tbuckley/cabot-search huggingface dataset:
Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure
Authors: Dipak Kotecha, Simrat K. Gill, Marcus D. Flather, Jane Holmes, Milton Packer, Giuseppe Rosano, Michael Böhm, John J.V. McMurray, John Wikstrand, Stefan D. Anker, Dirk J. van Veldhuisen, Luis Manzano, Thomas G. von Lueder, Alan S. Rigby, Bert Andersson, John Kjekshus, Hans Wedel, Frank Ruschitzka, John G.F. Cleland, Kevin Damman, Josep Redon, Andrew J.S. Coats
Journal: Journal of the American College of Cardiology (2019)

Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.
Abstract 11184: High Concordance of Non-ideal Cardiovascular Health Metrics in a Nation-wide Study of 5,364 Spouse-pairs
Authors: Dov Shiffman, Judy Z Louie, James J Devlin, Charles M Rowland, Samia Mora
Journal: Circulation (2019)

Introduction: Cardiovascular health (CVH) may be concordant in spouse-pairs because of similar environmental exposures and assortative mating. We investigated the concordance of AHA-defined Life’s ...
Levosimendan in Cardiac Surgery
Authors: Alessandro Putzu, Sara Clivio, Tiziano Cassina
Journal: New England Journal of Medicine (2017)

To the Editor: Landoni et al. (May 25 issue) 1 examined levosimendan administration versus placebo for patients requiring hemodynamic support after cardiac surgery.In their trial (Levosimendan to Reduce Mortality in High Risk Cardiac Surgery Patients: A Multicenter Randomized Controlled Trial [CHEETAH]), they found no significant difference in mortality between the two groups.The investigators aimed to include patients with shock after cardiac surgery and cardiopulmonary bypass.However, many of the patients were likely to have distributive shock (i.e., 57.7% received epinephrine, 45.3% norepinephrine, and 15.2% dopamine) rather than cardiogenic shock (28.3% received dobutamine and 12.5% enoximone) (Table S5 in the Supplementary Appendix, available with the full text of the article at NEJM.org).The vasodilator effect of levosimendan 2 may be detrimental in those with vasoplegia after cardiopulmonary bypass.Indeed, hypotension, possibly due to low diastolic and coronary perfusion pressure, 3 is associated with 30-day mortality in multivariate analysis (P = 0.005), whereas low cardiac output is not.In addition, the investigators did not target their drug administration to either cardiac output or markers of tissue hypoxia (e.g., lactate level, mixed venous oxygen saturation, or the venoarterial carbon dioxide gradient).Inotropic drugs are likely to exert only detrimental effects on myocardium 4 if an increase in cardiac output, along with oxygen delivery, 5 is not accompanied by evidence of improvement in oxygen consumption.
No Evidence for Hematopoietic Stem Cell Self-Renewal in-Vivo Following Inflammatory Challenge
Authors: Ruzhica Bogeska, Paul Kaschutnig, Stella V Paffenholz, Julia Knoch, Jan-Philipp Mallm, Malak Fawaz, Florian Buettner, Dagmar Walter, Felix Frauhammer, Tim Holland-Letz, Noboru Asada, Ana-Matea Mikecin Drazic, Marleen Buechler-Schaff, Martha Correno-Gonzalez, Melanie Ball, Sina Staeble, Julius Gräsel, Simon Haas, Daniel B. Lipka, Karsten Rippe, Benedikt Brors, Paul S. Frenette, Michael A. Rieger, Marieke A. G. Essers, Michael D. Milsom
Journal: Blood (2019)
Eradicating Metastatic Cancer and the Eco-Evolutionary Dynamics of Anthropocene Extinctions
Authors: Robert A. Gatenby, Yael Artzy-Randrup, Tamir Epstein, Damon R. Reed, Joel S. Brown
Journal: Cancer Research (2019)

Curative therapy for metastatic cancers is equivalent to causing extinction of a large, heterogeneous, and geographically dispersed population. Although eradication of dinosaurs is a dramatic example of extinction dynamics, similar application of massive eco-evolutionary force in cancer treatment is typically limited by host toxicity. Here, we investigate the evolutionary dynamics of Anthropocene species extinctions as an alternative model for curative cancer therapy. Human activities can produce extinctions of large, diverse, and geographically distributed populations. The extinction of a species typically follows a pattern in which initial demographic and ecological insults reduce the size and heterogeneity of the population. The surviving individuals, with decreased genetic diversity and often fragmented ecology, are then vulnerable to small stochastic perturbations that further reduce the population until extinction is inevitable. We hypothesize large, diverse, and disseminated cancer populations can be eradicated using similar evolutionary dynamics. Initial therapy is applied to reduce population size and diversity and followed by new treatments to exploit the eco-evolutionary vulnerability of small and/or declining populations. Mathematical models and computer simulations demonstrate initial reductive treatment followed immediately by demographic and ecological perturbations, similar to the empirically derived treatment of pediatric acute lymphocytic leukemia, can consistently achieve curative outcomes in nonpediatric cancers. SIGNIFICANCE: Anthropocene extinctions suggest a strategy for eradicating metastatic cancers in which initial therapy, by reducing the size and diversity of the population, renders it vulnerable to extinction by rapidly applied additional perturbations.
Malignant biliary obstruction: endoscopic ultrasound-guided versus endoscopic retrograde cholangiopancreatography-guided biliary drainage
Authors: Zheng Jin, Xiaofeng Zhang
Journal: Endoscopy (2019)

See also: Endoscopic ultrasound-guided transmural approach versus ERCP-guided transpapillary approach for primary decompression of malignant biliary obstruction: a meta-analysisEndoscopy 2019; 51(10): 950-960DOI: 10.1055/a-0901-7343 See also: Reply to Jin et al.Endoscopy 2019; 51(12): 1186-1186DOI: 10.1055/a-1012-1931
Johnson &amp; Johnson loses class action over vaginal mesh in Australia
Authors: Clare Dyer
Journal: BMJ (2019)

More than 1350 women have won a seven year class action in Australia against the pharmaceutical company Johnson & Johnson over harm they suffered from its transvaginal mesh and tape devices.

Federal Court judge Anna Katzmann ruled that Johnson & Johnson’s subsidiary Ethicon had sold the products without warning women or doctors of the gravity of the risks and was negligent in rushing them to market without proper testing.

The case, one of Australia’s largest class actions, is one of many lawsuits worldwide over the products, used to treat urinary incontinence and pelvic organ prolapse after childbirth. In …
The NCCN 2019 Annual Congress: Hematologic Malignancies
Authors: Robert W. Carlson
Journal: Journal of the National Comprehensive Cancer Network (2019)

Hematologic Malignancies provided an opportunity for more than 500 hematologists, hematologist/oncologists, and other healthcare professionals to see world-renowned experts in the management of hematologic malignancies present the latest treatment advances, updates to the standard of care as recommended in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), and unique and challenging patient cases.This special issue of JNCCN-Journal of the National Comprehensive Cancer Network presents these Highlights as a synopsis of the proceedings.
Highly Potent BTK Degradation Induced By NRX0492 As a Therapeutic Strategy for CLL
Authors: Deyi Zhang, Hailey Harris, Aileen Kelly, Daniel W Robbins, May Tan, Timothy Ingallinera, Neil Bence, Arthur T Sands, Sivasubramanian Baskar, Sarah E. M. Herman, Adrian Wiestner
Journal: Blood (2019)
Ibrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (iFCG) for First-Line Treatment of IGHV-Mutated CLL and without Del(17p)/Mutated TP53
Authors: Nitin Jain, Philip A. Thompson, Jan A. Burger, Alessandra Ferrajoli, Koichi Takahashi, Zeev E. Estrov, Gautam M. Borthakur, Prithviraj Bose, Tapan M. Kadia, Naveen Pemmaraju, Koji Sasaki, Naveen Garg, Xuemei Wang, Rashmi Kanagal-Shamanna, Keyur Patel, Jeffrey L. Jorgensen, Sa A Wang, Wanda Lopez, Ana Ayala, William Plunkett, Varsha Gandhi, Hagop M. Kantarjian, Susan O'Brien, Michael J Keating, William G. Wierda
Journal: Blood (2019)
Artificial intelligence in clinical and genomic diagnostics
Authors: Raquel Dias, Ali Torkamani
Journal: Genome Medicine (2019)

Abstract Artificial intelligence (AI) is the development of computer systems that are able to perform tasks that normally require human intelligence. Advances in AI software and hardware, especially deep learning algorithms and the graphics processing units (GPUs) that power their training, have led to a recent and rapidly increasing interest in medical AI applications. In clinical diagnostics, AI-based computer vision approaches are poised to revolutionize image-based diagnostics, while other AI subtypes have begun to show similar promise in various diagnostic modalities. In some areas, such as clinical genomics, a specific type of AI algorithm known as deep learning is used to process large and complex genomic datasets. In this review, we first summarize the main classes of problems that AI systems are well suited to solve and describe the clinical diagnostic tasks that benefit from these solutions. Next, we focus on emerging methods for specific tasks in clinical genomics, including variant calling, genome annotation and variant classification, and phenotype-to-genotype correspondence. Finally, we end with a discussion on the future potential of AI in individualized medicine applications, especially for risk prediction in common complex diseases, and the challenges, limitations, and biases that must be carefully addressed for the successful deployment of AI in medical applications, particularly those utilizing human genetics and genomics data.
Regulation of Recurrent Inhibition by Asynchronous Glutamate Release in Neocortex
Authors: Suixin Deng, Junlong Li, Quansheng He, Xiaoxue Zhang, Jie Zhu, Liang Li, Zhen Mi, Xiufeng Yang, Man Jiang, Qiang Dong, Ying Mao, Yousheng Shu
Journal: Neuron (2019)
Antimicrobial de-escalation in critically ill patients: a position statement from a task force of the European Society of Intensive Care Medicine (ESICM) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Critically Ill Patients Study Group (ESGCIP)
Authors: Alexis Tabah, Matteo Bassetti, Marin H. Kollef, Jean-Ralph Zahar, José-Artur Paiva, Jean-Francois Timsit, Jason A. Roberts, Jeroen Schouten, Helen Giamarellou, Jordi Rello, Jan De Waele, Andrew F. Shorr, Marc Leone, Garyphallia Poulakou, Pieter Depuydt, Jose Garnacho-Montero
Journal: Intensive Care Medicine (2019)
Activation of STAT3 by EGFR variant III: Tyrosine residue 1068 is the primary STAT3 docking site on EGFR
Authors: Jane Zhang, Timothy S. Schaefer, Robert M. Umek, Jacob N. Wohlstadter
Journal: Cancer Research (2006)

4827  A hallmark of glioblastoma multiforme (GBM) is the amplification and rearrangement of the epidermal growth factor receptor. One of the more frequently occurring rearrangements, termed variant III (vIII), has an in-frame deletion in the extracellular domain. EGFRvIII is constitutively active and subsequently activates several other downstream signaling pathways. Using EGFR and phospho-EGFR specific antibodies, we demonstrate that EGFRvIII is phosphorylated more extensively on tyrosine than the wildtype receptor. We also show, using transcriptional activation assays, that enforced expression of EGFRvIII results in the activation of the transcription factor STAT3 to a greater extent than the wildtype receptor. Using STAT3 carrying an electrochemiluminescent label, we quantified the interaction between immobilized EGFR and STAT3. We studied a panel of receptors containing single or combinations of mutations at the receptor’s known autophosphorylation sites and determined that tyrosine 1068 is the primary association site for STAT3 on EGFR. The importance of this residue in STAT3 signaling was confirmed independently using a STAT3 transcriptional activity assay and receptors containing or lacking tyrosine at position 1068. This panel of mutants will allow us to continue to characterize the role of STAT3 activity and that of other pathways on EGFR-initiated signaling pathways.
Real-world experience with electronic patient reported outcomes and missing items: "Don't ask me irrelevant questions".
Authors: Heather A Rosett, Susan C. Locke, Steven Paul Wolf, Kris Herring, Greg P. Samsa, Jesse D Troy, Thomas William LeBlanc
Journal: Journal of Clinical Oncology (2019)

99 Background: Electronic patient-reported outcomes (ePROs) can improve quality of life and prolong survival in patients with cancer by enhancing the detection and tracking of unmet supportive care needs. However, there remain unanswered questions about how to handle missing ePRO data. We hypothesized that patients may skip specific questions they feel do not apply to them. We aimed to examine the relationship between patient demographics and missing items in a real-world ePRO dataset. Methods: We utilized a prospectively collected database of ePROs from oncology clinics administering Patient Care Monitor 2.0 (PCM), a validated symptom survey of 78 items for men and 86 for women. We tabulated the frequency of missing items by item and domain (emotional, functional and symptom-related), and examined these by age, gender, education, race and marital status. Results: In 20,986 encounters there were responses to at least 1 PCM item from 6,933 patients. On average just 1% of items were skipped per encounter. By domain, 12.3% of functional, 8.4% of symptom-related, and 1.6% of emotional constructs contained at least one missing item. The highest frequency of item non-response was seen in older patients (&gt;60yo) and those with high school education or less. The most frequently skipped items included: “attend a paid job” (10.7%), “reduced sexual enjoyment” (3.8%), and “running” (3.7%). These questions may be less relevant to older individuals, who, for example, quit running years earlier or are retired. Men had less missingness overall, except for “cooks for self” and “house work”, which may reflect traditional gender roles in the Southeast US. Conclusions: In a real-world ePRO implementation, items pertaining to more universal issues for cancer patients, like emotional well-being, have much lower rates of missingness, especially compared to functional items like “attend a paid job.” These results suggest that patients differentially complete ePROs based on perceived question relevance to them. The underlying driver behind individual item non-response may itself be an important data point in clinical care, warranting further study and discussion during clinic visits.
Tuning the surface immunomodulatory functions of polyetheretherketone for enhanced osseointegration
Authors: Ang Gao, Qing Liao, Lingxia Xie, Guomin Wang, Wei Zhang, Yuzheng Wu, Penghui Li, Min Guan, Haobo Pan, Liping Tong, Paul K. Chu, Huaiyu Wang
Journal: Biomaterials (2019)
Noninvasive evaluation of pulmonary artery pressure during exercise: the importance of right atrial hypertension
Authors: Masaru Obokata, Garvan C. Kane, Hidemi Sorimachi, Yogesh N.V. Reddy, Thomas P. Olson, Alexander C. Egbe, Vojtech Melenovsky, Barry A. Borlaug
Journal: European Respiratory Journal (2019)

Introduction Identification of elevated pulmonary artery pressures during exercise has important diagnostic, prognostic and therapeutic implications. Stress echocardiography is frequently used to estimate pulmonary artery pressures during exercise testing, but data supporting this practice are limited. This study examined the accuracy of Doppler echocardiography for the estimation of pulmonary artery pressures at rest and during exercise. Methods Simultaneous cardiac catheterisation-echocardiographic studies were performed at rest and during exercise in 97 subjects with dyspnoea. Echocardiography-estimated pulmonary artery systolic pressure (ePASP) was calculated from the right ventricular (RV) to right atrial (RA) pressure gradient and estimated RA pressure (eRAP), and then compared with directly measured PASP and RAP. Results Estimated PASP was obtainable in 57% of subjects at rest, but feasibility decreased to 15–16% during exercise, due mainly to an inability to obtain eRAP during stress. Estimated PASP correlated well with direct PASP at rest (r=0.76, p&lt;0.0001; bias −1 mmHg) and during exercise (r=0.76, p=0.001; bias +3 mmHg). When assuming eRAP of 10 mmHg, ePASP correlated with direct PASP (r=0.70, p&lt;0.0001), but substantially underestimated true values (bias +9 mmHg), with the greatest underestimation among patients with severe exercise-induced pulmonary hypertension (EIPH). Estimation of eRAP during exercise from resting eRAP improved discrimination of patients with or without EIPH (area under the curve 0.81), with minimal bias (5 mmHg), but wide limits of agreement (−14–25 mmHg). Conclusions The RV–RA pressure gradient can be estimated with reasonable accuracy during exercise when measurable. However, RA hypertension frequently develops in patients with EIPH, and the inability to noninvasively account for this leads to substantial underestimation of exercise pulmonary artery pressures.
Two-year review of the electronic Patient Reported Outcome (ePRO) system in the Prostate Clinic at the Vancouver Prostate Centre (VPC).
Authors: Eugenia Wu, Olga Arsovska, Lindsay Hedden, Maria Spillane, Michaela Vivar, Martin Gleave, Peter C. Black, Alan So, Larry Goldenberg, Celestia S. Higano
Journal: Journal of Clinical Oncology (2019)

107 Background: The Vancouver Prostate Centre (VPC) implemented an electronic patient reported outcomes (ePRO) system in April 2017 to collect data on a research protocol in collaboration with University Health Network of Toronto, funded by Prostate Cancer Canada. Responses to ePRO questionnaires collected on iPads were entered into the national PC360 registry initially and a global TrueNorth registry thereafter funded by Movember Foundation. Herein we describe our experience implementing the ePRO system over the last two years. Methods: All patients (pts) with a new diagnosis of localized prostate cancer, either before or just after therapy, were identified using the electronic medical record and were consented in person in clinic. After signing consent, pts were asked to complete ePROs, including EPIC-26, EQ-5D-5L, WHODAS 2.0, and Distress Thermometer, on iPads at designated clinic appointment. Results: Between April 3, 2017-March 31, 2019, 1027 pts were identified as being eligible to complete ePRO: 878 pts (85.5%) consented and completed ePRO at least once. In Year 1 (Apr 2017-Mar 2018), 76.7% of the 1075 planned ePRO questionnaires were completed vs 75% completed of 1258 planned in year 2. Most pts (82.3%,723/878) agreed to be contacted for future research. Of those, 424/723 were recruited to at least one additional registry study. Data for consented pts was missing for 155/878 (17.7%) each year, usually due to difficulty locating the pt to give him the iPad before he left the clinic. In a small percentage of cases, ePRO reports were incomplete due to fluctuating WiFi connectivity, inadequate time to complete the questions before the clinic appointment, refusal, or no show. Conclusions: ePROs for research were successfully implemented into clinical practice in the PCSC program as evidenced by high completion and low refusal rates but required significant manpower due to ethics board requirements. Challenges encountered included: training clinic staff and coordinators to direct pts to the iPad system to minimize missing ePRO assessments, technical difficulties with WiFi connectivity, requirement of ethics board mandating that staff interact with each pt individually to ensure the ePRO assessments are completed. The next step is to incorporate ePROs into clinical practice, in which case consent will not be required.
Burden of Hospitalizations Due to Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disorder (EBV+PTLD) in Patients Who Failed First Line Rituximab or Rituximab Plus Chemotherapy Following Solid Organ Transplant (Post-SOT): A Retrospective Chart Review Study of German PTLD Registry
Authors: Heiner Zimmermann, Hairong Xu, Arie Barlev, Yang Zhang, Dhanalakshmi Thirumalai, Crystal Watson, Ralf Ulrich Trappe
Journal: Blood (2019)
Advancing Legislation on Drug Pricing — Is There a Path Forward?
Authors: Stacie B. Dusetzina, Jonathan Oberlander
Journal: New England Journal of Medicine (2019)

Interview with Dr. Jonathan Oberlander on legislation aimed at reducing spending on prescription drugs. (08:34)Download The Lower Drug Costs Now Act of 2019 represents a major departure from the U.S. status quo. It has several key but politically divisive provisions targeting prices paid to drug manufacturers and would reduce Medicare spending and beneficiaries' out-of-pocket costs.
HGCSG1601: A retrospective cohort study of the efficacy and safety of nab-paclitaxel plus gemcitabine (nab-P+GEM) for unresectable locally advanced pancreatic cancer (LAPC)
Authors: A. Tanimoto, M. Yagisawa, S. Nakano, Y. Kawamoto, S. Yuki, A. Ishiguro, T. Takahata, A. Sato, I. Iwanaga, N. Ehira, M. Uebayashi, O. Muto, T. Sasaki, K. Hatanaka, M. Tateyama, T. Wakabayashi, M. Dazai, S. Minami, Y. Sakata, Y. Komatsu
Journal: Annals of Oncology (2019)
Context-guided fully convolutional networks for joint craniomaxillofacial bone segmentation and landmark digitization
Authors: Jun Zhang, Mingxia Liu, Li Wang, Si Chen, Peng Yuan, Jianfu Li, Steve Guo-Fang Shen, Zhen Tang, Ken-Chung Chen, James J. Xia, Dinggang Shen
Journal: Medical Image Analysis (2019)
Current experiences of accessing and using HIV pre-exposure prophylaxis (PrEP) in the United Kingdom: a cross-sectional online survey, May to July 2019
Authors: Charlotte O’Halloran, Greg Owen, Sara Croxford, Lee B Sims, O Noel Gill, Will Nutland, Valerie Delpech
Journal: Eurosurveillance (2019)

The 2019 online pre-exposure prophylaxis (PrEP) user survey in the United Kingdom was conducted to assess HIV PrEP access, and user characteristics. One in five respondents continued experiencing difficulties accessing PrEP; users were almost exclusively gay or bisexual men at high risk of HIV. The majority obtained PrEP through health service clinics and rated PrEP positively. High STI rates were reported among users. Renal and sexual health checks are advised for those sourcing PrEP privately.