tbuckley/cabot-search huggingface dataset:
Abstract 18952: A Novel Engineered Neuregulin-hydrogel System Regenerates Mammalian Heart Muscle and Enhances Ventricular Function in a Preclinical Ovine Model of Ischemic Cardiomyopathy
Authors: Jeffrey E Cohen, Andrew B Goldstone, Brendan P Purcell, Yasuhiro Shudo, John W MacArthur, Jr., Bryan B Edwards, Jay B Patel, Michael S Hopkins, Anahita Eskandari, Amanda N Steele, Nicholas C Cheung, Chiaka N Aribeana, Jason A Burdick, Y. Joseph Woo
Journal: Circulation (2015)

Objective: The clinical efficacy of neuregulin (NRG), a ligand of the Her family receptors, is hindered by off-target exposure and requisite daily systemic infusions. We recently encapsulated NRG in a hydrogel (HG) for targeted and sustained myocardial delivery; beneficial results in a murine model of ischemic cardiomyopathy were clear. Here, we evaluate NRG-HG’s translational potential for myocardial regeneration and functional improvement in the clinical realm using a preclinical ovine model of ischemic cardiomyopathy. Methods: Male Dorset sheep (n=30) underwent baseline cardiac assessment with MRI and pressure-volume (PV) catheterization. Myocardial infarction (MI) was induced by ligating the 2 nd and 3 rd diagonal artery branches, and sheep were randomized to receive myocardial borderzone injection of 1mL saline, HG alone, NRG alone, or NRG-HG. Eight weeks post-infarction, repeat hemodynamic assessment was performed followed by tissue acquisition. A subset underwent sacrifice at 1 week for molecular analyses. Results: Analysis of myocardial borderzone 1-week post-infarction revealed NRG-HG augmented phosphorylated ErbB4, ErbB2, ERK, and histone h3 compared with all other groups. This marker activation suggests receptor activation, downstream signaling, and cardiac cell-cycle entry. At 8 weeks, NRG-HG significantly reduced scar size and augmented ventricular function (Table). There was no evidence of off-target NRG at 1 and 8 weeks, and no evidence of gel embolization or neurologic insult (by brain MRI) from intramyocardial hydrogel delivery. Conclusion: Targeted and sustained intramyocardial delivery of NRG with an engineered hydrogel platform triggers regeneration of mammalian heart muscle and augments ventricular function in a large animal model of ischemic cardiomyopathy. This novel, engineered delivery system realizes the true potential of NRG and its translation to clinical regenerative therapeutics.
Abstract 18245: Identifying Novel Predictors for Incident Heart Failure Using Statistical Learning Techniques in the Women’s Health Initiative (WHI) Cohort
Authors: Geoffrey H Tison, Gregory Nah, Jeffrey E Olgin, Eric Vittinghoff, Barbara V Howard, Randi Foraker, Matthew A Allison, Ramon L Casanova, Rachel H Blair, Khadijah K Breathett, Liviu Klein, Nisha I Parikh
Journal: Circulation (2016)

Introduction:  Machine learning (statistical learning) techniques applied to high-dimensional health data may aid in identifying novel predictors of heart failure (HF). We used machine learning to identify novel predictors of HF in post-menopausal women and compared these models to an established HF risk model.   Methods:  After performing minimum-necessary data cleaning on all baseline WHI variables, 1227 variables remained. Without  a priori  input, we separately applied the Least Absolute Shrinkage and Selection Operator (LASSO) technique with cross-validation, and Classification and Regression Trees (CART) to select sets of variables that are predictive for our primary outcome of incident heart failure hospitalization. We built Cox Proportional Hazards models using each set of predictors and using published predictors from the Atherosclerosis risk in Communities (ARIC) cohort. Model discrimination was compared using Receiver Operator Characteristic (ROC).   Results:  Total sample size was 44,173; there were 2,355 outcomes and the median time to event was 8.7 years. LASSO and CART identified 12 and 9 significant predictors, respectively. The highest correlation between selected variables was 0.56. Selected novel predictors include physical function, Hodgkin’s Lymphoma, prior pulmonary embolism, Medicare insurance, and use of cardiotonic, antiarrhythmic and mineral supplement medication among others. Other variables reflected known risk factors for HF (Table). In ROC analysis the model using CART variables had the highest C-statistic (0.794), followed by LASSO (0.775) and ARIC (0.712).   Conclusions:  When applied in the WHI, machine learning techniques can identify novel sets of variables without  a priori  input that yield risk prediction models with improved discrimination as compared to an established HF risk model. Both the models and the novel predictors provide a basis for hypothesis generation and future investigation.
High 18F-FDG Avidity of Low-Grade Esthesioneuroblastoma
Authors: Arnaud Jannin, Anthony Turpin, Clio Baillet, Sébastien Aubert, Christine Do Cao
Journal: Clinical Nuclear Medicine (2017)

Esthesioneuroblastoma is a rare neuroectodermic tumor of the olfactory tract. An F-FDG PET/CT was performed in a 75-year-old woman with cervical lymphadenopathy. It demonstrated focal intense uptake (SUVmax, 72 g/mL) in an occult sphenoclival tumor. Anatomopathological examination of the lymphadenopathy and the primary tumor biopsy revealed well-differentiated esthesioneuroblastoma. Explaining the paradox between tumor differentiation and PET findings, immunohistochemistry showed low Ki-67 but overexpression of GLUT-1 suggesting an activation of hypoxia pathways. Unlike many solid tumors, FDG avidity is not correlated with histological grade in esthesioneuroblastoma. The tumor biology may clarify the discrepancy between metabolic activity and cellular mitotic processes.
Abstract 15746: Trends in the Hospitalization Rates and Outcomes of Patients With Aortic Stenosis From 2004 to 2013
Authors: Andrew Czarnecki, David A Alter, Peter C Austin, Stephen E Fremes, Maria Koh, Jack V Tu, Harindra C Wijeysundera, Andrew T Yan, Dennis T Ko
Journal: Circulation (2016)

Background:  An aging population and the introduction of transcatheter aortic valve replacement (TAVR) have led to a major shift in how patients with aortic stenosis (AS) are managed. Although there is a need to understand the epidemiological aspects of AS for future resource planning, few studies have characterized recent trends in hospitalization and outcomes of these patients.   Methods:  We performed an observational study using population-based data in Ontario, Canada. Patients with a first hospitalization for a primary or secondary diagnosis of AS between 2004 and 2013 were included. The annual rates of AS-related hospitalization were determined and standardized by the Ontario population. Rates of aortic valve intervention and all-cause mortality at 30 days and 1 year after index hospitalization were assessed. The Cochrane-Armitage test was used to evaluate temporal trends. Logistic regression models were used to evaluate adjusted mortality.   Results:  A total of 37,970 patients were hospitalized with AS during the study period. The age- and sex-standardized hospitalization rate for AS increased from 36 to 39 per 100,000 between 2004 and 2013 (p    Conclusion:  Over the past decade when TAVR was introduced, rates of AS hospitalization have significantly increased in the elderly, beyond that expected with population growth. While rates of intervention have also increased, this has not been associated with a change in mortality.
PTH-060 Expression of madcam-1 in the upper gastrointestinal tract: is there a role for disrupting interactions between madcam-1 and alpha-4/beta-7 integrin in upper gi crohn’s disease?
Authors: A Ahmed, DM Pritchard, Burkitt
Journal: Gut (2017)

Introduction  MAdCAM-1 is expressed on the endothelial surfaces of intestinal blood vessels. Interaction between MAdCAM-1 and α4β7-integrin regulates intestinal lymphocyte recruitment and trafficking. Therapies targeting this interaction are licensed for use in Crohn’s disease (CD). Although intestinal expression of MAdCAM-1 is well established, its expression in the upper GI tract (UGIT) has been subject to little investigation, and may be relevant in the management of CD patients who have UGIT involvement.  We investigated expression of MAdCAM-1 in Helicobacter felis induced murine gastric inflammation, a model of minimally-inflamed gastric metaplasia (MIGM), and in cancer associated, microscopically normal human colon and oesophagus.  Method  To induce MIGM, groups of 5 female C57BL/6 (WT) mice were treated with tamoxifen (TAM) 150 mg/kg or vehicle by IP injection. Animals were culled 72 hours later. Gastric inflammation was studied in groups of 5 INS-GAS mice exposed to sham-gavage, or colonised with H. felis for 6 weeks. Samples of gastric corpus (GC) and forestomach (FS) were obtained for histology.  Liverpool Bio-Innovation Hub Biobank provided sections of histologically normal full-thickness tissue from patients undergoing resections for oesophageal squamous cell carcinoma (oesophagus n=5, GC n=1) or colorectal cancer (n=5) following ethical review. Sections were immunostained for MAdCAM-1; positively stained structures were quantified per unit area.  Results  Untreated WT mice demonstrated MAdCAM-1 staining density of 15.0 (±6.4 SD) structures/mm2 in the GC; staining was 7.6 fold more dense in submucosa cf mucosa (p=0.008). MAdCAM-1 staining density increased in mucosa (5.0 fold, p=0.008), but not submucosa after TAM administration. Untreated INS-GAS mice had lower GC MAdCAM-1 staining density than untreated WT mice (4.2 fold, p  MAdCAM-1 staining was not observed in association with the squamous epithelium of murine FS or human oesophagus, which was significantly different from control columnar epithelial tissues (p=0.0008, p=0.016 respectively).  Conclusion  Mucosal MAdCAM-1 expression in murine GC is upregulated during inflammation and tissue remodelling. MAdCAM-1 was not identified in murine or human squamous epithelium. Further studies in cohorts of CD patients are needed to determine whether targeting MAdCAM-1/α4β7-integrin interactions is useful for patients with upper GI CD.  Disclosure of Interest  None Declared
Abstract 17523: Pregnancy Outcomes in Women With Regurgitant Valve Lesions
Authors: Angelo Dave C Javier, Jasmine Grewal, Nadia Gabarin, Jack M Colman, Marla C Kiess, Rachel D Wald, Jennifer Mason, Matthew Sermer, Samuel C Siu, Candice K Silversides
Journal: Circulation (2016)

Introduction:  Pregnancy outcomes in women with significant regurgitant valve lesions have not been well defined. The primary objective of this study is to determine the frequency of maternal adverse cardiac events in pregnant women with significant regurgitant valve lesions. We also aim to describe obstetric and fetal/neonatal adverse outcomes in this population.   Methods:  Women with heart disease enrolled in a prospective study on pregnancy outcomes (Toronto and Vancouver, Canada) with moderate or greater regurgitant valve lesion were included. Women with coexisting significant stenotic lesions were excluded. Multivalve disease was defined as more than one regurgitant valve lesion. Adverse maternal cardiac events included: pulmonary edema or right heart failure requiring treatment, sustained or symptomatic tachyarrhythmia requiring treatment, cardiac arrest, or cardiac death.   Results:  There were 462 completed pregnancies in women with moderate or greater valvular regurgitation (mean maternal age 29.6 ± 5.7 years); 73% (337/462) of women had congenital heart disease and 13% (59/462) had rheumatic heart disease. Pregnancies were classified according to the most significant regurgitant valve lesions: systemic atrioventricular (AV) valve regurgitation (n=149), subpulmonary AV valve regurgitation (n=91), aortic valve regurgitation (n=44), pulmonary valve regurgitation (n=104), and multivalve regurgitation (n=74). Adverse cardiac events complicated 13% (61/462) of pregnancies. Among pregnancies in women with isolated regurgitant valve lesions, adverse maternal cardiac events occurred in 15% of women with systemic AV valve regurgitation, 13% with subpulmonary AV valve regurgitation, 5% with aortic regurgitation and 4% with pulmonary regurgitation. Adverse cardiac events were highest in women with multivalve disease (27%). Adverse fetal/neonatal and obstetric complications occurred in 22% and 9% of pregnancies, respectively.   Conclusions:  Women with moderate or greater AV valve regurgitation are at risk for cardiac complications during pregnancy. Pregnancies in women with aortic and pulmonary valve regurgitation are usually well tolerated. Women with more than one regurgitant valve lesion are at highest risk for complications.
Tuberculosis Update 2017
Authors: M.J. Friedrich
Journal: JAMA (2017)

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Immunoadsorption Followed by Rituximab as a Definitive Treatment for Insulin Autoimmune Syndrome (Hirata Syndrome): A Case Report
Authors: Tim M. Kroemer, Anne Erler, Elena Tsourdi, Matthias Gruber, Sergey Tselmin, Ulrich Julius, Martin Aringer, Lorenz C. Hofbauer, Tilman D. Rachner
Journal: Diabetes Care (2017)

A 59-year-old Caucasian man (170 cm, 78 kg, BMI 27 kg/m2) was referred for evaluation of recurrent episodes of severe hypoglycemia, which had commenced a week earlier. Computed tomography and MRI scans excluding abnormalities of the pancreas had already been performed. The patient had previously suffered from arterial hypertension, hyperlipoproteinemia, and an acute myocardial infarction the year before. Pharmacological therapy consisted of a β-receptor antagonist, a statin, low dose aspirin, clopidogrel, and vitamin D. Importantly, there was no history of alcohol abuse or diabetes and no previous exposure to antidiabetes medication (Fig. 1). Upon admission, the patient showed a sustained need for intravenous glucose supplementation with repetitive symptomatic declines of blood glucose to levels of relevant hypoglycemia (<2.5 mmol/L) immediately after discontinuation of parenteral glucose.



Figure 1 
Serum parameters in relation to the course of treatment. Results of IAB, protein, and IgG are depicted in the graph during the …
Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality With Treatment
Authors: Mei Lu, Yueren Zhou, Irina V. Haller, Robert J. Romanelli, Jeffrey J. VanWormer, Carla V. Rodriguez, Heather Anderson, Joseph A. Boscarino, Mark A. Schmidt, Yihe G. Daida, Amandeep Sahota, Jennifer Vincent, Christopher L. Bowlus, Keith Lindor, Talan Zhang, Sheri Trudeau, Jia Li, Loralee B. Rupp, Stuart C. Gordon
Journal: Clinical Gastroenterology and Hepatology (2017)
Comment on Han et al. Comparative Effectiveness of Diabetic Oral Medications Among HIV-Infected and HIV-Uninfected Veterans. Diabetes Care 2017;40:218–225
Authors: María Dolores García de Lucas, Julián Olalla Sierra
Journal: Diabetes Care (2017)

Regarding the article by Han et al. (1), we would like to add the following comments.

As the article points out, diagnosis, control objectives, and therapy in the patient with HIV and type 2 diabetes are similar to those in the non-HIV patient (2). At present the approach in patients with HIV and type 2 diabetes who are overweight or obese should be treatment with antidiabetic medications that, in addition to improving …
Prognostic Value of 99mTc-Sestamibi Parathyroid Scintigraphy in Predicting Future Surgical Eligibility in Patients With Asymptomatic Primary Hyperparathyroidism
Authors: Zhaoting Cheng, Sijuan Zou, Dan Peng, Guopeng Zhang, Xiaohua Zhu
Journal: Clinical Nuclear Medicine (2017)

Patients with asymptomatic primary hyperparathyroidism might have a positive Tc-sestamibi parathyroid but do not meet criteria for surgical resection when the disease is diagnosed. However, many of these asymptomatic patients will become symptomatic or meet criteria for surgery later on. The aim of this study was to determine whether a positive sestamibi scan can precede future surgical eligibility in these patients.This retrospective study reviewed the records of 94 asymptomatic patients who had hyperparathyroidism and underwent Tc-sestamibi study with SPECT/CT imaging. Among them, 35 patients, including 12 with positive and 23 with negative sestamibi parathyroid scan, did not meet the criteria for surgery at the time of imaging, and follow-up record for at least 1 year was assessed on these patients. The imaging findings and the eligibility for surgery at the end of the follow-up were compared.With a median follow-up of 2.4 years (range, 1-4 years), among all 35 patients who were initially not eligible for surgery, 6 of 12 patients with a positive sestamibi scan became eligible for surgery, whereas 20 of 23 patients with negative scans remained ineligible for surgery.Positive parathyroid SPECT/CT predicted a higher possibility of meeting surgical criteria over time in asymptomatic hyperparathyroidism patients who are not surgery eligible at the time of presentation.
Abstract 18097: PTEN Inhibition With VO-OHPIC Ameliorates Myocardial Ischemia-Reperfusion Injury Mediated by RISK Pathway Activation-Mediated Reduction of Apoptosis: An in vitro and in vivo Study
Authors: Carlos G Santos-Gallego, Belén Picatoste, Ida U Njerve, Kiyotake Ishikawa, Torsten P Vahl, Jagat Narula, Javier J Sanz, Roger J Hajjar, Valentin Fuster, Juan J Badimon
Journal: Circulation (2016)

Introduction: RISK is the main cardioprotective pathway against ischemia-reperfusion (I-R) injury, and starts with the phosphorylation (activation) of Akt. Phosphatase and tensin homolog deleted on...
Abstract 14835: Association of Underweight With Prognosis in Patients With Peripheral Artery Disease; From IMPACT-ABI Registry
Authors: Keisuke Senda, Takashi Miura, Tomoaki Mochidome, Yasushi Ueki, Tatsuya Saigusa, Soichiro Ebisawa, Hirohiko Motoki, Jun Koyama
Journal: Circulation (2016)

Introduction: Generally, it is reported that being underweight is associated with higher mortality. However, little is known about association of underweight with prognosis in patients with periphe...
Ectopic Undescended Parathyroid Adenoma—SPECT/CT Avoids False-Negative Interpretation on 99mTc-MIBI Dual-Phase Scintigraphy
Authors: Sonia Mahajan, Heiko Schoder
Journal: Clinical Nuclear Medicine (2017)

Undescended parathyroid adenomas are rare, and they are easily missed during neck exploration surgery in patients with hyperparathyroidism. Few reports have described ectopic parathyroid adenomas along the carotid arteries at or near the carotid bifurcation. These may be missed on planar Tc-MIBI dual-phase scintigraphy because of overlapping submandibular gland activity. Our case demonstrates the potential advantage of SPECT/CT in parathyroid scintigraphy to overcome this limitation.
Comparative Effectiveness of Implementation Strategies for Blood Pressure Control in Hypertensive Patients
Authors: Katherine T. Mills, Katherine M. Obst, Wei Shen, Sandra Molina, Hui-Jie Zhang, Hua He, Lisa A. Cooper, Jiang He
Journal: Annals of Internal Medicine (2017)

The prevalence of hypertension is high and is increasing worldwide, whereas the proportion of controlled hypertension is low.To assess the comparative effectiveness of 8 implementation strategies for blood pressure (BP) control in adults with hypertension.Systematic searches of MEDLINE and Embase from inception to September 2017 with no language restrictions, supplemented with manual reference searches.Randomized controlled trials lasting at least 6 months comparing the effect of implementation strategies versus usual care on BP reduction in adults with hypertension.Two investigators independently extracted data and assessed study quality.A total of 121 comparisons from 100 articles with 55 920 hypertensive patients were included. Multilevel, multicomponent strategies were most effective for systolic BP reduction, including team-based care with medication titration by a nonphysician (-7.1 mm Hg [95% CI, -8.9 to -5.2 mm Hg]), team-based care with medication titration by a physician (-6.2 mm Hg [CI, -8.1 to -4.2 mm Hg]), and multilevel strategies without team-based care (-5.0 mm Hg [CI, -8.0 to -2.0 mm Hg]). Patient-level strategies resulted in systolic BP changes of -3.9 mm Hg (CI, -5.4 to -2.3 mm Hg) for health coaching and -2.7 mm Hg (CI, -3.6 to -1.7 mm Hg) for home BP monitoring. Similar trends were seen for diastolic BP reduction.Sparse data from low- and middle-income countries; few trials of some implementation strategies, such as provider training; and possible publication bias.Multilevel, multicomponent strategies, followed by patient-level strategies, are most effective for BP control in patients with hypertension and should be used to improve hypertension control.National Institutes of Health.
Abstract 163: Ex Vivo Assessment of Normothermic Myocardial Ischemia/Reperfusion Injury in Winter-Active Arctic Ground Squirrels
Authors: Matthias L Riess, Brian M Barnes, Mihai V Podgoreanu
Journal: Circulation (2012)

Introduction:  Hibernating mammals display a striking degree of cardioprotection under extreme physiological conditions. We have shown a manifold reduction in myocardial ischemia/reperfusion (IR) injury in hibernating Arctic Ground Squirrels (AGS) undergoing deep hypothermic circulatory arrest compared to Brown Norway rats (BN). To further delineate the mechanistic basis of endogenous cardioprotection in hibernators, we used an isolated heart model to compare responses of winter active AGS and BN to normothermic IR.   Methods:  Langendorff-prepared AGS (n = 4) and BN hearts (n = 8) were perfused (80 mmHg perfusion pressure, 37°C) with Krebs solution (7.5 mM glucose). After 20 min stabilization and 5 min cardioplegic arrest, hearts underwent 45 min global normothermic ischemia and 60 min reperfusion. Left ventricular pressure (LVP) was measured isovolumetrically via a saline-filled latex balloon. Infarct size was determined using TTC staining and cumulative planimetry.   Results:  During late ischemia and throughout reperfusion, AGS hearts displayed significantly increased diastolic and systolic LVPs, decreased heart rate, but no difference in developed (systolic-diastolic) LVP, dLVP/dt, coronary flow, or infarct size compared to BN (table).   Conclusion:  These first-ever comparative isolated heart experiments in winter active AGS showed remarkable functional differences to the rat strain least susceptible to myocardial IR (BN). The lack of cardioprotection in our model in contrast to deep hypothermic in vivo conditions may be due to differences in hibernation state (torpid versus active AGS), metabolic fuel availability (fatty acid-free perfusate), response to temperature changes, and/or systemic IR injury-aggravating factors between the two species. Moreover, the significant diastolic contracture in AGS suggests fundamental differences in intracellular calcium handling and/or mitochondrial bioenergetics during normothermic IR.