Model-assisted predictions on prognosis in HNSCC: do we learn?

Dedicated software packages incorporating prognostic models are meant to aid physicians in making accurate predictions of prognosis. This study concerns 742 predictions of 5-year survival on consecutive newly diagnosed patients with head- and neck squamous cell carcinoma. The 5-year survival predictions made by the physicians are not compared with actual survival, but with a prediction made by OncologIQ, a dedicated software package. We used a linear regression and a linear mixed-effects model to look at absolute differences between both predictions and possible learning effects. Predictions made by the physicians were optimistic and inaccurate. Using the linear regression and linear mixed-effects models, the physicians’ learning effect showed little improvement per successive prediction. We conclude that prognostic predictions in general are imprecise. When given feedback on the model’s predicted survival, the accuracy increases, but only very modestly

Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs) and their relevance to proliferation and apoptosis in pulmonary arterial hypertension.</p> <p>Methods</p> <p>Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin), lipophobic (pravastatin) and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release.</p> <p>Results</p> <p>Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550) was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase.</p> <p>Conclusions</p> <p>Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.</p

A randomised, phase II, unblinded trial of an Exercise and Nutrition-based Rehabilitation programme (ENeRgy) versus standard care in patients with cancer: feasibility trial protocol

Acknowledgements - The authors would like to thank Marie Curie and the Chief Scientist Office (UK) for funding this work (MCRGS-07-16-73), as well as acknowledge the support offered from the trial sponsors (ACCORD & NHS Lothian Edinburgh, UK). Also the valued contributions from the Southampton Clinical Trials Unit (UK), the Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, Kings College London (UK) as well as colleagues from different institutes within Edinburgh University (UK). Thanks to all the St Columba’s staff who helped get the trial set up, or assisted with the administration and the smooth running of the trial. Particular thanks to St Columba’s day therapies team especially Yvonne Whitehouse. Thanks to our dedicated ENeRgy clinic volunteers, Gillian Reid and Tommy Dalgleish for their commitment and helping make our participants feel welcomed and at ease, and for keeping the clinics running smoothly. Thanks to the clinical administration team and both community nurse specialist teams who showed great enthusiasm in identifying potential participants. Thanks to Marie Curie Hospice Edinburgh and the support from Dr. Emma Carduff (Marie Curie Glasgow) for their engagement and assistance with the trial. Thanks also to Abbott Nutrition, for supplying the oral nutritional supplements for the trial (ProSure), also for support from the Abbott team, in particular Dr Anne Voss.Erna Haraldsdottir - ORCID: 0000-0002-6451-1374 https://orcid.org/0000-0002-6451-1374Patients are living longer with incurable cancer [1] such that in many cases, cancer is likened to a chronic disease [2, 3, 4]. This development has wide-ranging implications for both patients and wider society, with increased longevity comes increased morbidity and associated socio-economic burden [5, 6]. Primary cost drivers for patients with advanced cancer are hospitalisation, GP and domiciliary visits [7]. Rehabilitation has been advocated as one such way of optimising the function and quality of life in this group of patients [8]; however, the optimal components of a rehabilitation model for patients with incurable cancer remain to be elucidated...The trial was funded by Marie Curie and the Chief Scientist Office (funding reference MCRGS-07-16-73). The funding bodies specified where changes were required to the design of the trial (including incorporating the impact upon carers and any health-economic impact as outcomes of the trial).4pubpub19

Sequential High Pressure Extractions Applied To Recover Piceatannol And Scirpusin B From Passion Fruit Bagasse

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Passion fruit seeds are currently discarded on the pulp processing but are known for their high piceatannol and scirpusin B contents. Using pressurized liquid extraction (PLE), these highly valuable phenolic compounds were efficiently extracted from defatted passion fruit bagasse (DPFB). PLE was performed using mixtures of ethanol and water (50 to 100% ethanol, w/w) as solvent, temperatures from 50 to 70 degrees C and pressure at 10 MPa. The extraction methods were compared in terms of the global yield, total phenolic content (TPC), piceatannol content and the antioxidant capacity of the extracts. The DPFB extracts were also compared with those from non-defatted passion fruit bagasse (nDPFB). Identification and quantification of piceatannol were performed using UHPLC-MS/MS. The results showed that high TPC and piceatannol content were achieved for the extracts obtained from DPFB through PLE at 70 degrees C and using 50 and 75% ethanol as the solvent. The best PLE conditions for TPC (70 degrees C, 75% ethanol) resulted in 55.237 mg GAE/g dried and defatted bagasse, whereas PLE at 70 degrees C and 50% ethanol achieved 18.590 mg of piceatannol/g dried and defatted bagasse, and such yields were significantly higher than those obtained using conventional extraction techniques. The antioxidant capacity assays showed high correlation with the TPC (r > 0.886) and piceatannol (r > 0.772). The passion fruit bagasse has therefore proved to be a rich source of piceatannol and PLE showed high efficiency to recover phenolic compounds from defatted passion fruit bagasse. (C) 2016 Elsevier Ltd. All rights reserved.855158FAPESP [2014/00372-8, 2013/02203-6]CAPES [2952/2011]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES