tbuckley/cabot-search huggingface dataset:
P206 Achieving responsible oxygen prescribing to improve value: london care homes
Authors: C Lock, M Gardner, L Restrick, S Williams, M Buxton, M Haastrup, B Krishek, V Mak, D Roots, I Patel
Journal: Thorax (2016)

<h3>Background</h3> Around 85,000 patients are currently prescribed home oxygen (HO) in England, costing the NHS &gt; £100 million/yr. There are about 11000 HO users in London costing £12 million/yr. Department of Health data suggest 24%–43% of oxygen prescribed is not used/used inappropriately. The aim of this study was to better understand HO prescriptions/use in London nursing/care homes. <h3>Methods</h3> Air Liquide (AL), the London oxygen provider, reviewed their database to identify nursing/residential/care home and hospice residents with an active HO Order Form (HOOF) as of January 2016. Staff education and support was undertaken by the AL respiratory nurse advisor (ALRNA) from Jan–June 2016. Results were reviewed with the London Clinical Oxygen Network. <h3>Results</h3> 245 adult patients with a HO prescription were identified across 155 nursing/residential/care homes and hospices in London (mean age 77, range 22–102 years). Table 1 shows the Clinical codes on the HOOFs. The indication for oxygen was unknown in 52 (21%). HO prescription ranged from 0.5–15 LPM; equipment ranged from oxygen concentrators, ambulatory cylinders (89), static cylinders (22), portable oxygen concentrators (5) and liquid oxygen (2). 168 (68%) patients were underusing oxygen while 38 (15%) were overusing. 36 (14%) patients were not using their oxygen at all. Only 90 (36%) patients had a HOOF dating from 2016; 157 (64%) had a HOOF more than a year old. Issues noted included lack of information as to indication for HO and who to contact for guidance, absence of clinical directives from prescribers resulting in ‘PRN’ oxygen use and training needs around storage/use of oxygen equipment. <h3>Conclusion</h3> A sizable number of nursing/residential/care home and hospice residents in London are currently prescribed oxygen which is being over/under or inappropriately used without ongoing specialist support/review. For 1 in 5 patients the clinical indication is unknown. New oxygen prescriptions for ‘nursing home’ patients should include guidance on use, staff training and ongoing support. These data exemplify broader issues relating to a lack of commissioned HO pathways and the need for commissioned Home Oxygen Review (HOS-R) services across all CCGs to keep patients safe, maximise patient benefit and reduce waste.
Abstract A18: Targeting the MNK kinases for the treatment of NF1-mutant cancers
Authors: Rebecca Lock, Rachel Ingraham, Ophélia Maertens, Bruce Konicek, Sau-chi Yan, Jeremy Graff, Karen Cichowski
Journal: Clinical Cancer Research (2017)

Abstract NF1 mutant cancers are driven by excessive Ras signaling; however, there are currently no effective therapies for these or other Ras-dependent tumors. While MEK inhibitors promote regression of NF1-deficient premalignant lesions, they are ineffective in advanced cancers. Our lab and others have shown that the addition of a PI3K/AKT/mTORC1 inhibitor can co-operate with MEK inhibition to elicit tumor regression in pre-clinical Ras-driven tumor models; however, one concern is that these combinations might not be tolerated in the clinic due to toxicity. Therefore our goal has been to identify more refined, cancer-specific signaling nodes within these pathways. Here we find that eIF4E, a key downstream effector of mTORC1, is constitutively phosphorylated by the MAP kinase-interacting kinases (MNK1 and 2) in NF1 mutant malignant peripheral nerve sheath tumors (MPNSTs). Moreover, we find that combined genetic or chemical suppression of MNK kinases can cooperate with MEK inhibition to reduce cell viability to a similar extent as broad mTOR inhibition. Surprisingly, we find that the MNK kinases are important, previously unrecognized direct targets of the receptor tyrosine kinase inhibitor cabozantinib. Furthermore, we find that cabozantinib but not a more selective MET inhibitor kills NF1-deficient tumor cells when combined with MEK inhibition, and does so in part via eIF4E phosphorylation inhibition. Finally, we show that combining cabozantinib and MEK inhibitors triggers dramatic tumor regression in an aggressive genetically engineered mouse model of MPNSTs. Together, these results identify MNK/eIF4E as a targetable signaling axis when combined with MEK inhibition in these Ras-driven tumors and highlight the utility of both drug repurposing and developing more specific MNK inhibitors for these and other malignancies. Citation Format: Rebecca Lock, Rachel Ingraham, Ophélia Maertens, Bruce Konicek, Sau-chi Yan, Jeremy Graff, Karen Cichowski. Targeting the MNK kinases for the treatment of NF1-mutant cancers. [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 A18.
A Novel Murine GITR Ligand Fusion Protein Induces Antitumor Activity as a Monotherapy That Is Further Enhanced in Combination with an OX40 Agonist
Authors: Rebecca Leyland, Amanda Watkins, Kathy A. Mulgrew, Nicholas Holoweckyj, Lisa Bamber, Natalie J. Tigue, Emily Offer, John Andrews, Li Yan, Stefanie Mullins, Michael D. Oberst, Jane Coates Ulrichsen, David A. Leinster, Kelly McGlinchey, Lesley Young, Michelle Morrow, Scott A. Hammond, Philip Mallinder, Athula Herath, Ching Ching Leow, Robert W. Wilkinson, Ross Stewart
Journal: Clinical Cancer Research (2017)

Purpose: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy.Experimental Design: The EC50 value of the mGITRL-FP was compared with an anti-GITR antibody in an in vitro agonistic cell-based reporter assay. We assessed the impact of dose, schedule, and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared with an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models. Combination of the mGITRL-FP with antibodies targeting PD-L1, PD-1, or CTLA-4 was analyzed in mice bearing CT26 tumors.Results: The mGITRL-FP had an almost 50-fold higher EC50 value compared with an anti-murine GITR antibody. Treatment of CT26 tumor-bearing mice with mGITRL-FP-mediated significant antitumor activity that was dependent on isotype, dose, and duration of exposure. The antitumor activity could be correlated with the increased proliferation of peripheral CD8+ and CD4+ T cells and a significant decrease in the frequency of intratumoral Tregs. The combination of mGITRL-FP with mOX40L-FP or checkpoint inhibitor antagonists enhanced antitumor immunity above that of monotherapy treatment.Conclusions: These results suggest that therapeutically targeting GITR represents a unique approach to cancer immunotherapy and suggests that a multimeric fusion protein may provide increased agonistic potential versus an antibody. In addition, these data provide, for the first time, early proof of concept for the potential combination of GITR targeting agents with OX40 agonists and PD-L1 antagonists. Clin Cancer Res; 23(13); 3416-27. ©2017 AACR.
In Vivo Response to Cytarabine Chemotherapy Uncovers the Role of the Oxidative and Energetic Metabolism in the Chemoresistance of Human Primary AML Stem Cells
Authors: Nesrine Aroua, Jean-Emmanuel Sarry, Fabienne De Toni, Robin Carson, Francois Vergez, Estelle Saland, Mayumi Sugita, Martin Carroll, Christian Recher, Gwenn Danet
Journal: Blood (2015)
P1.03-026 Measurement of Pulmonary Artery on CT to Predict Acute Exacerbation of Interstitial Pneumonia after Pulmonary Resection for Lung Cancer
Authors: Akiko Ui, Masashi Kobayashi, Yu Kawada, Yasuyuki Kurihara, Yusuke Sugita, Sachiko Kumazawa, Chihiro Takasaki, Hironori Ishibashi, Kenichi Okubo
Journal: Journal of Thoracic Oncology (2017)
P3.03-050 Prognostic and Predictive Factors Affecting Course of Disease and Survival in Malignant Pleural Mesothelioma
Authors: Angela De Palma, Michele Loizzi, Elena Prisciandaro, Ondina Pizzuto, Federica Pezzuto, Alessandra Punzi, Anna Scattone, Andrea Marzullo, Gabriella Serio
Journal: Journal of Thoracic Oncology (2017)
P2.04-008 Diagnostic Performance of PET-CT for Anterior Mediastinal Lesions - The DECiMaL Study
Authors: Chiara Proli, Paulo De Sousa, Simon Jordan, Vladimir Anikin, Susannah Love, Michael Shackcloth, Nikolaos Kostoulas, Kostas Papagiannopoulos, Yama Haqzad, Mahmoud Loubani, F. Sellitri, Felice Granato, A. Bush, Adrian Marchbank, Swetha Iyer, Marco Scarci, Eric Lim
Journal: Journal of Thoracic Oncology (2017)
Salvage Therapy with Bortezomib Plus Lenalidomide for Relapsed/Refractory Mantle Cell Lymphoma: Initial Results of a Phase II Trial (Alliance/CALGB 50501)
Authors: Vicki A. Morrison, Sin-Ho Jung, Jeffrey Johnson, Ann LaCasce, Kristie A. Blum, Nancy L. Bartlett, Bruce D. Cheson
Journal: Blood (2012)
Endoscopic management of recurrent pyogenic cholangitis
Authors: Aleksey Novikov, Nikhil Kumta, Kunal Karia, Porfirio Reinoso, Benjamin Samstein, Michel Kahaleh
Journal: Endoscopy (2017)

Recurrent pyogenic cholangitis (RPC) can be challenging to manage. The case presented illustrates all the endoscopic techniques available to us to manage this difficult entity.
PUB051 Comprehensive Analysis of Chromosomal Alterations Involving CDKN2A and 22q in Malignant Pleural Mesothelioma
Authors: Assunta De Rienzo, Mary Dao, Nhien Dao, Paola Dal Cin, Adrian Dubuc, Jonathan Fletcher, William Richards, Raphael Bueno
Journal: Journal of Thoracic Oncology (2017)
Mesenchymal Stromal Cells Promote a Sustained Increase of the CD69 Marker on Activated CD3+ Lymphocytes: Potential Immunomodulatory Role
Authors: Felipe Saldanha Araujo, Rodrigo Alexandre Panepucci, Kelen Cristina Farias, Amelia G Araujo, Maristela Delgado Orellana, Camila Branquinho Menezes, Patricia bonini Palma, Dimas Tadeu Covas, Marco Antonio Zago
Journal: Blood (2008)
S134 How specific are fluorogenic substrates designed to analyse active protease biomarkers of respiratory disease?
Authors: CM Robb, TEG Ferguson, KL Moffitt, DG Downey, DF McCafferty, D Ribeiro, SL Martin, B Walker
Journal: Thorax (2016)

<h3>Introduction</h3> Active proteases, such as neutrophil elastase (NE) and matrix metalloproteinases (MMPs), have been established as inflammatory biomarkers in lung diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Therefore, biological samples collected during clinical investigations are often analysed using fluorogenic substrates to determine protease activity and identify correlations with clinical and/or demographic parameters. Due to the nature of these diseases, samples often contain numerous active proteases from both human and bacterial origins which collectively have significant substrate crossover. This study investigates the ability of fluorogenic substrates to distinguish between proteases in complex clinical samples and provide an indication of the predictive capability of this assay type. <h3>Methods</h3> Expectorated sputum was randomly collected from patients with CF who were hospitalised for an acute exacerbation. Samples were processed within 30 minutes of collection, and the aqueous sol recovered, pooled, aliquoted and stored at −80°C until analysis. The capacity of sputum proteases to hydrolyse fluorogenic substrates with and without the presence of inhibitors specific for serine (multiple subclasses), metallo and cysteine proteases was examined. Fluorogenic substrates analysed include those for various inflammatory proteases including elastase-like (MeOSuc-AAPV-AMC), MMPs (MCA-PLGL-Dpa-AR-NH2), trypsin-like (Z-GGR-AMC) and chymotrypsin-like (Suc-AAPF-AMC). Substrate hydrolysis by a relevant recombinant enzyme (± inhibitors) was analysed as a control. <h3>Results</h3> Data analysis indicates that alternative enzymes actively hydrolyse substrates designed to be specific for one group of proteases. Inhibitors specific for metallo, trypsin-like, chymotrypsin-like and cysteine proteases all decreased elastase-like substrate turnover (∼10–50%). A similar trend was seen for chymotrypsin-like substrate using metallo, trypsin-like and elastase-like protease inhibitors (∼10–40%). <h3>Conclusion</h3> This investigation has suggested that there is significant non-specific hydrolysis and cross-reactivity when fluorogenic substrates are utilised to measure active proteases in complex biological samples. Thus, using such fluorogenic substrates may produce elevated readings, impacting on the accuracy of results when such assays are used for clinical or research purposes.
The Use of Biomarker Ferritin and Albumin As Well As HCT-CI, but Not PAM, Was Predictive of Suvival, Gvhd and, Relapse in Myeloid Malignancies
Authors: Gary Simmons, Allison F. Scalora, Roy T Sabo, Catherine H. Roberts, William B. Clark, Harold M. Chung, Amir A. Toor, John M. McCarty
Journal: Blood (2015)
M8 Asthma management in an inner-city teaching hospital emergency department: real-life after national review of asthma deaths (NRAD)
Authors: FR Ali, Z Mangera, A Downes, S Obaray
Journal: Thorax (2016)

<h3>Background</h3> The National Review of Asthma Deaths (NRAD) made multiple recommendations in the form of quality indicators linked to improving care of asthma patients in light of a review of all asthma deaths.<sup>1</sup> We undertook an audit to establish the degree to which a busy Emergency Department in inner London adheres to these. <h3>Method</h3> Patients admitted in the month of June 2015 with an asthma related admission were identified via the coding department. This list was reviewed to include those patients confirmed to have an acute asthma admission and seen and discharged directly from the ED department (including the short stay ED ward). The electronic records of those included were reviewed using a data collection form relating to the NRAD quality indicators. <h3>Results</h3> A total of 42 patients were included. Our findings included the following: 83% had mild or moderate severity, the remainder having acute-severe. Almost one third of patients did not have their peak flow documented on arrival, 76% did not have their usual best or predicted best documented and 66% did not have a discharge peak flow documented. There was no documentation if any patient had been provided with a personal asthma action plan (PAAP). Checking of inhaler technique was only documented for 14% of patients. One third of patients were presenting for the 2nd or more time with acute asthma. Finally only 3 patients had a recommendation for GP follow up but no timeframe was suggested. <h3>Discussion</h3> Simple measurements and interventions were omitted in a significant number of patients, highlighting the need for improvement. Some of these were straightforward such as more meticulous recording of peak flow. Others may have reflected lack of competency in the healthcare professional e.g. inhaler technique training and PAAP. The development of an asthma care pathway that captures the essence of the NRAD quality indicators, together with staff training, is urgently required to ensure that EDs lead the way in reducing the morbidity and mortality associated with acute asthma presentations. <h3>Funding </h3> Sponsorship for the audit was provided by Novartis. <h3>Reference</h3> Royal College of Physicians. <i>Why Asthma still kills, The National review of asthma deaths. Confidential enquiry report</i>, 2014.
Anti-Thrombotic Action of DZ-697b, a Novel Anti-Platelet Agent, on Photochemically Induced Thrombosis with Lower Bleeding Risk in Guinea Pigs.
Authors: Tomoko Shibutani, Takako Iijima, Yuki Kaneda, Sumie Muramatsu, Yoshiyasu Ogihara, Toshiro Shibano
Journal: Blood (2005)
OA03.03 JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti-PD-L1) as First-Line Treatment in Patients with Advanced NSCLC
Authors: Guy Jerusalem, Franklin Chen, David Spigel, Nicholas Iannotti, Edward Mcclay, Charles Redfern, Jaafar Bennouna, Matthew Taylor, Howard Kaufman, Karen Kelly, Vikram Chand, Anja Von Heydebreck, Claire Verschraegen
Journal: Journal of Thoracic Oncology (2017)
P52 COPD and periodontitis: co-morbidity yes or no?
Authors: S Hobbins, A Usher, S Parmar, R Stockley
Journal: Thorax (2016)

<h3>Introduction</h3> Chronic obstructive pulmonary disease (COPD) is an inflammatory disease associated with comorbidities including periodontitis.<sup>1–2</sup> Periodontitis is characterised by plaque build-up, anaerobic bacterial overgrowth and gingival inflammation which promotes recruitment and activation of neutrophils leading to alveolar bone destruction and tooth loss. However, the characterisation of periodontitis varies between studies causing some uncertainty of any association. <h3>Aim</h3> To determine whether clinical indices of periodontitis affects its prevalence in COPD patients with and without Alpha-1-antitrypsin deficiency (AATD) and any association with lung function. <h3>Methods</h3> 108 COPD and 63 PiZ AATD patients underwent dental examinations and lung function testing as part of an EU FP7 cross sectional study. Varying definitions of periodontitis used in previous publications were applied; including criteria from the Centres for Disease Control and Prevention in collaboration with the American Academy of Periodontology CDC-AAP (CDC-AAP) and 5th European Workshop in Periodontology. Periodontal indices of probing depth (PD – depth from gingival margin to the base of periodontal pocket) and clinical attachment level (CAL – distance from the cemento-enamel junction to the gingival margin plus probing depth) were then compared to lung function parameters. <h3>Results</h3> The prevalence of periodontitis varied depending on the definition used. Prevalence ranged from 0.7–98.6% for the whole cohort, with the lowest prevalence for average probing depth &gt;4 mm, but CDC-AAP criteria gave a prevalence of 84.2% and 98.6% with the 5th European workshop criteria. Lung function was significantly correlated with indices of periodontitis for AATD patients; see Table. <h3>Conclusions</h3> The prevalence of periodontitis depends on the definition used. PD is a marker of current status, whilst CAL represents cumulative disease activity, rather like current lung function parameters. Periodontal indices are correlated with lung function parameters in AATD patients which could reflect the inflammatory and predominantly neutrophilic pathophysiology leading to excessive tissue destruction in both diseases. <h3>References</h3> Shen TC, <i>et al</i>. Risk of Periodontal Diseases in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Population-based Cohort Study. <i>Medicine (Baltimore)</i> 2015;<b>94</b>(46):e2047. Chung JH, et al. J Periodontol2016:1–11.
A Clinical Test for the Identification of Amyloid Proteins in Biopsy Specimens by a Novel Method Based on Laser Microdissection and Mass Spectrometry.
Authors: Julie A. Vrana, Jeffrey D. Gamez, Jason D. Theis, Timothy B. Plummer, Robert H. Bergen, Steven R. Zeldenrust, Paul J. Kurtin, Karen L. Grogg, Ahmet Dogan
Journal: Blood (2007)
P2.05-008 Can Stereotactic Body Radiation Therapy (SBRT) Be an Effective Treatment for Lung Metastases From “Radioresistant” Histologies?
Authors: Davide Franceschini, Fiorenza De Rose, Luca Cozzi, Tiziana Comito, Ciro Franzese, Pierina Navarria, Giuseppe D'Agostino, Marta Scorsetti
Journal: Journal of Thoracic Oncology (2017)
Regional Systems of Care Demonstration Project
Authors: James G. Jollis, Hussein R. Al-Khalidi, Mayme L. Roettig, Peter B. Berger, Claire C. Corbett, Harold L. Dauerman, Christopher B. Fordyce, Kathleen Fox, J. Lee Garvey, Tammy Gregory, Timothy D. Henry, Ivan C. Rokos, Matthew W. Sherwood, Robert E. Suter, B. Hadley Wilson, Christopher B. Granger
Journal: Circulation (2016)

Up to 50% of patients fail to meet ST-segment-elevation myocardial infarction (STEMI) guideline goals recommending a first medical contact-to-device time of <90 minutes for patients directly presenting to percutaneous coronary intervention-capable hospitals and <120 minutes for transferred patients. We sought to increase the proportion of patients treated within guideline goals by organizing coordinated regional reperfusion plans.
Clonal Analysis of Hematopoietic Stem Cells after Serial Transplantation of Animals Receiving MGMTP140K Gene Transduced Cells Following Chemotherapy.
Authors: Stephanie Laufs, Ursula Sorg, Veronika Kleff, Laila Gao, Michael Flasshove, W. Jens Zeller, Thomas Moritz, Stefan Fruehauf
Journal: Blood (2004)
Breast cancer control in Iran: Specialized breast unit/national screening: Which one is the urgent priority?
Authors: Mojgan Kalantari, Azadeh Joulaee, Maryam Kadivar, Soodabeh Joolaee, Naser Bahrani
Journal: Journal of Clinical Oncology (2012)

29 Background: Rapid correct diagnosis and treatment is the key point in breast cancer control worldwide. Though screening decreases mortality, due to high cost, the need for enough imaging centers and radiologists actually is not affordable for many populated low resource countries. Specialized Breast Unit is a cost-effective program. While increasing the accuracy and quality, the total cost of diagnosis and treatment is significantly decreased. The more there is limitation of budget, the more it is important to go through this program as an urgent act for breast cancer control. In this study we try to show the actual problems of breast cancer in Iran and the efficacy of Specialized Breast Unit to solve them. Methods: All published data about breast cancer in Iran are reviewed since 2001 to 2012 to list the problems. Then the workflow and outcome of our unit between 2003 to 2012 with total 60, 021 visits are analyzed to show how does it help to solve these problems. Results: Younger age, late presentation, delayed diagnosis, and small numbers of nonpalpable lesions are the major features. Diagnosis is based on excisional/incisional biopsy or frozen section. Mastectomy and axillary dissection is the dominant approach. Sentinel node biopsy, reconstruction and screening are offered in few centers. Multidisciplinary approach in specialized breast unit provides rapid assessment of breast symptoms with correct pre-operative imaging and trucut biopsy for diagnosis. This results in tailored surgery (conservative, mastectomy with or without immediate reconstruction) and sentinel node biopsy for all eligible cases. Team work has decreased the number of visits and surgeries. Conclusions: If screening as the standard for early detection in asymptomatic women is considered as an option, Specialized Breast Unit is an obligation for correct diagnosis and treatment of both symptomatic and asymptomatic breast cancers as a life threatening disease. It is cost effective and helps to shift from dominant Halstead concept through international standards even in low resource countries. Without these referral units no attempt can be done for breast awareness programs, training, and further screening.
P1.03-080 The SUVmax Ratio of Two Tumors on PET/CT May Differentiate Separate Primary Lung Cancers and Intrapulmonary Metastases
Authors: Yi Liu, Yanhua Tang, Xiangyang Chu, Zhiqiang Xue, Ping Yang, Po Zhao, Jie Gao, Guangyu Ma
Journal: Journal of Thoracic Oncology (2017)