tbuckley/cabot-search huggingface dataset:
P32 A new nurse led P.E clinic 2015
Authors: S Goodman
Journal: Thorax (2016)

<h3></h3> In 2015 Dr R Limbrey (Respiratory Physician) and Sr S.Goodman (CNS Pulmonary Vascular Service) set up a Nurse Led (new patient) Pulmonary Embolism (P.E) clinic to support increasing demand on the traditional model of consultant care. We aim for a CNS review of all new patients with P.E at 3 weeks following diagnosis, and provide follow up for 2 years. Previously a CNS led follow up clinic was in place. We aim to provide our patients with early high quality education and information to reduce anxiety, improve physical functioning and quality of life. We suggest that this will reduce perceived ongoing symptoms and lessen follow up requirement. Referral is made electronically. The referral system has been developed as a learning opportunity to enable medical referrers to identify provoking factors and quantify risk associated with the event. The data obtained from referrals provides support for service provision. In 2015, 260 patients were reviewed in the Nurse led clinic, 95 of these were new referrals. Of the 95 new referrals to the service 54 (57%) were provoked by an identifiable transient provoking factor. ESC (2014). Of these 42 (78%) also had persistent risk factors by ESC Unprovoked group: The remaining 41 (43%) had no identifiable transient provoking factor. Of these 32 (78%) did have persistent risk factors as per ESC 2014. We note that 44% of all identified PE patients in this cohort, provoked and unprovoked, had a BMI ≥ 30kg/m<sup>2</sup> In the provoked group 16 new patients were reviewed and discharged after an average of 2.62 appointments per person with an additional telephone review planned at the 2 year point. In the unprovoked group 12 patients have been discharged to date with an average of 3.3 appointments per person with an additional telephone review planned for the 2 year mark. The remainder of these patients can reasonably be expected to be discharged from follow up with similar levels of review. Feedback from our patients has been overwhelmingly positive, most commonly expressed as a significant reduction in anxiety and improvement in quality of life. Unprovoked group:
The CREBBP Acetyltransferase Is a Haploinsufficient Tumor Suppressor in B-cell Lymphoma
Authors: Jiyuan Zhang, Sofija Vlasevska, Victoria A. Wells, Sarah Nataraj, Antony B. Holmes, Romain Duval, Stefanie N. Meyer, Tongwei Mo, Katia Basso, Paul K. Brindle, Shafinaz Hussein, Riccardo Dalla-Favera, Laura Pasqualucci
Journal: Cancer Discovery (2017)

Inactivating mutations of the CREBBP acetyltransferase are highly frequent in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common germinal center (GC)-derived cancers. However, the role of CREBBP inactivation in lymphomagenesis remains unclear. Here, we show that CREBBP regulates enhancer/super-enhancer networks with central roles in GC/post-GC cell fate decisions, including genes involved in signal transduction by the B-cell receptor and CD40 receptor, transcriptional control of GC and plasma cell development, and antigen presentation. Consistently, Crebbp-deficient B cells exhibit enhanced response to mitogenic stimuli and perturbed plasma cell differentiation. Although GC-specific loss of Crebbp was insufficient to initiate malignant transformation, compound Crebbp-haploinsufficient/BCL2-transgenic mice, mimicking the genetics of FL and DLBCL, develop clonal lymphomas recapitulating the features of the human diseases. These findings establish CREBBP as a haploinsufficient tumor-suppressor gene in GC B cells and provide insights into the mechanisms by which its loss contributes to lymphomagenesis.Significance: Loss-of-function mutations of CREBBP are common and early lesions in FL and DLBCL, suggesting a prominent role in lymphoma initiation. Our studies identify the cellular program by which reduced CREBBP dosage facilitates malignant transformation, and have direct implications for targeted lymphoma therapy based on drugs affecting CREBBP-mediated chromatin acetylation. Cancer Discov; 7(3); 322-37. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 235.
Return of elevated blood pressure after withdrawal of antihypertensive drugs.
Authors: Edward Freis
Journal: Circulation (1975)

The rate at which arterial pressure rises after discontinuing active treatment was investigated in a group of 86 hypertensive patients who received treatment with hydrochlorothiazide, reserpine and hydralazine for two years or longer and whose diastolic pressures averaged below 96 mm Hg for the last year of treatment. Sixty patients were assigned double-blind to placebos and 26 were continued on active drugs. Forty-two of the placebo group of patients were removed over an 18 month follow-up because of return of elevated blood pressures, 39 being removed in the first six months. Six patients in the placebo group and none in the treated group were removed because of morbid events. Nine or 15% of the placebo patients remained normotensive. The rate of rise in arterial pressure in the placebo group appeared to be related directly to the height of the pressure prior to initiation of active treatment and inversely to the age of the patients. Serum uric acid fell significantly while serum potassium rose significantly after active treatment was discontinued. The glucose tolerance test changed slightly in a direction toward normal while serum creatinine showed no significant change.
P1.07-035 Circulating Cell-Free Tumor DNA (cfDNA) Testing in Small Cell Lung Cancer
Authors: Daniel Morgensztern, Siddhartha Devarakonda, Ashiq Masood, Saiama Waqar, Alicia Carmack, Kimberly Banks, Richard Lanman, Ramaswamy Govindan
Journal: Journal of Thoracic Oncology (2017)
BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer
Authors: Carlos López-García, Laurent Sansregret, Enric Domingo, Nicholas McGranahan, Sebastijan Hobor, Nicolai Juul Birkbak, Stuart Horswell, Eva Grönroos, Francesco Favero, Andrew J. Rowan, Nicholas Matthews, Sharmin Begum, Benjamin Phillimore, Rebecca Burrell, Dahmane Oukrif, Bradley Spencer-Dene, Michal Kovac, Gordon Stamp, Aengus Stewart, Havard Danielsen, Marco Novelli, Ian Tomlinson, Charles Swanton
Journal: Cancer Cell (2017)

Chromosomal instability (CIN) contributes to cancer evolution, intratumor heterogeneity, and drug resistance. CIN is driven by chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through genomic analysis of colorectal cancers and cell lines, we find frequent loss of heterozygosity and mutations in BCL9L in aneuploid tumors. BCL9L deficiency promoted tolerance of chromosome missegregation events, propagation of aneuploidy, and genetic heterogeneity in xenograft models likely through modulation of Wnt signaling. We find that BCL9L dysfunction contributes to aneuploidy tolerance in both TP53-WT and mutant cells by reducing basal caspase-2 levels and preventing cleavage of MDM2 and BID. Efforts to exploit aneuploidy tolerance mechanisms and the BCL9L/caspase-2/BID axis may limit cancer diversity and evolution.
P1.07-007 Clinical Outcomes of Patients with LS-SCLC Treated with Chemoradiotherapy. Can We Find Candidates for Salvage Surgery?
Authors: Junichi Shimizu, Yuko Oya, Kosuke Tanaka, Chiaki Kondo, Hiromi Furuta, Tatsuya Yoshida, Yoshitsugu Horio, Yukinori Sakao, Yasushi Yatabe, Toyoaki Hida
Journal: Journal of Thoracic Oncology (2017)
Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles
Authors: Alba García-Fernández, Guillermo García-Laínez, María Luisa Ferrándiz, Elena Aznar, Félix Sancenón, María José Alcaraz, José Ramón Murguía, María D. Marcos, Ramón Martínez-Máñez, Ana M. Costero, Mar Orzáez
Journal: Journal of Controlled Release (2017)
OA12.02 Excellent Survival Achieved by Stereotactic Body Radiotherapy for Medically Operable and Young (&lt; 75 Years) Patients with Stage I Lung Cancer
Authors: Hiroshi Onishi, Yoshiyuki Shioyama, Yasuo Matsumoto, Kenji Takayama, Yukinori Matsuo, Akifumi Miyakawa, Hideomi Yamashita, Haruo Matsushita, Masahiko Aoki, Keiji Nihei
Journal: Journal of Thoracic Oncology (2017)
Low Dose Lenalidomide and Dexamethasone Induction Followed by Autologous Transplantation In Untreated Patients with Myeloma Is Associated with High Response Rates and Preservation of CD8, but Not CD4 or NK Cellular Immunity
Authors: Simon J. Harrison, Amit S Khot, Tsin Tsin, Andy Hsu, Karen Chen, Maureen Loudovaris, Paul Neeson, Dominic Wall, Rebecca Sedunary, H. Miles Prince, David Ritchie
Journal: Blood (2011)
P127 Benefits and side effects of nasal irrigation in severe asthma
Authors: A Clarke, A H Mansur
Journal: Thorax (2016)

<h3>Introduction and aim</h3> Rhinosinus disease is common in asthma and causes nasal congestion, post nasal drip and pain. This can lead to altered breathing patterns, particularly mouth breathing which exposes patients airways to cold dehumidified air and may aggravate their asthma. Nasal irrigation is accepted as an appropriate early intervention for managing allergic rhinitis but may be under-utilised in severe asthma. This study aims to evaluate the effects of nasal irrigation in a severe asthma population. <h3>Method</h3> Thirty patients (23 females, mean age 47), with a confirmed diagnosis of severe asthma (22/30 73% atopic) and rhinosinusitis took part in this study, none of the participants had previous nasal irrigation. Patients were taught to irrigate with the netti pot system (0.9%saline), initially 1–2 times each day and to titrate to individual needs. Symptoms were assessed with snott-22 questionnaires before and after three months of treatment, snott scores range from 0–110, a difference of 8.9 points is the minimal change thought to be clinically significant. Data was also collected on ACQ scores, usage, reported benefits and side effects. <h3>Results</h3> 26 patients were using nasal irrigation at three month follow-up, mean initial snott scores were 63.2 ± 22.9 compared to 41.7 ± 26.8 post treatment (p = 0.0001). 69% (18/26) patients showed clinically significant decreased nasal symptoms, with a mean improvement of 33.7 points. 19% (5/26) showed no significant change and 12% (3/26) had a clinically significant increase in nasal symptoms. 88% (23/26) patients felt their nasal symptoms had improved, 62% (16/26) felt their chest symptoms had improved. Mean initial ACQ 3.42 ± 1.39 compared to 2.62 ± 1.58 post treatment (p = 0.01). Usage ranged from BD to 3–5 times per week. 17% (5/30) of patients reported side effects: headache (2) sneezing(1) Nose bleed(1) LBP(1) three patients stopped treatment due to the side effect. <h3>Conclusion</h3> After three months of nasal irrigation 88% of patients reported improved nasal symptoms, 62% reported improved chest symptoms, there were statistically significant improvements in mean snott 22 and ACQ scores. Nasal irrigation is therefore an effective and inexpensive intervention, with few side effects, in the treatment of rhinosinus and related asthma symptoms and should be advocated in severe asthma clinics.
P2.02-037 Final Results of Prospective Phase II Study of Adding Erlotinib to Chemoradiation for patients with Stage III Non-Small-Cell Lung Cancer
Authors: Ritsuko Komaki, Pamela Allen, Xiong Wei, George Blumenschein, Xi Ming Tang, J. Lee, James Welsh, Ignacio Wistuba, Diane Liu, Ray Meyn, Waun Hong
Journal: Journal of Thoracic Oncology (2017)
S108 Low skeletal muscle strength and physical activity are associated with poor outcomes in pulmonary arterial hypertension
Authors: BE Garfield, D Shao, L Parfitt, C Harries, L Price, K Dimopoulos, MI Polkey, P Kemp, SJ Wort
Journal: Thorax (2016)

<h3>Introduction</h3> Skeletal muscle wasting and low physical activity are emerging as important potentially modifiable complications of pulmonary arterial hypertension (PAH). In other conditions, such as COPD and heart failure, low muscle strength and low levels of activity have been shown to be associated with poor outcomes. We aimed to define the association of muscle strength and physical activity with hospital admission rates, long term quality of life and mortality in patients with PAH. <h3>Methods</h3> Twenty-eight patients with PAH had their quadriceps maximal volitional capacity (QMVC), step count, BNP and 6MWD measured. At least 1 year later, these patients’ records were reviewed and data were collected on mortality, transplantation, admission to hospital and quality of life using the EMPHASIS 10 questionnaire. QMVC was normalised to BMI and 24 patients with valid step count data were included in the analysis of activity. Kaplan-Meier plots were constructed to define mortality and ROC analysis was used to demonstrate which factors most closely predicted hospital admission. Pearson correlation was used to define the associations with follow-up quality of life. <h3>Results</h3> Kaplan–Meier plots demonstrated that patients with a QMVC/BMI &lt; 1.1 and those with a step count &lt; 2500 per day were significantly more likely to die or undergo transplant than those above these cut-offs (Figure 1 A and B). ROC analysis showed that a QMVC/BMI &lt;1.5 predicted hospital admission over the follow up period with a sensitivity of 93% and a specificity of 62%. It also demonstrated that QMVC was superior to the 6MWD in predicting hospital admission (AUC 0.83, p = 0.003 vs. AUC 0.73, p = 0.017). Finally QMVC/BMI was significantly correlated to quality of life at follow-up in this cohort (Pearson r = −0.47, p = 0.018). <h3>Discussion</h3> Our data suggests that, like in other chronic conditions, low muscle strength and low physical activity in PAH are associated with poor outcomes. Treatment strategies targeting the muscle and physical activity levels may improve outcomes in terms of both quality of life and mortality.
S79 Reduced CD200 receptor expression on monocytes in sarcoidosis
Authors: SD Fraser, LR Sadofsky, PM Kaye, SP Hart
Journal: Thorax (2016)

<h3>Background</h3> Sarcoidosis is characterised by release of pro-inflammatory cytokines in affected tissues. Lung macrophages, derived from blood monocytes, are potent producers of tumour necrosis factor (TNF) and interleukin-6 (IL-6) which contribute to the formation of sarcoid granulomata. Abnormalities of regulatory pathways that normally act to dampen inflammation could explain the hyper-active immunological state seen in sarcoidosis. The aim of the study was to assess the role of regulatory receptors in modulating monocyte cytokine production in sarcoidosis. <h3>Methods</h3> Patients with sarcoidosis and healthy controls were recruited. Whole blood cytokine release in response to stimuli was measured by ELISA. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was determined using blocking antibodies. <h3>Results</h3> Patients with sarcoidosis had less than half the number of T-lymphocytes in blood compared with healthy controls (p &lt; 0.0001). Despite this, patients with sarcoidosis produced higher concentrations of TNF and IL-6 from whole blood in response to stimulation with phytohaemagglutinin. Kinetic analysis of TNF was consistent with release from monocytes. Expression of the monocyte regulatory receptor CD200R in patients with sarcoidosis showed a bimodal distribution (Figure 1), with 52.9% patients of patients having a CD200Rlow phenotype compared with 11.7% of healthy control subjects (p &lt; 0.0001). CD200Rlow subjects produced more IL-6 in whole blood assays compared with CD200Rhigh subjects (p &lt; 0.05). Experimental blockade of the CD200R axis increased pro-inflammatory cytokine responses, recapitulating the hyperactive monocyte phenotype seen in sarcoidosis. <h3>Conclusions</h3> Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyper-activation in sarcoidosis.
P3.05-018 Assessment of Skeletal Muscle Mass as a Predictive Factor for Chemotherapy Toxicity and TTP in Advanced NSCLC Patients with Cancer Cachexia
Authors: Drazena Srdic, Sanja Plestina, Ana Sverko-Peternac, Nora Nikolac, Ana Bacelic Gabelica, Olivera Maletic, Marko Jakopovic, Miroslav Samarzija
Journal: Journal of Thoracic Oncology (2017)
P76 Initiation of long-term non-invasive ventilation (NIV) in a specialist respiratory failure unit in the uk
Authors: SJ Tetlow, PS Marino, PD Murphy, H Pattani, J Steier, N Hart
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> There are currently no guidelines for the provision of long-term NIV and little data into the settings and interfaces employed by different centres. Our aim was to assess long-term NIV provision in a Specialist Respiratory Failure Unit (SRFU). <h3>Methods</h3> A retrospective observational study was performed of all patients commenced on long-term NIV by the SRFU. Data was collected from electronic patient records and technician databases on all initiations from August 2014 to January 2015. <h3>Results</h3> Data was obtained from 113 patients. Oronasal masks were used in 87% of patients, nasal pillows in 10%, total face masks in 2% and nasal masks in 1%. Oronasal masks were used to deliver higher inspiratory positive airway pressures (IPAP) (mean ± SD 23.3 ± 5.3 cm H<sub>2</sub>O). Nasal interface use was associated with lower IPAPs (mean ± SD 12.5 ± 4.5). A relatively higher IPAP was applied at initiation to the study group (mean ± SD 22.3 ± 6.2 cm H<sub>2</sub>O) but this varied according to diagnosis; patients with obstructive sleep apnoea (OSA), chronic obstructive pulmonary disease (COPD) and motor neurone disease (MND) received a mean ± SD IPAP of 24.3 ± 5.4 cm H<sub>2</sub>O, 23.4 ± 4.2 cm H<sub>2</sub>O and 12.4 ± 3.6 cm H<sub>2</sub>O respectively. <h3>Conclusions</h3> Oronasal masks were predominantly used reflecting the frequent application of IPAPs above 20 cm H<sub>2</sub>O as high pressures are poorly tolerated with nasal interfaces. High mean IPAPs were used in OSA and COPD patients, whilst lower IPAPs were administered to MND patients. No guidelines exist for long-term NIV use, with practice on the SRFU differing from the British Thoracic Society’s guidelines on acute NIV that recommend a “pressure target” of 20 cm H<sub>2</sub>O (Royal College Of Physicians et al. Concise Guidance to Good Practice Series, 11). However, the relevance of these guidelines to long-term NIV provision is unclear, and the lack of data has impeded the development of specific guidance. A database of patients receiving long-term NIV in the UK would facilitate research and the formulation of evidence-based best practice guidelines.
Single and Repeated Dose First-in-Human Study with the Anti-Hepcidin Spiegelmer Nox-H94.
Authors: Kai Riecke, Stefan Zöllner, Malcolm Boyce, Stephanie Vauléon, Dorine W. Swinkels, Thomas Dümmler, Luciana Summo, Coby Laarakkers, Frank Schwoebel, Frank Fliegert
Journal: Blood (2012)
P137 Why is erdosteine recommended as a treatment for acute exacerbations of chronic bronchitis? a systematic review of clinical trials
Authors: CL Johnson, DF Rogers
Journal: Thorax (2016)

<h3>Background</h3> Exacerbations of chronic bronchitis or chronic obstructive pulmonary disease (COPD) are a significant health burden. A substantial component of these exacerbations in many patients is mucus-hypersecretion. Mucolytics, drugs that ‘thin’ mucus, have potential efficacy in these patients. Currently, erdosteine is the only mucolytic in the British National Formulary (BNF) indicated for “symptomatic treatment of acute exacerbations of chronic bronchitis”, while other BNF mucolytics (carbocisteine, mecysteine and <i>N</i>-acetylcysteine) have had more general or non-respiratory indications, e.g. “reduction in sputum viscosity”. It is theorised that there is clinical evidence that erdosteine is useful in treatment of acute exacerbations of chronic bronchitis, unlike any of the other aforementioned mucolytics. <h3>Methods</h3> In this narrative systematic review, databases utilised included: Medline, Embase and PubMed. Studies for inclusion had to be Randomised Controlled Trials (RCTs) primarily investigating the effect of erdosteine in exacerbations of chronic bronchitis or COPD. For comparison, RCTs were also included if they investigated carbocisteine, mecysteine and <i>N</i>-acetylcysteine’s effects in exacerbations. A secondary outcome was to investigate the use of these mucolytics in improving COPD signs and symptoms. Once selected, a two-stage publication elimination process was devised by the author to assess the quality of the trials. <h3>Results</h3> Very few trials of adequate quality assessed the efficacy of mucolytics in chronic bronchitis or COPD. Of the 5,560 search results, only 62 trials investigated the aforementioned mucolytics use in chronic bronchitis or COPD, 41 were RCTs. Of the 41 RCTs only 13 were found to be of adequate quality; erdosteine (1 RCT), carbocisteine (3 RCTs), mecysteine (0 RCTs) and <i>N</i>-acetylcysteine (9 RCTs). There was no evidence that erdosteine is useful in treating exacerbations, and very limited, weak evidence for some efficacy in exacerbation prevention. In contrast, carbocisteine showed some strong evidence of efficacy in preventing exacerbations, especially in Asian populations. <i>N</i>-acetylcysteine trial results were variable, and evenly distributed between positive and no effects, with one study showing adverse effects. There were no trials of adequate quality investigating mecysteine. <h3>Conclusion</h3> There is little evidence that erdosteine is useful in treating chronic bronchitis exacerbations, whereas, overall carbocisteine seems to be more efficacious in exacerbation prevention.
Clinical Implications of Focal Intimal Disruption in Patients With Type B Intramural Hematoma
Authors: Sergio Moral, Hug Cuéllar, Gustavo Avegliano, Esther Ballesteros, Maria Teresa Salcedo, Ignacio Ferreira-González, David García-Dorado, Arturo Evangelista
Journal: Journal of the American College of Cardiology (2017)
The GPIIbIIIa Antagonist Drugs Eptifibatide and Tirofiban Inhibit Caspase-3 Activation in Thrombin- and Calcium Ionophore-Stimulated Human Platelets.
Authors: Valery Leytin, Asuman Mutlu, Sergiy Mykhaylov, David J. Allen, Armen V. Gyulkhandanyan, Elena Lyubimov, John Freedman
Journal: Blood (2009)
P2.03b-013 Outcome of Patients with ALK+ NSCLC and Brain Metastases in Relation to Disease Burden and Clinical Management
Authors: Luigi De Petris, Signe Friesland, Daniel Brodin, Hanna Carstens, Johan Falkenius, Oscar Grundberg, Magnus Löfdahl, Clara Lenneby Helleday, Reza Karimi, Anna Öjdahl-Boden, Georgios Tsakonas, Simon Ekman, Karl-Gustav Kölbeck
Journal: Journal of Thoracic Oncology (2017)
MA09.10 A NaPi2b Antibody-Drug Conjugate Induces Durable Complete Tumor Regressions in Patient-Derived Xenograft Models of NSCLC
Authors: Donald Bergstrom, Natalya Bodyak, Alex Yurkovetskiy, Laura Poling, Mao Yin, Marina Protopopova, Mike Devit, Liuliang Qin, Dmitry Gumerov, Elena Ter-Ovanesyan, Rebecca Mosher, Timothy Lowinger
Journal: Journal of Thoracic Oncology (2017)
Fas-Dependent Apoptosis in Early MDS Erythroid Precursors Involves Endoplasmic Reticulum.
Authors: Emmanuel Gyan, Emilie Frisan, Odile Beyne-Rauzy, Cecile Pierre-Eugene, Jean-Christophe Deschemin, Clotilde Randriamampita, Anne Dubart-Kupperschmitt, Carmen Garrido, Francois Dreyfus, Martine Guesnu, Catherine Lacombe, Patrick Mayeux, Eric Solary, Michaela Fontenay
Journal: Blood (2007)
Interstitial nephritis in melanoma patients secondary to PD-1 checkpoint inhibitor
Authors: Julia Escandon, Stephanie Peacock, Asaad Trabolsi, David B. Thomas, Ayman Layka, Jose Lutzky
Journal: Journal for ImmunoTherapy of Cancer (2017)

Immune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases.