tbuckley/cabot-search huggingface dataset:
Abstract 15693: Comorbidities in Heart Failure: A Population-Based Case-control Study
Authors: Alanna M Chamberlain, Cynthia M Boyd, Sheila M Manemann, Shannon M Dunlay, Yariv Gerber, Jill M Killian, Susan A Weston, Veronique L Roger
Journal: Circulation (2015)

Background: Whether age alone explains the comorbidity burden in heart failure (HF) is unclear. In particular, differences in the burden of co-morbid conditions in HF patients compared to population controls has not been well documented. Methods: The prevalence of 17 chronic conditions defined by the US Department of Health and Human Services were obtained in 1746 incident HF patients from 2000-2010 and controls matched 1:1 on sex and age from Olmsted County, MN. Conditions were ascertained requiring 2 occurrences of a diagnostic code. Logistic regression determined associations of each condition with HF. Results: Among the 1746 matched pairs (mean age 76.2 years, 43.5% men), the prevalence was higher in HF cases for all conditions (p&lt;0.05) except dementia and osteoporosis. After adjusting for all conditions, hypertension, coronary artery disease, arrhythmia, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hepatitis, and substance abuse were significantly more common in HF (figure). More than a 2-fold increased odds of hepatitis, arrhythmia, and coronary artery disease was observed among HF cases. Arrhythmia (34.2%), hypertension (31.1%), and coronary artery disease (27.8%) had the largest attributable risk of HF; for example, assuming a causal relationship, if arrhythmias were eliminated, 34% of HF would be avoided. Conclusions: Compared to age- and sex-matched controls, HF patients have a higher prevalence of many chronic conditions, indicating the excess comorbidity in HF is not due to age alone. Some cardiovascular conditions, including arrhythmia, coronary artery disease, and hypertension were more common in HF. Of the non-cardiovascular conditions, hepatitis had the strongest association with HF and was an unanticipated finding that deserves additional investigation. It is important to understand comorbidities as they play a key role in the excess mortality and healthcare utilization experienced by HF patients.
Targeting nuclear β-catenin as therapy for post-myeloproliferative neoplasm secondary AML
Authors: Dyana T. Saenz, Warren Fiskus, Taghi Manshouri, Christopher P. Mill, Yimin Qian, Kanak Raina, Kimal Rajapakshe, Cristian Coarfa, Raffaella Soldi, Prithviraj Bose, Gautam Borthakur, Tapan M. Kadia, Joseph D. Khoury, Lucia Masarova, Agnieszka J. Nowak, Baohua Sun, David N. Saenz, Steven M. Kornblau, Steve Horrigan, Sunil Sharma, Peng Qiu, Craig M. Crews, Srdan Verstovsek, Kapil N. Bhalla
Journal: Leukemia (2018)
Differential Evolution of the Epidermal Keratin Cytoskeleton in Terrestrial and Aquatic Mammals
Authors: Florian Ehrlich, Heinz Fischer, Lutz Langbein, Silke Praetzel-Wunder, Bettina Ebner, Katarzyna Figlak, Anton Weissenbacher, Wolfgang Sipos, Erwin Tschachler, Leopold Eckhart
Journal: Molecular Biology and Evolution (2018)

Keratins are the main intermediate filament proteins of epithelial cells. In keratinocytes of the mammalian epidermis they form a cytoskeleton that resists mechanical stress and thereby are essential for the function of the skin as a barrier against the environment. Here, we performed a comparative genomics study of epidermal keratin genes in terrestrial and fully aquatic mammals to determine adaptations of the epidermal keratin cytoskeleton to different environments. We show that keratins K5 and K14 of the innermost (basal), proliferation-competent layer of the epidermis are conserved in all mammals investigated. In contrast, K1 and K10, which form the main part of the cytoskeleton in the outer (suprabasal) layers of the epidermis of terrestrial mammals, have been lost in whales and dolphins (cetaceans) and in the manatee. Whereas in terrestrial mammalian epidermis K6 and K17 are expressed only upon stress-induced epidermal thickening, high levels of K6 and K17 are consistently present in dolphin skin, indicating constitutive expression and substitution of K1 and K10. K2 and K9, which are expressed in a body site-restricted manner in human and mouse suprabasal epidermis, have been lost not only in cetaceans and manatee but also in some terrestrial mammals. The evolution of alternative splicing of K10 and differentiation-dependent upregulation of K23 have increased the complexity of keratin expression in the epidermis of terrestrial mammals. Taken together, these results reveal evolutionary diversification of the epidermal cytoskeleton in mammals and suggest a complete replacement of the quantitatively predominant epidermal proteins of terrestrial mammals by originally stress-inducible keratins in cetaceans.
Progress in <i>BRCA</i> -Mutated Ovarian Cancer
Authors: David R. Spriggs, Dan L. Longo
Journal: New England Journal of Medicine (2018)

The article by Moore et al.1 in this issue of the Journal is the culmination of a long march for olaparib in the treatment of BRCA-mutated high-grade serous ovarian cancer — one that began with its discovery by means of synthetic lethality screening, followed by years of clinical trials to define its activity and refine its uses, and finally led to its implementation in a population of women with potentially curable ovarian cancer. Olaparib is the first in a wave of poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors, a class of agents that is changing primary treatment of ovarian cancer for the . . .
Abstract 11665: Incidence and Determinants of Acute Kidney Injury Among Old Adults Hospitalized for Acute Myocardial Infarction: The SILVER-AMI Study
Authors: John A Dodson, Jeptha Curtis, Mary Geda, Alexandra Hajduk, Xuemei Song, Chirag Parikh, Paula Miller, Caroline Blaum, Harlan Krumholz, Sarwat Chaudhry
Journal: Circulation (2018)

Background: Among older adults hospitalized for acute myocardial infarction (AMI) undergoing cardiac catheterization, acute kidney injury (AKI) is common and associated with poor long-term outcomes...
Central Nervous System Involvement Detected By Flow Cytometry Is a Risk Factor for Relapse in Childhood Acute Lymphoblastic Leukemia
Authors: Maria Thastrup, Hanne Vibeke Marquart, Mette Levinsen, Kathrine Grell, Jonas Abrahamsson, Birgitte Klug Albertsen, Thomas Leth Frandsen, Arja Harila-Saari, Päivi Maria Lähteenmäki, Riitta Niinimäki, Cornelis Jan Pronk, Aina Ulvmoen, Goda Vaitkeviciene, Mervi Taskinen, Kjeld Schmiegelow
Journal: Blood (2018)
Abstract 19031: Prediction and Incidence of Non-PV Trigger Foci of Atrial Fibrillation With Regard to Clinical Profile
Authors: Yasushi Mukai, Shujiro Inoue, Susumu Takase, Shunsuke Kawai, Akiko Chishaki, Kenji Sunagawa
Journal: Circulation (2015)

Introduction: Non-PV triggers play significant roles in initiating atrial fibrillation (Af). We hypothesized that location of non-PV Af triggers is predictable to some extent from clinical background and may have influence on clinical outcome after ablation. Methods: We analyzed consecutive 109 patients (76 men) with Af who underwent catheter ablation and investigation of Af triggers. Af was induced under recordings of intra-cardiac electrograms before ablation procedure in the following ways (1) watching spontaneous firing, (2) induction with intravenous infusion of isoproterenol and adenosine, (3) burst atrial pacing and/or intentional defibrillation to watch immediate recurrence of Af. Af triggers were analyzed and compared to clinical profiles and therapeutic outcome. Results: Eighty-four were paroxysmal Af and 25 were persistent. Any ectopic trigger of Af was identified in 73 patients (66%) with 99 foci. Seventy-eight foci were PVs (79%) whereas 21 (21%) were non-PV triggers. In general, non-PV foci were notably identified in female (P&lt;0.01) whereas age, LA diameter or Af type was not significantly relevant to the presence of non-PV foci. Among non-PV foci, superior vena cava (SVC, n=5), crista terminals (CT, n=5) and left atrium (LA, n=5) were prevalent sites. CT was prevalently noted in younger females (P&lt;0.01), whereas SVC was regardless of age. Non-PV foci in the LA were preferably noted in patients with persistent Af (P&lt;0.05). Importantly, multiple or non-PV foci were not significantly correlated to Af recurrence after ablation, whereas LA diameter was weakly correlated. Conclusion: Presence and sites of non-PV foci are rather predictable by simple clinical profiles such as gender, age and type of Af. Multiple or non-PV foci may not be associated with worse clinical outcome as long as they can be successfully targeted and ablated.
Comment on Umpierrez and Klonoff. Diabetes Technology Update: Use of Insulin Pumps and Continuous Glucose Monitoring in the Hospital. Diabetes Care 2018;41:1579–1589
Authors: Juan Jose Delgado-Hurtado, Alicia Armstrong, Sushela Chaidarun
Journal: Diabetes Care (2018)

We read the interesting literature review article by Umpierrez and Klonoff (1) on the use of insulin pumps and continuous glucose monitoring in the hospital. Figure 1 in the article gives recommendations on the changes to pump therapy with imaging studies. It suggests that for patients managed with an insulin pump in the hospital who are having an MRI, the pump and metal infusion set should be removed. It also suggests that when having an X-ray or CT …
Abstract 17437: No Significant Correlations Identified Between Carotid Intima-Media Thickness Measurements and Coronary Artery Calcium Scores or CT Coronary Angiography-Derived Plaque Compositional Characteristics in Asymptomatic Diabetic Patients
Authors: Anees Daud, Heidi T May, Alan C Kwan, George Cater, Boaz D Rosen, David A Bluemke, Donald L Lappé, Jeffrey L Anderson, Kirk U Knowlton, Jaoa A Lima, Joseph B Muhlestein
Journal: Circulation (2017)

Introduction: Coronary artery calcium (CAC) scores have been found to be highly predictive of future major adverse cardiovascular events among patients with no prior history of coronary artery dise...
Emergency Departments — A 24/7/365 Option for Combating the Opioid Crisis
Authors: Gail D’Onofrio, Ryan P. McCormack, Kathryn Hawk
Journal: New England Journal of Medicine (2018)

For people with opioid use disorder, an emergency department visit represents a critical, time-sensitive point at which initiating lifesaving treatment is possible. But there has been reluctance among emergency physicians to start patients on opioid-agonist treatment.
Abstract 15924: Early Non-contrast Head Computed Tomography for Prognostication of Neurologic Outcomes Following Cardiac Arrest
Authors: Jaidip Chakravartti, Joshua P Klein, Molly O'Brien, Galen V Henderson, Anthony Massaro, Carol Pierce, Raghu R Seethala, Stefan Strojwas, Michael G Kyller, AnnMarie Chase, Michael G Silverman, Benjamin M Scirica
Journal: Circulation (2015)

Introduction: Prognostication of neurologic outcomes in patients achieving return of spontaneous circulation (ROSC) following cardiac arrest poses a difficult challenge. A low ratio of gray matter to white matter (GWR) attenuation on early non-contrast head computed tomography (NCHCT) may be a specific predictor of poor neurologic outcome following arrest. We sought to validate this finding and to determine if there is a GWR cutoff that is completely specific for predicting poor neurologic outcomes. Methods: We identified 145 patients from our institution with a cardiac arrest between February 2007 and March 2015 who underwent NCHCT within 24 hours following ROSC. GWRs were calculated by measuring the attenuation of 10-15 mm 2 regions of interest in Hounsfield units, identifying the head of the caudate nucleus for gray matter and the posterior limb of the internal capsule for white matter. Neurologic outcomes were recorded by cerebral performance category (CPC) upon hospital discharge. A CPC score of 1 or 2 defined a favorable neurologic outcome, whereas a score of 3, 4, or 5 marked a poor neurologic outcome. Results: Fifty patients had favorable neurologic outcomes, with a median GWR of 1.29 and an interquartile range (IQR) of 1.24-1.34. Ninety-five patients had poor neurologic outcomes, with a median GWR of 1.25 and an IQR of 1.18-1.30. Performance of the GWR as a predictor of neurologic outcome was examined by plotting a receiver operating characteristic curve; the area under the curve was 0.658. However, a GWR below 1.16 was found to have 100% specificity for predicting a poor neurologic outcome following arrest (20 cases, 21.1% sensitivity). Conclusion: In our study, a GWR below 1.16 was shown to be a completely specific predictor of poor neurologic outcome following cardiac arrest. In combination with other modalities, GWR on NCHCT could help guide management by lending prognostic information early in the post arrest course.
Analysis of Value-Based Costs of Undesignated School Stock Epinephrine Policies for Peanut Anaphylaxis
Authors: Marcus S. Shaker, Matthew J. Greenhawt
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Children experiencing anaphylaxis at school may lack access to a personal epinephrine device, prompting recent legislation permitting undesignated (eg, non–student specific) stock epinephrine autoinjector units at school. However, epinephrine device costs vary, and the cost-effectiveness of undesignated school stock epinephrine is uncharacterized to date. <h3>Objective</h3> To define value-based strategies for undesignated school stock epinephrine programs. <h3>Design, Setting, and Participants</h3> Markov simulations of the Chicago Public Schools system were used over extended time horizons to model 2 school stock epinephrine autoinjector policies to provide access for at-risk students. The dates of the data used in the analysis were September 2017 to June 2018 (the 2017-2018 school year). <h3>Main Outcomes and Measures</h3> This study compared the following 3 strategies: no school undesignated epinephrine supply, school undesignated supplemental epinephrine supply (supplemental model), and school undesignated universal epinephrine supply (universal model). The base-case model assumed a 10-fold reduced fatality risk with having undesignated stock epinephrine units available vs not having undesignated stock epinephrine units available. Costs of school stock epinephrine units available for acquisition by schools were evaluated from a societal perspective. Quality-adjusted life-years (QALYs) and total epinephrine acquisition expenses were calculated. <h3>Results</h3> Based on Markov simulations of the Chicago Public Schools system (371 382 students), the cost was $107 816 (95% CI, $107 382-$108 250) for no school undesignated epinephrine supply compared with $108 160 (95% CI, $107 725-$108 595) for the supplemental model and $100 397 (95% CI, $99 979-$100 815) for the universal model. Undesignated stock epinephrine improved outcomes, with 26.869 (95% CI, 26.841-26.897) QALYs accrued as the model concluded compared with 26.867 (95% CI, 26.839-26.896) QALYs for the strategy without undesignated stock epinephrine. When comparing supplemental model stock epinephrine to the strategy without undesignated devices, the incremental cost-effectiveness ratio was high at $268 811 per QALY in the base-case simulation. However, the cost of the supplemental model fell below $100 000 per QALY when the annual undesignated epinephrine acquisition costs did not exceed $338 per school (compared with stock epinephrine unavailability). The universal model dominated all others and was associated with significant cost savings ($7419 per student at risk who would otherwise be prescribed an individual school epinephrine supply). <h3>Conclusions and Relevance</h3> Undesignated school stock epinephrine is cost-effective at device acquisition costs not exceeding $338 per school per year, although a universal model vs a supplemental model is associated with superior health and economic outcomes.
Epigenome-wide meta-analysis of DNA methylation and childhood asthma
Authors: Sarah E. Reese, Cheng-Jian Xu, Herman T. den Dekker, Mi Kyeong Lee, Sinjini Sikdar, Carlos Ruiz-Arenas, Simon K. Merid, Faisal I. Rezwan, Christian M. Page, Vilhelmina Ullemar, Phillip E. Melton, Sam S. Oh, Ivana V. Yang, Kimberley Burrows, Cilla Söderhäll, Dereje D. Jima, Lu Gao, Ryan Arathimos, Leanne K. Küpers, Matthias Wielscher, Peter Rzehak, Jari Lahti, Catherine Laprise, Anne-Marie Madore, James Ward, Brian D. Bennett, Tianyuan Wang, Douglas A. Bell, Judith M. Vonk, Siri E. Håberg, Shanshan Zhao, Robert Karlsson, Elysia Hollams, Donglei Hu, Adam J. Richards, Anna Bergström, Gemma C. Sharp, Janine F. Felix, Mariona Bustamante, Olena Gruzieva, Rachel L. Maguire, Frank Gilliland, Nour Baïz, Ellen A. Nohr, Eva Corpeleijn, Sylvain Sebert, Wilfried Karmaus, Veit Grote, Eero Kajantie, Maria C. Magnus, Anne K. Örtqvist, Celeste Eng, Andrew H. Liu, Inger Kull, Vincent W.V. Jaddoe, Jordi Sunyer, Juha Kere, Cathrine Hoyo, Isabella Annesi-Maesano, Syed Hasan Arshad, Berthold Koletzko, Bert Brunekreef, Elisabeth B. Binder, Katri Räikkönen, Eva Reischl, John W. Holloway, Marjo-Riitta Jarvelin, Harold Snieder, Nabila Kazmi, Carrie V. Breton, Susan K. Murphy, Göran Pershagen, Josep Maria Anto, Caroline L. Relton, David A. Schwartz, Esteban G. Burchard, Rae-Chi Huang, Wenche Nystad, Catarina Almqvist, A. John Henderson, Erik Melén, Liesbeth Duijts, Gerard H. Koppelman, Stephanie J. London
Journal: Journal of Allergy and Clinical Immunology (2018)

Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.
CD38low Natural Killer Cells Transiently Expressing CD16F158V m-RNA Potentiates the Therapeutic Activity of Daratumumab Against Multiple Myeloma with Minimal Effector NK Cell Fratricide
Authors: Subhashis Sarkar, Sachin Chauhan, Arwen Stikvoort, Alessandro Natoni, John Daly, Robert Henderson, Tuna Mutis, Michael E O'Dwyer
Journal: Blood (2018)
High-dose interleukin-2 (HD IL-2) in the treatment of advanced melanoma: The University of Pittsburgh experience.
Authors: Diwakar Davar, Melissa Saul, Ahmad A. Tarhini, An Tran, Kerry Trent, Cindy Sander, John M. Kirkwood, Hussein Abdul-Hassan Tawbi
Journal: Journal of Clinical Oncology (2013)

9075 Background: IL-2 is a T-cell growth factor tested in a variety of regimens for advanced melanoma (MEL) and renal cell carcinoma (RCC). High-dose IL-2 (600,000-720,000 IU/kg administered intravenously every 8 hours for up to 14 consecutive doses) was approved by FDA for advanced MEL and RCC in 1998 based upon the durability of responses observed. Early studies of HD IL-2 reported overall (OR) and complete response (CR) rates of 16% and 8% respectively. Severe toxicity limited use to specialized centers with standardized protocols, either intensive care (ICU) or oncology specialty settings. The U Pittsburgh has treated 1022 patients with IL-2 at any dosage and we here present outcomes of 550 MEL pts treated with HD IL-2 in an oncology specialty non-ICU setting. Methods: Clinical and radiological data were collected on all pts treated with IL-2 using the UPCI Cancer Registry and Medical Archival System (MARS). Pharmacy records were reviewed for dosing details. The influence of baseline characteristics on treatment outcomes was assessed using Cox proportional hazards analysis. Results: A total of 848 pts received HD IL-2, of which 298 pts had RCC while 550 had MEL. Detailed pharmacy dosing records were reviewed from 176 pts treated over the past 12 years (2000-2012) who received a total of 3738 cycles. Of 165 pts evaluable for response, OR was documented in 24 pts (14.8%) and CR in 5 pts (3.0%). Median overall survival (OS) was 10.0 mos for all patients and 21.5 mos for responders (CR+PR). Median number of doses per cycle was 7. Toxicity was consistent with prior reports. HD IL-2 required ICU transfers in 5% and 1 death was attributed to HD IL-2. Pts with higher baseline lactate dehydrogenase (LDH) had poorer OS (p &lt; 0.05). Conclusions: In this large and uniformly treated series of recent patients treated with IL-2 OR/CR rates with HD IL-2 are 14.8% and 3.0% respectively. Higher LDH is associated with poorer outcome. Biomarkers of response are currently being evaluated in banked clinical specimens collected from patients under the SPORE in Skin Cancer (P50 CA121973).
A Phase 1b Study Investigating the Combination of the Tetravalent Bispecific NK Cell Engager AFM13 and Pembrolizumab in Patients with Relapsed/Refractory Hodgkin Lymphoma after Brentuximab Vedotin Failure: Updated Safety and Efficacy Data
Authors: Nancy L. Bartlett, Robert W. Chen, Eva Domingo-Domenech, Andres Forero-Torres, Ramon Garcia-Sanz, Philippe Armand, Sumana Devata, Antonia Rodriguez Izquierdo, Izidore S. Lossos, Craig B. Reeder, Taimur Sher, Cassandra Choe-Juliak, Kim Prier, Sylvia Schwarz, Andras Strassz, Leila Alland, Stephen M. Ansell
Journal: Blood (2018)
P1.03-014 Saline Alone vs Saline plus Mannitol Hydration for the Prevention of Acute Cisplatin Nephrotoxicity: A Randomized Trial
Authors: W. Dela Cruz, F. Flynt, S. Terrazzino, N. Hullinger, M. King, J. Aden, D. Nelson, T. Byrd
Journal: Journal of Thoracic Oncology (2017)
Abstract 19380: Synchronized Pulsatile Extracorporeal Life Support Preserves Left Ventricular Functions in Comparison With Continuous Extracorporeal Flow in Porcine Model of Cardiogenic Shock
Authors: Petr Ostadal, Mikulas Mlcek, Svitlana Strunina, Matej Hrachovina, Andreas Kruger, Dagmar Vondrakova, Marek Janotka, Otomar Kittnar, Petr Neuzil
Journal: Circulation (2015)

Introduction: Veno-arterial extracorporeal life support (ECLS) is increasingly used for the therapy of rapidly progressing or severe cardiogenic shock. However, it has been repeatedly shown that increased afterload associated with ECLS significantly deteriorates left ventricular (LV) performance. Recently, new ECG-synchronized pulsatile cardiac assist system was introduced that offers full circulatory support with increased diastolic and decreased systolic extracorporeal flow. The aim of the present study was to compare the parameters of LV function during standard continuous flow ECLS support and ECG-synchronized pulsatile flow ECLS in cardiogenic shock. Methods: Ten female swine (body weight 45 kg) underwent ECLS implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock with signs of tissue hypoperfusion was induced by global myocardial hypoxia. Hemodynamic and cardiac performance parameters were then measured at different levels of continuous or pulsatile ECLS flow (ranging from 1 L/min to 4 L/min) using arterial and venous catheters, a pulmonary artery catheter and a LV pressure-volume loop catheter. Results: Myocardial hypoxia resulted in a decline in mean (±SD) cardiac output to 2.3±1.2 L/min, systolic blood pressure to 61±7 mmHg and LV ejection fraction (EF) to 21±7%. Synchronized pulsatile flow was associated with significant reduction of LV end-systolic volume (ESV), increase in LV stroke volume (SV), and higher EF at all ECLS flow levels in comparison with continuous ECLS flow (Figure 1). At selected ECLS flow levels, pulsatile flow reduced also LV end-diastolic pressure (EDP), end-diastolic volume (EDV), and systolic pressure (SP) (Figure 1). Conclusion: Our results indicate that ECG-synchronized pulsatile ECLS flow preserves LV function in comparison with standard continuous-flow ECLS in cardiogenic shock.
Prevalence and short-term mortality of acute-on-chronic liver failure: A national cohort study from the USA
Authors: Ruben Hernaez, Jennifer R. Kramer, Yan Liu, Aylin Tansel, Yamini Natarajan, Khozema B. Hussain, Pere Ginès, Elsa Solà, Richard Moreau, Alexander Gerbes, Hashem B. El-Serag, Fasiha Kanwal
Journal: Journal of Hepatology (2018)
Whole Blood Transcriptional Profiling Reveals Highly Deregulated Atherosclerosis Genes in Myeloproliferative Cancer
Authors: Vibe Skov, Mads Thomassen, Lasse Kjær, Caroline Riley, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Journal: Blood (2018)