tbuckley/cabot-search huggingface dataset:
Abstract 16764: Locally Produced SAMHD1 Immune Complexes Are Associated With the Development of Idiopathic Pulmonary Arterial Hypertension
Authors: Toshie Saito, Rasa Tamosiuniene, Orr Sharpe, William H Robinson, Mark Nicolls, Marlene Rabinovitch
Journal: Circulation (2014)

Introduction: Autoimmunity has been related to the pathophysiology of idiopathic pulmonary arterial hypertension (IPAH). We previously reported 35 IPAH-related antigens identified in immune complexes (ICs) in lungs from IPAH patients. Among these antigens, we validated increased ICs containing SAMHD1, an HIV1 restriction factor, in IPAH vs. donor control lungs. Hypotheses: We hypothesized that 1) viruses and/or inflammatory stimuli increase SAMHD1, which is released in exosomes and induces local production of antibodies, 2) SAMHD1 ICs are observed in experimental inflammatory pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. Methods: The viral signature of IPAH vs. control lung tissue was determined by high-throughput sequencing and validated by qPCR. Localization of SAMHD1 or SAMHD1 antibodies was determined by immunohistochemistry. Protein expression was analyzed by western blot in lung tissue and in pulmonary arterial endothelial cells (PAEC) stimulated with TNFα. Experimental PH was induced in rats by MCT injection. Results: Viral sequencing confirmed by qPCR indicated that only human endogenous retrovirus K5 (HERVK5) was increased threefold in lung tissue from IPAH vs. controls (P&lt;0.05, n=10 per group). The ratio of perivascular SAMHD1 positive cells to total cells was also increased more than twofold in IPAH vs. controls (P&lt;0.05, n=4 per group), with SAMHD1 mainly localized to macrophages and PAECs, consistent with the increase in SAMHD1 by western blot (P&lt;0.05, n=4 per group). SAMHD1 was detectable in exosomes from IPAH plasma, explaining how it might be released from cells. SAMHD1 recombinant protein was captured in tertiary lymphoid tissue in IPAH lungs, suggesting that specific SAMHD1 antibodies were produced locally. An inflammatory stimulus (TNFα) caused a twofold increase in SAMHD1 in PAECs by western blot (P&lt;0.05, n=3 per group). A similar increase in SAMHD1 ICs was observed in lung tissues from MCT vs. control rats (P&lt;0.05, n=7 and 6, respectively). Conclusions: Our data suggest that human endogenous retroviruses or inflammatory stimuli (TNFα) can increase SAMHD1, inducing local ICs and chronic inflammation associated with the pathological changes causing experimental and clinical PH.
Inflammation biomarkers of lung tissue damage in acute exacerbation of COPD patients
Authors: Emilija Lozo Vukovac, Kornelija Mise, Ivan Gudelj, Irena Peric
Journal: European Respiratory Journal (2013)

Introduction: The inflammatory process in COPD is characterized by infiltration of the airways by neutrophils and inflammatory markers, although laboratory findings are normal or slightly abnormal.  Objective: Primary endpoint: to examine relationship between markers of systemic inflammation and local lung inflammation markers in patients with COPD. Secondary endpoints: to determine the pH status of bronchoalveolar aspirate (BA) in patients with COPD.  Materials: We studied 84 hospital patients with diagnosed COPD in acute exacerbation who underwent video bronchoscopy. LDH in the BA (L-LDH), C-reactive proteine in the BA (L-CRP), serum LDH (S-LDH) and serum CRP (S-CRP) and lung pH were measured.  Results: The values of S-LDH with L-LDH (P=0.001), S-CRP with L-CRP (P=0.037) correlated. Lung pH values correlate with L-LDH values (P  Conclusions: Analysis of L-LDH is a potentially useful tool for evaluating lung tissue damage and can serve as an estimate of bacterial infection in the lungs. Alkaline lung pH environment, caused by long lasting infection, as well as acidic environment destroy the lung tissue.
Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease
Authors: Michael Pavlides, Rajarshi Banerjee, Joanne Sellwood, Catherine J. Kelly, Matthew D. Robson, Jonathan C. Booth, Jane Collier, Stefan Neubauer, Eleanor Barnes
Journal: Journal of Hepatology (2015)

<h3>Background & Aims</h3> Multiparametric magnetic resonance (MR) imaging has been demonstrated to quantify hepatic fibrosis, iron, and steatosis. The aim of this study was to determine if MR can be used to predict negative clinical outcomes in liver disease patients. <h3>Methods</h3> Patients with chronic liver disease (n=112) were recruited for MR imaging and data on the development of liver related clinical events were collected by medical records review. The median follow-up was 27months. MR data were analysed blinded for the Liver Inflammation and Fibrosis score (LIF; <1, 1–1.99, 2–2.99, and ⩾3 representing normal, mild, moderate, and severe liver disease, respectively), T<sub>2</sub>∗ for liver iron content and proportion of liver fat. Baseline liver biopsy was performed in 102 patients. <h3>Results</h3> Liver disease aetiologies included non-alcoholic fatty liver disease (35%) and chronic viral hepatitis (30%). Histologically, fibrosis was mild in 54 (48%), moderate in 17 (15%), and severe in 31 (28%) patients. Overall mortality was 5%. Ten patients (11%) developed at least one liver related clinical event. The negative predictive value of LIF<2 was 100%. Two patients with LIF 2–2.99 and eight with LIF⩾3 had a clinical event. Patients with LIF⩾3 had a higher cumulative risk for developing clinical events, compared to those with LIF<1 (<i>p</i>=0.02) and LIF 1–1.99 (<i>p</i>=0.03). Cox regression analysis including all 3 variables (fat, iron, LIF) resulted in an enhanced LIF predictive value. <h3>Conclusions</h3> Non-invasive standardised multiparametric MR technology may be used to predict clinical outcomes in patients with chronic liver disease.
Anemia in diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) patients.
Authors: C. L. Gallagher, K. D. Glinert, I. F. Kohut, D. H. Henry
Journal: Journal of Clinical Oncology (2010)

e18550 Background: RCHOP chemotherapy is a standard treatment for DLBCL. Recent studies of DLBCL patients treated with RCHOP report varying rates of 3-year overall survival (OS), ranging from 67%-84%, with anemic DLBCL patients not responding as well to chemotherapy. We conducted a retrospective study to determine the response to RCHOP therapy in DLBCL patients treated in our outpatient oncology clinic. Methods: Between 2004 and 2009, 59 DLBCL patients (22 female, 37 male) were treated with RCHOP. We defined anemia as hemoglobin <11.0 g/dL at any time during RCHOP treatment or within 10 days after the last dose. Progression-free survival (PFS) was measured from last RCHOP dose to date of progression. OS was measured from diagnosis to death or until December 2009. Results: Of the 59 patients, 8 (15%) have relapsed; 1(2%) is in partial remission (PR); 1(2%) has residual disease; and 42 (71%) are in complete remission (CR). 15 (25%) patients have expired: 5 before remission; 3 after remission, 5 after remission and subsequent relapse, and 2 while in PR. The median PFS for the 54 patients who initially reached remission was 28 months (0.7-57+). The median OS of all 59 patients was 30 months (0.8-60+). 27 (46%) patients were anemic during treatment. Anemic patients had a lower rate of CR (59% vs. 81%), a higher mortality rate, (37% vs. 16%), shorter median PFS [18 (0.7-52+) vs. 30 (2-57+) mos.], and shorter median OS [17 (0.8-59+) vs. 34 (5-60+) mos.] as compared to non-anemic patients. 15 (56%) of the 27 anemic patients received erythropoietin stimulating agents (ESAs). Anemic patients who received ESAs had a lower rate of CR (53% vs. 67%). But, anemic patients given ESAs who responded to ESA treatment (4/15) had a higher rate of CR (3/4 vs. 4/11). Conclusions: While our study is small in size, our data reveal that anemia in DLBCL patients may be associated with a lower rate of CR and shorter PFS and OS. Anemic patients given ESAs had a lower rate of CR, but those who responded to ESAs had a higher rate of CR. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Ortho Biotech, Watson Pharmaceuticals Amgen, Ortho Biotech, Watson Pharmaceuticals
Final survival and safety results for 21,064 non-small-cell lung cancer (NSCLC) patients who received compassionate use gefitinib in a U.S. expanded access program (EAP)
Authors: J. Ochs, J. J. Grous, K. L. Warner
Journal: Journal of Clinical Oncology (2004)

7060 Background: Effective chemotherapy results in 1-year survival rates of approximately 30% in consenting patients with advanced and recurrent NSCLC who are able to tolerate chemotherapy. We present final analyses from >21,000 patients who received gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor in an EAP. Methods: Eligibility criteria included stage III/IV NSCLC patients who failed or were unable to tolerate chemotherapy. Patients received oral gefitinib 250 mg/day as long as treatment provided clinical benefit without unacceptable toxicity. Duration of therapy and survival were measured from the start of initial therapy to the last resupply date for ongoing patients or the date of last dose for withdrawn patients. For surviving patients who withdrew, periodic follow-up data were not collected, and patients were censored for survival at withdrawal until death was reported. Results: As of July 2003, 23,383 patients were enrolled and 21,064 received ≥ 1 dose of gefitinib. Of 21,064 patients, 9979 were women and 11,040 were men, 87.8% were white, median age was 67 years, and 72.7% had stage IV disease. Median survival was 5.3 months (CI, 5.1–5.5 mo) and 1-year survival was 29.9% (95% CI, 28.8–31.1). Better survival was seen in women, Asian/Oriental ethnic groups, and stage III patients. Of a 9501 patient subset who received gefitinib and had potential for a 1-year follow-up, 20.1% received drug for ≥ 6 months. In 2.3% of patients, a serious treatment-related adverse (AE) event was reported: 1.1% discontinued therapy due to a serious drug-related AE, and 0.3% had an investigator-assessed, drug-related death. Conclusions: One-year survival rates in over 20,000 patients treated with gefitinib on a compassionate basis are comparable to that obtained with chemotherapy in a second-line clinical setting. Reported safety was favorable when compared with chemotherapy. These findings are consistent with 2 large randomized phase II trials (IDEAL 1 and 2) and reported single institution EAP clinical experience. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Pharmaceuticals Mutual funds
Adverse Lifestyle Trends Counter Improvements in Cardiovascular Risk Factor Management in Coronary Patients
Authors: Kornelia Kotseva, Dirk De Bacquer, Catriona Jennings, Viveca Gyberg, Guy De Backer, Lars Rydén, Philippe Amouyel, Jan Bruthans, Renata Cifkova, Jaap W. Deckers, Johan De Sutter, Zlatko Fraz, Ian Graham, Irena Keber, Seppo Lehto, David Moore, Andrzej Pajak, David Wood
Journal: Journal of the American College of Cardiology (2015)
Abstract 18737: Sex Differences in Mortality in Women and Men with Obstructive Coronary Artery Disease and Acute Coronary Syndrome
Authors: Edina Cenko, Sasko Kedev, Slobodan Antov, Zorana Vasiljevic, Maria Dorobantu, Olivija Gustiene, Bozidarka Knezevic, Davor Milicic, Mirza Dilic, Dijana Trninic, Olivia Manfrini, Raffaele Bugiardini
Journal: Circulation (2014)

Introduction:  There is controversy whether there are sex differences in mortality following ACS.   Hypothesis:  Comparisons are confounded by the lower likelihood of obstructive CAD in women than men, and by the less frequent use of coronary angiography, revascularization and evidence-based therapies. All of these factors may affect prognosis.   Methods:  The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC, NCT01218776), enrolled 6811 ACS patients (4908 men and 1903 women) who underwent coronary angiography during their hospitalization. We investigated sex differences in-hospital mortality among patients with confirmed obstructive CAD, defined as ≥50% stenosis in ≥1 epicardial coronary artery. Cox proportional hazards regression model was adjusted to covariates significantly different between groups in univariate analysis. The primary endpoint was in-hospital death; the secondary endpoint was the composite of in-hospital death, stent thrombosis, and stroke or major bleeding.   Results:  Among patients who underwent coronary angiography, the majority had obstructive CAD (6531/6811, 95.9%). Women (1786/1903, 93.9%) with obstructive CAD had a higher rate of death than men (6.4% vs. 3.2%, p   Conclusions:  Women with ACS and documented obstructive CAD have higher short term mortality despite adjustment for clinical factors, revascularization and evidence-based therapies as compared with men. These data suggest that knowledge of coronary anatomy and treatment variables are critical to the accurate assessment of differences in outcomes among ACS women and men.
Prehabilitation during the neoadjuvant treatment for rectal cancer surgery: A pilot study.
Authors: Lidia Brea, Ana Ruiz-Casado, Maria Jesus Ortega, Ana Soria, Itziar Pagola, Carmen Fiuza, Daniel Huerga, Maria Victoria De Torres, Blanca Ludena, Hector Cebolla, Jesus Olivan, Fernando Pereira, Alejandro Lucia
Journal: Journal of Clinical Oncology (2015)

e20668 Background: There is limited research on the effect of exercise during neoadjuvant (NA) periods. Prehabilitation is a program to increase functional capacity in anticipation of an upcoming stressor. VO2max is a predictor of perioperative morbidity and mortality. The objective of this study was to evaluate the feasibility of training rectal cancer patients during NA treatment measured as 70% attending 4 out of 6 educational sessions. Methods: Pts older than 18 yo, diagnosed with stage II-III rectal cancer, ECOG < 3 and candidates to NA treatment. They were offered six educational sessions during the NA period. The program consisted of: education about theoretical advantages of exercise, heart rate monitoring, aerobic training, strength training, stretching, total training and relaxation. Anthropometry, estimated aerobic capacity (VO2max) through the one-mile test, strength, QoL (EORTC QLQ-30) and psychological distress (HADS) were evaluated before the program and before the surgery. An objective evaluation of weekly PA was done through accelerometer. Results: Twelve pts were recruited. One patient early withdrew because of rapid metastatic progression. A second patient attended 4/6 sessions and abandoned the sessions because of radiotherapy-related adverse events. Adherence was 83.3%. ACCELEROMETERS: Basal weekly moderate-vigorous physical activity (MVPA) was 364 min. Before surgery MVPA was 516 (p = 0.091). CARDIORESPIRATORY FITNESS: Estimated cardiorespiratory fitness significantly improved from 22,8 ml/kg/min (basal) to 29,4 ml/kg/min (before surgery) (p = 0.015). ANXIETY AND DEPRESSION: Scores for depression significantly improved after the sessions (p = 0.017). Anxiety did not improve (p = 0.371). QUALITY OF LIFE: Global scores did not improve. Conclusions: A program of physical activity is feasible during neoadjuvant treatment of rectal cancer. After receiving an education in benefits of physical activity and some basic training, there was a significant improvement in cardiorespiratory fitness and depression as well as a numerical increase in weekly physical activity. Though a selection bias cannot be excluded, these encouraging results warrant further research.
Hypoxia Created Human Mesenchymal Stem Cell Sheet for Prevascularized 3D Tissue Construction
Authors: Lijun Zhang, Qi Xing, Zichen Qian, Mitchell Tahtinen, Zhaoqiang Zhang, Emily Shearier, Shaohai Qi, Feng Zhao
Journal: Advanced Healthcare Materials (2015)

3D tissue based on human mesenchymal stem cell (hMSC) sheets offers many interesting opportunities for regenerating multiple types of connective tissues. Prevascularizing hMSC sheets with endothelial cells (ECs) will improve 3D tissue performance by supporting cell survival and accelerating integration with host tissue. It is hypothesized that hypoxia cultured hMSC sheets can promote microvessel network formation and preserve stemness of hMSCs. This study investigates the vascularization of hMSC sheets under different oxygen tensions. It is found that the HN condition, in which hMSC sheets formed under physiological hypoxia (2% O 2 ) and then cocultured with ECs under normoxia (20% O 2 ), enables longer and more branched microvessel network formation. The observation is corroborated by higher levels of angiogenic factors in coculture medium. Additionally, the hypoxic hMSC sheet is more uniform and less defective, which facilitates fabrication of 3D prevascularized tissue construct by layering the prevascularized hMSC sheets and maturing in rotating wall vessel bioreactor. The hMSCs in the 3D construct still maintain multilineage differentiation ability, which indicates the possible application of the 3D construct for various connective tissues regeneration. These results demonstrate that hypoxia created hMSC sheets benefit the microvessel growth and it is feasible to construct 3D prevascularized tissue construct using the prevascularized hMSC sheets.
Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet?
Authors: Kara L. Kliewer, Carina Venter, Alison M. Cassin, J. Pablo Abonia, Seema S. Aceves, Peter A. Bonis, Evan S. Dellon, Gary W. Falk, Glenn T. Furuta, Nirmala Gonsalves, Sandeep K. Gupta, Ikuo Hirano, Amir Kagalwalla, John Leung, Vincent A. Mukkada, Jonathan M. Spergel, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract P3-04-14: Prognostic impact of Her2 and hormone receptor expression in inflammatory breast cancer: A SEER database analysis
Authors: Anna Maria Affan, Babu P Mohan, Kali Praveena Iruku, Keyvan Ravakhah
Journal: Cancer Research (2015)

Abstract INTRODUCTION: Inflammatory breast cancer (IBC) is known to be one of the most aggressive forms of breast cancer. Patients with IBC generally present with early metastases and are frequently resistant to conventional chemotherapies. By using the SEER database, we explored the clinical relevance of Her2 and hormone receptor (HR) expression in IBC tumors and the possible impact it may have on management. METHODS: Data for patients with IBC was extracted from the Surveillance, Epidemiology, and End Results (SEER 18) database from 2010 to 2011. A sub-analysis with the available receptor status data for the same period was analyzed using CanSurv survival software. The Actuarial method was used to construct survival curves according to the following receptor variables; Her2+/HR+, Her2+/HR-, Her2-/HR+, and triple negative IBC groups. Demographic data including race and age was also extracted. RESULTS: Of 354 cases of IBC reported, 5% (n=18) of the tumors were Her2+/HR+, 7.9% (n=28) Her2+/HR-, 15.3% (n=54) Her2-/HR+, and 12.4% (n=44) triple negative. Highest 1 year survival rates were seen in those patients with Her2-/HR+ tumors at &amp;gt;95% while Her2+/HR+ had the lowest 1 yr survival rates at 65%. Caucasian patients above 30 years represented the highest racial group at approximately 70% (n=105). Analysis of this subgroup showed 38% (n=40) of these patients having HER2-/HR+. Despite more than 75% (n=33) of these patients presenting with advanced disease, the 1 year survival remained highest among all the receptor combinations analyzed. This observation held true across all racial groups even with those population numbers for IBC being less. CONCLUSION: The Her2-/HR+ receptor combination group showed the greatest 1 year relative survival when compared to the other groups. These results suggest that HR expression in the absence of Her2 is associated with an increased survival. This can play in a role in the management of IBC by incorporating hormonal therapy into the treatment protocols for patients with IBC to possibly improve survival. Citation Format: Anna Maria Affan, Babu P Mohan, Kali Praveena Iruku, Keyvan Ravakhah. Prognostic impact of Her2 and hormone receptor expression in inflammatory breast cancer: A SEER database analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-14.
Moderate sleep apnoea: a “silent” disorder, or not a disorder at all?
Authors: Edward O. Bixler, Alexandros N. Vgontzas, Jordan Gaines, Julio Fernandez-Mendoza, Susan L. Calhoun, Duanping Liao
Journal: European Respiratory Journal (2015)

Most sleep clinicians and scientists will agree that if a patient with sleep apnoea is symptomatic and has an apnoea/hypopnea index (AHI) of more than 15 events per hour, he or she deserves treatment. However, there is a large group of patients with mild and moderate sleep apnoea who are asymptomatic. For these individuals, the decision of when to treat is a grey area, and current guidelines leave clinicians wondering what to do. New ERJ study adds to the evidence casting doubt on the utility of recommended cut-offs for sleep apnoea treatment <http://ow.ly/VgjBL>
Abstract 18422: NLRP3 Inflammasome Promote Myocardial Remodeling During Diet-Induced Obesity
Authors: Trine Ranheim, Marina Sokolova, Ivar Sjaastad, Katrine Alfsnes, Mieke Louwe, Magnus Aronsen, Lily Shang, Solveig B Haugstad, Marte Bliksøen, Egil Lien, Pål Aukrust, Arne Yndestad
Journal: Circulation (2014)

Introduction: Type 2 diabetes (T2D) is a risk factor for heart failure. We have demonstrated that NLRP3 inflammasome is functional in the heart and may regulate cardiac dysfunction and cell death. Hypothesis: This led us to hypothesize that the NLRP3 inflammasome may play a role in development of cardiomyopathy in T2D. The present project aims to explore this hypothesis by examining NLRP3 and ASC deficient mice in a model of metabolic stress-induced cardiomyopathy. Methods: Wt (C57Bl/6J), NLRP3-/- and ASC-/- male mice were fed a high-fat diet (HFD; 60%cal from fat) or control diet for 52 weeks. Echocardiography and measurements of fasting plasma glucose were performed during the study period. Systolic and diastolic blood pressures were measured using the tail-cuff method. Results: HFD induced increase in body weight in all mice, but Wt mice gained significantly more. Wt mice on HFD also had significantly higher fasting plasma glucose levels. Long-term exposure to HFD induced elevation in left ventricle (L...