tbuckley/cabot-search huggingface dataset:
Effect of Beta-Blockade on Mortality in Patients With Heart Failure: A Meta-Analysis of Randomized Clinical Trials
Authors: Paul A Heidenreich, Tina T Lee, Barry M Massie
Journal: Journal of the American College of Cardiology (1997)

Objectives. We sought to evaluate the current evidence for an effect of beta-blockade treatment on mortality in patients with congestive heart failure (CHF). Background. Although numerous small studies have suggested a benefit with beta-blocker therapy in patients with heart failure, a clear survival benefit has not been demonstrated. A recent combined analysis of several studies with the alpha- and beta-adrenergic blocking agent carvedilol demonstrated a significant survival advantage; however, the total number of events was small. Furthermore, it is unclear if previous studies with other beta-blockers are consistent with this finding. Methods. Randomized clinical trials of beta-blockade treatment in patients with CHF from January 1975 through February 1997 were identified using a MEDLINE search and a review of reports from scientific meetings. Studies were included if mortality was reported during 3 or more months of follow-up. Results. We identified 35 reports, 17 of which met the inclusion criteria. These studies included 3,039 patients with follow-up ranging from 3 months to 2 years. Beta-blockade was associated with a trend toward mortality reduction in 13 studies. When all 17 reports were combined, beta-blockade significantly reduced all-cause mortality (random effect odds ratio [OR] 0.69, 95% confidence interval [CI] 0.54 to 0.88). A trend toward greater treatment effect was noted for nonsudden cardiac death (OR 0.58, 95% CI 0.40 to 0.83) compared with sudden cardiac death (OR 0.84, 95% CI 0.59 to 1.2). Similar reductions in mortality were observed for patients with ischemic (OR 0.69, 95% CI 0.49 to 0.98) and nonischemic cardiomyopathy (OR 0.69, 95% CI 0.47 to 0.99). The survival benefit was greater for trials of the drug carvedilol (OR 0.54, 95% CI 0.36 to 0.81) than for noncarvedilol drugs (OR 0.82, 95% CI 0.60 to 1.12); however, the difference did not reach statistical significance (p = 0.10). Conclusions. Pooled evidence suggests that beta-blockade reduces all-cause mortality in patients with CHF. Additional trials are required to determine whether carvedilol differs in its effect from other agents. (J Am Coll Cardiol 1997;30:27–34)
The University of Wisconsin Medical School. A Chronicle, 1848-1948.
Authors: Paul F. Clark
Journal: Annals of Internal Medicine (1967)

Book Reviews Bartholin and Rudbeck.During the eighteenth century the humours and qualities of Galenic theory were gradually replaced by physico-chemical conceptions.In the nineteenth century the rise of the cell theory was reflected in hepatology by Purkinje and Henle's description of liver cell structure and crowned by Claude Bernard's characterization of the liver cell as a chemical laboratory and centre of metabolism.After a brief eclipse of the importance of the liver-when it seemed no more than an excretory organ-it regained a position in the new physiology as important and central as that which it had once held in the old.In a curious way it even regained something of its old status as a centre of blood formation when Reichert and Koelliker described the formation of blood cells in the foetal liver.Dr. Mani has enriched medical history with a fine and scholarly work.One hopes that his book will prove to be the first of a genre to include eventually (with the co-operation of other medical historians) all of the organs and tissues of the body.I have only some minor complaints to make.In view of the importance rightly accorded to Galen it seems a pity that he is dismissed in somewhat less than two thousand words.While it is true that some aspects of Galen's hepatology were touched on in Dr. Mani's earlier monograph, cited above, in neither work are the foundations of Galen's physiology adequately presented.Secondly, the text has been overly subdivided into a plethora of numbered and lettered sections and subsections.Many paragraphs consist of only one or two sentences and sometimes resemble notebook entries rather than a fully worked up text.This gives rise to an excess of white paper on the printed page.Together with the jerkiness of style the effect, unfortunately, is to interfere somewhat with the reader's pleasure.
Abstract 2882: p53MVA therapy in patients with refractory gastrointestinal malignancies primes robust CD8+ T cell responses
Authors: Nicola Hardwick, Mary Carroll, Teodora Kaltcheva, Dajun Qian, Jonathan Espenschied, Lucille Leong, Peiguo Chu, Joseph Kim, Joseph Chao, Marwan Fakih, Joshua Ellenhorn, Don Diamond, Vincent Chung
Journal: Cancer Research (2014)

Abstract PURPOSE: To conduct a Phase I safety trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in patients with refractory gastrointestinal malignancies. EXPERIMENTAL DESIGN: Three patients were vaccinated with 108 pfu p53MVA followed by nine patients at 5.6 x 108 pfu. Toxicity was classified using the NCI Common Toxicity Criteria and clinical responses were assessed by CT scan. Peripheral blood samples were collected pre vaccine and post vaccination for immunophenotyping and assessment of p53MVA induced immune response. RESULTS: p53MVA immunization was well tolerated at both doses, with no adverse events above grade 2. Induction of strong T cell and antibody responses to the MVA backbone were apparent. CD4+ and CD8+ T cells showing enhanced recognition of a p53 overlapping peptide library were detectable after the first immunization, particularly in the CD8+ T cell compartment (p=0.03). However in most patients this did not expand further with the second and third immunization. Some patients exhibited a decline in myeloid-derived suppressor cells post vaccine, but this was not statistically significant. The frequency of PD-1+ T cells detectable in patients PBMC was significantly higher than healthy controls. Furthermore, the frequency of PD-1+ CD8+ T cells showed an inverse correlation with the peak CD8+ T cell response to p53 (p=0.02). CONCLUSION: p53MVA was well tolerated and induced robust CD8+ T cell responses. Combination of p53MVA with immune checkpoint inhibition could improve sustained immune responses and lead to clinical benefit. Citation Format: Nicola Hardwick, Mary Carroll, Teodora Kaltcheva, Dajun Qian, Jonathan Espenschied, Lucille Leong, Peiguo Chu, Joseph Kim, Joseph Chao, Marwan Fakih, Joshua Ellenhorn, Don Diamond, Vincent Chung. p53MVA therapy in patients with refractory gastrointestinal malignancies primes robust CD8+ T cell responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2882. doi:10.1158/1538-7445.AM2014-2882
Abstract 70: Mouse models of human lung adenocarcinoma: Identification of potential tumor suppressors by functional <i>in vivo</i> shRNA screening
Authors: Narayana Yeddula, Yifeng Xia, Inder Verma
Journal: Cancer Research (2014)

Abstract Lung cancer is one of the leading human cancer malignancies, and histopathologically divided into Non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Lung adenocarcinoma is a major form of NSCLC. We have developed a lentiviral-vector-mediated mouse model, which enables generation of lung adenocarcinoma from less than 100 alveolar epithelial cells, and investigated the role of IKK2 and NF-κB in lung-cancer development. IKK2 depletion in tumour cells significantly attenuated tumour proliferation and significantly prolonged mouse survival. We identified Timp1, one of the NF-κB target genes, as a key mediator for tumour growth by activating ERK signaling pathway. Knockdown of either Ikbkb or Timp1 by short hairpin RNAs reduced tumour growth in both xenograft and lentiviral models. Further, by utilizing lentiviral mediated mouse models, we performed a genome wide in vivo shRNA screen to findout tumor suppressors or tumor suppressor like genes that will cooperate with KRasG12D expression. The screen identified several novel molecules as potential tumor suppressor properties, which will cooperate with KRasG12D. Several of these molecules were also altered in human patient cohorts of The Cancer Genome Atlas. Ephrin receptor A2, EphA2, is one of the molecule knockdown of which cooperated with KRasG12D expression to generate lung adenocarcinomas comparable to knockdown of potent tumorsuppressor P53 thus validating our screen. The mechanisms underlying EPhA2 mediated tumorsuppression are being studied. Overall, our study identified novel potential tumorsuppressors. Citation Format: Narayana Yeddula, Yifeng Xia, Inder Verma. Mouse models of human lung adenocarcinoma: Identification of potential tumor suppressors by functional in vivo shRNA screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 70. doi:10.1158/1538-7445.AM2014-70
Optimal PEEP in the first week of life in mechanically ventilated extremely preterm newborn infants: Clinical setting vs. optimal seeting as registered by forced oscillation technique (FOT)
Authors: Chiara Veneroni, Linda Wallström, Emanuela Zannin, Raffaele Dellacà, Richard Sindelar
Journal: European Respiratory Journal (2012)

Recently it has been shown that the use of forced oscillation technique (FOT) allows identifying an optimal open-lung PEEP minimizing mechanical stress to the lungs (Kostic P, Crit Care. 2011).  The aim of this study is to characterize the optimal mechanical PEEP settings in the first week of life in mechanically ventilated preterm newborns and to compare it to the PEEP set by current clinical approach.  Four preterm newborns (GA=23-27wks, BW=467-964g) were studied at the first, third and seventh day of life. PEEP was increased by 2cmH2O above the clinically set PEEP and then decreased by four 5-minute steps of 1cmH2O. For each step total respiratory input reactance (Xrs) at 10Hz was measured at end-expiration by sinusoidal FOT overimposed on ventilation waveform. The optimal mechanical PEEP was defined as the PEEP at which the maximum of Xrs was reached (Dellaca9, Int Care Med, 2011).  Mean±SD values of the clinically set PEEPs and the mechanically optimal PEEPs are shown in Figure.  The higher inter-subject and day-by-day variability of the mechanically optimal PEEP suggests that FOT could help in fine tuning PEEP settings related to the lung mechanical changes over time in each patient. Future studies will be address whether setting the mechanically optimal PEEP could be beneficial from a clinical point of view.
Total Parenteral Nutrition.
Authors: R Del Giglio
Journal: Annals of Internal Medicine (1976)

A short historical introduction is followed by an account of the indications and counter-indications for total parenteral feedings, together with its administration modalities, bearing in mind the importance this technique currently enjoys in the stomatological and maxillo-faccial field. The metabolic situation of average patients subjected to this form of treatment is described, along with the hydric, caloric, plastic and electrolytic aspects of a given method, and the way in which the success or failure of an adopted technique can be ascertained.
Abstract 13172: Gender Differences in Impact of Vascular Endothelial Dysfunction or CYP2C19 Polymorphism on Clinical Outcome Following Coronary Stenting in Patients with Coronary Heart Disease
Authors: Seiji Hokimoto, Tmonori Akasaka, Noriaki Tabata, Yuichiro Arima, Koichi Kaikita, Kazuko Nakagawa, Hisao Ogawa
Journal: Circulation (2014)

Background: Vascular endothelial dysfunction and CYP2C19 polymorphism are associated with increased risk of cardiovascular event in patients with coronary heart disease (CHD). The aim was to examine the gender differences in vascular endothelial dysfunction or CYP2C19 genotype on clinical outcomes following stent implantation. Methods: We enrolled 600 patients following stent implantation, taking dual antiplatelet therapy. Patients were divided into male (n=426) and female (n=174) groups. Platelet reactivity (PR) by a light transmission aggregometry, reactive hyperemia index (RHI) using reactive hyperemia peripheral arterial tonometry as an index of endothelial dysfunction, and CYP2C19 polymorphism were examined. CYP2C19 genotype was classified into carrier (at least one CYP2C19 loss-of function allele carriage) and non-carrier. Cardiovascular event (cardiovascular death, myocardial infarction (MI), stroke, unstable angina, revascularization, intraprocedural thrombotic event and heart failure) was assessed according to male or female over 18 months follow-up. Results: There were no significant differences in distribution of CYP2C19 carrier and non-carrier (78.9 vs. 64.3%, P=0.126), PR (4474 vs. 4223 AU*min, P=0.485) and clinical outcomes (17.8 vs. 16.7%, P=0.731) between male and female. In male group alone, the incidence of cardiovascular event was significantly associated with CYP2C19 carrier, renal failure, high PR, previous MI, and peripheral artery disease. While in female group alone, low RHI was significant (0.47 vs. 0.61, P=0.015). Multivariate analysis identified CYP2C19 carrier (HR, 1.908, 95% CI, 1.043-3.489; P=0.032), previous MI (HR, 1.918, 95% CI, 1.125-3.269, P=0.017), and peripheral artery disease (HR, 1.872, 95% CI, 1.079-3.247, P=0.026) as predictors of cardiovascular events in male group, while low RHI alone was a predictor in female (HR, 0.129, 95% CI, 0.021-0.811, P=0.029). Conclusions: The impact of CYP2C19 polymorphism on clinical outcome is more significant in male, not female, while effect of endothelial dysfunction is more significant in female, not male, respectively. There are gender differences in impact of CYP2C19 genotype or endothelial dysfunction on clinical outcome in CHD patients.
Abstract 11602: Impact of Pre-Operative Type-B Natriuretic Peptide Level on Survival After Aortic Valve Replacement for Aortic Stenosis
Authors: Marie-Annick Clavel, Christophe Tribouilloy, Joseph Malouf, Hector I Michelena, Rakesh M Suri, Dan Rusinaru, Allan S Jaffe, Maurice Enriquez-Sarano
Journal: Circulation (2014)

Introduction: Levels of type-B natriuretic peptide (BNP) adjusted for age and sex are a powerful predictor of mortality after the diagnosis of aortic stenosis (AS). Objective: To assess whether BNP activation (compared to normal values) affects mortality after aortic valve replacement (AVR). Methods: In 494 patients with AS, plasma level of BNP was measured pre-operatively at the time of Doppler-Echocardiography. BNP was normalized as BNPratio (BNP measured/BNP maximum normal value for age and sex) to evaluate the impact of BNP activation on post-operative outcomes. Results: Mean age was73±11 years and 300 (61%) patients were male. Mean aortic valve area was 0.82±0.20cm2, mean gradient 51±16mmHg, and mean Left Ventricular Ejection Fraction 59±15%. Incidence of hypertension was 65%, diabetes 27% and chronic kidney disease 22%. Median of BNP was 211 (interquartile: 87-508) and BNPratio 2.2 (1.0-5.2). After adjustment age, gender, body surface area, Charlson score index, presence of symptoms, creatinine, hemoglobin, systolic blood pressure, indexed aortic valve area and left ventricular ejection fraction, the BNPratio (log transformed) was a predictor of long-term mortality (p&lt;0.0001) with an hazard ratio 1.34 (1.14-1.60). Moreover, stratification by BNPratio showed increasing long-term post-operative mortality with BNPratios&gt;2 (Figure). Conclusions: BNP activation defined using BNPratios (normalized for age and sex) is a powerful independent predictor of long-term mortality after aortic valve replacement for AS. Furthermore, patients with a BNPratio&gt;2 before aortic valve replacement incur excess mortality during follow-up in relation to the increasing BNPratio. These data support the use of the BNPratio to guide the timing of AVR.
Abstract #3611: Differential expression of microRNAs in metastatic melanoma correlates with resistance to alkylator-based chemotherapy.
Authors: Hussein Tawbi, Shama Buch, Ying-Chih Lin, John Kirkwood
Journal: Cancer Research (2009)

Background:  The prognosis for patients (pts) with MM remains poor, with a 5-year survival rate  Methods:  Frozen tumor tissues were obtained from 21 pts with MM treated with alkylator-based chemotherapy (DTIC/TMZ). Pts were classified as chemotherapy- sensitive (S) if pts showed stable disease (SD) for > 4 months, partial response or complete response by RECIST criteria; and chemotherapy-resistant (R) if progressive disease was observed after 2 or fewer cycles of treatment. RNA was extracted using the miRNeasy kit from Qiagen and analyzed using Illumina\#8217;s MicroRNA Expression Profiling Panel containing 739 miRNA probes. Statistical analysis was performed using BeadStudio Software from Illumina for differential expression and STATA 9 for survival analysis.  Results:  Among the 21 pts, 9 were classified as S and 12 as R. The mean age was 48.3±14 years and the mean follow up time was 20.7 months. Median survival among R was 9 months (range-2-57 months) and among S was 21 months (range- 7-40 months). Differential miRNA expression was calculated using the rank invariant normalization method with background subtraction using Illumina\#8217;s BeadStudio software. Eight miRNA\#8217;s (miR-597, miR-802, miR-563, miR-484, miR-640, miR-493-5p, miR-647, miR-519d) were significantly overexpressed among S compared to R (p MGMT ,  PARP1  and  MUTYH  suggesting a role of miRNA in DNA repair modulation.  Conclusion:  This study to our knowledge is the first to demonstrate an association between differential expression of miRNAs with resistance to alkylator-based chemotherapy in melanoma. These results are promising but require validation in a larger sample size.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3611.
Abstract MP80: Increased Physical Fitness Is Associated With Greater Improvement In Cardiac Parasympathetic Function Among The Obese Than Overweight Or Normal Weight Individuals
Authors: Ehimen Aneni, Ebenezer Oni, Lara Roberson, Romeu Meneghelo, Michael Blaha, Roger Blumenthal, Janisse Post, Arthur S Agatston, Theodore Feldman, Raquel D Conceiçao, Jose Carvalho, Raul D Santos, Khurram Nasir
Journal: Circulation (2014)

Introduction: The impact of physical fitness on heart rate recovery (HRR), a marker of cardiac parasympathetic activity, has rarely been studied across weight categories. We examined the effect of physical fitness across different weight categories on HRR at 2 minutes after exercise stress test in an asymptomatic cohort. Methods: This is a cross-sectional analysis of 525 Brazilian subjects, free of known cardiovascular disease that underwent exercise stress test. Metabolic equivalents at maximal exercise (METS) were calculated from the volume of oxygen consumed during maximal exercise (VO2max). HRR was defined as peak exercise HR minus HR after 2minutes rest. Weight was classified into obese (BMI ≥ 30), overweight (BMI 25 -29) and normal weight (BMI &lt;25). Results: The prevalence of overweight and obesity was 51% and 19% respectively. There was a positive significant correlation between METS and HRR (r= 0.34 p&lt;0.001). The mean HRR was higher among the normal weight than the overweight or obese (92 vs. 89 vs.76 beats; p&lt;0.001) while the average (mean) METS decreased across increasing weight categories (10.6 vs. 10.4 vs. 9.1 METS; p &lt;0.001). In a fully adjusted linear regression model, for every unit increase in METS the HRR increased by 2.0 beats among the obese (p&lt;0.005), 1.1 beats among the overweight (p&lt;0.001) and 0.8 beats among the normal weight (p=0.143). These increases were significantly different among the 3 groups (p&lt;0.001). Line fitted plots (figure below) showed that the increase in HRR associated with increasing METS was greater among the obese than the other weight groups and at high METS value (about 13 METS) the HRR are similar regardless of BMI. Conclusion: Our findings suggest that increasing fitness increases HRR, with greater benefit in the obese than other weight groups. Physical fitness, not simply weight loss, should be advocated in the obese. More studies are required to fully understand the temporal relationship between BMI, physical fitness and HRR.
Cellular Reprogramming Erases Aberrant DNA Methylation and the Malignant Phenotype in Chronic Myeloid Leukemia
Authors: Giovanni Amabile, Annalisa Di Ruscio, Fabian Muller, Robert S Welner, Henry Yang, Alexander K Ebralidze, Hong Zhang, Lihua Qi, Giovanni Martinelli, Thijn Brummelkamp, Michelle M. Le Beau, Maria E Figueroa, Christoph Bock, Daniel G Tenen
Journal: Blood (2014)
Abstract 17213: Serum Alkaline Phosphatase Elevation is an Independent Predicting Factor of Worsening Renal Function in the Patients with Acute Heart Failure
Authors: Masahiro Yamazoe, Atsushi Mizuno, Yutaro Nishi, Koichiro Niwa, Mitsuaki Isobe
Journal: Circulation (2014)

Background: Worsening renal function (WRF) has been associated with poor outcome in the patients with acute heart failure (AHF). Recently, venous congestion had been paid attention to the important predictor of WRF in AHF. Abnormal serum alkaline phosphatase (ALP) was reported as a biological marker of liver congestion and of the extent of right sided filling pressure in AHF. In this study, we evaluated the relationship between ALP and development of WRF in AHF. Method: We enrolled consecutive patients hospitalized due to AHF in cardiovascular center of St Luke’s International Hospital, Tokyo, Japan from January, 2004 to December, 2013. We excluded the patients either on dialysis, estimated glomerular filtration rate (eGFR) under 15 ml/min/m2, or primary liver disease. We defined WRF as elevation of serum creatinine of 0.3 mg/dl or above raised from admission to discharge. We classified patients into tertiles by baseline measurements of ALP. We performed multivariate analysis to make the prediction model of WRF. Result: Total 1245 patients (age 76.4±12.9 years old, male 54.8%) were enrolled. During hospitalization, 166 (13.3%) patients developed WRF. Patients were classified into tertiles (&lt;77, 77 to 203, &gt;203 IU/L). Compared with the lowest ALP tertile, middle and the highest ALP tertile groups developed WRF more frequently (8.4% vs 15.5% vs 16.8%, P=0.003). In multivariate logistic regression, after adjustment of age, gender, and other risk factors, we found eGFR (Odds ratio (OR) 0.978, 95%Confidence Interval (CI) 0.967 to 0.987, P&lt;0.001), diabetes mellitus (OR 1.83, CI 1.19 to 2.80, P=0.005), norepinephrine use (OR 1.65, CI 1.04 to 2.61, P=0.03), albumin (OR 0.507, CI 0.337 to 0.764, P=0.001), middle tertile ALP (OR 1.81, CI 1.07 to 3.06, P=0.02), and highest tertile ALP (OR 2.08, CI 1.24 to 3.48, P=0.005) compared with lowest tertile were independent variable to predict WRF. Conclusion: Our study showed that elevated serum ALP is an independent predicting factor for WRF in the patients with AHF.