tbuckley/cabot-search huggingface dataset:
Studies on non-alcoholic fatty liver disease should stratify by disease severity
Authors: Matthew T McKenna-Barry, John D Ryan
Journal: BMJ (2019)

In a large, population based cohort study, Alexander and colleagues report that a diagnosis of non-alcoholic fatty liver disease (NAFLD) does not confer an increased risk of ischaemic heart disease or stroke.1 To translate these findings into clinical practice, we must appreciate the spectrum of NAFLD severity, especially as patients with advanced fibrosis have …
Abstract 14921: A Multicenter Study of Systolic Stretch in Patients With Right Bundle Branch Block and Their Potential to Respond to Cardiac Resynchronization Therapy
Authors: Nobuyuki Kagiyama, Joost Lumens, Masataka Sugahara, Ryan M Gage, Kevin Vernooy, Alan J Bank, Evan Adelstein, John Gorcsan
Journal: Circulation (2018)

Introduction: Patients with right bundle branch block (RBBB) are controversial candidates for cardiac resynchronization therapy (CRT). Systolic stretch index (SSI) is a novel marker developed by co...
Analysis of factors that characterize health impairment in patients with chronic respiratory failure
Authors: M. Carone, G. Bertolotti, F. Anchisi, A.M. Zotti, C.F. Donner, P.W. Jones, None on behalf of the “quality of Life in Chronic Respiratory Failure Group”
Journal: European Respiratory Journal (1999)

This study was designed to identify a core set of items that may characterize impaired health in chronic respiratory failure (CRF) since none of the questionnaires commonly used to measure impaired health in patients with CRF were developed for use in such patients. Questionnaire items, identified from several sources, were administered to 92 patients with stable severe chronic hypoxia or hypercapnia, together with physiological measures of disease severity, the Sickness Impact Profile (SIP) and the St George′s Respiratory Questionnaire (SGRQ). Of the 152 items identified, only 28 correlated with patients′ perceptions of overall health and were also independent of age, sex, disease or type of treatment and did not show floor or ceiling effects. Principal components analysis identified three specific factors: “daily activities”, “cognitive function”, and “invalidity”. The total score for the whole 28-item set correlated with other measures of disease activity, including SGRQ (r=0.86) and SIP (r=0.70), but not spirometry. The interquartile range of the 28-item set was wider than that of the SGRQ or the SIP. This study characterized two areas of health impairment in chronic respiratory failure that had not previously been identified: effects of impaired cognitive function on daily life, and a sense of invalidity. The measurements properties of this 28-item set suggest that it may be a more discriminative instrument for patients with chronic respiratory failure than existing questionnaires.
A phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in patients with advanced hepatocellular carcinoma (HCC).
Authors: Jennifer J. Knox, Rui Qin, Jonathan R. Strosberg, Andreas Kaubisch, Anthony B. El-Khoueiry, Tanios B Bekaii-Saab, Charles Erlichman
Journal: Journal of Clinical Oncology (2012)

4099 Background: There is strong rationale to combine an m-TOR inhibitor (TEM) with a VEGF inhibitor (BEV) as a potentially active and well tolerated treatment for HCC. Both agents have shown modest single agent activity in HCC and so evaluated here in a phase II trial. Methods: A modified 2-stage Simon design planned 25 or 50 patients (pts) to test the null hypothesis that true tumor response rate is at most 10% andtrue 6-mo progression-free survival rate (PFS) (by RECIST) is at most 65%, or no better than single agent BEV (6 mo PR &gt;2 pts or PFS 6 mo &gt;18 out of 25.) Toxicity, TTP, PFS and survival were 2nd endpoints. Eligible pts had confirmed HCC with disease unresectable or amenable to other localised therapies, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR class of agents. TEM was administered at starting dose 25 mg IV d1,8,15,22 with BEV at 10mg/kg IV d 1, 15, all q 28 days (1 cycle). Imaging was q 8 wks. Results: From 09/09 to 09/11, 27 eligible pts were enrolled with 25 evaluable for toxicity and efficacy. Med age 59 yrs, 85% male, PS 0/1: 35/65, 58% metastatic, &gt;85% BCLC stage C. With med 6 cycles (range 1-14) delivered, most pts (88%) experienced a grade 3+ adverse event (a/e.) Common grade 3 a/es related to treatment included thrombocytopenia (40%), neutropenia (20%), leucopenia (12%), fatigue (8%), anemia, mucositis, dyspnea, diarrhea, bleeds, fistula, infections (4% each). There was one possible treatment related death. Per protocol dose reductions/discontinuation for TEM-related a/es were most common. There were 2 confirmed PRs and 16 pts progression-free by 6 mos. A third pt developed a late PR at cycle 13. Median TTP on study was 6 mos, median PFS was 7.4 mos and median survival was 8.3 mos, with 13 pts still alive. Accrual closed at end of stage 1 as neither the number of responses nor the PFS at 6 mos passed the futility stopping rule set for this combination. Conclusions: This multicenter study is the first HCC trial evaluating the BEV/TEM doublet. Despite manageable toxicity, the ORR and 6 mo PFS did not surpass assumptions based on single agent BEV in HCC. Further study of BEV/TEM combination in this advanced HCC population is not recommended.
Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial
Authors: Richard S. Finn, Baek-Yeol Ryoo, Philippe Merle, Masatoshi Kudo, Mohamed Bouattour, Ho Yeong Lim, Valeriy Breder, Julien Edeline, Yee Chao, Sadahisa Ogasawara, Thomas Yau, Marcelo Garrido, Stephen L. Chan, Jennifer Knox, Bruno Daniele, Scot W. Ebbinghaus, Erluo Chen, Abby B. Siegel, Andrew X. Zhu, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2019)

Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population.This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug.Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified.In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.
Validation of the optimum timing of assessment of tumour infiltrating lymphocytes during preoperative chemotherapy for breast cancer
Authors: S. Kashiwagi, Y. Asano, R. Kouhashi, S. Ishihara, Y. Tauchi, T. Morisaki, S. Noda, T. Takashima, N. Onoda, K. Hirakawa, M. Ohira
Journal: Annals of Oncology (2019)
Airway G-CSF identifies neutrophilic inflammation and contributes to asthma progression
Authors: Young-Min Kim, Hyekang Kim, Seungwon Lee, Sora Kim, Jong-Uk Lee, Youngwoo Choi, Han Wook Park, Gihoon You, Hansol Kang, Seyoung Lee, Jong-Sook Park, Yunji Park, Hae-Sim Park, Choon-Sik Park, Seung-Woo Lee
Journal: European Respiratory Journal (2019)

Stratification of asthmatic patients based on relevant biomarkers enables the prediction of responsiveness against immune-targeted therapies in patients with asthma. Individualised therapy in patients with eosinophilic asthma has yielded improved clinical outcomes; similar approaches in patients with neutrophilic asthma have yet to be developed. We determined whether colony-stimulating factors (CSFs) in the airway reflect the inflammatory phenotypes of asthma and contribute to disease progression of neutrophilic asthma.We analysed three different mouse models of asthma and assessed cytokine profiles in sputum from human patients with asthma stratified according to inflammatory phenotype. In addition, we evaluated the therapeutic efficacy of various cytokine blockades in a mouse model of neutrophilic asthma.Among the CSFs, airway granulocyte CSF (G-CSF) contributes to airway neutrophilia by promoting neutrophil development in bone marrow and thereby distinguishes neutrophilic inflammation from eosinophilic inflammation in mouse models of asthma. G-CSF is produced by concurrent stimulation of the lung epithelium with interleukin (IL)-17A and tumour necrosis factor (TNF)-α; therefore, dual blockade of upstream stimuli using monoclonal antibodies or genetic deficiency of the cytokines in IL-17A×TNF-α double-knockout mice reduced the serum level of G-CSF, leading to alleviation of neutrophilic inflammation in the airway. In humans, the sputum level of G-CSF can be used to stratify patients with asthma with neutrophil-dominated inflammation.Our results indicated that myelopoiesis-promoting G-CSF and cytokines as the upstream inducing factors are potential diagnostic and therapeutic targets in patients with neutrophilic asthma.
Author Correction: eHealth tools for the self-testing of visual acuity: a scoping review
Authors: Wai Kent Yeung, Piers Dawes, Annie Pye, Anna-Pavlina Charalambous, Malcolm Neil, Tariq Aslam, Christine Dickinson, Iracema Leroi
Journal: npj Digital Medicine (2019)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Development and preliminary validation of the Adolescent Psoriasis Quality of Life instrument: a disease‐specific measure of quality of life in adolescents with psoriasis
Authors: H. Randa, L.R. Khoury, T.K. Grønborg, J.J. Lomholt, L. Skov, R. Zachariae
Journal: British Journal of Dermatology (2019)

Background No age-appropriate and disease-specific instrument currently exists to measure health-related quality of life in adolescents with psoriasis (patients aged 12–17 years). Objectives To develop and provide preliminary validation of the Adolescent Psoriasis Quality of Life instrument. Methods Qualitative interviews with adolescents with psoriasis, parents of adolescents with psoriasis, and healthcare professionals informed the development of an initial item pool for the instrument, which was subsequently refined through cognitive interviews. Finally, data from an independent sample of adolescents with psoriasis (n = 50) were used for item reduction, scale construction and initial validation, using a combination of techniques from classical test theory and Rasch modelling. Results Rich qualitative data concerning health-related quality of life in adolescents with psoriasis (from 18 adolescents, 14 parents and four healthcare professionals), combined with cognitive interview testing (n = 12), resulted in a 41-item draft version. Item reduction led to the final version, a 17-item instrument consisting of two subscales showing good fit to their respective Rasch models: psychosocial impact (12 items) and the impact of physical symptoms and treatment (five items). All a priori stated hypotheses regarding construct validity were supported. Both subscales and the total scale showed acceptable test–retest reliabilities (intraclass correlations 0·97, 0·89 and 0·96) and internal consistencies (Cronbach's α 0·94, 0·81 and 0·95). Conclusions The preliminary form of the Adolescent Psoriasis Quality of Life instrument shows promising psychometric properties. It can be used in daily clinical practice and research to support a patient-centred approach and inform treatment planning. What's already known about this topic? Health-related quality of life (HRQoL) instruments should be targeted towards narrowly defined age groups, as life contexts of children, adolescents and adults may differ substantially. Dermatology-specific instruments have been used to measure HRQoL in adolescents with psoriasis, but it is not known whether these instruments accurately capture all relevant HRQoL aspects in adolescent psoriasis. Age-appropriate and psoriasis-specific instruments may be more sensitive for HRQoL issues experienced by this unique group. What does this study add? The Adolescent Psoriasis Quality of Life instrument represents the first age-appropriate and disease-specific instrument for measuring HRQoL in adolescents (12–17 years old) with psoriasis. It is intended for use in daily clinical practice to support dermatologists and other healthcare professionals in providing optimal care for adolescents with psoriasis. Linked Comment: Blome. Br J Dermatol 2020; 183:9.
A Phase 2 Trial of Inotuzumab Ozogamicin (InO) in Children and Young Adults with Relapsed or Refractory (R/R) CD22+ B-Acute Lymphoblastic Leukemia (B-ALL): Results from Children's Oncology Group Protocol AALL1621
Authors: Maureen M O'Brien, Lingyun Ji, Nirali N. Shah, Susan R. Rheingold, Deepa Bhojwani, Joanna S. Yi, Constance M. Yuan, Andrew C Harris, Patrick A. Brown, Michael J. Borowitz, Olga Militano, Meenakshi Devidas, Elizabeth A. Raetz, Lia Gore, Mignon L. Loh
Journal: Blood (2019)
The Dendritic Cell HLA-Class-II/Therapeutic Factor VIII (FVIII) Peptidome Is Influenced in Unanticipated Ways By the B-Domain of FVIII and the FVIII Chaperon Protein, Von Willebrand Factor: The Outrigger and Glycosylation-Umbrella (GUMB) Hypotheses
Authors: Tom E. Howard, Bernadette W. Luu, Marco Hofmann, Marcio A. Almeida, Satish Kumar, Long V. Dinh, Henry Mead, Jerry S. Powell, Miguel A. Escobar, Raja Rajalingam, Sarah Williams-Blangero, John Blangero, Maraskovsky Eugene, Vincent P. Diego
Journal: Blood (2019)
First China-manufactured trastuzumab biosimilar HLX02 global phase III trial met primary endpoint in breast cancer
Authors: B. Xu, Q. Zhang, T. Sun, W. Li, Y. Teng, X. Hu, I. Bondarenko, H. Adamchuk, Y. Li, B. Shan, J. Cheng, T. Peng, X. Wang, Y. Chen, W. Jiang, S. Liu, X. Zhang, E. Liu, A. Luk, Q. Wang
Journal: Annals of Oncology (2019)
Dasatinib-Blinatumomab Combination for the Front-Line Treatment of Adult Ph+ ALL Patients. Updated Results of the Gimema LAL2116 D-Alba Trial
Authors: Sabina Chiaretti, Renato Bassan, Antonella Vitale, Loredana Elia, Alfonso Piciocchi, Cristina Puzzolo, Martina Canichella, Felicetto Ferrara, Monia Lunghi, Francesco Fabbiano, Massimiliano Bonifacio, Nicola Fracchiolla, Prassede Salutari, Alessandra Mancino, Marco Vignetti, Anna Guarini, Alessandro Rambaldi, Robin Foà
Journal: Blood (2019)
How Did We Get Here?: A Historical Review and Critical Analysis of Anticoagulation Therapy Following Mechanical Valve Replacement
Authors: Sarah MacIsaac, Iqbal H. Jaffer, Emilie P. Belley-Côté, Graham R. McClure, John W. Eikelboom, Richard P. Whitlock
Journal: Circulation (2019)

Managing severe valvular heart disease with mechanical valve replacement necessitates lifelong anticoagulation with a vitamin K antagonist. Optimal anticoagulation intensity for patients with mechanical valves remains uncertain; current recommendations are inconsistent across guideline bodies and largely based on expert opinion. In this review, we outline the history of anticoagulation therapy in patients with mechanical heart valves and critically evaluate current antithrombotic guidelines for these patients. We conclude that randomized trials evaluating optimal anticoagulation intensity in patients with mechanical valves are needed, and that future guidelines must better justify antithrombotic treatment recommendations.
Abstract 15707: MYK-491, a Novel Small-Molecule Cardiac Myosin Activator Increases Cardiac Systolic Function and Preserves Mechanical Efficiency: Pre-Clinical in vivo and in vitro Evidence
Authors: Sarah Fernandes, Angelos Oikonomopoulos, Sarah K Jimenez-MacInnes, Roozbeh Aschar-Sobbi, Marcus Henze, Marius Sumandea, Qing-Fen Gan, Robert L Anderson, Carlos L del Rio
Journal: Circulation (2019)

Introduction: Cardiac myosin motors have been shown to efficiently convert ATP to mechanical force. MYK-491 is a novel small-molecule selective allosteric activator of cardiac acto-myosin that leve...
Living with multiple myeloma: A life disrupted.
Authors: Matthew Roger LeBlanc, Thomas William LeBlanc, Ashley Leak Bryant, Kathryn Ilonka Pollack, Chip Bailey, Sophia Kustas Smith
Journal: Journal of Clinical Oncology (2019)

95 Background: Multiple myeloma (MM) an incurable cancer of the plasma cells is the second most common hematologic malignancy. Over 30,000 new diagnoses and over 12,000 deaths are attributed to MM annually in the United States. Dramatic improvements in survival over the past fifteen years have been fueled by the rapid introduction of new therapies and resulting changes in treatment patterns. Extended survival coupled with complex and ongoing treatment contributes to significant disruptions to daily living. Therefore, the purpose of this study was to explore the many ways that a MM diagnosis disrupts and interferes with a person’s life in the current treatment era. Methods: A cross sectional qualitative descriptive study was conducted to explore the impacts of MM diagnosis and treatment on patients’ lives in the era of novel MM treatment. Semi-structured one-hour interviews were conducted at the Duke Cancer Center with MM patients and MM clinicians to explore MM’s impact on patients’ lives. Results: Fifteen MM patients and ten MM clinicians were interviewed between September 2017 and September 2018. Themes arose around ways that a MM diagnosis and treatment had far reaching and serious impacts on patients’ lives. Four major themes emerged: ‘Impacts on Social Life and Hobbies’, Maintaining Employment’, ‘Financial Pressure’, and ‘Relationship Stress'. Conclusions: The care of MM patients has made great strides as new and more effective treatments have extended survival for many patients. Health care at its best endeavors to reduce suffering as well as extend life. This study highlights the far-reaching impacts MM has on all aspects of patients’ lives. Understanding how a myeloma diagnosis and its treatment may interfere in patients’ lives could inform the development of interventions that target management strategies to limit these negative impacts.
Improved metagenomic analysis with Kraken 2
Authors: Derrick E. Wood, Jennifer Lu, Ben Langmead
Journal: Genome biology (2019)

Abstract Although Kraken’s k -mer-based approach provides a fast taxonomic classification of metagenomic sequence data, its large memory requirements can be limiting for some applications. Kraken 2 improves upon Kraken 1 by reducing memory usage by 85%, allowing greater amounts of reference genomic data to be used, while maintaining high accuracy and increasing speed fivefold. Kraken 2 also introduces a translated search mode, providing increased sensitivity in viral metagenomics analysis.
A Dose-Finding Study of Lenalidomide As Post-Remission Therapy for Older Adults with Acute Myeloid Leukemia (AML)
Authors: Matthew C. Foster, Hendrik W. Van Deventer, Katarzyna Jamieson, Benjamin G. Vincent, Melissa Matson, Karen McKinnon, Shannon Reisdorf, Jack Zhang, Will Pulley, Hyman Muss, Anastasia Ivanova, Joshua F Zeidner
Journal: Blood (2017)
Tepotinib in NSCLC patients harboring METex14 skipping: Cohort A of phase II VISION study
Authors: K. Park, E. Felip, R. Veillon, A. Cortot, J. Mazieres, H. Sakai, N. Reinmuth, S. Viteri, Y.-M. Chen, J.-Y. Han, T.-W. Jang, M. Morise, T. Sakamoto, T. Tokito, B.C. Cho, R. Bruns, J. Scheele, J. Straub, X. Le, P.K. Paik
Journal: Annals of Oncology (2019)
Biological Citizenship — A 53-Year-Old Man with Schizoaffective Disorder and PTSD Applying for Supplemental Security Income
Authors: Ippolytos Kalofonos
Journal: New England Journal of Medicine (2019)

Interview with Dr. Ippolytos Kalofonos on the gatekeeper role played by U.S. physicians in facilitating vulnerable patients’ access to disability benefits. (09:52)Download A man with multiple mental health conditions stops attending the clinic where he received wrap-around services. Denied Supplemental Security Income because his psychiatrist had documented his improvement, he had ceased taking his medications and ended up hospitalized.
Phase II Trial of Concurrent Atezolizumab With Chemoradiation for Unresectable NSCLC
Authors: Steven H. Lin, Yan Lin, Luyang Yao, Neda Kalhor, Brett W. Carter, Mehmet Altan, George Blumenschein, Lauren A. Byers, Frank Fossella, Don L. Gibbons, Jonathan M. Kurie, Charles Lu, George Simon, Ferdinandos Skoulidis, Joe Y. Chang, Melenda D. Jeter, Zhongxing Liao, Daniel R. Gomez, Michael O’Reilly, Vali Papadimitrakopoulou, Peter Thall, John V. Heymach, Anne S. Tsao
Journal: Journal of Thoracic Oncology (2019)
Strong T <sub>H</sub> 1-biased CD4 T cell responses are associated with diminished SIV vaccine efficacy
Authors: Venkateswarlu Chamcha, Pradeep B. J. Reddy, Sunil Kannanganat, Courtney Wilkins, Sailaja Gangadhara, Vijayakumar Velu, Richard Green, G. Lynn Law, Jean Chang, James R. Bowen, Pamela A. Kozlowski, Michelle Lifton, Sampa Santra, Traci Legere, Lynette S. Chea, Lakshmi Chennareddi, Tianwei Yu, Mehul S. Suthar, Guido Silvestri, Cynthia A. Derdeyn, Michael Gale, Francois Villinger, Eric Hunter, Rama Rao Amara
Journal: Science Translational Medicine (2019)

Activated CD4 T cells are a major target of HIV infection. Results from the STEP HIV vaccine trial highlighted a potential role for total activated CD4 T cells in promoting HIV acquisition. However, the influence of vaccine insert-specific CD4 T cell responses on HIV acquisition is not known. Here, using the data obtained from four macaque studies, we show that the DNA prime/modified vaccinia Ankara boost vaccine induced interferon γ (IFNγ+) CD4 T cells [T helper 1 (TH1) cells] rapidly migrate to multiple tissues including colon, cervix, and vaginal mucosa. These mucosal TH1 cells persisted at higher frequencies and expressed higher density of CCR5, a viral coreceptor, compared to cells in blood. After intravaginal or intrarectal simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV) challenges, strong vaccine protection was evident only in animals that had lower frequencies of vaccine-specific TH1 cells but not in animals that had higher frequencies of TH1 cells, despite comparable vaccine-induced humoral and CD8 T cell immunity in both groups. An RNA transcriptome signature in blood at 7 days after priming immunization from one study was associated with induction of fewer TH1-type CD4 cells and enhanced protection. These results demonstrate that high and persisting frequencies of HIV vaccine-induced TH1-biased CD4 T cells in the intestinal and genital mucosa can mitigate beneficial effects of protective antibodies and CD8 T cells, highlighting a critical role of priming immunization and vaccine adjuvants in modulating HIV vaccine efficacy.