tbuckley/cabot-search huggingface dataset:
Livedo Reticularis in Cold Agglutinin Disease
Authors: Konika Sharma, Anush Patel
Journal: New England Journal of Medicine (2019)

A 70-year-old woman presented with dizziness, rash, and hemolytic anemia 2 weeks after the onset of a viral respiratory tract infection. The rash was consistent with livedo reticularis, and a diagnosis of cold agglutinin disease was made.
TCT-538 Can an Entirely Extracardiac, Minimally Invasive Pacing System Be Helpful in TAVR Patients?
Authors: Martin Burke, Anne-Floor Quast, Adrian Ebner, Richard Wasley, Jim Vehmeijer, Alan Marcovecchio, Rick Sanghera, Reinoud Knops, Gary Gershony
Journal: Journal of the American College of Cardiology (2019)
Effective Cessation Treatment for Patients With Cancer Who Smoke—The Fourth Pillar of Cancer Care
Authors: Michael C. Fiore, Heather D’Angelo, Timothy Baker
Journal: JAMA Network Open (2019)

Paul M. Cinciripini, PhD; Maher Karam-Hage, MD; George Kypriotakis, PhD; Jason D. Robinson, PhD; Vance Rabius, PhD; Diane Beneventi, PhD; Jennifer A. Minnix, PhD; Janice A. Blalock, PhD
Plasma 25-Hydroxyvitamin D Levels and Survival in Patients with Advanced or Metastatic Colorectal Cancer: Findings from CALGB/SWOG 80405 (Alliance)
Authors: Chen Yuan, Kaori Sato, Bruce W. Hollis, Sui Zhang, Donna Niedzwiecki, Fang-Shu Ou, I-Wen Chang, Bert H. O'Neil, Federico Innocenti, Heinz-Josef Lenz, Charles D. Blanke, Richard M. Goldberg, Alan P. Venook, Robert J. Mayer, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kimmie Ng
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer. Experimental Design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. Results: At study entry, 63% of patients were vitamin D deficient (&amp;lt;20 ng/mL) and 31% were vitamin D insufficient (20–&amp;lt;30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend = 0.0009 and 0.03, respectively). Compared with patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95% CI, 0.53–0.83) for OS and 0.81 (95% CI, 0.66–1.00) for PFS. The improved survival associated with higher 25(OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. Conclusions: In this large cohort of patients with advanced or metastatic colorectal cancer, higher plasma 25(OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in patients with colorectal cancer are warranted.
Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification
Authors: Sam O Kleeman, Viktor H Koelzer, Helen JS Jones, Ester Gil Vazquez, Hayley Davis, James E East, Roland Arnold, Martijn AJ Koppens, Andrew Blake, Enric Domingo, Chris Cunningham, Andrew D Beggs, Valerie Pestinger, Maurice B Loughrey, Lai-Mun Wang, Tamsin RM Lannagan, Susan L Woods, Daniel Worthley, Ian Tomlinson, Philip D Dunne, Timothy Maughan, Simon J Leedham
Journal: Gut (2019)

Objective Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins ( Adenomatous polyposis coli , β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis ( RNF43 , RSPO -fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours. Design We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups. Results Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of RSPO may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes ( AXIN2 , NKD1 ) occurring even in CIMP-negative LD cancers. AXIN2 mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve &gt;0.93). Conclusions Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential AXIN2 expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors.
TCT-542 Impact of Baseline Anemia and Thrombocytopenia on 1-Year Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention
Authors: Ridhima Goel, Davide Cao, Roxana Mehran, Rishi Chandiramani, Anastasios Roumeliotis, Moritz Blum, Rachel Singleton, Zaha Waseem, Samantha Sartori, Giulio Stefanini, George Dangas, Usman Baber, Asaad Khan, Nitin Barman, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2019)
Consensus recommendations for the use of noninvasive melanoma detection techniques based on results of an international Delphi process
Authors: Reid A. Waldman, Jane M. Grant-Kels, Clara N. Curiel, Julia Curtis, Salvador González Rodríguez, Shasa Hu, Philip Kerr, Ashfaq Marghoob, Orit Markowitz, Giovanni Pellacani, Harold Rabinovitz, Babar Rao, Alon Scope, Jennifer A. Stein, Susan M. Swetter
Journal: Journal of the American Academy of Dermatology (2019)
TCT-12 Results From the CAMI1 Study: Selective CRP Apheresis as a New Treatment Option in Acute Myocardial Infarction
Authors: Wolfgang Ries, Jan Torzewski, Ahmed Sheriff, Hüseyin Ince, Steffen Mitzner, Peter Nordbeck, Christian Butter, Michael Zaenker, Christoph Garlichs
Journal: Journal of the American College of Cardiology (2019)
TCT-227 Efficacy of Coronary Sinus Reducer in Patients With Nonrevascularized Chronic Total Occlusions: A Multicenter Experience
Authors: Carlo Zivelonghi, Stefan Verheye, Francesco Giannini, Jan Peter van Kuijk, George Tzanis, Masieh Abawi, Pieter Stella, Pierfrancesco Agostoni
Journal: Journal of the American College of Cardiology (2019)
Tailored Black Phosphorus for Erythrocyte Membrane Nanocloaking with Interleukin-1<i>α</i> siRNA and Paclitaxel for Targeted, Durable, and Mild Combination Cancer Therapy
Authors: Wenquan Ou, Jeong Hoon Byeon, Zar Chi Soe, Bo Kyun Kim, Raj Kumar Thapa, Biki Gupta, Bijay Kumar Poudel, Sae Kwang Ku, Chul Soon Yong, Jong Oh Kim
Journal: Theranostics (2019)

Several therapeutic nanosystems have been engineered to remedy the shortcomings of cancer monotherapies, including immunotherapy (stimulating the host immune system to eradicate cancer), to improve therapeutic efficacy with minimizing off-target effects and tumor-induced immunosuppression.Light-activated components in nanosystems confer additional phototherapeutic effects as combinatorial modalities; however, systemic and thermal toxicities with unfavorable accumulation and excretion of nanoystem components now hamper their practical applications.Thus, there remains a need for optimal multifunctional nanosystems to enhance targeted, durable, and mild combination therapies for efficient cancer treatment without notable side effects.Methods: A nanosystem constructed with a base core (poly-L-histidine [H]-grafted black phosphorus [BP]) and a shell (erythrocyte membrane [EM]) is developed to offer a mild photoresponsive (near-infrared) activity with erythrocyte mimicry.In-flight electrostatic tailoring to extract uniform BP nanoparticles maintains a hydrodynamic size of <200 nm (enabling enhanced permeability and retention) after EM cloaking and enhances their biocompatibility.Results: Ephrin-A2 receptor-specific peptide (YSA, targeting cancer cells), interleukin-1α silencing small interfering RNA (ILsi, restricting regulatory T cell trafficking), and paclitaxel (X, inducing durable chemotherapeutics) are incorporated within the base core@shell constructs to create BP-H-ILsi-X@EM-YSA architectures, which provide a more intelligent nanosystem for combination cancer therapies. Conclusion:The in-flight tailoring of BP particles provides a promising base core for fabricating <200 nm EM-mimicking multifunctional nanosystems, which could be beneficial for constructing smarter nanoarchitectures to use in combination cancer therapies.
TCT-111 Clinical Implication of Quantitative Flow Ratio After Percutaneous Coronary Intervention for Three Vessel Disease
Authors: Norihiro Kogame, Kuniaki Takahashi, Mariusz Tomaniak, Ply Chichareon, Rodrigo Modolo, Yuki Katagiri, Taku Asano, Rod Stables, Simon Walsh, Manel Sabate, Justin Davies, Jan Piek, Robert-Jan Van Geuns, Johan Reiber, Vasim Farooq, Adrian Banning, Javier Escaned, Patrick Serruys, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2019)
Incidence and Determinants of Mental Health Service Use After Bariatric Surgery
Authors: David J. R. Morgan, Kwok M. Ho, Cameron Platell
Journal: JAMA Psychiatry (2019)

Obesity is associated with an increased prevalence of psychiatric disorders. The association of bariatric surgery with mental health outcomes is poorly understood.To investigate the association of bariatric surgery with the incidence of outpatient, emergency department (ED), and inpatient mental health service use.This statewide, mirror-image, longitudinal cohort study used data from Western Australian Department of Health Data Linkage Branch records from all patients undergoing index (ie, first) bariatric surgery in Western Australia over a 10-year period (January 2007-December 2016), with mean (SD) follow-up periods of 10.2 (2.9) years before and 5.2 (2.9) years after index bariatric surgery. The data analysis was performed between November 2018 and March 2019.Index bariatric surgery.The incidence and predictors for mental health presentations, deliberate self-harm, and suicide in association with the timing of bariatric surgery.A total of 24 766 patients underwent index bariatric surgery; of these, the mean (SD) age was 42.5 (11.7) years and 19 144 (77.3%) were women. Use of at least 1 mental health service occurred in 3976 patients (16.1%), with 1401 patients (35.2%) presenting only before surgery, 1025 (25.8%) presenting before and after surgery, and 1550 patients (39.0%) presenting only after surgery. There was an increase in psychiatric illness presentations after bariatric surgery (outpatient clinic attendance: incidence rate ratio [IRR], 2.3; 95% CI, 2.3-2.4; ED attendance: IRR, 3.0; 95% CI, 2.8-3.2; psychiatric hospitalization: IRR, 3.0; 95% CI, 2.8-3.1). There was also a 5-fold increase in deliberate self-harm presentations to an ED after surgery (IRR, 4.7; 95% CI, 3.8-5.7), with 25 of 261 postoperatives deaths (9.6%) due to suicide. Complications after bariatric surgery requiring further surgical intervention and a history of mental health service provision before surgery were the most important associations with subsequent mental health presentations after surgery. Deliberate self-harm and mental and behavioral disorders due to psychoactive substance use before bariatric surgery were the main associations with subsequent deliberate self-harm or suicide after surgery.We observed an increase in mental health service presentations after bariatric surgery, particularly among those who had prior psychiatric illnesses or developed surgical complications requiring further surgery. These findings caution the hypothesis that weight reduction by bariatric surgery will improve mental health in patients with obesity.
TCT-455 Right Ventricular Remodeling Reduces Heart Failure Readmissions in Patients Undergoing Transcatheter Mitral Valve Repair
Authors: Abhishek Sawant, Nidhi Kanwar, Srilekha Sridhara, Edward Distler, Siamac Yazdchi, Srujal Patel, Janelle Rodriguez, Meghana Prakash Hiriyur Prakash, Adnan Habib, Meenakshi Sridhar, Arnav Kumar, Philipp Wiesner, Ashish Pershad
Journal: Journal of the American College of Cardiology (2019)
Abstract P075: Five Dietary Patterns Emerge in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Abraham J Letter, Suzanne E Judd, James M Shikany, David L Roth, P. K Newby
Journal: Circulation (2012)

Introduction: Examining diet as a whole using dietary patterns methods rather than focusing on single food group or nutrient exposures may be more informative when studying associations of diet and disease. Several large cohorts have used factor analysis to empirically derive dietary patterns but few have employed a cohort as geographically and racially diverse as the REGARDS study. Methods: The REGARDS study is a cohort of 30,239 Black and White adults age 45 and older, half of whom reside in the Southeastern US (also known as the stroke belt); the remainder reside elsewhere in the continental US. The present analysis included 21,636 participants who completed the Block 98 food frequency questionnaire at baseline. Principal Component Analysis (PCA) with varimax rotation was used on a split sample to determine dietary patterns based on 56 food groups. Race, sex, and region-specific solutions were evaluated for congruence alongside scree plots, eigenvalues, and interpretability. Confirmatory Factor Analysis (CFA) was utilized on the second half of the sample for validation of the PCA findings. Results: Sub-group analyses showed acceptable congruence and interpretability, thus we performed PCA on the entire sample in the final solution. Five dietary patterns emerged: the “traditional” pattern was characterized by mixed dishes; the “healthy” pattern by fruits and vegetables; the “sweets” pattern by sweet snacks and desserts; the “Southern” pattern by fried food, organ meat, and sweetened beverages; and the “alcohol” pattern by beer, wine, liquor, and salads. There were marked differences in factor score means across demographic and socioeconomic groups. For example, Blacks were much more likely than Whites to have a Southern diet. Discussion: Clear and meaningful dietary patterns emerged in this large cohort of Black and White Americans. Variability in dietary intake across demographic factors emphasizes the need to explore how these factors contribute to differential susceptibility to stroke and other chronic diseases.
TCT-192 Late Coronary Healing Assessed With Optical Coherence Tomography After Magnesium Bioresorbable Scaffold Implantation
Authors: Christian Fallesen, Akiko Maehara, Kirstine Hansen, Manijeh Noori, Julia Ellert, Ole Ahlehoff, Karsten Veien, Anders Junker, Henrik Hansen, Jens Lassen, Lisette Okkels Jensen
Journal: Journal of the American College of Cardiology (2019)
TCT-74 Baseline Left Ventricular Hypertrophy and 5-Year Outcomes after Transcatheter Aortic Valve Replacement: An Analysis of the PARTNER Trials and Registries
Authors: Holly Gonzales, Pamela Douglas, Philippe Pibarot, Rebecca Hahn, Omar Khalique, Wael Jaber, Paul Cremer, Neil Weissman, Federico Asch, Yiran Zhang, Zachary Gertz, Sammy Elmariah, Marie-Annick Clavel, Vinod Thourani, Melissa Daubert, Maria Alu, Martin Leon, Brian Lindman
Journal: Journal of the American College of Cardiology (2019)
TCT-525 Predictors of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement in Patients With Very Large Annuli: Data From the 34mm Self-Expanding CoreValve Evolut R Prospective Multicenter Registry
Authors: Victor Alfonso Jimenez Diaz, Diego López Otero, Ignacio Cruz-Gonzalez, Ignacio Amat-Santos, Fernando Rivero, Enrique Gutierrez Ibanes, Antonio Munoz-Garcia, Beatriz Vaquerizo, Jose Carlos Moreno Samos, Tania Rodriguez Gabella, Hugo Gonzalez Saldivar, Ramiro Trillo Nouche, Jose Antonio Baz Alonso, Andres Iñiguez
Journal: Journal of the American College of Cardiology (2019)
TCT-377 Use of Direct Oral Anticoagulation Therapy Alone Versus DOAC in Conjunction With Aspirin for Anticoagulation Following Implantation of the Watchman Left Atrial Appendage Closure Device
Authors: Joseph Aragon, Benita Tjoe, Hoang Nguyen, Michael Shenoda, Jessica Quintos
Journal: Journal of the American College of Cardiology (2019)
TCT-554 Laser Atherectomy and Drug-Coated Balloons for the Treatment of Femoropopliteal In-Stent Restenosis: 2-Year Outcomes.
Authors: Damianos Kokkinidis, Sean Behan, Omar Jawaid, Prio Hossain, Gagan Singh, Stephen Waldo, Ehrin Armstrong
Journal: Journal of the American College of Cardiology (2019)
Reply
Authors: Elizabeth C. Goode, Gideon M. Hirschfield, Simon M. Rushbrook
Journal: Hepatology (2019)

Potential conflict of interest: Dr. Rushbrook advises Falk. Primary sclerosing cholangitis (PSC) is a rare liver disease with high clinical burden and significant heterogeneity in outcome. The UK‐PSC risk score, based on a national observational cohort study of over 1,000 patients from across the United Kingdom, provides a robust evaluation of PSC risk for individual patients based on clinical predictors of outcome. In recognition of the fact that early and late risk may be driven by different covariates, we applied a novel approach and have thus built stronger predictive models (defined as a C‐statistic > 0.8) for both short‐term and long‐term PSC risk. Additionally, we have validated our models in separate national and internationally derived cohorts. Importantly, we provide a simple means of interpreting the UK‐PSC risk score with low‐risk and high‐risk groups. Furthermore, we directly compare its predictive power with two well‐established risk scores: the Mayo score and the aspartate aminotransferase–to‐platelet ratio index, in the same external validation cohort, establishing superior predictive value of the UK‐PSC risk scores. Our work therefore addresses some of the challenges raised by patients as priority areas for research. We appreciate Dr. Wang et al. for their correspondence. As noted by Wang et al., our manuscript makes comment on the recently reported C‐statistic (C = 0.68) of the Amsterdam‐Oxford model (AOM)1 in the introduction to our paper, but at no point do we draw a direct comparison with it. With general agreement that strong models have a reported C‐statistic greater than 0.8, we read with interest that the AOM could have been improved (with higher C‐statistic) if they had chosen to create short‐term and long‐term models, as was reported in our manuscript. In this, they further support an argument that future PSC risk models may better serve the clinical and patient community if they recognize different periods of risk, as per the UK‐PSC model. It has been encouraging for both patients and clinicians that in recent years, several PSC risk prediction tools have been published, and it will take time for these to be evaluated and interrogated. The AOM score has recently been validated,2 and over time we look forward to the UK‐PSC score being similarly tested. It was beyond the scope of our manuscript to compare and externally validate every existing PSC risk score. We remain encouraged by the interest in our work and the field's commitment to work together to overcome the challenges that patients with PSC face. We are therefore pleased by ongoing efforts for a meta‐analysis of existing data sets, such as our own data and, among others, the Amsterdam team's data. This, we believe, will most effectively help patients and clinicians navigate a difficult and challenging disease.
Abstract 1646: Discovery and characterization of BAY-6035, a novel benzodiazepine-based SMYD3 inhibitor
Authors: Stefan Gradl, Holger Steuber, Jörg Weiske, Norbert Schmees, Stephan Siegel, Detlef Stoeckigt, Clara D. Christ, Fengling Li, Shawna Organ, Dalia Barsyte-Lovejoy, Magdalena M. Szewczyk, Steven Kennedy, Viacheslav Trush, Masoud Vedadi, Cheryl H. Arrowsmith, Peter J. Brown, Manfred Husemann, Amaury E. Fernandez-Montalvan, Volker Badock, Marcus Bauser, Andrea Haegebarth, Ingo V. Hartung, Carlo Stresemann
Journal: Cancer Research (2018)

Abstract SMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase (PKMT) which was initially described as H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has recently been reported to methylate and regulate several non-histone cancer relevant proteins such as mitogen-activated protein kinase kinase kinase 2 (MAP3K2), vascular endothelial growth factor receptor 1 (VEGFR1), and the human epidermal growth factor receptor 2 (HER2). In addition overexpression of SMYD3 has been linked to poor prognosis in certain cancers, thus supporting a possible oncogenic role for SMYD3 and making it an attractive target for anticancer drug development. Here we report the discovery of a novel potent and selective SMYD3 inhibitor series. We performed a thermal shift assay based (TSA) high throughput screening followed by extensive biophysical validation resulting in identification of a benzodiazepine-based SMYD3 inhibitor series. The co-crystallization structures revealed that this series binds to the substrate binding site and occupies the hydrophobic pocket for lysine binding using an unprecedented hydrogen bond pattern. The competitive behavior of the inhibitor in biochemical assays was consistent with the binding mode observed in the crystal structure. Further optimization generated BAY-6035, which showed improved nanomolar potency and was selective against kinases and other PKMTs. Furthermore, BAY-6035 specifically inhibited methylation of MAP3K2 by SMYD3 in a cellular assay with similar potency. In summary, BAY-6035 is a novel selective and potent SMYD3 inhibitor probe and will foster the exploration of the biologic role of SMYD3 in diseased and non-diseased tissues. Citation Format: Stefan Gradl, Holger Steuber, Jörg Weiske, Norbert Schmees, Stephan Siegel, Detlef Stoeckigt, Clara D. Christ, Fengling Li, Shawna Organ, Dalia Barsyte-Lovejoy, Magdalena M. Szewczyk, Steven Kennedy, Viacheslav Trush, Masoud Vedadi, Cheryl H. Arrowsmith, Peter J. Brown, Manfred Husemann, Amaury E. Fernandez-Montalvan, Volker Badock, Marcus Bauser, Andrea Haegebarth, Ingo V. Hartung, Carlo Stresemann. Discovery and characterization of BAY-6035, a novel benzodiazepine-based SMYD3 inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1646.
TCT-785 Outcomes of Distal Versus Proximal Trans-Radial Approach for Coronary Angiogram and Percutaneous Coronary Intervention
Authors: Marwan Saad, Mohanad Hamandi, Rimsha Hasan, Michael Megaly, Srini Potluri, Molly Szerlip, J. Dawn Abbott, Amir Lotfi, Ferdinand Kiemeneij, Karim Al-Azizi
Journal: Journal of the American College of Cardiology (2019)