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Breathe (Sheffield, England) Dec 2023https://bit.ly/4a7dh1S.
https://bit.ly/4a7dh1S.
PubMed: 38127543
DOI: 10.1183/20734735.0230-2023 -
Breathe (Sheffield, England) Dec 2023Malignant pleural disease represents a growing healthcare burden. Malignant pleural effusion affects approximately 1 million people globally per year, causes disabling... (Review)
Review
Malignant pleural disease represents a growing healthcare burden. Malignant pleural effusion affects approximately 1 million people globally per year, causes disabling breathlessness and indicates a shortened life expectancy. Timely diagnosis is imperative to relieve symptoms and optimise quality of life, and should give consideration to individual patient factors. This review aims to provide an overview of epidemiology, pathogenesis and suggested diagnostic pathways in malignant pleural disease, to outline management options for malignant pleural effusion and malignant pleural mesothelioma, highlighting the need for a holistic approach, and to discuss potential challenges including non-expandable lung and septated effusions.
PubMed: 38351947
DOI: 10.1183/20734735.0145-2023 -
American Journal of Respiratory and... Dec 2023Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized... (Randomized Controlled Trial)
Randomized Controlled Trial
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.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively ( = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) ( = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) ( = 0.023). One serious adverse event was reported in the VATS arm. This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).
Topics: Humans; Thoracic Surgery, Video-Assisted; Feasibility Studies; Communicable Diseases; Pleural Diseases; Sepsis; Enzyme Therapy
PubMed: 37820359
DOI: 10.1164/rccm.202305-0854OC -
Ugeskrift For Laeger Apr 2024The incidence of pleural disease is increasing and the mortality and morbidity is high. Many recent RCTs have resulted in evidence-based guidelines published in 2023,... (Review)
Review
The incidence of pleural disease is increasing and the mortality and morbidity is high. Many recent RCTs have resulted in evidence-based guidelines published in 2023, pointing towards a more individualized and specialized management. Most patients with pleural disease are admitted at the A and E but can be managed in outpatient clinics. Thus, there is a need to establish specialized, multidisciplinary pleural clinics to ensure optimal, individualized and evidence-based management of the increasing number of patients with pleural disease in Denmark, as argued in this review.
Topics: Humans; Pleural Diseases; Ambulatory Care Facilities
PubMed: 38606707
DOI: 10.61409/V09230618 -
Breathe (Sheffield, England) Mar 2024The pleural space is a "potential" anatomical space which is formed of two layers: visceral and parietal. It normally contains a trace of fluid (∼10 mL in each... (Review)
Review
The pleural space is a "potential" anatomical space which is formed of two layers: visceral and parietal. It normally contains a trace of fluid (∼10 mL in each hemithorax). Diseases of the pleura can manifest with thickening of the pleural membranes or by abnormal accumulation of air or liquid. Chest radiographs are often the first imaging tests to point to a pleural pathology. With the exception of pneumothorax, and due to the inherent limitations of chest radiographs, ultrasound and/or computed tomography are usually required to further characterise the pleural pathology and guide management. This review summarises the utility of different imaging tools in the management of pleural disease and discusses new and evolving tools in imaging of the pleura.
PubMed: 38482187
DOI: 10.1183/20734735.0172-2023 -
Journal For Immunotherapy of Cancer Aug 2023Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop...
BACKGROUND
Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop acquired resistance due to the existence of abundant immunosuppressive cells. Tumor-associated macrophages (TAMs), as the dominant immunosuppressive population, impede the antitumor immune response; however, the underlying mechanisms have not been fully elucidated yet.
METHODS
Single-cell RNA sequencing analysis was performed to portray macrophage landscape and revealed the underlying mechanism of component 1q (C1q) TAMs. Malignant pleural effusion (MPE) of human and mouse was used to explore the phenotypes and functions of C1q TAMs.
RESULTS
C1q TAMs highly expressed multiple inhibitory molecules and their high infiltration was significantly correlated with poor prognosis. C1q TAMs promote MPE immunosuppression through impairing the antitumor effects of CD8 T cells. Mechanistically, C1q TAMs enhance fatty acid binding protein 5 (FABP5)-mediated fatty acid metabolism, which activate transcription factor peroxisome proliferator-activated receptor-gamma, increasing the gene expression of inhibitory molecules. A high-fat diet increases the expression of inhibitory molecules in C1q TAMs and the immunosuppression of MPE microenvironment, whereas a low-fat diet ameliorates these effects. Moreover, FABP5 inhibition represses the expression of inhibitory molecules in TAMs and tumor progression, while enhancing the efficacy of ICB therapy in MPE and lung cancer.
CONCLUSIONS
C1q TAMs impede antitumor effects of CD8 T cells promoting MPE immunosuppression. Targeting C1q TAMs effectively alleviates the immunosuppression and enhances the efficacy of ICB therapy. C1q TAMs subset has great potential to be a therapeutic target for cancer immunotherapy.
Topics: Humans; Animals; Mice; Complement C1q; Pleural Effusion, Malignant; Tumor-Associated Macrophages; CD8-Positive T-Lymphocytes; Immunosuppression Therapy; Immunosuppressive Agents; Tumor Microenvironment; Fatty Acid-Binding Proteins
PubMed: 37604643
DOI: 10.1136/jitc-2023-007441 -
Journal of Thoracic Disease Mar 2024
PubMed: 38617759
DOI: 10.21037/jtd-24-4