tbuckley/cabot-search huggingface dataset:
P195 CURB-65, rea-icu or smart-cop: time to rethink cap severity scores?
Authors: S Zaat, CL Tey, B Prathibha
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> An accurate assessment of severity of community acquired pneumonia (CAP) on admission is pivotal in early identification of patients who are critically ill. CURB-65 is recommended by BTS, but is a poor predictor of ICU admissions and often underestimates severity in young patients. We compared this with REA-ICU and SMART-COP in predicting severity and mortality. <h3>Methods</h3> The notes of all adult patients admitted with a diagnosis of CAP in June 2016 were reviewed. Inclusion criteria consisted of consolidation on chest radiograph and raised inflammatory markers. Scores were calculated from results obtained within 24 hours of admission. The patients were followed up to ascertain length of stay, complications (effusions, empyema) antibiotic escalation, delivery of non-invasive ventilation (NIV), ICU escalation and death. <h3>Results</h3> 43 patients identified with CAP were included in our analysis. 76.7% of patients were ≥65 years old. 24 hours after admission, 39.5% had ward-based ceilings of care in place and 27.9% had no escalation plan documented. 11.6% were still inpatients at the time of analysis. No patients were escalated to ICU. CURB-65 was 0 to 1 in 23.3%, 2 in 18.6%, and ≥3 in 58.1%. In the low risk group, 50% developed complications, 10% required NIV and there were no inpatient deaths. Amongst the moderate and high risk patients, NIV was administered in 25% and 16% respectively, primarily as the patient’s ceiling of care. Inpatient deaths occurred in 12.5% of moderate risk and 16% of high risk patients. As shown in Table 1, there was variation in REA-ICU and SMART-COP scores amongst moderate and high risk CURB-65 scores. A high risk CURB-65 score did not correlate with high REA-ICU and SMART-COP scores. We found that higher REA-ICU and SMART-COP scores did not correlate with increased mortality. However, length of stay and antibiotic escalation was increased with higher SMART-COP scores, particularly in those with low CURB-65 scores. <h3>Conclusions</h3> CURB-65 score correlates well with mortality, particularly in the elderly group of patients studied. REA-ICU and SMART-COP are better at identifying younger, morbidly ill patients with misleadingly low CURB-65 scores requiring early decisions regarding escalation of care.
S80 Mesenchymal stromal cells (MSC) modulate human macrophages in acute respiratory distress syndrome (ARDS) via secretion of extracellular vesicles (EV) which enhance oxidative phosphorylation and regulate jak/stat signalling
Authors: TJ Morrison, MV Jackson, C O’Kane, DF McAuley, A Krasnodembskaya
Journal: Thorax (2016)

<h3>Background</h3> ARDS remains a major cause of respiratory failure in critically ill patients with no effective treatment. MSC are a promising candidate for therapy. However the mechanisms of MSC effects in lung injury are not well understood. We have recently shown that alveolar macrophages are critical cellular mediators of the therapeutic effect of MSC in the mouse model of <i>E.coli</i> pneumonia.<sup>1</sup> Here we focused on the paracrine effect of MSC on macrophage polarisation and intracellular signalling. <h3>Methods</h3> Primary human macrophages were co-cultured with human bone marrow derived-MSC, without contact, at a 5:1 ratio, MSC-conditioned medium (CM) or EV with or without LPS or bronchoalveolar lavage fluid (BALF) from ARDS patients. A phospho-kinase array was performed on lysates for analysis of signalling cascades. Levels of pSTAT, Suppressor of Cytokine Signalling (SOCS) 1 and 3 proteins were tested by Western blot. Cell metabolism was investigated using Seahorse technology. <h3>Results</h3> Cytokine and surface marker expression show that MSC promote an M2-like macrophage phenotype with enhanced phagocytic activity. MSC-CM enhanced mitochondrial respiration in macrophages and oligomycin inhibited the effect of MSC-CM on cytokine secretion and phagocytosis, suggesting that MSC-CM induced a metabolic switch to oxidative phosphorylation, characteristic of M2 macrophages. Consistently with the M2 phenotype, MSC induced a high SOCS1:SOCS3 protein expression ratio, accompanied with activation of STAT6 and inhibition of STAT1 phosphorylation. MSC effects were reversed by anti-CD44 antibody (important for internalisation of MSC-derived EV) suggesting that EV in MSC-CM are mediators of their effect. Importantly, adoptive transfer of EV-treated alveolar macrophages conferred protection in the mild model of murine LPS-induced pneumonia. EV contents responsible for these effects are currently being investigated. <h3>Conclusion</h3> MSC promote M2-like macrophage polarisation via secretion of EV. This effect is associated with enhanced oxidative phosphorylation and altered JAK/STAT signalling, potentially regulated by differential expression of SOCS1 and 3 proteins. <h3>Reference</h3> Jackson MV, Morrison TJ, Doherty DF, <i>et al</i>. Mitochondrial Transfer via Tunnelling Nanotubes (TNT) is an important mechanism by which mesenchymal stem cells enhance macrophage phagocytosis in the in vitro and in vivo models of ARDS. <i>Stem Cells</i> 2016;<b>34</b>(8):2210–23.
P2.04-021 Role of Adjuvant Radiotherapy and Prognostic Factor Analysis in Thymic Malignancies: A Retrospective Analysis of 129 Consecutive Patients
Authors: Alessio Bruni, Vieri Scotti, Elisa D'Angelo, Paolo Bastiani, Stefano Scicolone, Carla De Luca Cardillo, Sara Cecchini, Marco Perna, Laura Rubino, Polina Vasilyeva, Carlotta Becherini, Camilla Comin, Frank Lohr, Lorenzo Livi
Journal: Journal of Thoracic Oncology (2017)
EUTOS Score Identifies Cases with Poor Outcome in Patients with Early Chronic Phase Chronic Myeloid Leukemia, Though Not Predictive for Optimal Response to Imatinib
Authors: Mario Tiribelli, Massimiliano Bonifacio, Elisabetta Calistri, Gianni Binotto, Elena Maino, Luciana Marin, Emanuele Guardalben, Antonio Branca, Filippo Gherlinzoni, Gianpietro Semenzato, Renato Bassan, Giovanni Pizzolo, Renato Fanin
Journal: Blood (2012)
P118 How do foreign-born patients with tuberculosis access healthcare? a cohort analysis of referrals from general practice and the emergency department to a tertiary tuberculosis service
Authors: S Conway, A Pitcher, S Dart, D Vaghela, MGK Burman, J Potter, VLC White, S Tiberi, H Kunst
Journal: Thorax (2016)

<h3>Introduction</h3> More than Seventy percent of active Tuberculosis (TB) cases in England are in patients born outside the United Kingdom (UK). Lack of access to primary healthcare is often cited as a barrier to TB control. We considered how patients with TB referred directly to outpatient services initially access healthcare. <h3>Method</h3> A retrospective cohort analysis of all patients with active TB on the London TB register (LTBR) between April 2014 and April 2015 at a large urban tertiary referral centre. The route of referral to TB services was confirmed by a review of electronic patient records. We compared demographic, disease and outcome variables between groups as recorded in the LTBR. We excluded those requiring admission; identified through contact tracing; referrals from other secondary care outpatient services and those with inadequate data. Chi squared or Exact tests were used in the analysis. <h3>Results</h3> We compared patients diagnosed with TB who were referred directly to outpatient services from General Practice (GP) (97 patients) and the Emergency Department (ED) (35 patients). There was no significant difference in age or sex between groups. Of those patients born outside the UK (105), 78 percent (82/105) were referred to clinic from their GP compared to only 56 percent (15/27) of those born within the UK (15/27). This difference was statistically significant (p &lt; 0.05). There was no statistically significant difference between the mean length of stay in the UK amongst migrants that presented via ED or GP (MD 2.33 years, 95% CI: −2 to 7, p &lt; 0.4). There was no statistically significant difference in the number of patients who had at least one social risk factor between groups. Comparing disease between the groups, there was a higher proportion of multisite disease amongst those referred from ED compared to GP (23% [8/35] vs 14% [14/97], p &lt; 0.025), there was no statistical difference between the numbers of pulmonary cases identified or smear status between the groups. <h3>Conclusion</h3> Amongst patients with active TB referred directly to outpatient services, those born outside the UK were more likely to have been referred by their GP than UK-born patients.
Role of IL-4 in Inducing Immunosuppressive Tumor Microenvironment in Follicular Lymphoma
Authors: Seema Rawal, Hyun Jun Park, Fuliang Chu, Min Zhang, Durga Nattamai, Shibi Chakravarthy Kannan, Rakesh Sharma, David A Delgado, Tina Chou, Richard Eric Davis, Sattva S. Neelapu
Journal: Blood (2011)
Identification of Inherited Macrothrombocytopenias Based on Mean Platelet Volume among Patients Diagnosed with Idiopathic Thrombocytopenia.
Authors: Fumito Gohda, Hideki Uchiumi, Hiroshi Handa, Matsushima Takafumi, Norifumi Tsukamoto, Kimio Morita, Hatsuo Amagai, Masami Murakami, Hirokazu Murakami, Yoshihisa Nojima, Masamitsu Karasawa
Journal: Blood (2005)
P1.02-058 EGFR Amplification and Sensitizing Mutations Correlates with Survival from Erlotinib in Lung Adenocarcinoma Patients (MutP-CLICAP)
Authors: Andrés Cardona, Oscar Arrieta, Luis Corrales, Leonardo Rojas, Mauricio Cuello, Claudio Martin, Hernan Carranza, Carlos Vargas, Rafael Rosell
Journal: Journal of Thoracic Oncology (2017)
P3.05-019 Patients with Advanced Lung Cancer: What Do They Know, What Would They Like to Know, What Should They Know about Their Disease
Authors: Annelies Janssens, Sofie Derijcke, Elke Vandenbroucke, Anneke Lefebure, Veerle Surmont, Dieter Coeman, Daniëlle Galdermans, Ann-Marie Morel, Birgitta Hiddinga, Jan Van Meerbeeck
Journal: Journal of Thoracic Oncology (2017)
P299 Effects of symptom severity at baseline on lung-function and sgrq responses in the otemto® studies
Authors: FJ Martinez, R Abrahams, GT Ferguson, L Bjermer, L Grönke, F Voß, D Singh
Journal: Thorax (2016)

<h3>Rationale</h3> In the randomised, double-blind, Phase IIIb OTEMTO<sup>®</sup> 1 and 2 studies (NCT01431274; NCT01431287), the combination of tiotropium (T), a long-acting muscarinic antagonist, plus olodaterol (O), a long-acting β<sub>2</sub>-agonist, showed meaningful improvements in quality of life (St George’s Respiratory Questionnaire [SGRQ]) and lung function in patients with moderate to severe COPD after 12 weeks’ treatment compared to T alone or placebo. This <i>post hoc</i> analysis investigated whether symptomatic status at inclusion, as measured by the modified Medical Research Council (mMRC) dyspnoea scale and the Baseline Dyspnoea Index (BDI), influenced lung-function and SGRQ responses. <h3>Methods</h3> Patients aged ≥40 years received T/O 2.5/5 µg, T/O 5/5 µg, T 5 µg or placebo once daily for 12 weeks via Respimat<sup>®</sup> inhaler. SGRQ total score and lung function (FEV<sub>1</sub> area under the curve from 0–3 hours [AUC<sub>0–3</sub>] and trough FEV<sub>1</sub> responses) were primary end points. Patients completed the mMRC and BDI scales at baseline. We report comparisons between T/O 5/5 µg, T 5 µg and placebo. <h3>Results</h3> 1621 patients were evaluated: 736 patients (45%) had mMRC scores &lt;2, 883 patients (54%) ≥2 (scored from grade 0–5, lower is better); 418 patients (26%) had BDI scores &lt;6, 1201 patients (74%) ≥6 (scored from 0–12, higher is better). Patients were distributed evenly across treatment arms with respect to mMRC and BDI scores, and baseline characteristics were consistent across treatment arms. Improvements in FEV<sub>1</sub> AUC<sub>0–3</sub> and trough FEV<sub>1</sub> were observed with T/O compared to T and placebo in patients with mMRC score &lt;2 and ≥2, as well as in patients with BDI score ≥6 and &lt;6 (Table). All BDI and mMRC groups demonstrated improvements in SGRQ with T/O compared to placebo above the minimal clinically important difference. <h3>Conclusions</h3> There was a trend towards better lung-function improvement with T/O versus T or placebo in less symptomatic patients assessed by baseline BDI. More severe dyspnoea by mMRC category was associated with improved SGRQ with T/O versus T or placebo, but did not affect lung-function improvement. Overall, T/O provided lung-function and quality of life benefits regardless of symptomatic status prior to treatment. <h3>Funding</h3> Boehringer Ingelheim. Please refer to page A274 for declarations of interest in relation to abstract P299.
A Multicenter Phase 1 Clinical Trial of Tanespimycin (KOS-953) + Bortezomib (BZ): Encouraging Activity and Manageable Toxicity in Heavily Pre-Treated Patients with Relapsed Refractory Multiple Myeloma (MM).
Authors: Paul Richardson, Asher Alban Chanan-Khan, Sagar Lonial, Amrita Krishnan, Melissa Alsina, Michael Carroll, Karen Adler, G. Cropp, C. Mitsiades, Robert Johnson, Alison Hannah, Kenneth C. Anderson
Journal: Blood (2006)
Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease
Authors: Katrina M de Lange, Loukas Moutsianas, James C Lee, Christopher A Lamb, Yang Luo, Nicholas A Kennedy, Luke Jostins, Daniel L Rice, Javier Gutierrez-Achury, Sun-Gou Ji, Graham Heap, Elaine R Nimmo, Cathryn Edwards, Paul Henderson, Craig Mowat, Jeremy Sanderson, Jack Satsangi, Alison Simmons, David C Wilson, Mark Tremelling, Ailsa Hart, Christopher G Mathew, William G Newman, Miles Parkes, Charlie W Lees, Holm Uhlig, Chris Hawkey, Natalie J Prescott, Tariq Ahmad, John C Mansfield, Carl A Anderson, Jeffrey C Barrett
Journal: Nature Genetics (2017)
P1.02-020 The Effect of EGF-Pathway Targeted Immunization (EGF PTI) on STAT3 and Cancer Stem Cells in EGFR Mutant NSCLC Cells
Authors: Jordi Codony Servat, Miguel Angel Molina Vila, Jordi Bertrán-Alamillo, Silvia García, Niki Karachaliou, Erik D'Hondt, Rafael Rosell
Journal: Journal of Thoracic Oncology (2017)
P184 Calculation of conductive inhomogeneity in children with severe cf lung disease: which method works?
Authors: N Verger, M Arigliani, E Raywood, JA Duncan, A Bush, P Aurora
Journal: Thorax (2016)

<h3>Introduction</h3> Convection Dependent Inhomogeneity (CDI, a measure of ventilation inequality among larger lung units) quantified by Scond cannot be assessed in subjects with severe ventilation inhomogeneity (VI) as assumptions underlying the calculation are invalid; an alternate index that has been suggested is Scond.<sup>1</sup> <h3>Aim</h3> To compare these two methods of CDI assessment in CF children <h3>Methods</h3> Children with cystic fibrosis (CF; 67) and healthy controls (61) performed multiple breath washout with sulphur hexaflouride measured using mass spectrometry. Scond was calculated from 1.5 to 6 turnovers and Scond* from breath 2 to 3 turnovers. <h3>Results</h3> All measures of VI were significantly higher for CF vs control, mean difference: LCI 4.0, Scond 0.054, Scond* 0.081. In CF, LCI correlated better with Scond* than Scond (See figure: correlation coefficient LCI vs. Scond* 0.75; LCI vs. Scond 0.42). If children with moderate-severe VI (LCI &gt; 11) were excluded there was an improved correlation for both relationships (correlation coefficient LCI vs. Scond 0.83; LCI vs. Scond* 0.86). An asymptote for the Scond vs LCI relationship was at Scond 0.07 and Scond* 0.13. <h3>Conclusion</h3> Scond* quantifies the mechanism of VI in moderate to severe lung disease, but it may reach asymptote in very severe VI. <h3>Reference</h3> Verbanck. <i>Respiratory Physiology &amp; Neurobiology</i>, 2013.
S111 Differences in characteristics and outcomes in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension
Authors: S Ramjug, N Hussain, J Hurdman, C Billings, CA Elliot, DG Kiely, I Sabroe, S Rajaram, AJ Swift, R Condliffe
Journal: Thorax (2016)

<h3>Background</h3> Previous studies have demonstrated survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) to be worse than in idiopathic pulmonary arterial hypertension (IPAH). Possible explanations include age, differences in the underlying pulmonary vasculopathy and the ability of the right ventricle to compensate for the increased afterload.<sup>1</sup> We investigated differences between these conditions by comparing demographic, haemodynamic and cardiac magnetic resonance imaging (MRI) characteristics and outcomes in a large cohort of incident, treatment-naive patients. <h3>Methods</h3> 183 patients with IPAH and 192 patients with SSc-PAH were identified from departmental databases including the ASPIRE registry.<sup>2</sup> Sub-group analysis in 83 patients who had undergone cardiac MRI within 14 days of right heart catheterisation was performed. <h3>Results</h3> Median survival in IPAH was 7.8 years and in SSc-PAH was 3 years (p &lt; 0.001). Patients with SSc-PAH were older with milder pulmonary haemodynamics but lower gas transfer (DL<sub>CO</sub>). Independent prognostic factors at multivariate Cox regression analysis were age, presence of systemic sclerosis, DL<sub>CO</sub>, pulmonary artery saturation and stroke volume. For a given resistance (R), pulmonary arterial compliance (C) was reduced (lower RC) in SSc-PAH (Figure). The relationship between mean pulmonary arterial pressure (mPAP) and systolic pulmonary arterial pressure (sPAP) in IPAH was identical to that previously reported (mPAP = 0.61 sPAP + 2 mmHg). The relationship in SSc-PAH was found to be: mPAP = 0.58 sPAP + 2 mmHg (p-value for difference with IPAH = 0.095). There was no significant difference in compensatory right ventricular hypertrophy when corrected for afterload while the correlation between ventricular mass index (right ventricular mass/left ventricular mass) and pulmonary vascular resistance was stronger in SSc-PAH. <h3>Conclusion</h3> The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial including, but not limited to, older age, increased pulmonary arterial stiffness and reduced gas transfer. <h3>References</h3> Condliffe R, Howard LS. Connective tissue disease-associated pulmonary arterial hypertension. <i>F1000 Prime Rep</i>. 2015;<b>7</b>:06. Hurdman J, Condliffe R, Elliot CA, <i>et al</i>. ASPIRE registry: assessing the spectrum of pulmonary hypertension Identified at a REferral centre. <i>Eur Respir J</i>. 2012;<b>39</b>(4):945–955.
Uruguayan experience in uveal melanoma: Results on 63 patients followed during a 20 year period
Authors: G. D. Krygier, C. Castillo, A. Dellavalle, E. Ugartemendia, G. Sabini, A. Viola, I. Muse
Journal: Journal of Clinical Oncology (2004)

7568 Background: Uveal melanoma is the most common primary malignant intraocular tumor in adults (70%). They generally occur sporadically and familiy uveal melanoma only accounts for 0.6 % of patients. Methods: Data was collected from 63 patients assisted at six different institutions in Montevideo, Uruguay, during a 20-year period. Diagnosis was histopathologically confirmed in 55/63(87%) patients. Radical surgery (predominately enucleation) was performed in 54/63(86%) patients. Other treatment options included orbit excenteration, braquitherapy, and proton beam therapy. 25/63 (40%) developed distant metastasis, mainly in the liver. Results: The mean age at diagnosis was 59 years old. The most common symptom was decreased visual acuity in 50/63 (77%). Three patients had extrascleral extension of the tumor and presented with pigmented lesions. There was a statistical significant correlation between tumors of mixed and epithelioid type and survival (p<0.01) but there was not correlation between tumor diameter and survival.(p=0.06 ).There were three clinical cases of familial uveal melanoma involving first generation members of the same family (siblings) one of which also had a malignant breast tumor diagnosed 2 years before the ocular tumor. A BRCA2 mutation was then identified. The three were enucleated and died with a mean time of 19 months because of distant metastasis. Secondary metastasis in the liver was imagenollogy confirmed in 23/63(36.5%) patients. The median time from the diagnosis of the ocular tumor to the metastasis was 40.5 months and the median survival for the metastasic disease was 4 months. The median overall survival was 88 months (C.I. 95% 75–100). Conclusions: This abstract illustrates the natural history of this entity taking into account the heterogeneous behaviour of it in our country, mainly with the occurrence of the extremely rare and fatal familial uveal melanoma (three siblings), and the extraescleral compromise as the presenting feature of three other cases. No significant financial relationships to disclose.
P2.02-041 The Impact of Surgical Resection after Concurrent Chemotherapy and High Dose (61 Gy) Radiation in Stage IIIA/N2 Non-Small Cell Lung Cancer
Authors: Akif Turna, Osman Yaksi, Hasan Kara, Ezel Ersen, Zeynep Turna, H Fazilet Dinçbaş, Serdar Erturan, Günay Aydin, Kamil Kaynak
Journal: Journal of Thoracic Oncology (2017)
Appearance of Mature 6-Sulfo LacNAc+ Dendritic Cells In Early and Late Engraftment After Allogeneic Stem Cell Transplantation.
Authors: Sebastian Tuve, Konrad Mager, Rebekka Wehner, Felix Bahr, Uta Ölschlegel, Nona Shayegi, Jan Moritz Middeke, Conrad Heuchel, Christoph Röllig, Jörgen Radke, Martin Wermke, Uwe Platzbecker, Johannes Schetelig, Christian Thiede, Gerhard Ehninger, Martin Bornhaeuser, Marc Schmitz
Journal: Blood (2010)
Cardiac Disease in Pregnancy
Authors: Julius Abramson, Benjamin Tenney
Journal: New England Journal of Medicine (1955)

IN considering the problem of cardiac disease in pregnancy one must have a reasonable knowledge of the physiologic changes that appear in the pulmonocardiovascular systems during normal pregnancy. Much investigation has been done in this field. Although there are differences of opinion about the exact physiologic findings, certain definite concepts are becoming generally accepted. In this paper an attempt is made to state these concepts, although one must realize that they are not, as yet, scientific facts.The reports of various clinics throughout the country show the incidence of organic heart disease in pregnancy to vary from 0.3 per cent . . .
Low or Undetectable Levels of Thrombopoietin Receptor (Tpo-R; c-mpl) Expression on Tumor Cell Lines and Primary Tumors Compared with Epo-R, ErbB2, and IGF-1R
Authors: Connie L Erickson-Miller, Antony Chadderton, Anna Gibbard, Jennifer Kirchner, Lone Ottesen, Katherine Baker, Lini Pandite, Iman El-Hariry, Yasser Mostafa Kamel, Yuan Liu, Anne-Marie Martin, Conrad Messam
Journal: Blood (2008)