Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml−1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.

Malignant pleural effusion (MPE) is a common but serious condition that is related with poor quality of life, morbidity and mortality. Its incidence and associated healthcare costs are rising and its management remains palliative, with median survival ranging from 3 to 12 months. During the last decade there has been significant progress in unravelling the pathophysiology of MPE, as well as its diagnostics, imaging, and management. Nowadays, formerly bed-ridden patients are genotyped, phenotyped, and treated on an ambulatory basis. This article attempts to provide a comprehensive overview of current advances in MPE from bench to bedside. In addition, it highlights unanswered questions in current clinical practice and suggests future directions for basic and clinical research in the field. @ERSpublications This review provides up to date knowledge for malignant pleural effusion covering aspects from bench to bedside http://ow.ly/10w7vN

MCP-1 produced by tumor cells is an important determinant of their capacity to induce the formation of MPE and may be a useful target for the treatment of malignant pleural disease.

No abstract

Malignancy involving the pleura is the third leading cause of pleural effusions, with an annual incidence of Ͼ 150,000 cases in the United States (1, 2). Adenocarcinomas account for ‫ف‬ 70% of all malignant pleural effusions (MPEs), with lung adenocarcinomas being the most frequent underlying malignancy (3). The appearance of a MPE is an ominous prognostic sign for patients with cancer, because the presence of the MPE indicates that the tumor is incurable by surgery and life expectancy is short (1). In addition, the presence of the pleural effusion can cause dyspnea that severely compromises the quality of the patient's life (4, 5). Pleurodesis, the iatrogenic induction of pleural fibrosis to obliterate the pleural cavity, is commonly used to prevent symptomatic re-accumulation of pleural effusions; however, this therapy is often ineffective and is associated with significant It is generally believed that disruption of the endothelialmesothelial barrier, increased capillary permeability, tumorinduced angiogenesis, and lymphatic obstruction are responsible for the exudation of increased amounts of fluid into the pleural cavity (1, 7). However, the specific mechanisms underlying pleural fluid accumulation are poorly defined because studies of MPE pathogenesis are limited by a lack of animal models that reproduce the pathobiology of human MPE. Although mouse models that require immunocompromised mice for propagation of human cancer cells mice have provided insights into the biological behavior of tumor cells in the pleural cavity (7-9), these models are not ideal because the host is immunocompromised, and, therefore, the host immune response is attenuated or missing. The immune response against tumor may be an important component in the development of MPE because host inflammatory cells may contribute to or regulate the production of mediators that affect pathogenesis (10).Nuclear factor (NF)-B is a ubiquitous family of transcription regulatory proteins that affects a variety of cellular functions and influences tumor biology and host-tumor interactions. NF-B is activated by a number of tumor-promoting agents and is involved in the production of proteins that enhance cell survival and proliferation (11). High basal NF-B activation is present in lung adenocarcinoma cells and human lung cancer, and inhibition of NF-B sensitizes tumor cells to apoptosis and the effects of chemotherapeutic agents (11)(12)(13)(14)(15).Lewis lung cancer (LLC) cells are derived from a spontaneously arising lung adenocarcinoma in C57B/6 mice. These cells are characterized by short doubling times in vitro and in vivo and aggressive biological behavior. They can be propagated in wild-type C57B/6 mice, giving rise to lung adenocarcinomas (16)(17)(18). In these studies, we have developed and characterized a new murine model of MPE after instillation of lung adenocarcinoma cells in the pleural space of immunocompetent mice. We used this model to investigate whether the NF-B pathway in tumor cells is linked to MPE formation and progression of pl...

Electronic cigarettes (e-cig) are advertised as a less harmful nicotine delivery system or as a new smoking cessation tool. We aimed to assess the in vivo effects of e-cigarette vapor in the lung and to compare them to those of cigarette smoke (CS). We exposed C57BL/6 mice for either 3 days or 4 weeks to ambient air, CS or e-cig vapor containing: i) propylene glycol/vegetable glycerol (1:1; PG:VG-Sol), ii) PG:VG with nicotine (G:VG-N), or iii) PG:VG with nicotine and flavor (PG:VG- N+F) and determined oxidative stress, inflammation and pulmonary mechanics. E-cig vapors, especially PG:VG- N+F, increased bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers at least comparably and in many cases more than CS. BALF protein content at both time points studied was only elevated in the PG:VG- N+F group. After 3 days, PG:VG-Sol altered tissue elasticity, static compliance and airway resistance, while after 4 weeks, CS was the only treatment adversely affecting these parameters. Airway hyperresponsiveness in response to methacholine was increased similarly in the CS and PGVG-N+F groups. Our findings suggest that exposure to e-cig vapor can trigger inflammatory responses and adversely affect respiratory system mechanics. In many cases, the added flavor in e-cigs exacerbated the detrimental effects of e-cig vapor. We conclude that both e-cig vaping and conventional cigarette smoking negatively impact lung biology.

SummaryBackgroundSince the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.MethodsThis randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov, NCT02287467.Findings313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the pr...

Eosinophilic pleural effusions, defined as a pleural effusion that contains at least 10% eosinophils, may be caused by almost every condition that can cause pleural disease. Eosinophilic pleural effusion occurs most commonly during conditions associated with the presence of blood or air in the pleural space, infections, and malignancy. Drug-induced pleural effusions, pleural effusions accompanying pulmonary embolism, and benign asbestos pleural effusions are also among the common causes of eosinophilic pleural effusion. No etiology is found in as many as one third of patients. Because studies evaluating different diagnostic approaches with eosinophilic pleural effusions are lacking, the authors suggest that certain noninvasive and invasive diagnostic tools must be used based on the patient's clinical characteristics.