Taking a Deep Breath : an Examination of Current Controversies in Surgical Procedures in Lung Transplantation

Purpose of Review: This article reviews controversial questions within the field of lung transplantation, with a focus on data generated within the last 3 years. We aim to summarize differing opinions on a selection of topics, including bridge-to-transplantation, intraoperative machine circulatory support, bronchial anastomosis, size mismatch, delayed chest closure, and ex vivo lung perfusion.Recent Findings: With the growing rate of lung transplantations worldwide and increasing numbers of patients placed on waiting lists, the importance of determining best practices has only increased in recent years. Factors which promote successful outcomes have been identified across all the topics, with certain approaches promoted, such as ambulation in bridge-to-transplant and widespread intraoperative ECMO as machine support.Summary: While great strides have been made in the operative procedures involved in lung transplantation, there are still key questions to be answered. The consensus which can be reached will be instrumental in further improving outcomes in recipients

Current Status and Future Perspectives on Machine Perfusion: A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy : A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy

Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of available donor organs given critical shortages. As transplantation is the only option for patients with end-stage lung disease, advancements in technology are needed to decrease wait-list time and mortality. This review summarizes the results from the application of EVLP as a therapeutic intervention and focuses on the use of the platform with regard to cell therapies, cell product therapies, and cytokine filtration among other technologies. This review will summarize both the clinical and translational science being conducted in these aspects and will highlight the opportunities for EVLP to be developed as a powerful tool to increase the donor lung supply

Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome

Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In the present study, plasma was collected at three timepoints and analyzed using proximity extension assay technology and quantitative real-time polymerase chain reaction in patients with primary NSCLC stages IA–IIIA undergoing surgery. Results were adjusted for patient demographics, tumor, node, metastasis (TNM) stage, and multiple testing. Major histocompatibility (MHC) class 1 polypeptide-related sequence A/B (MIC-A/B) and tumor necrosis factor ligand superfamily member 6 (FASLG) were significantly increased post-surgery, suggesting radical removal of cancerous cells. Levels of hepatocyte growth factor (HGF) initially increased postoperatively but were later lowered, potentially indicating radical removal of malignant cells. The levels of FASLG in patients who later died or had a relapse of NSCLC were lower at all three timepoints compared to surviving patients without relapse, indicating that FASLG may be used as a prognostic biomarker. The biomarkers were confirmed using microarray data. In conclusion, quantitative proteomics could be used for NSCLC identification but may also provide information on radical surgical removal of NSCLC and post-surgical prognosis

Nothing but NETs : Cytokine adsorption correlates with lower circulating nucleosomes and is associated with decreased primary graft dysfunction

Elevated levels of neutrophil extracellular traps (NETs) have been reported in primary graft dysfunction, making methods to reduce or remove them highly valuable. The mechanisms behind primary graft dysfunction remain rudimentarily understood but its relation to higher rates of acute and chronic rejection necessitates the development of preventative treatments. This case series explores the use of a cytokine adsorber during lung transplantation with the focus of reducing circulating nucleosome levels as a measure of neutrophil extracellular traps. Treated patients showed reduced levels of circulating nucleosomes and remained free from primary graft dysfunction and histopathological signs of acute rejection at 1-and 3-month post-transplant. In contrast, patients without the adsorber experienced higher levels of circulating nucleosomes, primary graft dysfunction grades 1 and 3, and histopathological signs of acute rejection. Using a cytokine adsorber during transplantation may provide a reduced systemic inflammatory state with lower levels of NETs and consequently support graft acceptance

Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19

BACKGROUND: SARS-CoV-2 has been shown to predominantly infect the airways and the respiratory tract and too often have an unpredictable and different pathologic pattern compared to other respiratory diseases. Current clinical diagnostical tools in pulmonary medicine expose patients to harmful radiation, are too unspecific or even invasive. Proteomic analysis of exhaled breath particles (EBPs) in contrast, are non-invasive, sample directly from the pathological source and presents as a novel explorative and diagnostical tool.METHODS: Patients with PCR-verified COVID-19 infection (COV-POS, n = 20), and patients with respiratory symptoms but with > 2 negative polymerase chain reaction (PCR) tests (COV-NEG, n = 16) and healthy controls (HCO, n = 12) were prospectively recruited. EBPs were collected using a "particles in exhaled air" (PExA 2.0) device. Particle per exhaled volume (PEV) and size distribution profiles were compared. Proteins were analyzed using liquid chromatography-mass spectrometry. A random forest machine learning classification model was then trained and validated on EBP data achieving an accuracy of 0.92.RESULTS: Significant increases in PEV and changes in size distribution profiles of EBPs was seen in COV-POS and COV-NEG compared to healthy controls. We achieved a deep proteome profiling of EBP across the three groups with proteins involved in immune activation, acute phase response, cell adhesion, blood coagulation, and known components of the respiratory tract lining fluid, among others. We demonstrated promising results for the use of an integrated EBP biomarker panel together with particle concentration for diagnosis of COVID-19 as well as a robust method for protein identification in EBPs.CONCLUSION: Our results demonstrate the promising potential for the use of EBP fingerprints in biomarker discovery and for diagnosing pulmonary diseases, rapidly and non-invasively with minimal patient discomfort

Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome

Abstract Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 106 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options

Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation

Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient

What's New in New Forms of Organizing? On the Construction of Gender in Project-Based Work

In several industries, projects are now the normal form of work for individuals. The consequences of project work have not so far been subject to critical inquiry, however. This implies inquiry not only on how people handle project work at work, it also means inquiring into how they live their lives when working by projects. In this paper, we study this from a constructionist gender perspective, in which project work is seen as an ongoing construction of patterns of femininity and masculinity in society. The aim of the paper is to contribute to an understanding of how project work is related to the ongoing construction of femininity and masculinity in the work and lives of human beings. Copyright Blackwell Publishing Ltd 2006.