• Extracellular DNA, hyaluronic acid, HIF pathways, and LncRNAs as predictive biomarkers of severe COVID-19.
    3 months ago
    The clinical course of COVID-19 ranges from mild symptoms to severe complications, and common laboratory markers such as D-dimer, ferritin, interleukin-6 (IL-6), and C-reactive protein (CRP) often do not accurately predict which patients will develop severe disease. In this study, we reviewed current literature and analyzed additional data to assess emerging biomarkers that may help identify high-risk cases earlier. These include circulating cell-free DNA (cfDNA) produced during neutrophil extracellular trap formation (NETosis), hyaluronic acid (HA), hypoxia-inducible factor (HIF) isoforms, and related long non-coding RNAs such as HAS2-AS1 and HIF1-AS1. Increased levels of cfDNA/NETs, HA, and elevated expression of HIF isoforms and their lncRNAs are closely associated with key features of severe COVID-19, including immune-related blood clotting, low oxygen levels, vascular damage, and chronic inflammation. These biomarkers show promise for use in risk assessment tools that could support earlier clinical decisions and improve outcomes in patients with COVID-19.
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  • Delivering home-based palliative care during COVID-19 in Taiwan: a qualitative study with interdisciplinary team members.
    3 months ago
    The COVID-19 pandemic disrupted palliative care globally, but its impact on home-based palliative care (HBPC) within universal healthcare systems, particularly in Asian contexts, remains understudied. Taiwan's National Health Insurance system supports a well-established HBPC program. This background offers a unique lens to examine how interdisciplinary teams adapted HBPC delivery during different pandemic phases.

    This qualitative study used telephone-based semi-structured interviews with 14 HBPC providers from two medical centers: one in a rural area and one in an urban area. Transcripts were analyzed using inductive thematic analysis. The study design and reporting were guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ).

    Four themes related to the impact of the COVID-19 pandemic on the delivery of HBPC were identified: (1) variation in impacts across time, (2) divergent views of the impact on the uptake of HBPC, (3) difficulties in providing adequate care under restrictions, and (4) disrupted care coordination.

    Despite Taiwan's well-established palliative care programs, HBPC delivery faced ethical, clinical, and coordination challenges during the pandemic. This experience reveals an urgent need to strengthen virtual care infrastructure, establish clearer interdisciplinary coordination protocols, and provide sustained support for caregivers. These lessons should inform future public health preparedness strategies to ensure that infection control measures do not come at the expense of holistic, patient- and family-centered palliative care.
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  • Moving Towards an Integrated Approach to Allergic Rhinitis Management: ARIA and EUFOREA Guidelines Similarities and Differences.
    3 months ago
    This review aims to raise awareness of the Allergic Rhinitis and its Impact on Asthma (ARIA) and European Forum for Research and Education in Allergy and Airway Disease (EUFOREA) guidelines for allergic rhinitis (AR) by presenting a side-by-side summary of their key elements. Drawing on the authors' direct involvement in the development of both, it highlights their evolution toward precision medicine and patient-centred care to support stronger doctor-patient partnerships.

    Both ARIA and EUFOREA offer evidence-based guidance to support AR management, with increasing emphasis on personalisation and digital integration. While aligned in goals, they differ in patient classification, treatment delivery, and implementation strategies. Barriers to real-world use include the need for contextual adaptation, targeted education for healthcare providers and patients, and inconsistent alignment between guideline-based prescriptions and patient behaviour. Mobile health (mHealth) tools offer valuable support but require sustained engagement. Greater awareness of these guidelines can improve implementation, harmonise treatment approaches, and ultimately enhance care delivery and outcomes for individuals with AR.
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  • Systemic cytokines drive conserved severity-associated myeloid responses across bacterial and viral infections.
    3 months ago
    Both bacterial and viral infections can trigger an overwhelming host response, leading to immunopathology and organ dysfunction. Multiple studies have reported dysregulated myeloid cell states in patients with bacterial sepsis or severe SARS-CoV-2 infection. However, their relevance to viral infections other than COVID-19, the factors driving their induction, and their role in tissue injury remain poorly understood. Here, we performed a multi-cohort analysis of single cell and bulk transcriptomic data from 1845 patients across 25 studies. Our meta-analysis revealed a conserved severity-associated gene signature pointing to emergency myelopoiesis (EM) and increased IL1R2 expression in monocytes and neutrophils from patients with bacterial sepsis, COVID-19, and influenza. Analysis of tocilizumab-treated COVID-19 patients showed that IL-6 signaling blockade partially reduces this signature and results in a compensatory increase in G-CSF. To validate the role of these cytokines in vivo, we used a mouse model of influenza infection that recapitulates severity-associated increases in IL1R2+ monocytes and IL1R2hi neutrophils, and demonstrate that combined IL-6 and G-CSF blockade inhibits their production. Our study demonstrates the cooperative role of G-CSF and IL-6 in driving the production of severity-associated IL1R2+ myeloid cells and highlights the link between myeloid dysregulation and tissue injury during severe infection.
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  • Realistic wave-optics simulation of X-ray dark-field imaging at a human scale.
    3 months ago
    X-ray dark-field imaging (XDFI) has been explored as a superior alternative to conventional X-ray imaging for diagnosing many pathologic conditions. However, a simulation tool capable of reliably predicting clinical XDFI images at a human scale, is currently lacking. In this paper, we demonstrate, to the best of our knowledge, the first human-scale XDFI simulation. Using the developed simulation tool, we illustrate the strengths and limitations of XDFI for the diagnosis of emphysema, fibrosis, atelectasis, edema, and pneumonia. We augment the XCAT phantom with Voronoi grids to simulate the alveolar substructure responsible for the lung's dark-field signal, assign material properties to each tissue type, and simulate X-ray wave propagation through the augmented XCAT phantom using a multi-layer wave-optics propagation. By altering the density and thickness of the Voronoi grids, as well as the material properties, we simulate XDFI images of normal and diseased lungs. Our simulation framework can generate realistic XDFI images of a human chest with normal or diseased lungs. The simulation confirms that the normal, emphysematous, and fibrotic lungs produce clearly distinct dark-field signals. It also shows that alveolar fluid accumulation in pneumonia, wall thickening in interstitial edema, and deflation in atelectasis all result in similar reductions in dark-field signal. It is feasible to augment XCAT with pulmonary substructure and generate realistic XDFI images using multi-layer wave optics. By providing the most realistic XDFI images of lung pathologies to date, the developed simulation framework enables in-silico clinical trials and the optimization of both hardware and software for XDFI.
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  • Open-source computational pipeline flags instances of acute respiratory distress syndrome in mechanically ventilated adult patients.
    3 months ago
    Physicians in critical care settings face information overload and decision fatigue, contributing to under-recognition of acute respiratory distress syndrome, which affects over 10% of intensive care patients and carries over 40% mortality rate. We present a reproducible computational pipeline to automatically identify this condition retrospectively in mechanically ventilated adults. This computational pipeline operationalizes the Berlin Definition by detecting bilateral infiltrates from radiology reports and a pneumonia diagnosis from attending physician notes, using interpretable classifiers trained on labeled data. Here we show that our integrated pipeline achieves high performance-93.5% sensitivity and 17.4% false positive rate-when applied to a held-out and publicly-available dataset from an external hospital. This substantially exceeds the 22.6% documentation rate observed in the same cohort. These results demonstrate that our automated adjudication pipeline can accurately identify an under-diagnosed condition in critical care and may support timely recognition and intervention through integration with electronic health records.
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  • Treating connective tissue disease-associated interstitial lung disease - think outside the box: a perspective.
    3 months ago
    Connective tissue disease-associated interstitial lung disease is one of the most common subtypes of interstitial lung disease, which is a leading cause of morbidity and mortality in patients with these systemic autoimmune rheumatic diseases. A spectrum of disease trajectories exists within individual and across different connective tissue diseases. In individuals with connective tissue diseases who are at risk or at the early asymptomatic stage with interstitial lung changes, we have potential windows of opportunity for interventions to prevent the development of or progression to interstitial lung disease. In this perspective, we use systemic sclerosis and rheumatoid arthritis as sample cases to discuss emerging knowledge on disease pathogenesis, as well as to apply the preventative medicine concept for pharmacotherapeutic approaches at different disease stages of connective tissue disease-associated interstitial lung disease.
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  • Beyond classical collagen: basement membrane collagen IV in age-associated lung diseases.
    3 months ago
    Chronic lung diseases such as COPD, asthma, idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension are characterised by aberrant remodelling and degradation of the extracellular matrix. This is particularly evident within the basement membrane. Collagen IV, a major component of the basement membrane, is essential for maintaining structural support and regulating cell behaviour. However, disruptions in collagen IV metabolism and basement membrane integrity have been implicated in the pathogenesis of chronic lung diseases, especially in ageing populations where basement membrane turnover is compromised. Cleavage of collagen IV during basement membrane remodelling generates bioactive fragments known as matrikines, which serve as markers of tissue remodelling and potential diagnostic biomarkers. Despite the prominence of collagen IV in the basement membrane, its role in chronic lung diseases remains understudied compared to other collagen types. This review provides a comprehensive exploration of the roles of basement membrane collagen IV and its matrikines in COPD, asthma, IPF and pulmonary hypertension, emphasising their significance beyond classical matrix components. Through an analysis of clinical studies, animal models and in vitro experiments, the contributions of collagen IV to disease pathogenesis and progression are discussed. Furthermore, potential diagnostic and therapeutic implications of targeting collagen IV are outlined. By providing insights into the relationship between collagen IV and chronic lung diseases, this review aims to guide future research and clinical interventions in the field.
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  • Exercise and pulmonary embolism: a systematic review of exercise safety, feasibility and effectiveness.
    3 months ago
    Long-term survivors of pulmonary embolism (PE) exhibit decreased exercise capacity, dyspnoea and a diminished quality of life. Exercise may represent a beneficial strategy for ameliorating persistent symptoms following PE.

    Is exercise training beneficial for improving exercise capacity and quality of life in patients with PE? Additionally, is it safe and feasible?

    The aim of this systematic review was to evaluate the safety, feasibility and efficacy of exercise training in improving exercise capacity and quality of life in patients with PE. In order to comprehensively assess the available evidence, we conducted a systematic review using a combination of free-text terms and medical subject headings according to database requirements in PubMed, Medline, Web of Science, Scopus, Embase and the Cochrane Library from inception until 17 September 2024.

    We included a total of nine trials including 583 patients, including 391 in the interventional group and 190 in the control group. The difference in the average adverse event rates between the exercise group (0.5%) and the control group (0%) was not significant. The overall recruitment rate was approximately 51% (range: 38-65%), the withdrawal rate was approximately 5% (range: 0-13%) and the adherence rate was 87% (range: 61-100%). The studies reported average improvements in peak oxygen consumption (exercise group: 7.55 mL·kg-1·min-1; control group: 1.95 mL·kg-1·min-1), incremental shuttle walk test distance (exercise group: 142 m; control group: 69.5 m), vitality scores (exercise group: 13.95; control group: 3.95), and role emotional scores (exercise group: 12.05; control group: -0.1). However, due to considerable discrepancies in the scoring systems, an average improvement in Pulmonary Embolism Quality of Life questionnaire score could not be determined. Notably, no improvement in dyspnoea was reported.

    This systematic review indicates that exercise training seems to be safe and feasible for patients with PE. It appears to enhance patients' exercise capacity and quality of life, although its impact on alleviating dyspnoea remains limited. However, given the absence of large-scale randomised controlled trials, these findings should be interpreted with caution.
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  • A beginner's guide to using personalised three-dimensional airway stents.
    3 months ago
    Conventional silicone airway stents are effective in relieving stenoses but are prone to complications such as migration and granulation tissue formation. These complications reduce patients' tolerance and induce unwanted procedures, limiting their overall benefit. Over the past decade, personalised, three-dimensional (3D)-printed silicone stents have emerged as a possible solution to some of these concerns. In this narrative review, the authors aim to guide the physician into understanding the relatively straightforward creative process behind 3D stents and the selection process of the best patients for their use. Current use is limited to complex anatomical airway stenoses, but more indications could blossom from future trials as technology, expertise and access develop going forward.
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