tbuckley/cabot-search huggingface dataset:
Randomized phase II trial with an uPA inhibitor (WX-671) in patients with locally advanced nonmetastatic pancreatic cancer.
Authors: V. Heinemann, M. P. Ebert, T. Pinter, P. Bevan, N. G. Neville, C. Mala
Journal: Journal of Clinical Oncology (2010)

4060 Background: WX-671 (Mesupron) is an orally available prodrug of WX-UK1, a serine protease inhibitor that inhibits uPA as well as other serine proteases. WX-UK1 (Setyono-Han et al., Thromb Haemost 2005) and WX-671 have shown to efficiently reduce primary tumor growth and metastasis formation in a variety of animal models. The proteolytic factor uPA and its inhibitor PAI-1 belong to those biological factors which have provided the highest level of evidence (LOE1) in terms of their prognostic and predictive significance. WX-671 is currently the only drug in Phase II aiming at this target. Methods: 95 patients with locally advanced, non- resectable, non metastatic pancreatic cancer were randomized to three cohorts receiving daily oral WX-671 as hydrogen sulfate corresponding to 200 and 400 mg WX-671 free base or no WX-671. In addition, all patients were treated with weekly gemcitabine (1,000 mg/m2 i.v. as per SPC). Treatment continued until disease progression or toxicity. Safety was assessed by measuring vital signs, laboratory parameters (hematology, blood chemistry, coagulation) and ECGs. Efficacy endpoints were response rate at the various staging intervals, progression free survival, time to first metastasis, overall survival as well as changes in tumor- and uPA-system-related markers. Results: All 95 patients were accrued between Jun 2007 and Aug 2008. Efficacy is assessed by a central reader at regular intervals based on digital CT images. By end of 2009, 2 patients were still on treatment without signs of progression, 64 patients had died. Preliminary analysis of overall survival showed an increase in overall survival from 10.2 mo (gemcitabine alone) to 13.5 mo for the combination of gemcitabine and WX-671. 1-year survival increased from 37% with gemcitabine to 53% when combined with 400 mg WX- 671. Conclusions: The combination of daily oral WX-671 in combination with weekly i.v. gemcitabine was well tolerated. According to the preliminary data, patients have received combination treatment for more than 25 cycles. The final analyses of the efficacy and safety endpoints will be presented at the meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration WILEX WILEX WILEX
Abstract 3280: Heart Failure Quality of Care in the Outpatient Cardiology Practice Setting: A Report from IMPROVE HF
Authors: Gregg C Fonarow, Clyde W Yancy, Nancy M Albert, Anne Curtis, Wendy Gattis Stough, Mihai Gheorghiade, J Thomas Heywood, Mark L McBride, Mandeep Mehra, Christopher O’Connor, Dwight Reynolds, Mary N Walsh
Journal: Circulation (2007)

Introduction: Few data exist regarding adherence to evidence-based HF guidelines in the outpatient setting. IMPROVE HF is a prospective cohort study designed to characterize the current management of chronic systolic HF (EF&lt;35%) in a national registry of outpatient cardiology practices and to evaluate the effect of practice-specific performance improvement interventions. Methods: Baseline performance data were collected by chart abstraction. To quantify care, IMPROVE HF performance measures were constructed for use of: ACEI/ARB, beta-blocker, aldosterone antagonist, anticoagulation for atrial fibrillation, ICD, CRT and HF education. Conformity with guideline indicated care includes only patients documented to be eligible without contraindications or intolerance. Results: 131 practices are enrolled with baseline data abstracted for 12331 patients. 71.7% of practices are non-teaching. Patients are 71% male, with a median age of 70.5 years and a median EF of 25%. Baseline conformity with indicated HF therapies is shown in Fig 1 . While ACEI/ARB and beta-blocker use were relatively high in eligible patients in the outpatient cardiology setting, other measures showed large treatment gaps. Conclusions: These data are among the first to assess conformity to the latest national HF guidelines in the outpatient setting and demonstrate an opportunity to improve the quality of HF care delivered. IMPROVE HF will explore the impact of practice-specific performance improvement tools on closing the outpatient HF treatment gap.
Abstract 170: Theoretical Model for Weighting Chest Compression Fraction During Cardiopulmonary Resuscitation
Authors: David Salcido, James J Menegazzi
Journal: Circulation (2011)

Background: The quality of cardiopulmonary resuscitation (CPR) is often measured by the metric of chest compression fraction, which has been associated with survival to hospital discharge. However, this metric may not provide the optimum information when analyzing the relationship between CPR quality and its effectiveness. Objective: We sought to demonstrate that a simple mathematical model that weights chest compression fraction by the chest compression rate would provide more textured and detailed information about CPR quality, with results that are disparate from unweighted measures. Methods: Using a hypothetical bout of CPR, we weighted the chest compression fraction by the chest compression rate (in beats/minute), incorporating periods of no CPR during which a patient might be moved or undergoing airway management. Different chest compression rates could represent different rescuers, or rescuer fatigue. These data can be captured with current defibrillator/monitor technologies. Results: Hypothetical Example: Consider a 16-minute period of resuscitation. Minutes 1-2: No chest compressions (2 min) Minutes 3-6: chest compressions (4 min) @ 100/min (Weight = 1) Minutes 7-8: No chest compressions (2 min) Minutes 9-11: chest compressions (3 min) @ 50 / min (Weight = 0.5) Minutes 12-13: No chest compressions (2 min) Minutes 14-16: chest compressions (3 min) @ 75 / min (Weight = 0.75) Chest compression Fraction = (4+3+3) / (2 + 4 + 2 + 3 + 2 + 3) = 0.63 Weighted Chest Compression Fraction = (4*1 + 3*0.5 + 3*0.75) / (2 + 4 + 2 + 3 + 2 + 3) = 0.48 Conclusion: In this theoretical example, the simple chest compression fraction (0.63) may overestimate the true quality of the CPR performed. The weighted measure value (0.48) may be a better indicator of the true quality of the CPR and may be useful in further differentiating CPR metrics.
Abstract 8951: Assessment of Pressure Reflection in the Pulmonary Circulation Using Echocardiography Identifies Patients with Normal as Well as Increased Pulmonary Vascular Resistance
Authors: Odd Bech-Hanssen, Bengt Rundqvist, Fredrik Lindgren, Nedim Selimovic
Journal: Circulation (2011)

Background and aim. Pulmonary hypertension (PH) is a frequent finding in patients with cardiopulmonary disorders. It is important to recognize PH due to increased pulmonary vascular resistance (PVR). In a recent study we describe a new echocardiography method to identify patients with increased PVR (&gt;3 WU) based on detection of pressure reflection (PR) in the pulmonary artery (PA). The patient population was biased towards high PVR and therefore, in the present study we evaluate the method in a more representative population undergoing right heart catheterization. Methods and results. Echocardiography and catheterization were performed within one week in 108 patients. We selected 3 variables related to PR: the interval from valve opening to peak velocity in the PA (AcT, ms), the interval between PA peak velocity and peak tricuspid velocity (tPV-PP, ms), and the right ventricular pressure increase after peak velocity in the PA (augmented pressure, AP, mm Hg). Cut-of values indicating increased PVR for Act/tPV-PP/AP were 89 ms/&gt;8 mmHg. Forty-six percent had left heart disease, 21% were heart transplant patients and 18% had pulmonary arterial hypertension. The proportion with increased PAMP (&gt;25 mmHg) was 54%, increased pulmonary capillary wedge pressure (PCWP&gt;12 mHg) 40%, increased PVR (&gt;3 WU) 36% or both increased PVR and PCWP 15%. The table shows how the number of PR variables affected the diagnostic performance. The positive predictive value was 94% with equal to or &gt; 2 PR variables and the negative predictive value was 92% with no PR variables present. Conclusions. Assessment of PR in the pulmonary circulation identifies patients with normal as well as increased PVR.
Blood coagulation and fibrinolysis in relation to coronary heart disease. A comparative study of normal White men, White men with overt coronary heart disease, and normal Bantu men.
Authors: C. Merskey, H. Gordon, H. Lackner, V. Schrire, B. J. Kaplan, R. Sougin-Mibashan, H. L. Nossel, A. Moodie
Journal: BMJ (1960)
Abstract 707: Nonuniformity of Left Ventricular Apical-to-Basal Diastolic Lengthening in Patients with Hypertrophic Nonobstructive Cardiomyopathy
Authors: Takeo Tanaka, Kazuya Murata, Eizo Akagawa, Chikage Kihara, Hiroko Yoshino, Yoshio Nose, Yasuhiro Fukagawa, Takehisa Susa, Shinichi Okuda, Yasuaki Wada, Masunori Matsuzaki
Journal: Circulation (2008)

Quantification of left ventricular (LV) apex-to-base dispersion has been feasible with two-dimensional echocardiographic tissue tracking system (2DTT, Hitachi EUB7500), which based on pattern matching algorithm. Although impairment of LV relaxation was characterized in patients with hypertrophic cardiomyopathy (HCM), the behavior of LV apical and basal diastolic lengthening and its relation to LV filling are unknown. We obtained basal and apical LV short-axis views in 22 patients with non-obstructive HCM and 25 healthy volunteers (N). Eight equiangular points on endo-myocardium at end-diastole were placed in each view, and the shortening ratios of four directions were calculated and averaged by 2DTT. Then, the time-LV shortening and lengthening curves were obtained. The time intervals from the aortic valve closure to the point of the first 40% of peak lengthening (T 40 ) were measured in each view. Isovolumic relaxation time (IRT) was measured by pulsed Doppler LV in- and out-flow recordings. Although both apical and basal T 40 were similar in N (145.8±38.4 vs. 134.3±34.2msec 0.5 , ns.), the apical T 40 in HCM was longer compared to base (118.7±51.1 vs. 168.8±52.5msec 0.5 , p&lt;0.0001). The time difference of T 40 between apex and base was related to LV IRT (r=0.59, p&lt;0.0001). Nonuniformity of apical-to-basal left ventricular lengthening during early diastole was present in HCM. This apex-to-base dispersion, especially apical delay in timing of LV lengthening may have a physiologic importance for impairment of LV relaxation in HCM.
Abstract 9402: Diffuse Myocardial Fibrosis Negatively Correlates with Exercise Capacity in Children with Subclinical Anthracycline Cardiotoxicity
Authors: Edythe B Tham, Mark J Haykowsky, Kelvin Chow, Sachie Kaneko, Maria Spavor, Nee S Khoo, Joseph J Pagano, Andrew S Mackie, Richard B Thompson
Journal: Circulation (2011)

Background The effectiveness of anthracycline chemotherapy in improving survival is limited by late cardiotoxicity. The aim of this study was to examine novel cardiac MRI and echocardiography measures to detect subclinical cardiotoxicity in childhood cancer survivors, and to determine its relationship to exercise capacity. Methods Thirty patients (15±3years, 50% male), 8±5 years after anthracycline therapy (cumulative dose 197±84 mg/m 2 ), underwent cardiac MRI, echocardiography and cardiopulmonary (cycle ergometer) exercise testing (VO 2peak ). Cardiac MRI assessed volumetric function, mass, and myocardial extra-cellular volume (ECV), a measure of diffuse fibrosis based on changes in blood and myocardial T1 values pre and post gadolinium. Tissue Doppler annular velocities (E’, A’) and peak circumferential and longitudinal strain, strain rate (SR) and torsion, from speckle tracking, were compared to 35 healthy controls (13±4 years). Data (mean ± SD) was analysed using Pearson's product-moment coefficient and unpaired t-tests (p&lt;0.05). Results Patients were asymptomatic with normal LVEF (59±7%) but VO 2peak was 15% lower than age and gender determined healthy predicted values. Myocardial ECV was inversely correlated with mass/volume ratio (r = -0.5, p&lt;0.01), and VO 2peak (r = -0.5, p&lt;0.01), and lower VO 2peak correlated with increased cumulative dose (r = 0.4, p&lt;0.05). Echocardiographic measures of systolic function were significantly reduced compared to controls (decreased circumferential and longitudinal strain, longitudinal SR and torsion, p&lt;0.01). Diastolic dysfunction was evident with decreased circumferential and longitudinal diastolic SR and decreased annular velocities (p&lt;0.01) relative to controls. There was no correlation between echocardiographic parameters and ECV or VO 2peak . Conclusion Diffuse myocardial fibrosis (increased ECV) is correlated with reduced mass/volume ratios and VO 2peak in children post anthracyline. While there were abnormalities of systolic and diastolic function, these metrics did not correlate with ECV or VO 2peak . Myocardial ECV provides a non-invasive early marker of ventricular remodelling that is related to exercise capacity which may be of prognostic value in childhood cancer survivors.
Abstract 17074: T1-Weighted MR Imaging of Aortic Angiogenesis in Rabbits with an Ultralow New Low Gadolinium
Authors: Dipanjan Pan, Kezheng Wang, Anne H Schmieder, Shelton D Caruthers, Angana Senpan, Samuel A Wickline, Baozhong Shen, Gregory M Lanza
Journal: Circulation (2011)

Background: The recent discontinuation of the AIM-HIGH study suggests that even HDL and TG levels do not adequately predict cardiovascular disease outcome. Angiogenesis, an integrated intramural biomarker of plaque progression, has been quantitatively and rapidly used for T1-weighted MR imaging with targeted gadolinium nanoparticles (PFC NPs), but new agents with even lower lanthanide levels are desired. Objective: We hypothesized that targeted manganese-oleate core NCs that present 30-fold less Gd than PFC NPs could provide strong, T1-weighted MR imaging of neovascular α v β 3 -integrin expression in vivo. Methods and Results: Vascularly-constrained (D av =140 nm, ζ=-13mV) nanocolloids (NC) of Mn oleate (20% v/v) were synthesized using only 1.25mole% of Gd as (versus 30 mole% for PFC NPs), 0.25 mole% of a quinolone-derived α v β 3 -integrin antagonist, and 98.5 mole% lecithin. Cholesterol fed New Zealand White rabbits (n=8/group) received α v β 3 -Mn(Gd)-NC or nontargeted Mn(Gd)-NC i.v. (1ml/kg); 8 rabbits on normal chow received α v β 3 -Mn(Gd)-NC. Dynamic MR imaging (3.0T) of the descending thoracic aorta wall revealed a marked signal enhancement (47±5%) at 2h. In comparison, the nontargeted-MnGd-NC had lower (20±5%) signal enhancement than targeted NPs (p&lt;0.05). Rabbits fed a normal diet and treated with α v β 3 -MnGd NP had the lowest signal increase, 12±3%, which did not differ from the nontargeted treatment. Histology corroborated the prominent, neointimal proliferation among cholesterol-fed, and homing specificity. Conclusions: Angiogenesis imaging offers a direct intramural measure of atherosclerotic disease progression and α v β 3 -Mn(Gd)-NC provides a sensitive MR molecular imaging approach with gadolinium decreased to 300-fold less than clinical single dose Gd-DTPA.
Abstract 15903: Platelet Glycoprotein IIb/IIIa Receptor Controls the Pro-Angiogenic Effect of Platelet Releasate
Authors: Muhammad Arshad, Michael Staedele, Muhammad Aslam, Imran Hussain, Muhammad A Riaz, Daniel G Sedding, Mehmet Bilgin, Hans M Piper, Thomas Noll, Dursun Guenduez
Journal: Circulation (2011)

Background: Platelet releasate is known to have pro-angiogenic effect on endothelial cells, however, the role of platelet surface receptors in the control of platelet releasate and its pro-angiogen...
Abstract 12575: Nucleoside Diphosphate Kinase C is a Novel Regulator of cAMP Levels and G{beta}{gamma} Signaling in Cardiomyocytes
Authors: Issam Abu-Taha, Nadine Wolf, Susanne Lutz, Ali El-Armouche, Dobromir Dobrev, Thomas Wieland, Hans-Joerg Hippe
Journal: Circulation (2011)

Introduction: Nucleoside diphosphate kinases (NDPKs) regulate Gβγ signaling and cAMP formation under basal conditions and during β-adrenoceptor stimulation and are enhanced in human heart failure. ...
Controlled Study of Self-Exposure Treatment for Phobics: Preliminary Communication
Authors: A Ghosh, I M Marks, A C Carr
Journal: Journal of the Royal Society of Medicine (1984)

Patients with phobic disorder (mainly agoraphobics) of minimum one year duration were treated by self-administered exposure in vivo treatment. Seventyone patients were randomly assigned to one of three groups: (A) book-instructed, (B) computer-instructed, or (C) therapist-instructed. All three groups improved significantly to a similar extent on various phobic measures at the end of the treatment and maintained their treatment gains at 6-month follow up. Mean clinicians' time spent with each patient was 40 minutes, 4.2 hours and 3.2 hours in group A, B and C respectively. Similar small numbers of patients defaulted from each group.
Abstract 6105: Clinical Impact of In-Vivo Coronary Stent Fracture as a Cause of In-Stent Restenosis: its Morphological Characteristics Provided By Multislice Computed Tomography
Authors: Mariko Ehara, Masato Kawai, Shunichi Matsushita, Kazuki Shimizu, Toshihiro Kobayashi, Tetsuo Matsubara, Hitoshi Matsuo, Yasushi Asakura, Mitsuyasu Terashima, Etsuo Tsuchikane, Yoshihisa Kinoshita, Masashi Kimura, Kenya Nasu, Nobuyoshi Tanaka, Hiroshi Fujita, Maoto Habara, Koyo Sato, Takahiko Suzuki
Journal: Circulation (2008)

Some cases have been reported concerning in-vivo coronary stent fracture as an alternative cause of in-stent restenosis (ISR) to neointimal hyperplasia. Conventional cine-angiogram is apt to miss c...
Abstract 19336: Vein of Marshall Triggers and Pulmonary Vein Reconnection in Recurrent Atrial Fibrillation After Catheter Ablation: Therapeutic Role of Ethanol Infusion
Authors: Miguel Valderrabano, Christine M Sasaridis, Amish S Dave
Journal: Circulation (2010)

Background: Atrial fibrillation (AF) recurrences occur after pulmonary vein (PV) antral isolation (PVAI). We have shown safety and feasibility of ethanol infusion in the vein of Marshall (VOM) as a...
Abstract 16471: Illness Perception in Patients Hospitalized for Acute Coronary Syndrome
Authors: Mariana Suarez-Bagnasco, Ariel O Estevez, Claudio Higa, Maria Laura Monsalvo
Journal: Circulation (2014)

Introduction: Studies of Illness perception in patients with acute coronary syndrome (ACS) conducted in Canada and Finland showed that genetic factors, stress and lifestyle behaviors are the most common perceived cause of ACS (unstable angina, myocardial infarction). As illness perception is influenced by the personal experience of the illness and its management, as well as by cultural and social factors, we conducted a study to assess illness perception in patients with acute coronary syndrome in Argentina. Methods: Descriptive, cross-sectional, multicenter study. Adults over 18 years old hospitalized for ACS participated in the study. The day of discharge from the Coronary Care Unit, each subject completed a questionnaire generated and validated in Argentina aimed at assessing illness perception. Clinical data were collected by the treating physician at each participating institution. Results: 109 patients between 33 and 84 years old (mean [SD] age = 61 [12] years, 70% male) were enrolled; 57% was diagnosed with ACS without ST-segment elevation and 37% was diagnosed with acute myocardial infarction (MI) with ST-segment elevation; in 6% the acute MI was indeterminate. Many patients attributed the heart disease to their traditional cardiovascular risk factors: 93% to hypertension, 81% to cholesterol, 71% to diabetes mellitus, 69% to physical inactivity, 67% to obesity, 63% to smoking. Only 30% of patients with a positive family history identified it as a risk factor. Stress, anxiety, and personality were identified as the cause for their heart disease in 71%, 64%, and 42% of patients, respectively. The majority of patients (74%) considered that they should improve the adherence to medications after discharge and 80% that should attend the medical follow-ups. Conclusion: Most patients identified their modifiable risk factors as causal for coronary heart disease. Only 30% of participants with a positive family history recognized it as a risk factor. A high percentage of patients recognized suboptimal behaviors in relation to medication adherence and medical follow-ups.
Studying only admissions is a source of potential bias
Authors: C. Weston, P. Donnelly
Journal: BMJ (1995)

EDITOR,--U M Guly and colleagues state that their study, which claims to show that “paramedics and technicians are equally successful at managing cardiac arrest outside hospital,” does not “diminish the role of paramedics.”1 Yet the paragraph about their paper in This week in BMJ concludes that such patients “are best treated” by technicians and calls into question the requirement of having a paramedic in …
Extrapolating results of trial of simvastatin gives room for doubt
Authors: J Hippisley-Cox
Journal: BMJ (1995)

in better paediatric care, education, or social environment, which are more likely than in vitro fertilisation to maximise utility.When resources for health care are scarce we need to consider the opportunity costs of any investment.While infertility can cause psychological distress, a better use of resources may be to offer counselling to allow couples to accept their condition, or to attempt to alter the expectations of relatives and friends.
Abstract 3960: Management of Patients With Severe Aortic Regurgitation: Appropriateness of Current Guidelines Criteria
Authors: Jean-Louis Vanoverschelde, Christophe de Meester de Ravestein, David Vancraeynest, Bernhard Gerber, Sophie Pierard, Stephanie Seldrum, Jean-Benoit Le Polain De Waroux, Patrick Montant, Fabien Chenot, Celine Goffinet, Agnes Pasquet
Journal: Circulation (2009)
Abstract 17928: Upregulation of Type 1 Angiotensin Ii Receptor in Arterioles is Associated With the Hypertension in D3 Dopamine Receptor Heterozygous Mice
Authors: Xiaoyan Wang, Dan Wang, Crisanto S Escano, Laureano Asico, John E Jones, Christopher S Wilcox, Pedro A Jose
Journal: Circulation (2010)

D3 dopamine receptor (D3R) homozygous (D3−/−) and heterozygous knockout (D3−/+) mice have renin-dependent hypertension that is normalized by type 1 angiotensin II (AngII) receptor (AT1R) blockade; ...