tbuckley/cabot-search huggingface dataset:
P1.08-036 Thoracotomy and VATS-Surgery in Local Non-Small Cell Lung Cancer: Differences in Long-Term Health Related Quality of Life
Authors: Ville Rauma, Saana Andersson, Jari Räsänen, Harri Sintonen, Jarmo Salo, Ilkka Ilonen
Journal: Journal of Thoracic Oncology (2017)
PUB031 PRIMAL: A Phase 1b Study of PEGPH20 plus Docetaxel in Patients with Previously Treated Hyaluronan (HA)-High Advanced NSCLC
Authors: Megan Baumgart, Lyudmila Bazhenova, Daniel Haggstrom, Joaquina Baranda, Chandra Belani
Journal: Journal of Thoracic Oncology (2017)
P207 Self-fill oxygen systems – benefits for patients, healthcare providers and the environment
Authors: P Murphie, S Little, J Setters, N Hex
Journal: Thorax (2016)

<h3>Introduction</h3> ‘Non-delivery’ Home oxygen concentrator systems that allow self-filling of ambulatory oxygen (AO) cylinders are emerging. They offer a relatively unlimited supply of AO in suitably assessed people who require Long term oxygen therapy (LTOT) with the proviso that they can use these systems safely and effectively, thus allowing users of LTOT to be self-sufficient and facilitating longer periods of time away from their home. <h3>Methods</h3> A national review of the home oxygen service in Scotland was undertaken resulting in consolidation of all home oxygen delivery systems under a single contractor with the transition to this new service delivered over 2013. A health economics analysis was conducted following the transition to compare the differences between the previous conventional AO cylinder home delivery service and the HomeFill (HF) system. <h3>Results</h3> Conservative calculations indicate a cost for 3 AO cylinders of about £84 per week, or £4247 per year, compared with a cost for HF of £920 per annum, giving a benefit of around £3344 for each patient. The costs savings related to reduced travel and delivery in 1213 HF users compared to the AO cylinder delivery model is 1.25 million Km’s and the estimated carbon emission (CO<sub>2</sub>e) reduction for the HF system is 261.29 tonnes of CO<sub>2</sub>e. <h3>Conclusion</h3> Evidence is emerging that ‘Self-fill’/‘non-delivery’ oxygen systems can meet the AO needs of many patients using LTOT and can have a positive impact on quality of life; increased time spent away from place of residence and can offer significant financial savings to health care providers. Even with conservative estimates in the health economics analysis, the provision of the HF system to around 1000 patients saves about £1.67 million per year in Scotland. Self-fill oxygen delivery systems have been available in the UK for &gt;5 years and whilst one could argue for a larger randomised controlled trial, the authors would propose that with the available evidence, particularly the financial impact, it should be more widely utilised.
Anchoring the snare tip by means of a small incision facilitates en bloc endoscopic mucosal resection and increases the specimen size
Authors: Jérémie Jacques, Romain Legros, Aurélie Charissoux, Jérôme Rivory, Thierry Ponchon, Denis Sautereau, Mathieu Pioche
Journal: Endoscopy (2017)

Endoscopic mucosal resection (EMR) allows curative resection of superficial colorectal neoplasms up to 2 cm in diameter. En bloc resection is generally not possible for larger lesions and for some smaller very flat lesions because of the difficulty in capturing them appropriately [1]. Piecemeal EMR is possible for larger colonic lesions, but carries a high risk (~20 %) of recurrence [2]. Hybrid procedures, involving use of an endoscopic submucosal dissection (ESD) device to make mucosal incisions around the lesion, have been proposed for the colon, to increase the lesion size for which en bloc snare resection is possible, and to achieve snare resection in all cases of very flat lesions. However, in the colon, ESD is particularly technically challenging [3], and mucosal incision can be quite time-consuming and risky in nonexpert hands in this location because of the folded anatomy and the bowel movement. Moreover the ESD devices are expensive, with no specific reimbursement in most European countries.
S46 Neutrophil vascular endothelial growth factor (VEGF) as a driving force for angiogenesis in bronchiectasis?
Authors: CC Cole, SC Carnell, KJ Jiwa, JB Birch, KH Hester, CW Ward, JS Simpson, ADS De Soyza
Journal: Thorax (2016)

<h3>Introduction</h3> Bronchiectasis (BR) in a pulmonary disease thought to involve a characteristic dilation of the bronchi resulting from a cycle of airway infection and inflammation. This inflammation is believed to be driven by neutrophils, which are present in the BR lung in high number. Vascular endothelial growth factor (VEGF) is a pro-angiogenic cytokine that may be upregulated in BR and could contribute towards creating a pro-angiogenic airway environment by supporting neutrophil migration into the airway tissue, however this has yet to be shown. <h3>Aims</h3> 1) Examine the BR airway for any indications of increased angiogenesis, 2) Assess the ability of neutrophils to secrete VEGF upon stimulation <i>in vitro</i>, 3) Evaluate sera/sputa samples VEGF concentration to determine if VEGF could act as a biomarker for BR severity. <h3>Methods</h3> Healthy volunteer (HV) and BR endobronchial biopsies were stained with a HRP conjugated anti-CD31 antibody, allowing blood vessels to be counted in a blinded manner. Peripheral blood neutrophils isolated from HV were stimulated (e.g. with TNF-α or bacterial PAMPs) for 4 hours, VEGF levels in supernatants were then quantified using ELISA. A VEGF ELISA was also used to determine VEGF concentration in sera and sputa samples from BR patients (n = 115), categorised by bronchiectasis severity index (BSI) scores and sera samples from HV controls (n = 26) <h3>Results</h3> Endobronchial biopsies from BR airways had a significantly (p &lt; 0.05) higher number of blood vessels per mm of basement membrane than HV samples (18 and 9 blood vessels/mm basement membrane respectively). Stimulation of HV neutrophils with a variety of molecules (PMA, fMLP, LPS, TNF-α etc.) resulted in a significant increase in VEGF secretion compared to unstimulated (p &lt; 0.05). Although elevated VEGF was found in some patient samples there was no significant correlation between sera/sputa VEGF and individual patient BSI scores. <h3>Conclusion</h3> The increased presence of vascular tissue seen in BR could indicate a pro-angiogenic airway environment in BR. The in vitro data collected also show that a variety of stimulants can initiate secretion of VEGF by neutrophils. However, our data does not suggest that VEGF levels in sera or sputa can be used to predict disease severity.
Abstract B11: HER2 regulates PARP-1 expression via the let-7a microRNA in HER2+ breast cancer
Authors: Monicka Wielgos, Rajani Rajbhandari, Susan Nozell, Shi Wei, Eddy S. Yang
Journal: Clinical Cancer Research (2017)

Abstract Background: HER2+ breast cancers are sensitive to PARP inhibition and express elevated levels of the PARP-1 protein. However, the mode of regulation of PARP-1 expression by HER2 is not well understood. In this study, we report that the let-7a microRNA is regulating PARP-1 expression at the post-transcriptional level in HER2+ breast cancer cells. Methods: Human HER2+ breast cancer cell lines BT-474 and SKBR3 were used in this study. MDA-MB-231 (non-HER2 expressing breast cancer cells) were also stably transfected with a HER2 wild-type plasmid (231 HER2) or the vector control (231 NEO). Further, to identify candidate microRNAs regulated by HER2 overexpression we used the nCounter miRNA Expression Assay. MicroRNA and mRNA expression were validated via qRT-PCR analysis in breast cancer cell lines or patient primary tumors. Cells were also transfected with a HER2 siRNA, a let-7a mimic, and an inhibitor of let-7a as well as their respective controls. Western blot analysis and firefly luciferase assays were used to determine whether the 3'UTR of PARP1 was being directly targeted by the let-7a microRNA. Results: HER2 did not regulate PARP-1 at the mRNA level but increased PARP-1 protein in HER2+ breast cancer cells. Specifically, ectopic HER2 overexpression correlated with increased PARP-1 protein levels in the 231 HER2 cell line. Conversely, silencing HER2 reduced PARP-1 protein levels in the BT-474 and SKBR3 cell lines. NanoString nCounter analysis revealed that the HER2+ breast cancer cell lines expressed low levels of the let-7a microRNA. Further, let-7a expression was upregulated after HER2 knockdown in the two native HER2+ breast cancer cell lines. The let-7a mimic also reduced both PARP1 protein expression and luciferase activity in the 231 HER2 and BT-474 cell lines, whereas the let-7a inhibitor reversed these effects in the 231 NEO cell line. Importantly, HER2+ breast tumors expressed higher levels of PARP-1 and lower levels of let-7a; whereas, the HER2- breast tumors expressed lower levels of PARP-1 and higher levels of let-7a. Conclusions: These results suggest that let-7a regulates PARP-1 expression in HER2+ breast tumors. Let-7a may also be a potential therapeutic target and predictive biomarker of PARPi sensitivity in HER2+ breast cancer patients. Citation Format: Monicka Wielgos, Rajani Rajbhandari, Susan Nozell, Shi Wei, Eddy S. Yang. HER2 regulates PARP-1 expression via the let-7a microRNA in HER2+ breast cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B11.
A Prognostic Factor Under the Surgeon’s Control
Authors: Suguru Yamashita, Claudius Conrad
Journal: JAMA Surgery (2017)

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P241 Eosinophil apoptosis is negatively associated with body mass index in asthma
Authors: A Thavakumar, AKA Wright, MA Ghebre, T Thornton, CE Brightling
Journal: Thorax (2016)

<h3>Background</h3> Obese asthmatics are known to have reduced eosinophils in sputum, as well as poor control of asthma symptoms.<sup>1</sup> We have shown that, compared to non-obese patients, there is an elevated number of eosinophils in the airway submucosa of obese asthmatic patients.<sup>2</sup> This study aims to determine whether a differential susceptibility to apoptosis, between obese and non-obese patients, could contribute to these clinical observations. <h3>Method</h3> Patients with a clinical diagnosis of asthma were recruited (n = 28) and consented at Glenfield Hospital for blood donation to study eosinophil apoptosis; the patients recruited had varying severities of asthma and BMI. Eosinophils were isolated from whole blood by negative immunomagnetic selection using CD16 microbeads to a purity of mean ± SD 95.7% (± 4). Purified eosinophils (Time 0) were placed into culture in RPMI (1640 + GlutaMAX-1 supplemented with 10% FBS and 1% penicillin and streptomycin) and harvested at 17 and 21 hours later to measure apoptosis by flow cytometry using Annexin V and Propidium Iodide (Becton Dickinson). Cells were considered apoptotic if they were Annexin V positive/PI negative and reported as a percentage of total eosinophils. <h3>Results</h3> At 0 hours, the mean% of annexin V positive cells was 0.47% and there was no significant association with BMI (r = −0247, p value = 0.245). At 17 and 21 hours there were 12.68% and 21.0% annexin V positive cells, respectively, and we noted a significant negative Pearson’s correlation between eosinophil apoptosis and BMI at time 17 (r = −0.449; p = 0.028) and time 21 (r = −0.448; p = 0.028). These correlations were independent of lung function, steroid medication and percentage eosinophil purity. <h3>Conclusion</h3> Eosinophils from obese asthmatic patients are less susceptible to apoptosis compared to those from non-obese patients. This may contribute to the differential presence of eosinophils in the lamina propria and airway of obese patients compared to non-obese individuals. <h3>References</h3> Haldar P, Pavord ID, Shaw DE, <i>et al</i>. Cluster analysis and clinical asthma phenotypes. <i>Am J Respir Crit Care Med</i> 2008;<b>178</b>(3):218–224. Desai D, Newby C, Symon FA, <i>et al</i>. Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. <i>Am J Respir Crit Care Med</i> 2013;<b>188</b>(6):657–663.
P132 Factors associated with near-fatal asthma requiring extracorporeal membrane oxygenation
Authors: S Patel, NM Shah, L Camporota, N Barrett, BD Kent, DJ Jackson
Journal: Thorax (2016)

<h3>Introduction</h3> Until recently the ceiling of management for life-threatening asthma exacerbation involved intubation and mechanical ventilation. In many cases these measures were inadequate given the degree of airflow obstruction. The emergence of extracorporeal membrane oxygenation (ECMO) has offered a management strategy for these otherwise fatal events, however there is a dearth of published data regarding ECMO use in asthma. We sought to investigate factors associated with the requirement for and success of using ECMO in near-fatal asthma. <h3>Methods</h3> Patients requiring mechanical ventilation (MV) and/or ECMO for acute asthma at our tertiary centre between 2011–2015 were retrospectively identified from an electronic database. <h3>Results</h3> Seventy-five patients were identified. 56/75 (75%) received MV and 19/75 (25%) received ECMO. The proportion of females in the ECMO group was significantly greater than in the MV group (68% vs. 29%, P = 0.002). Median age in the ECMO group was lower (24 years old vs. 41, P = 0.003). There was no statistically significant difference in the smoking history or 30- and 90-day survival between ECMO and MV groups. Bronchoscopy was undertaken in all ECMO and in 28/56 MV patients on admission. Respiratory viruses were identified in significantly more patients requiring ECMO than MV (58% vs. 29%, P = 0.04). The proportion of patients with positive bacterial and fungal cultures was not significantly different between groups. In a subgroup analysis there was no difference in duration of ECMO or MV between patients with and without positive virology. <h3>Conclusion</h3> In a single regional intensive care unit we demonstrate that requirement for ECMO due to acute asthma is associated with female gender, younger age and positive virology on admission. To our knowledge, this is the first case series analysing factors relating to ECMO use in asthma in the United Kingdom. It highlights the role of respiratory viruses in near-fatal exacerbations and the need for novel anti-viral approaches to reduce morbidity and mortality. Further research is needed in this population to identify whether differences in underlying inflammatory mechanisms exist that may explain the development of such severe events.
P68 To screen or not to screen for Obstructive Sleep Apnoea (OSA) pre-operatively?
Authors: CD Turnbull, D Ball, ML Estevez, H Du Plessis, M Hardinge, A Nickol
Journal: Thorax (2016)

<h3>Background</h3> Anaesthesia worsens OSA, and may lead to respiratory and cardiac complications. Three critical incidents have occurred in the Oxford Hospitals in recent years. OSA is very common at around 5–25%, but half the cases are not diagnosed. So should we screen for OSA pre-operatively? <h3>Audit</h3> Over 9 months from July 2015 all patients completed a STOP-BANG questionnaire in a gynaecology pre-operative clinic. Those with snoring and a score of 3 or greater were referred for a sleep study. Data is presented for 102 patients (100 female; 2 transgender) with a mean ± SD age of 55.7 ± 11.4 yrs, BMI 35.8 ± 7.6 kg/m<sup>2</sup> and collar size 40.0 ± 4.8 cm. The rate of non-attendance was high at 19/102 (19%), with those with a lower STOP-BANG score being more likely not to attend. Of those undergoing a sleep study, a new diagnosis was made in 53/83 (52%) patients. Symptoms and OSA/hypoventilation were sufficient for CPAP to be started in 23 patients and NIV in 1 (29% of those screened), with positive diagnoses more likely with higher STOP-BANG scores. The median (IQR) time to CPAP set-up was 80 (52, 100) days, thus a substantial proportion of patients had surgery before treatment. <b>How should we ensure anaesthetic safety for patients at risk of OSA?</b> Completing a sleep study and establishing OSA patients on CPAP prior to surgery would significantly slow the surgical pathway, and there is no evidence that this would improve outcome. However it seems sensible for anaesthesia of all patients deemed <i>at risk </i>of OSA (STOP-BANG 3+) to be managed with special precautions. We pragmatically recommend that all patients found to have a STOP-BANG score of 5+ or strong clinical suspicion of OSA, who are undergoing major surgery AND in whom it is reasonable to delay surgery, are referred for a sleep study prior to surgery. Patients with a STOP-BANG of 3+ not falling into this category should be informed they are at risk of OSA, and advised to seek a referral from their GP to the sleep clinic if they find symptoms of sleepiness troublesome.
P2.06-010 AZD9291 as 1st-Line Therapy for EGFR Mutant NSCLC Patients with Concomitant Pretreatment EGFR T790M Mutation. The AZENT Study
Authors: Niki Karachaliou, Daniela Morales-Espinosa, Miguel Angel Molina Vila, Javier Garde, Francisco Baron, Manuel Cobo, Guillermo López-Vivanco, Margarita Majem, José Miguel Sánchez, Santiago Viteri, Clara Mayo, Margarida García, Rafael Rosell
Journal: Journal of Thoracic Oncology (2017)
Ethics of the on-call rota
Authors: Daniel Sokol
Journal: BMJ (2017)

Some criteria for selecting cover for rota gaps are more contentious than others



A colleague is sick. Someone is needed to cover for him tomorrow. There are no locums and no volunteers. Who should be selected?

Few issues generate more passion and cause more heartache to doctors than filling a gap in the on-call rota. Over Christmas it is likely that tears have been shed and friendships lost over who would cover the absent colleague.

So what is the fairest way to choose? There are three uncontroversial criteria.

First, the potential candidates must be available. Candidates who are abroad or too far away to make it back in time cannot be selected. As the philosopher Immanuel Kant wrote, “Ought implies can.” …
S19 The impact of clotting abnormalities on the natural history of idiopathic pulmonary fibrosis: an extended follow up of a population based cohort
Authors: V Navaratnam, AW Fogarty, T McKeever, N Thompson, G Jenkins, SR Johnson, M Kumaran, K Pointon, RB Hubbard
Journal: Thorax (2016)

<h3>Background</h3> We have previously demonstrated that people with idiopathic pulmonary fibrosis (IPF) are more likely to have a prothrombotic state and that people with IPF and a prothrombotic state have a higher risk of death at a year’s follow up. The aim of this study was to establish the impact of clotting abnormalities on the natural history of IPF with respect to median survival and lung function (forced vital capacity (FVC)). <h3>Methods</h3> We recruited 211 incident cases of radiologically diagnosed definite or probable IPF and collected longitudinal information on pulmonary function tests done as part of routine care. All participants were tagged with the NHS Information Centre to enable us to collect data on mortality. Blood samples were tested for a prothrombotic state defined as at least one inherited or acquired clotting defect or marker of fibrinolytic dysfunction. Kaplan-Meir methods were used to calculate median survival. Random effects linear regression modelling was used to estimate decline in FVC. <h3>Results</h3> Median follow-up was four years, during which 148 (70.1%) people died. Median survival in those with and without prothrombotic state was 2.7 and 3.7 years respectively (see Figure 1). We found evidence of effect modification between risk of death and follow-up time (p = 0.031). There was more than a three-fold increase risk of death in individuals with IPF and a prothrombotic state in the first half of follow-up (HR 3.36, 95% CI: 1.35 to 8.36), but this was reduced (HR 1.79, 95% CI: 1.08 to 2.94) in the second half. The estimated decline in FVC was 288mls (95% CI: 184 to 392mls) in those with normal clotting and 328mls (95% CI: 269 to 387mls) in those with one or more clotting defects. <h3>Conclusions</h3> Coagulation dysfunction has an adverse impact on the natural history of IPF, both in terms of median survival and lung function decline. Our findings suggest that a prothombotic state may be a useful biomarker to predict prognosis as part of routine care.