tbuckley/cabot-search huggingface dataset:
Abstract 3960: Rapid and efficient large-scale somatic mutation validation approaches for cancer genome sequencing
Authors: Kristian Cibulskis, Andrey Sivachenko, Peter Hammerman, Ivan Imaz, Trevor Pugh, Carrie Sougnez, Wendy Winckler, Stacey Gabriel, Gaddy Getz
Journal: Cancer Research (2012)

Abstract The landscape of somatic alterations in cancer is being rapidly uncovered by large-scale cancer genome sequencing projects in individual laboratories as well as consortia such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). The decreasing cost of sequencing has resulted in an increase in the number of cancer genomes that are being sequenced, and thus the numbers of candidate somatic mutations being identified are rapidly expanding. A single cancer genome from a cancer with an average mutation background rate, such as ovarian or breast cancer, will have 3000-6000 mutations. A high mutation rate cancer such as melanoma or colon cancer can have as many as 100,000 mutations/genome. Multiplying these numbers by the dozens of sequenced genomes and hundreds of sequenced exomes across a wide spectrum of tumor types yields a staggering number of candidate mutations. However, approaches for rapidly validating these findings at scale have been lagging behind. Current approaches, such as custom designed hybrid capture arrays followed by sequencing, can take months to complete and cannot begin until the initial sequencing is complete and mutations are called. This can lead to long delays in the interpretation and publication of biological findings. Here we describe the results of several approaches for rapid and efficient validation on large-scale projects, such as TCGA. We will share our approach and results using Fluidigm and PacBio sequencing for validation and sample extension at a small scale with rapid turnaround where we have validated PIK3CA and TP53 mutations in breast cancer samples of varying purity as well as significantly mutated genes in medulloblastoma. Ideally one could validate mutations and gene fusions concurrent with their discovery. To that end, we will also describe our validation results using RNA-Seq data, commonly produced concurrently with genome and exome sequencing, in lung squamous and renal cancer. Finally, we will explore an approach for instant-validation through simultaneous sequencing of barcoded discovery and cross-validation libraries. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3960. doi:1538-7445.AM2012-3960
The rediscovery of endoscopic ultrasound (EUS) in gastric cancer staging
Authors: G. Caletti, P. Fusaroli
Journal: Endoscopy (2012)

Although its incidence varies greatly between Eastern and Western countries, gastric carcinoma still represents the second leading cause of cancer deaths worldwide [1]. Although modern surgical techniques allow high curative resection rates, long-term survival outcomes are still very disappointing [2]. For this reason, neoadjuvant radiochemotherapy regimens are increasingly adopted in attempts to improve the survival of patients with advanced gastric cancer [3]. To identify which patients should be allocated to preoperative treatments, reliable and accurate staging techniques are crucial.
Preservation of the Pyloric Ring Confers Little Benefit in Patients Undergoing Total Pancreatectomy
Authors: Hideki Takami, Tsutomu Fujii, Mitsuro Kanda, Masaya Suenaga, Kazuo Yamamura, Yoshikuni Inokawa, Suguru Yamada, Chie Tanaka, Daisuke Kobayashi, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Yasuhiro Kodera
Journal: Annals of Oncology (2013)
Biliary tumor thrombus of hepatocellular carcinoma containing lipiodol mimicking a calcified bile duct stone
Authors: T. Sasaki, N. Takahara, Y. Kawaguchi, H. Takao, K. Matsusaka, K. Miyabayashi, N. Yamamoto, K. Hirano, H. Isayama, J. Kaneko, N. Kokudo, K. Kazuhiko
Journal: Endoscopy (2012)

Corrected by: Biliary tumor thrombus of hepatocellular carcinoma containing lipiodol mimicking a calcified bile duct stoneEndoscopy 2012; 44(S 02): E255-E255DOI: 10.1055/s-0032-1310049
THU0307 Validation of JADAS in international league against rheumatism (ILAR) subtypes of juvenile idiopathic arthritis (JIA):
Authors: F. Mcerlane, M.W. Beresford, E.M. Baildam, S.E. Chieng, J. Davidson, H.E. Foster, J. Gardner-Medwin, M. Lunt, L.R. Wedderburn, K.L. Hyrich, W. Thomson
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global assessment (PGA), parent/child global evaluation (PGE) and ESR). Much of the original validation data were derived from clinical trials (predominance of polyarticular course disease). The validity of JADAS for all ILAR subtypes of JIA in the routine clinical setting is unknown. <h3>Objectives</h3> To investigate the construct validity of JADAS in all ILAR JIA subtypes in a prospective inception cohort of UK children with new onset inflammatory arthritis at the time of initial presentation. <h3>Methods</h3> JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all ILAR subtypes of JIA (Spearman's rank statistic). <h3>Results</h3> 354/1041 (34%) children had all 4 variables available at baseline. 994/1041 (95%) had AJC available, 811 (78%) PGA, 694 (67%) PGE and 647 (62%) ESR. Median age at disease onset was 6.8 years (IQR 2.8-10.8), median disease duration at diagnosis was 5.2 mths (IQR 2.5-10.9) and 64% were female. Correlation for the whole cohort between JADAS 71 and both JADAS 27 and 10 was 0.99, approaching 1 for all ILAR subtypes. There was a significant difference in median JADAS scores between subtypes (p&lt;0.01) with the lowest in oligo-articular JIA and highest in systemic and polyarticular JIA. Correlation of JADAS71 with single markers of DA ranged from 0.48-0.75 for the whole cohort (see Table 1). Within the individual subtypes, the strongest correlation was with AJC (range 0.71-0.94). Correlation with PGA and PGE was moderate (range 0.29-0.75) and correlation with the ESR was strongest for undifferentiated and systemic JIA (0.76 and 0.59) but low to moderate for all other subtypes of JIA (range 0.2-0.41). <h3>Conclusions</h3> JADAS71 correlated well with AJC, PGE and PGA but did not correlate well with the ESR in all ILAR subtypes. Correlation of JADAS71 with measures of disease severity is moderate, with some variation between subtypes. The ESR is not routinely measured in all children with JIA in the UK, as illustrated by its availability in just 62% of this cohort at baseline. Given the high frequency of unmeasured ESR assessments, we suggest further work is required to assess the validity of JADAS without inclusion of the ESR. <h3>Disclosure of Interest</h3> None Declared
S104 The culture microbiome in the lungs of patients with COPD
Authors: G. G. Einarsson, D. Comer, M. M. Tunney, J. S. Elborn
Journal: Thorax (2011)

<h3>Introduction and Aims</h3> Previous studies have shown that the lungs of Cystic Fibrosis (CF) and bronchiectasis (BE, not caused by CF) patients are colonised by a range of aerobic and anaerobic bacteria. As bacteria are also implicated in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD), this study aimed to determine the culture microbiome of the COPD airways. <h3>Methods</h3> Samples were collected from 13 stable COPD patients during routine bronchoscopy. Bronchial washings were taken at a single location in the right middle lobe by flushing and removing 30 ml of sterile saline. Samples were cultured under strict anaerobic conditions with bacteria detected by plating on both selective and non-selective agar media and quantified by total viable count (TVC). Identification of the cultured bacteria was performed by amplification and subsequent sequencing of the 16sRNA gene. <h3>Results</h3> Mean FEV<sub>1</sub> was 1.36 (range 0.84–2.26, mean per cent predicted FEV<sub>1</sub>, 54%), and the mean ratio (FEV<sub>1</sub>/FVC) was 51%. Bacteria were detected in 12/13 samples (92%) with bacteria from the genera <i>Streptococcus</i> [12/13 samples, 92%; mean (range) TVC 9.62×10<sup>5</sup> cfu/ml (1.50×10<sup>3</sup>–1.42×10<sup>7</sup>)] and <i>Haemophilus</i> [4/13 samples, 31%; mean (range) 6.40×10<sup>4</sup> cfu/ml (2.20×10<sup>3</sup>–1.60×10<sup>5</sup>)] most frequently detected. Anaerobic bacteria primarily from the genera <i>Prevotella</i> [8/13 samples, 62%; mean (range) TVC 1.12×10<sup>4</sup> cfu/ml (1.30×10<sup>3</sup>–4.20×10<sup>4</sup>)] and <i>Veillonella</i> [5/13 samples, 38%; mean (range) TVC 1.29×10<sup>5</sup> cfu/ml (4.20×10<sup>3</sup>–3.60×10<sup>5</sup>)] were also detected. <i>Pseudomonas</i> and <i>Moraxella</i> were not detected in any samples. <h3>Conclusions</h3> Our results show that bacteria from the genera <i>Streptococcus, Haemophilus, Prevotella and Veillonella</i> are frequently present the airways of patients suffering from COPD. Taking account of the dilutional effect of the bronchial wash procedure and extrapolating to allow comparison with sputum data in our laboratory for CF and BE, the relative load of bacteria from the genera <i>Streptococcus</i>, <i>Prevotella</i> and <i>Veillonella</i> is similar in these three airway diseases. The potential role of these bacteria in the progression and pathogenesis of COPD requires further investigation.
Functional Aortic Root Parameters and Expression of Aortopathy in Bicuspid Versus Tricuspid Aortic Valve Stenosis
Authors: Evaldas Girdauskas, Mina Rouman, Kushtrim Disha, Beatrix Fey, Georg Dubslaff, Bernhard Theis, Iver Petersen, Matthias Gutberlet, Michael A. Borger, Thomas Kuntze
Journal: Journal of the American College of Cardiology (2016)
Acute Pulmonary Embolism Detected by Perfusion SPECT/CT Masquerading as an Intermediate Probability Planar V/Q Scan
Authors: Yang Lu, Josef J. Fox
Journal: Clinical Nuclear Medicine (2010)

A 51-year-old man with renal cell carcinoma, renal insufficiency, and a remote pulmonary embolism (PE) was referred for a ventilation-perfusion (V/Q) scan because of dyspnea and chest pain one day after left partial nephrectomy. Planar V/Q scan revealed an intermediate probability for PE. As the pretest probability for PE was high, a perfusion SPECT/CT was obtained, which clearly demonstrated a large segmental perfusion defect on a background of clear lung parenchyma, consistent with the presence of PE. Follow-up planar V/Q scan after 1 month of anticoagulation therapy was normal.
Food-Dependent Cushing's Syndrome Mediated by Aberrant Adrenal Sensitivity to Gastric Inhibitory Polypeptide
Authors: Yves Reznik, Veronique Allali-Zerah, Jean A. Chayvialle, Robert Leroyer, Pierre Leymarie, Georges Travert, Marie-Christine Lebrethon, Ilse Budi, Anne-Marie Balliere, Jacques Mahoudeau
Journal: New England Journal of Medicine (1992)

Some patients with Cushing's syndrome have nodular adrenal hyperplasia. In most the disease is corticotropin-dependent, but in others it is corticotropin-independent. The cause of the adrenal hyperplasia in the latter patients is not known.
Characteristics of Non-Small Cell Lung Cancer with Rare Epidermal Growth Factor Receptor Gene Mutations
Authors: Y. Namba, Y. Nakazawa, M. Niinaka, Y. Yano, T. Yoneda, H. Kimura, M. Mori, T. Okada, T. Yamaguchi, S. Yokota
Journal: Annals of Oncology (2013)
P390 IMPACT IN DAILY PRACTICE OF THE CONCEPT OF TREATMENT RESPONSE IN PRIMARY BILIARY CIRRHOSIS. A NATIONAL COHORT STUDY
Authors: M. Leeman, W.J. Lammers, C.Y. Ponsioen, K. Boonstra, K.J. van Erpecum, F.H.J. Wolfhagen, J.P. Kuyvenhoven, J.M. Vrolijk, J.P.H. Drenth, E.M. Witteman, C.M.J. van Nieuwkerk, B.W. van der Spek, B.J.M. Witteman, G.W. Erkelens, M.A.M.T. Verhagen, S.A.C. van Tuyl, A.C. Poen, J.T. Brouwer, F. ter Borg, G.H. Koek, T.J.M. van Ditzhuijsen, B.E. Hansen, H.R. van Buuren
Journal: Journal of Hepatology (2014)
Abstract LB-163: Immunotherapy utilizing MUC-1-messangerRNA encoding DC and MUC-1 specific CTL in combination with Gemcitabine targeting unresectable or recurrent pancreatic cancer
Authors: Kiyoshi Yoshimura, Yoshinari Maeda, Yoshitaro Shindo, Yusaku Watanabe, Shigefumi Yoshino, Shoichi Hazama, Masaaki Oka
Journal: Cancer Research (2011)

Abstract Background; Mucin1 (MUC1) is known as a mucin core protein expressing in inv asive ductal carcinomas of the pancreas. MUC1-specific cytotoxic T lymphocyt es (CTLs) recognize MUC1 moleculesin a HLA-unrestricted manner. We have prev iously reported that the adoptive immunotherapy (AIT) utilizing MUC1-CTLs stimulated with a MUC1-expressing human pancreatic cancer cell line, named Y PK-1, was useful and safe. We also reported the development of an AIT of MUC 1-CTLs in combination with dendritic cells (DCs) pulsed with MUC1-peptide as well. Here we report that the therapy using DC encoding MUC1-mRNA and MUC1-CTLs targeting unresectable or recurrent pancreatic cancer is safe and effective. Purpose; We assessed whether this immunotherapy is safe and effective. Objective and Methods; Twenty patients with unresectable or recurrent pancreatic cancer had the therapy what we planned, one week later, peripheral blood mononuclear cells (PBMC) were harvested by leukapheresis. The PBMCs were separated and induced to be DCs and CTLs. Matured DCs received MUC-1-mRNA by electroporation, then administrated via subcutaneously. CTLs were co-cultured with YPK-1 pancreatic cancer cell line expressing MUC-1 under the stimulation with IL-2, then administrated via intravenously. Results; Male/Female ratio was 1 to 1 (10/10), Mean age was 60.6 y.o. (37–78), Mean times of administration of cells was 3.35 (1.5–27.9), Mean number of c ells that were administrated was 46 million (DCs) and 1800 million (CTLs), Median observation period was 16.2 months (1.5–27.9). One-year survival rate was 39% (median survival time, 6.9 months). When we focus on the patients with unresectable cancer, their one-year survival rate was 54% (median surviva 1 time, 18.4 months). In addition, patients received DCs of more than 10 million had 58% of one-year survival rate, whereas no patient received less than 10 million's DCs did survive in one year (median survival time, 5.8 months) (p=0.048, Logrank). All of patients received the therapy as outpatients and showed no side effect. Conclusion; First of all, this therapy is quit safe. Second, patients received DCs of more than 10 million had high one-year survival rate suggesting high volume DCs in this combination therapy had high potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-163. doi:10.1158/1538-7445.AM2011-LB-163
Computed tomography-guided endoscopic recanalization of a completely obstructed rectal anastomosis
Authors: Andreas Probst, Stefan Gölder, Egbert Knöpfle, Lukas Axt, Helmut Messmann
Journal: Endoscopy (2015)

A 44-year-old man presented with complete obstruction of a colorectal anastomosis. He had undergone laparoscopic resection of the sigmoid colon 9 months previously for colonic perforation caused by endoscopic resection of a Peutz–Jeghers polyp. Surgical resection and reconstruction of the anastomosis, including diverging ileostomy, had been performed 6 months later because of anastomotic stricture and leakage. Closure of the ileostomy had been planned for 3 months later but high-pressure fluoroscopy showed no passage of contrast medium through the anastomosis and endoscopy confirmed complete obstruction with the former lumen being unidentifiable ([Fig. 1]). The anastomosis could not be reached endoscopically through the ileostomy because of peritoneal adhesions.
DERIVATION AND VALIDATION OF A SIMPLE DIASTOLIC FUNCTION PARAMETER FOR THE PREDICTION OF LEFT ATRIAL APPENDAGE THROMBUS IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION
Authors: Mita Patel, Marwan Wassouf, Enrique Garcia-Sayan, Rojina Pant, Giv Bateni Heidari, Saurabh Shah, Oliver D’Silva, Richard Kehoe, Rami Doukky
Journal: Journal of the American College of Cardiology (2016)
A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery
Authors: Patrick Meybohm, Berthold Bein, Oana Brosteanu, Jochen Cremer, Matthias Gruenewald, Christian Stoppe, Mark Coburn, Gereon Schaelte, Andreas Böning, Bernd Niemann, Jan Roesner, Frank Kletzin, Ulrich Strouhal, Christian Reyher, Rita Laufenberg-Feldmann, Marion Ferner, Ivo F. Brandes, Martin Bauer, Sebastian N. Stehr, Andreas Kortgen, Maria Wittmann, Georg Baumgarten, Tanja Meyer-Treschan, Peter Kienbaum, Matthias Heringlake, Julika Schön, Michael Sander, Sascha Treskatsch, Thorsten Smul, Ewa Wolwender, Thomas Schilling, Georg Fuernau, Dirk Hasenclever, Kai Zacharowski
Journal: New England Journal of Medicine (2015)

Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains.We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90.A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed.Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).
TCT-626 Impact of Periprocedural Myocardial Infarction on In-Hospital and 2-Year Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention with Drug-Eluting Stents
Authors: Seung-Woon Rha, Byoung Geol Choi, Sang-Ho Park, A-Ra Cho, Hyeok-Gyu Lee, Won-Yong Shin, Seung Jin Lee, Dong-Kyu Jin, Se Yeon Choi, Amro Elnagar, Sung Il Im, Sun Won Kim, Jin Oh Na, Seong Woo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2012)
SAT0466 Bisphosphonate Drug Holiday: Results from the ESTRATOS Survey
Authors: E. Casado, J. Malouf, E. Salas, M. Caamaño, S. Castañeda, J.M. Sánchez-Bursόn, G. Herrero-Beaumont
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Long-term treatment with bisphosphonates (BP) has been associated with atypical femoral fractures and other complications, so some experts recommend a temporary discontinuation of these drugs in patients with osteoporosis who are receiving them for several years. However, scientific evidence is scarce and scientific societies have not established some detailed recommendations. <h3>Objectives</h3> To evaluate the opinion of bone specialists regarding the concept "BP drug holiday" and to ascertain their routine clinical practice. <h3>Methods</h3> The ESTRATOS (from Spanish: Treatment Strategy in Osteoporosis) is a 19-item survey regarding the concept "BP drug holiday" and decision-making criteria in clinical practice, addressing members of the Spanish Bone Mineral Metabolism and Research Society (SEIOMM). SPSS v.13.00 software (Chicago, IL) was used for data analysis. Categorical variables were expressed as absolute and relative frequencies; and continuous variables as mean and standard deviation or, as median and range. <h3>Results</h3> We collected 146 completed surveys from bone specialists (62% Rheumatologists, and the remaining 58% from Internal Medicine, General Practitioners, Orthopaedic Surgeons and others). About 88% of the participants had good knowledge of the concept "BP drug holiday", and only 3% stated this should never or exceptionally be considered. More than half (57%) of the participants usually take a time off BP after several years of treatment because of the sustained efficacy of BP after withdrawal, while 40% of them due to the risk of long-term complications, especially atypical femoral fractures. DXA and spine X-ray are the most used tools to make a decision of BP discontinuation, and 1 out of 3 participants believe both are necessary. According to 55% of the participants, BP drug holiday should be considered after 5 to 10 years of treatment, although 35% thought it should be considered after 3-5 years. 99% of the participants have already recommended drug holiday to some of their patients, and 90% consider that it should last 2 or more years, regardless of the type of BP. The main indicators for reintroducing treatment are the occurrence of a new fragility fracture or a significant decrease in BMD. <h3>Conclusions</h3> According to our survey bone specialists withdraw temporarily the treatment with BP (drug holiday) in their osteoporotic patients after 3 to 10 years of treatment. Nevertheless, for them it is important to monitor BMD and the incidence of new fragility fractures during the untreated period. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4749