Publications by authors named "Walter Klepetko"

387 Publications

Thymomectomy plus total thymectomy versus simple thymomectomy for early-stage thymoma without myasthenia gravis: a European Society of Thoracic Surgeons Thymic Working Group Study.

Eur J Cardiothorac Surg 2021 May 23. Epub 2021 May 23.

Department of Thoracic Surgery, Zurich University Hospital, Zurich, Switzerland.

Objectives: Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short- and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database.

Methods: A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT).

Results: TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group.

Conclusion: Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate.
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http://dx.doi.org/10.1093/ejcts/ezab224DOI Listing
May 2021

Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study.

Transl Lung Cancer Res 2021 Apr;10(4):1594-1607

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM).

Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome.

Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [≥1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS.

Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.
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http://dx.doi.org/10.21037/tlcr-20-1114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107750PMC
April 2021

Dysbalance of ACE2 levels - a possible cause for severe COVID-19 outcome in COPD.

J Pathol Clin Res 2021 May 12. Epub 2021 May 12.

Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to healthcare systems worldwide. Binding of the virus to angiotensin-converting enzyme 2 (ACE2) is an important step in the infection mechanism. However, it is unknown if ACE2 expression in patients with chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary arterial hypertension (IPAH), or pulmonary fibrosis (PF), is changed as compared to controls. We used lung samples from patients with COPD (n = 28), IPAH (n = 10), and PF (n = 10) as well as healthy control donor (n = 10) tissue samples to investigate the expression of ACE2 and related cofactors that might influence the course of SARS-CoV-2 infection. Expression levels of the ACE2 receptor, the putative receptor CD147/BSG, and the viral entry cofactors TMPRSS2 (transmembrane serine protease 2), EZR, and FURIN were determined by quantitative PCR and in open-access RNA sequencing datasets. Immunohistochemical and single-cell RNA sequencing (scRNAseq) analyses were used for localization and coexpression, respectively. Soluble ACE2 (sACE2) plasma levels were analyzed by enzyme-linked immunosorbent assay. In COPD as compared to donor, IPAH, and PF lung tissue, gene expression of ACE2, TMPRSS2, and EZR was significantly elevated, but circulating sACE2 levels were significantly reduced in COPD and PF plasma compared to healthy control and IPAH plasma samples. Lung tissue expressions of FURIN and CD147/BSG were downregulated in COPD. None of these changes were associated with changes in pulmonary hemodynamics. Histological analysis revealed coexpression of ACE2, TMPRSS2, and Ezrin in bronchial regions and epithelial cells. This was confirmed by scRNAseq analysis. There were no significant expression changes of the analyzed molecules in the lung tissue of IPAH and idiopathic PF as compared to control. In conclusion, we reveal increased ACE2 and TMPRSS2 expression in lung tissue with a concomitant decrease of protective sACE2 in COPD patients. These changes represent the possible risk factors for an increased susceptibility of COPD patients to SARS-CoV-2 infection.
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http://dx.doi.org/10.1002/cjp2.224DOI Listing
May 2021

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

Ann Thorac Surg 2021 May 5. Epub 2021 May 5.

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

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 end point; secondary end points 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 1,157 patients were identified. These studies were uniformly retrospective reports. Pooled estimates for 3- 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- and 5-year OS were 47.6% [95% CI 36.1-59.4] and 33.8% (95% CI 26.8-41.5). 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).

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.
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.063DOI Listing
May 2021

Lung Cancer in Austria.

J Thorac Oncol 2021 05;16(5):725-733

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

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http://dx.doi.org/10.1016/j.jtho.2020.10.158DOI Listing
May 2021

Transient perioperative inflammation following lung transplantation and major thoracic surgery with elective extracorporeal support: a prospective observational study.

Ann Transl Med 2021 Mar;9(5):385

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

Background: The clinical relevance of inflammation induced by elective perioperative extracorporeal membrane oxygenation (ECMO) usage as an integral part of modern lung transplantation (LUTX) remains elusive. The aim of this study was to determine the perioperative cytokine response accompanying major thoracic surgery employing different extracorporeal devices comprising ECMO, cardiopulmonary bypass (CPB), or no extracorporeal circulation in relation to inflammation, clinically tangible as increased sequential organ failure assessment (SOFA) score, called SOFA.

Methods: In this prospective, observational pilot study 42 consecutive patients with end-stage pulmonary disease undergoing LUTX; 15 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy and 15 patients with lung cancer undergoing major lung resections were analysed. Cytokine serum concentrations and SOFA were determined before, at end of surgery and in the following postoperative days.

Results: LUTX on ECMO and pulmonary endarterectomy (PEA) on CPB triggered an immediate increase in cytokine serum concentrations at end of surgery: IL-6: 66-fold and 71-fold, IL-10: 3-fold and 2.5-fold, ST2/IL-33R: 5-fold and 4-fold and SOFA: 10.5±2.8 and 10.7±1.7, that decreased sharply to baseline levels from postoperative day 1-5. Despite low perioperative mortality (3 patients, 4.1%) extremely high SOFA ≥13 was associated with mortality after LUTX. Delta-SOFA distinguished survivors from non-survivors: -4.5±3.2 . -0.3±1.5 (P=0.001). Increased IL-6 serum concentrations were predictive for increased SOFA (sensitivity: 97%, specificity: 80%). Peak cytokine serum concentrations correlated with ECC duration, maximal lactate, transfusion of red-blood-cells, fresh-frozen-plasma, and catecholamine support.

Conclusions: LUTX and PEA on extracorporeal circulation with an excellent outcome triggered an immediate rise and concomitant fall of inflammation as observed in cytokine serum concentrations and SOFA. High absolute SOFA in the presence of an uncomplicated postoperative course may pertain to specific management strategies rather than organ failure.
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http://dx.doi.org/10.21037/atm-20-4771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033292PMC
March 2021

Procedural mechanical support for lung transplantation.

Curr Opin Organ Transplant 2021 Jun;26(3):309-313

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

Purpose Of Review: The use of procedural mechanical support during lung transplantation (LTx) varies between centers and the optimal support strategy is still controversially discussed. The two main questions are if cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) should be preferred and whether mechanical support should be reserved for specific patient groups or a routine use can be recommended.

Recent Findings: Recent cohort studies have consistently shown that LTx on CPB leads to inferior outcomes when compared to venoarterial (va)-ECMO. Thus, ECMO should be preferred in lung transplantation except for special indications. Despite its higher invasiveness, ECMO offers some pivotal advantages over off-pump lung transplantation. It has been shown to remarkably reduce rates of primary graft dysfunction, supporting the concept of a routine intraoperative ECMO use in LTx.

Summary: Although randomized-controlled trials addressing this question are still lacking, current evidence appears to favor the routine use of ECMO support during lung transplantation.
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http://dx.doi.org/10.1097/MOT.0000000000000873DOI Listing
June 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

Molecular profiles of small cell lung cancer subtypes: therapeutic implications.

Mol Ther Oncolytics 2021 Mar 6;20:470-483. Epub 2021 Feb 6.

Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.

Small cell lung cancer (SCLC; accounting for approximately 13%-15% of all lung cancers) is an exceptionally lethal malignancy characterized by rapid doubling time and high propensity to metastasize. In contrast to the increasingly personalized therapies in other types of lung cancer, SCLC is still regarded as a homogeneous disease and the prognosis of SCLC patients remains poor. Recently, however, substantial progress has been made in our understanding of SCLC biology. Advances in genomics and development of new preclinical models have facilitated insights into the intratumoral heterogeneity and specific genetic alterations of this disease. This worldwide resurgence of studies on SCLC has ultimately led to the development of novel subtype-specific classifications primarily based on the neuroendocrine features and distinct molecular profiles of SCLC. Importantly, these biologically distinct subtypes might define unique therapeutic vulnerabilities. Herein, we summarize the current knowledge on the molecular profiles of SCLC subtypes with a focus on their potential clinical implications.
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http://dx.doi.org/10.1016/j.omto.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917449PMC
March 2021

Laryngotracheal resection can be performed safely without a guardian Chin stitch-a single-centre experience including 165 consecutive patients.

Eur J Cardiothorac Surg 2021 Mar 10. Epub 2021 Mar 10.

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

Objectives: A tension-free anastomosis is crucial to minimize the risk of airway complications after laryngotracheal surgery. The 'guardian' chin stitch is placed to prevent hyperextension of the neck in the early postoperative period. This manoeuvre was introduced early in tracheal surgery and is now routinely performed by many airway surgeons. However, the evidence for or against is sparse.

Methods: We performed a retrospective analysis of all adult patients receiving a (laryngo-)tracheal resection at our department from October 2011 to December 2019. According to our institutional standard, none of the patients received a chin stitch. Instead, a head cradle was used to obtain anteflexion of the neck during the first 3 days and patients were instructed to avoid hyperextension of the neck during the hospital stay. The postoperative outcome and the rate of anastomotic complications were analysed.

Results: A total of 165 consecutive patients were included in this study. Median age at surgery was 53 years (18-80). Seventy-four patients received a tracheal resection, 24 a cricotracheal resection, 52 an extended cricotracheal resection including dorsal mucosectomy and 15 a single-stage laryngotracheal reconstruction. The median resection length was 25 mm (range 10-55 mm). One hundred and sixty-two out of 165 (98.2%) patients had an unremarkable postoperative course. One patient (0.6%) had partial anastomotic rupture after a traumatic reintubation, which required revision surgery and re-anastomosis. Two patients (1.2%) after previous radiation therapy (>60 Gy) developed a partial necrosis of the anastomosis, resulting in prolonged airleak and fistulation. At follow-up, bronchoscopy 3 months after surgery, 92.7% (127/137) of the patients had a proper anastomosis, 6.6% (9/137) had minor granuloma formations at the site of the anastomosis, which were all treated successfully by endoscopic removal. One patient received dilatation for restenosis (0.7%).

Conclusions: After sufficient mobilization of the central airways, postoperative anteflexion of the neck supported by a head cradle is sufficient to prevent excessive anastomotic tension and dehiscence. Considering the risk for severe neurological complications associated with the chin stitch, the routine use of this manoeuvre in laryngotracheal surgery should not be recommended.
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http://dx.doi.org/10.1093/ejcts/ezab092DOI Listing
March 2021

Functional outcome after single-stage laryngotracheal reconstruction with rib cartilage grafting.

J Thorac Cardiovasc Surg 2020 Dec 11. Epub 2020 Dec 11.

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

Objective: Single-stage laryngotracheal reconstruction (SSLTR) provides a definite surgical treatment for patients with complex glotto-subglottic stenosis. To date, the influence of SSLTR on the functional outcome after surgery has not been analyzed.

Methods: A retrospective analysis of all patients receiving a SSLTR between November 2012 and October 2019 was performed. Preoperatively and 3 months postoperatively, patients received a full functional evaluation, including spirometry; voice measurements (eg, fundamental frequency; dynamic range, singing voice range, and perceptual voice evaluation using the Roughness-Breathiness-Hoarseness [RBH] score, and fiberoptic endoscopic evaluation of swallowing [FEES]).

Results: A total of 15 patients with a mean age of 45 ± 17 years underwent SSTLR. Two (13%) patients were men and 13 (87%) were women. The majority of patients (67%) had undergone previous surgical or endoscopic treatment attempts that had failed. At the 3-month follow-up visit, none of the patients had signs of penetration or aspiration in their swallowing examination. Voice measurements revealed a significantly lower fundamental voice frequency (201.0 Hz vs 155.5 Hz; P = .006), whereas voice range (19.1 semitones vs 14.9 semitones; P = .200) and dynamic range (52.5 dB vs 53.0 dB; P = .777) was hardly affected. The median RBH score changed from R1 B0 H1 to R2 B1 H2. In spirometry, breathing capacity increased significantly (peak expiratory flow, 44% vs 87% [P < .001] and mean expiratory flow at 75% of vital capacity, 48% vs 90% [P < .001]). During a median follow-up of 32.5 months (range, 7-88 months), none of the patients developed re-stenosis.

Conclusions: For complex glotto-subglottic stenoses, durable long-term airway patency together with reasonable voice quality and normal deglutition can be achieved by SSLTR.
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http://dx.doi.org/10.1016/j.jtcvs.2020.11.155DOI Listing
December 2020

Fractional heat shock protein 27 urine excretion as a short-term predictor in acute exacerbation of chronic obstructive pulmonary disease.

Ann Transl Med 2021 Jan;9(2):117

Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Austria.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown.

Methods: In this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data.

Results: HSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival.

Conclusions: Our findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality.
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http://dx.doi.org/10.21037/atm-20-3683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867877PMC
January 2021

Neutrophil extracellular traps promote fibrous vascular occlusions in chronic thrombosis.

Blood 2021 Feb;137(8):1104-1116

Division of Cardiology, Department of Internal Medicine II, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.

Acute pulmonary embolism generally resolves within 6 months. However, if the thrombus is infected, venous thrombi transform into fibrotic vascular obstructions leading to chronic deep vein thrombosis and/or chronic thromboembolic pulmonary hypertension (CTEPH), but precise mechanisms remain unclear. Neutrophils are crucial in sequestering pathogens; therefore, we investigated the role of neutrophil extracellular traps (NETs) in chronic thrombosis. Because chronic pulmonary thrombotic obstructions are biologically identical to chronic deep venous thrombi, the murine inferior vena cava ligation model was used to study the transformation of acute to chronic thrombus. Mice with staphylococcal infection presented with larger thrombi containing more neutrophils and NETs but less resolution. Targeting NETs with DNase1 diminished fibrosis and promoted thrombus resolution. For translational studies in humans, we focused on patients with CTEPH, a severe type of deep venous and pulmonary artery fibrotic obstruction after thrombosis. Neutrophils, markers of neutrophil activation, and NET formation were increased in CTEPH patients. NETs promoted the differentiation of monocytes to activated fibroblasts with the same cellular phenotype as fibroblasts from CTEPH vascular occlusions. RNA sequencing of fibroblasts isolated from thrombo-endarterectomy specimens and pulmonary artery biopsies revealed transforming growth factor-β (TGF-β) as the central regulator, a phenotype which was replicated in mice with fibroblast-specific TGF-β overactivity. Our findings uncover a role of neutrophil-mediated inflammation to enhance TGF-β signaling, which leads to fibrotic thrombus remodeling. Targeting thrombus NETs with DNases may serve as a new therapeutic concept to treat thrombosis and prevent its sequelae.
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http://dx.doi.org/10.1182/blood.2020005861DOI Listing
February 2021

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

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

J Heart Lung Transplant 2021 01 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 2021 Jun 13;21(6):2132-2144. Epub 2020 Dec 13.

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
June 2021

Ventilation parameters and early graft function in double lung transplantation.

J Heart Lung Transplant 2021 01 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

Prostaglandin D strengthens human endothelial barrier by activation of E-type receptor 4.

Biochem Pharmacol 2020 12 8;182:114277. Epub 2020 Oct 8.

Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Graz, Austria; BioTechMed, Graz, Austria. Electronic address:

Life-threatening inflammatory conditions such as acute respiratory distress syndrome or sepsis often go hand in hand with severe vascular leakage. During inflammation, endothelial cell integrity and intact barrier function are crucial to limit leukocyte and plasma extravasation. Prostaglandin D (PGD) is a potent inflammatory lipid mediator with vasoactive properties. Previous studies suggest that PGD is involved in the regulation of endothelial barrier function; however, it is unclear whether this is also true for primary human pulmonary microvascular endothelial cells. Furthermore, as PGD is a highly promiscuous ligand, we set out to determine which receptors are important in human pulmonary endothelial cells. In the current study, we found that PGD and the DP1 agonist BW245c potently strengthened pulmonary and dermal microvascular endothelial cell barrier function and protected against thrombin-induced barrier disruption. Yet surprisingly, these effects were mediated only to a negligible extent via DP1 receptor activation. In contrast, we observed that the EP4 receptor was most important and mediated the barrier enhancement by PGD and BW245c. Stimulation with PGE or PGD reduced AKT phosphorylation which could be reversed by prior blockade of EP4 receptors. These data demonstrate a novel mechanism by which PGD may modulate inflammation and emphasizes the role of EP4 receptors in human endothelial cell function.
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http://dx.doi.org/10.1016/j.bcp.2020.114277DOI Listing
December 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

Heat shock protein 90α in thymic epithelial tumors and non-thymomatous myasthenia gravis.

Oncoimmunology 2020 05 13;9(1):1756130. Epub 2020 May 13.

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

Background: Thymic epithelial tumors (TETs) are rare malignancies with unique association to the autoimmune disease myasthenia gravis (MG). Heat shock proteins (HSPs) harbor great potential as cancer biomarkers and HSP inhibitors approach clinical cancer therapy.

Methods: To explore HSP pathophysiology, we assessed sera (immunoassays) and tissues (immunohistochemistry) of TETs (and thymic tissues) for HSP27, phosphorylated (p)HSP27, HSP70 and HSP90α expression in 114 TETs and 26 non-thymomatous MG patients undergoing extended thymectomy.

Results: Serum concentrations of HSP90α were significantly increased in patients with thymic carcinomas, thymomas, thymic neuroendocrine tumors and non-thymomatous MG compared to patients who underwent thymectomy revealing regular thymic morphology or controls. In thymoma patients, high serum HSP90α represented a significantly worse prognostic factor for free-from-recurrence, and complete tumor resection led to decreased levels. The expression of HSP90 in nuclei and cytoplasm of tumor cells and non-neoplastic lymphocytes varied with WHO histological subtype. HSP90 was expressed in centroblasts of thymic germinal centers in MG patients. Higher pHSP27 serum concentrations were observed in seropositive MG and those not treated with steroids.

Conclusions: HSP data suggest high potential for HSPs as TET cancer biomarkers or as candidates for targeted therapy. Caution is warranted in TET patients with associated MG overexpressing HSPs.
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http://dx.doi.org/10.1080/2162402X.2020.1756130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458630PMC
May 2020

Endothelial Dysfunction Following Enhanced TMEM16A Activity in Human Pulmonary Arteries.

Cells 2020 08 28;9(9). Epub 2020 Aug 28.

Ludwig Boltzmann Institute for Lung Vascular Research, Neue Stiftingtalstraße 6, 8010 Graz, Austria.

Endothelial dysfunction is one of the hallmarks of different vascular diseases, including pulmonary arterial hypertension (PAH). Ion channelome changes have long been connected to vascular remodeling in PAH, yet only recently has the focus shifted towards Ca-activated Cl channels (CaCC). The most prominent member of the CaCC TMEM16A has been shown to contribute to the pathogenesis of idiopathic PAH (IPAH) in pulmonary arterial smooth muscle cells, however its role in the homeostasis of healthy human pulmonary arterial endothelial cells (PAECs) and in the development of endothelial dysfunction remains underrepresented. Here we report enhanced TMEM16A activity in IPAH PAECs by whole-cell patch-clamp recordings. Using adenoviral-mediated TMEM16A increase in healthy primary human PAECs in vitro and in human pulmonary arteries ex vivo, we demonstrate the functional consequences of the augmented TMEM16A activity: alterations of Ca dynamics and eNOS activity as well as decreased NO production, PAECs proliferation, wound healing, tube formation and acetylcholine-mediated relaxation of human pulmonary arteries. We propose that the ERK1/2 pathway is specifically affected by elevated TMEM16A activity, leading to these pathological changes. With this work we introduce increased TMEM16A activity in the cell membrane of human PAECs for the development of endothelial dysfunction in PAH.
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http://dx.doi.org/10.3390/cells9091984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563136PMC
August 2020

Platinum Drug Sensitivity Polymorphisms in Stage III Non-small Cell Lung Cancer With Invasion of Mediastinal Lymph Nodes.

Cancer Genomics Proteomics 2020 Sep-Oct;17(5):587-595

Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania

Background/aim: Patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) with no progression after induction chemotherapy are usually selected for surgery. Nowadays, response to chemotherapy is not predictable. We aimed to identify genomic predictive markers for response to induction chemotherapy in stage IIIA (N2) NSCLC patients.

Patients And Methods: Whole-exome sequencing (WES) was performed on samples from 11 patients with no response after induction chemotherapy and 6 patients with documented pathological response, admitted to the Hotel Dieu Hospital, Paris or Allegemeines Krakenhaus University, Vienna.

Results: A higher alternative allele frequency was found on SENP5, rs63736860, rs1602 and NCBP2, rs553783 in the non-responder group, and on RGP1, rs1570248, SLFN12L, rs2304968, rs9905892, and GBA2, rs3833700 in the responder group.

Conclusion: These polymorphisms contribute to inter-individual sensibility to chemotherapy response. Interrogation of these genetic variations may have potential applicability when deciding the treatment strategy for patients with stage III NSCLC (N2).
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http://dx.doi.org/10.21873/cgp.20215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472447PMC
May 2021

[Recommendations for Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Patients].

Wien Klin Mag 2020 Jun 10:1-6. Epub 2020 Jun 10.

Universitätsklinik für Innere Medizin I, Allgemeines Krankenhaus der Stadt Wien, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Wien, Österreich.

The pandemic from the SARS-CoV‑2 Virus is currently challenging health care systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe work environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develops respiratory or circulatory failure that is refractory to conventional therapies, it is of utmost importance to clearly define criteria for the use of ECMOs in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.
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http://dx.doi.org/10.1007/s00740-020-00349-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286215PMC
June 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

TWIST1 Drives Smooth Muscle Cell Proliferation in Pulmonary Hypertension via Loss of GATA-6 and BMPR2.

Am J Respir Crit Care Med 2020 11;202(9):1283-1296

Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany; and.

The bHLH (basic helix-loop-helix) transcription factor TWIST1 (Twist-related protein 1) controls cell proliferation and differentiation in tissue development and disease processes. Recently, endothelial TWIST1 has been linked to pulmonary hypertension (PH) and endothelial-to-mesenchymal transition, yet the role of TWIST1 in smooth muscle cells (SMCs) remains so far unclear. To define the role of TWIST1 in SMCs in the pathogenesis of PH. SMC-specific TWIST1-deficient mice, SMC-specific TWIST1 silencing in rats, mass spectrometry, immunoprecipitation, and chromatin immunoprecipitation were used to delineate the role of SMC TWIST1 in PH. In pulmonary vessels from patients with PH and rodent PH models, TWIST1 expression was markedly increased and predominantly localized to SMCs. SMC-specific TWIST1 deficiency or silencing attenuated the development of PH and distal vessel muscularization in chronically hypoxic mice and in monocrotaline-treated rats. , TWIST1 inhibition or silencing prevented pulmonary artery SMC proliferation and migration. Mechanistically, the observed effects were mediated, at least in part, by TWIST1-dependent degradation of GATA-6 (GATA-binding protein 6). BMPR2 (bone morphogenetic protein receptor-2) was identified as a novel downstream target of GATA-6, which directly binds to its promoter. Inhibition of TWIST1 promoted the recruitment of GATA-6 to the promoter and restored BMPR2 functional expression. Our findings identify a key role for SMC TWIST1 in the pathogenesis of lung vascular remodeling and in PH that is partially mediated via reduced GATA-6-dependent expression. Inhibition of SMC TWIST1 may constitute a new therapeutic strategy for the treatment of PH.
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http://dx.doi.org/10.1164/rccm.201909-1884OCDOI Listing
November 2020

Recommendations for extracorporeal membrane oxygenation (ECMO) in COVID-19 patients : Consensus paper of the Medical University of Vienna.

Wien Klin Wochenschr 2020 Nov 3;132(21-22):671-676. Epub 2020 Jul 3.

University Department of Medicine I, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

The pandemic from the SARS-CoV‑2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.
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http://dx.doi.org/10.1007/s00508-020-01708-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332739PMC
November 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