tbuckley/cabot-search huggingface dataset:
PL04a.02: OAK, a Randomized Ph III Study of Atezolizumab vs Docetaxel in Patients with Advanced NSCLC: Results from Subgroup Analyses
Authors: Shirish Gadgeel, Fortunato Ciardiello, Achim Rittmeyer, Fabrice Barlesi, Diego Cortinovis, Carlos Barrios, Toyoaki Hida, Keunchil Park, Dariusz Kowalski, Manuel Cobo Dols, Joseph Leach, Jonathan Polikoff, Christina Matheny, Pei He, Marcin Kowanetz, Daniel Chen, Daniel Waterkamp, Marcus Ballinger, Alan Sandler, David R. Gandara, Joachim Von Pawel
Journal: Journal of Thoracic Oncology (2017)
S119 Inducible laryngeal obstruction masquerading as work-related asthma; a new approach
Authors: J Feary, B Fitzgerald, J Szram, J Hull, J Selby, M Mataksori, G Scadding, P Cullinan
Journal: Thorax (2016)

<h3>Introduction</h3> The specific inhalation challenge (SIC) is the reference standard test for diagnosis of occupational asthma in people with immunological sensitisation to a specific agent. In our occupational lung disease clinic, we recognise a separate group of patients who report symptoms consistent with inducible laryngeal obstruction (ILO) triggered by one or more agents which are generally not recognised sensitisers. Symptoms, which include throat and chest tightening, voice change, dyspnoea and wheeze, are frequently misdiagnosed as work-related asthma, “allergy” and even anaphylaxis. In such cases securing the correct diagnosis can avoid unnecessary medication use, excessive health care utilisation and occasionally loss of employment. We have designed a SIC to provide objective confirmation of the diagnosis of ILO in the occupational setting. <h3>Method</h3> Patients are carefully selected to undergo ILO-SIC. After histamine challenge testing, spirometry and direct laryngoscopy, they are exposed, in a specialist exposure chamber, to the agent(s) which provoke their symptoms. Each challenge is bespoke according to the patient’s triggers, work environment and comorbidities. Exposure is usually continued until the symptoms experienced in the workplace are reproduced, or to a level expected to cause airway irritation in a control individual. Direct laryngoscopy and measurement of spirometry is repeated and any anatomical and physiological changes noted. <h3>Results</h3> We have carried out 30 such challenges (90% women; mean age 45 years (SD 9.4)) to date. Agents have included perfumes, household paint and hospital cleaning products. In 87% of cases, we replicated symptoms experienced in the workplace. In 53% of cases, clear changes of ILO were seen. In those with normal laryngoscopy, the SIC is equally useful in reassuring patients that symptoms experienced are not dangerous, nor consistent with anaphylaxis or similar. Following careful explanation of the diagnosis, patients are managed conservatively or referred to specialist physiotherapists or voice therapists if indicated. Asthma treatment can often be withdrawn over time. <h3>Conclusion</h3> A precise diagnosis in cases of occupational asthma is key to successful outcome; in this setting, we increasingly see patients with occupational (or other environmental) ILO. ILO-SIC testing in specialist centres can provide objective evidence to assist diagnosis avoiding unnecessary investigation and treatment of other conditions.
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) as a Curative Therapy in Primary and Secondary Myelofibrosis (MF): A 14-Year Period Oligocentric French Experience.
Authors: Severine Lissandre, Jacques-Olivier Bay, Jean-Yves Cahn, Victoria Cacheux, Aurélie Cabrespine, Denis Guyotat, Bruno Cassinat, Regis Peffault de Latour, Gerard Socie, Marie Robin
Journal: Blood (2008)
Prognostic factors for chemotherapy-related toxicity in primary central nervous system lymphoma (PCNSL) treated with high-dose methotrexate (HDMTX) with or without ifosfamide: Results from a German phase III trial (G-PCNSL-SG-1).
Authors: P. Martus, K. Jahnke, A. Korfel, T. Rose, L. Fischer, R. Moehle, H. A. Klasen, M. Rauch, A. Roeth, B. Hertenstein, T. Fischer, T. Hundsberger, H. Mergenthaler, M. Leithäuser, T. Birnbaum, U. Herrlinger, J. Schubert, J. Birkmann, M. Weller, E. Thiel
Journal: Journal of Clinical Oncology (2011)

2005 Background: Acute chemotherapy-associated toxicity is an important issue in PCNSL since these patients are usually of advanced age, in impaired clinical condition, and often suffer from comorbidities. We present an analysis of prognostic factors for chemotherapy-related acute toxicity from a German multicenter phase III trial (G-PCNSL-SG-1). Methods: Five-hundred and twenty-six eligible patients (median age 63 years, median Karnofsky performance status (KPS) 70%) treated with at least one chemotherapy course were analyzed using univariate and multivariate logistic regression analyses to identify prognostic factors for grade 3-4 chemotherapy toxicity. Chemotherapy consisted of HDMTX (4 g/m² on day 1) alone in 401 patients and HDMTX plus ifosfamide (1.5 g/m² on days 3-5) in 125 patients. Toxicity was graded according to the World Health Organization toxicity criteria. Results: On multivariate analysis, the following variables were highly predictive (p <0.01) for the respective toxicities: HDMTX plus ifosfamide vs. HDMTX monotherapy for anemia and infections, KPS (<70 vs. ≥70%), age (≥60 vs. <60 years), and preexisting pulmonary disease for thrombocytopenia, fully dosed HDMTX vs. dose reduction for elevated transaminases, and elevated serum lactate dehydrogenase (LDH) for infections. Further variables associated with diverse treatment-related toxicities (0.05 >p ≥0.01) on multivariate analysis were: age ≥60 years, fully dosed ifosfamide, KPS <70%, body mass index ≤25, elevated serum LDH, and preexisting cardiovascular disease. Conclusions: This is the first report on prognostic factors for toxicity of HDMTX-based chemotherapy in PCNSL. The findings can be helpful when HDMTX-based chemotherapy in PCNSL patients is planned.
S90 The nature and duration of symptoms and time to starting treatment comparing older with younger pulmonary tuberculosis patients
Authors: A Abbara, E Hardman, SM Collin, OM Kon, Z Mahomed, JAL Sullivan, K Buell, T Hansel, T Corrah, RN Davidson
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> In 2013, Public Health England (PHE) reported that 39% of pulmonary tuberculosis (TB) patients &gt;65 years old started treatment &gt;4 months after symptom onset compared to 25% of patients aged 15–44 years. A longer symptomatic period, particular if smear positive, may result in increased transmission and poorer treatment outcomes. We investigated age-related differences in symptom duration and time to starting TB treatment in a large UK cohort of TB patients. <h3>Methods</h3> The cohort comprised patients on the London TB register (LTBR) who were treated at Northwick Park Hospital between 2002–2015. Patients aged &gt;65 years were compared with a random sample of patients aged 18–40 years, with respect to symptoms, symptom duration at presenting to secondary care and time to starting treatment after presenting to secondary care. <h3>Results</h3> 357 patients over 65 and 517 younger patients were identified. Demographics for the total number of patients are included in Table 1. Data were available for 489 of the younger group and 73 of the older group. 26 of the &gt;65s (35.6%) and 9 (1.8%) of the 65s were diabetic. <h3>Conclusions</h3> This study has identified that a potential cause for a delay in diagnosis in the elderly may be related to the decreased frequency of ‘classical’ TB symptoms in those &gt;65 years of age. Clinicians need to be vigilant despite the lack of these symptoms. Median duration of symptoms was twice that in older patients versus younger patients (90 days versus 45) with a longer time to starting treatment (7 days versus 2). The total duration (in months) from symptom onset was also higher at 3 months versus 2 months. A higher proportion of older patients (32%) started treatment greater than 4 months from symptom onset compared to 13.1% in younger patients. Biases in this work including recording bias due to the retrospective nature of symptom recording, the effect of selecting younger patients from more recent years (to improve data availability) and the low proportion of patients over 65 which had symptom and treatment data available.
Immunomodulatory Effects of the Triterpenoid CDDO after Allogeneic Bone Marrow Transplantation in Mice: Reduction of Acute Graft-Versus-Host Disease Lethality.
Authors: William J. Murphy, Olga Frolova, Marina Konopleva, Michael Andreeff, Weihong Ma, Danice Wilkins, Lisbeth A. Welniak, Kai Sun
Journal: Blood (2005)
OA08.02 Phase II Study of Erlotinib in Advanced Non-Small Cell Lung Cancer Patients with Leptomeningeal Metastasis (LOGIK1101)
Authors: Keiichi Ota, Yoshimasa Shiraishi, Taishi Harada, Daisuke Himeji, Takeshi Kitazaki, Noriyuki Ebi, Akinobu Hamada, Takeharu Yamanaka, Kaname Nosaki, Mitsuhiro Takenoyama, Kenji Sugio
Journal: Journal of Thoracic Oncology (2017)
Characterization of Bone Marrow (BM)- and Fat Tissue-Derived (F) Mesenchymal Stem Cells (MSC) From Patients without Bone Marrow Involvement.
Authors: Renata Dmitrieva, Izida Minullina, Anna Bilibina, Olga Tarasova, Sergey Anisimov, Andrey Zaritskey
Journal: Blood (2010)
Screen and intervene to prevent diabetes?
Authors: Norman Waugh
Journal: BMJ (2017)

Adherence to lifestyle changes across whole populations is the key to prevention

The BMJ includes a review of screening tests for non-diabetic hyperglycaemia (“pre-diabetes” is unsatisfactory because many people so labelled do not develop diabetes) and of interventions to reduce or delay progression to type 2 diabetes. If we screen for diabetes, we may, depending on test and cut-offs used, identify more people with impaired glucose tolerance and impaired fasting glucose (the two forms of non-diabetic hyperglycaemia) than with diabetes. Screening for impaired glucose tolerance, however, meets most, but not all, of the National Screening Committee criteria.1

In their study, Barry and colleagues2 conclude that there is no perfect screening test for non-diabetic hyperglycaemia. They report that glycated haemoglobin (HbA1c) is only about 50% sensitive, but the review does not provide sensitivities for a range of thresholds. HbA1c could be 100% sensitive if a low enough threshold was chosen, but at the cost of substantially more false positives. In screening, there is usually a trade-off between sensitivity and specificity. The researchers found that fasting …
Markers of Oxidative Stress Do Not Correlate with Labile Plasma Iron Blood in Patients with Myelodysplastic Syndromes
Authors: Christian Rose, Fathi Driss, Veronique Mansat De Mas, Odile Beyne-Rauzy, Emmanuel Gyan, Yongmin MA, Robert Hider, Pierre Fenaux, Carole Beaumont
Journal: Blood (2015)
Letter by Koh Regarding Article, “Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial”
Authors: Kwang Kon Koh
Journal: Circulation (2017)

guideline therapy will be further defined in the reduction of residual cardiovascular risk in the future.
P1.08-027 Evolution of Survival in a Regional Population-Based US Lung Cancer Resection Cohort
Authors: Raymond Osarogiagbon, Nicholas Faris, Matthew Smeltzer, Meredith Ray, Carrie Fehnel, Cheryl Houston-Harris, Paul Levy, Chris Mutrie, Brad Wolf, Lawrence Deese, Lynn Wiggins, Vishal Sachdev, Sam Signore, Edward Robbins
Journal: Journal of Thoracic Oncology (2017)
P234 Sputum cytokines and clinical biomarkers in severe asthma
Authors: R Shrimanker, S Go, S Thulborn, L Xue, ID Pavord
Journal: Thorax (2016)

<h3>Introduction</h3> Emerging treatments for type-2 high asthma such as anti-IL-5 (mepolizumab) and anti-IL-4 and IL-13 (dupilumab) target specific cytokine pathways resulting in type-2 inflammation. Whether patients with type 2 inflammation respond equally to both treatment or have distinct IL-13 and IL-5 profiles is currently unclear. We have tested the hypothesis that these pathways may function independently of each other and that simple biomarkers can help differentiate IL-13 and IL-5 high patients. <h3>Methods</h3> Patients with well characterised, severe asthma were evaluated with the blood eosinophil count and fractional exhaled nitric oxide (FeNO). Patients also had paired measurements of type-2 cytokines in induced sputum samples. Sputum cytokines were measured using a Luminex assay. <h3>Results</h3> We found that there was no relationship between the blood eosinophil count and FeNO. There was a positive correlation between FeNO and sputum IL-13 (r = 0.51, p &lt; 0.01) and blood eosinophils and sputum IL-5 (r = 0.47, p &lt; 0.01). <h3>Conclusions</h3> These findings suggest that readily available, non-invasive biomarkers may be able to differentiate sub-phenotypes in type-2 high asthma. Post-hoc analysis of clinical trial data of anti-IL-5 and anti-IL-4 and IL-13 treatments based on the predominant clinical biomarker would be of interest to see if these predict response to treatment. Simple biomarkers may be of use in deciding which of the emerging biological treatments to use in severe, type-2 high asthma.
<i>Notes from the Field</i>: Detection of Sabin-Like Type 2 Poliovirus from Sewage After Global Cessation of Trivalent Oral Poliovirus Vaccine — Hyderabad and Ahmedabad, India, August–September 2016
Authors: Sunil Bahl, Lee M. Hampton, Pankaj Bhatnagar, Gadala Srinivasa Rao, Pradeep Haldar, Lucky Sangal, Puttaraju AK Jetty, Uma P Nalavade
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

During September 2-October 4, 2016, four sewage samples collected during August 3-September 19 (Hyderabad, Telangana State, India) and one sewage sample collected on August 30 (Ahmedabad, Gujarat State, India) tested positive for Sabin-like type 2 polioviruses.These polioviruses were detected approximately 4 months after April 25, 2016, when India officially ceased use of trivalent oral poliovirus vaccine (tOPV), containing Sabin attenuated types 1, 2, and 3 polioviruses, and switched to bivalent OPV (bOPV), containing Sabin attenuated types 1 and 3 polioviruses (1).Detection of Sabin-like type 2 poliovirus approximately 4 months after the switch from tOPV to bOPV suggested that tOPV use might have continued after it was supposed to stop globally, creating a risk for emergence of new type 2 vaccinederived polioviruses (VDPV2s), which can cause paralysis.Genetic sequencing of the 903-nucleotide VP1 region of the isolated viruses showed zero, one, two, and four nucleotide changes in the four Hyderabad isolates and one nucleotide change in the Ahmedabad isolate, compared with the type 2 polioviruses in tOPV.These findings indicated that the isolated polioviruses had not replicated sufficiently to accumulate more than a few mutations on a potential pathway to becoming VDPV2s, and that the tOPV they originated from had likely been used during the preceding 4 months.In accordance with global guidelines for responding to poliovirus events (2), detailed investigations were initiated within 48 hours of detection of the type 2 poliovirus in Hyderabad and the neighboring Rangareddy district, and in Ahmedabad (Box).As part of global poliovirus containment efforts (3), laboratories in those areas potentially storing type 2 polioviruses had previously been found to not have such polioviruses, so they were not searched.Telangana and Gujarat state officials met with immunization program stakeholders in the affected districts and other districts in their states regarding the need to reconfirm withdrawal of all tOPV.In Hyderabad and Rangareddy districts, the two main district vaccine cold stores, along with 13 private vaccine retailers and distributors and 4,498 public and private health facilities,
P1.02-041 Characterization of MET-N375S as an Activating Mutation in Squamous Cell Carcinoma of the Lung
Authors: Li Ren Kong, Nur Afiqah Binte Mohamed Salleh, Tuan Zea Tan, Dennis Kappei, Boon Cher Goh
Journal: Journal of Thoracic Oncology (2017)
P231 Breathing pattern disorders in a complex breathlessness service; classification and clinical characteristics
Authors: RM Stacey, A Vyas, SJ Fowler
Journal: Thorax (2016)

<h3>Background and aim</h3> Many patients presenting to our complex breathlessness service appear to have breathing pattern disorders (BPDs). When suspected clinically, they are referred to a specialist respiratory physiotherapist for assessment and treatment. Here we describe the prevalence of identifiable breathing patterns and their clinical characteristics <h3>Methodology</h3> We performed a retrospective review of our clinical database including patients seen for initial physiotherapy assessment between December 2015 and June 2016. Patients underwent a standardised diagnostic assessment (clinical history, physiotherapy assessment, lung function and Nijmegan questionnaire). <h3>Results</h3> Data from 43 patients with confirmed BPD were included, 77% female, mean age 58 yrs. Relevant respiratory comorbidities included chronic cough (33%), asthma (30%) and vocal cord dysfunction (30%), with no comorbidity in 23%. Other associated conditions included musculoskeletal conditions (47%), chronic pain (44%), obesity (44%), nasal blockage (42%) and anxiety (31%). Four categories of breathing patterns were identified: thoracic dominant (58%), irregular/crescendo (51%), forced abdominal expiration (30%), and thoraco-abdominal asynchrony (2%). More than one BPD was seen in 35% of patients; only forced abdominal expiration and thoracic dominant didn’t co-exist. Conversely all pattern types could be found in isolation, although irregular/crescendo was more likely to co-exist with another pattern type. <h3>Conclusion</h3> Four separate breathing pattern types were identified, in isolation or in combination. Although anxiety was fairly common, many other associated disease and conditions were seen, especially relating to biomechanical factors. This preliminary data may enable clinicians to identify breathing pattern types, lead to the development of targeted treatment options and promote screening of particular conditions associated with BPD.
The F-BAR Protein PACSIN2 Regulates Platelet Intracellular Membrane Architecture and in Vivo Hemostatic Functions
Authors: Terese Jönsson, Fred G Pluthero, Antonija Jurak Begonja, Jan Kormann, Mélanie Demers, Denisa D Wagner, Markus Plomann, John H Hartwig, Walter H Kahr, Hervé Falet
Journal: Blood (2014)
P216 Associations between the psychological health of patients and their informal carers in advanced copd: what are the risk factors for anxiety and depression in patients, carers and patient-carer dyads?
Authors: EZ Mi, EZ Mi, S Mendonca, AC Gardener, MC Farquhar
Journal: Thorax (2016)

<h3>Introduction</h3> Anxiety and depression (AD) are highly prevalent in patients with advanced COPD and their informal carers, and are associated with lower quality of life and increased healthcare use. Previous studies have postulated risk factors for patient AD in COPD (including dyspnoea, poor functional status and poor self-management) and carer AD (including female gender, insufficient support and high subjective symptom burden). However, little is known about the association between patient and carer AD. We aimed to determine this and factors associated with patient, carer and dyad AD. <h3>Methods</h3> Prospective mixed-method interviews with a population-based cohort of 109 pairs of well-characterised advanced COPD patients and their carers. Clinical anxiety and depression (defined as Hospital Anxiety and Depression Scale [HADS] anxiety or depression score &gt;11) were identified and a dichotomous ‘psychological morbidity’ (PM) variable created (HADS score &gt;11 for either anxiety or depression) due to small sample size. Mann-Whitney U tests and multivariate logistic regression identified factors associated with patient (n = 39) or carer (n = 30) PM. <h3>Results</h3> Prevalence of anxiety and depression was 31.2% and 15.6% in patients and 26.6% and 11% in carers respectively. In univariate analysis, patient and carer PM were significantly associated with each other (p = 0.005), with odds ratio 3.388 (95% CI: 1.414–8.118), and mainly disease-related variables and carer characteristics (including poor coping and unmet support needs), respectively. No demographic factors were significantly associated with patient PM but female gender was associated with carer PM. Table 1 shows the results of multivariate analysis. Finally, dyad PM was associated with male patients/female carers, living apart, parent-child relationship, and more exacerbations. <h3>Conclusions</h3> For patients, more exacerbations may indicate disease progression resulting in anxiety, fatigue may limit activity leading to social isolation and depression, and poor self-management may increase symptom burden leading to AD. Patient PM could lead to carer PM by increasing carer burden and impairing intra-dyad communication. Our study, with the strength of a prospective approach and recruitment from primary care, highlights the need to assess AD in carers of COPD patients (particularly with AD), to prevent it with more information and support for carers, and for interventions targeting the dyad.
Interleukin-1 Beta Promotes the Expression of Prox-1 and Vascular Endothelial Growth Factor Receptor Type-3 in Adult Human Dermal Fibroblasts
Authors: Matsuo Takuji, Ryosuke Shirasaki, Haruko Tashiro, Yoko Oka, Tadashi Yamamoto, Nobu Akiyama, Kazuo Kawasugi, Naoki Shirafuji
Journal: Blood (2012)
BMET-22. DOES WHOLE BRAIN RADIOTHERAPY FOR OLIGOMETASTATIC BRAIN METASTASES TRANSLATE INTO A SURVIVAL BENEFIT FOR PATIENTS WITH A LIMITED COMPETING RISK FROM EXTRA-CRANIAL DISEASE? A SECONDARY ANALYSIS OF EORTC 22952-26001
Authors: Thomas Churilla, Elizabeth Handorf, Sandra Collette, Laurence Collette, Yanqun Dong, Ayal Aizer, Brian Alexander, Martin Kocher, Stephanie Weiss, Riccardo Soffietti
Journal: Neuro-Oncology (2016)
P1.07-004 Updated Analysis of Phase II Study of HA-Irinotecan, a CD44-Targeting Formulation of Hyaluronic Acid and Irinotecan, in Small Cell Lung Cancer
Authors: Muhammad Alamgeer, Peter Briggs, Ben Markman, Peter Midolo, Neil Watkins, Beena Kumar, Vinod Ganju
Journal: Journal of Thoracic Oncology (2017)
Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies
Authors: Nikolas Herold, Sean G Rudd, Linda Ljungblad, Kumar Sanjiv, Ida Hed Myrberg, Cynthia B J Paulin, Yaser Heshmati, Anna Hagenkort, Juliane Kutzner, Brent D G Page, José M Calderón-Montaño, Olga Loseva, Ann-Sofie Jemth, Lorenzo Bulli, Hanna Axelsson, Bianca Tesi, Nicholas C K Valerie, Andreas Höglund, Julia Bladh, Elisée Wiita, Mikael Sundin, Michael Uhlin, Georgios Rassidakis, Mats Heyman, Katja Pokrovskaja Tamm, Ulrika Warpman-Berglund, Julian Walfridsson, Sören Lehmann, Dan Grandér, Thomas Lundbäck, Per Kogner, Jan-Inge Henter, Thomas Helleday, Torsten Schaller
Journal: Nature Medicine (2017)