tbuckley/cabot-search huggingface dataset:
Molecular Evolution of <i>IDH</i> Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study
Authors: Kaspar Draaisma, Aikaterini Chatzipli, Martin Taphoorn, Melissa Kerkhof, Astrid Weyerbrock, Marc Sanson, Ann Hoeben, Slávka Lukacova, Giuseppe Lombardi, Sieger Leenstra, Monique Hanse, Ruth Fleischeuer, Colin Watts, Joseph McAbee, Nicos Angelopoulos, Thierry Gorlia, Vassilis Golfinopoulos, Johan M. Kros, Roel G.W. Verhaak, Vincent Bours, Martin J. van den Bent, Ultan McDermott, Pierre A. Robe, Pim J. French
Journal: Journal of Clinical Oncology (2019)

Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design.We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. MGMT, TERT, and EGFRvIII status was individually determined.The molecular profile of our cohort was identical to that of other GBM cohorts (IDH wild-type [WT], 95%; EGFR amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in IDH WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for TERT and EGFR mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within MGMT promoter-methylated tumors. MGMT promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments.This large cohort of matched primary and recurrent IDH WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate.
Sex Disparity Observed for Oncotype DX Breast Recurrence Score in Predicting Mortality Among Patients with Early Stage ER-Positive Breast Cancer
Authors: Fei Wang, Sonya Reid, Wei Zheng, Tuya Pal, Ingrid Meszoely, Ingrid A. Mayer, Christina E. Bailey, Ben Ho Park, Xiao-Ou Shu
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Prognostic value of Oncotype DX Breast Recurrence Score (RS) in male patients with breast cancer is understudied. We evaluated associations of RS with overall mortality in male patients with breast cancer and compared it with female counterparts. Experimental Design: With a cohort of 848 male and 110,898 female patients with breast cancer identified from the National Cancer Database (2010–2014), we estimated HRs and 95% confidence intervals (CI) for overall mortality associated with RS using Cox regression models. RS was evaluated continuously, as well as by categorization following respective traditional (≤17, 18–30, and ≥31) and TAILORx (≤10, 11–25, and ≥26) cutoffs. Results: RS was positively associated with mortality in male patients (HR = 1.13; 95% CI, 1.02–1.26 per unit RS increment) up to RS &amp;gt; 21, after which the risk plateaued. Among female patients, mortality began to increase with RS only when RS &amp;gt; 23 (HR = 1.02; 95% CI, 1.01–1.02 per unit of RS increment). The intermediate- (HR = 5.37; 95% CI, 1.79–16.11) and high-risk diseases (HR = 4.28; 95% CI, 1.22–14.97) defined by TAILORx, but not traditional cutoffs established for female patients, were associated with elevated mortality risk in men even after adjustment for demographic, clinical characteristics, and treatments, except chemotherapy. Conclusions: RS is associated with mortality in male patients with breast cancer at a much lower threshold than that for female patients. Studies are needed to establish specific guidelines for RS thresholds for male patients with breast cancer.
Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries
Authors: David R. Holmes, Vivek Y. Reddy, Nicole T. Gordon, David Delurgio, Shephal K. Doshi, Amish J. Desai, James E. Stone, Saibal Kar
Journal: Journal of the American College of Cardiology (2019)

Long-term data on the safety and efficacy of left atrial appendage closure (LAAC) for stroke prevention in patients with nonvalvular atrial fibrillation remain limited. The purpose of this study was to evaluate 4.5- to 5-year data in 2 U.S. Food and Drug Association LAAC mandated registries (CAP [Continued Access to PROTECT-AF] and CAP2 [Continued Access to PREVAIL]) for safety and efficacy. Two registries of patients implanted with LAAC devices provide the largest source of follow-up data. Both accompanied their respective randomized clinical trials, PROTECT-AF (Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device In Patients with Atrial Fibrillation versus Long Term Warfarin Therapy), which used the same endpoints (primary efficacy of composite of stroke, systemic embolism, cardiovascular/unexplained death, and safety). CAP included 566 patients with an average follow-up of 50.1 months (2,293 patient-years), and CAP2 included 578 patients with an average follow-up of 50.3 months (2,227 patient-years). CAP2 patients were significantly older and had higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) scores (4.51 vs. 3.88; p < 0.001). Procedural success was similar in both (94%). The primary composite endpoint occurred at a rate of 3.05 per 100 patient-years in CAP and 4.80 per 100 patient-years in CAP2; events contributing to this endpoint were most commonly cardiovascular/unexplained death (1.69 per 100 patient-years for CAP and 2.92 per 100 patient-years for CAP2). Hemorrhagic stroke was significantly less than ischemic stroke (0.17 per 100 patient-years in CAP and 0.09 per 100 patient-years in CAP2), and total stroke rates were significantly less than predicted by CHA2DS2-VASc score (78% reduction with CAP, 69% reduction with CAP2). These registries, which contain the longest and largest follow-up data of patients with the Watchman device, support LAAC as a safe and effective therapy for long-term anticoagulation in patients with nonvalvular atrial fibrillation, and document the lowest rate of hemorrhagic stroke identified in this population.
Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline
Authors: Mhairi Campbell, Joanne E McKenzie, Amanda Sowden, Srinivasa Vittal Katikireddi, Sue E Brennan, Simon Ellis, Jamie Hartmann-Boyce, Rebecca Ryan, Sasha Shepperd, James Thomas, Vivian Welch, Hilary Thomson
Journal: BMJ (2020)

In systematic reviews that lack data amenable to meta-analysis, alternative synthesis methods are commonly used, but these methods are rarely reported. This lack of transparency in the methods can cast doubt on the validity of the review findings. The Synthesis Without Meta-analysis (SWiM) guideline has been developed to guide clear reporting in reviews of interventions in which alternative synthesis methods to meta-analysis of effect estimates are used. This article describes the development of the SWiM guideline for the synthesis of quantitative data of intervention effects and presents the nine SWiM reporting items with accompanying explanations and examples.
Interactome of Aiolos/Ikaros in Diffuse Large B-Cell Lymphoma (DLBCL) Reveals Novel Combination of Cereblon Modulators (CELMoD) and Histone Deacetylase (HDAC) Inhibitors
Authors: Patrick R. Hagner, Hsiling Chiu, Vivek S. Chopra, Martino S. Colombo, Nisha Patel, Maria Ortiz, Remco S. Loos, Fadi Towfic, Michelle Waldman, Anita K Gandhi
Journal: Blood (2019)
Ketogenic Diet for Obesity and Diabetes
Authors: William S. Yancy, Nia S. Mitchell, Eric C. Westman
Journal: JAMA Internal Medicine (2019)

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Italy's health performance, 1990–2017: findings from the Global Burden of Disease Study 2017
Authors: Lorenzo Monasta, Cristiana Abbafati, Giancarlo Logroscino, Giuseppe Remuzzi, Norberto Perico, Boris Bikbov, Giorgio Tamburlini, Ettore Beghi, Eugenio Traini, Sofia Boston Redford, Filippo Ariani, Antonio M Borzì, Cristina Bosetti, Giulia Carreras, Valeria Caso, Giulio Castelpietra, Massimo Cirillo, Sara Conti, Paolo Angelo Cortesi, Giovanni Damiani, Lucia Sara D'Angiolella, Jessica Fanzo, Carla Fornari, Silvano Gallus, Giorgia Giussani, Giuseppe Gorini, Giuseppe Grosso, Davide Guido, Carlo La Vecchia, Paolo Lauriola, Matilde Leonardi, Miriam Levi, Fabiana Madotto, Stefania Mondello, Luigi Naldi, Stefano Olgiati, Raffaele Palladino, Cristiano Piccinelli, Marco Piccininni, Elisabetta Pupillo, Alberto Raggi, Salvatore Rubino, Paola Santalucia, Marco Vacante, Simone Vidale, Francesco S Violante, Mohsen Naghavi, Luca Ronfani
Journal: The Lancet Public Health (2019)

Through a comprehensive analysis of Italy's estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we aimed to understand the patterns of health loss and response of the health-care system, and offer evidence-based policy indications in light of the demographic transition and government health spending in the country.
Economics and mental health: the current scenario
Authors: Martin Knapp, Gloria Wong
Journal: World Psychiatry (2020)

Economics and mental health are intertwined. Apart from the accumulating evidence of the huge economic impacts of mental ill-health, and the growing recognition of the effects that economic circumstances can exert on mental health, governments and other budget-holders are putting increasing emphasis on economic data to support their decisions. Here we consider how economic evaluation (including cost-effectiveness analysis, cost-utility analysis and related techniques) can contribute evidence to inform the development of mental health policy strategies, and to identify some consequences at the treatment or care level that are of relevance to service providers and funding bodies. We provide an update and reflection on economic evidence relating to mental health using a lifespan perspective, analyzing costs and outcomes to shed light on a range of pressing issues. The past 30 years have witnessed a rapid growth in mental health economics, but major knowledge gaps remain. Across the lifespan, clearer evidence exists in the areas of perinatal depression identification-plus-treatment; risk-reduction of mental health problems in childhood and adolescence; scaling up treatment, particularly psychotherapy, for depression; community-based early intervention and employment support for psychosis; and cognitive stimulation and multicomponent carer interventions for dementia. From this discussion, we pull out the main challenges that are faced when trying to take evidence from research and translating it into policy or practice recommendations, and from there to actual implementation in terms of better treatment and care.
Myocardial Ischemic Burden and Differences in Prognosis Among Patients With and Without Diabetes: Results From the Multicenter International REFINE SPECT Registry
Authors: Donghee Han, Alan Rozanski, Heidi Gransar, Tali Sharir, Andrew J. Einstein, Mathews B. Fish, Terrence D. Ruddy, Philipp A. Kaufmann, Albert J. Sinusas, Edward J. Miller, Timothy M. Bateman, Sharmila Dorbala, Marcelo Di Carli, Joanna X. Liang, Lien-Hsin Hu, Guido Germano, Damini Dey, Daniel S. Berman, Piotr J. Slomka
Journal: Diabetes Care (2019)

OBJECTIVE Prevalence and prognostic impact of cardiovascular disease differ between patients with or without diabetes. We aimed to explore differences in the prevalence and prognosis of myocardial ischemia by automated quantification of total perfusion deficit (TPD) among patients with and without diabetes. RESEARCH DESIGN AND METHODS Of 20,418 individuals who underwent single-photon emission computed tomography myocardial perfusion imaging, 2,951 patients with diabetes were matched to 2,951 patients without diabetes based on risk factors using propensity score. TPD was categorized as TPD = 0%, 0% &amp;lt; TPD &amp;lt; 1%, 1% ≤ TPD &amp;lt; 5%, 5% ≤ TPD ≤ 10%, and TPD &amp;gt;10%. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, unstable angina, or late revascularization. RESULTS MACE risk was increased in patients with diabetes compared with patients without diabetes at each level of TPD above 0 (P &amp;lt; 0.001 for interaction). In patients with TPD &amp;gt;10%, patients with diabetes had greater than twice the MACE risk compared with patients without diabetes (annualized MACE rate 9.4 [95% CI 6.7–11.6] and 3.9 [95% CI 2.8–5.6], respectively, P &amp;lt; 0.001). Patients with diabetes with even very minimal TPD (0% &amp;lt; TPD &amp;lt; 1%) experienced a higher risk for MACE than those with 0% TPD (hazard ratio 2.05 [95% CI 1.21–3.47], P = 0.007). Patients with diabetes with a TPD of 0.5% had a similar MACE risk as patients without diabetes with a TPD of 8%. CONCLUSIONS For every level of TPD &amp;gt;0%, even a very minimal deficit of 0% &amp;lt; TPD &amp;lt; 1%, the MACE risk was higher in the patients with diabetes compared with patients without diabetes. Patients with diabetes with minimal ischemia had comparable MACE risk as patients without diabetes with significant ischemia.
Developing a population health tool to identify patients with serious mental illness at cancer diagnosis.
Authors: Catherine Pappano, Vicki Fung, Maura Barry, Tanya Zucconi, Jing Chen, Kelly Irwin
Journal: Journal of Clinical Oncology (2019)

82 Background: Individuals with serious mental illness (SMI) experience increased cancer mortality and are less likely to receive timely cancer care. Despite increasing recognition that psychosocial care is essential for quality cancer care, mental illness remains underrecognized and undertreated. Involving psychiatry early may prevent cancer care disruptions. We developed an EHR-based algorithm to identify patients with SMI and cancer who may benefit from targeted interventions. Methods: We utilized structured codes from a widely-used, commercial EHR to identify patients with preexisting SMI and new breast, lung, head/neck, and gastrointestinal cancers seen in the Massachusetts General Cancer Center. We developed and refined an algorithm using ICD-10 diagnostic codes, medical history, appointment types, and consultations from across the health system. The algorithm updates every 24 hours to facilitate rapid intervention. We embedded a classification system to prioritize high-risk subgroups and key time points. We validated psychiatric diagnoses, cancer types, and appointments by randomly selecting 20 charts within each category and conducting a manual chart review. Results: Over 60 days from May to July 2019, the center saw 7674 patients in breast, thoracic, head/neck, and gastrointestinal oncology including 1674 patients (22%) with documented SMI. We identified 69 people (0.9%) with psychotic disorders, 111 (1.4%) with bipolar disorder, and 1,494 (19.5%) with major depression. Among patients with major depression, we prioritized recurrent major depression (N = 199), inpatient psychiatry consultation (N = 84), alcohol use disorders (N = 77), and opioid use disorders (N = 25). SMI was well-represented across cancers including 24% (916/3,815) of patients seen in breast, 25% (291/1,164) of thoracic, 24% (180/738) of head/neck, and 15% (287/1,956) of gastrointestinal oncology. Conclusions: We developed an EHR-based tool that identified a substantial population with SMI and cancer, prioritizing subgroups at high risk of cancer care disruptions. Leveraging data in the EHR is a feasible and promising strategy to detect a vulnerable population in need of targeted psychosocial interventions. Clinical trial information: NCT03360695.
Immune receptor repertoires in pediatric and adult acute myeloid leukemia
Authors: Jian Zhang, Xihao Hu, Jin Wang, Avinash Das Sahu, David Cohen, Li Song, Zhangyi Ouyang, Jingyu Fan, Binbin Wang, Jingxin Fu, Shengqing Gu, Moshe Sade-Feldman, Nir Hacohen, Wuju Li, Xiaomin Ying, Bo Li, X. Shirley Liu
Journal: Genome Medicine (2019)

Abstract Background Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T cells and B cells, remain poorly characterized. Methods In this study, we systematically analyzed the T cell receptor and B cell receptor (TCR and BCR) repertoires from the RNA-seq data of 145 pediatric and 151 adult AML samples as well as 73 non-tumor peripheral blood samples. Results We inferred over 225,000 complementarity-determining region 3 (CDR3) sequences in TCR α, β, γ, and δ chains and 1,210,000 CDR3 sequences in B cell immunoglobulin (Ig) heavy and light chains. We found higher clonal expansion of both T cells and B cells in the AML microenvironment and observed many differences between pediatric and adult AML. Most notably, adult AML samples have significantly higher level of B cell activation and more secondary Ig class switch events than pediatric AML or non-tumor samples. Furthermore, adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive microenvironment, are associated with regulatory T cells and worse overall survival. Conclusions Our comprehensive characterization of the AML immune receptor repertoires improved our understanding of T cell and B cell immunity in AML, which may provide insights into immunotherapies in hematological malignancies.
Dysregulated IL-6/GP130/JAK Signaling in Calreticulin Mutated Myeloproliferative Neoplasms (MPN)
Authors: Manjola Balliu, Laura Calabresi, Niccolò Bartalucci, Laura Maggi, Francesco Annunziato, Paola Guglielmelli, Alessandro M. Vannucchi
Journal: Blood (2019)
Time from Diagnosis to Treatment Does Not Affect Outcome in Intensively Treated Patients with Newly Diagnosed Acute Myeloid Leukemia
Authors: Christoph Röllig, Michael Kramer, Christoph Schliemann, Jan-Henrik Mikesch, Björn Steffen, Alwin Krämer, Tim Sauer, Mathias Hänel, Regina Herbst, Kerstin Schäfer-Eckart, Richard Noppeney, Edgar Jost, Tim H Brümmendorf, Stefan W Krause, Volker Kunzmann, Hermann Einsele, Sebastian Scholl, Andreas Hochhaus, Lars R. Fransecky, Martin Kaufmann, Andreas Neubauer, Dirk Niemann, Markus Schaich, Norbert Frickhofen, Alexander Kiani, Frank Heits, Ulrich Krümpelmann, Ulrich Kaiser, Johannes Kullmer, Maxi Wass, Stefan Klein, Malte Von Bonin, Jan Moritz Middeke, Christian Thiede, Friedrich Stoelzel, Johannes Schetelig, Gerhard Ehninger, Claudia D Baldus, Carsten Müller-Tidow, Uwe Platzbecker, Hubert Serve, Martin Bornhäuser
Journal: Blood (2019)
Impact of Competing Treatment Scenarios on Lifetime Disease Burden and Quality Adjusted Life Expectancy (QALE) Among Survivors of High-Risk Childhood Hodgkin Lymphoma (HR-HL): A Modeling Study Based on the St. Jude Lifetime (SJLIFE) Cohort
Authors: Nickhill Bhakta, Kalatu Davies, Jesse Turner, Yichen Chen, Jaime Flerlage, I-Chan Huang, Melissa M. Hudson, John T. Lucas, Monika Metzger, Leslie L. Robison, F. Lennie Wong
Journal: Blood (2019)
Sex and Race/Ethnicity Differences in Atrial Fibrillation
Authors: Annabelle Santos Volgman, C. Noel Bairey Merz, Emelia J. Benjamin, Anne B. Curtis, Margaret C. Fang, Kathryn J. Lindley, Carl J. Pepine, Marmar Vaseghi, Albert L. Waldo, Nanette K. Wenger, Andrea M. Russo
Journal: Journal of the American College of Cardiology (2019)
Genotype-phenotype relationships in patients with relatively mild mutations in abcb11 : Results from the napped consortium.
Authors: Daan van Wessel, Richard J. Thompson, Emmanuel M. Gonzales, Irena Jankowska, Etienne M. Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Patryk Lipinski, Piotr Czubkowski, Emmanuel Jacquemin, Anne Spraul, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Talal Algoufi, Nejat Mazhar, Emanuele Nicastro, Deirdre A. Kelly, Gabriela Nebbia, Henrik Arnell, Bjorn Fischler, Jan Hulscher, Daniele Serranti, Cigdem Arikan, Esra Polat, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Munoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsofi, Pier Luigi Calvo, Enke Grabhorn, Ekkehard Sturm, Wendy Van der Woerd, Binita M. Kamath, Jian-She Wang, Liting Li, Ozlem Durmaz, Bettina E. Hansen, Henkjan J. Verkade
Journal: Hepatology (2019)
The VITAL Trial: Phase II Trial of Vosaroxin and Infusional Cytarabine for Frontline Treatment of acute Myeloid Leukemia
Authors: Stephen A Strickland, Nikolai A. Podoltsev, Sanjay R Mohan, Amer M. Zeidan, Merrida A Childress, Gregory D Ayers, Michael T Byrne, Steven D. Gore, Robert K. Stuart, Michael R. Savona
Journal: Blood (2019)
Impact of Lisocabtagene Maraleucel (liso-cel) Treatment on Health-Related Quality of Life and Health Utility in Patients (pts) with Relapsed/Refractory (R/R) Aggressive B Cell Non-Hodgkin Lymphoma (NHL): Transcend NHL 001
Authors: Donald L. Patrick, Annette Powers, Monika Parisi, Yeonhee Kim, Jacob Garcia, Christine Dehner, David G. Maloney
Journal: Blood (2019)
Activity of afatinib in patients (pts) with NSCLC harboring uncommon EGFR mutations: Pooled analysis of three large phase IIIB trials
Authors: A. Passaro, F. De Marinis, H. Tu, K.K. Laktionov, J. Feng, A. Poltoratskiy, J. Zhao, E.-H. Tan, M. Gottfried, V. Lee, D. Kowalski, C.-T. Yang, B. Srinivasa, L. Clementi, W. Tang, D.C.-L. Huang, A. Cseh, K. Park, C. Zhou, Y.-L. Wu
Journal: Annals of Oncology (2019)