tbuckley/cabot-search huggingface dataset:
CONGENITAL HEART DISEASES AND SPORT ACTIVITY: AN OBSERVATIONAL STUDY
Authors: Martina Rosselli, Loira Toncelli, Chiara Giannelli, Gabriele Mascherini, Giorgio Galanti
Journal: British Journal of Sports Medicine (2017)

Background Regular physical activity promotes the cardiovascular fitness and the physical and psychological health. However, exercise can acutely increase the cardiovascular risk in athletes with congenital and acquired heart disease. In Italy, pre-participation cardiovascular screening to obtain eligibility is mandatory for both agonistic and non-agonistic sports, whereas in the United States it is not requested. Objective In this study, we aimed at investigating the clinical characteristics of subjects with congenital heart diseases who requested the judgment of eligibility to sport practice at the Sport Medicine Center, University of Florence. Participants Over the period 2010–2016 approximately 3000 athletes aged 6–50 year-old per year underwent eligibility visits at our Center. We found 227 patients with Congenital Heart Disease. Interventions The eligibility visits included an accurate familiar and personal history and physical examination, basal ECG interpretation, Stress Test with treadmill or cycle-ergometer and basal echocardiography. The stress echocardiography can be especially helpful in athletes with cardiovascular disease, evaluating directly the effect of physical effort on heart by ultrasound. Main Outcome Measurements We considered age and sex, the presence of cardiovascular risk factors or familiarity for cardiovascular, the type of congenital disease, the type of sport and the ECG/echocardiography findings. Results Over the period 2010–2016 we assessed 227 athletes with congenital heart diseases, most of which were Bicuspid aortic valve (n=94), Ventricular Septal Defect (n=43); Atrial Septal Defect (n=27), Pulmonary Stenosis (n=15), Patent Ductus Arteriosus (n=14). The median age was 23.4 years (M/F=176/51). Conclusions We found a remarkable amount of patients with congenital heart disease who apply to obtain the judgement of fitness to practice sport. We are evaluating the data and deepening the study to comprehensively assess the demographical and clinical characteristics of these subjects and to evaluate the predictors of eligibility to sport practice in safety.
02.02 Pharmaceutical disruption of B2GPI CXCL4 complex using computationally designed oligopeptides
Authors: Markos D Patsouras, Eleni D Papakonstantinou, Elias E Eliopoulos, Panayiotis G Vlachoyiannopoulos
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterised by recurrent thromboembolism and or pregnancy morbidity in the presence of antiphospholid antibodies (aPL). Major auto antigen is B2 Glycoprotein I (Β2GPI). APL form immunocomplexes with B2GPI and activate platelets leading to thrombus formation. Previous studies have shown that APS patients have higher circulating levels of platelet derived chemokines. Among them CXCL4, a proinflammatory chemokine with antiangiogenic properties, has already been proven to bind and dimerize B2GPI leading to the formation of a triple complex, aPl-B2GPI-CXCL4, which strongly activates platelets. Therefore, we aimed to investigate the pharmaceutical disruption of the B2GPI-CXCL4 interaction. <h3>Methods</h3> An <i>in vitro</i> binding assay was developed for the study of B2GPI-CXCL4 interaction. Briefly, 1 µg/ml B2GPI was coated overnight on high binding polystyrene plates and CXCL4 was incubated in various concentrations for 2 hours. Detection of CXCL4 was performed using a biotinylated polyclonal goat anti-human antibody against CXCL4 followed by Streptavidin-HRP incubation with TMB as substrate. Next <i>in silico</i> molecular docking experiments using the MAESTRO and GLIDE (Schrodinger Inc.) software determined the exact interaction residues of CXCL4 and B2GPI. A number of oligopeptide CXCL4 fragments was screened according to their capacity to bind on B2GPI on the interaction interface with CXCL4. The amino acid sequence of the most promising was further modified in order to achieve high binding strength and optimal solubility properties. Finally, four oligopeptides were designed and synthesised. These oligopeptides were tested using the aforementioned assay for their ability to bind on B2GPI and consequently to inhibit B2GPI-CXCL4 interaction. B2GPI was incubated with the oligopeptides prior to the addition of 10 ng/ml of CXCL4. <h3>Results</h3> Preincubation of B2GPI with the peptides resulted in partial inhibition of B2GPI-CXCL4 interaction in all cases. Among them one presented the highest inhibiting properties which resulted in 40% inhibition of CXCL4 binding on B2GPI. <h3>Conclusions</h3> Preliminary results show that the designed peptides exhibit inhibiting properties. Further experiments and possibly amino acid alterations are required to determine their exact efficiency. Once desirable inhibition and solubility properties are achieved these oligopeptides could be tested as lead compounds for potential therapeutic agents.
Current and Emerging Options for the Management of Inherited von Willebrand Disease
Authors: Jessica M. Heijdra, Marjon H. Cnossen, Frank W. G. Leebeek
Journal: Drugs (2017)

Von Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in approximately 1:10,000 individuals. VWD is caused by a deficiency and/or defect of von Willebrand factor (VWF). The most common symptoms are mucocutaneous bleeding, hematomas, and bleeding after trauma or surgery. For decades, treatment to prevent or treat bleeding has consisted of desmopressin in milder cases and of replacement therapy with plasma-derived concentrates containing VWF and Factor VIII (FVIII) in more severe cases. Both are usually combined with supportive therapy, e.g. antifibrinolytic agents, and maximal hemostatic measures. Several developments such as the first recombinant VWF concentrate, which has been recently licensed for VWD, will make a more "personalized" approach to VWD management possible. As research on new treatment strategies for established therapies, such as population pharmacokinetic-guided dosing of clotting factor concentrates, and novel treatment modalities such as aptamers and gene therapy are ongoing, it is likely that the horizon to tailor therapy to the individual patients' needs will be extended, thus, further improving the already high standard of care in VWD in most high-resource countries.
Smoking Cessation and Risk of Esophageal Cancer by Histological Type: Systematic Review and Meta-analysis
Authors: Qiao-Li Wang, Shao-Hua Xie, Wen-Tao Li, Jesper Lagergren
Journal: JNCI Journal of the National Cancer Institute (2017)

Tobacco smoking strongly increases risk of esophageal squamous cell carcinoma and moderately increases risk of esophageal adenocarcinoma. How smoking cessation influences esophageal cancer risk across histological subtypes, time latencies, and geographic regions is not clear.Studies were systematically searched on Medline, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Pooled estimates of risk ratios (RRs) were derived using a random effects model. Cochran's Q test and I2 statistic were used to detect heterogeneity.Among 15 009 studies, 52 fulfilled the inclusion criteria. Using nonsmokers as a reference, risk of esophageal squamous cell carcinoma was lower among former smokers (RR = 2.05, 95% confidence interval [CI] = 1.71 to 2.45) than among current smokers (RR = 4.18, 95% CI = 3.42 to 5.12). Compared with current smokers, a strong risk reduction was evident after five or more years (RR = 0.59, 95% CI = 0.47 to 0.75), and became stronger after 10 or more years (RR = 0.42, 95% CI = 0.34 to 0.51) and 20 or more years (RR = 0.34, 95% CI = 0.25 to 0.47) following smoking cessation. The risk reduction was strong in Western populations, while weak in Asian populations. Using nonsmokers as reference, the risk of esophageal adenocarcinoma was only slightly lower among former smokers (RR = 1.66, 95% CI = 1.48 to 1.85) than among current smokers (RR = 2.34, 95% CI = 2.04 to 2.69). The risk of esophageal adenocarcinoma did not show any clear reduction over time after smoking cessation, with a risk ratio of 0.72 (95% CI = 0.52 to 1.01) 20 or more years after smoking cessation, compared with current smokers.Smoking cessation time-dependently decreases risk of esophageal squamous cell carcinoma, particularly in Western populations, while it has limited influence on the risk of esophageal adenocarcinoma.
HDL and atherosclerotic cardiovascular disease: genetic insights into complex biology
Authors: Robert S. Rosenson, H. Bryan Brewer, Philip J. Barter, Johan L. M. Björkegren, M. John Chapman, Daniel Gaudet, Daniel Seung Kim, Eric Niesor, Kerry-Anne Rye, Frank M. Sacks, Jean-Claude Tardif, Robert A. Hegele
Journal: Nature Reviews Cardiology (2017)
がん:p53はNEAT1lncRNAを含むパラスペックル形成を誘導し,これが複製ストレス応答や化学療法感受性を調整する
Authors: Adriaens Carmen, Standaert Laura, Barra Jasmine, Leucci Eleonora, Marine Jean‐Christophe, Latil Mathilde, Lapouge Gaeelle, Beck Benjamin, Blanpain Cedric, Verfaillie Annelien, Aerts Stein, Kalev Peter, Sablina Anna A, Boeckx Bram, Lambrechts Diether, Wijnhoven Paul W G, Radaelli Enrico, Vermi William, Van Den Oord Joost, Nakagawa Shinichi, Hirose Tetsuro
Journal: Nature Medicine (2016)
Temporal Changes in the Racial Gap in Survival After In-Hospital Cardiac Arrest
Authors: Lee Joseph, Paul S. Chan, Steven M. Bradley, Yunshu Zhou, Garth Graham, Philip G. Jones, Mary Vaughan-Sarrazin, Saket Girotra
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Previous studies have found marked differences in survival after in-hospital cardiac arrest by race. Whether racial differences in survival have narrowed as overall survival has improved remains unknown. <h3>Objectives</h3> To examine whether racial differences in survival after in-hospital cardiac arrest have narrowed over time and if such differences could be explained by acute resuscitation survival, postresuscitation survival, and/or greater temporal improvement in survival at hospitals with higher proportions of black patients. <h3>Design, Setting, and Participants</h3> In this cohort study from Get With the Guidelines–Resuscitation, performed from January 1, 2000, through December 31, 2014, a total of 112 139 patients with in-hospital cardiac arrest who were hospitalized in intensive care units or general inpatient units were studied. Data analysis was performed from April 7, 2015, to May 24, 2017. <h3>Exposure</h3> Race (black or white). <h3>Main Outcomes and Measures</h3> The primary outcome was survival to discharge. Secondary outcomes were acute resuscitation survival and postresuscitation survival. Multivariable hierarchical (2-level) regression models were used to calculate calendar-year rates of survival for black and white patients after adjusting for baseline characteristics. <h3>Results</h3> Among 112 139 patients with in-hospital cardiac arrest, 30 241 (27.0%) were black (mean [SD] age, 61.6 [16.4] years) and 81 898 (73.0%) were white (mean [SD] age, 67.5 [15.2] years). Risk-adjusted survival improved over time in black (11.3% in 2000 and 21.4% in 2014) and white patients (15.8% in 2000 and 23.2% in 2014;<i>P</i>for trend &lt;.001 for both), with greater survival improvement among black patients on an absolute (<i>P</i>for trend = .02) and relative scale (<i>P</i>for interaction = .01). A reduction in survival differences between black and white patients was attributable to elimination of racial differences in acute resuscitation survival (black individuals: 44.7% in 2000 and 64.1% in 2014; white individuals: 47.1% in 2000 and 64.0% in 2014;<i>P</i>for interaction &lt;.001). Compared with hospitals with fewer black patients, hospitals with a higher proportion of black patients with in-hospital cardiac arrest achieved larger survival gains over time. <h3>Conclusions and Relevance</h3> A substantial reduction in racial differences in survival after in-hospital cardiac arrest has occurred that has been largely mediated by elimination of racial differences in acute resuscitation survival and greater survival improvement at hospitals with a higher proportion of black patients. Further understanding of the mechanisms of this improvement could provide novel insights for the elimination of racial differences in survival for other conditions.
β LACTA test performance for detection of extended-spectrum β-lactamase-producing Gram-negative bacilli directly on bronchial aspirates samples: a validation study
Authors: S. Gallah, Y. Benzerara, J. Tankovic, P.-L. Woerther, H. Bensekri, J.-L. Mainardi, G. Arlet, S. Vimont, M. Garnier
Journal: Clinical Microbiology and Infection (2017)
The Evolution of Metastatic Colorectal Cancer Clinical Trials: Application of the ASCO Framework for Assessing Value
Authors: Doreen A. Ezeife, Sunil Parimi, Ellen R. Cusano, Matthew K. Smith, Tony H. Truong, Soundouss Raissouni, Yongtao Lin, Jose G. Monzon, Haocheng Li, Vincent C. Tam, Patricia A. Tang
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Phase III trials in metastatic colorectal cancer (mCRC) have collectively led to progressive advancements in patient outcomes over the past decades. This study characterizes the evolution of mCRC phase III trials through assessing the value of cancer therapy, as measured by the ASCO Value Framework. Methods: Phase III trial results of systemic therapy for mCRC published between 1980 and 2015 were identified, and their outcome, statistical significance, journal impact factor, and citation by the 2016 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CRC were recorded. For each trial, the net health benefit (NHB) score was calculated using the June 2015 (original) and May 2016 (revised) ASCO Value Framework: Advanced Disease. Results: There were 114 mCRC phase III trials eligible for calculation of the NHB score. Using the revised framework, the median NHB score was 4.6 (range, −30 to 43.5); 12% of trials received bonus points. Trials with statistically significant results had higher NHB scores compared with nonsignificant trials (median NHB score, 21.6 vs 2.9; P<.0001). Clinical trials cited in the NCCN Guidelines had higher NHB scores than those not cited (median score, 8.0 vs 0.3; P=.02). In multivariate linear regression analysis, the only significant predictor of high NHB score was statistically significant studies. Conclusions: The median NHB score for mCRC phase III trials was 4.6. Higher NHB scores are associated with statistically significant studies and are cited in the NCCN Guidelines, a surrogate for practice-changing trials. The 2016 ASCO Value Framework may not fully capture the benefits on an individual patient level.
Worcestershire hospital trust told to make urgent improvements
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

A hospital trust in the West Midlands has been issued with a warning notice to make urgent improvements, after inspectors found that it had become standard practice to treat emergency patients in the corridors and that patients’ care had been compromised.

Inspectors from the Care Quality Commission made unannounced visits to Worcestershire Acute Hospitals NHS Trust in April to check progress after extending the period of special measures that had been placed on the hospital. The trust was placed in special measures in December 2015, and this was reinforced after further inspections a year later.

The latest round of visits to Worcestershire …
Effect of selenium on anthracycline induced cardiotoxicity in children that treated for cancer: Correlation with pro-brain natriuretic peptide levels
Authors: N. Tacyildiz, T. Ucar, D. Ozyoruk, G. Yavuz, E. Unal, S. Atalay, G. Ozelci Kavas, P. Aribal, H. Dincaslan, A. Cavdar
Journal: Journal of Clinical Oncology (2009)

10061 Background: High cumulative doses of an anthracyclin (300–500 mg/m 2 ) are used in the several treatment protocols of children with Cancer. Probrain natriuretic peptit (Pro-BNP), is relased by cardiac cells and elevated even before overt cardiac distress symptoms. Selenium, is an antioxidant which its’ absence cause cardiomyopathy in people living in the poor selenium soil area. Aim 1: Assesment of anthracycline-induced cardiotoxicity with Pro-BNP levels, correlated with echo-cardiographic (ECHO) findings. Aim 2: Determine possible effects of selenium levels and supplemantation on cardiac toxicity. Methods: Plasma levels of Pro-BNP have been measured in 58 pediatric cancer patients (leukemias, lymphomas,solid tumors; 38 boys, 20 girls; between 2–18 years, median:12) after completed their anthracycline containing regimens. Serum selenium levels examined in 12 patients (six patients were with high and other six with normal pro-BNP levels). Three of four Patients with low level of selenium showed cardiac failure according to ECHO and supplemanted with selenium besides digoxine, ACE inhibitors. Results: Eleven patients have found with high pro-BNP levels (120–8022 pg/ml; normal: lower than 120 pg/ml).Six of these patients (with 170–8022 pg/ml, median:798pg/ml pro-BNP) and other six patients with normal levels of pro-BNP (10–74pg/ml, median: 67pg/ml) examined for their serum selenium levels. All patients with normal pro-BNP levels have found in normal levels of selenium levels (71–150 μg/L,median:125 μg/L). Four patients in high pro-BNP group showed low levels of selenium (52–129 μg/L; median:67.5 μg/L). Since three of that four patients have cardiac failure, treated accordingly and supplemented with 100 μg/day selenium to maintain normal levels. During follow-up periods of 27; 8 and 2 months, all 3 patients are doing well with normal ECHO finding. Two patients reached normal Pro-BNP levels while one of them has 80 % decrease. Conclusions: Serum Pro-BNP levels can be used as a marker for anthracycline toxicity and as follow-up marker for protective agents. Selenium suplemantation may have a potential role to protect and/or overcome the difficulties related anthracyclin-induced toxicities. No significant financial relationships to disclose.
03.11 Apolipoprotein e stimulates inflammation and joint destruction during antigen-induced arthritis (aia)
Authors: Giuliana Ascone, Irene DiCeglie, Wouter de Munter, Birgitte Walgreen, Annet Sloetjes, Peter van der Kraan, Ernst Lindhout, Mike Martens, Peter van Lent
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease largely driven by immune complexes and their interaction with FcγRs on synovial macrophages. In RA, joint destruction has been associated with high levels of cholesterol (LDL) which become oxidised (oxLDL) within the inflamed synovium. Apolipoprotein E (ApoE) regulates LDL levels and its absence strongly elevates LDL in the serum. In this study we investigated the role of ApoE in inflammation and joint destruction during antigen-induced arthritis (AIA). <h3>Materials and methods</h3> Experimental arthritis was induced by injection of mBSA into the right knee joint of ApoE<sup>-/-</sup> and wild type (WT) mice previously immunised with mBSA/CFA. Joint swelling was measured by <sup>99m</sup> Technecium (<sup>99m</sup>Tc) uptake and expressed as a ratio of the uptake in the right (injected) and left (non injected) knee joint. Serum mBSA antibody titer was measured by ELISA. WT BM-MΦ were stimulated for 24 hours <i>in vitro</i> with or without 50 µg/ml oxLDL and the FcγRs mRNA expression was measured by qPCR. Joint inflammation and damage were measured by histology using an arbitrary scale from 0 to 3. <h3>Results</h3> ApoE<sup>-/-</sup> mice showed significantly less joint swelling at day 1, 3 and 7 after AIA induction compared to WT controls (21%, 17%, 18% lower, respectively). Serum mBSA antibody levels (total IgG, IgG1, IgG2a and IgG2b) were comparable between WT and ApoE<sup>-/-</sup>mice. LDL serum levels were significantly higher in ApoE<sup>-/-</sup> mice and LDL/oxLDL was found within synovial macrophages. At day 21, histology showed less inflammatory cells within the synovium and joint cavity (22% and 44% lower, respectively) in the ApoE<sup>-/-</sup> mice compared to WT controls. WT BM-MΦ stimulated with oxLDL displayed a significant down-regulation of mRNA levels of FcγR I and FcγR II when compared to their non stimulated controls (1,7 and 2,3 fold change, respectively). Joint destruction was significantly reduced in the ApoE<sup>-/-</sup> mice, as indicated by the reduction of chondrocyte death (32% reduction) and bone erosion (25% reduction from 1.5±0.2 to 1.1±0.1). <h3>Conclusions</h3> ApoE stimulates joint destruction during AIA by lowering LDL/oxLDL levels, thereby promoting Fcγ- mediated macrophage activation within the synovium.
68Ga-PSMA-Ligand PET/CT Uptake in Anthracosilicosis
Authors: Madeleine McGuiness, Brett Sounness
Journal: Clinical Nuclear Medicine (2017)

This interesting image illustrates a case of biopsy-proven pulmonary anthracosilicosis, a mixed dust pneumoconiosis, associated with 68Ga-PSMA-ligand uptake. Prostate-specific membrane antigen (PSMA) is an emerging imaging biomarker, with clinical application in evaluation of prostate cancer using 68Ga-PSMA-ligand PET/CT. Contrary to its name, PSMA is expressed in a number of other normal tissues and pathological states. Prostate-specific membrane antigen expression has been linked to tumor angiogenesis in various other epithelial neoplasms, as well as neovasculature associated with tissue regeneration and repair. Awareness of nonneoplastic inflammatory conditions associated with 68Ga-PSMA-ligand uptake aids in patient assessment and management.