tbuckley/cabot-search huggingface dataset:
First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies
Authors: Gregory L. Beatty, Peter J. O'Dwyer, Jason Clark, Jack G. Shi, Kevin J. Bowman, Peggy A. Scherle, Robert C. Newton, Richard Schaub, Janet Maleski, Lance Leopold, Thomas F. Gajewski
Journal: Clinical Cancer Research (2017)

Purpose: Indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the degradation of tryptophan to N-formyl-kynurenine. Overexpressed in many solid malignancies, IDO1 can promote tumor escape from host immunosurveillance. This first-in-human phase I study investigated the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of epacadostat (INCB024360), a potent and selective inhibitor of IDO1.Experimental Design: Fifty-two patients with advanced solid malignancies were treated with epacadostat [50 mg once daily or 50, 100, 300, 400, 500, 600, or 700 mg twice daily (BID)] in a dose-escalation 3 + 3 design and evaluated in 28-day cycles. Treatment was continued until disease progression or unacceptable toxicity.Results: One dose-limiting toxicity (DLT) occurred at the dose of 300 mg BID (grade 3, radiation pneumonitis); another DLT occurred at 400 mg BID (grade 3, fatigue). The most common adverse events in >20% of patients overall were fatigue, nausea, decreased appetite, vomiting, constipation, abdominal pain, diarrhea, dyspnea, back pain, and cough. Treatment produced significant dose-dependent reductions in plasma kynurenine levels and in the plasma kynurenine/tryptophan ratio at all doses and in all patients. Near maximal changes were observed at doses of ≥100 mg BID with >80% to 90% inhibition of IDO1 achieved throughout the dosing period. Although no objective responses were detected, stable disease lasting ≥16 weeks was observed in 7 of 52 patients.Conclusions: Epacadostat was generally well tolerated, effectively normalized kynurenine levels, and produced maximal inhibition of IDO1 activity at doses of ≥100 mg BID. Studies investigating epacadostat in combination with other immunomodulatory drugs are ongoing. Clin Cancer Res; 23(13); 3269-76. ©2017 AACR.
Evaluation qualitative du dépistage par coloscopie en Autriche
Authors: N. Musquer
Journal: Endoscopy (2016)

Depuis 2005, l’Autriche a mis en place un programme institutionnel de dépistage systématique du cancer colo-rectal par coloscopie pour les personnes à risque moyen, à partir de 50 ans. Ce programme s’est vu doublé d’une politique qualité dès 2007 visant à garantir et améliorer les performances du programme. Cette étude consistait en un bilan du programme après 7 ans de pratique.
Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys
Authors: Kazuhisa Takahashi, Tsutomu Igarashi, Koichi Miyake, Maika Kobayashi, Chiemi Yaguchi, Osamu Iijima, Yoshiyuki Yamazaki, Yuko Katakai, Noriko Miyake, Shuhei Kameya, Takashi Shimada, Hiroshi Takahashi, Takashi Okada
Journal: Molecular Therapy (2017)

The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 μL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.
Long Term Outcomes for Patients with Cyclic Neutropenia Treated with Granulocyte Colony-Stimulating Factor (G-CSF)
Authors: David C. Dale, Audrey Anna Bolyard, Merideth L. Kelley, Vahagn Makaryan, Mary Ann Bonilla, Laurence A. Boxer, Sabine Mellor-Heineke, Karl H. Welte, Peter E. Newburger, Cornelia Zeidler
Journal: Blood (2015)
P1.07-024 EGFR Mutations in Small Cell Lung Cancer (SCLC): Genetic Heterogeneity and Prognostic Impact
Authors: Huarong Tang, Jianjun Zhang, Xiao Hu, Yujin Xu, Baiqiang Dong, Jin Wang, Yue Kong, Honglian Ma, Zhongxin Liao, Jianhua Zhang, Lauren Averett Byers, Don Lynn Gibbons, Bonnie S. Glisson, Ignacio Wistuba, John Heymach, Daniel Richard Gomez, Andrew Futreal, Ming Chen
Journal: Journal of Thoracic Oncology (2017)
P1.05-017 The Prognostic Impact of EGFR, KRAS and TP53 Somatic Mutations in Curatively Resected Early-Stage Lung Adenocarcinomas
Authors: Bonnie Gould Rothberg, Rahul Das, Laura Jackson, Heather Lazowski, Yalai Bai, Daniel O'Neill, Sophia Roberts, Jonathan Rothberg, Roy Herbst, Anthony Kim, Daniel Boffa, David Rimm, Frank Detterbeck, Lynn Tanoue
Journal: Journal of Thoracic Oncology (2017)
S4 Implications of guidance in scotland on eligibility for treatment with mepolizumab and omalizumab – an ideal study analysis
Authors: CEA Hartmann, C Gait, NB Gunsoy, RA Mehta, FC Albers
Journal: Thorax (2016)

<h3>Rationale</h3> Severe asthma is a heterogeneous disease in which patients have diverse clinical characteristics and biomarkers, like eosinophils and IgE. It is important to understand their relationship in a severe asthma population. The IDEAL (Identification and Description of Severe Asthma Patients in a Cross-Sectional Study) study aimed to identify the proportion of patients with severe asthma who could be eligible for an anti IL-5 (mepolizumab) or anti-IgE (omalizumab) directed treatment, and those who may be eligible for either therapy. <h3>Methods</h3> IDEAL, an observational study included subjects aged ≥12 years with severe asthma defined according to ATS/ERS guidelines by treatment with high-dose ICS plus additional controller(s) for ≥12 months. Assessments included spirometry, a blood sample, and symptom/burden of illness questionnaires. Eligibility to mepolizumab and omalizumab were defined according to SMC advice (2016) and NICE MTA guidance (2013), which has been adopted in Scotland, respectively. Mepolizumab eligibility is defined as per SMC advice: patients who have eosinophils of at least 150 cells per microlitre (0.15 x 109/L) at initiation of treatment and have had at least four asthma exacerbations in the preceding year or are receiving maintenance treatment with oral corticosteroids. Omalizumab eligibility (NICE MTA guidance) is defined as evidence of severe persistent allergic asthma and need for continuous or frequent treatment with oral corticosteroids (defined as 4 or more courses in the previous year), and meeting bodyweight and IgE criteria for omalizumab treatment. <h3>Results</h3> 748 subjects with severe asthma were enrolled in the study of which 670 met analysis criteria. After exclusion of subjects currently treated with omalizumab (n = 168), 502 subjects were included in this post-hoc analysis (mean age = 50.9 years; 62% female). 60 subjects (12% [95% Exact CI: 9.2–15.1%]) were eligible for mepolizumab (SMC advice) and 16 (3.2% [1.8–5.1]) were eligible for omalizumab (NICE MTA guidance). Among the 60 mepolizumab eligible subjects, 10 (16.7% [8.3–28.5%]) were also eligible for omalizumab. <h3>Conclusions</h3> This is the first cross-sectional study providing estimation of the proportion of severe asthma patients eligible for biologic therapy in accordance with Scottish guidance, indicating 12% mepolizumab-eligible and 3.2% omalizumab-eligible patients with limited overlap. <h3>Funding</h3> GSK; 201722
Higher Intakes of Vegetables, Vitamin E, Manganese and Zinc Are Associated with a Lower Risk of Non-Hodgkin Lymphoma (NHL): Results from a Case-Control Study
Authors: Shernan G. Holtan, Timothy G. Call, Zachary S. Fredericksen, Helen M. O’Connor, Mark Liebow, William R. Macon, Neil E. Kay, Ivana N. Micallef, Alice H. Wang, Susan L. Slager, Thomas M. Habermann, James R. Cerhan
Journal: Blood (2008)
Nonsurgical Management of Urinary Incontinence in Women
Authors: Sandra Culbertson, Andrew M. Davis
Journal: JAMA (2017)

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Happy corporate holidays from Coca-Cola
Authors: Robin Ireland, John R Ashton
Journal: BMJ (2017)

Selling sugary drinks at Christmas

I suppose we should have realised that Coca-Cola was up to something when it opened a head office next to the Royal Society of Medicine in Wimpole Street. The path of associating unhealthy products with health, wellbeing, and healthy lifestyles is one that has been well trodden down the years by the tobacco industry. The lessons have not been lost on Coca-Cola. In fact, you could argue that Coca-Cola started even earlier than tobacco.1

And the stakes have never been higher for the UK sugary drinks industry. In October 2015, Public Health England (PHE) published a report stating that not only is the consumption of sugar sweetened drinks particularly high in school age children but tends to be highest among the most disadvantaged.2 It suggested the introduction of a tax or levy on full sugar soft drinks. In August 2016, the government did just this, announcing a soft drinks …
P1.01-039 Does Distance between Chest and Surgery Departments Impact Outcome in Lung Cancer Patients? Results of KBP-2010-CPHG Study
Authors: Didier Debieuvre, Violaine Frappat, Stéphanie Dehette, Jacky Crequit, Michel Carbonnelle, Patricia Barre, Daniel Coëtmeur, François Goupil, Olivier Molinier, Michel Grivaux
Journal: Journal of Thoracic Oncology (2017)
The evolving concept of liver cancer stem cells
Authors: Kouki Nio, Taro Yamashita, Shuichi Kaneko
Journal: Molecular Cancer (2017)

Liver cancer is an often fatal malignant tumor with a high recurrence rate and chemoresistance. The major malignant phenotypes of cancer, including recurrence, metastasis, and chemoresistance, are related to the presence of cancer stem cells (CSCs). In the past few decades, CSCs have been identified and characterized in many tumors including liver cancer. Accumulated evidence has revealed many aspects of the biological behavior of liver CSCs and the mechanism of their regulation. Based on these findings, a number of studies have investigated eradication of liver CSCs. This review focuses on the recent advances in our understanding of the biology of liver CSCs and the development of strategies for their treatment.
Genomic Microarray Alterations Add Prognostic Power to the IPSS-R in MDS with Normal Karyotype
Authors: Mar Mallo, Heinz Tuechler, Lee-Yung Shih, Seishi Ogawa, Masashi Sanada, Tung-Liang Lin, Christina Ganster, Katayoon Shirneshan, Detlef Haase, Maria López-Pavia, Jose Cervera, Esperanza Such, Leonor Arenillas, Olga Garcia, Vera Adema, Laura Palomo, Marti Mascaro, Elisa Luño, Jose Maria Raya, Peter L. Greenberg, Benjamin L Ebert, Francesc Sole
Journal: Blood (2014)
After the Party’s Over
Authors: James N. George, Jordan M. Morton, Nathan W. Liles, Carla M. Nester
Journal: New England Journal of Medicine (2017)

While driving home from a party, a 35-year-old previously healthy woman had a sudden onset of chills, myalgias, nausea, and abdominal cramping. That night fever, explosive nonbloody diarrhea, frequent vomiting, and abdominal and low back pain developed.
The Expression of LI-Cadherin in Bone Marrow Is Correlated with Clinical Outcome in Children with Acute Lymphoblastic Leukemia at First Relapse.
Authors: Shuling Wu, Anay Marquetti Hernández, Corinna Dietel, Arend von Stackelberg, Guenter Henze, Karl Seeger, Reinhard Gessner
Journal: Blood (2005)
MA07.06 Crizotinib in ROS1 Rearranged or MET Deregulated Non-Small-Cell Lung Cancer (NSCLC): Preliminary Results of the METROS Trial
Authors: Lorenza Landi, Antonio Chella, Rita Chiari, Marcello Tiseo, Roberta Buosi, Claudio Dazzi, Cesare Gridelli, Fausto Barbieri, Angelo Delmonte, Greta Alì, Gabriella Fontanini, Lucio Crinò, Frederico Cappuzzo
Journal: Journal of Thoracic Oncology (2017)
PL03.03: Randomized Phase III Study of Osimertinib vs Platinum-Pemetrexed for EGFR T790M-Positive Advanced NSCLC (AURA3)
Authors: Vassiliki Papadimitrakopoulou, Yi Long Wu, Myung-Ju Ahn, Suresh Ramalingam, Marina Garassino, Hye Ryun Kim, Frances Shepherd, Hiroaki Akamatsu, Willemijn Theelen, Chee Khoon Lee, Martin Sebastian, Alison Templeton, Marcelo Marotti, Serban Ghiorghiu, Tony Mok
Journal: Journal of Thoracic Oncology (2017)
Neutrophil Elastase Mutations and the Risk of Leukemia In Patients with Cyclic and Congenital Neutropenia.
Authors: David C. Dale, Vahagn Makaryan, Audrey Anna Bolyard, Rodger Elin, Andrew AG Aprikyan, Mary Ann Bonilla, Peter E. Newburger, Laurence A Boxer, Dan Link
Journal: Blood (2010)
Pleiotropic Effects of Statins on the Cardiovascular System
Authors: Adam Oesterle, Ulrich Laufs, James K. Liao
Journal: Circulation Research (2017)

The statins have been used for 30 years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol. Statins may exert cardiovascular protective effects that are independent of LDL-cholesterol lowering called pleiotropic effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small GTP-binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of proinflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis. The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matter of debate and are hard to quantify because the degree of isoprenoid inhibition by statins correlates to some extent with the amount of LDL-cholesterol reduction. This review examines some of the currently proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any clinical relevance in cardiovascular disease.
Appearance of Stress-Inducible Membrane Proteins ULBP on Blood Cells of Patients with PNH, Aplastic Anemia, and MDS: Possible Implication of ULBP in Immune-Mediated Marrow Injury.
Authors: Nobuyoshi Hanaoka, Kentaro Horikawa, Yasuchika Tsuzuki, Shoichi Nagakura, Sonoko Ishihara, Hiroaki Mitsuya, Hideki Nakakuma, Tatsuya Kawaguchi
Journal: Blood (2005)
P224 Towards person-centred care: development of a patient support needs tool for patients with advanced chronic obstructive pulmonary disease (copd) in primary care
Authors: AC Gardener, G Ewing, M Farquhar
Journal: Thorax (2016)

<h3>Introduction</h3> Patients with advanced COPD have difficulty articulating their support needs to clinicians, undermining person-centred care and support. A new approach, the Support Needs Approach for Patients (SNAP), informed by, and modelled on, the evidence-based Carer Support Needs Assessment Tool (CSNAT), may enable patients to identify and express their support needs and start person-centred conversations with clinicians. SNAP is underpinned by an evidence-based tool (a brief set of questions) to help patients consider and express their support needs. This study aimed to develop the SNAP tool, suitable for use in clinical practice. <h3>Methods</h3> Two-stage qualitative study. Stage 1: domains of support need in advanced COPD were identified through a rapid review of the literature, analysis of data from the Living with Breathlessness Study (n = 20 purposively sampled patients with advanced COPD) and patient focus groups. Stage 2: the draft SNAP tool was developed based on the identified domains of support need, then reviewed and refined in stakeholder workshops with patients, carers and clinicians (from primary, secondary and community care, including specialist respiratory care) to ensure acceptability and suitability for clinical practice. <h3>Results</h3> A comprehensive range of evidence-based domains of support need were identified in Stage 1 which were then formulated into questions for inclusion on the draft SNAP tool in Stage 2. The draft tool asks patients to consider whether they need more support in relation to 16 broad areas (domains) of support need such as practical help in the home, knowing what to expect in the future, understanding their condition, getting out and about, and support for their carer. Patients, carers and clinical stakeholders from community respiratory care endorsed the content and wording of the draft SNAP tool and the proposed Support Needs Approach for Patients which it underpins (forthcoming workshops with primary and secondary care clinicians will identify their views which will also be reported). <h3>Discussion</h3> The SNAP tool has the potential to help patients with advanced COPD identify and express their support needs to clinicians in order to enable delivery of person-centred care. Future work will test the tool’s validity and feasibility of use in everyday clinical practice.
Validation of the EBMT Risk Score for Patients with Hematologic Malignancies Receiving Allogeneic Hematopoietic Stem Cell Transplant in a Transplant Center in Colombia over 20 Years
Authors: Virginia Abello, Carmen Rosales, Manuel Rosales, Javier Figueroa, Iris Cordoba, Andres Armando Borda Molina, Enrique Pedraza, Herman Esguerra, Liceth Villamizar
Journal: Blood (2015)
P11 Utility of a novel prognostic tool in unselected patients with malignant pleural mesothelioma
Authors: R Wollerton, J Goodliffe, M Slade
Journal: Thorax (2016)

<h3>Introduction</h3> Malignant pleural mesothelioma (MPM) has a poor, but heterogeneous prognosis. Previously developed prognostic scores have been derived from patient cohorts not typical of routine UK practice. Recently, a novel prognostic tool, validated in unselected UK patients was published.<sup>1</sup> <h3>Objective</h3> To evaluate the utility of a novel prediction model by Brims <i>et al</i>,<sup>1</sup> to predict prognosis in mesothelioma patients presenting to a two-site UK district general hospital. <h3>Methods</h3> Consecutive patients diagnosed with mesothelioma between January 2010 and December 2015 were identified. Data were collected from electronic records at diagnosis (age, gender, histology, performance score, haemoglobin, albumin, weight loss) as well as dates of diagnosis and of death or last follow-up. Patients were allocated to prognostic groups as described by Brims et al. Groups were compared using Kaplan-Meier survival analysis. The proportion of patients whose survival fell within ± 33% of the survival predicted from the validation cohort of Brims et al. was calculated. <h3>Results</h3> 71 patients (60 male) were diagnosed with MPM during the study period, median age 74 (interquartile range (IQR) 15). Histological diagnosis was available in 66 (93%) patients (43.9% epithelioid, 21.2% undefined mesothelioma, 18.2% sarcomatoid, 13.6% biphasic, 3.0% atypical/mixed). Median overall survival was 262 days (IQR 284 days). 97% of patients could be allocated to a prognostic group. Median survival by Brims group, compared with predicted survival, is shown in Table 1. <h3>Conclusions</h3> The “Brims Score” can be retrospectively calculated in a high proportion of patients, using routinely collected data. It appears reliably to separate patients into cohorts with statistically significant difference in survival. The large within-group variation in survival, however, limits the utility of the score as a means of answering the question, “How long have I got, doc?” for individual patients. <h3>Reference</h3> Brims F, Meniawy T, Duffus I, <i>et al</i>. A novel clinical prediction model for prognosis in malignant pleural mesothelioma using decision tree analysis. <i>Journal of Thoracic Oncology</i> 2016;<b>11</b>(4);573–582.
P260 The utility of atypical pneumonia screening in community acquired pneumonia: the leicester experience
Authors: JA Bennett, S Robinson, R Rupesinge, J Skeemer, D Jenkins, G Woltmann
Journal: Thorax (2016)

<h3>Introduction</h3> Microbiological testing for atypical pathogens in patients attending hospital with community acquired pneumonia (CAP) is recommended for moderate or severe disease (NICE CG191 2014) or for patients failing to respond to treatment. Although it is unclear whether testing improves outcome even in severe disease, many patients have such tests performed regardless of severity. Having revised our pathways for assessment, treatment and documentation of patients with community acquired pneumonia we hypothesised that testing for atypical organisms has no impact on treatment decisions for these patients. <h3>Method</h3> We retrospectively identified all patients with a diagnosis of CAP who had investigations for atypical microbiology, September 2013 to May 2014, via our pneumonia database. We assessed CURB-65 score, atypical microbiology results and laboratory costings. The notes for all patients with positive atypical microbiological results were reviewed. <h3>Results</h3> 343 patients were identified for whom 329 were analysed. 329 patients generated 991 samples in total (825 serum, 165 urine antigen, 1 urine virology) at a laboratory cost of £5,594.29. Five samples were positive, one for urine legionella antigen. Greater than 50% of serological samples had no second (paired) sample sent. There was no correlation between CURB-65 scores and requesting of atypical microbiology requesting. One patient with positive legionella antigen had prolongation of treatment from 5 days to 14 days. No other patients had treatment changes as a consequence of atypical microbiological testing. <h3>Conclusion</h3> Atypical microbiological testing, in hospital, for CAP patients is commonly performed at significant cost with minimal clinical utility. We recommend that non-selective serological sampling is abandoned. The impact of legionella urinary antigen testing on outcome in moderate and severe cases requires a prospective study.