Publications by authors named "Stijn Verleden"

Currently, lung transplantation outcome remains inferior compared to other solid organ transplantations. A major cause for limited survival after lung transplantation is chronic lung allograft dysfunction. Numerous animal models have been developed to investigate chronic lung allograft dysfunction to discover adequate treatments.

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Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD.

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Background & Aims: Cystic fibrosis (CF) is considered a multisystemic disorder in which CF-associated liver disease (CFLD) is the third most common cause of mortality. Currently, no effective treatment is available for CFLD because its pathophysiology is still unclear. Interestingly, CFLD exhibits identical vascular characteristics as non-cirrhotic portal hypertension, recently classified as porto-sinusoidal vascular disorders (PSVD).

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In European countries, nearly 10% of all hospital admissions are related to respiratory diseases, mainly chronic life-threatening diseases such as COPD, pulmonary hypertension, IPF or lung cancer. The contribution of blood vessels and angiogenesis to lung regeneration, remodeling and disease progression has been increasingly appreciated. The vascular supply of the lung shows the peculiarity of dual perfusion of the pulmonary circulation (vasa publica), which maintains a functional blood-gas barrier, and the bronchial circulation (vasa privata), which reveals a profiled capacity for angiogenesis (namely intussusceptive and sprouting angiogenesis) and alveolar-vascular remodeling by the recruitment of endothelial precursor cells.

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Article Synopsis
  • * Researchers are looking into new ways to diagnose CLAD using tests and scans, but there are still challenges to get a clear understanding of the problem.
  • * Even though there have been some improvements, more studies are needed to find better treatments and understand the risks for people with CLAD.
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Chronic obstructive pulmonary disease (COPD), a devastating and irreversible lung disease, causes structural and functional defects in the bronchial epithelium, the (ir)reversibility of which remains unexplored in vitro. This study aimed to investigate the persistence of COPD-related epithelial defects in long-term airway epithelial cultures derived from non-smokers, smokers, and COPD patients. Barrier function, polarity, cell commitment, epithelial-to-mesenchymal transition, and inflammation were evaluated and compared with native epithelium characteristics.

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Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs.

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  • A study on combined pulmonary fibrosis and emphysema (CPFE) explored how these conditions impact mortality and lung function decline compared to patients with just idiopathic pulmonary fibrosis (IPF).
  • CPFE patients with more than 10% emphysema had a history of stronger smoking habits and experienced more pronounced declines in lung function, particularly in diffusing capacity, which correlated better with mortality than overall lung capacity measures.
  • The findings suggest that when evaluating disease progression in IPF, specific measures like diffusing capacity should be prioritized for patients with significant emphysema, while a relative decline in forced vital capacity (FVC) should be monitored in non-CPFE IPF patients.
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  • - The 2022 Banff Foundation for Allograft Pathology Conference focused on non-rejection lung allograft pathology and new technologies for identifying allograft injury.
  • - A panel discussed current histopathologic methods, serological studies, and innovations like digital pathology using AI and gene expression analysis, highlighting the need for better assessment of allograft injury and its implications for lung transplant results.
  • - Key takeaways included recognizing the limitations of current methods, the necessity for a standardized approach to data collection, and excitement about emerging minimally invasive diagnostic tools that require further testing in broader studies to enhance personalized treatment strategies.
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  • - The assessment of donor lungs for transplantation is mostly subjective and varies greatly, lacking standardized criteria; researchers explored using a CT-based machine learning algorithm to evaluate donor lungs before surgery.
  • - The study collected clinical data and CT scans from 100 cases, training a machine learning method called dictionary learning to identify specific image patterns related to lung health.
  • - The algorithm successfully detected lung abnormalities, highlighting patients with a higher risk of complications post-transplant and emphasizing the need for objective screening methods as the use of less-than-ideal donor lungs increases.
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  • - The study investigates the relationship between right ventricular function and lung injury during lung transplantation, focusing on how ischemia-reperfusion injury affects the transplanted lung itself, using a porcine model for research.
  • - Researchers observed that forcing blood through a lung affected by ischemia-reperfusion injury significantly increased resistance and led to right ventricular failure in some animals, highlighting distinct responses in failing versus non-failing ventricles.
  • - The findings suggest a complex interplay between lung injury and right ventricular function, emphasizing the potential benefits of using extracorporeal life support during lung transplantation procedures to mitigate these effects.
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In the last two decades, robotic-assisted thoracoscopic surgery (RATS) has gained popularity as a minimally invasive surgical (MIS) alternative to multi- and uniportal video-assisted thoracoscopic surgery (VATS). With this approach, the surgeon obviates the known drawbacks of conventional MIS, such as the reduced in-depth perception, hand-eye coordination, and freedom of motion of the instruments. Previous studies have shown that a robotic approach for operable lung cancer has treatment outcomes comparable to other MIS techniques such as multi-and uniportal VATS, but with less blood loss, a lower conversion rate to open surgery, better lymph node dissection rates, and improved ergonomics for the surgeon.

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Objective: Diagnosing lung injury is a challenge in lung transplantation. It has been unclear if a single biopsy specimen is truly representative of the entire organ. Our objective was to investigate lung inflammatory biomarkers using human lung tissue biopsies and ex vivo lung perfusion perfusate.

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Surgical resection is still the standard treatment for early-stage lung cancer. A multimodal treatment consisting of chemotherapy, radiotherapy and/or immunotherapy is advised for more advanced disease stages (stages IIb, III and IV). The role of surgery in these stages is limited to very specific indications.

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  • The human lung plays a crucial role in oxygenating blood, with high-resolution x-ray phase-contrast computed tomography (XPCT) enabling detailed imaging of lung structures and functions at a microscopic level.
  • The study employs XPCT on various preparation methods of postmortem lung tissue, revealing distinct pulmonary pathologies and showcasing the technology's ability to produce high-quality images even from laboratory settings.
  • By leveraging synchrotron radiation, this method enhances imaging contrast, allowing researchers to analyze complex 3D lung structures and their associated physiological and pathological mechanisms, potentially improving clinical diagnostics.
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Background: Assessment and selection of donor lungs remains largely subjective and experience based. Criteria to accept or decline lungs are poorly standardized and are not compliant with the current donor pool. Using ex vivo CT images, we investigated the use of a CT-based machine learning algorithm for screening donor lungs prior to transplantation.

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Background: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP).

Methods: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98).

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Background Interstitial lung abnormalities (ILAs) reflect imaging features on lung CT scans that are compatible with (early) interstitial lung disease. Despite accumulating evidence regarding the incidence, risk factors, and prognosis of ILAs, the histopathologic correlates of ILAs remain elusive. Purpose To determine the correlation between radiologic and histopathologic findings in CT-defined ILAs in human lung explants.

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  • Pulmonary fibrosis (PF) and pulmonary hypertension (PH) are chronic lung and circulatory diseases that can occur together, but the reasons behind this connection are not well understood.
  • The study investigates the role of the GCN2 gene and its pathway in the development of PH in patients with PF and in a rat model, using lung tissue samples and induced lung disease.
  • Results indicate that GCN2 protein levels are reduced in both human PF cases and bleomycin-treated rats, suggesting that GCN2 dysregulation may play a role in the progression of PF and PH, warranting further research.
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  • COVID-19 patients can experience various heart symptoms that significantly affect their health outcomes, yet the specific causes of cardiac issues related to the virus are still not well understood.
  • A study analyzed heart samples from COVID-19 autopsies and found distinct changes such as increased macrophages and unique gene expression patterns linked to blood vessel growth, differing from other viral infections like Influenza H1N1.
  • The results suggest that the heart involvement in COVID-19 may be driven by a unique inflammatory process focused on blood vessel changes, which traditional methods may overlook.
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