Local and systemic RAGE axis changes in pulmonary hypertension: CTEPH and iPAH.

Objective: The molecular determinants of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH) remain poorly understood. The receptor for advanced glycation endproducts (RAGE) and its ligands: HMGB1 and S100A9 are involved in inflammatory disorders. We sought to investigate the role of the RAGE axis in patients with CTEPH undergoing pulmonary endarterectomy (PEA), iPAH undergoing lung transplantation (LuTX).

Awake extracorporeal membrane oxygenation bridging for pulmonary retransplantation provides comparable results to elective retransplantation.

Background: Lung retransplantation became an accepted treatment for bronchiolitis obliterans syndrome (BOS). However, the value of different bridging modalities for these patients is controversial.

Methods: We analyzed outcomes of 39 patients listed for retransplantation between 2008 and 2012.

Lung transplantation in an intensive care patient with pulmonary alveolar microlithiasis - a case report.

Introduction: Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease characterized by the deposition of phosphate and calcium in the alveoli. The disease progresses asymptomatically until later stages. When it becomes symptomatic, lung transplantations performed before the onset of right heart failure may improve life expectancy and quality.

High CXCL-16 levels correlate with symptomatic disease in lung transplant recipients with human cytomegalovirus replication in the allograft.

Human cytomegalovirus (HCMV) is an important pathogen in lung transplant recipients (LTRs). In LTRs, HCMV may replicate in the transplanted lung, and this is indicated by HCMV DNA detection in the bronchoalveolar lavage fluid (BALF). Local replication may occur without causing clinical symptoms or, in some patients, it may lead to symptomatic HCMV disease.

Extrapleural pneumonectomy after induction chemotherapy: perioperative outcome in 251 mesothelioma patients from three high-volume institutions.

Background: Several publications have suggested that induction chemotherapy followed by extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma (MPM) patients is associated with exceedingly high morbidity and mortality, and the role of EPP is controversially debated. The present retrospective study analyzed the perioperative outcome in 251 consecutively treated patients at three high-volume mesothelioma centers.

Methods: 251 MPM patients completed EPP after platinum-based induction chemotherapy at three institutions for thoracic surgery over more than 10 years.

[Chronic thromboembolic pulmonary hypertension--a position paper].

This position paper summarises current developments in chronic thromboembolic pulmonary hypertension (CTEPH) including diagnostic approaches and treatment options. Based on the guidelines of the task force of CTEPH experts at the 5th World Symposium on Pulmonary Hypertension in Nice 2013. Open questions arising during the treatment of patients with CTEPH are addressed.

Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation.

Background: Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS.

Methods: This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C2) levels, and corticosteroids.

Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study.

Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil.

Antimicrobial peptides are highly abundant and active in postoperative pleural drainage fluids.

Background: The human lung is considered a nonsterile organ, and surgical interventions therefore take place in a more or less contaminated operating field. Nevertheless, infectious complications of the pleural cavity are low after major lung resections. Antimicrobial peptides (AMPs) are part of the innate immunity and display a broad capacity to kill pathogens.

Comprehensive analysis of inflammatory markers in chronic thromboembolic pulmonary hypertension patients.

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with chronic inflammation but the pathological mechanisms are largely unknown. Our study aimed to simultaneously profile a broad range of cytokines in the supernatant of pulmonary endarterectomy (PEA) surgical material, as well as prospectively in patients with CTEPH to investigate whether circulating cytokines are associated with haemodynamic and physical characteristics of CTEPH patients. Herein, we show that PEA specimens revealed a significant upregulation of interleukin (IL)-6, monocyte chemoattractant protein-1, interferon-γ-induced protein-10 (IP)-10, macrophage inflammatory protein (MIP)1α and RANTES compared to lung tissue from healthy controls.

Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.

Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function.

Endothelin-1 driven proliferation of pulmonary arterial smooth muscle cells is c-fos dependent.

Pulmonary hypertension (PH) is characterized by enhanced pulmonary artery smooth muscle cell (PASMC) proliferation leading to vascular remodeling. Although, multiple factors have been associated with pathogenesis of PH the underlying mechanisms are not fully understood. Here, we hypothesize that already very short exposure to hypoxia may activate molecular cascades leading to vascular remodeling.

Pulmonary metastasectomy for soft tissue sarcoma--report from a dual institution experience at the Medical University of Vienna.

Background: Pulmonary metastasectomy when possible has become therapeutic standard in soft tissue sarcoma patients. However, published reports frequently describe mixed series of patients with bone or soft tissue sarcoma. We report the outcome of 46 soft tissue sarcoma (STS) patients who underwent pulmonary metastasectomy (PM).

Apelin promotes lymphangiogenesis and lymph node metastasis.

Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs in vitro, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their in vitro capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels in vivo in the matrigel plug assay.

Extended cervico-thoracic metastasectomy for testicular non-seminomatous germ cell tumour masses through an inverse T and combined collar incision.

Non-seminomatous germ cell tumours (NSGCT) are the most common malignancy from testicular origin in young males. They are characterized by early formation of metastases along retroperitoneal and subsequent mediastinal lymph node stations. Following cisplatin-based induction chemotherapy, residual tumour masses should be removed surgically, although this implies the need for extended procedures.

Distinct differences in gene expression patterns in pulmonary arteries of patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis with pulmonary hypertension.

Rationale: The development of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) is associated with increased morbidity.

Objectives: To elucidate whether vascular remodeling in a well-characterized PH-COPD and PH-IPF patient cohort results from similar or divergent molecular changes.

Methods: Vascular remodeling of donor, PH-COPD, and PH-IPF pulmonary arteries was assessed.

Lobar lung transplantation--is it comparable with standard lung transplantation?

Lobar lung transplantation is used mainly for urgent small recipients who are less likely to obtain size matched lungs in due time. Only limited numbers have been published, and we herewith report the largest series of lobar-LuTX. We analyzed our LuTX database from 1/2001 to 12/2012 and compared the outcome of lobar-LuTX recipients with those receiving standard LuTX.

NPY/Y₁ receptor-mediated vasoconstrictory and proliferative effects in pulmonary hypertension.

Background And Purpose: Pulmonary arteries (PAs) are innervated, but little is known about the role of neuronal axis in pulmonary hypertension (PH). Here, we have examined the role of the neuropeptide Y (NPY) and its Y₁ receptor in PH pathogenesis.

Experimental Approach: NPY was localized by immunofluorescence.

Subtype-specific KRAS mutations in advanced lung adenocarcinoma: a retrospective study of patients treated with platinum-based chemotherapy.

Background: Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy.

Methods: 505 Caucasian stage III-IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included.

Extracorporeal membrane oxygenation support for complex tracheo-bronchial procedures†.

Objectives: The published experience with advanced broncho-plastic procedures performed with extracorporeal membrane oxygenation (ECMO) support is very limited. We examined our results to assess the risks and benefits of this approach.

Methods: We retrospectively analysed all patients with thoracic malignancies who underwent complex tracheo-bronchial reconstruction under ECMO support in our department between 2001 and 2013.

Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema.

Rationale: Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. No therapy stopping progress of the disease is available.

Objectives: To investigate the role of the soluble guanylate cyclase (sGC)-cGMP axis in development of lung emphysema and pulmonary hypertension (PH) and to test whether the sGC-cGMP axis is a treatment target for these conditions.

Clinical-radiological, histological and genetic analyses in a lung transplant recipient with Mounier-Kuhn syndrome and end-stage chronic obstructive pulmonary disease.

Background And Aims: The Mounier-Kuhn syndrome (MKS) is a rare disease characterized by a pathological dilation of the trachea and the bronchial system. The etiology of the disorder remains elusive, but genetic alterations and degradation of elastic fibers are thought to be involved in the pathogenesis. No causative treatment is available although transplantation is an option for end-stage disease.

Expression of RAGE and HMGB1 in thymic epithelial tumors, thymic hyperplasia and regular thymic morphology.

Recently, a role of the receptor for advanced glycation endproducts (RAGE) in myasthenia gravis was described. RAGE and its ligand high mobility group box 1 (HMGB1) play key roles in autoimmunity and cancer. To test whether these molecules are involved in patients with thymic abnormalities we applied immunohistochemical analysis in 33 cases of thymic epithelial tumors, comprising 27 thymomas and 6 thymic carcinomas, and 21 nonneoplastic thymuses.