tbuckley/cabot-search huggingface dataset:
Abstract 12724: Chronic Heart Failure Patients whose Ejection Fraction Improves Above 35% With Medical Therapy are Still at Risk for Sudden Cardiac Death
Authors: Masato Kawasaki, Takahisa Yamada, Tahashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Atushi Kikuchi, Takashi Naito, Tadao Fujimoto, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Tutomu Kawai, Satoshi Takahashi, Masatake Fukunami
Journal: Circulation (2012)

Background: Patients with chronic heart failure (CHF) with left ventricular ejection fraction (LVEF) less than 35% are well known to be at risk of sudden cardiac death. However, little is known whe...
Loss of Chromosomes 9P and 14Q: Re-Profiling Metastatic Tissue for Re-Targeting Patients with Metastatic Renal Cell Carcinoma
Authors: F. Massari, C. Ciccarese, S. Knuutila, F. La Russa, D. Bimbatti, A. Modena, C. Zampini, A.B. Porcaro, T. Sava, W. Artibani, G. Martignoni, M. Brunelli, G. Tortora
Journal: Annals of Oncology (2014)
Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey
Authors: Tendani Gaolathe, Kathleen E Wirth, Molly Pretorius Holme, Joseph Makhema, Sikhulile Moyo, Unoda Chakalisa, Etienne Kadima Yankinda, Quanhong Lei, Mompati Mmalane, Vlad Novitsky, Lillian Okui, Erik van Widenfelt, Kathleen M Powis, Nealia Khan, Kara Bennett, Hermann Bussmann, Scott Dryden-Peterson, Refeletswe Lebelonyane, Shenaaz el-Halabi, Lisa A Mills, Tafireyi Marukutira, Rui Wang, Eric J Tchetgen Tchetgen, Victor DeGruttola, M Essex, Shahin Lockman
Journal: The Lancet HIV (2016)
Abstract MP81: Community Characteristics Are Associated With Blood Pressure Levels in a Racially Integrated Community
Authors: Laura J Samuel, Roland J Thorpe, Thomas A LaVeist
Journal: Circulation (2015)

Some community characteristics, such as perceived problems, have been associated with higher blood pressure levels, while access to community resources and community social cohesion have been associated with lower blood pressure levels. However, potential confounding by residential racial segregation has previously been ignored, despite positive correlations between segregation and hypertension. This study tests the hypothesis that results differ in a racially integrated community.  Blood pressure was measured as the average of three readings from 1326 black and white adults residing in two racially integrated, contiguous, low income, urban US Census Tracts. Hypertension was defined as systolic BP≥140 mmHg and/or diastolic BP≥90 mmHg or use of antihypertensive medication(s). Neighborhood problems were measured with 15 questions about lack of resources, safety and crime. Participants were asked if people work together to solve problems to measure social cohesion and if the neighborhood has a leader. The presence of any desirable community resources on the participant’s block was also observed. Regression models were racially stratified because the effect of residential integration likely differs by race.  Perceptions of community problems and social cohesion and rates of community resources did not differ by race. Models adjusted for all community characteristics, age, sex, income, marital status, residency length, and in blood pressure models, antihypertensive medication use. In whites, each standard deviation increase in community problems was associated with lower systolic (β =-2.312, p=0.011) and diastolic (β =-1.484, p=0.014) blood pressure levels. Also, whites living on blocks with community resources had lower systolic (β=-4.079, p=0.011) and diastolic (β=-2.251, p=0.034) blood pressure levels and a lower likelihood of hypertension (PR=0.83, 95% CI: 0.73, 0.93), compared with whites lacking such resources. In African Americans, community social cohesion was associated with higher systolic (β =4.923, p=0.008) and diastolic (β=3.397, p=0.008) blood pressure levels. No associations were found for reporting a community leader. Results were unchanged after additional adjustment for behavioral variables.  Despite a shared community environment, perceptions of the community varied and some were associated with blood pressure levels, but not prevalent hypertension. Directions of associations oppose those of prior studies. This may be due to adverse features of this low income setting, which may contribute to hypertensive disparities. Closer proximity to community resources was associated with lower blood pressure levels and prevalent hypertension in whites. In conclusion, in this racially integrated and low income urban community, some community characteristics were associated with blood pressure levels, though some results differ from prior studies.
Abstract 19311: Obesity is Associated with Increased Rates of Revascularization in Coronary Artery Bypass Grafting Patients: A Large Cohort Study
Authors: Billie-Jean Martin, Adriane M Lee, Danielle A Southern, P D Galbraith, Colleen M Norris, Merill L Knudtson, None APPROACH Investigators
Journal: Circulation (2012)

Introduction: While excess mass has been demonstrated to be associated with improved survival in subjects with coronary artery disease (CAD), other potential outcomes have not been considered. The objective of this study was to assess the relationship between obesity and repeat revascularization in subjects who have undergone coronary artery bypass grafting (CABG). METHODS: The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease database was used to obtain information on subjects who underwent CABG between 1995 and 2010. Subjects were classified as normal weight (BMI 18.5-24.9), overweight (25-29.9), obese class I (30-34.9), obese class II (35-39.9), or obese class III (≥40 kg/m2). Outcome of interest was time to repeat revascularization: the 1st percutaneous coronary intervention or CABG after index CABG. Cox proportional hazard models were used to determine the association between adiposity and freedom from repeat revascularization. Results: There were 13416 subjects included in this study, 23% normal weight. The more obese subjects were younger and had a higher prevalence of diabetes (p&lt;0.0001 across categories). Median follow-up time was 6.3 years; there were 1029 subjects who underwent repeat revascularization. In unadjusted models BMI was associated with increased revascularization (overweight Hazard Ratio (HR), 1.22, 95%CI 1.03, 1.45; Obese Class I 1.22, 95%CI 1.01, 1.48; Obese Class II/III 1.60, 95%CI 1.28, 2.00). This association persisted following adjustment for sex, age and clinical characteristics in overweight (HR 1.20, 95%CI 1.01, 1.42) and obese class II/III subjects (HR 1.41, 95% CI 1.12, 1.77). Discussion: Despite improved survival in obese subjects with CAD, we found obesity is associated with an increased risk of revascularization. This may represent elevated residual risk in obese patients. This finding is novel, and highlights the need to pay particular attention to residual risk in obese subjects with CAD.
A randomized study of individually tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy (FEC) for early breast cancer.
Authors: H. Lindman, M. Andersson, P. Edlund, K. D. Bjerre, T. Hatschek, H. T. Mouridsen, H. Anderson, B. Ejlertsen, S. Møller, E. Lidbrink, C. Kamby, J. Ahlgren, J. Bergh, C. Blomqvist
Journal: Journal of Clinical Oncology (2011)

1017 Background: Dosage of chemotherapy based on body surface area (BSA) does not consider differences in drug clearance and sensitivity, which could result in over- or under-treatment. Several retrospective studies have demonstrated a worse outcome in patients not achieving leucopenia during adjuvant chemotherapy. The SBG 2000−1 trial is the first adjuvant randomized trial designed to compare individually dosed chemotherapy based on grade of leucopenia to standard dosed chemotherapy based on BSA only. Methods: Patients with early breast cancer were included and received the first cycle at a standard dose of FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophophamide 600 mg/m2). Patients with nadir leucopenia grade 0−2 after first cycle were randomized between either 6 tailored FEC with increased doses (E 75−90 mg/m2, C 900−1200 mg/m2) or continuos treatment with 6 standard FEC. Patients with nadir leucopenia grade 3−4 after the first cycle were not randomized but represented a second control group treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). Results: A total of 1,535 patients were included in the study. After cycle one 1052 patients with low toxicity (leucopenia grade 0−2) were randomized to tailored FEC (n=524) or standard FEC (n=528) whereas 401 patients with leucopenia grade 3−4 continued standard FEC and were registered. With a median follow-up of 5.5 years the 5-year DDFS was 85% and 84% (HR 0.80, CI 0.59−1.08, p=0.14) with a disease-free survival of 82% and 79% (HR 0.76, CI 0.58−0.99, p=0.04) for the tailored and standard FEC group respectively. The overall survival was 90% and 89% (HR 0.80, CI 0.56−1.13, p=0.20,). The 5-year DDFS for the registered second control group was 85% and did not differ from the group of patients allocated to tailored FEC (HR 0.94, CI 0.67−1.32). Conclusions: The SBG 2000−1 study failed to show a statistically significant improvement of tailored dosed chemotherapy compared with standard BSA based chemotherapy. However, all efficacy parameters showed trends towards a better outcome for the tailored treatment with estimated hazard ratios of considerable magnitude.
Renal denervation in heart failure with preserved ejection fraction (<scp>RDT‐PEF</scp>): a randomized controlled trial
Authors: Hitesh C. Patel, Stuart D. Rosen, Carl Hayward, Vassilios Vassiliou, Gillian C. Smith, Ricardo R. Wage, James Bailey, Ronak Rajani, Alistair C. Lindsay, Dudley J. Pennell, S. Richard Underwood, Sanjay K. Prasad, Raad Mohiaddin, J. Simon R. Gibbs, Alexander R. Lyon, Carlo Di Mario
Journal: European Journal of Heart Failure (2016)
PWE-259 Colorectal cancer (CRC) patients with inflammatory bowel disease (IBD) are at increased risk of poor outcomes post surgery in england
Authors: A Askari, S Nachiappan, J Murphy, S Mills, A Bottle, T Athanasiou, N Arebi, S Clark, O Faiz
Journal: Gut (2015)

<h3>Introduction</h3> Colorectal cancer (CRC) patients with Ulcerative Colitis (UC) and Crohn's Disease (CD) can be challenging to manage in the perioperative period. The aim of this study is to examine differences between Inflammatory Bowel Disease (IBD) and sporadic CRC patients in terms of the emergency admission rates, length of stay and post operative complications. <h3>Method</h3> A national study was carried out using the Hospital Episode Statistics (HES) database between the years of 1997 to 2012. Multivariable binary logistic regression was undertaken to determine whether IBD was independently associated with the development of a postoperative complication. <h3>Results</h3> During the study time period, 286,591 patient underwent colorectal cancer resection, 0.8% of which (n = 2,322) had IBD. A greater proportion of IBD patients underwent a colorectal cancer resection as an emergency than sporadic patients (UC 25.1%, CD 34.7% and sporadic 24.3%, p &lt; 0.001). IBD patients had a significantly prolonged length of stay after elective surgery for CRC (median number of days length of stay 10 vs. 7, p = 0.001). The overall rate of serious medical complication such as myocardial infarction, stroke, pulmonary embolism was 7.8%, the overall rate of 30-day re-operation was 4.2% (n = 11,987) with a further 0.6% (n = 1,633) requiring radiological re-intervention. A diagnosis of IBD (adjusted for age, gender, comorbidity, mode of admission and type of operation) was an independent predictor of 30-day re-operation (OR 1.32, CI 1.12–1.56, p = 0.001). <h3>Conclusion</h3> IBD patients, particularly Crohn's patients commonly have their colorectal cancer resected in an emergency setting. IBD patients are more likely to require 30-day re-intervention, irrespective of other factors. A multi-disciplinary team approach incorporating surgeons, gastroenterologists, anaesthetists and radiologists is essential in the management of these complex patients in the peri-operative period <h3>Disclosure of interest</h3> None Declared.
PWE-132 A re-evaluation of epidemiology and resistance patterns of culture-positive spontaneous bacterial peritonitis in leeds: Abstract PWE-132 Table 1
Authors: L Harrison, J Sandoe, M Aldersley, J Jennings
Journal: Gut (2015)

<h3>Introduction</h3> Spontaneous bacterial peritonitis (SBP) is a frequent and serious condition with significant morbidity and mortality in patients with liver cirrhosis. Early diagnosis and prompt treatment of SBP reduces in-hospital mortality from 90% to &lt;20%.<sup>1</sup>As a result of an audit of SBP in 2006–2008, first line antibiotic for treatment was changed to piperacillin/tazobactam and cotrimoxazole was recommended for secondary prophylaxis. The outcome of these changes was evaluated. <h3>Method</h3> A retrospective microbiology database search was carried out on fluid samples in Leeds, a teaching hospital with liver transplantation services. The samples were obtained between December 2008 and October 2014, grew a single organism, and had an ascitic fluid neutrophil count of ≥0.25 × 10<sup>9</sup>/L. Case notes were reviewed to establish a diagnosis of SBP. Resistance patterns were compared to samples received 2006–2008. <h3>Results</h3> Of 2679 samples, 43 met criteria for single organism SBP. The mean age was 53.1 and 30/43 (70%) were men. Nine patients were Child’s Pugh Score B and 34 were Child’s Pugh Score C with a 30 day mortality of 22.2% and 56% respectively. The 30 day mortality was 48.8% (21/43) consistent with data from 2006–2008 audit. 74.4% patients had underlying alcohol related liver disease. 78.8% of organisms were Gram-negative with the majority being <i>E coli</i>. There was a large proportion of Gram-positive organisms which were mostly streptococci. Nine patients had prior SBP infections and twelve patients were prescribed secondary prophylaxis. <h3>Conclusion</h3> SBP remains a poor prognostic indicator with a 48.8%, 30-day mortality. A high index of suspicion is essential and empirical antibiotic therapy should be provided. Our results demonstrate a shift from Gram-negative to Gram-positive organisms. This is likely to be due to previous exposure to antibiotics and secondary prophylaxis. Nationally there is an increase in multidrug-resistant Gram-negative organisms. Prior to 2010, quinolone antibiotics such as ciprofloxacin and cephalosporins were more widely used and recommended by BSG guidelines. This reaudit demonstrates a reduction in resistant organisms, especially to ciprofloxaxin. This demonstrates the importance of auditing and reviewing local antimicrobial guidelines. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: variceal haemorrhage, ascites and spontaneous bacterial peritonitis. Gastroenterology. 2001;120:726-48
Scientific Advances in Lung Cancer 2015
Authors: Anne S. Tsao, Giorgio V. Scagliotti, Paul A. Bunn, David P. Carbone, Graham W. Warren, Chunxue Bai, Harry J. de Koning, A. Uraujh Yousaf-Khan, Annette McWilliams, Ming Sound Tsao, Prasad S. Adusumilli, Ramón Rami-Porta, Hisao Asamura, Paul E. Van Schil, Gail E. Darling, Suresh S. Ramalingam, Daniel R. Gomez, Kenneth E. Rosenzweig, Stefan Zimmermann, Solange Peters, Sai-Hong Ignatius Ou, Thanyanan Reungwetwattana, Pasi A. Jänne, Tony S. Mok, Heather A. Wakelee, Robert Pirker, Julien Mazières, Julie R. Brahmer, Yang Zhou, Roy S. Herbst, Vassiliki A. Papadimitrakopoulou, Mary W. Redman, Murry W. Wynes, David R. Gandara, Ronan J. Kelly, Fred R. Hirsch, Harvey I. Pass
Journal: Journal of Thoracic Oncology (2016)
New Treatments for Renal Cell Carcinoma: Targeted Therapies
Authors: Philip J. Saylor, M. Dror Michaelson
Journal: Journal of the National Comprehensive Cancer Network (2009)

Systemic treatment options for advanced renal cell carcinoma (RCC) have expanded considerably with the development of targeted therapies. Clear cell RCC commonly features mutation or inactivation of the von Hippel-Lindau gene and resultant overexpression of vascular endothelial growth factor (VEGF). The first drug to validate VEGF as a target in the treatment of clear cell RCC was the monoclonal antibody bevacizumab. Since then, anti-VEGF receptor therapy with multitargeted kinase inhibitors also has shown substantial efficacy. Sunitinib is now a standard first-line therapy for advanced disease and sorafenib is among the second-line treatment options. Other kinase inhibitors are in development. Mammalian target of rapamycin (mTOR) is a second validated therapeutic target as the mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies. Everolimus is an oral mTOR inhibitor and has been shown to prolong progression-free survival when used in second-line treatment. Non-clear cell and sarcomatoid RCC are both underrepresented in completed trials but are the subject of active research. Ongoing and planned studies will also evaluate the use of combinations of targeted agents, a strategy that is not advisable outside of clinical trials. Finally, postnephrectomy adjuvant treatment with targeted agents is not yet standard but is under investigation in phase III trials.
Initiation of T cell signaling by CD45 segregation at 'close contacts'
Authors: Veronica T Chang, Ricardo A Fernandes, Kristina A Ganzinger, Steven F Lee, Christian Siebold, James McColl, Peter Jönsson, Matthieu Palayret, Karl Harlos, Charlotte H Coles, E Yvonne Jones, Yuan Lui, Elizabeth Huang, Robert J C Gilbert, David Klenerman, A Radu Aricescu, Simon J Davis
Journal: Nature Immunology (2016)
Metronomic capecitabine (cape) and cyclophosphamide (CTX) for refractory metastatic colorectal cancer (mCRC): Results of a phase II trial.
Authors: Federica Marmorino, Chiara Cremolini, Fotios Loupakis, Lisa Salvatore, Marta Schirripa, Carlotta Antoniotti, Teresa Di Desidero, Bastianina Canu, Paola Orlandi, Anna Fioravanti, Gianluca Masi, Guido Bocci, Alfredo Falcone
Journal: Journal of Clinical Oncology (2013)

e14577 Background: The protracted exposure to low doses of cytotoxics according to metronomic schedules reported encouraging results in the treatment of different malignancies. In a recent trial from our group, the association of a single standard dose of CTX followed by metronomic UFT and CTX with celecoxib showed a very favourable safety profile and promising activity in a cohort of heavily pre-treated patients (pts) with gastrointestinal tumors (Allegrini, 2012). The aim of the present trial was to prospectively evaluate the activity of metronomic cape and CTX in a population of refractory mCRC pts. Methods: Pts with documented diagnosis of CRC, progressed during or within 3 mos from the last administration of standard therapies, were eligible. They received cape 800 mg PO bid and CTX 50 mg PO once daily. Treatment was administered continuously until disease progression. Primary endpoint was 2 mos-progression free rate (2m-PFR). Hypothesizing a 2m-PFR of 10% for refractory mCRC pts with no therapeutic options, metronomic cape plus CTX would have been judged promising for an estimated increase from 10 to 35% in 2m-PFR. According to the Fleming single-stage design, setting α and β errors 0.05 and 0.10, 25 evaluable pts were required. The null hypothesis would have been rejected if at least 6 pts were progression free at 2 mos. Results: Between June 2011 and June 2012, 26 pts were enrolled. Main characteristics were: M/F 19/7; median age: 71 yrs; single/multiple sites of metastases: 2/24, KRAS wt/mut: 18/8, BRAFwt/mut 25/1. 16 (62%) pts had received at least 3 previous lines of chemotherapy. Five pts were progression free at 2 mos, for a 2m-PFR of 19%. At a median follow up of 14.4 mos, median PFS and OS were 2.1 and 6.0 mos. No chemo-related G3/4 adverse events were reported. Conclusions: Metronomic cape and CTX demonstrated low clinical activity in heavily pretreated mCRC. Ongoing pharmacokinetic and dynamic analyses might provide additional data to interpret results and further insights into the antiangiogenic properties of this metronomic combination. Clinical effects of metronomic cape and CTX are under investigation in earlier settings and in association with other antiangiogenic agents.
Measurement of gene amplification in FFPE tumor tissues by quantitative real-time PCR in comparison with FISH
Authors: S. Boyer, J. Yang
Journal: Journal of Clinical Oncology (2007)

14086 Background: Amplified oncogenes such as HER2 and EGFR have proven to be good targets for molecular therapy. Recent retrospective analyses suggest that EGFR amplification predicate better responses to EGFR kinase inhibitors. However, different methods were used to measure EGFR gene amplification and polysomy in these studies, including FISH and various real-time quantitative PCR platforms, which may have led to the different conclusions reported by these groups. In this study, we compared Taqman- QPCR with FISH in scoring EGFR and HER2 amplification and EGFR polysomy on 42 FFPE tumor samples. Methods: DNA was prepared from 42 FFPE tumor tissues of breast, colon, lung, and stomach origin. Taqman QPCR was carried out according to manufacturer’s protocol on an ABI-7900HT instrument. FISH analysis for EGFR and HER2 amplification was carried out according to Vysis standard protocols. Results: QPCR reference probes for measuring EGFR and HER2 amplification were designed against DNA fragments near the centromeric regions of chromosome 7 and chromosome 17, respectively. A QPCR probe for RNase P on chromosome 6 was designed and used as a reference for measuring EGFR polysomy. HER2 amplification was detected in ∼25% FFPE breast tumor samples by both FISH and QPCR methods, although amplification scores were consistently higher by QPCR than by FISH. EGFR amplification was rare in all samples screened but high polysomy (6 copy and above) was detected in 40% FFPE gastric tumor samples. Again there was high concordance between FISH and Taqman QPCR results. Conclusions: Our data showed high concordance between Taqman QPCR and FISH in scoring EGFR and HER2 amplification. Taqman QPCR is a highly sensitive, accurate, convenient, and economical technology for measuring EGFR and HER2 amplification and EGFR polysomy in FFPE tissues. With well validated target and reference primers/probes, Taqman QPCR provides an attractive alternative to FISH for measuring oncogene amplification for retrospective studies on archived FFPE samples and for screening patients for clinical trials. No significant financial relationships to disclose.