tbuckley/cabot-search huggingface dataset:
OP0298-PC How General Practitioners Diagnose Polymyalgia Rheumatica
Authors: T. Helliwell, S. Muller, S. L. Hider, C. D. Mallen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The initial diagnosis of polymyalgia rheumatica (PMR) is often made in primary care. Given the non-specific nature of PMR symptoms, diagnosis can be challenging especially as many disorders can mimic the symptoms of PMR. Although guidelines are available<sup>1</sup>, studies suggest guidelines are rarely followed<sup>2</sup> and that diagnostic accuracy is poor<sup>3</sup>. However, previous studies have relied upon data from retrospective case review or data from referral letters. <h3>Objectives</h3> The aim of this study was to describe how general practitioners (GPs) in the UK, report that they diagnose PMR based on symptoms, investigations and exclusion of other disorders. <h3>Methods</h3> 5000 randomly selected GPs in the UK were mailed a questionnaire on PMR. As part of the survey GPs were asked, in their routine practice, which clinical features were most important in diagnosing PMR and, what investigations they performed. They were also asked, what they would do if the inflammatory markers were normal and which disorders they would routinely try to exclude before making a formal diagnosis of PMR. <h3>Results</h3> 1249 (25.1%) GPs responded. Responders were generally from practices with larger list sizes and more GP principals than non-responders. GPs rated bilateral shoulder pain, raised inflammatory markers and response to corticosteroids as the most important clinical features for diagnosing PMR. Most respondents performed full blood count and ESR or CRP. Other recommended blood tests were performed less frequently (figure 1 ). 25% (n=315) of GPs reported that they would exclude PMR in patients with normal inflammatory markers, whilst 31% (n=392) would refer their patients to secondary care for specialist review. 80% (n=1001) of GPs sought to exclude giant cell arteritis (GCA). 61% (n=759) routinely excluded other rheumatological disorders, but just 55% (n=682) considered excluding relevant malignancies. <h3>Image/graph</h3> <h3>Conclusions</h3> This large GP survey suggests that despite using recommended clinical features to diagnose PMR and seeking to exclude GCA, many GPs do not routinely exclude other diagnoses as a cause of symptoms. This has significant implications for diagnostic accuracy which could result in prolonged, inappropriate treatment with corticosteroids or a missed opportunity for timely more appropriate intervention in disorders such as malignancy or rheumatoid arthritis. Further work is needed to investigate the accuracy of the diagnosis of PMR in primary care. <h3>References</h3> Rheumatology, 49(1), pp. 186-90. Family Practice, 25(5), pp. 328-333. Clinical rheumatology, 19(4), pp. 278-280. <h3>Disclosure of Interest</h3> None Declared
Abstract 1904: B vitamin intake and incidence of colorectal cancer by tumor site and stage: Results from the Women's Health Initiative cohort
Authors: Stefanie Zschäbitz, Ting-Yuan D. Cheng, Marian L. Neuhouser, Yingye Zheng, Roberta M. Ray, Joshua W. Miller, Xiaoling Song, Lynn B. Bailey, David R. Maneval, Shirley AA Beresford, Cornelia M. Ulrich
Journal: Cancer Research (2011)

Abstract Introduction: The role of one-carbon metabolism related nutrients (folate, riboflavin (B2), B6, and B12) in colorectal carcinogenesis is still not fully understood. Folate and other B vitamins are essential for DNA methylation and repair and higher levels have been associated with a decreased risk for colorectal cancer (CRC) in some studies; however, non-linear relationships have been observed. We investigated the dietary intake of one-carbon nutrients and CRC risk in the WHI Observational Study, a large cohort of postmenopausal women. Methods: Dietary intake of folate and other B vitamins was determined via a Food Frequency Questionnaire and supplement inventory in 88,045 healthy women (aged 50 – 79 years, recruited between 1994 – 1998). Multivariate Cox proportional hazards regression models was used to estimate associations between nutrient intake and CRC risk and to evaluate differences in the associations by tumor site and stage. Hazard ratios (HR) for the 4th vs. 1st quartile were estimated. Results: In age-adjusted analyses significantly reduced risks for CRC were observed for the total (supplemental plus dietary) intake of folate (HR=0.82, 95%CI=0.68-0.97), vitamin B12 (HR=0.82, 0.69-0.99), vitamin B6 (HR=0.77, 0.65-0.92), and riboflavin (HR=0.75, 0.63-0.90). After multivariate adjustment (age, BMI, race, prior colonoscopy, smoking, physical activity, postmenopausal HT use) only the total intake of riboflavin (HR=0.80, 0.66-0.96) remained associated with a reduced risk for CRC. For the intake of vitamin B6 a borderline significance was observed (p=0.06, HR=0.85, 0.70-1.02). A site-specific observation was notable for supplemental and total riboflavin intake with a reduced risk for cancer of the distal colon (HRsupp=0.56, 0.33-0.96; HRtotal=0.69, 0.46-1.04) but not in proximal and rectal cancer. In regards to tumor stage, no significant difference was detected for localized and distant disease; the inverse association between the supplemental and total intake of riboflavin and vitamin B6 was limited to regionally spread disease (HRB2;supp=0.66, 0.45-0.96; HRB2;total=0.73, 0.54-0.99; HRB6;supp=0.69, 0.49-0.98; HRB6;total=0.72, 0.53-0.97). Conclusion: Higher riboflavin and vitamin B6 intake was linked to decreased risk for colorectal cancer in a large cohort of postmenopausal women, with some suggestion for stage- and site-specific associations. Our study provides limited support for an association of other B vitamins with CRC risk. (NIH R01 CA120523, N01WH22110) 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 1904. doi:10.1158/1538-7445.AM2011-1904
Microcystic reticular schwannoma of the colon
Authors: J. Kienemund, B. Liegl, F. Siebert, M. Jagoditsch, E. Spuller, C. Langner
Journal: Endoscopy (2010)

Peripheral nerve sheath tumors (PNST) form the third commonest group of mesenchymal tumors within the gastrointestinal tract. They occur with a frequency of approximately 5 %, which compares with 50 % for gastrointestinal stromal tumors (GIST) and 30 % for smooth-muscle neoplasms [1]. In 2008, Liegl et al. described 10 cases of microcystic reticular schwannoma as a distinct variant with predilection for visceral sites [2]. Herein, we present two additional tumors that were detected upon screening colonoscopy in asymptomatic patients.
Abstract 2962: FOXM1 mediates Dox resistance in breast cancer by enhancing DNA repair
Authors: Yun-Yong Park, Sung Yun Jung, Cristian Rodriguez-Aguayo4, Guang Peng, Se-Ra Lee, Sang Bae Kim, Kyounghyun Kim, Sunhee Leem, Shiaw-Yih Lin, Gabriel Lopez-Berestein, Anil K. Sood, Ju-Seog Lee
Journal: Cancer Research (2012)

Abstract Transcription factors (TFs) are direct effectors of altered signaling pathways in cancer. To uncover new TFs that would determine clinical outcomes in breast cancer patients, we systematically analyzed gene expression data from breast cancer patients. Our results revealed that forkhead box protein M1 (FOXM1) is the top-ranked survival-associated TF with triple-negative breast cancer. Surprisingly, silencing FOXM1 expression led breast cancer cells to become more sensitive to doxorubicin (Dox). We found that FOXM1-dependent resistance to Dox is mediated by regulating DNA repair genes. We further demonstrated that NF-κB1 interacts with FOXM1 in the presence of Dox to protect breast cancer cells from DNA damage. Finally, silencing FOXM1 expression in a mouse xenograft model significantly sensitized the cells to Dox. Our systematic approaches identified an unexpected role of FOXM1 in Dox resistance by regulating DNA repair genes and FOXM1 may be a promising therapeutic target for sensitizing breast cancer cells to Dox. 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 2962. doi:1538-7445.AM2012-2962
Science, medicine, and the future: Therapeutic angiogenesis
Authors: T. D Henry
Journal: BMJ (1999)

Therapeutic angiogenesis is the clinical use of growth factors to enhance or promote the development of collateral blood vessels in ischaemic tissue. Progress in understanding the process of angiogenesis, the isolation of angiogenic growth factors, successful preclinical studies, and promising early results in clinical trials have created great excitement about the potential of therapeutic angiogenesis.1 Although many questions remain, therapeutic angiogenesis may be the next major advance in the treatment of ischaemic heart disease.
Abstract 1540: Targeting PI3K/mTOR inhibitor induced survival programs abrogates resistance to cell death in ECM-attached cancer cells
Authors: Taru E. Muranen, Fabiana Morales, Laura Selfors, Devin Worster, John Albeck, Sizhen Gao, Marcin Iwanicki, Gordon Mills, Joan S. Brugge
Journal: Cancer Research (2011)

Abstract Alterations in the PI3-kinase pathway are common in breast, endometrial, and ovarian cancer and are thought to serve as major drivers of proliferation and survival. Multiple compounds targeting PI3-kinase pathway are currently in clinical trials. We have examined the sensitivity of ovarian and breast tumor cell lines to dual PI3K/mTOR inhibitors in 3D tumor spheroid assays. Interestingly, tumor cells in the center of the spheroids that are not attached to matrix are generally highly sensitive to NVP-BEZ235 and undergo apoptosis, whereas those in contact with matrix are highly resistant. In order to understand the basis for the differential sensitivity to NVP-BEZ235 and to identify candidate targets to abrogate this resistance, we performed reverse phase protein array of tumor spheroids treated with NVP-BEZ235. While NVP-BEZ235 inhibited known downstream targets of PI3K/mTOR, there was significant up-regulation of multiple proteins known to regulate cell survival including IGF1R, p-EGFR and several Bcl-2 family members. This response raised the question whether combined inhibition of PI3K/mTOR and any of the induced proteins would sensitize the matrix-attached cells. Interestingly, inhibition of Bcl-2 by ABT737 caused widespread apoptosis in the 3D structures, but only in combination with NVP-BEZ235. In addition, matrix-resistance was abrogated by combined treatment with NVP-BEZ235 and inhibition of EGFR or knockdown IGF1R. These results indicate that inhibition of PI3K/mTOR leads to induction of several protective pathways and that suppression of these pathways can significantly enhance sensitivity to PI3K/mTOR targeted therapies. In addition, these studies suggest a rational approach to the development of combination therapies – that is, through identification of drug-induced survival pathways and targeting these pathways in combination. Our current efforts center on investigating the mechanisms of PI3K/mTOR inhibition resistance and addressing the efficacy of the dual treatment in preclinical models. 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 1540. doi:10.1158/1538-7445.AM2011-1540
EVALUATION OF MYOCARDIAL GLUCOSE METABOLISM IN HYPERTROPHIC CARDIOMYOPATHY BY 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY: IMPACT OF ALCOHOL SEPTAL ABLATION THERAPY
Authors: Rie Aoyama, Hitoshi Takano, Yasuhiro Kobayashi, Mitsunobu Kitamura, Kuniya Asai, Shin-Ichirou Kumita, Wataru Shimizu
Journal: Journal of the American College of Cardiology (2016)
Abstract 3202: Imetelstat inhibits telomerase activities in xenograft tumors and bone marrow cells and inhibits tumor growth in xenograft models at plasma exposures equivalent to current clinical exposures in Phase I trials
Authors: Ning F. Go, Lyssa Villarreal, Preeti Pattamata, Denise Nazzal, Tong Lin, Soo-Peang Khor, Karen Delavan-Boorsma, Robert Tressler
Journal: Cancer Research (2010)

Abstract Telomerase activation is a hallmark of cancer and is critical for dysregulated cell proliferation and cell immortality. Increased telomerase activities were detected in essentially all epithelium derived cancers tested up-to-date and in many hematological malignancies as well, such as multiple myeloma and leukemia. Levels of telomerase activities in the malignant tissues are significantly higher compared to those detected in the normal, regenerating somatic tissues, such as liver and bone marrow cells. Given the differential activation states of telomerase in malignant and normal tissues, telomerase is considered an attractive cancer target by controlling telomere extension and cell immortality. Imetelstat is a first-in-class, lipidated oligonucleotide thio-phosphoramidate telomerase inhibitor. It is a potent and specific telomerase RNA template antagonist, currently in phase I clinical development. Objectives of this study were to demonstrate the in vivo telomerase activity inhibition in xenograft tumors and in bone marrow tissue in animal models, and to correlate the telomerase inhibition effect with mouse plasma drug exposure and xenograft tumor growth inhibition. Our preliminary results showed that treatment with imetelstat at 15-30 mg/kg tiw resulted in plasma concentrations greater than the IC50 for in vitro telomerase inhibition and a plasma exposure level comparable to the tolerable exposure in the clinic. Imetelstat treatment at 15-30 mg/kg tiw for 6 weeks inhibited OVCAR-5 xenograft tumor growth in vivo. Moreover, telomerase inhibition in the xenograft tumors and in the mouse bone marrow was demonstrated. Our results provided evidence of the specific target inhibition by imetelstat treatment in an in vivo system. Our data also suggested a pharmacodynamically efficacious dose level may have been achieved in the clinic. 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 3202.
RIGHT VENTRICLE FUNCTION RECOVERY AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT IN SEVERE AORTIC STENOSIS PATIENTS
Authors: Edward Koifman, Romain Didier, Federico Asch, Zack Jerusalem, Sarkis Kiramijyan, Smita Negi, Zuyue Wang, Steven Goldstein, Ricardo Escarcega Alarcon, Rebecca Torguson, Arie Steinvil, Sang Yeub Lee, Won Yu Kang, Lowell Satler, Itsik Ben-Dor, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2016)
Potential Role for YB-1 in Castration-Resistant Prostate Cancer and Resistance to Enzalutamide Through the Androgen Receptor V7
Authors: Masaki Shiota, Naohiro Fujimoto, Kenjiro Imada, Akira Yokomizo, Momoe Itsumi, Ario Takeuchi, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito
Journal: JNCI Journal of the National Cancer Institute (2016)

Background:Although androgen deprivation therapy for advanced prostate cancer initially exerts excellent anticancer effects, most prostate cancer treated with androgen deprivation therapy eventually recurs as castration-resistant prostate cancer (CRPC). Although aberrant kinase activation has been proposed as a mechanism of castration resistance, comprehensive kinase profiles in CRPC remain unknown. Therefore, we aimed to elucidate the kinome in CRPC as well as the role of key molecules.
P36 Physical activity levels according to gold grouping in patients with COPD
Authors: JI Canavan, SSC Kon, CM Nolan, SE Jones, MI Polkey, WD-C Man
Journal: Thorax (2013)

<h3>Background</h3> The updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recognise the limitations of using grading systems based on spirometry alone. Understanding the impact of COPD on an individual patient should combine symptomatic assessment (using MRC Dyspnoea scale or COPD Assessment Test), spirometric classification and/or risk of exacerbations. GOLD recommends classifying patients into four groups: A (Low Risk, Less Symptoms), B (Low Risk, More Symptoms), C (High Risk, Less Symptoms) and D (High Risk, More Symptoms). Physical inactivity level is an important predictor for hospital admissions and mortality in patients with COPD. The aim of the study was to document objective physical activity parameters according to GOLD grouping. We hypothesised that physical activity levels would be highest in Group A and lowest in Group D. <h3>Methods</h3> 220 patients with COPD (mean age 69 years, 81F:139M, mean FEV1 51%predicted) were classified into GOLD groups A-D. Physical activity (PA) was measured for seven days using an accelerometer (Sensewear®) as previously described (Watz <i>et al</i>., 2009). Physical activity parameters were analysed by researcher blinded to GOLD grouping, and included physical activity level (PAL: Total energy expenditure / resting energy expenditure), step count (steps per day) and time spent in at least moderate activity, defined as greater than 3 METS. Kruskal-Wallis was used to compare physical activity parameters across groups and Dunn’s multiple comparison post-hoc test to compare between individual groups. <h3>Results</h3> Parameters of physical activity according to GOLD group are shown in Figure 1. Although multiple group comparison showed significant differences in physical activity (PAL: p = 0.04, Step Count: p = 0.005, 3METS: p = 0.02), post-hoc tests revealed no significant differences in PAL or 3METS between individual groups. For step count, there was a significant difference in rank sum between groups B and D (p &lt; 0.05), but not between any other individual group comparisons. <h3>Conclusions</h3> There are complex and multifactorial determinants of physical activity levels in patients with COPD which cannot be distinguished by new GOLD grouping.
The Treatment of Arterial Embolism
Authors: Richard Warren, Robert R. Linton
Journal: New England Journal of Medicine (1948)

ALTHOUGH doctors since the time of William Harvey may have had some conception of the pathologic physiology of thrombosis and embolism and although John Hunter,1 in 1794, reported intravascular coagulation occurring during life, it was not until the time of Virchow2 (1845) that arterial embolism was clearly described and until later in the century (1895) that the operation of embolectomy was first attempted by Ssabanejeff3 in Russia. From then until 1911 embolectomy was performed a dozen or more times without success before Labey4 first successfully removed an embolus from the femoral artery. A short time later Key,5 , 6 in Sweden, was . . .
PTH-293 Surveillance after excision of malignant colorectal polyps – is there a need for standardisation?
Authors: M Courtney, L Newton, G Harris, S Mills
Journal: Gut (2015)

<h3>Introduction</h3> Bowel cancer screening has resulted in a greater incidence of early colorectal cancers, or malignant polyps (MPs). Increasingly MPs are being resected endoscopically, hence avoiding the associated risks of major surgery. There remains, however, concern regarding local cancer recurrence and residual loco-regional lymph node disease, along with the future risk of metachronous disease in the remaining bowel. Detection of these adverse outcomes of endoscopic resection suggests a need for regular surveillance, though this has to be contrasted with the risks of unnecessary surveillance; e.g. morbidity, false negatives, and cost. The ACPGBI position statement<sup>1</sup>gives guidance on post-resection colonoscopies, though there is little guidance on other surveillance modalities. This study aimed to review post-MP excision surveillance practice in a single NHS Trust. <h3>Method</h3> All excised MPs were identified from a prospective consecutive database of all colorectal cancers with a date of diagnosis 01/04/10 – 31/03/14 diagnosed in a UK NHS Foundation Trust. Electronic records were reviewed to ascertain the number of endoscopic and radiological tests that patients underwent post-MP excision (excluding initial staging scans). Primary outcomes were tumour recurrence, metastases or detection of metachronous disease. Investigations for reasons other than surveillance (e.g. emergency admission) were excluded. <h3>Results</h3> There were 130 MPs excised over a four year period, 96 of which were excised initially endoscopically (28 underwent further formal resection, in which there were four cases of residual disease: 3 nodal diseases and 1 local disease). Median follow-up was 34 months (range 3–58). A total of 106 surveillance CT scans were performed and eight surveillance MRI scans (range 0 to 5 CTs, and 0–3 MRIs per patient). 194 surveillance endoscopies were performed (98 colonoscopies, 96 flexible sigmoidoscopies), ranging from zero to seven per patient. There was no association with duration of follow-up for either scans or endoscopies, though on average, surgically managed patients had more surveillance scans, whereas those managed endoscopically had more surveillance endoscopies. In total there were no recurrences, 1 case of metastases and 2 detected metachronous tumours. <h3>Conclusion</h3> Surveillance of patients following MP excision remains controversial; this experience highlights a wide variation in practice, and low yield from surveillance tests. Although each case should be managed individually according to a local multi-disciplinary team, there appears to be a requirement for a larger evidence base and subsequent guidance on optimal surveillance for these patients. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Williams JG, <i>et al</i>. Management of the malignant colorectal polyp: ACPGBI position statement. <i>Colorectal Dis.</i>2013;15(Suppl 2):1–38