tbuckley/cabot-search huggingface dataset:
Role of occupational exposure on the outcome of sinus surgery: an observational study
Authors: Valérie Hox, Stefan Delrue, Hans Scheers, Erwin Adams, Stephan Keirsbilck, Mark Jorissen, Peter Hoet, Jeroen Vanoirbeek, Benoit Nemery, Peter Hellings
Journal: Allergy (2010)

Background: Functional endoscopic sinus surgery (FESS) is performed in patients with recurrent acute or chronic rhinosinusitis, insufficiently controlled by medical treatment. Several endogenous and exogenous factors may be responsible for failure of FESS with persisting symptoms. The association between occupational exposure and failure of FESS is not known.

Aim: The aim of this study was to evaluate the exposure to occupational agents in patients undergoing FESS and to relate the exposure to the number of FESS procedures needed to control symptoms.

Methods: Questionnaires were sent to 890 patients who had undergone one ore more FESS procedures and to 182 control subjects. Besides general medical health questions, the questionnaire asked about professional and recreational activities and exposure levels to high and low molecular weight (HMW and LMW) occupational agents. Exposure was assessed as a binary variable. A chi-square test was used to investigate the relationship between number of FESS and exposure state. Odds ratios were calculated by a Proportional Odds Model.

Results: Occupational exposure was reported in 11.6% of the controls (n=69) and in 24.6% of FESS patients (n=467). There is a significant relationship between increasing FESS and occupational exposure (chi=12.74, p<0.001). Exposed patients had a higher risk for needing at least 1 (OR=2.45, p<0.05) or at least 2 (OR=1.63, p<0.05) FESS procedures compared to unexposed ones. Mainly LMW agents were reported as occupational substances.

Conclusions: Exposure to occupational agents is associated with higher risk of failure after primary FESS, and hence underlines the importance of occupational exposure in the postoperative healing.
A phase 3, open-label, randomized study of the FLT3 inhibitor gilteritinib versus salvage chemotherapy in adults with first relapse or primary refractory FLT3 mutation-positive acute myeloid leukemia.
Authors: Alexander E. Perl, Jorge E. Cortes, Stephen Anthony Strickland, Ellen K. Ritchie, Andreas Neubauer, Giovanni Martinelli, Tomoki Naoe, Arnaud Pigneux, Philippe H. Rousselot, Christoph Röllig, Maria R. Baer, Richard A. Larson, Angela Joubert James, Caroline Chen, Lei Shu, Nahla Hasabou, Erkut Bahceci
Journal: Journal of Clinical Oncology (2016)

TPS7072 Background: FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML) and FLT3 internal tandem duplication (ITD) mutations are associated with high relapse rates, short remission durations, and poor overall survival (OS). Gilteritinib (ASP2215) is a highly selective FLT3 tyrosine kinase inhibitor with activity against FLT3-ITD mutations. It also inhibits FLT3-D835 mutations that can confer clinical resistance to other FLT3 inhibitors. A phase 1/2 study of gilteritinib in relapsed/refractory AML showed favorable tolerability across a wide dose range and consistent, potent, FLT3 inhibition in correlative assays. Cohort expansion in FLT3-mutated patients generated an overall response rate of 55% (CR/CRp/CRi = 44%, PR = 11%) and survival that was longer than in prior reports of cytotoxic chemotherapy or other FLT3 inhibitors. Therefore, a phase 3 trial was initiated. Methods: This randomized phase 3 study (NCT02421939) will enroll 369 adult AML subjects at ~140 centers across North America, Europe, and Asia. Subjects must be in first relapse or refractory to frontline therapy and have a centrally confirmed FLT3 mutation. Subjects will be randomized 2:1 to treatment with either 120 mg gilteritinib QD or to investigator's pre-randomization choice of specified salvage chemotherapy. Randomization will be stratified by prior chemotherapy response and salvage chemotherapy regimen intensity. Subjects randomized to gilteritinib or low-intensity chemotherapy will receive continuous 28-day cycles until a discontinuation event occurs; high-intensity chemotherapy subjects will receive up to 2 cycles before response measurement. The primary objective is OS; key secondary objectives are event-free survival and complete remission (CR) rate. Other secondary objectives include leukemia-free survival, remission duration, composite CR rate, subsequent transplantation rate, patient-reported fatigue, and overall safety. A formal interim analysis is planned after ~50% of deaths have occurred. Study enrollment began October 23, 2015; as of February 1, 2016, 10 subjects have been randomized. Clinical trial information: NCT02421939.
Inhibition of Complement Activation by Pexelizumab Reduces Death and Myocardial Infarction in Cardiac Surgical Patients With Selected Risk Profiles: Results from the International Multi-Center PRIMO-CABG Study
Authors: A Haverich, KM Taylor, M Carrier, JC Chen, SK Shernan, Frans Van de Werf, MF Newman, JH Levy, PX Adams, TG Todaro, van, er, Lm, ED Verrier
Journal: Circulation (2004)
Establishing CD8+ T Cell Immunity by Adoptive Transfer of Autologous, IL-15 Expanded, Anti-Tumor CTL with a Central/Effector Memory Phenotype Can Induce Objective Clinical Responses.
Authors: Marcus Butler, Philip Friedlander, Mary Mooney, Linda Drury, Martha Metzler, Matthew Milstein, Alla Berezovskaya, Marisa Flavin, Osamu Imataki, Makito Tanaka, Heather Daley, F. Stephen Hodi, Lee Nadler, Naoto Hirano
Journal: Blood (2009)
Translating neuroscience to the front lines: point-of-care detection of neuropsychiatric disorders
Authors: Jayashree Dasgupta, Supriya Bhavnani, Georgia Lockwood Estrin, Debarati Mukherjee, Arpan Banerjee, Matthew K Belmonte, Bhismadev Chakrabarti, Gauri Divan, Geraldine Dawson, Mark H Johnson, James C McPartland, Nandini C Singh, Vikram Patel
Journal: The Lancet Psychiatry (2016)
New Insights into Potential Driver Mutations in Pediatric Burkitt Lymphoma
Authors: Marius Rohde, Martin Zimmermann, Bettina R. Bonn, Monika Szczepanowski, Ilske Oschlies, Wolfram Klapper, Anja Möricke, Martin Schrappe, Inga Nagel, Reiner Siebert, Alfred Reiter, Birgit Burkhardt
Journal: Blood (2014)
P197 Efficacy of a Local Domiciliary Non-invasive Ventilation (NIV) Service for Motor Neurone Disease (MND): Patient Survival, Safety and Satisfaction: Abstract P197 Table 1
Authors: A Lane, J Tollit, R Lewis, P Murray
Journal: Thorax (2015)

<h3>Background</h3> NIV is an established treatment for MND patients with ventilatory failure and improves survival by an average of 219 days.<sup>1</sup> NHS England (2013)<sup>2</sup> recommend that MND patients are managed by complex weaning and ventilation centres. However, many patients find travel to hospitals difficult and distressing and therefore will not consider NIV. A Domiciliary NIV service was set up in April 2012 to provide integrated care in patients’ homes. A small prospective audit was carried out to investigate survival rates, adverse events and satisfaction with the service. <h3>Method</h3> Data were collected prospectively from 18 consecutive patients between April 2012 and June 2015 (169 weeks). NIV was started on onset of reported symptoms. All assessments, titration onto NIV and treatment was carried out in patients’ homes. <h3>Results</h3> 12 of 16 (75%) patients returned satisfaction questionnaires. 8 of 12 (67%) scored the service 10 (highly recommended) on the visual analogue scale, 4 patients left this blank. 100% responded that they had confidence and trust in the team and preferred to be seen at home. No adverse events were reported by these patients. <h3>Discussion</h3> NIV survival with home based care is comparable with the current literature. Of the patients who died, the longest survival was 339 days, 60 days under median survival for those still alive. The reason for this is unclear but may be partly explained by 3 patients with bulbar involvement in this group. Further investigation into this cohort may reveal differences, such as long term feeding. Analysis is required to establish if home care is cost effective. <h3>Conclusion</h3> MND patients requiring NIV can be safely and effectively managed in a home setting and find this preferable to hospital care. This patient centred model could increase the number of patients offered NIV, subsequently improving uptake. <h3>References</h3> 1 Bourke S, Tomlinson M, Williams TL, <i>et al</i>. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. <i>Lancet Neurol</i>. 2006;<b>5</b>:140–47 2 NHS England. NHS standard contract for respiratory: Complex home ventilation – adult. Service specification A14/S/a, 2013
Outcome of Patients with Chemotherapy Refractory and Early Progressive Diffuse Large B Cell Lymphoma After R-CHOP Treatment
Authors: Felicitas Hitz, Joseph M. Connors, Randy D. Gascoyne, Paul Hoskins, Alden A. Moccia, Kerry Joanne Savage, Laurie H. Sehn, Tamara Shenkier, Richard Klasa
Journal: Blood (2010)
Global differences in chemotherapeutic regimens of soft tissue sarcoma (STS): Results of PALETTE, an EORTC 62072/GSK VEG110727 global network phase III trial of pazopanib versus placebo.
Authors: Sandrine Marreaud, Winette T.A. Van der Graaf, Jean-Yves Blay, Sant P. Chawla, Jeeyun Lee, Binh Bui Nguyen, Paolo Giovanni Casali, Massimo Aglietta, Arthur P. Staddon, Yasuo Beppu, Axel Le Cesne, Hans Gelderblom, Ian Robert Judson, Nobuhito Araki, Monia Ouali, Mohamedraza Dewji, Alex Powell, George D. Demetri, Peter Hohenberger
Journal: Journal of Clinical Oncology (2012)

10067 Background: The global PALETTE EORTC/GSK network study on advanced STS patients (pts) randomized 223 European (EU), 43 American (US), 81 Asian, and 22 Australasian (AUS) pts between pazopanib and placebo. Prior to study entry pts should have received at least one anthracycline containing regimen, and preferably, if pts’condition allowed, all available standard chemotherapy treatments for STS in their countries. We investigated the differences in chemotherapy pts received prior- and post-protocol at a global level. Methods: Pts were grouped by continent. Pre- and post-protocol chemotherapeutic treatments (txs) were analyzed. The number of prior lines of systemic tx for advanced STS was divided between 0-1 vs 2 or more. Chemotherapy was studied in detail between Asian and other countries. Fisher’s exact test was used for statistical analysis. Results: Data from all 369 pts were analyzed. (Neo-) adjuvant systemic tx was given in 21% of EU, 23% of US, 36 % of Asian and 41% of AUS pts. In advanced STS: 2 or more lines of prior systemic txs were administered in 60% of EU, 84% of US, 42% of Asian, 22% of AUS pts before study entry. Prior to study entry 68% of EU, 65% of US, 84% of Asian and 68% of AUS pts received ifosfamide(or analogs); after protocol 21 % of EU, 14% of US, 13% of Asian and 5% of AU pts. There were significant differences in chemotherapy between Asian (n=81) and other (n=288) pts: prior to protocol trabectedin was administered in 1 vs 21%; gemcitabine 19 vs 39 %; cisplatin: 36 vs 5%; etoposide 32 vs 4% (all p&lt;0.001), and docetaxel: 17 vs 31 % (p=0.004) of pts. Post-protocol trabectedin was given to 4 vs 34% (p&lt;0.001), gemcitabine both in 19%; cisplatin 10 vs 4% (p=0.01); etoposide 12 vs 6%, and docetaxel 20 vs 12 % (both, p=0.02) of pts. Conclusions: The PALETTE study showed considerable intercontinental differences in chemotherapeutic txs for advanced STS pre- and post study drug. These differences might be due to availability and reimbursement of drugs, clinical studies and the practice patterns of sarcoma specialists world-wide. This is of particular interest for the design of future randomised global clinical trials in advanced STS.
The Endothelial Nitric Oxide Synthase Modulator Folic Acid Reduces Acute Doxorubicin-Induced Cardiac Damage and Mortality
Authors: Yanti Octavia, Melissa Swinnen, Fons K Verheyen, Marie-Helene Lenders, Hans Duimel, Hilde Gillijns, Rinrada Kietadisorn, Stefan Janssens, An L Moens
Journal: Circulation (2012)
Treatment strategies for low-risk febrile neutropenia in adult cancer patients: A cost-utility analysis.
Authors: O. Teuffel, E. Amir, L. Sung, S. M. Alibhai
Journal: Journal of Clinical Oncology (2010)

6102 Background: Febrile neutropenia remains a frequent complication of chemotherapy for adult cancer patients. There is uncertainty as to whether low-risk episodes are best managed in the inpatient or outpatient setting. Methods: A cost-utility model was created to compare four treatment strategies for low-risk febrile neutropenia in adult cancer patients. Event probabilities were retrieved from a formal systematic review and meta-analysis. Utilities were obtained from adult cancer patients. The base case was assumed to be an adult cancer patient with a first episode of low- risk febrile neutropenia. The model used a healthcare payer perspective in Ontario/Canada, and a time horizon of 30 days corresponding to one episode of febrile neutropenia. Four treatment strategies were evaluated: (1) entire treatment in hospital with intravenous antibiotics (HospIV), (2) early discharge strategy consisting of 48 hours inpatient observation with intravenous antibiotics, subsequently followed by oral outpatient treatment (EarlyDC), (3) entire outpatient management with intravenous antibiotics (HomeIV), and (4) entire outpatient management with oral antibiotics (HomePO). Outcome measures were quality-adjusted life months (QALMs), costs, and incremental cost-effectiveness ratios (ICER). Results: HomeIV was associated with both better health outcomes (0.797 QALM) and lower costs ($2,129) as compared to the other 3 strategies. Since HomePO (0.763 QALM; $2,309), EarlyDC (0.664 QALM; 5,647), and HospIV (0.661 QALM; $13,517) were all dominated, ICERs could not be determined. These results were sensitive to several event probabilities, utilities and costs. Beyond certain thresholds, the best strategy changed from HomeIV to the HomePO strategy. However, HospIV or EarlyDC management were never the preferred strategy in sensitivity analyses. Conclusions: For adult cancer patients with a first episode of febrile neutropenia, outpatient strategies were more effective and less costly compared with standard inpatient management. However, uncertainty remains whether intravenous or oral treatment might be the preferable route of drug administration in an ambulatory setting. No significant financial relationships to disclose.
Ibrutinib Treatment Reduces Both T-Regulatory Cells and B-Regulatory Cell Phenotype in Malignant B Cells in Chronic Lymphocytic Leukemia Patients
Authors: Meixiao Long, Kyle A. Beckwith, Kami J. Maddocks, Carolyn Cheney, Jennifer A. Woyach, Amy J. Johnson, Natarajan Muthusamy, John C. Byrd
Journal: Blood (2015)
Carotid body resection for sympathetic modulation in systolic heart failure: results from first‐in‐man study
Authors: Piotr Niewinski, Dariusz Janczak, Artur Rucinski, Stanislaw Tubek, Zoar J. Engelman, Pawel Piesiak, Przemyslaw Jazwiec, Waldemar Banasiak, Marat Fudim, Paul A. Sobotka, Shahrokh Javaheri, Emma C.J. Hart, Julian F.R. Paton, Piotr Ponikowski
Journal: European Journal of Heart Failure (2016)
Re: Thomas Seisen, Benoit Peyronnet, Jose Luis Dominguez-Escrig, et al. Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel. Eur Urol 2016;70:1052–68
Authors: Hao Lun Luo, Yen Ta Chen, Yuan Tso Cheng, Po Hui Chiang
Journal: European Urology (2016)
A5-06: Heat shock protein 27 - a novel target for non-small cell lung cancer and possible marker of metastasis
Authors: Tanguy Seiwert, Palma Rocchi, Lynn Bracht, Varalakshmi Janamanchi, Ramasamy Jagadeeswaran, Aliya Husain, Dongfeng Tan, Li Qiang, Martin Gleave, Ravi Salgia
Journal: Journal of Thoracic Oncology (2007)
Contrasting expression pattern of RNA-sensing receptors TLR7, RIG-I and MDA5 in interferon-positive and interferon-negative patients with primary Sjögren's syndrome
Authors: Naomi I Maria, Eline C Steenwijk, Arne S IJpma, Cornelia G van Helden-Meeuwsen, Petra Vogelsang, Wouter Beumer, Zana Brkic, Paul L A van Daele, P Martin van Hagen, Peter J van der Spek, Hemmo A Drexhage, Marjan A Versnel
Journal: Annals of the Rheumatic Diseases (2016)

The interferon (IFN) type I signature is present in over half of patients with primary Sjögren's syndrome (pSS) and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered as the main source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of patients with pSS.Blood samples from 42 healthy controls (HC) and 115 patients with pSS were stratified according to their IFN type I signature. CD123+BDCA4+ pDCs and CD14+ monocytes were isolated from peripheral blood mononuclear cells (PBMCs). Genome-wide microarray analysis was conducted on sorted pDCs in a small sample set, followed by validation of differentially expressed genes of interest in pDCs and monocytes.We found an upregulation of endosomal toll-like receptor (TLR) 7, but not TLR9, in IFN-positive (IFNpos) pDCs (p<0.05) and monocytes (p=0.024). Additionally, the downstream signalling molecules MyD88, RSAD2 and IRF7 were upregulated, as were the cytoplasmic RNA-sensing receptors DDX58/retinoic acid inducible gene-I (RIG-I) and IFIH1/melanoma differentiation associated gene-5 (MDA5). In vitro triggering of the TLR7-pathway in HC PBMCs induced upregulation of DDX58/RIG-I and IFIH1/MDA5, and downregulated TLR9. The upregulation of TLR7, its downstream signalling pathway, DDX58/RIG-I and IFIH1/MDA5 were confined to patients with IFN-positive pSS. IFN-negative patients had a contrasting expression pattern-TLR7 normal, and decreased TLR9, RIG-I and MDA5.Here we conclude a contrasting expression pattern of the RNA-sensing receptors TLR7, RIG-I and MDA5 in pDCs and monocytes of patients with IFNpos pSS. This profile could explain the pathogenic IFN production and might reveal novel therapeutic targets in these patients.
P1-065: Prognostic significance of thin-section CT findings in small-sized lung adenocarcinoma
Authors: Toshihiko Hashizume, Kouzo Yamada, Naoyuki Okamoto, Haruhiro Saito, Fumihiro Oshita, Yasufumi Kato, Hiroyuki Ito, Haruhiko Nakayama, Youichi Kameda, Kazumasa Noda
Journal: Journal of Thoracic Oncology (2007)
Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a
Authors: Ka Lun Cheung, Rachael Jarrett, Sumithra Subramaniam, Maryam Salimi, Danuta Gutowska-Owsiak, Yi-Ling Chen, Clare Hardman, Luzheng Xue, Vincenzo Cerundolo, Graham Ogg
Journal: The Journal of Experimental Medicine (2016)

Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells. In this study, we observed expression of a cytoplasmic PLA2 (PLA2G4D) in psoriatic mast cells but, unexpectedly, also found PLA2G4D activity to be extracellular. This was explained by IFN-α–induced mast cell release of exosomes, which transferred cytoplasmic PLA2 activity to neighboring CD1a-expressing cells. This led to the generation of neolipid antigens and subsequent recognition by lipid-specific CD1a-reactive T cells inducing production of IL-22 and IL-17A. Circulating and skin-derived T cells from patients with psoriasis showed elevated PLA2G4D responsiveness compared with healthy controls. Overall, these data present an alternative model of psoriasis pathogenesis in which lipid-specific CD1a-reactive T cells contribute to psoriatic inflammation. The findings suggest that PLA2 inhibition or CD1a blockade may have therapeutic potential for psoriasis.
A randomized, open-label, multicenter study evaluating thrombovascular events (TVEs) in subjects with cancer receiving chemotherapy and administered epoetin alfa (EPO) once weekly (QW) or three times a week (TIW) for the treatment of anemia.
Authors: R. Schlag, A. Lisyanskaya, L. Roman, M. M. Samama, Y. Wan, K. Deprince, E. Vercammen
Journal: Journal of Clinical Oncology (2010)

e19550 Background: Extensive clinical experience has demonstrated the safety and efficacy of EPO for treatment of chemotherapy- induced anemia. An increased incidence of TVEs is a known and labeled event in cancer patients receiving ESAs. This study compared the incidence of clinically relevant and objectively confirmed TVEs in the 2 approved dosing regimens (QW and TIW) of EPO when used per label instructions to treat anemia in subjects with nonmyeloid malignancies who are receiving chemotherapy. Methods: Eligible subjects (n = 504) were randomly assigned in a 1:1 ratio to receive EPO either TIW or QW. The sample size was estimated to provide at least 80% power (with 2 sided type I error of 0.05) to rule out an absolute difference of 6% in the TVE rates between the 2 groups assuming a TVE rate of approximately 6% in the TIW group. Randomization was stratified by study center and ECOG performance status (0 or 1 versus 2). The primary endpoint was the proportion of subjects with at least 1 clinically relevant and objectively confirmed TVE as determined by an Independent Adjudication Committee (IAC) from randomization through Week 16. Results: The proportion of subjects with at least 1 clinically relevant and objectively confirmed TVE from randomization through Week 16 was similar between the QW and TIW groups (2.1% and 3.8%, respectively (diff = −1.8%, 95% CI −5.1% to 1.6%, p = 0.25). The odds ratio for incidence rate was 0.53 (95% CI 0.18 to 1.58, p = 0.25). The proportion of subjects with a Hb increase of ≥2 g/dL or reaching a Hb of 12 g/dL by the end of the study, was 74% and 71%, respectively (diff = 2.6%, 95% CI −5.6% to 10.8%, p = 0.51). The proportion of subjects receiving at least 1 RBC transfusion during treatment period was 16% for both treatment groups (diff = −0.3%, 95% CI −7.1% to 6.5%, p = 0.92). The mortality was also similar in both treatment groups. Conclusions: The incidence of clinically relevant and objectively confirmed TVEs by an IAC was comparable in the 2 approved dosing regimens (QW and TIW) of EPO and generally consistent with TVE rates reported in oncology settings with EPO within the label guidance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Bristol-Myers Squibb, Sankyo Pharma, sanofi-aventis Johnson & Johnson