tbuckley/cabot-search huggingface dataset:
Califf for the FDA
Authors: Jeffrey M. Drazen
Journal: New England Journal of Medicine (2015)

Robert M. Califf, M.D., has been nominated to be the next head of the Food and Drug Administration (FDA); he currently serves as Deputy Commissioner for the Office of Medical Products and Tobacco. We think his confirmation as commissioner should proceed as quickly as possible. Because the FDA oversees the safety and, in some spheres, the efficacy of products that constitute about 25% of our economy, the country needs a strong and experienced leader who can keep the FDA focused on its mission.Since Califf was nominated to succeed Margaret Hamburg, numerous individuals and groups have endorsed his candidacy.1– . . .
Surgical operating environment procedures should be standardised to improve safety, taskforce recommends
Authors: M. Limb
Journal: BMJ (2014)

A taskforce set up to review surgical “never events” (those that should never happen) in English hospitals has recommended new standards and systems to improve safety.

It said that national standard operating procedures should be developed to avoid variation in surgical practice. It also called for more consistency in surgical safety education and training and the creation of an independent panel that could review …
P64 * QUANTITATIVE MGMT METHYLATION ANALYSIS BY PYROSEQUENCING REVEALS A STRONG CORRELATION BETWEEN 1P/19Q CO-DELETION AND HIGH LEVEL METHYLATION IN HIGH GRADE GLIOMAS
Authors: R. Laxton, L. Doey, M. Aizpurua, I. Bodi, A. King, C. Chandler, R. Bhangoo, R. Beaney, L. Brazil, K. Ashkan, S. Al-Sarraj
Journal: Neuro-Oncology (2014)

INTRODUCTION: Pyrosequencing is a method that allows MGMT methylation to be measured in a quantitative manner. MGMT methylation, along with 1p/19q co-deletion and IDH1 mutation, is an important biomarker in high grade gliomas. MGMT methylation indicates an improved response to temozolomide chemotherapy; patients with 1p/19q co-deleted anaplastic oligodendrogliomas benefit from the addition of chemotherapy to radiotherapy. Aim: To compare the average MGMT promoter methylation level of high grade gliomas and correlate it with other clinical parameters and markers including IDH1&2 mutation and 1p/19q co-deletion. METHOD: For 171 high grade gliomas MGMT methylation analysis was performed by pyrosequencing, mutations to IDH1 and IDH2 genes were also detected by pyrosequencing, or immunohistochemistry (n = 166). Screening for 1p/19q deletion was by fluorescence in situ hybridisation (n = 46). Statistical analysis was performed using R-Stats v2.15.2. RESULTS: The results show that higher methylation was correlated with lower grade and mutation to either IDH1 or IDH2 (27.0% vs. 16.6% p = 0.008; and 27.5 vs. 16.1 p = 0.002 respectively). Interestingly 1p/19q co-deletion versus non co-deletion was associated with a particularly high level of methylation (42.2% vs. 17.7% p = 0.001). No significant differences were seen for age or gender. CONCLUSION: The results offer a potential explanation for the improved prognosis seen in glioma patients with 1p/19q co-deletion and when combined with IDH mutation status may provide an extra control to confirm true 1p/19q co-deletion.
Abstract 1331: Ethnic-specific polymorphisms in CHRNA3 and CHRNA9 genes.
Authors: Anna Chikova, Sergei Grando
Journal: Cancer Research (2013)

Abstract Several recent studies demonstrated significant association of numerous common polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster encoding the α5, α3 and β4 nicotinic acetylcholine receptor (nAChR) subunits with the risk of lung cancer. However, due to high linkage disequilibrium, role of each protein in the tumorigenesis remains unclear. Large number of the single nucleotide polymorphisms (SNPs) including a majority of amino acid substitutions escaped the focus of previous research. Although some ethnic variations in this cluster are known, previous research was focused on the SNPs common for various ethnic groups. Little is currently known about epidemiological role of haplotypes specific for ethnical groups. We have assessed the global frequency distributions of coding and some non-coding nAChR SNPs by direct sequencing of 3 regions of CHRNA3 and 5 regions of CHRNA9 genes in 330 individuals from anthropologically defined human populations. The results revealed statistically significant ethnic-specific differences. In CHRNA3, for 8 SNPs, including one non-synonymous amino acid substitution, and in CHRNA9 for 7, including 2 non-synonymous SNPs. Among these SNPs, some were unique to one or two ethnical groups. For example, Arg110His in CHRNA3 (rs77574318) was seen only in Russians with heterozygosity 0.06. Thus, analysis of any amino acid substitution uniquely present in a particular ethnic group may guide further studies of the role of nAChRs gene polymorphism in various types of cancer Citation Format: Anna Chikova, Sergei Grando. Ethnic-specific polymorphisms in CHRNA3 and CHRNA9 genes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1331. doi:10.1158/1538-7445.AM2013-1331 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
MULTICENTER EVALUATION OF CHARGES, LENGTH OF STAY AND MORTALITY DURING HOSPITALIZATION AFTER PEDIATRIC OPEN-HEART SURGERY ATTRIBUTABLE TO ADVERSE PATIENT-CARE EVENTS
Authors: Shaji C. Menon, Yingying Zhang, L. LuAnn Minich, Tom Greene, Jacob Wilkes, Richard E. Nelson
Journal: Journal of the American College of Cardiology (2015)
A pilot study of safety and efficacy of pandimex with or without paclitaxel in the treatment of advanced solid tumors
Authors: X. Ouyang, Z. Yu, Z. Chen, F. Xie, W. Fang, Y. Peng, X. Chen, W. Chen, W. Wang, P. Qi, W. Jia
Journal: Journal of Clinical Oncology (2005)

3188 Background: PBD2131 (Pandimex) is a preparation of aglycone saponins obtained from ginseng. The main active molecules in PBD2131 are 20(S)protopanaxadiol(aPPD) and 20(S)protopanaxatriol(aPPT). Both have shown strong anti-cancer effects in various cancer models(G.Liu, et al. AACR 2004). Both compounds induce apoptosis through caspase-dependent and -independent pathways and inhibit p-glycoprotein. This study was to investigate the safety and efficacy of PBD2131 used with or without paclitaxel. Methods: Twenty-three patients with advenced solid tumors (lung, gastric, breast, and pancreatic), among whom 9 had distant metastasis, and all failed in previous chemotherapies, were randomized into 3 arms: 1) PBD2131 1000 mg i.v. plus paclitaxel 90 mg/m2 i.v. every 3 weeks for 2 cycles; 2) PBD2131 1000 mg i.v. twice weekly plus paclitaxel 60 mg/m2 i.v. once a week for 2 weeks. Repeat the cycle after a 2-week rest; and 3)PBD2131 1000 mg i.v. alone twice weekly for 4 weeks. Repeat the cycle after a 2-week rest. All patients were pre-treated with dexamethasone, diphenhydramine and cimetidine to reduce hypersensitivity. Blood, liver and kidney functions were tested weekly. Toxicity and adverse events were assessed according NCI Common Toxicity Criteria Manual. Tumor responses as shown in image were assessed according to RECIST. Results: As summarized in the TableI, there were 6 Grade I and 1 Grade II adverse events (AE) observed. Two of the AEs (Grade I) were in the PBD2131 alone arm and 5 were in the PBD2131-paclitaxel combination arms. There were 4 PRs and 13 SDs observed (1 patient was lost to follow-up). Conclusions: PBD2131 used alone or in combination with paclitaxel appears to be clinically active in advanced and metastatic solid tumors. The regimens are well-tolerated at the doses studied. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration British Columbia Cancer Research Centre, Tianbo Biotech
FRI0167 Anti-TNF do not modify the interferon signature in patients with rheumatoid arthritis and lupus (“rhupus”)
Authors: L. Sparsa, C. Sordet, G. Alsaleh, M. Ardizzone, R.M. Javier, J.F. Kleinman, J.E. Gottenberg, J. Sibilia
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We recently reported the clinical efficacy and safety of anti-TNF-alpha in a cohort of 15 rhupus patients with rheumatoid arthris and systemic lupus (“rhupus”). TNF-alpha and type I interferon (IFN) were reported to be crossregulated in a gene expression study of patients with juvenile idiopathic arthritis. Treating with anti-TNF these patients could raise the concern of a potential overexpression of IFN-inducible genes and chemokines, which play a pathogenic role in SLE. <h3>Objectives</h3> To evaluate changes in levels of IFN-inducible genes and chemokines under treatment with anti-TNF for RA associated with SLE. <h3>Methods</h3> Among the 15 patients with RA and SLE, PBMCs and serum were collected before and after anti-TNF initiation (median: 8 months) in 6 patients. Total RNA was extracted from PBMC using the Nucleospin RNA II extraction kit according to the manufacturer’s instructions and reverse transcribed using the First Strand cDNA Synthesis Kit according to the manufacturer’s instructions (In Vitrogen). Real-time quantitative RT-PCR was performed in a total volume of 20 μl using SensiMix Plus SYBR kit (Quantace, Corbett Life Science)and gene specific primers for BAFF, IFTIMMX-1,PKR. Serum CXCL10, CCL2 and CCL19 levels were assessed using R&amp;D ELISA. <h3>Results</h3> All 15 patients were women with a mean age of 51 years [20-75]. The mean duration of treatment was 34.7 and 33.7 (4-69) months with etanercept and adalimumab, respectively. 8.3 infections for 100 patient years occurred. No mycobacteria infection, no lymphoproliferation and no cancer were observed. Also, no cutaneous, renal or other systemic flare of SLE occurred. No death was observed. After 2 years of follow-up, the mean decrease of DAS 28 and SLEDAI was -3 [-0.75 to -4.89] -5.13 [0 – 6], respectively. Corticosteroid dosage significantly decreased from 10mg/d to 5mg/d. No statistical significant increase in gene expressions of 4 different IFN-inducible genes, BAFF (2.2 to 0 fold), MX1 (17.2 to 0 fold), IFITM (1.2 to 0 fold), and PKR (19.3 to 0 fold) Likewise, no significant change was observed in serum levels of 3 IFN-inducibles chemokines: CXCL10 (82 to 56.2 pg/ml, p=0.87), CCL2 (343.8 to 729.4 pg/ml, p=0.375) and CCL19 (316.3 to 335.9 pg/ml, p=0.875). <h3>Conclusions</h3> This study shows good short term tolerance and efficacy of anti-TNF in patients with SLE and RA (“rhupus”). The absence of increase in IFN-inducible genes and chemokines, which are validated prognostic markers of disease activity in SLE, might contribute to the absence of SLE flares observed in rhupus patients treated with anti-TNF. <h3>Disclosure of Interest</h3> None Declared
Endoscopic ultrasound-guided angiotherapy of a large bleeding gastrointestinal stromal tumor
Authors: Vivek Kumbhari, Bilal Gondal, Patrick Okolo III, Anne Lennon, Joanna Law, Vikesh Singh, Payal Saxena, Eun Shin, Marcia Canto, Anthony Kalloo, Mouen Khashab
Journal: Endoscopy (2013)

Bleeding gastrointestinal stromal tumors (GISTs) have historically been managed with either surgical resection or radiologic embolization. Occasional reports exist of endoscopic therapies such as hemoclips [1], endoloop ligation [2], and endoscopic ultrasound (EUS)-guided angiotherapy [3]. We herein present the case of an elderly patient with recurrent bleeding from a large gastric GIST who was successfully treated with EUS-guided angiotherapy.
AB0386 Impact of a smoking cessation awareness campaign on smokers with rheumatoid arthritis in scotland
Authors: H. Harris, F. Tweedie, Y. Skaparis, M. White, N. Scott, K. Samson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Smoking increases the risk of developing rheumatoid arthritis (RA) by 50% and is associated with a reduced response to RA drug treatments<sup>1-6</sup>. <h3>Objectives</h3> 1. Determine the smoking status of RA patients in Fife and their knowledge about RA and smoking before and after an awareness campaign. 2. Launch a public health awareness campaign about the link between RA and smoking. <h3>Methods</h3> 1200 seropositive RA patients in Fife were identified and were contacted informing them of the study. Telephone questionnaires were undertaken with RA patients before and after the RA and smoking cessation awareness campaign. The materials for the campaign were developed by NHS Fife, Gingernut creative, Rudder Finn, Pfizer and the National Rheumatoid Arthritis Society. Approved materials were used for the campaign and also mailed to all RA patients in Fife. <h3>Results</h3> Of the 306 Fife RA patients questionned before the campaign only 5% were aware of a link between RA and smoking. 20% of RA patients were current smokers and 53% were thinking about stopping. 48% of RA patients were ex-smokers and half stated that a major illness had been the motivation to quit smoking. Most had used pharmacotherapy and 63% had quit on their 1st attempt. The “RA and smoking - a joint problem” public awareness campaign was launched in September 2011 and local radio and newspapers as well as social networks and websites reported the story. Over 300,000 media impressions were created. 350 RA patients are being questionned following the campaign and preliminary analysis indicates a change in some patients attitudes including increased smoking cessation. <h3>Conclusions</h3> This study has identified that 1 in 5 RA patients in Fife currently smokes cigarettes and that more than half of RA smokers are thinking about quitting. Patients cite “a health scare” as motivation to quit which suggests that a “Golden Moment” opportunity exists for Rheumatologists to give advice on smoking cessation especially at the time of RA diagnosis. A public health awareness campaign was launched and its impact is currently being assessed. <h3>References</h3> J Rheumatol 1999;26:47–54. Arthritis &amp; Rheumatism 2006;54:38–46. Ann Rheum Dis 2010;69:70-81. Rheumatology 2008;47:849–854. Arthritis &amp; Rheumatism 2011;63:26-36. Journal of Clinical Rheumatology 2010;16:15-18. <h3>Disclosure of Interest</h3> None Declared
Endoscopic ultrasound-guided portal-systemic pressure gradient measurement
Authors: Larissa Fujii-Lau, Michael Leise, Patrick Kamath, Ferga Gleeson, Michael Levy
Journal: Endoscopy (2014)

Portal hypertension is defined by the hepatic venous pressure gradient and is measured via a percutaneous transhepatic route [1]. We describe a novel technique for direct portal pressure measurement using endoscopic ultrasound (EUS).
The Ratio of Waist-to-Hip Circumference, Plasma Insulin Level, and Glucose Intolerance as Independent Predictors of the HDL<sub>2</sub>Cholesterol Level in Older Adults
Authors: Richard E. Ostlund, Myrlene Staten, Wendy M. Kohrt, Joan Schultz, Mary Malley
Journal: New England Journal of Medicine (1990)

High plasma levels of HDL2, a subfraction of high-density lipoprotein (HDL) cholesterol, are associated with a reduced risk of coronary heart disease. To investigate the characteristics related to HDL2 cholesterol levels, we measured lipoprotein levels and several metabolic and anthropometric variables in 146 healthy subjects (77 men and 69 women) in the seventh decade of life.
The Cost Effectiveness of Preoperative Autologous Blood Donations
Authors: Jeff Etchason, Lawrence Petz, Emmett Keeler, Loni Calhoun, Steven Kleinman, Cynthia Snider, Arlene Fink, Robert Brook
Journal: New England Journal of Medicine (1995)

Since the recognition that human immunodeficiency virus is transmissible by blood transfusion there has been increasing public and professional support for autologous blood donations before elective surgery. Autologous blood donation is, however, a more expensive process than the donation of allogeneic blood by community volunteers. Furthermore, there have been recent improvements in the safety of the volunteer blood supply.
CLINICAL EFFICACY OF FORWARD STROKE-VOLUME IN PATIENTS WITH ORGANIC MITRAL REGURGITATION AND NORMAL LEFT VENTRICULAR EJECTION FRACTION
Authors: Ana González-Mansilla, Sara Diaz-Lancha, Virginia Gallo, Candelas Perez Del Villar, Raquel Yotti, Yolanda Benito, Francisco Fernandez-Aviles, Javier Bermejo
Journal: Journal of the American College of Cardiology (2015)
Acute Vestibular Syndrome
Authors: John R. Hotson, Robert W. Baloh
Journal: New England Journal of Medicine (1998)

Rapid, unilateral injury to either peripheral or central vestibular structures produces the acute vestibular syndrome, which consists of severe vertigo, nausea and vomiting, spontaneous nystagmus, and postural instability. When this syndrome evolves over days in a healthy person, it is usually attributed to a viral vestibular neuritis, also called vestibular neuronitis or, when acute hearing loss occurs, neurolabyrinthitis.16 Infarction and hemorrhage of the inferior cerebellum, however, may simulate vestibular neuritis (Figure 1).9,10 As many as 25 percent of patients with risk factors for stroke who present to an emergency medical setting with isolated, severe vertigo, nystagmus, and postural . . .
Predicting Survival in Adenocarcinomas of the Ampulla of Vater: Retrospective Analysis of a Single-Center Experience
Authors: Joaquina Martinez-Galán, Jesús Soberino-García, Cynthia González-Rivas, Julia Ruiz-Vozmediano, Lucia Castillo-Portellano, Verónica Conde-Herrero, Javier García-García, Beatriz González-Astorga, Juan Ramón lgado De Pérez
Journal: Annals of Oncology (2013)
SAT0064 The expression of HDAC6 is reduced in rheumatoid arthritis synovial fibroblasts
Authors: K. Klein, J. Stanczyk Feldges, B.A. Michel, R.E. Gay, S. Gay, C. Ospelt
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Since rheumatoid synovial cells produce large amounts of various cytokines and proteases, up to 30% of all newly synthesized proteins are unfolded, leading to a cellular stress condition. Histone-deacetylase (HDAC) 6, a mainly cytoplasmatic member of class II HDACs, plays a key role in the major response pathways to the cytotoxic accumulation of misfolded proteins, which are aggresome formation, autophagy activation, and heat shock protein accumulation. <h3>Methods</h3> Expression of HDAC6 mRNA was measured in rheumatoid arthritis synovial fibroblasts (RASF, n=8) and osteoarthritis (OA) SF (n=7) by SYBR green Real-time PCR and normalized to expression levels of GAPDH. HDAC6 protein expression in SF (n=6-7), as well as in synovial tissues of RA and OA patients (n=5) was determined by Western blotting. <i>In silico</i> analysis of the 3'untranslated region of HDAC6 was performed using the miRWalk database. Pooled samples of 3 OASF and 3 RASF cultures were screened for differentially expressed micro RNAs (miR) by expression arrays. Expression levels of miR-221 and miR-222 in cultured SF derived from human RA (n=6) and OA (n=12) patients were measured by TaqMan Real-time PCR and normalized to expression levels of RNU6B. SF were transfected with precursor molecules (pre-miR) of miR-221 and miR-222 or control molecules by lipofectamine (n=2). <h3>Results</h3> HDAC6 mRNA expression levels were significantly lower in RASF compared to OASF (RASF: dCt: 14.4±0.4, OASF: dCt: 13.8±0.2; p&lt;0.05). Corresponding results were obtained when HDAC6 protein levels were measured, with a 43% downregulation in SF and a 62% downregulation in synovial tissues from RA compared to OA patients. <i>In silico</i> analysis of the 3'untranslated region predicted that HDAC6 is regulated by miR-221 and miR-222. These miRs were also significantly elevated in RASF compared to OASF in a screen of 260 differentially expressed miRs. Accordingly, the expression levels of miR-221 and miR-222 were higher in RASF compared to OASF (miR-221: RASF dCt: 3.0±0.3, OASF dCt: 4.5±0.3; miR-222: RASF dCt: 6.0±0.5, OASF dCt: 7.9±0.3; p&lt;0.01) and HDAC6 negatively correlated with the expression of miR-221 (Pearson r: 0.78; p=0.01) and miR-222 (Pearson r: 0.67; p&lt;0.05). Furthermore, overexpression of miR-221 and miR-222 by transfection of OASF with pre-miRs decreased HDAC6 levels by 35% ±4.5. <h3>Conclusions</h3> Here we show impaired expression of HDAC6 in SF and synovial tissues of RA patients and identified miR-221 and miR-222 as possible mediators of this deregulated HDAC6 expression. Since HDAC6 is a critical component of the cellular stress response, which has most recently been linked to inflammation, lower levels of HDAC6 in RASF might contribute to the pathological inflammatory response seen in these cells. <h3>Acknowledgements</h3> IAR Epalinges, FP7 Masterswitch, IMI-BT Cure, EMDO-Stiftung <h3>Disclosure of Interest</h3> None Declared
Abstract 5184: Breast cancer cells express glycoprotein and glycolipid ligands for E-selectin
Authors: Venktesh S. Shirure, Monica M. Burdick
Journal: Cancer Research (2010)

Abstract E-selectin, an adhesion molecule expressed by endothelial cells, has been implicated in various cancer metastatic processes. The hypothesis of the present study is that endothelial E-selectin is involved in the adhesion of breast cancer cells under physiological flow conditions. The characterization of E-selectin ligands expressed by BT-20 and MDA-MB-468 human breast cancer cells was performed. E-selectin ligands were broadly classified into glycoprotein and glycolipid ligands. Purified fractions of glycolipids containing sialic acid residues, known as gangliosides, were found to be E-selectin ligands at wall shear stress of 0.80 dynes/cm2. Immunostaining of breast cancer cells for various proteins known for E-selectin activity on non breast cancer cells revealed that P-selectin glycoprotein ligand-1 (PSGL-1), CD-43, podocalyxin like protein (PCLP), carcinoembryonic antigen (CEA) were absent, but CD44 was expressed by both breast cancer cell lines. Dynamic antigen capture assay at wall shear stress of 0.80 dynes/cm2 indicated that CD44 expressed by breast cancer cells is an E-selectin ligand; however, E-selectin ligand activity of CD44 was weak compared to LS-174T colon carcinoma cells. Efforts were then made to characterize novel glycoprotein ligands using immunoprecipitation and western blotting techniques. BT-20 cells showed presence of protein E-selectin ligands. The characterization of glycans decorating protein E-selectin ligands was performed by immunoprecipitation and western blot staining with various carbohydrate antibodies. In summary breast cancer cells express CD44 and novel glycoproteins as well as glycolipids as E-selectin ligands. Further characterization and identification of novel E-selectin ligands can lead to new diagnostic and prognostic approaches. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5184.