The impact of poor asthma control among asthma patients treated with inhaled corticosteroids plus long-acting β2-agonists in the United Kingdom : a cross-sectional analysis

This study was sponsored by Boehringer Ingelheim Ltd UK, which was involved in all stages of the study conduct and analysis and also funded all costs associated with the development of the manuscript. The authors acknowledge Kantar Health and Errol J Philip for providing medical writing support. Editorial assistance and medical writing support was also provided by Michelle Rebello, PhD, and Suchita Nath-Sain, PhD, of Cactus Communications. This study was sponsored by Boehringer Ingelheim Ltd., UK, which also funded all costs associated with the development of the manuscript. Author Correction, npj Primary Care Respiratory Medicine 27, Article number: 65 (2017) doi:10.1038/s41533-017-0063-5, 05 December 2017 Correction to:npj Primary Care Respiratory Medicine (2017); doi:10.1038/s41533-017-0014-1; Published 09 March 2017Peer reviewedPublisher PD

Towards the production of radiotherapy treatment shells on 3D printers using data derived from DICOM CT and MRI: preclinical feasibility studies

Background: Immobilisation for patients undergoing brain or head and neck radiotherapy is achieved using perspex or thermoplastic devices that require direct moulding to patient anatomy. The mould room visit can be distressing for patients and the shells do not always fit perfectly. In addition the mould room process can be time consuming. With recent developments in three-dimensional (3D) printing technologies comes the potential to generate a treatment shell directly from a computer model of a patient. Typically, a patient requiring radiotherapy treatment will have had a computed tomography (CT) scan and if a computer model of a shell could be obtained directly from the CT data it would reduce patient distress, reduce visits, obtain a close fitting shell and possibly enable the patient to start their radiotherapy treatment more quickly. Purpose: This paper focuses on the first stage of generating the front part of the shell and investigates the dosimetric properties of the materials to show the feasibility of 3D printer materials for the production of a radiotherapy treatment shell. Materials and methods: Computer algorithms are used to segment the surface of the patient’s head from CT and MRI datasets. After segmentation approaches are used to construct a 3D model suitable for printing on a 3D printer. To ensure that 3D printing is feasible the properties of a set of 3D printing materials are tested. Conclusions: The majority of the possible candidate 3D printing materials tested result in very similar attenuation of a therapeutic radiotherapy beam as the Orfit soft-drape masks currently in use in many UK radiotherapy centres. The costs involved in 3D printing are reducing and the applications to medicine are becoming more widely adopted. In this paper we show that 3D printing of bespoke radiotherapy masks is feasible and warrants further investigation

An ex vivo porcine spleen perfusion as a model of bacterial sepsis

An ex vivo, porcine spleen perfusion model was established to study the early events occurring in the spleen prior to the onset of bacterial sepsis, using organs retrieved from animals slaughtered for food production. Porcine spleens were harvested from adult pigs and connected to a normothermic extracorporeal perfusion circuit. Constant perfusion of heparinized blood was performed for 6 hours. After injection of Streptococcus pneumoniae to the circuit, serial samples of both blood and spleen biopsies were collected and analyzed. Functionality of the perfused organs was assessed by monitoring the blood-gas parameters, flow rate and filtering capability of the organ. Interestingly, we observed full clearance of bacteria from the blood and an increase in bacterial counts in the spleen. Classical histology and immunohistochemistry on biopsies also confirmed no major damage in the organ architecture and no changes in the immune cell distribution other than the presence of clusters of pneumococci. A time-course study confirmed that each focus of infection derived from the replication of single pneumococcal cells within splenic macrophages. The model proposed – in line with the 3Rs principles – has utility in the replacement of experimental animals in infection research. Murine models are prevalently used to study pneumococcal infections but are often not predictive for humans due to substantial differences in the immune systems of the two species. This model is designed to overcome these limitations, since porcine immunology, and splenic architecture in particular, closely resemble those of humans

Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC