tbuckley/cabot-search huggingface dataset:
A specific anti-inflammatory effect of salmeterol in symptomatic asthmatic patients already on low dose ICS
Authors: G. Westall, C. Ward, B. Orsida, R. Ward, R. Bish, D. Reid, E. H. Walters
Journal: Thorax (2000)

Introduction. In asthmatic patients, already on inhaled corticosteroids (ICS), who remain symptomatic, studies have demonstrated better outcomes by introducing long-acting inhaled β-agonists rather than increasing ICS (Greening A. Lancet 1994; 344:219-224). However, there remains an on-going debate on whether salmeterol has pro-or anti-inflammatory effects. To contribute to this debate, we undertook a bronchoscopic study looking at the role of endogenously produced nitric oxide (NO). Methods. 45 asthmatics, symptomatic despite treatment with ICS (100-500 μg/day), were enrolled into a double-blind, randomised, placebo-controlled and parallel-grouped trial. Patients remained on their normal dose of ICS and were subsequently randomised to receive either salmeterol (50 μg bd), fluticasone (100 μg bd) or placebo for 12 weeks. Airway biopsies and bronchoalveolar fluid (BALF) were obtained at baseline and after 12 weeks. Frozen biopsies were immunostained for inducible (iNOS) and constitutive nitric oxide synthase (cNOS) using monoclonal antibodies. Staining in the epithelium and in cells of the lamina propria (LP) was assessed using image analysis (Image Pro Plus), as were measurements of epithelial integrity. The BAL nitrite content was analysed with a modified fluorometric assay. For each treatment arm comparisons were made with regard to epithelial integrity (mean height above the basement membrane), inflammatory cells in the LP staining for iNOS or cNOS, vascularity (number and area occupied by cNOS staining vessels), epithelial iNOS staining and BALF nitrite concentration as a surrogate of exhaled NO. Results. There was no significant difference between pre and post treatment levels with regard to epithelial integrity, number of iNOS and cNOS positive cells in the LP, epithelial iNOS staining nor in BALF nitrite levels. There was however a significant increase in the number of vessels staining positive for cNOS (77±63 vs 140±113, p=0.03) in those asthmatics who had salmeterol added to the ICS (p=0.03 vs placebo). Summary. We have previously shown in this group that the addition of salmeterol leads to an overall reduction in vascularity (Orsida et al, Respirology; 2000: 5: Suppl.). In this study salmeterol was associated with an increased number of vessels positive for cNOS. Salmeterol was not associated with either an increase or a decrease in inflammation with regard to iNOS staining or nitrite production. Conclusion: Salmeterol was not pro-inflammatory in this study, indeed the increased vessel cNOS positiviry following salmeterol is anti-inflammatory, since endogenous NO production by cNOS would modulate inflammation by reducing cell migration through the vascular endothelium (Kubes P. Proc Natl Acad Sci USA. 1991; 88: 4651-55).
THU-138-High efficacy and improvement in CPT class with sofosbuvir/velpatasvir plus ribavirin for 12 weeks in patients with CPT C decompensated cirrhosis
Authors: Steven Flamm, Eric Lawitz, Brian Borg, Michael Charlton, Charles Landis, Rajender Reddy, Mitchell Shiffman, Didier Samuel, Angel Alsina, Charissa Chang, Natarajan Ravendhran, Gulan Zhang, Shampa De-Oertel, Luisa Stamm, Anuj Gaggar, Christophe Hezode
Journal: Journal of Hepatology (2019)
The dual SRC-ABL inhibitors in Ph+ acute lymphoblastic leukemia to enhance synergy between targeted BCR-ABL and BCL-2 inhibitors.
Authors: Jessica Taft Leonard, Stephen Edward Forbes Spurgeon, Elie A. Traer, Brandon M. Hayes-Lattin, Marc Loriaux, Jeffrey Tyner, Brian J. Druker, Bill H. Chang
Journal: Journal of Clinical Oncology (2015)

7073 Background: Outcomes in adult Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL) remain poor with a 5 year overall survival of less than 40%. Addition of the targeted BCR-ABL inhibitors (TKI) to standard cytotoxic therapy has greatly improved upfront treatment, yet relapse remains common with a median survival of just 4.5 months. Therefore identification of targeted agents that could enhance the activity of TKIs is urgently needed. ABT 199 is a BCL-2 inhibitor which has shown pre-clinical activity against a variety of B cell malignancies. Here we evaluate the combination of ABT199 across a panel of TKIs to explore potential mechanisms of synergy in hopes to better define the optimal combination for future clinical studies. Methods: Drug efficacy in vitro was determined using the Ph+ALL cell line SupB15. Cells were incubated with varying concentrations of dasatinib, imatinib, nilotinib or ponatinib in combination with ABT199 for 72 hours. Cell viability was assessed using a colorimetric MTS assay, and cell apoptosis was assessed with annexin V staining. Combination effects were calculated using Calculsyn software. Standard immunoblots were used to assess inhibition of downstream pathways. Results: The combination index (CI) values for each of the TKIs with ABT199 ranged between 0.13 – 1.4 for Imatinib, 0.4 – 1.05 for Nilotinib, 0.06 – 0.33 for Ponatinib, and 0.07 – 0.64 for Dasatinib, where CI < 1 predicted synergy. As a single agent, ABT199 induced the highest degree of apoptosis, enhanced preferentially by dasatinib and ponatinib. Evaluation of key phosphorylated kinases showed that all four TKIs effectively inhibited the downstream ABL1 target pCRKL. In addition, both dasatinib and ponatinib inhibited pLYN while dasatinib also inhibited pBTK. Conclusions: Combination of BCL-2 and BCR-ABL targeting in Ph+ALL is synergistic in vitro. The enhanced synergy seen with dasatinib and ponatinib may be due to the ability of these agents to target additional pathways active in leukemic cells. The addition of ABT-199 as part of TKI therapy for adult Ph+ALL warrants further clinical investigation, particularly in patients with relapsed or refractory disease.
Transcription factor Fra-1 targets arginase-1 to enhance macrophage-mediated inflammation in arthritis
Authors: Nicole Hannemann, Shan Cao, Daniel Eriksson, Anne Schnelzer, Jutta Jordan, Martin Eberhardt, Ulrike Schleicher, Jürgen Rech, Andreas Ramming, Steffen Uebe, Arif Ekici, Juan D. Cañete, Xiaoxiang Chen, Tobias Bäuerle, Julio Vera, Christian Bogdan, Georg Schett, Aline Bozec
Journal: Journal of Clinical Investigation (2019)

The polarization of macrophages is regulated by transcription factors such as nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1). In this manuscript, we delineated the role of the transcription factor Fos-related antigen 1 (Fra-1) during macrophage activation and development of arthritis. Network level interaction analysis of microarray data derived from Fra-1- or Fra-2-deficient macrophages revealed a central role of Fra-1, but not of Fra-2 in orchestrating the expression of genes related to wound response, toll-like receptor activation and interleukin signaling. Chromatin-immunoprecipitation (ChIP)-sequencing and standard ChIP analyses of macrophages identified arginase 1 (Arg1) as a target of Fra-1. Luciferase reporter assays revealed that Fra-1 down-regulated Arg1 expression by direct binding to the promoter region. Using macrophage-specific Fra-1- or Fra-2- deficient mice, we observed an enhanced expression and activity of Arg1 and a reduction of arthritis in the absence of Fra-1, but not of Fra-2. This phenotype was reversed by treatment with the arginase inhibitor Nω-hydroxy-nor-L-arginine, while ʟ-arginine supplementation increased arginase activity and alleviated arthritis, supporting the notion that reduced arthritis in macrophage-specific Fra-1-deficient mice resulted from enhanced Arg1 expression and activity. Moreover, patients with active RA showed increased Fra-1 expression in the peripheral blood and elevated Fra-1 protein in synovial macrophages compared to RA patients in remission. In addition, the Fra-1/ARG1 ratio in synovial macrophages was related to RA disease activity. In conclusion, these data suggest that Fra-1 orchestrates the inflammatory state of macrophages by inhibition of Arg1 expression and thereby impedes the resolution of inflammation.
Public Health Implications of Rising Marijuana Use in Pregnancy in an Age of Increasing Legalization—Reply
Authors: Arpana Agrawal, Richard A. Grucza, Cynthia E. Rogers
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Association of Caloric Intake From Sugar-Sweetened Beverages With Water Intake Among US Children and Young Adults in the 2011-2016 National Health and Nutrition Examination Survey
Authors: Asher Y. Rosinger, Hilary Bethancourt, Lori A. Francis
Journal: JAMA Pediatrics (2019)

This study uses data from the 2011 through 2016 National Health and Nutrition Examination Survey to assess the association between intake of sugar-sweetened beverages and water intake status among US children and young adults.
Abstract 17016: T Wave Variability and T Wave Morphology Predict Ventricular Tachyarrhythmias in Arvc Patients
Authors: Barbara Szepietowska, Xiaojuan Xia, Bronislava Polonsky, Jean-Philippe Couderc, Wojciech Zareba
Journal: Circulation (2016)

Introduction: Predicting episodes of ventricular tachyarrhythmia (VT) and especially fast VT events in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients could be useful for identifica...
UK hospital uses AI to predict which patients are most likely to miss appointments
Authors: Gareth Iacobucci
Journal: BMJ (2019)

An algorithm that can predict which patients are most likely to miss appointments could save the NHS millions of pounds, say the UK clinicians who developed the tool.

A team from University College London Hospital created a mathematical modelling tool using records from 22 000 appointments for MRI scans across two NHS hospitals. Findings published in the journal Digital Medicine showed that using the artificial intelligence tool enabled correct identification of 90% of patients who would not attend.1

The tool was not wholly precise, incorrectly identifying around half of patients who attended appointments as being at risk of not attending. But the targeted approach enabled the hospital to …
THU-492-Role of regulatory T cells and checkpoint inhibition in hepatocellular carcinoma
Authors: Bettina Langhans, Hans Dieter Nischalke, Benjamin Kraemer, Leona Dold, Philipp Lutz, Raphael Mohr, Annabelle Vogt, Marieta Toma, Anna-Maria Eis-Hubinger, Jacob Nattermann, Christian Strassburg, Maria Gonzalez-Carmona, Ulrich Spengler
Journal: Journal of Hepatology (2019)
SAT-451-Gallbladder disease in the absence of cirrhosis is a significant risk factor for hepatocellular carcinoma
Authors: Kenda Al-Assi, Rikita Hatia, Vijayashri Rallapalli, Yehia Abugabal, Ahmed Abdelhakeem, Reham Abdel-Wahab, Kanwal Raghav, Prasun Jalal, Ahmed Kaseb, Asif Rashid, Donghui Li, Manal Hassan
Journal: Journal of Hepatology (2019)
Treatment of Progressive Multifocal Leukoencephalopathy with Pembrolizumab
Authors: Sebastian Rauer, Reinhard Marks, Horst Urbach, Klaus Warnatz, Avindra Nath, Steve Holland, Cornelius Weiller, Bodo Grimbacher
Journal: New England Journal of Medicine (2019)

Treatment of PML with Pembrolizumab A patient with variable immunodeficiency and progressive multifocal leukoencephalopathy was treated with five pembrolizumab infusions. The CSF JC viral load went...
FRI-495-Post transarterial chemoembolization fever can predict poor survival in patients with TNM stage I hepatocellular carcinoma
Authors: Chien-Wei Peng, Wei Teng, Yi-Chung Hsieh, Rachel Wen-Juei Jeng, Chien-Hao Huang, Kar-Wai Lui, Chen-Fu Hung, Yi-Cheng Chen, Chen-Chun Lin, Chun-yen Lin, Shi-Ming Lin, I-Shyan Sheen
Journal: Journal of Hepatology (2019)
TCTAP A-141 Initial Experience in Managing Anatomical Snuff Box Access Site Following Invasive Coronary Procedures
Authors: Michael Mao-Chen Liang, Zhan Yun Lim, Syed Saqib Imran, Teck-Kee Ang, Pinakin Vijaykumar Parekh, Joyce Pooi Wan Lee
Journal: Journal of the American College of Cardiology (2019)
AIRE expression controls the peripheral selection of autoreactive B cells
Authors: Joel Sng, Burcu Ayoglu, Jeff W. Chen, Jean-Nicolas Schickel, Elise M. N. Ferre, Salomé Glauzy, Neil Romberg, Manfred Hoenig, Charlotte Cunningham-Rundles, Paul J. Utz, Michail S. Lionakis, Eric Meffre
Journal: Science Immunology (2019)

T cells and their proper AIRE-dependent selection prevent the accumulation of autoreactive naïve B cells in the periphery.
Lung resection for cancer in patients with heart disease: Management and postoperative outcome
Authors: F.S. Caushi, I. Skenduli, A. Hatibi, A. Mezini, S. Telo, S. Bala, E. Shima, A. Cani
Journal: Annals of Oncology (2019)

Background: Patients with lung cancer sometimes presents with concomitant heart disease. That kind of patients represents a high risk group necessitating prompt diagnosis and treatment. As lung resection still is the treatment of choice for early stages of lung cancer, its feasibility depends on the severity of the cardiac impairment. The aim of this study was to analyze the results of lung resection in patients with heart disease in terms of 30 day postoperative mortality, hospital stay and 5 year survival. Methods: This was a retrospective analysis of 161 patients with lung cancer who underwent complete lung resection between January 2011 and January 2014 at our department. Results: Surgery consisted in 140 lobectomies, 21 pneumonectomies. 24,2% of patients (39) of this study had a cardiac disease as co-morbidity where 14 of them was suffering from hyper tension of second stage, 10 of them from chronic atrial fibrillation, 14 patients (8.7%) with coronary artery disease where 10 of them have been treated previously by CABG or PTCA revascularization procedure meanwhile in 4 patients the disease was diagnosed in routine examinations. One patient had undergone a cardiac surgery for mitral valve replacement. In both of 4 patients that were diagnosed with coronary disease was not required myocardial revascularization despite presented a medium-high cardiac risk and the surgery was performed under the continuous control of cardiologists. The mortality rate was 3%. There was one intraoperative death because of cardiac arrhythmia, and 4 deaths in first 30 days post operation (one of them because of heart attack in a pre-treated coronary disease by PTCA and 3 others by severe pneumonia). Hospital stay was longer for patients who had cardiac co-morbidity (12.3±4 vs. 8.5±3 days). The overall 5-year survival rate was 60%. In patients cardiopulmonary co-morbidity the 5-year survival rate was 40%. Conclusions: Lung resection in patients with cardiac disease is feasible. Careful preoperative evaluation can identify patients who might benefit from myocardial revascularization prior to surgery. A careful cardiac treatment and follow-up of such patients its necessary to achieve better results regarding mortality and 5-year survival. Legal entity responsible for the study: Fatmir Caushi. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract MP077: Longitudinal Associations Between Venous Disease Progression and Change in Quality of Life: San Diego Population Study
Authors: Adrienne M Schlang, Jessica Wallace, Julie Denenberg, Michael Criqui, Matthew Allison
Journal: Circulation (2017)

Background: Chronic venous disease, one of the most common chronic diseases in the United States, is associated with lower quality of life (QOL). Although earlier studies have identified a significant association between the cross-sectional prevalence of venous disease and QOL, few studies have investigated the association between venous disease progression and change in QOL. Therefore, the aim of this study was to investigate the relationship between progression of venous disease and change in QOL in a longitudinal cohort. Methods: A population-based cohort of 1103 participants were examined at baseline and 11 years later. At both visits, QOL and risk factors were assessed by questionnaire, anthropometric measures obtained by clinical examination, and venous disease assessed by visual inspection and duplex ultrasound. QOL was measured with the Medical Outcomes Study 36-Item Short Form (SF-36) with the resulting physical component (PCS) and mental component scores (MCS) being used in the analysis. Using ANCOVA methods to control for age, gender, and ethnicity, changes in venous disease were compared against QOL stratified into tertiles. Then, linear regression models were used to examine the longitudinal association of venous disease at baseline and change in QOL score at follow-up after controlling for covariates. Results: In the study population of 1103 individuals, 78 had regression, 340 had progression, and 685 were stable. The average age was 58.7 years (SD 10.4); 33% were male, 61% were non-Hispanic White, 15% were Hispanic, 12% were African American, and 12% were Asian. Mean BMI was 27.1 (SD 5.3), 45.4% had hypertension, 9.9% were diabetic, 3.6% were current smokers, and 34.8% were on medication for hyperlipidemia. Progression of venous disease was significantly associated with change in PCS after controlling for age, gender, and ethnicity ( β =-0.075; p =.04). The association was only slightly attenuated ( β =-.065, p=.08) after adjustment for BMI, high blood pressure, injury to either leg, smoking history, previous vein procedure, previous hernia surgery, flat feet, marital status, education level, occupation, cardiovascular-related morbidity, diabetes, and heaviness in either leg. No association was found with MCS before or after multiple covariate adjustment. Conclusions: This study confirms that individuals with progression of chronic venous disease have a greater decrease in QOL as identified by the physical component score of SF-36. Prevention of chronic venous disease progression may help retain QOL.
Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy
Authors: Seunghee Hong, Romain Banchereau, Bat-Sheva L. Maslow, Marta M. Guerra, Jacob Cardenas, Jeanine Baisch, D. Ware Branch, T. Flint Porter, Allen Sawitzke, Carl A. Laskin, Jill P. Buyon, Joan Merrill, Lisa R. Sammaritano, Michelle Petri, Elizabeth Gatewood, Alma-Martina Cepika, Marina Ohouo, Gerlinde Obermoser, Esperanza Anguiano, Tae Whan Kim, John Nulsen, Djamel Nehar-Belaid, Derek Blankenship, Jacob Turner, Jacques Banchereau, Jane E. Salmon, Virginia Pascual
Journal: The Journal of Experimental Medicine (2019)

Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4+ T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes.
Prognostic value of <i>BRAF<sup>V600</sup></i> mutations in American Joint Committee on Cancer (AJCC) stage 3 cutaneous melanoma patients in the MelanCohort prospective cohort.
Authors: Philippe Saiag, Philippe Aegerter, Celeste Lebbe, Pierre Wolkenstein, Nicolas Dupin, Vincent Descamps, Selim Aractingi, Maxime Battistella, Zofia Helias-Rodzewicz, Samia Mourah, Jean-François Emile
Journal: Journal of Clinical Oncology (2015)

9037 Background: Prognosis of AJCC stage 3 melanoma pts is heterogeneous. The prognostic value of BRAFV600 mutations in melanoma is debated. In a retrospective study of 105 stage 3 pts with a nodal deposit of > 2 mm, we showed that BRAFV600mutation was an independent factor of decreased both overall and distant metastasis free survivals (DMFS). We aimed to validate this finding in an independent prospective data set and to expand it to the entire AJCC stage 3 spectrum. Methods: We selected all pts with AJCC stage 3 cutaneous melanoma at inclusion or during follow-up that were included in Melancohort (NCT00839410), which recruited prospectively during 2003-8. BRAFV600mutations were detected by pyrosequencing of DNA in nodal or in transit met samples with > 60 %melanoma cells. Melanoma was considered mutated when > 10% of DNA was mutated. Endpoints were melanoma-specific survival (MSS) and DMFS. Kaplan-Meier curves and multivariate Cox PH regression model were used. 9 pts receiving targeted therapy were censored at first dose given. A sample of 155 pts gave 89% power to detect an HR of 2 for survival, with α risks set at 0.05. Results: Median follow-up for stage 3 pts was 56 months. BRAF status was assessed in 158 melanomas. BRAFV600mut (V600E & V600K in 89 and 9 % of cases, respectively) were detected in 50.6 % of melanomas. The only significant differences according to BRAF at entry in AJCC stage 3 were histological subtypes and age (younger for BRAFV600mut). The only characteristics associated with worst MSS in multivariate model were higher AJCC stage (P = 10-5, HR: 2.74, 95%CI: 1.69-4.43), age > 50 (P = 0.02, HR: 1.86, 95%CI: 1.1-3.14), BRAFV600mut (P = 0.02, HR: 1.9, 95%CI: 1.1-2.78), male sex (P = 0.02, HR 1.71, 95%CI 1.06-2.75), and mitosis in primary melanoma (P = 0.04, HR 1.6, 95%CI 1.01-2.54). Worst DMFS was associated with higher AJCC stage (P = 0.003, HR: 1.9, 95%CI: 1.27-2.85), age > 50 (P = 0.0007, HR: 2.11, 95%CI: 1.34-3.33), and BRAFV600mut (P = 0.02, HR: 1.59, 95%CI: 1.05-2.38). Conclusions: BRAFV600mut was an independent prognostic criteria in stage 3 pts. This may help to better characterize this stage. Results of adjuvant trials in BRAFV600mut stage 3 pts are urgently needed. Clinical trial information: NCT00839410.