donor intubation time, donor smoking history, donor partial pressure of carbon dioxide, aspiration, chest trauma, and pathologic chest X-ray. This model performed poorly (multiple R-squared = 0.063). In a second model, donor ventilation parameters were included, and C was identified as the strongest predictor for LMV. The third model was extended by recipient factors, which significantly improved the robustness of the model (multiple R-squared = 0.293).

Conclusion: In this prospective evaluation of donor lung parameters, currently used donor quality criteria poorly predicted recipient LMV. Our data suggest that C is a strong donor-bound parameter to predict short-term graft performance; however, recipient factors are similarly relevant.
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http://dx.doi.org/10.1016/j.healun.2020.10.008DOI Listing
January 2021

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

Am J Transplant 2020 Nov 19. Epub 2020 Nov 19.

Division of Thoracic Surgery, Medical University of Vienna, Wien, Austria.

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.
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http://dx.doi.org/10.1111/ajt.16402DOI Listing
November 2020

Ventilation parameters and early graft function in double lung transplantation.

J Heart Lung Transplant 2021 Jan 13;40(1):4-11. Epub 2020 Oct 13.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post-lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU).

Methods: A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (P), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest.

Results: In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16-47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27-50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5-78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27-86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (P, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679.

Conclusions: The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.
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http://dx.doi.org/10.1016/j.healun.2020.10.003DOI Listing
January 2021

[Masterplan 2025 of the Austrian Society of Pneumology (ASP)-the expected burden and management of respiratory diseases in Austria].

Wien Klin Wochenschr 2020 Sep;132(Suppl 3):89-113

Klinik für Lungenheilkunde, Kepler Universitätsklinikum, Linz, Österreich.

Scientific Members of the Austrian Society of Pneumology describe the expected development in respiratory health and provide guidance towards patient-oriented and cost-efficient respiratory care in Austria.Methods: In November 2017, respiratory care providers (physicians, nurses, physiotherapists) together with patient's advocacy groups and experts in health development, collaborated in workshops on: respiratory health and the environment, bronchial asthma and allergy, COPD, pediatric respiratory disease, respiratory infections, sleep disorders, interventional pneumology, thoracic oncology and orphan diseases.Results: Respiratory disease is extremely prevalent and driven by ill-health behavior, i.e. cigarette smoking, over-eating and physical inactivity. For the majority of respiratory diseases increased prevalence, but decreased hospitalizations are expected.The following measures should be implemented to deal with future challenges:1. Screening and case-finding should be implemented for lung cancer and COPD.2. E-health solutions (telemedicine, personal apps) should be used to facilitate patient management.3. Regional differences in respiratory care should be reduced through E‑health and harmonization of health insurance benefits across Austria.4. Patient education and awareness, to reduce respiratory health illiteracy should be increased, which is essential for sleep disorders but relevant also for other respiratory diseases.5. Respiratory care should be inter-professional, provided via disease-specific boards beyond lung cancer (for ILDs, sleep, allergy)6. Programs for outpatient's pulmonary rehabilitation can have a major impact on respiratory health.7. Increased understanding of molecular pathways will drive personalized medicine, targeted therapy (for asthma, lung cancer) and subsequently health care costs.
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http://dx.doi.org/10.1007/s00508-020-01722-wDOI Listing
September 2020

Molecular T-cell‒mediated rejection in transbronchial and mucosal lung transplant biopsies is associated with future risk of graft loss.

J Heart Lung Transplant 2020 12 26;39(12):1327-1337. Epub 2020 Aug 26.

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Background: We previously developed molecular assessment systems for lung transplant transbronchial biopsies (TBBs) with high surfactant and bronchial mucosal biopsies, identifying T-cell‒mediated rejection (TCMR) on the basis of the expression of rejection-associated transcripts, but the relationship of rejection to graft loss is unknown. This study aimed to develop molecular assessments for TBBs and mucosal biopsies and to establish the impact of molecular TCMR on graft survival.

Methods: We used microarrays and machine learning to assign TCMR scores to an expanded cohort of 457 TBBs (367 high surfactant plus 90 low surfactant) and 314 mucosal biopsies. We tested the score agreement between TBB-TBB, mucosal-mucosal, and TBB-mucosal biopsy pairs in the same patient. We also assessed the association of molecular TCMR scores with graft loss (death or retransplantation) and compared it with the prognostic associations for histology and donor-specific antibodies.

Results: The molecular TCMR scores assigned in all the TBBs performed similarly to those in high-surfactant TBBs, indicating that variation in alveolation in TBBs does not prevent the detection of TCMR. Mucosal biopsy pieces showed less piece-to-piece variation than TBBs. TCMR scores in TBBs agreed with those in mucosal biopsies. In both TBBs and mucosal biopsies, molecular TCMR was associated with graft loss, whereas histologic rejection and donor-specific antibodies were not.

Conclusions: Molecular TCMR can be detected in TBBs regardless of surfactant and in mucosal biopsies, which show less variability in the sampled tissue than TBBs. On the basis of these findings, molecular TCMR appears to be an important predictor of the risk of future graft failure.

Trial Registration: ClinicalTrials.gov NCT02812290.
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http://dx.doi.org/10.1016/j.healun.2020.08.013DOI Listing
December 2020

NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD.

Nat Metab 2020 06 8;2(6):532-546. Epub 2020 Jun 8.

Department of Surgery, Justus-Liebig University, Giessen, Germany.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the superoxide source and an essential driver of smoke-induced emphysema and pulmonary hypertension development in mice. NOXO1 is consistently upregulated in two models of lung emphysema, Cybb (also known as NADPH oxidase 2, Nox2)-knockout mice and wild-type mice with tobacco-smoke-induced emphysema, and in human COPD. Noxo1-knockout mice are protected against tobacco-smoke-induced pulmonary hypertension and emphysema. Quantification of superoxide, nitrotyrosine and multiple NOXO1-dependent signalling pathways confirm that peroxynitrite formation from nitric oxide and superoxide is a driver of lung emphysema. Our results suggest that NOXO1 may have potential as a therapeutic target in emphysema.
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http://dx.doi.org/10.1038/s42255-020-0215-8DOI Listing
June 2020

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

Am J Transplant 2021 01 4;21(1):410-414. Epub 2020 Aug 4.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1111/ajt.16180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818405PMC
January 2021

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

Transfus Med Hemother 2020 Jun 5;47(3):205-213. Epub 2020 May 5.

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1159/000508170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315205PMC
June 2020

Single running suture technique is associated with low rate of bronchial complications after lung transplantation.

J Thorac Cardiovasc Surg 2020 Oct 19;160(4):1099-1108.e3. Epub 2020 Feb 19.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Lung transplantation has evolved to a routinely performed surgical procedure in patients with end-stage pulmonary disease. Bronchial healing problems are rare but represent a potential life-threatening complication. Herein, we aimed to define the incidence, classification, and treatment of bronchial complications after lung transplantation.

Material And Methods: All patients receiving lung transplantation between January 1999 and December 2017 were included in this retrospective study. All bronchial anastomoses were performed in a standardized technique using a single, polydioxanone running suture. The rate of anastomotic complications requiring an intervention, type of complication according the 2018 International Society for Heart and Lung Transplantation classification, and the clinical management were retrospectively analyzed.

Results: A total of 2941 anastomoses were performed in 1555 patients. The overall incidence of relevant anastomotic complications was 1.56%, 0.68% for left anastomoses, and 2.44% for right anastomoses. In 6 patients, a surgical revision or retransplantation was performed, whereas endoscopic treatment alone was sufficient in 39 patients. One patient underwent right-sided retransplantation 6 months after the first lung transplantation after failed endoscopic treatment attempts. International Society for Heart and Lung Transplantation grade "S Lc Ec" was the most common type of anastomotic complication. The overall incidence decreased within the study period from 2.4% in the era 1999 to 2003 to 0.8% in the era 2014 to 2017. We found no significant difference in overall survival of patients with and without anastomotic complications (P = .995; hazard ratio, 0.99; 95% confidence interval, 0.63-1.58).

Conclusions: The single running suture technique is associated with a very low rate of true anastomotic complications. Close follow-up and early endoscopic treatment of patients with anastomotic complications result in excellent long-term outcomes.
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http://dx.doi.org/10.1016/j.jtcvs.2019.12.119DOI Listing
October 2020

Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9 May 2020) : Statement of the Austrian Society of Pneumology (ASP).

Wien Klin Wochenschr 2020 Jul;132(13-14):365-386

Division of Paediatric Pulmonology and Allergology, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria.

The coronavirus disease 2019 (COVID-19) pandemic is currently a challenge worldwide. In Austria, a crisis within the healthcare system has so far been prevented. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV‑2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic; however, COVID-19 specific adjustments are useful. The treatment of patients with chronic lung diseases has to be adapted during the pandemic but must still be guaranteed.
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http://dx.doi.org/10.1007/s00508-020-01691-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291190PMC
July 2020

Plasma Levels of the Bioactive Sphingolipid Metabolite S1P in Adult Cystic Fibrosis Patients: Potential Target for Immunonutrition?

Nutrients 2020 Mar 14;12(3). Epub 2020 Mar 14.

Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.

Recent research has linked sphingolipid (SL) metabolism with cystic fibrosis transmembrane conductance regulator (CFTR) activity, affecting bioactive lipid mediator sphingosine-1-phosphate (S1P). We hypothesize that loss of CFTR function in cystic fibrosis (CF) patients influenced plasma S1P levels. Total and unbound plasma S1P levels were measured in 20 lung-transplanted adult CF patients and 20 healthy controls by mass spectrometry and enzyme-linked immunosorbent assay (ELISA). S1P levels were correlated with CFTR genotype, routine laboratory parameters, lung function and pathogen colonization, and clinical symptoms. Compared to controls, CF patients showed lower unbound plasma S1P, whereas total S1P levels did not differ. A positive correlation of total and unbound S1P levels was found in healthy controls, but not in CF patients. Higher unbound S1P levels were measured in ΔF508-homozygous compared to ΔF508-heterozygous CF patients ( = 0.038), accompanied by higher levels of HDL in ΔF508-heterozygous patients. Gastrointestinal symptoms were more common in ΔF508 heterozygotes compared to ΔF508 homozygotes. This is the first clinical study linking plasma S1P levels with CFTR function and clinical presentation in adult CF patients. Given the emerging role of immunonutrition in CF, our study might pave the way for using S1P as a novel biomarker and nutritional target in CF.
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http://dx.doi.org/10.3390/nu12030765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146441PMC
March 2020

Human Cytomegalovirus (HCMV)-Specific Antibody Response and Development of Antibody-Dependent Cellular Cytotoxicity Against HCMV After Lung Transplantation.

J Infect Dis 2020 07;222(3):417-427

Center for Virology, Medical University of Vienna, Vienna, Austria.

Background: Human cytomegalovirus (HCMV) may cause severe infections in lung transplant recipients (LTRs). The impact of the host antibody (AB)-dependent cytotoxicity (ADCC) on HCMV is still unclear. Therefore, we analyzed the AB-response against HCMV glycoprotein B (gB) and the pentameric complex (PC) and the ADCC response in HCMV-seropositive (R+) LTRs and in seronegative recipients of positive organs (D+/R-).

Methods: Plasma samples were collected from 35 R+ and 28 D+/R- LTRs for 1 (R+) or 2 (D+/R-) years posttransplantation and from 114 healthy control persons. The PC- and gB-specific ABs were assessed by enzyme-linked immunosorbent assay. The ADCC was analyzed by focal expansion assay and CD107 cytotoxicity assay.

Results: In R+ LTRs, significantly higher gB-specific AB levels developed within 1 year posttransplantation than in controls (immunoglobulin [Ig]G1, P < .001; IgG3, P < .001). In addition, higher levels of ADCC were observed by FEA and CD107 assay in R+ patients compared with controls (P < .001). In 23 D+R- patients, HCMV-specific ABs developed. Antibody-dependent cytotoxicity became detectable 3 months posttransplantation in these, with higher ADCC observed in viremic patients. Depletion of gB- and PC-specific ABs revealed that, in particular, gB-specific Abs were associated with the ADCC response.

Conclusions: We show that a strong ADCC is elicited after transplantation and is especially based on gB-specific ABs.
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http://dx.doi.org/10.1093/infdis/jiaa097DOI Listing
July 2020

Chest CT in patients after lung transplantation: A retrospective analysis to evaluate impact on image quality and radiation dose using spectral filtration tin-filtered imaging.

PLoS One 2020 5;15(2):e0228376. Epub 2020 Feb 5.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Objectives: The purpose of this study was to investigate the impact of a 150kV spectral filtration chest imaging protocol (Sn150kVp) combined with advanced modeled iterative reconstruction (ADMIRE) on radiation dose and image quality in patients after lung-transplantation.

Methods: This study included 102 patients who had unenhanced chest-CT examinations available on both, a second-generation dual-source CT (DSCT) using standard protocol (100kVp, filtered-back-projection) and, on a third-generation DSCT using Sn150kVp protocol with ADMIRE. Signal-to-noise-ratio (SNR) was measured in 6 standardized regions. A 5-point Likert scale was used to evaluate subjective image quality. Radiation metrics were compared.

Results: The mean time interval between the two acquisitions was 1.1±0.7 years. Mean-volume-CT-dose-index, dose-length-product and effective dose were significantly lower for Sn150kVp protocol (2.1±0.5mGy;72.6±16.9mGy*cm;1.3±0.3mSv) compared to 100kVp protocol (6.2±1.8mGy;203.6±55.6mGy*cm;3.7±1.0mSv) (p<0.001), equaling a 65% dose reduction. All studies were considered of diagnostic quality. SNR measured in lung tissue, air inside trachea, vertebral body and air outside the body was significantly higher in 100kVp protocol compared to Sn150kVp protocol (12.5±2.7vs.9.6±1.5;17.4±3.6vs.11.8±1.8;0.7±0.3vs.0.4±0.2;25.2±6.9vs.14.9±3.3;p<0.001). SNR measured in muscle tissue was significantly higher in Sn150kVp protocol (3.2±0.9vs.2.6±1.0;p<0.001). For SNR measured in descending aorta there was a trend towards higher values for Sn150kVp protocol (2.8±0.6 vs. 2.7±0.9;p = 0.3). Overall SNR was significantly higher in 100kVp protocol (5.0±4.0vs.4.0±4.0;p<0.001). On subjective analysis both protocols achieved a median Likert rating of 1 (25th-75th-percentile:1-1;p = 0.122). Interobserver agreement was good (intraclass correlation coefficient = 0.73).

Conclusions: Combined use of 150kVp tin-filtered chest CT protocol with ADMIRE allows for significant dose reduction while maintaining highly diagnostic image quality in the follow up after lung transplantation when compared to a standard chest CT protocol using filtered back projection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228376PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001933PMC
April 2020

Low molecular weight heparin versus unfractioned heparin for anticoagulation during perioperative extracorporeal membrane oxygenation: A single center experience in 102 lung transplant patients.

Artif Organs 2020 Jun 18;44(6):638-646. Epub 2020 Feb 18.

Department of Anesthesiology, Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria.

Extracorporeal membrane oxygenation (ECMO) is gaining importance in the perioperative management of lung transplant patients. To date, the ideal substance for anticoagulation of ECMO patients is still a matter of debate. In this study, we describe our experience with the use of low molecular weight heparin (LMWH) in comparison with unfractioned heparin (UFH) in lung transplant patients undergoing perioperative ECMO support. We retrospectively analyzed data from all lung transplant patients who underwent perioperative ECMO support at our institution between 2013 and 2017. Bleeding events served as primary outcome parameter. Secondary outcome parameters consisted of thromboembolic events. 102 patients were included in this study, of which 22 (21.6%) received UFH for anticoagulation, and 80 (78.4%) received LMWH. There was no difference between the two groups in regard to serious bleeding events (22.7% in the UFH group vs 12.5% in the LMWH group, P = .31). However, the proportion of patients experiencing thromboembolic events was significantly higher in the UFH group than in the LMWH group (50% vs 20%, P = .01). After adjusting for baseline differences between the two groups, we still observed a difference with respect to thromboembolic events. These data remain to be validated in future prospective, randomized trials.
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http://dx.doi.org/10.1111/aor.13642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317732PMC
June 2020

Lung transplantation for pulmonary hypertension with giant pulmonary artery aneurysm.

J Thorac Cardiovasc Surg 2020 06 26;159(6):2543-2550. Epub 2019 Oct 26.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Aneurysm of the main pulmonary artery trunk (PAA) is a rare but severe complicating factor in patients suffering from pulmonary arterial hypertension (PAH). Many centers consider PAA an indication for a heart-lung transplantation. We aimed to summarize our institutional experience with a lung-only strategy in this complex group of patients.

Methods: We performed a retrospective single-center analysis of patients with PAH and a severe PAA who underwent lung transplantation between January 1996 and November 2018.

Results: A total of 127 patients with PAH underwent lung transplantation during the study period. Seven patients presented with severe PAA (mean diameter, 70.4 mm). Donor lungs were procured together with the main pulmonary artery (PA). In the recipient, cardiopulmonary bypass with bicaval cannulation was established, and bilateral pneumonectomy together with resection of the entire PA trunk was performed. The right donor lung was implanted, and the attached PA trunk was pulled through behind the superior vena cava and ascending aorta. Anastomosis was performed just above the level of the pulmonary valve. Thereafter, the left lung was implanted by reconnecting the left PA to the main PA trunk. All but 1 patient, who died from sepsis on postoperative day 13, were successfully discharged.

Conclusions: To the best of our knowledge, this is the largest published experience of patients with PAH and severe PAA who underwent lung transplantation. We show that these patients are eligible for double lung transplantation and do not require heart-lung transplantation.
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http://dx.doi.org/10.1016/j.jtcvs.2019.09.178DOI Listing
June 2020

Molecular phenotyping of rejection-related changes in mucosal biopsies from lung transplants.

Am J Transplant 2020 04 1;20(4):954-966. Epub 2019 Dec 1.

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Diagnosing lung transplant rejection currently depends on histologic assessment of transbronchial biopsies (TBB) with limited reproducibility and considerable risk of complications. Mucosal biopsies are safer but not histologically interpretable. Microarray-based diagnostic systems for TBBs and other transplants suggest such systems could assess mucosal biopsies as well. We studied 243 mucosal biopsies from the third bronchial bifurcation (3BMBs) collected from seven centers and classified them using unsupervised machine learning algorithms. Using the expression of a set of rejection-associated transcripts annotated in kidneys and validated in hearts and lung transplant TBBs, the algorithms identified and scored major rejection and injury-related phenotypes in 3BMBs without need for labeled training data. No rejection or injury, rejection, late inflammation, and recent injury phenotypes were thus scored in new 3BMBs. The rejection phenotype correlated with IFNG-inducible transcripts, the hallmarks of rejection. Progressive atrophy-related changes reflected by the late inflammation phenotype in 3BMBs suggest widespread time-dependent airway deterioration, which was especially pronounced after two years posttransplant. Thus molecular assessment of 3BMBs can detect rejection in a previously unusable biopsy format with potential utility in patients with severe lung dysfunction where TBB is not possible and provide unique insights into airway deterioration. ClinicalTrials.gov NCT02812290.
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http://dx.doi.org/10.1111/ajt.15685DOI Listing
April 2020

Maribavir for Preemptive Treatment of Cytomegalovirus Reactivation.

N Engl J Med 2019 09;381(12):1136-1147

From the Hematology Department, University Hospitals Leuven, KU Leuven, Leuven (J.M.), and the Section of Hematology, Cliniques Universitaires Saint-Luc, Brussels (X.P.) - both in Belgium; the Hematology Department, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) and University Paris-Est-Créteil, Créteil (C.C.), and AP-HP Hôpital Paul Brousse, Villejuif (F.S.) - all in France; the Medical University of Vienna, General Hospital, Vienna (P.J.); Shire, Wayne, PA (M.U., S.V.); Shire, Lexington, MA (J.W., A.W.); and the Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany (O.W.).

Background: Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known.

Methods: In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment.

Results: Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir.

Conclusions: Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).
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http://dx.doi.org/10.1056/NEJMoa1714656DOI Listing
September 2019

Risk factors for early bleeding complications after lung transplantation - a retrospective cohort study.

Transpl Int 2019 Dec 30;32(12):1313-1321. Epub 2019 Aug 30.

Division of Cardiac Thoracic Vascular Anesthesia and Intensive Care Medicine, Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Wien, Austria.

Risk factors for early bleeding complications after lung transplantation are not well described. Our aim was to evaluate coagulation test results and the use of extracorporeal membrane oxygenation as risk factors for bleeding after lung transplantation. We analyzed a single-center cohort of bilateral lung transplants between January 2009 and August 2015. Predictors of severe postoperative bleeding (bleeding requiring reoperation within 48 h of transplantation) were assessed using multivariable logistic regression. The effect of bleeding on survival was assessed using a Cox proportional-hazards model. Twenty-nine (4.5%) of 641 patients experienced severe postoperative bleeding. Postoperative fibrinogen levels (OR = 0.99, 95% CI 0.98-0.995, P = 0.001; per mg/dl increase) and pre- and postoperative use of extracorporeal membrane oxygenation (OR = 14.41% 95% CI 5.4-40.19, P < 0.001 and OR = 4.25, 95% CI 1.0-11.09, P = 0.002, respectively) were associated with an increased risk of severe postoperative bleeding. Severe postoperative bleeding was associated with decreased survival within 60 days after transplantation (adjusted HR = 5.73, 95% CI 2.52-13.02, P < 0.001). Low postoperative fibrinogen levels, and pre- and postoperative use of extracorporeal membrane oxygenation were risk factors for bleeding after lung transplantation.
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http://dx.doi.org/10.1111/tri.13491DOI Listing
December 2019

Interobserver variability impairs radiologic grading of primary graft dysfunction after lung transplantation.

J Thorac Cardiovasc Surg 2019 09 11;158(3):955-962.e1. Epub 2019 May 11.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Objectives: The current score for primary graft dysfunction after lung transplantation relies heavily on chest radiographs, and radiologic judgment can make the difference between the lowest (primary graft dysfunction 0) and the highest (primary graft dysfunction 3) grade. This study aimed to evaluate interobserver variability of the scoring of postoperative chest radiographs and its impact on primary graft dysfunction grades in a large single-center cohort.

Methods: We retrospectively analyzed 497 lung transplantations performed between January 2010 and July 2016 at the Medical University of Vienna. Five trained thoracic radiologists were asked to independently examine postoperative chest radiographs performed at 0 to 6 hours, 24 hours, 48 hours, and 72 hours after arrival at the intensive care unit. Interobserver variability was calculated using Fleiss' kappa (κ) statistics.

Results: A total of 1988 chest radiographs were evaluated. Consensus among all 5 radiologists was found in only 826 cases (43.0%). At 0 to 6 hours and 24 hours, only a moderate agreement was found among the 5 radiologists (κ = 0.456 and 0.456, respectively), and agreement was even worse at 48 and 72 hours (κ = 0.405 and κ = 0.409). On the basis of this high interobserver variability, best and worst case scenarios were calculated leading to primary graft dysfunction 3 rates of 8.4% versus 28.4% at 0 to 6 hours, 1.8% versus 4.8% at 24 hours, 2.0% versus 5.3% at 48 hours, and 0.2% versus 3.1% at 72 hours. A high recipient body mass index and size-reduced transplants were found to be factors associated with higher rates of interobserver variability.

Conclusions: The substantial interobserver variability found in this retrospective analysis underlines the difficulty to adequately grade post-transplant organ function. Future revisions of the primary graft dysfunction grading should take this problem into consideration.
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http://dx.doi.org/10.1016/j.jtcvs.2019.02.134DOI Listing
September 2019