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Hansell D.M.,Royal Brompton and Harefield National Health Service Foundation Trust | Goldin J.G.,University of California at Los Angeles | King T.E.,University of California at San Francisco | Lynch D.A.,Jewish Medical and Research Center | And 2 more authors.
The Lancet Respiratory Medicine | Year: 2015

CT is increasingly being used to stage and quantify the extent of diffuse lung diseases both in clinical practice and in treatment trials. The role of CT in the assessment of patients entering treatment trials has greatly expanded as clinical researchers and pharmaceutical companies have focused their efforts on developing safe and effective drugs for interstitial lung diseases, particularly for idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous approval by the US Food and Drug Administration of two new drugs for the treatment of idiopathic pulmonary fibrosis. CT features are a key part of the inclusion criteria in many drug trials and CT is now being used to refine the type of patients enrolled. Interest in the potential use of serial CT as an effectiveness endpoint is increasing. For chronic progressive diseases, mortality may not be a feasible endpoint and many surrogate markers have been explored, ranging from pulmonary function decline to biomarkers. However, these surrogate markers are not entirely reliable and combinations of endpoints, including change in disease extent on CT, are being investigated. Methods to assess disease severity with CT range from simple visual estimates to sophisticated quantification by use of software. In this Position Paper, which cannot be regarded as a comprehensive set of guidelines in view of present knowledge, we examine the uses of serial CT in clinical practice and in drug trials and draw attention to uncertainties and challenges for future research. © 2015 Elsevier Ltd. Source


Kuo W.,Erasmus University Rotterdam | Van De Corput M.P.C.K.,Erasmus University Rotterdam | Perez-Rovira A.,Erasmus University Rotterdam | De Bruijne M.,Erasmus University Rotterdam | And 36 more authors.
European Respiratory Journal | Year: 2016

Progressive cystic fibrosis (CF) lung disease is the main cause of mortality in CF patients. CF lung disease starts in early childhood. With current standards of care, respiratory function remains largely normal in children and more sensitive outcome measures are needed to monitor early CF lung disease. Chest CT is currently the most sensitive imaging modality to monitor pulmonary structural changes in children and adolescents with CF. To quantify structural lung disease reliably among multiple centres, standardisation of chest CT protocols is needed. SCIFI CF (Standardised Chest Imaging Framework for Interventions and Personalised Medicine in CF) was founded to characterise chest CT image quality and radiation doses among 16 participating European CF centres in 10 different countries. We aimed to optimise CT protocols in children and adolescents among several CF centres. A large variety was found in CT protocols, image quality and radiation dose usage among the centres. However, the performance of all CT scanners was found to be very similar, when taking spatial resolution and radiation dose into account. We conclude that multicentre standardisation of chest CT in children and adolescents with CF can be achieved for future clinical trials. Copyright © ERS 2016. Source


Kemp S.J.,Imperial College London | Goldstraw P.,Royal Brompton and Harefield National Health Service Foundation Trust | Tetley T.D.,Imperial College London | Stevens M.M.,Institute of Biomedical Engineering
Biophysical Journal | Year: 2010

Researchers have previously questioned the suitability of cell lines as models for primary cells. In this study, we used Raman microspectroscopy to characterize live A549 cells from a unique molecular biochemical perspective to shed light on their suitability as a model for primary human pulmonary alveolar type II (ATII) cells. We also investigated a recently developed transduced type I (TT1) cell line as a model for alveolar type I (ATI) cells. Single-cell Raman spectra provide unique biomolecular fingerprints that can be used to characterize cellular phenotypes. A multivariate statistical analysis of Raman spectra indicated that the spectra of A549 and TT1 cells are characterized by significantly lower phospholipid content compared to ATII and ATI spectra because their cytoplasm contains fewer surfactant lamellar bodies. Furthermore, we found that A549 spectra are statistically more similar to ATI spectra than to ATII spectra. The spectral variation permitted phenotypic classification of cells based on Raman spectral signatures with >99% accuracy. These results suggest that A549 cells are not a good model for ATII cells, but TT1 cells do provide a reasonable model for ATI cells. The findings have far-reaching implications for the assessment of cell lines as suitable primary cellular models in live cultures. © 2010 by the Biophysical Society. Source


Martin-Sanchez F.J.,Institute Investigacion Sanitaria Hospital Clinico San Carlos IdISSC | Martin-Sanchez F.J.,Complutense University of Madrid | Miro O.,Hospital Clinic | Miro O.,Institute Of Recerca Biomadica August Pi I Sunyer Idibaps | And 16 more authors.
International Journal of Cardiology | Year: 2016

Acute heart failure (AHF) is a multi-organ dysfunction syndrome. In addition to known cardiac dysfunction, non-cardiac comorbidity, frailty and disability are independent risk factors of mortality, morbidity, cognitive and functional decline, and risk of institutionalization. Frailty, a treatable and potential reversible syndrome very common in older patients with AHF, increases the risk of disability and other adverse health outcomes. This position paper highlights the need to identify frailty in order to improve prognosis, the risk–benefits of invasive diagnostic and therapeutic procedures, and the definition of older-person-centered and integrated care plans. © 2016 Elsevier Ireland Ltd Source


Al Halabi S.,Cleveland Clinic | Qintar M.,Cleveland Clinic | Hussein A.,Cleveland Clinic | Alraies M.C.,University of Minnesota | And 17 more authors.
JACC: Clinical Electrophysiology | Year: 2015

Objectives The objective of the study was to compare rate control versus atrial fibrillation (AF) catheter ablation strategies in patients with AF and heart failure (HF). Background Rhythm control with antiarrhythmic drugs (AADs) is not superior to rate control in patients with HF and AF, but AF ablation may be more successful at achieving rhythm control than are AADs. However, risks for both ablation and AADs are probably higher and success rates lower in patients with HF. Methods We conducted a meta-analysis of trials that randomized HF patients (left ventricular ejection fraction [LVEF] <50%) with AF to a rate control or AF catheter ablation strategy and reported changes in LVEF, quality of life, 6-min walk test, or peak oxygen consumption. Study quality and heterogeneity were assessed through the use of Jadad scores and Cochran's Q statistics, respectively. Mantel-Haenszel relative risks and mean differences were calculated through the use of random effect models. Results Four trials (N = 224) met inclusion criteria; 82.5% (n = 185) had persistent AF. AF ablation was associated with an increase in LVEF (mean difference, 8.5%; 95% confidence interval [CI]: 6.4% to 10.7%; p < 0.001) compared with rate control. AF ablation was superior in improving quality of life by Minnesota Living With Heart Failure (MLWHF) questionnaire scores (mean difference, -11.9; 95% CI: -17.2 to 6.6; p < 0.001). Peak oxygen consumption and 6-min walk distance increased in AF ablation compared with rate-control patients (mean difference, 3.2; 95% CI: 1.1 to 5.3; p = 0.003; mean difference, 34.8; 95% CI: 2.9 to 66.7; p = 0.03, respectively). In the persistent AF subgroup, LVEF and MLWHF were significantly improved with AF ablation. Major adverse event rates (risk ratio: 1.3; 95% CI: 0.4 to 3.9; p = 0.64) were not significantly different. No significant heterogeneity was evident. Conclusions In patients with HF and AF, AF catheter ablation is superior to rate control in improving LVEF, quality of life, and functional capacity. Before accepting a rate-control strategy in HF patients with persistent or drug-refractory AF, consideration should be given to AF ablation. © 2015 American College of Cardiology Foundation Published By Elsevier Inc. Source

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