The cellular composition of the lung lining fluid gradually changes from bronchus to alveolus

Although large advances have recently been made mapping out the cellular composition of lung tissue using single cell sequencing, the composition and distribution of the cellular elements within the lining fluid of the lung has not been extensively studied. Here, we assessed the cellular composition of the lung lining fluid by performing a differential cell analysis on bronchoalveolar lavage fluid (BALF) and epithelial lining fluid (ELF) at four different locations within the lung in post-lung transplantation patients. The percentage of neutrophils and lymphocytes is reduced in more distal regions of the lungs, while the percentage of macrophages increases in these more distal regions. These data provide valuable information to determine which lung lining fluid sampling technique and location is best to use for measuring specific factors and biomarkers, and to increase the understanding of different cell populations in specific lung regions

The development, validation, and in vivo testing of a high-precision bronchial epithelial lining fluid sampling device.

INTRODUCTION: Analysis of respiratory biomarkers or pharmaceutical drug concentrations in bronchial epithelial lining fluid (bELF) using a high-precision sampling method is crucial for effective clinical respiratory diagnostics and research. Here, we utilized a cellulose matrix as an absorptive probe for bELF sampling, subsequently testing the design of a device and sampling technique in vivo. METHODS: The absorptive matrix [Whatman® qualitative filter paper (Grade CF-12)] was first tested through tissue-contact experiments on porcine airway tissue. The absorption and elution capacity of the matrix, as well as the laboratory processing and analysis method, was validated with a range of Interleukin-8 (CXCL8) and C-Reactive protein (CRP) stock solutions. Subsequently, the device's design was optimized for universal in-house production and both, safe and efficient sampling. The airway sampling method was then tested in a group of 10 patients with Chronic Obstructive Pulmonary Disease (COPD). For each patient, a bELF sample was obtained using the newly developed bELF probe, as well as a reference 20 mL saline bronchial wash sample. Supernatants were assessed, using an immunoassay, for levels of the pro-inflammatory markers CXCL8, Myeloperoxidase (MPO), and CRP. The bELF samples were compared to bronchial wash. RESULTS: The Whatman® qualitative filter paper (Grade CF-12) bELF probes adhered to porcine airway tissue, softening slightly upon wetting. The material maintained architectural integrity following the removal of the probes, leaving no residual fibers on the porcine airway mucosa. The bELF probe design was optimized for bronchoscopic delivery and in-house production. On average, a fully saturated bELF probe carried 32 μL of protein-rich fluid. The mean return of CXCL8 and CRP from samples collected from a serial dilution series (1, 5, 10, 20 ng/mL) was 69% (range 48%-87%). The bELF probe detected, on average, 7 (MPO), 14 (CRP), and 59 (CXCL8) times higher equivalent inflammatory protein concentrations in the collected bELF probe samples compared to the bronchial wash. CONCLUSION: The bELF probe is an effective absorptive technology for high-precision bELF sampling without dilution. With a simple in-house production procedure and bronchoscopic sampling technique, this method can be introduced in any bronchoscopic center for a consistent sampling of bELF.</p

Gastric Fistula in the Chest After Sleeve Gastrectomy: a Systematic Review of Diagnostic and Treatment Options

This study aimed to establish the optimal diagnostic and treatment algorithm for the management of gastric fistula in the chest (GFIC) after sleeve gastrectomy (SG) through a systematic review of published cases. A multi-database search was performed, which produced 1182 results, of which 26 studies were included in this systematic review. The initial presentation included subphrenic collections, leaks, or (recurrent) pneumonia with associated symptoms such as persistent cough, fever, and/or dyspnea. Computed tomography (CT) scan in combination with either upper gastrointestinal (UGI) series or an esophagogastroduodenoscopy (EGD) was used to adequately diagnose the fistulas. Initial treatment was either with clips and/or clips and stents that were placed endoscopically. When unsuccessful in the majority of the cases, the surgical treatment consisted of total gastrectomy and Roux-en-Y esophagojejunostomy in a laparoscopic or open fashion

Crosslink bio-adhesives for bronchoscopic lung volume reduction:current status and future direction

Several bronchoscopic lung volume reduction (BLVR) treatments have been developed to reduce hyperinflation in emphysema patients. Lung bio-adhesives are among the most promising new BLVR treatment options, as they potentially provide a permanent solution for emphysematous patients after only a single application. To date, bio-adhesives have mainly been used as haemostats and tissue sealants, while their application in permanently contracting and sealing hyperinflated lung tissue has recently been identified as a novel and enticing opportunity. However, a major drawback of the current adhesive technology is the induction of severe inflammatory responses and adverse events upon administration. In our review, we distinguish between and discuss various natural, semi-synthetic and synthetic tissue haemostats and sealants that have been used for pulmonary applications such as sealing air/fluid leaks. Furthermore, we present an overview of the different materials including AeriSeal and autologous blood that have been used to achieve lung volume reduction and discuss their respective advantages and drawbacks. In conclusion, we describe the key biological (therapeutic benefit and biocompatibility) and biomechanical (degradability, adhesive strength, stiffness, viscoelasticity, tunability and self-healing capacity) characteristics that are essential for an ideal lung bio-adhesive material with the potential to overcome the concerns related to current adhesives

Intensive care unit (ICU)-acquired bacteraemia and ICU mortality and discharge:Addressing time-varying confounding using appropriate methodology

Background: Studies often ignore time-varying confounding or may use inappropriate methodology to adjust for time-varying confounding. Aim: To estimate the effect of intensive care unit (ICU)-acquired bacteraemia on ICU mortality and discharge using appropriate methodology. Methods: Marginal structural models with inverse probability weighting were used to estimate the ICU mortality and discharge associated with ICU-acquired bacteraemia among patients who stayed more than two days at the general ICU of a London teaching hospital and remained bacteraemia-free during those first two days. For comparison, the same associations were evaluated with (i) a conventional Cox model, adjusting only for baseline confounders and (ii) a Cox model adjusting for baseline and time-varying confounders. Findings: Using the marginal structural model with inverse probability weighting, bacteraemia was associated with an increase in ICU mortality (cause-specific hazard ratio (CSHR): 1.29; 95% confidence interval (CI): 1.02-1.63)and a decrease in discharge (CSHR: 0.52; 95% CI: 0.45-0.60). By 60 days, among patients still in the ICU after two days and without prior bacteraemia, 8.0% of ICU deaths could be prevented by preventing all ICU-acquired bacteraemia cases. The conventional Cox model adjusting for time-varying confounders gave substantially different results [for ICU mortality, CSHR: 1.08 (95% CI: 0.88-1.32); for discharge, CSHR: 0.68 (95% CI: 0.60-0.77)]. Conclusion: In this study, even after adjusting for the timing of acquiring bacteraemia and time-varying confounding using inverse probability weighting for marginal structura

Splenic Abscess Following Sleeve Gastrectomy: A Systematic Review of Clinical Presentation and Management Methods

BACKGROUND: Splenic abscess is a rare complication following sleeve gastrectomy. METHODS: We performed a systematic review to clarify its clinical significance, presentation, and management. PubMed, Embase, MEDLINE, Google Scholar, and the Cochrane Library were searched up to the 19th of July 2020. A total of 18 patients were included, of which 11 were female and 7 were male. The mean age was 34.1 ± 12.3 years, and the mean body mass index was 45.8 ± 7.6 kg/m2. Type 2 diabetes mellitus was reported in 11.1% of patients and hypertension in 22.2%. Fever was the most common presenting symptom seen in 17 (94.4%) patients, followed by abdominal pain in 10 (55.6%). The mean duration from surgery to presentation was 98.6 ± 132.7 days (range 10–547 days). Computed tomography was used for investigations in 17/18 (94.4%) patients. Seven patients had reported leak, three reported bleeding, and 2 reported pleural effusion. Thirteen patients had unilocular abscess. All patients were treated with antibiotics. Four patients needed total parenteral nutrition, and three were given proton pump inhibitor. In total, 11 patients needed percutaneous drainage as a part of treatment and 11 patients needed total splenectomy and 1 needed partial splenectomy. CONCLUSION: Splenic abscess following sleeve gastrectomy is a rare identity. The etiology of formation of splenic abscess needs further studies. A computed tomography of the abdomen with contrast is the preferred diagnostic tool. There is no gold standard treatment for splenic abscess

Actual versus 'ideal' antibiotic prescribing for common conditions in English primary care

Previous work based on guidelines and expert opinion identified 'ideal' prescribing proportions-the overall proportion of consultations that should result in an antibiotic prescription-for common infectious conditions. Here, actual condition-specific prescribing proportions in primary care in England were compared with ideal prescribing proportions identified by experts. All recorded consultations for common infectious conditions (cough, bronchitis, exacerbations of asthma or chronic obstructive pulmonary disease, sore throat, rhinosinusitis, otitis media, lower respiratory tract infection, upper respiratory tract infection, influenza-like illness, urinary tract infection, impetigo, acne, gastroenteritis) for 2013-15 were extracted from The Health Improvement Network (THIN) database. The proportions of consultations resulting in an antibiotic prescription were established, concentrating on acute presentations in patients without relevant comorbidities. These actual prescribing proportions were then compared with previously established 'ideal' proportions by condition. For most conditions, substantially higher proportions of consultations resulted in an antibiotic prescription than was deemed appropriate according to expert opinion. An antibiotic was prescribed in 41% of all acute cough consultations when experts advocated 10%. For other conditions the proportions were: bronchitis (actual 82% versus ideal 13%); sore throat (actual 59% versus ideal 13%); rhinosinusitis (actual 88% versus ideal 11%); and acute otitis media in 2- to 18-year-olds (actual 92% versus ideal 17%). Substantial variation between practices was found. This work has identified substantial overprescribing of antibiotics in English primary care, and highlights conditions where this is most pronounced, particularly in respiratory tract conditions

Understanding the gender gap in antibiotic prescribing:a cross-sectional analysis of English primary care

OBJECTIVES:To explore the causes of the gender gap in antibiotic prescribing, and to determine whether women are more likely than men to receive an antibiotic prescription per consultation. DESIGN:Cross-sectional analysis of routinely collected electronic medical records from The Health Improvement Network (THIN). SETTING:English primary care. PARTICIPANTS:Patients who consulted general practices registered with THIN between 2013 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES:Total antibiotic prescribing was measured in children (<19 years), adults (19-64 years) and the elderly (65+ years). For 12 common conditions, the number of adult consultations was measured, and the relative risk (RR) of being prescribed antibiotics when consulting as female or with comorbidity was estimated. RESULTS:Among 4.57 million antibiotic prescriptions observed in the data, female patients received 67% more prescriptions than male patients, and 43% more when excluding antibiotics used to treat urinary tract infection (UTI). These gaps were more pronounced in adult women (99% more prescriptions than men; 69% more when excluding UTI) than in children (9%; 0%) or the elderly (67%; 38%). Among adults, women accounted for 64% of consultations (62% among patients with comorbidity), but were not substantially more likely than men to receive an antibiotic prescription when consulting with common conditions such as cough (RR 1.01; 95% CI 1.00 to 1.02), sore throat (RR 1.01, 95% CI 1.00 to 1.01) and lower respiratory tract infection (RR 1.00, 95% CI 1.00 to 1.01). Exceptions were skin conditions: women were less likely to be prescribed antibiotics when consulting with acne (RR 0.67, 95% CI 0.66 to 0.69) or impetigo (RR 0.85, 95% CI 0.81 to 0.88). CONCLUSIONS:The gender gap in antibiotic prescribing can largely be explained by consultation behaviour. Although in most cases adult men and women are equally likely to be prescribed an antibiotic when consulting primary care, it is unclear whether or not they are equally indicated for antibiotic therapy

Regulation of cellular senescence by extracellular matrix during chronic fibrotic diseases

The extracellular matrix (ECM) is a complex network of macromolecules surrounding cells providing structural support and stability to tissues. The understanding of the ECM and the diverse roles it plays in development, homoeostasis and injury have greatly advanced in the last three decades. The ECM is crucial for maintaining tissue homoeostasis but also many pathological conditions arise from aberrant matrix remodelling during ageing. Ageing is characterised as functional decline of tissue over time ultimately leading to tissue dysfunction, and is a risk factor in many diseases including cardiovascular disease, diabetes, cancer, dementia, glaucoma, chronic obstructive pulmonary disease (COPD) and fibrosis. ECM changes are recognised as a major driver of aberrant cell responses. Mesenchymal cells in aged tissue show signs of growth arrest and resistance to apoptosis, which are indicative of cellular senescence. It was recently postulated that cellular senescence contributes to the pathogenesis of chronic fibrotic diseases in the heart, kidney, liver and lung. Senescent cells negatively impact tissue regeneration while creating a pro-inflammatory environment as part of the senescence-associated secretory phenotype (SASP) favouring disease progression. In this review, we explore and summarise the current knowledge around how aberrant ECM potentially influences the senescent phenotype in chronic fibrotic diseases. Lastly, we will explore the possibility for interventions in the ECM-senescence regulatory pathways for therapeutic potential in chronic fibrotic diseases.</p

Explaining variation in antibiotic prescribing between general practices in the UK

Objectives:Primary care practices in England differ in antibiotic prescribing rates, and, anecdotally, prescribers justify high prescribing rates based on their individual case mix. The aim of this paper was to explore to what extent factors such as patient comorbidities explain this variation in antibiotic prescribing. Methods:Primary care consultation and prescribing data recorded in The Health Improvement Network (THIN) database in 2013 were used. Boosted regression trees (BRTs) and negative binomial regression (NBR) models were used to evaluate associations between predictors and antibiotic prescribing rates. The following variables were considered as potential predictors: various infection-related consultation rates, proportions of patients with comorbidities, proportion of patients with inhaled/systemic corticosteroids or immunosuppressive drugs, and demographic traits. Results:The median antibiotic prescribing rate was 65.6 (IQR 57.4-74.0) per 100 registered patients among 348 English practices. In the BRT model, consultation rates had the largest total relative influence on antibiotic prescribing rate (53.5%), followed by steroid and immunosuppressive drugs (31.6%) and comorbidities (12.2%). Only 21% of the deviance could be explained by an NBR model considering only comorbidities and age and gender, whereas 57% of the deviance could be explained by the model considering all variables. Conclusions:The majority of practice-level variation in antibiotic prescribing cannot be explained by variation in prevalence of comorbidities. Factors such as high consultation rates for respiratory tract infections and high prescribing rates for corticosteroids could explain much of the variation, and as such may be considered in determining a practice's potential to reduce prescribing