Publications
Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleMaher TM, Tudor VA, Saunders P, et al., 2024,
Rituximab compared to intravenous cyclophosphamide in adults with connective tissue disease-associated interstitial lung disease: the RECITAL RCT
, Efficacy and Mechanism Evaluation, Pages: 1-68, ISSN: 2050-4365<jats:sec id="abs1-1"><jats:title>Background</jats:title><jats:p>Interstitial lung disease frequently complicates systemic autoimmune disorders including scleroderma, idiopathic inflammatory myositis and mixed connective tissue disease, resulting in considerable morbidity and mortality. Based on the results of trials undertaken in scleroderma, cyclophosphamide is the standard of care for individuals with severe or progressive connective tissue disease-associated interstitial lung disease. Observational studies suggest that the anti-CD20 monoclonal antibody, rituximab is an effective rescue therapy in treatment of refractory connective tissue disease-associated interstitial lung disease, but it has not been studied as first-line therapy in clinical trials.</jats:p></jats:sec><jats:sec id="abs1-2"><jats:title>Objectives</jats:title><jats:p>To compare the safety and efficacy of rituximab against that of cyclophosphamide as treatment for individuals with severe, progressive interstitial lung disease associated with scleroderma, idiopathic inflammatory myositis or mixed connective tissue disease.</jats:p></jats:sec><jats:sec id="abs1-3"><jats:title>Methods</jats:title><jats:p>This was a Phase IIb, multicentre, randomised, double-blind, double-dummy study assessing the superiority of rituximab compared with cyclophosphamide, conducted in rheumatology or interstitial lung disease units at 11 UK centres. The study recruited individuals with extensive and/or progressive connective tissue disease-associated interstitial lung disease, excluding those with significant comorbidities, including airflow obstruction. Participants were randomised 1 : 1 to receive either rituximab 1 g given intravenously, twice at an interval of 2 weeks, or intravenous cyclophosphamide given monthly for 6 months at a dose of 600 mg/m<jats:sup>2</jats:sup> body surf
-
Journal articleBaltas I, Kavallieros K, Konstantinou G, et al., 2024,
The effect of ciprofloxacin prophylaxis during haematopoietic cell transplantation on infection episodes, exposure to treatment antimicrobials and antimicrobial resistance: a single-centre retrospective cohort study.
, JAC Antimicrob Resist, Vol: 6OBJECTIVES: Fluroquinolone prophylaxis during haematopoietic cell transplantation (HCT) remains contentious. We aimed to determine its effectiveness and association with exposure to treatment antimicrobials and antimicrobial resistance. METHODS: All admission episodes for HCT (N = 400 , 372 unique patients) in a tertiary centre between January 2020 and December 2022 were studied. Allogeneic HCT (allo-HCT) recipients received prophylaxis with ciprofloxacin during chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. RESULTS: Allo-HCT was performed for 43.3% (173/400) of patients, auto-HCT for 56.7% (227/400). Allo-HCT was associated with an average of 1.01 fewer infection episodes per 100 admission days (95% CI 0.62-1.40, P < 0.001) compared with auto-HCT. In allo-HCT, the total exposure to all antimicrobials was higher [+24.8 days of therapy (DOT)/100 admission days, P < 0.001], as was exposure to ciprofloxacin (+40.5 DOT/100 admission days, P < 0.001). By contrast, exposure to meropenem (-4.5 DOT/100 admission days, P = 0.02), piperacillin/tazobactam (-5.2 DOT/100 admission days, P < 0.001), aminoglycosides (-4.5 DOT/100 admission days, P < 0.001) and glycopeptides (-6.4 DOT/100 admission days, P < 0.001) was reduced. Enterobacteriaceae isolated during allo-HCT were more resistant to ciprofloxacin (65.5%, 19/29 versus 6.1%, 2/33, P < 0001), ceftriaxone (65.5%, 19/29 versus 9.1%, 3/33, P < 0.001), other antimicrobial classes. Vancomycin-resistant enterococci were more common in allo-HCT recipients (11%, 19/173 versus 0.9%, 2/227, P < 0.001). Inpatient mortality during allo- and auto-HCT was 9.8% (17/173) and 0.4% (1/227). respectively (P < 0.001). CONCLUSIONS: Ciprofloxacin prophylaxis in allo-HCT was associated with fewer infection episodes and reduced exposure to treatment antimicrobials. Mortality in auto-HCT remained low. A significant burden of antimicrobial resistance was detected in allo-HCT recipi
-
Journal articleWan Y, Myall AC, Boonyasiri A, et al., 2024,
Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes.
, J Infect DisBACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.
-
Journal articleMoriyama H, Kotta-Loizou I, Kim K-H, 2024,
Editorial: Community series in mycoviruses and related viruses infecting fungi, lower eukaryotes, plants and insects, volume II
, Frontiers in Microbiology, Vol: 15, ISSN: 1664-302X -
Journal articleLord JM, Veenith T, Sullivan J, et al., 2024,
Accelarated immune ageing is associated with COVID-19 disease severity
, Immunity and Ageing, Vol: 21, ISSN: 1742-4933BACKGROUND: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. RESULTS: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3-5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28-ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 sur
-
Journal articleDarvishi F, Rafatiyan S, Abbaspour Motlagh Moghaddam MH, et al., 2024,
Applications of synthetic yeast consortia for the production of native and non-native chemicals
, Critical Reviews in Biotechnology, Vol: 44, Pages: 15-30, ISSN: 0738-8551The application of microbial consortia is a new approach in synthetic biology. Synthetic yeast consortia, simple or complex synthetic mixed cultures, have been used for the production of various metabolites. Cooperation between the members of a consortium and cross-feeding can be applied to create stable microbial communication. These consortia can: consume a variety of substrates, perform more complex functions, produce metabolites in high titer, rate, and yield (TRY), and show higher stability during industrial fermentations. Due to the new research context of synthetic consortia, few yeasts were used to build these consortia, including Saccharomyces cerevisiae, Pichia pastoris, and Yarrowia lipolytica. Here, application of the yeasts for design of synthetic microbial consortia and their advantages and bottlenecks for effective and robust production of valuable metabolites from bioresource, including: cellulose, xylose, glycerol and so on, have been reviewed. Key trends and challenges are also discussed for the future development of synthetic yeast consortia.
-
Journal articleXu Y, Tang L, Nok-Iangthong C, et al., 2024,
Functionally Gradient Macroporous Polymers: Emulsion Templating Offers Control over Density, Pore Morphology, and Composition
, ACS Applied Polymer MaterialsGradient macroporous polymers were produced by polymerization of emulsion templates comprising a continuous monomer phase and an internal aqueous template phase. To produce macroporous polymers with gradient composition, pore size, and foam density, we varied the template formulation, droplet size, and internal phase ratio of emulsion templates continuously and stacked those prior to polymerization. Using the outlined approach, it is possible to vary one property along the resulting macroporous polymer while retaining the other properties. The elastic moduli and crush strengths change along the gradient of the macroporous polymers; their mechanical properties are dominated by those of the weakest layers in the gradient. Macroporous polymers with gradient chemical composition and thus stiffness provide both high impact load and energy adsorption, rendering the gradient foam suitable for impact protective applications. We show that dual-dispensing and simultaneous blending of two different emulsion formulations in various ratios results in a fine, bidirectional change of the template composition, enabling the production of true gradient macroporous polymers with a high degree of design freedom.
-
Journal articleDelhaye G, van der Linde S, Bauman D, et al., 2024,
Ectomycorrhizal fungi are influenced by ecoregion boundaries across Europe
, Global Ecology and Biogeography, ISSN: 1466-822XAim: Ecoregions and the distance decay in community similarity are fundamental concepts in biogeography and conservation biology that are well supported across plants and animals, but not fungi. Here we test the relevance of these concepts for ectomycorrhizal (ECM) fungi in temperate and boreal regions. Location: Europe. Time Period: 2008–2015. Major Taxa Studied: Ectomycorrhizal fungi. Methods: We used a large dataset of ~24,000 ectomycorrhizas, assigned to 1350 operational taxonomic units, collected from 129 forest plots via a standardized protocol. We investigated the relevance of ecoregion delimitations for ECM fungi through complementary methodological approaches based on distance decay models, multivariate analyses and indicator species analyses. We then evaluated the effects of host tree and climate on the observed biogeographical distributions. Results: Ecoregions predict large-scale ECM fungal biodiversity patterns. This is partly explained by climate differences between ecoregions but independent from host tree distribution. Basidiomycetes in the orders Russulales and Atheliales and producing epigeous fruiting bodies, with potentially short-distance dispersal, show the best agreement with ecoregion boundaries. Host tree distribution and fungal abundance (as opposed to presence/absence only) are important to uncover biogeographical patterns in mycorrhizas. Main Conclusions: Ecoregions are useful units to investigate eco-evolutionary processes in mycorrhizal fungal communities and for conservation decision-making that includes fungi.
-
Journal articleGuillen-Guio B, Paynton ML, Allen RJ, et al., 2024,
Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.
, ERJ Open Res, Vol: 10, ISSN: 2312-0541INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. METHODS: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. RESULTS: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. CONCLUSION: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.
-
Journal articleSouthern KW, Addy C, Bell SC, et al., 2024,
Standards for the care of people with cystic fibrosis; establishing and maintaining health.
, J Cyst Fibros, Vol: 23, Pages: 12-28This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.