tbuckley/cabot-search huggingface dataset:
Abstract 14761: Comparing Patient Profiles of Clopidogrel versus Ticagrelor: A Systematic Literature Review and Meta-Analysis
Authors: Thomas Cuisset, Zuleika Aponte, Dara Paek, Michael del Aguila, Shalini Girotra, Dirk Sibbing
Journal: Circulation (2018)

Introduction: The ischemic benefit of ticagrelor over clopidogrel seen in randomized trial data has not been fully reproduced in real world data. The discrepancies in efficacy or safety outcomes be...
151P The landscape of patients with metastatic breast cancer enrolled in phase I trials
Authors: None Marra, C. Criscitiello, S. Morganti, P. Zagami, G. Viale, P. Tarantino, D. Trapani, E. Nicolò, M. Repetto, E. Ferraro, P. D'Amico, M. Locatelli, A. Esposito, G. Curigliano
Journal: Annals of Oncology (2020)
CLL and COVID-19 at the Hospital Clinic of Barcelona: an interim report
Authors: Tycho Baumann, Julio Delgado, Emili Montserrat
Journal: Leukemia (2020)

COVID-19 caused by SARS-CoV-2 has lead to a global pandemic already affecting over 3.5 million persons with more than 243,000 confirmed deaths [1].Early reports from China indicate that persons with cancer are more susceptible to SARS-CoV-2 [2].However, there are no data on the prevalence of COVID-19 in different types of cancer, including chronic lymphocytic leukemia (CLL).CLL is the most frequent leukemia in Western countries with an incidence of 4.2:100,000/year, increasing to more than 30:100,000/year at an age of >80 years.The median age at diagnosis is 72 years, and most patients are older than 60 years.Data from US SEER estimated >20,000 newly diagnosed cases of CLL in 2019 [3].CLL is frequently accompanied by immunodefiency (that can be aggravated by therapy) and comorbidity.Infections are the first cause of death in CLL.Cancer, older age, inmmunodeficiency, and chronic diseases are all risk factors for COVID-19 [4].It could be hypothesized, therefore, that patients with CLL are among those with a higher risk to contract COVID-19.However, the prevalence, clinical characteristics, and outcome of patients with CLL and COVID-19 infection have not yet been established, and to obtain the full picture will take time.Meanwhile, preliminary information from large series of patients can be useful.The Hospital Clinic from Barcelona is a reference center for CLL.In the period 2000-2019, 804 patients with CLL were registered.The median age was 67 years.The median overall survival is 11.8 years.Three hundred and eightyfour patients have died; in 236 with available information, infection was the cause of death in 35% subjects.The
Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer
Authors: Dinoop Ravindran Menon, Heinz Hammerlindl, Joachim Torrano, Helmut Schaider, Mayumi Fujita
Journal: Theranostics (2020)

Despite the recent advances in the treatment of cancers, acquired drug resistance remains a major challenge in cancer management. While earlier studies suggest Darwinian factors driving acquired drug resistance, recent studies point to a more dynamic process involving phenotypic plasticity and tumor heterogeneity in the evolution of acquired drug resistance. Chronic stress after drug treatment induces intrinsic cellular reprogramming and cancer stemness through a slow-cycling persister state, which subsequently drives cancer progression. Both epigenetic and metabolic mechanisms play an important role in this dynamic process. In this review, we discuss how epigenetic and metabolic reprogramming leads to stress-induced phenotypic plasticity and acquired drug resistance, and how the two reprogramming mechanisms crosstalk with each other.
Outbreak Investigation of COVID-19 Among Residents and Staff of an Independent and Assisted Living Community for Older Adults in Seattle, Washington
Authors: Alison C. Roxby, Alexander L. Greninger, Kelly M. Hatfield, John B. Lynch, Timothy H. Dellit, Allison James, Joanne Taylor, Libby C. Page, Anne Kimball, Melissa Arons, Albert Munanga, Nimalie Stone, John A. Jernigan, Sujan C. Reddy, James Lewis, Seth A. Cohen, Keith R. Jerome, Jeffrey S. Duchin, Santiago Neme
Journal: JAMA Internal Medicine (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused epidemic spread of coronavirus disease 2019 (COVID-19) in the Seattle, Washington, metropolitan area, with morbidity and mortality concentrated among residents of skilled nursing facilities. The prevalence of COVID-19 among older adults in independent/assisted living is not understood.To conduct surveillance for SARS-CoV-2 and describe symptoms of COVID-19 among residents and staff of an independent/assisted living community.In March 2020, public health surveillance of staff and residents was conducted on site at an assisted and independent living residence for older adults in Seattle, Washington, after exposure to 2 residents who were hospitalized with COVID-19.Surveillance for SARS-CoV-2 infection in a congregate setting implementing social isolation and infection prevention protocols.SARS-CoV-2 real-time polymerase chain reaction was performed on nasopharyngeal swabs from residents and staff; a symptom questionnaire was completed assessing fever, cough, and other symptoms for the preceding 14 days. Residents were retested for SARS-CoV-2 7 days after initial screening.Testing was performed on 80 residents; 62 were women (77%), with mean age of 86 (range, 69-102) years. SARS-CoV-2 was detected in 3 of 80 residents (3.8%); none felt ill, 1 male resident reported resolved cough and 1 loose stool during the preceding 14 days. Virus was also detected in 2 of 62 staff (3.2%); both were symptomatic. One week later, resident SARS-CoV-2 testing was repeated and 1 new infection detected (asymptomatic). All residents remained in isolation and were clinically stable 14 days after the second test.Detection of SARS-CoV-2 in asymptomatic residents highlights challenges in protecting older adults living in congregate settings. In this study, symptom screening failed to identify residents with infections and all 4 residents with SARS-CoV-2 remained asymptomatic after 14 days. Although 1 asymptomatic infection was found on retesting, a widespread facility outbreak was avoided. Compared with skilled nursing settings, in assisted/independent living communities, early surveillance to identify asymptomatic persons among residents and staff, in combination with adherence to recommended preventive strategies, may reduce viral spread.
Covid-19: A wake-up call
Authors: Fiona Godlee
Journal: BMJ (2020)

There will be things that the UK government has got right in managing the covid pandemic, but at this point in the proceedings it is hard to identify what those are. Some readers have questioned whether The BMJ ’s bleak assessment (doi:10.1136/bmj.m1918) is justified and asked us to be more supportive (https://bit.ly/3g6DG43). Few can doubt the size of the government’s challenge or the good faith and expertise of its chief advisers. But if ministers won’t share the thinking and evidence behind their decisions, we can only judge them on the results. They are in power, and we and others must hold them to account.

“Too little, too late, too flawed” is the verdict of our editorialists (doi:10.1136/bmj.m1932), as …
Gaps in Ethics Consultation Support for Patients and Families and Practical Guidance for Future Research or Quality Work Involving These Stakeholders
Authors: Hilary Mabel, Sundus Riaz, Marguerite Augustine, Jane Jankowski
Journal: The American Journal of Bioethics (2020)

Cho and colleagues pay valuable attention to the ethical concerns experienced by patients and families (Cho et al. 2020). In this commentary, we share some of the insights we gained by conducting a...
Abstract 14363: Cardiac Amyloidosis in Patients With Suspected Hypertrophic Cardiomyopathy
Authors: Ian C Chang, Angela Dispenzieri, Kyle W Klarich, Martha Grogan
Journal: Circulation (2018)

Introduction: Light-chain (AL) and transthyretin amyloidosis (ATTR) commonly lead to increased myocardial thickness and may mimic hypertrophic cardiomyopathy. At Mayo Clinic, hypertrophic cardiomyo...
73P microRNA expression profiles of single hormone receptor-positive breast cancers
Authors: M. Kunc, M. Popeda, A. Szalkowska, M. Niemira, A. Lacko, B.S. Radecka, M. Braun, J. Pikiel, M. Litwiniuk, K. Pogoda, A. Szwajkosz, E. Izycka-Swieszewska, A.J. Zaczek, W. Biernat, E. Senkus-Konefka
Journal: Annals of Oncology (2020)
Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials
Authors: Birgit Sawitzki, Paul N Harden, Petra Reinke, Aurélie Moreau, James A Hutchinson, David S Game, Qizhi Tang, Eva C Guinan, Manuela Battaglia, William J Burlingham, Ian S D Roberts, Mathias Streitz, Régis Josien, Carsten A Böger, Cristiano Scottà, James F Markmann, Joanna L Hester, Karsten Juerchott, Cecile Braudeau, Ben James, Laura Contreras-Ruiz, Jeroen B van der Net, Tobias Bergler, Rossana Caldara, William Petchey, Matthias Edinger, Nathalie Dupas, Michael Kapinsky, Ingrid Mutzbauer, Natalie M Otto, Robert Öllinger, Maria P Hernandez-Fuentes, Fadi Issa, Norbert Ahrens, Christoph Meyenberg, Sandra Karitzky, Ulrich Kunzendorf, Stuart J Knechtle, Josep Grinyó, Peter J Morris, Leslie Brent, Andrew Bushell, Laurence A Turka, Jeffrey A Bluestone, Robert I Lechler, Hans J Schlitt, Maria C Cuturi, Stephan Schlickeiser, Peter J Friend, Tewfik Miloud, Alexander Scheffold, Antonio Secchi, Kerry Crisalli, Sang-Mo Kang, Rachel Hilton, Bernhard Banas, Gilles Blancho, Hans-Dieter Volk, Giovanna Lombardi, Kathryn J Wood, Edward K Geissler
Journal: The Lancet (2020)
58P Detection of PIK3CA mutations in plasma ctDNA by Crystal Digital PCR for the selection of alpelisib treatment in routine clinical practice in advanced breast cancer patients
Authors: T. de La Motte Rouge, F. Le Du, J. Corne, F. Godey, H. Bourien, A. Brunot, L. Crouzet, C. Perrin, C. Lefeuvre-Plesse, V.C. Dieras, V. Quillien
Journal: Annals of Oncology (2020)
Public reporting of hydraulic fracturing chemicals in the USA, 2011–18: a before and after comparison of reporting formats
Authors: Kevin Trickey, Nicholas Hadjimichael, Prachi Sanghavi
Journal: The Lancet Planetary Health (2020)

BackgroundHydraulic fracturing often involves the injection of millions of gallons of fracturing fluids into underground shales to extract oil and natural gas, raising health concerns over potential water contamination. Many state and federal governmental agencies rely on the third-party FracFocus online registry for disclosure of chemical ingredients in fracturing fluids, but withholding chemicals as trade secrets is common. In 2016, a new format, known as the systems approach was widely encouraged as a method of reducing withholding by decoupling disclosed chemicals from their functions, protecting against reverse-engineering of fracture fluid formulas by competitors. In this study, we assess the extent to which elevated use of the systems approach in FracFocus version 3.0 translated into greater chemical disclosure.MethodsWe analysed 108 137 disclosure forms submitted to FracFocus between Jan 1, 2011, and Dec 31, 2018, to estimate the effect of expanded use of the systems approach on chemical withholding. We compared the proportion of forms withholding at least one chemical ingredient across time, between approaches, and by state and drilling operator.FindingsSince the 2016 expansion of the systems approach, 15 677 (82%) of systems approach forms have withheld an ingredient. 13 462 (89%) of 15 062 traditional FracFocus version 3.0 forms withheld an ingredient. In the quarter following the transition (July, to September, 2016), 1211 (93%) of 1304 traditional forms withheld an ingredient, compared with only 958 (76%) of 1262 systems approach forms. However, withholding rates increased throughout 2017 and, by 2018, 6949 (87%) of 8016 systems approach forms were withholding ingredients. At the end of our analysis period in the fourth quarter of 2018, systems approach forms had even greater withholding (903 [88%] of 1025 forms) than did traditional forms (855 [85%] of 1004 forms). We did not find that states or operators that submitted more systems approach forms had lower withholding.InterpretationThe systems approach has not reduced FracFocus chemical withholding, which continues to occur in around 87% of well fracture disclosures. FracFocus might not be an appropriate substitute for regulatory action, and measures are urgently needed for environmental and public safety.FundingUniversity of Chicago Argonne National Laboratory Seed Grant.
Abstract 9569: Evaluation Method of Pulmonary Perfusion by Sequential Radiography : Preliminary Study in Monkey
Authors: Hidemitsu Miyatake, Fujino Kazunori, Tabata Tosihisa, Yasuyuki Tsujita, Yutaka Eguchi
Journal: Circulation (2019)

Intro: Recently, dynamic chest radiography (DCR) has been developed to evaluate pulmonary function by flat panel detector (FPD). It can evaluate flow of the pulmonary artery and the movements of bo...
Legal and Ethical Considerations for Requiring Consent for Apnea Testing in Brain Death Determination
Authors: Ivor Berkowitz, Jeremy R. Garrett
Journal: The American Journal of Bioethics (2020)

The past decade has witnessed escalating legal and ethical challenges to the diagnosis of death by neurologic criteria (DNC). The legal tactic of demanding consent for the apnea test, if successful, can halt the DNC. However, US law is currently unsettled and inconsistent in this matter. Consent has been required in several trial cases in Montana and Kansas but not in Virginia and Nevada. In this paper, we analyze and evaluate the legal and ethical bases for requiring consent before apnea testing and defend such a requirement by appealing to ethical and legal principles of informed consent and battery and the right to refuse medical treatment. We conclude by considering and rebutting two major objections to a consent requirement for apnea testing: (1) a justice-based objection to allocate scarce resources fairly and (2) a social utility objection that halting the diagnosis of brain death will reduce the number of organ donors.
Prolonging Tamoxifen Therapy for Primary Breast Cancer
Authors: Bernard Fisher, Ann Brown, Norman Wolmark, Carol Redmond, D. Lawrence Wickerham, James Wittliff, Nikolay Dimitrov, Sandra Legault-Poisson, Harvey Schipper, David Prager
Journal: Annals of Internal Medicine (2020)

Abstract Objective:To determine whether prolonging the duration of tamoxifen administration beyond the cessation of a combined chemotherapy regimen benefits patients with primary breast cancer with...
Matt Morgan: Treating a VIP patient
Authors: Matt Morgan
Journal: BMJ (2020)

When the UK prime minister returned to Downing Street just two weeks after leaving hospital, some people questioned whether he had really needed to be treated in the intensive care unit (ICU) in the first place.

Without speculating on Boris Johnson’s individual case or the amazing work of the staff who treated him at St Thomas’ Hospital, the uncomfortable truth is that most hospitals have “VIP policies” to admit presidents, politicians, or even celebrities to isolation rooms in the ICU, even when they may not medically need it. However, this is designed to protect not the “high value” individuals themselves but rather the care system and other patients around them. And, bizarrely, this policy …
Cardiac Energetics in Patients With Aortic Stenosis and Preserved Versus Reduced Ejection Fraction
Authors: Mark A. Peterzan, William T. Clarke, Craig A. Lygate, Hannah A. Lake, Justin Y.C. Lau, Jack J. Miller, Errin Johnson, Jennifer J. Rayner, Moritz J. Hundertmark, Rana Sayeed, Mario Petrou, George Krasopoulos, Vivek Srivastava, Stefan Neubauer, Christopher T. Rodgers, Oliver J. Rider
Journal: Circulation (2020)

Why some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and flux is associated with this transition.We recruited 102 participants to 5 groups: moderate aortic stenosis (ModAS) (n=13), SevAS, left ventricular (LV) ejection fraction ≥55% (SevAS-preserved ejection fraction, n=37), SevAS, LV ejection fraction <55% (SevAS-reduced ejection fraction, n=15), healthy volunteers with nonhypertrophied hearts with normal systolic function (normal healthy volunteer, n=30), and patients with nonhypertrophied, non-pressure-loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (non-pressure-loaded heart biopsy, n=7). All underwent cardiac magnetic resonance imaging and 31P magnetic resonance spectroscopy for myocardial energetics. LV biopsies (AS and non-pressure-loaded heart biopsy) were analyzed for CK total activity, CK isoforms, citrate synthase activity, and total creatine. Mitochondria-sarcomere diffusion distances were calculated by using serial block-face scanning electron microscopy.In the absence of failure, CK flux was lower in the presence of AS (by 32%, P=0.04), driven primarily by reduction in phosphocreatine/ATP (by 17%, P<0.001), with CK kf unchanged (P=0.46). Although lowest in the SevAS-reduced ejection fraction group, CK flux was not different from the SevAS-preserved ejection fraction group (P>0.99). Accompanying the fall in CK flux, total CK and citrate synthase activities and the absolute activities of mitochondrial-type CK and CK-MM isoforms were also lower (P<0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity (r=0.86, P=0.003).Total CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo magnetic resonance spectroscopy measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS and suggest that a fall in CK flux is not by itself a necessary cause of transition to systolic failure. However, because ATP demands increase with AS severity, this could increase susceptibility to systolic failure. As such, targeting CK capacity and flux may be a therapeutic strategy to prevent and treat systolic failure in AS.
CITED4 Protects Against Adverse Remodeling in Response to Physiological and Pathological Stress
Authors: Carolin Lerchenmüller, Charles P Rabolli, Ashish Suresh Yeri, Robert Kitchen, Ane M Salvador, Laura X Liu, Olivia Ziegler, Kirsty M Danielson, Colin Platt, Ravi Shah, Federico Damilano, Piyusha Kundu, Eva Riechert, Hugo A Katus, Jeffrey E Saffitz, Hasmik Keshishian, Steve Carr, Vassilios J Bezzerides, Saumya Das, Anthony Rosenzweig
Journal: Circulation Research (2020)

Rationale: Cardiac CITED4 is induced by exercise and is sufficient to cause physiological hypertrophy and mitigate adverse ventricular remodeling after ischemic injury. However, the role of endogenous CITED4 in response to physiological or pathological stress is unknown. Objective: To investigate the role of CITED4 in murine models of exercise and pressure overload. Methods and Results: We generated cardiomyocyte-specific CITED4 knockout mice (C4KO) and subjected them to an intensive swim exercise protocol as well as transverse aortic constriction (TAC). Echocardiography, western blotting, qPCR, immunohistochemistry, immunofluorescence, and transcriptional profiling for mRNA and miRNA expression were performed. Cellular crosstalk was investigated in vitro. CITED4 deletion in cardiomyocytes did not affect baseline cardiac size or function in young adult mice. C4KO mice developed modest cardiac dysfunction and dilation in response to exercise. After TAC, C4KOs developed severe heart failure with left ventricular dilation, impaired cardiomyocyte growth accompanied by reduced mammalian target of rapamycin (mTOR) activity and maladaptive cardiac remodeling with increased apoptosis, autophagy, and impaired mitochondrial signaling. Interstitial fibrosis was markedly increased in C4KO hearts after TAC. RNAseq revealed induction of a pro-fibrotic miRNA network. miR30d was decreased in C4KO hearts after TAC and mediated crosstalk between cardiomyocytes and fibroblasts to modulate fibrosis. miR30d inhibition was sufficient to increase cardiac dysfunction and fibrosis after TAC. Conclusions: CITED4 protects against pathological cardiac remodeling by regulating mTOR activity and a network of miRNAs mediating cardiomyocyte to fibroblast crosstalk. Our findings highlight the importance of CITED4 in response to both physiological and pathological stimuli.
95TiP Gruppo Italiano Mammella (GIM) 10 – CONSENT: A phase III randomized study comparing concurrent versus sequential administration of adjuvant chemotherapy (CT) and aromatase inhibitors (AIs) in post-menopausal patients (pts) with hormone receptor-positive (HR+) early breast cancer (EBC)
Authors: M. Lambertini, V. Guarneri, E.R. Caremoli, A. Rocca, F. Montemurro, M. De Laurentiis, M. Giordano, S. De Placido, G. Bisagni, O. Garrone, A. Ferzi, F. Giovanardi, F. Cognetti, L. Amaducci, A. Bernardo, L. Livi, C. Bighin, F. Poggio, A. Ballestrero, L. Del Mastro
Journal: Annals of Oncology (2020)
Prolonged Survival of Human-Kidney Homografts by Immunosuppressive Drug Therapy
Authors: Joseph E. Murray, John P. Merrill, J. Hartwell Harrison, Richard E. Wilson, Gustave J. Dammin
Journal: New England Journal of Medicine (1963)

THIS report is a summary of our experience with kidney homografts in 13 patients treated with drugs as the sole modality for the suppression of immunity (Table 1). Five recent cases are reported in detail: 1 patient with a cadaveric kidney is still alive after one year; 1 died from cerebral hemorrhage more than five months after transplantation from an unrelated infant; 1 is alive three months after transplant from his mother; the fourth is alive six weeks after receiving a kidney from his brother; and the fifth is living four weeks after a transplant from an unrelated adult volunteer. . . .