tbuckley/cabot-search huggingface dataset:
EVERSUN: A phase II trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (RCC) (ANZUP trial 0901).
Authors: Ian D. Davis, Val Gebski, Mark D. Chatfield, Peter S. Grimison, George Kannourakis, Amy L Boland, Jennifer Thompson, Martin R. Stockler
Journal: Journal of Clinical Oncology (2012)

TPS4681 Background: Treatment of RCC has improved due to better understanding of its biology. New targeted therapies have improved time to progression and overall survival but the optimal sequencing of agents is unknown. Currently drugs are given sequentially, usually starting with sunitinib and often followed by an mTOR inhibitor or another VEGFR-targeted therapy, but resistance to both drugs eventually occurs probably due to host adaptive responses. We hypothesize that resistance might be delayed by planned alternation of treatments. Methods: EVERSUN is a single-arm, two-stage, multicenter, phase II clinical trial aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced RCC. Key eligibility criteria: RCC with a clear cell component; metastatic or locally advanced disease not suitable for resection; ECOG performance status 0-1; low or intermediate MSKCC prognostic score. The primary endpoint is the status of being alive and progression-free (RECIST 1.1) 6 months after registration. Target accrual of 55 subjects gives 95% power and 95% confidence to distinguish between 6-month progression free survival rates of 64% or lower vs 84% or higher using a Simon 2-stage minimax design. The criteria for further evaluation come from the pivotal trial of single agent sunitinib as first line therapy for RCC, in which the 6-month progression free survival rate was 74%. Trial treatment is administered in 12-week (wk) cycles consisting of 4 wks of sunitinib (50 mg daily) followed by 2 wks rest, followed by 5 wks of everolimus (10 mg daily) followed by 1 wk rest. Disease progression is interpreted as failure of the most recent drug taken. Participants who stop one drug because of toxicity or disease progression, on or before the 6 month assessment, will continue the other drug until subsequent progression or prohibitive toxicity on the second drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre. Accrual commenced in September 2010 with 38/55 participants recruited as of the 31-Jan-12 from 17 Australian sites (ACTRN12609000643279).
Fibroblast Growth Factor Receptor 1 and Related Ligands in Small-Cell Lung Cancer
Authors: Liping Zhang, Hui Yu, Andrzej Badzio, Theresa A. Boyle, Hans-Ulrich Schildhaus, Xian Lu, Rafal Dziadziuszko, Jacek Jassem, Marileila Varella-Garcia, Lynn E. Heasley, Ashley A. Kowalewski, Kim Ellison, Gang Chen, Caicun Zhou, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2015)

Small-cell lung cancer (SCLC) accounts for 15% of all lung cancers and has been understudied for novel therapies. Signaling through fibroblast growth factors (FGF2, FGF9) and their high-affinity receptor has recently emerged as a contributing factor in the pathogenesis and progression of non-small-cell lung cancer. In this study, we evaluated fibroblast growth factor receptor 1 (FGFR1) and ligand expression in primary SCLC samples.
Abstract 9113: Therapeutic Neovascularization Targeting Notch Signaling
Authors: Kaoru Tateno, Tohru Minamino, Yohko Yoshida, Junji Moriya, Sho Okada, Ippei Shimizu, Masataka Yokoyama, Takashi Ito, Aika Nojima, Issei Komuro, Yoshio Kobayashi
Journal: Circulation (2011)

Implantation of mononuclear cells (MNC) has become a widely used method to induce therapeutic angiogenesis. However, according to multiple clinical trials published recently, MNC transplantation shows no beneficial effect upon approximately forty percent of the critical limb ischemia cases. To improve such outcomes, it may be a reasonable strategy to clarify the precise molecular mechanism underlying the therapeutic responsiveness, and to establish a novel molecular targeting therapy. Here, we show that Notch signaling can be a promising candidate. We previously reported that, in mice hind limb ischemia model, MNC therapy induced therapeutic muscle regeneration and neovascularization through activation of Notch signaling. We newly found that expression of Jagged-1, a Notch ligand, was significantly decreased in MNC harvested from patients who later suffered major limb amputation following cell therapy, indicating that Notch signaling has a pivotal role in the determination of therapeutic responsiveness by MNC implantation, also in a clinical setting. These results warranted us to further investigate and establish therapeutic neovascularization targeting Notch signaling. We first introduced Jagged-1 into hematopoietic cell line Ba/F3 with retrovirus, and transplanted them into ischemic limb of mice. The cells over-expressing Notch ligands were capable not only to enhance Notch signaling in ischemic muscle tissue, but also to significantly improve limb perfusion. To overcome safety concerns using viral constructs, we established another method utilizing agonistic antibody designed specifically against mice Notch-1 receptor. Like the retroviral cells, the antibody enhanced Notch signaling in ischemic muscle. When used in combination with MNC transplantation, the agonistic antibody significantly improved blood flow recovery from limb ischemia. These results warrant us to design a translational research that utilizes antibody medicine targeting Notch signaling for patients with critical limb ischemia.
Oseltamivir-resistant influenza A(H1N1)pdm09 virus in Dutch travellers returning from Spain, August 2012
Authors: A Meijer, M Jonges, P van Beek, C M Swaan, A D Osterhaus, R S Daniels, A C Hurt, M P Koopmans
Journal: Eurosurveillance (2012)

Two Dutch travellers were infected with oseltamivir-resistant influenza A(H1N1)pdm09 viruses with an H275Y neuraminidase substitution in early August 2012. Both cases were probably infected during separate holidays at the Catalonian coast (Spain). No epidemiological connection between the two cases was found, and neither of them was treated with oseltamivir before specimen collection. Genetic analysis of the neuraminidase gene revealed the presence of previously described permissive mutations that may increase the likelihood of such strains emerging and spreading widely.
beta-lapachone, a novel topoisomerase I inhibitor, has significant cytotoxicity against multiple myeloma (MM) cell lines and patient cells.
Authors: D Gupta, YT Tai, K Podar, BK Lin, M Akiyama, R LeBlanc, LP Catley, C Mitsiades, D Chauhan, N Mitsiades, T Hideshima, RL Schlossman, PG Richardson, KC Anderson
Journal: Blood (2001)
Studies of the epidemiology of peptic ulcer in a rural community: prevalence and natural history of dyspepsia and peptic ulcer.
Authors: R D Weir, E M Backett
Journal: Gut (1968)

Underlying any description of the prevalence and natural history of peptic ulceration is the problem of definition.The classification of patients (and much of their treatment) will depend upon the severity and persistence of symptoms, individual tolerance, the experience, work load and interests of the doctor, and the extent and availability of local facilities for diagnosis.These sources of variation could render studies of prevalence and natural history so inaccurate as to be hardly worth making.Yet without some under-FIG.1. Organization offour related studies.75 ty
Abstract 5752: Epicardial Fat Assessed by Multi-Detector Computed Tomography (mdct) is a New Risk Factor of Coronary Artery Disease in Non-Obese Patients
Authors: Tadateru Iwayama, Joji Nitobe, Mitsunori Ishino, Harutoshi Tamura, Tetsurou Shishido, Satoshi Nishiyama, Takehiko Miyashita, Takuya Miyamoto, Tetsu Watanabe, Isao Kubota
Journal: Circulation (2008)

Objective: An increment of abdominal visceral fat has been reported to be a coronary risk factor associated with metabolic syndrome. However, adipose tissue surrounding heart has not been fully determined as coronary risk factors. Accurate volumetric measurement of epicardial fat can be easily obtained by MDCT. We examined the relationship between epicardial fat volume and clinical parameters in patients with coronary artery disease (CAD). Method: We evaluated epicardial fat volume by 64 detector row CT scanner in CAD patients (obese, 13; non-obese, 11 patients) who underwent elective coronary artery bypass graft surgery and in non-CAD patients who showed normal coronary arteries on angiography (obese, 3; non-obese, 11 patients). Epicardial fat volume was obtained as the sum of fat areas on short axis images. Obese patients were defined as over 25 in body mass index (BMI). Result: Epicardial fat volume was significantly higher in patients with CAD than in those without CAD (40.6 ± 14.7 ml vs. 20.0 ± 14.7 ml, p &lt; 0.05). Epicardial fat volume was not correlated to following coronary risk factors such as HbA1c, fasting plasma glucose, lipid and blood pressure except for BMI. Although there was no difference epicardial fat volume between in obese patients with CAD and in those without CAD (48.3 ± 27.9 ml vs. 41.2 ± 11.0 ml, NS), it was significantly higher in non-obese patients with CAD than in those without CAD (32.1 ± 9.2 ml vs. 14.2 ± 9.2 ml, p &lt; 0.05). Conclusions: The quantity of epicardial fat using MDCT is related with the presence of CAD. Especially in non-obese patients, epicardial fat may affect directly progression of CAD independent of pathophysiological process of metabolic syndrome.
Abstract 15115: Reduction in Bleeding with Apixaban versus Warfarin is Consistent Across Subgroups and Locations: Insights from the ARISTOTLE Trial
Authors: Elaine M Hylek, Claes Held, John H Alexander, Renato D Lopes, Raffaele DeCaterina, Kurt Huber, Petr Jansky, Gabriel Steg, Michael Hanna, Lars Wallentin, Christopher Granger
Journal: Circulation (2012)

Background: While oral anticoagulation is effective at preventing stroke, bleeding complications are common and are a major limitation of treatment. We describe the incidence, location, and severit...
Abstract 3355: Relationship Between Electrocardiographic Remodeling, Mechanical Remodeling and the Occurrence of Appropriate Therapy in Biventricular Implantable Cardioverter Defibrillator Patients
Authors: Nicolas Lellouche, Carlos De Diego, Gina Akopyan, David A Cesario, Osamu Fujimura, Isaac Wiener, Noel G Boyle, John Child, Kalyanam Shivkumar
Journal: Circulation (2007)

Background: Cardiac Resynchronization Therapy (CRT) is associated with reverse left ventricular (LV) remodeling. However, the effect of CRT on electrical remodeling, reverse mechanical remodeling, occurrence of ventricular arrhythmias is not well established. Methods: D ata from 45 patients who underwent implantable cardioverter defibrillator(ICD)-CRT implantation was retrospectively analyzed. Patients had New York Heart Association (NYHA) functional class III or IV heart failure symptoms, left ventricular ejection fraction (LVEF) &lt;35%, and QRS duration &gt;130 ms or QRS ≤130ms with left intraventricular dyssynchrony. Significant LV reverse remodeling was defined by a decrease of left ventricular end diastolic diameter (LVEDd) by at least 10% after 1 year of follow up. Electrocardiographic indices of dispersion of repolarization (DR) (QTc, T peak-Tend (Tp-e) and their dispersion) were measured immediately and 1 year after implantation. The occurrence of appropriate ICD therapy was noted for each patient. Results: Patients with significant LV reverse remodeling (n=21) and without LV reverse remodeling (n=24) had similar baseline characteristics. After one year of follow up, patients with LV reverse remodeling exhibited a significant decrease in DR parameters (Tp-e, QT dispersion and Tp-e dispersion), and lower rate of appropriate ICD therapy (log rank p=0.002), compared to those without reverse remodeling who experienced an increase in DR parameters (QT dispersion and Tp-e dispersion), figure 1 . Conclusion: Mechanical LV reverse remodeling is associated with an electrical reverse remodelling and a lower rate of appropriate ICD therapy. Figure 1: Occurence of appropriate CD therapy according to LV reverse remodelling
Organotherapy, or Treatment by Means of Preparations of Various Organs.
Authors: H. Batty Shaw
Journal: JAMA (1906)

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The use of live three-dimensional Doppler echocardiography in the measurement of cardiac output
Authors: James Pemberton, Xiaokui Li, Tara Karamlou, Chloe A. Sandquist, Karl Thiele, Irving Shen, Ross M. Ungerleider, Antoinette Kenny, David J. Sahn
Journal: Journal of the American College of Cardiology (2005)
Abstract 18187: Shone's Complex: Single Center Experience Over 22 Years
Authors: Caridad M de la Uz, Nancy A Ayres, William A Payne, Ricardo H Pignatelli, Christopher J Petit
Journal: Circulation (2011)

Background: Children with Shone's Complex (SC) have multiple levels of left heart obstruction and often require a number of left heart interventions. They are at risk of long-term morbidity and mortality. However, long-term outcomes in children with SC are limited. Methods: SC was defined as a mitral valve (MV) anomaly and ≥ 1 other left heart obstructive lesion including coarctation of the aorta (CoA), subvalvar, supravalvar and aortic valvar stenosis (AS). MV morphology type was classified as typical (MVtyp) - hypoplastic annulus, thickened leaflets; mitral ring (MVr); arcade or other papillary muscle anomaly (MVarc); parachute (MVpap); and other including double-orifice (MVo). Pts who underwent Norwood palliation were excluded. We reviewed overall outcomes and focused on the impact of pulmonary hypertension (PH) and pre-existing atrial septal defect (ASD) on left heart growth, number of interventions, and death/transplant (OHT). Results: A total of 129 SC pts presented at 35d (0d - 18yrs) of age and were followed for 7.0 ± 6.8 years. MV morphology included MVtyp (n=89, 68%), MVr (n=23, 18%), MVpap (n=21, 16%), MVarc (n=25, 19%). A total of 113 pts underwent 232 (median 2, 0-5) interventions including ASD closure (n=49), VSD closure (n=30), AVR (n=8), MVR (n=10), MV repair (n=39), AS repair (n=37), balloon valvuloplasty (n=36) and CoA dilation/repair (n=60). Pre-intervention, ASD was associated with lower mean LA pressure 11.7±5.6 vs 18.5±6.5 mmHg (p=0.02) and lower mitral gradient 5.3 ± 5.6 vs 10.9 ± 10.6 mmHg (p&lt;0.01) on catheterization. Following first surgical intervention, residual ASD was associated with decreased annular growth of AV (p=0.042) and MV (p=0.01), smaller increase in LVEDD (p=0.001) and LVESD (p=0.018). MVpap was associated with smaller MV (p&lt;0.001) and less MV annular growth by latest follow-up (p=0.001). Twenty-year OHT-free survival was 87%. By multivariate analysis, PH was associated with death/OHT (OR 6.8, 1.7-27.8). Survival in pts without residual ASD was 88% vs 77% with an ASD (p=0.017). Conclusions: SC pts with residual ASD have a higher rate of interventions. Left heart growth is optimized with ASD closure, while MVpap is associated with decreased growth. Pts who develop PH and have residual ASDs are at higher risk of mortality.
Abstract 3414: Mortality Incidence and the Severity of Coronary Atherosclerosis Assessed by CT Angiography
Authors: Matthew P Ostrum, Eric Yang, SongShou mao, Ambarish gopal, Naser Ahmadi, Matthew J Budoff
Journal: Circulation (2007)

Objectives: This study was performed to investigate the relationship between the degree of coronary artery disease (CAD) and incidence of mortality in patients who were referred for Cardiovascular Computed Tomographic Angiography (CTA) in an outpatient setting. Background: Non invasive coronary angiography is being increasingly performed by CTA to assess for significant obstructive CAD. While there is extensive literature on mortality incidence with respect to degree of CAD defined by conventional coronary angiography and coronary artery calcification, no such outcome data exists for coronary CTA. Methods: We observed over a mean follow-up of 5±2 yrs, 2971 consecutive patients who underwent cardiac CTA. Significant CAD, defined as greater or equal to 50% luminal narrowing of an epicardial vessel, was determined by CTA. All cause mortality was detected through a search of the national death registry by patient’s social security number. Multivariable Cox proportional hazards models were developed to predict all-cause mortality. Results: Among this cohort, we detected a total of 102 deaths (3.4%). We observed the following mortality rates among patients with varying degrees of atherosclerotic disease burden; 3 vessel disease 18.8% (3/16), 2 vessel disease 6.1% (6/99), 1 vessel disease 3.5% (12/347), non obstructive disease 2.1% (22/1062), no detectable disease 1.8% (15/849). Patients with increasing severity of both non-obstructive and obstructive disease were more likely to die over the subsequent 5 years (Table 1 ). Conclusions: The severity of coronary artery disease assessed by noninvasive CT angiography independently correlates with all cause mortality.
Impact of microsatellite instability and p53 expression on stage III colon cancer disease-free survival in patients treated by fluorouracil and leucovorin with or without oxaliplatin
Authors: A. Zaanan, P. Cuilliere-Dartigues, Y. Parc, C. Louvet, E. Tiret, B. Gayet, P. Validire, J. Fléjou, A. Duval, F. Praz
Journal: Journal of Clinical Oncology (2008)

15017 Background: The addition of oxaliplatin to fluorouracil and leucovorin (FL) regimen was recently demonstrated to improve the adjuvant treatment of stage III colon cancer at the cost of an increased incidence in adverse effects (André et al, NEJM, 2004). The aim of the study was to determine the values of the tumor microsatellite instability (MSI) phenotype and p53 expression as markers to predict benefit from adjuvant chemotherapy of colon cancer by FL alone or with oxaliplatin (FOLFOX4). Patients and Methods: MSI phenotype and p53 status were determined by immunohistochemistry (IHC) in a series of 192 consecutive stage III colon cancer patients, treated by either FL (n = 123) or FOLFOX4 (n = 69). The 2 groups of patients were well balanced concerning the main characteristics and prognostic factors. Disease-free survival (DFS) was analyzed according to the IHC results and to the treatment received. Results: Thirty tumors (15.6%) were MSI due a complete loss of MLH1, MSH2 or MSH6 expression and 97 tumors (51.1%) overexpressed p53 (p53pos). The addition of oxaliplatin to a regimen of FL significantly improved DFS in the group of 30 patients with MSI tumors regardless of p53 status (3-yr DFS : 100% vs 57.9%; Hazard ratio : 0.19, 95% CI 0.05 to 0.79; P = 0.02), while the benefit for the 162 patients with MSS tumors was not significant (3-yr DFS : 80.8% vs 73.3%; HR : 0.65, 95% CI 0.34 to 1.22; P = 0.18). However, among the 88 patients with MSS-p53pos tumor, a significant benefit in DFS was observed in the group of patients treated by FOLFOX4 compared to FL regimen (3-yr DFS : 87.7% vs 69.8%; HR : 0.38, 95% CI 0.16 to 0.89; P = 0.03). By contrast, there was no detectable benefit of oxaliplatin in the group of 73 patients with MSS-p53neg tumors (3-yr DFS : 71.8% vs 76.7%; HR : 1.22, 95% CI 0.47 to 3.22; P = 0.68). Conclusion: This retrospective study suggests that adding oxaliplatin to FL improves DFS of patients with stage III colon cancer whose tumor displays MSI and/or overexpresses p53, but not that of patients with MSS-p53neg tumors. These results should be confirmed in larger and prospective studies. No significant financial relationships to disclose.
Abstract 15463: Penn Alliance for Therapeutic Hypothermia: the First US Registry of Post-Cardiac Arrest Hypothermia Patients - Hemodynamics, Mortality, and Therapeutic Hypothermia
Authors: Anne V Grossestreuer, Benjamin S Abella, Marion Leary, Robert W Neumar, Lance B Becker, David F Gaieski
Journal: Circulation (2011)

Background: Therapeutic hypothermia (TH) is the only approved therapy for victims of sudden cardiac arrest who have a return of spontaneous circulation but have post-cardiac arrest syndrome (PCAS)....
Abstract 13676: Circulating Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Cardiac Amyloidosis
Authors: Komei Tanaka, Eric E Essick, Lawreen H Connors, David C Seldin, Flora Sam
Journal: Circulation (2011)

Background: Cardiac amyloidosis (CA) is characterized by amyloid infiltration resulting in extracellular matrix (ECM) disruption. Cardiomyopathy (CMP) and symptomatic heart failure (HF) due to card...
Deaths related to 2009 pandemic influenza A (H1N1) among American Indian/Alaska natives - 12 states, 2009.
Authors: L. Castrodale, J. McLaughlin, S. Imholte, K. Komatsu, E. Wells, M. Landen, D. Selvage, M. Sewell, C. Smelser, D. Thompson, K. Bradley, C. McDonald, R. Leman, M. Powell, T. Miller, L. VanderBusch, L. Kightlinger, R. Boulton, K. Lofy, A. A. Marfin, R. McClinton, M. Hoopes, T. Kim, J. M. Hayes, Z. Mahal, E. Chao
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
The Binding of Haemoglobin by Plasma Proteins (Haptoglobins)
Authors: A. C. Allison, W. ap Rees
Journal: BMJ (1957)

The cases are presented of 24 patients with various diseases who had negative tuberculin reactions.Whilst treated with cortisone or prednisolone in moderate or low dosage the tuberculin reaction became positive at the same or higher dilutions in 20 of the cases.The -patients were mostly elderly, or showed frank signs of suprarenal cortical suppression.The suggestion is made that steroid treatment, although able to suppress a positive tuberculin reaction when given in high dosage, may, given in lower dosage, actually restore a reaction which has been suppressed by age, infection, or suprarenal deficiency.The implications of these findings and their possible application to the treatment of severe infections, especially in the elderly, are discussed.I thank the physicians of the Aylesbury Hospitals for permission to investigate their patients, and in particular Dr. Wilfred Stokes and Dr. M. Saxty Good for much valuable advice and criticism.I also thank Dr. L. Nunn for the biochemical investigations and the nursing staff for
Abstract 126: The Impact of Rapid Response Team Training on Team Dynamics and Provider Self-Confidence
Authors: Ivette Motola, Robert E Soto, Al A Brotons, Hector F Rivera, S Barry Issenberg
Journal: Circulation (2011)

Introduction Rapid Response Team (RRT) training is essential to early recognition and management of the critically ill patient. Using the Rapid Response Team Training curriculum (SimMedical and Lae...
Safety and Effectiveness of Drug-Eluting Versus Bare-Metal Stents in Saphenous Vein Bypass Graft Percutaneous Coronary Interventions
Authors: Vikas Aggarwal, Maggie A. Stanislawski, Thomas M. Maddox, Brahmajee K. Nallamothu, Gary Grunwald, Jill C. Adams, P. Michael Ho, Sunil V. Rao, Ivan P. Casserly, John S. Rumsfeld, Emmanouil S. Brilakis, Thomas T. Tsai
Journal: Journal of the American College of Cardiology (2014)