1,720,960 research outputs found

    Hyperoxia and surfactant dysfunction in critical illness: insights and future therapeutic prospects

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    Supplemental oxygen is an essential therapy during critical illness. However, patients with severe hypoxemic respiratory failure and/or acute respiratory distress syndrome (ARDS) often require high oxygen concentrations, exposing lungs to alveolar hyperoxia despite systemic hypoxemia, with consequent pulmonary oxygen toxicity. Pulmonary oxygen toxicity causes disruption of surfactant, which is essential for maintenance of alveolar functional anatomy as well as efficient and effective gas exchange and immune regulation. Surfactant dysregulation can increase alveolar surface tension, causing alveolar collapse with atelectasis, resulting in poor lung compliance and impaired gas exchange. Hyperoxia-induced lung injury mechanisms may interact with mechanisms of harm associated with infections and mechanical ventilation. The intricate relationship between these different, inter-related, stressors and altered surfactant metabolism and function has yet to be fully delineated, particularly in humans. This review examines current understanding of hyperoxia-induced surfactant dysregulation. We discuss potential mechanisms, including biochemical/compositional and functional changes to lipids and proteins including surfactant protein A (SP-A) and SP-D, epithelial atrophy, impaired surfactant synthesis/metabolism, redox imbalances, phospholipase-A2, and altered macrophage clearance. Key areas for future research are outlined, emphasising the need for clinically relevant human models that discriminate between the effects of oxygen therapy dose and duration, as well as other iatrogenic effects and underlying disease processes. We propose a roadmap to progress current knowledge and outline opportunities for well-designed human studies, novel surfactant preparations resistant to functional inhibition and breakdown, and technological developments, with the potential for leveraging these to identify innovative biomarkers individualised therapeutic targets and novel therapies in the future.</p

    Evaluation of the physiological variables and scoring systems at intensive care discharge as predictors of clinical deterioration and readmission: a single-centre retrospective study

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    Objectives We aim to determine, using routinely collected data and common scoring systems, whether parameters seen at intensive care unit (ICU) discharge can be predictive of subsequent clinical deterioration.Design/setting A single-centre retrospective study located in a tertiary hospital in the south of England.Participants 1868 patients who were admitted and discharged from ICU between 1 April 2023 and 31 March 2024 were screened for eligibility. A total of 1393 patients were included in the final analysis, including 122 patients who were classified in the ‘deteriorated’ subgroup.Interventions Assessment of vital signs, blood markers of infection and inflammation and three scoring systems (National Early Warning Score 2 (NEWS2), Acute Physiology and Chronic Health Evaluation II Score and Sequential Organ Failure Assessment (SOFA) score) taken within 24 hours prior to ICU discharge.Primary outcomes Assessment of predictors of deterioration after ICU discharge.Secondary outcomes Reasons for readmission to ICU, hospital mortality, ICU length of stay and time before readmission to ICU.Results Heart rate, conscious level (alert, voice, pain, unresponsive scale) and SOFA score were independent predictors of deterioration after ICU discharge (under the curve 0.85, CI 0.79 to 0.90, specificity 82.3%, sensitivity 79.7%) in multivariable models. Of these, a reduced level of consciousness was the most significant predictor of clinical deterioration (OR 19.6, CI 11.4 to 35.0). NEWS2 was an independent predictor for deterioration on univariable analysis. Mortality was significantly increased in patients who experienced deterioration after ICU discharge, as was ICU length of stay.Conclusions Predictive models may be useful in assisting clinicians with ICU discharge decisions. Further research is required to develop patient-tailored scoring systems that incorporate other factors that are needed for decisions around ICU discharge

    Corticosteroids for the management of severe community-acquired pneumonia: a UK-wide survey

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    The use of corticosteroids in severe community-acquired pneumonia (sCAP) management is a contentious issue with current practices of United Kingdom (UK) intensivists largely unknown. To investigate this, we surveyed UK intensive care clinicians from 20 September 2024 to 19 December 2024, collecting 160 responses from 115 intensive care units (response rate 48.3%). 56.1% of responders use corticosteroids in the treatment of sCAP. There were large variabilities in practice. Hydrocortisone started within 24 h of admission 50 mg four times a day for 4-5 days was the most reported regime. The variation in practice coupled with relative equipoise requires further evaluation and guidance.</p

    Physiology and pathophysiology of mucus and mucolytic use in critically ill patients

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    Airway mucus is a highly specialised secretory fluid which functions as a physical and immunological barrier to pathogens whilst lubricating the airways and humifying atmospheric air. Dysfunction is common during critical illness and is characterised by changes in production rate, chemical composition, physical properties, and inflammatory phenotype. Mucociliary clearance, which is determined in part by mucus characteristics and in part by ciliary function, is also dysfunctional in critical illness via disease related and iatrogenic mechanisms. The consequences of mucus dysfunction are potentially devastating, contributing to prolonged ventilator dependency, increased risk of secondary pneumonia, and worsened lung injury. Mucolytic therapies are designed to decrease viscosity, improve expectoration/suctioning, and thereby promote mucus removal. Mucolytics, including hypertonic saline, dornase alfa/rhDNase, nebulised heparin, carbocisteine/N-Acetyl cysteine, are commonly used in critically ill patients. This review summarises the physiology and pathophysiology of mucus and the existing evidence for the use of mucolytics in critically ill patients and speculates on journey to individualised mucolytic therapy.</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    The role of corticosteroids in the management of non-COVID-19 severe community-acquired pneumonia in the intensive care unit: a narrative review

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    Severe community-acquired pneumonia (sCAP) is associated with a significant health burden, both in the UK and globally, with intensive care support needed for many patients. The high morbidity and mortality associated with sCAP has led to the exploration of adjunctive therapies that may help reduce disease burden and improve clinical outcomes. One such proposed treatment is corticosteroids, aiming to moderate the disproportionate inflammation caused by sCAP. Despite several studies suggesting potential benefits, the use of corticosteroids in patients with sCAP remains contentious, with recent large trials producing conflicting results. These variations in trial outcomes have resulted in conflicting national and international guidelines. Such discrepancies align with findings from a recent national survey that indicated ongoing clinical uncertainty regarding the use of corticosteroids for sCAP in UK intensive care units. Several factors contribute to these conflicting outcomes, including patient population, the severity classification utilised, the type and duration of interventions provided, and, perhaps most importantly, the lack of pre-phenotyping to identify patients who may benefit most from the treatment. This narrative review aims to examine the recent literature, current guidelines, and evidence for using corticosteroids in sCAP, while exploring the candidate phenotypes of relevance in the design of clinical trials

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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