An invisible threat? Aspergillus positive cultures and co-infecting bacteria in airway samples.

Background: Aspergillus fumigatus (Af) infection is associated with poor lung health in chronic suppurative lung diseases but often goes undetected. We hypothesised that inhibition of Af growth by Pseudomonas aeruginosa (Pa) increases the frequency of false-negative Af culture in co-infected people. Using a substantial group of cystic fibrosis (CF) airway samples, we assessed the relationship between Af and bacterial pathogens, additionally comparing fungal culture with next-generation sequencing.

Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression.

We developed a novel lentiviral vector, pseudotyped with the F and HN proteins from Sendai virus (rSIV.F/HN), that produces long-lasting, high-efficiency transduction of the respiratory epithelium. Here we addressed whether this platform technology can secrete sufficient levels of a therapeutic protein into the lungs to ameliorate a fatal pulmonary disease as an example of its translational capability.

Spirometry parameters used to define small airways obstruction in population-based studies: systematic review.

Background: The assessment of small airways obstruction (SAO) using spirometry is practiced in population-based studies. However, it is not clear what are the most used parameters and cut-offs to define abnormal results.

Methods: We searched three databases (Medline, Web of Science, Google Scholar) for population-based studies, published by 1 May 2021, that used spirometry parameters to identify SAO and/or provided criteria for defining SAO.

A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children ≥ 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant.

Background: Two previous Phase 3 studies ("parent studies") showed that tezacaftor/ivacaftor was generally safe and efficacious for up to 24 weeks in children 6 through 11 years of age with cystic fibrosis (CF) and F508del/F508del (F/F) or F508del/residual function (F/RF) genotypes. We assessed the safety and efficacy of tezacaftor/ivacaftor in an open-label, 96-week extension study.

Methods: This was a Phase 3, 2-part, multicenter, open-label, extension study in children 6 through 11 years of age at treatment initiation (Study VX17-661-116; NCT03537651).

Issue 1 - "Update on adverse respiratory effects of outdoor air pollution". Part 1): Outdoor air pollution and respiratory diseases: A general update and an Italian perspective.

Objective: to summarize the main updated evidence about the health effects of air pollution and to focus on Italian epidemiological experiences on the respiratory effects.

Results: the recent literature indicates that there is strong evidence for causal relationships between PM air pollution exposure and all-cause mortality as well as mortality from acute lower respiratory infections, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer. A growing body of evidence also suggests causal relationships with type II diabetes and impacts on neonatal mortality from low birth weight and short gestation as well as neurologic effects in both children and adults.

Respiratory-related death in individuals with incident asthma and COPD: a competing risk analysis.

Background: Distinguishing between mortality attributed to respiratory causes and other causes among people with asthma, COPD, and asthma-COPD overlap (ACO) is important. This study used electronic health records in England to estimate excess risk of death from respiratory-related causes after accounting for other causes of death.

Methods: We used linked Clinical Practice Research Datalink (CPRD) primary care and Office for National Statistics mortality data to identify adults with asthma and COPD from 2005 to 2015.

Assessment and outcomes of firefighter applicants with possible asthma.

Background: Firefighter applicants (FFAs) with a history of asthma may be refused entry to the fire service because of potentially putting themselves and others at risk.

Aims: We undertook a service evaluation to identify respiratory and employment outcomes of FFAs with a history of asthma who had undergone additional respiratory assessment at our specialist occupational lung disease clinic during 2005-19.

Methods: We reviewed FFA medical records and categorized them as having either no current asthma or definite/probable asthma at the time of clinic assessment.

Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells.

Calcific aortic valve disease (CAVD) is an athero-inflammatory process. Growing evidence supports the inflammation-driven calcification model, mediated by cytokines such as interferons (IFNs) and tumor necrosis factor (TNF)-α. Our goal was investigating IFNs' effects in human aortic valve endothelial cells (VEC) and the potential differences between aortic (aVEC) and ventricular (vVEC) side cells.

Device Design Modifications Informed by In Vitro Testing of Bacterial Attachment Reduce Infection Rates of Cochlear Implants in Clinical Practice.

Recalcitrant chronic infections of implanted medical devices are often linked to the presence of biofilms. The prevention and treatment of medical device-associated infections is a major source of antibiotic use and driver of antimicrobial resistance globally. Lowering the incidence of infection in patients that receive implanted medical devices could therefore significantly improve antibiotic stewardship and reduce patient morbidity.

Evidence and Applicability of Stress Cardiovascular Magnetic Resonance in Detecting Coronary Artery Disease: State of the Art.

Cardiovascular magnetic resonance is increasingly used in clinical practice, as it has emerged over the years as an invaluable imaging technique for diagnosis and prognosis, with clear-cut applications in managing patients with both ischemic and non-ischemic heart disease. In this review, we focus on the evidence and clinical application of stress CMR in coronary artery disease from diagnosis to prognosis.

Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.

Our understanding of cystic fibrosis (CF) has grown exponentially since the discovery of the cystic fibrosis transmembrane conductance regulator () gene in 1989. With evolving genetic and genomic tools, we have come to better understand the role of genotypes in the pathophysiology of the disease. This, in turn, has paved the way for the development of modulator therapies targeted at mutations in the , which are arguably one of the greatest advances in the treatment of CF.

GARFIELD-AF risk score for mortality, stroke, and bleeding within 2 years in patients with atrial fibrillation.

Aims: To determine whether the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) integrated risk tool predicts mortality, non-haemorrhagic stroke/systemic embolism, and major bleeding for up to 2 years after new-onset AF and to assess how this risk tool performs compared with CHA2DS2-VASc and HAS-BLED.

Methods And Results: Potential predictors of events included demographic and clinical characteristics, choice of treatment, and lifestyle factors. A Cox proportional hazards model was identified for each outcome by least absolute shrinkage and selection operator methods.

Bacteriophage infection of leads to the formation of membrane vesicles via both explosive cell lysis and membrane blebbing.

Membrane vesicles (MVs) are membrane-bound spherical nanostructures that prevail in all three domains of life. In Gram-negative bacteria, MVs are thought to be produced through blebbing of the outer membrane and are often referred to as outer membrane vesicles (OMVs). We have recently described another mechanism of MV formation in that involves explosive cell-lysis events, which shatters cellular membranes into fragments that rapidly anneal into MVs.

Cardiovascular Disease Risk Reduction in Mild-Moderate Hypertriglyceridemia: Integrating Prescription of Omega-3 with Standard Treatment.

Purpose Of Review: This reviews aims to evaluate the role of omega-3 for cardiovascular disease (CVD) risk reduction in mild-moderate hypertriglyceridemia.

Recent Findings: Epidemiological and Mendelian randomization studies have demonstrated that hypertriglyceridemia is strongly correlated to CVD. Even in patients with optimal low-density lipoprotein cholesterol (LDL-C) levels, triglycerides remain an important predictor to lower residual cardiovascular risk.

Health impact assessment to predict the impact of tobacco price increases on COPD burden in Italy, England and Sweden.

Raising tobacco prices effectively reduces smoking, the main risk factor for chronic obstructive pulmonary disease (COPD). Using the Health Impact Assessment tool "DYNAMO-HIA", this study quantified the reduction in COPD burden that would occur in Italy, England and Sweden over 40 years if tobacco prices were increased by 5%, 10% and 20% over current local prices, with larger increases considered in secondary analyses. A dynamic Markov-based multi-state simulation modelling approach estimated the effect of changes in smoking prevalence states and probabilities of transitioning between smoking states on future smoking prevalence, COPD burden and life expectancy in each country.

Multiple holins contribute to extracellular DNA release in biofilms.

Bacterial biofilms are composed of aggregates of cells encased within a matrix of extracellular polymeric substances (EPS). One key EPS component is extracellular DNA (eDNA), which acts as a 'glue', facilitating cell-cell and cell-substratum interactions. We have previously demonstrated that eDNA is produced in biofilms via explosive cell lysis.

is capable of natural transformation in biofilms.

Natural transformation is a mechanism that enables competent bacteria to acquire naked, exogenous DNA from the environment. It is a key process that facilitates the dissemination of antibiotic resistance and virulence determinants throughout bacterial populations. is an opportunistic Gram-negative pathogen that produces large quantities of extracellular DNA (eDNA) that is required for biofilm formation.

GARFIELD-AF: a worldwide prospective registry of patients with atrial fibrillation at risk of stroke.

The Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) examined real-world practice in a total of 57,149 (5069 retrospective, 52,080 prospective) patients with newly diagnosed AF at risk of stroke/systemic embolism, enrolled at over 1000 centers in 35 countries. It aimed to capture data on AF burden, patients' clinical profile, patterns of clinical practice and antithrombotic management, focusing on stroke/systemic embolism prevention, uptake of new oral anticoagulants, impact on death and bleeding. GARFIELD-AF set new standards for quality of data collection and analysis.

The changing demography of the cystic fibrosis population: forecasting future numbers of adults in the UK.

Improvements in management of cystic fibrosis (CF) through specialist centres in the UK have been associated with a step-change in life expectancy. With increasing numbers of adult patients there is a need to review health care provision to ensure it is sufficient to meet future needs. We used UK CF Registry data to project the number of patients aged 16-17 and 18 and older  up to 2030, and numbers therefore requiring specialist adult CF care.