Bedside to bench and back again-translational research in interventional pulmonology.

Purpose Of Review: Translational research in Interventional Pulmonology has made significant advances in recent years, ranging from novel biomarkers and imaging to practice-changing clinical trials in lung cancer and pleural disease. This review article aims to summarize key research studies in the field to understand the latest published evidence and to highlight areas of growing academic interest.

Recent Findings: In lung cancer, the role of novel imaging and biomarkers and their potential utility in early lung cancer diagnosis will be highlighted.

PneumoLLM: Harnessing the power of large language model for pneumoconiosis diagnosis.

The conventional pretraining-and-finetuning paradigm, while effective for common diseases with ample data, faces challenges in diagnosing data-scarce occupational diseases like pneumoconiosis. Recently, large language models (LLMs) have exhibits unprecedented ability when conducting multiple tasks in dialogue, bringing opportunities to diagnosis. A common strategy might involve using adapter layers for vision-language alignment and diagnosis in a dialogic manner.

Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103 T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear.

Clinical identification of malignant pleural effusions.

Introduction: Pleural effusions frequently signal disseminated cancer. Diagnostic markers of pleural malignancy at presentation that would assess cancer risk and would streamline diagnostic decisions remain unidentified.

Methods: A consecutive cohort of 323 patients with pleural effusion (PE) from different etiologies were recruited between 2013 and 2017 and was retrospectively analyzed.

Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3.

Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.

Malignant pleural effusion: Updates in diagnosis, management and current challenges.

Malignant pleural effusion (MPE) is a common condition which often causes significant symptoms to patients and costs to healthcare systems. Over the past decade, the management of MPE has progressed enormously with large scale, randomised trials answering key questions regarding optimal diagnostic strategies and effective management strategies. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy.

Achieving Molecular Profiling in Pleural Biopsies: A Multicenter, Retrospective Cohort Study.

Background: Pleural biopsy findings offer greater diagnostic sensitivity in malignant pleural effusions compared with pleural fluid. The adequacy of pleural biopsy techniques in achieving molecular marker status has not been studied, and such information (termed "actionable" histology) is critical in providing a rational, efficient, and evidence-based approach to diagnostic investigation.

Research Question: What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions?

Study Design And Methods: This study analyzed anonymized data on 183 patients from four sites across three countries in whom pleural biopsy results had confirmed a malignant diagnosis and molecular profiling was relevant for the diagnosed cancer type.

The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study.

Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection, but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection matched with ultrasound and clinical outcome data. To assess the presence and severity of septations against baseline PF PAI-1 (Plasminogen-Activator Inhibitor-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes.

The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing.

Background: Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients.

Objective Thoracoscopic Criteria in Differentiation between Benign and Malignant Pleural Effusions.

Background: Thoracoscopy is the "gold standard" diagnostic modality for investigation of suspected pleural malignancy. It is postulated that meticulous assessment of the pleural cavity may be adequate to indicate malignancy through the macroscopic findings of nodules, pleural thickening, and lymphangitis. We attempted to critically assess this practice, by precisely defining objective macroscopic criteria which might differentiate benign from malignant pleural diseases according to intrapleural pattern and anatomical location, and thereby to explore the predilection of abnormalities to specific sites on pleural surfaces.

The Association Between Pleural Fluid Exposure and Survival in Pleural Mesothelioma.

Background: Most patients with malignant pleural mesothelioma (MPM) seek treatment with malignant pleural effusion (MPE). In vitro evidence suggests that MPE may not be a simple bystander of malignancy, but rather potentially has biological properties that improve cancer cell survival and promote cancer progression. If this is the case, MPE management may need to shift from current symptomatic strategies to aggressive fluid removal to impact survival.

Pleural Fluid Has Pro-Growth Biological Properties Which Enable Cancer Cell Proliferation.

Objectives: Patients with malignant pleural mesothelioma (MPM) or pleural metastases often present with malignant pleural effusion (MPE). This study aimed to analyze the effect of pleural fluid on cancer cells.

Materials And Methods: Established patient-derived cancer cell cultures derived from MPE (MPM, breast carcinoma, lung adenocarcinoma) were seeded in 100% pleural fluid (exudate MPM MPE, transudate MPE, non-MPE transudate fluid) and proliferation was monitored.

Evaluation of cardiovascular risk in a lung cancer screening cohort: what value does it bring?

https://bit.ly/3a6Ha41.

Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments.

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity.

Intercostal vessel screening prior to pleural interventions by the respiratory physician: a prospective study of real world practice.

Introduction: The rising incidence of pleural disease is seeing an international growth of pleural services, with physicians performing an ever-increasing volume of pleural interventions. These are frequently conducted at sites without immediate access to thoracic surgery or interventional radiology and serious complications such as pleural bleeding are likely to be under-reported.

Aim: To assess whether intercostal vessel screening can be performed by respiratory physicians at the time of pleural intervention, as an additional step that could potentially enhance safe practice.

Clinically important associations of pleurodesis success in malignant pleural effusion: Analysis of the TIME1 data set.

Background And Objective: Chemical pleurodesis is performed for patients with MPE with a published success rate of around 80%. It has been postulated that inflammation is key in achieving successful pleural symphysis, as evidenced by higher amounts of pain or detected inflammatory response. Patients with mesothelioma are postulated to have a lower rate of successful pleurodesis due to lack of normal pleural tissue enabling an inflammatory response.

Management of incidental nodules in lung cancer screening: ready for prime-time?

http://bit.ly/2oMIEwQ.

Osteopontin drives KRAS-mutant lung adenocarcinoma.

Increased expression of osteopontin (secreted phosphoprotein 1, SPP1) is associated with aggressive human lung adenocarcinoma (LADC), but its function remains unknown. Our aim was to determine the role of SPP1 in smoking-induced LADC. We combined mouse models of tobacco carcinogen-induced LADC, of deficiency of endogenous Spp1 alleles, and of adoptive pulmonary macrophage reconstitution to map the expression of SPP1 and its receptors and determine its impact during carcinogenesis.

Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients.

Background: Pleural infection (PI) is a major global disease with an increasing incidence, and pleural fluid (PF) drainage is essential for the successful treatment. The MIST2 study demonstrated that intrapleural administration of tissue plasminogen activator (t-PA) and DNase, or t-PA alone increased the volume of drained PF. Mouse model studies have suggested that the volume increase is due to the interaction of the pleura with the t-PA via the monocyte chemoattractant protein 1 (MCP-1) pathway.

Novel mouse model of indwelling pleural catheter in mice with malignant pleural effusion.

bit.ly/2W2kzO0.

Club cells form lung adenocarcinomas and maintain the alveoli of adult mice.

Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents.

Tobacco chemical-induced mouse lung adenocarcinoma cell lines pin the prolactin orthologue proliferin as a lung tumour promoter.

Lung adenocarcinoma (LADC) is the leading cause of cancer death worldwide. Nevertheless, syngeneic mouse models of the disease are sparse, and cell lines suitable for transplantable and immunocompetent mouse models of LADC remain unmet needs. We established multiple mouse LADC cell lines by repeatedly exposing two mouse strains (FVB, Balb/c) to the tobacco carcinogens urethane or diethylnitrosamine and by culturing out the resulting lung tumours for prolonged periods of time.