tbuckley/cabot-search huggingface dataset:
PWE-167 Effect Of Linaclotide On Ibs-qol Sexual Subscale Scores In Patients With Irritable Bowel Syndrome With Constipation: Results From 2 Phase 3 Trials: Abstract PWE-167 Table 1
Authors: M Currie, S Shiff, X Hao, R Carson, M Baird, J Johnston
Journal: Gut (2014)

<h3>Introduction</h3> Linaclotide is a minimally absorbed guanylate cyclase-C agonist approved for treatment of IBS with constipation (IBS-C). IBS often results in diminished quality of life (QOL), including decreased sexual desire and activity. This post-hoc analysis aimed to determine if linaclotide treatment improved IBS-QOL sexual subscale scores in IBS-C patients, compared to placebo. <h3>Methods</h3> Data from 2 randomised, double-blind Phase 3 linaclotide trials in IBS-C were pooled. The IBS-QOL was administered at baseline and Week 12. The sexual subscale includes items on difficulty with sexual activity and reduced sexual desire, both rated on a 5-point scale (1=not at all, 2=slightly, 3=moderately, 4=quite a bit, 5=extremely/a great deal); the sum of both items is scaled to 0 (worst) to 100 (best). Changes in the scores from baseline to Week 12 were compared for linaclotide- vs placebo-treated patients in the intent-to-treat (ITT) population and the Impaired Sexuality (IS) subgroup (baseline sexual subscale scores ≤50). <h3>Results</h3> Of 1598 ITT patients with baseline sexual subscale scores, 522 (33%) had a score ≤50 indicating significant impact of IBS on sexual desire and activity (females: 484/1439 [34%]; males: 38/159 [24%]). At Week 12, linaclotide significantly improved change-from-baseline sexual subscale scores vs placebo in the ITT population and IS subgroup (Table, p &lt; 0.001 for both). Although baseline scores for males were higher (better) than for females, improvement vs placebo for males was similar to females in the ITT population and greater for the IS subgroup. However, the male sample size was too small to establish statistical significance. <h3>Conclusion</h3> Linaclotide treatment significantly improves IBS-QOL sexual subscale scores in IBS-C patients compared with placebo, in both the total population and in patients with impaired sexuality at baseline. Study funded by Forest Laboratories, Inc., and Ironwood Pharmaceuticals, Inc. <h3>Disclosure of Interest</h3> M. Currie Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, S. Shiff Shareholder of: Forest Research Institute, Employee of: Forest Research Institute, X. Hao Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, R. Carson Shareholder of: Forest Research Institute, Employee of: Forest Research Institute, M. Baird Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, J. Johnston Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals.
Research assessment – still opera in theatres
Authors: Arthur R Jones
Journal: Journal of the Royal Society of Medicine (2011)

Research assessments, reviewed recently in this journal,1 are now the key to unlock funds for research, an unsettling development for medical schools2 and perhaps one which will encourage discrimination against personal and applied research. The impetus for this change was the rapid rise of regional economies around some universities which awarded research degrees, sparking the tenet repeated recently from Downing Street:3 ‘excellent research leads to economic growth’, a slogan which may be a hostage to fortune rather than a universal truth. Nevertheless, medical schools hoping to get government (HEFCE) funding to create knowledge will only do so after achieving research which excels according to bibliometric scores, probably not an easy task as none of the definitive discoveries of modern medicine listed by Levanue4 appeared between the covers of Nature. But despite criticism and the availability of other scoring methods the trend is to use a simple metric to arrange organizations with multiple qualities into international league tables, and there seems little prospect of medical schools escaping bibliometric evaluation. The outcome of this selective policy may be a split of education between research and non-research universities, and within the research universities failure to support departments unable or unwilling to score highly. Unless researchers outside the magic circle of publishers can remedy their situation there will be no way to adjust the present bias of English research away from physical and applied sciences, such as surgery, a discipline averse from iconoclasm and without high-impact journals, yet providing one-quarter of procedures in the UK while receiving a tiny fraction of research funding.5 Its research has been likened to comic opera, but its lack of support is no laughing matter.
AB0337 Blood b cell counts as predictor of early clinical response after rituximab in patients with rheumatoid arthritis
Authors: Y. J. Kim, B. S. Koo, M.-W. So, W. J. Seo, Y.-G. Kim, C.-K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> B cell depletion with rituximab is effective for reducing the symptoms and inhibiting the progression of joint damage in patients with rheumatoid arthritis (RA). However, the use of peripheral B cell counts as a predictive factor of clinical response is limited. <h3>Objectives</h3> We aimed to investigate the potential value of measurement of peripheral blood B cell counts after rituximab therapy in patients with active RA refractory to anti-tumor necrosis factor inhibitors. <h3>Methods</h3> A total of twenty-seven RA patients whom received more than 1 cycle (two 1-gram infusion) of rituximab were included in this study. Absolute B cell counts on day 1 and 15 before each rituximab infusion was measured by conventional flow cytometry. On day 15, peripheral B cell levels below 2.5 X 10<sup>6</sup> cells/liter was defined as B cell depletion and the clinical response was analyzed between the 2 groups; depletion vs. non-depletion. Clinical response at 18 weeks after 1<sup>st</sup> infusion of rituximab was measured by Disease Activity Score in 28 joints (DAS28) using the erythrocyte sedimentation rate. The analysis of B cell depletion with regard to DAS28 and continuous variables were performed using Mann-Whitney test. <h3>Results</h3> The mean age at rituximab treatment was 55 ± 13.8 (25-83) years and the baseline DAS28 was 6.6 ± 0.9 (4.4-8.1). The positive rate of RF and ACPA was 90% (27/30) and 72.2% (13/18), respectively. B cells on day 15 was depleted in 17 (56.7%) patients with median value of B cell counts as 1.2 X 10<sup>6</sup> cells/liter [range 0.0∼2.5 X 10<sup>6</sup>/liter]). Patients in whom B cell depletion was not achieved showed persistently high DAS28 (4.7 ± 0.6 versus 3.3 ± 1.0 [<i>p</i> = 0.007]) by 18 weeks and significant short duration of B cell depletion time (4.0 ± 2.3 versus 8.2 ± 4.3, months [<i>p</i> = 0.008]) than those in depletions. <h3>Conclusions</h3> Data derived from B cell depletion with rituximab in active RA patients suggest that measurement of peripheral B cell counts on 15<sup>th</sup> day might provide clinical information on early response and non-depletion of B cells can be used as a predictive factor of poor response. <h3>References</h3> Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. NEJM (2004) 350(25). 2572-81 <h3>Disclosure of Interest</h3> None Declared
Abstract 139: Alcohol and breast cancer subtypes in a Spanish cohort.
Authors: Manuela Gago-Dominguez, Carmen M. Redondo, Manuel Enguix, Maite Peña Fernandez, Maria Elena Martinez, Victor Munoz, Angel Carracedo, Francisco Gude, Jose Esteban Castelao
Journal: Cancer Research (2013)

Abstract Background Although alcohol intake is an established risk factor for overall breast cancer, few studies have looked at the relationship between alcohol use and breast cancer risk by subtype of breast cancer. Materials and Methods A population-based study was conducted in Galicia, Spain. A total of 1211 Spanish women diagnosed with operable invasive breast cancer between 1997 and 2010 and 550 controls participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics were collected. The four major breast cancer subtypes [hormone-receptor-positive, HER2-negative (luminal A); hormone-receptor-positive, HER2-positive (luminal B); hormone-receptor-negative, HER2-negative (triple-negative); and hormone-receptor-negative, HER2-positive (HER2 over-expressing)] were compared on their clinico-pathological characteristics and risk factor profiles, particularly alcohol intake and reproductive variables. Results With the exception of Her2 overexpressing, the risk of all subtypes of breast cancer increased with increasing alcohol intake (luminal A: OR=2.32, 95%CI:1.43-3.77; luminal B: OR=2.03, 95%CI 1.01-4.06, and triple negative: OR=2.36, 95%CI 1.11-5.00). The association of alcohol with breast cancer was similar among women who drank wine exclusively and other drinkers. The alcohol-breast cancer association appeared to be more pronounced among lobular breast cancers (OR= 2.70, 95% CI:1.33-5.52) than among ductal type breast cancers (OR= 2.09, 95%CI:1.33-3-01). It has been suggested that the association of alcohol intake with breast cancer may be stronger in women who are current or past users of hormone replacement therapy compared with never users, or among non-ovariectomized compared to ovariectomized women, we found no such differences. Conclusions To our knowledge, no prior study has examined the association of breast cancer with alcohol intake according to breast cancer subtypes and the type of wine consumed in Spanish women. Our findings indicate that breast cancer risk increased with increasing alcohol intakes for three out of the four major subtypes of breast cancer and that the risk was similar in women who drank wine, beer and/or liquor exclusively or in mixture. Citation Format: Manuela Gago-Dominguez, Carmen M. Redondo, Manuel Enguix, Maite Peña Fernandez, Maria Elena Martinez, Victor Munoz, Angel Carracedo, Francisco Gude, Jose Esteban Castelao. Alcohol and breast cancer subtypes in a Spanish cohort. [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 139. doi:10.1158/1538-7445.AM2013-139
SP0049 Mindfulness Training to Support Well Being of People with Rheumatic and Musculoskeletal Diseases (RMDs)
Authors: H. A. Zangi
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Over the past decade there has been an increasing interest in mindfulness training as an adjunct to medical treatment. Practicing mindfulness has demonstrated potential to alleviate emotional distress and promote well being in people with various chronic conditions. Mindfulness is adapted from ancient Buddhist traditions and has been defined in a Western secular context as "the awareness that emerges through paying attention in a particular way: on purpose, in the present moment and non-judgementally, to the unfolding experience moment to moment" (Kabat-Zinn 1996). An attitude of openness, curiosity and acceptance towards emotions, thoughts and bodily sensations as they are experienced in the present moment is essential. The purpose is to strengthen people's capacity to sustain mindful awareness. The most frequently applied training program is mindfulness-based stress reduction (MBSR), which was originally developed for people with chronic pain and has later been applied to people with a wide variety of chronic diseases, including rheumatoid arthritis and fibromyalgia. MBSR comprises 8 - 10 group sessions, lasting for 2.5 - 3 hours, for up to 30 participants. The basic methods used are different awareness exercises with the breath as an anchor, body scan, mindful movement through yoga exercises and awareness in daily activities. Additionally, group participants discuss their experiences. Training of mindfulness is also an important component of other programs, such as acceptance and commitment therapy (ACT) and the Norwegian vitality training program (VTP), which have been applied to people with chronic pain conditions and inflammatory arthritis, respectively. People with RMDs have increased risk of developing emotional distress, anxiety and depressed mood. Mindfulness training may therefore be a valuable adjunct to medical treatment for these patients. Although the evidence is still limited, mindfulness training has demonstrated improvements in distress, mood states, fatigue, self-efficacy and overall well being in people with fibromyalgia and inflammatory arthritis. The effects on pain are less conclusive. Further high quality studies in people with RMDs are needed. <h3>Disclosure of Interest</h3> None Declared
Afferent Loop Syndrome
Authors: ASHOK MUTHUKRISHNAN, NYLLA SHANTHLY, SHYAM KUMAR
Journal: Clinical Nuclear Medicine (2000)

MUTHUKRISHNAN, ASHOK M.B.B.S.; SHANTHLY, NYLLA M.B.B.S., D.R.M.; KUMAR, SHYAM M.B.B.S., D.M.R.D., D.N.B. Author Information
IMPACT OF AGE ON OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION IN CHRONIC TOTAL OCCLUSIONS: INSIGHTS FROM A MULTICENTER US REGISTRY
Authors: Rahel Iwnetu, Aris Karatasakis, Barbara Danek, Dimitrios Karmpaliotis, Khaldoon Alaswad, Farouc Jaffer, Robert Yeh, William Lombardi, Ray Wyman, James Grantham, David Kandzari, Nicholas Lembo, Anthony Doing, Mitul Patel, John Bahadorani, Jeffrey Moses, Ajay Kirtane, Manish Parikh, Matthew Finn, Phuong-Khanh Nguyen-Trong, Bavana Rangan, Philip Green, Craig Thompson, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2016)
PTU-091 Anti-tnf Therapy Reduces Ionising Radiation Exposure In Patients With Crohn’s Disease
Authors: D Aggarwal, JK Limdi
Journal: Gut (2014)

<h3>Introduction</h3> Patients with Crohn’s Disease [CD] are often exposed to ionising radiation for the diagnosis and evaluation of disease with inherent risks from protracted exposure. Meanwhile, bolder definitions of disease control have changed treatment paradigms with earlier introduction of biological therapy in many. Our aim was to compare the effective radiation dose a year prior and 1 and 3 years after initiating anti-TNF therapy or corticosteroid. <h3>Methods</h3> We performed a retrospective review of CD patients treated with anti-TNF (infliximab or adalimumab) or corticosteroids at our institution from 2005 to 2013. Clinical data (demographics, disease characteristics, treatment) were obtained from patient records. All instances of imaging in the previous year and 1 and 3 years after initiation of therapy were recorded. Effective and cumulative radiation doses were calculated from published tables [Royal College of Radiologists, UK]. <h3>Results</h3> We analysed 170 patients with CD (114 anti-TNF, 56 corticosteroid). In the anti-TNF group, 55% were female (median age 35 yrs;mean disease duration 8.2yrs). Disease location was ileal (46%), colonic (21%), ileocolonic (31%) and perianal (22%) with inflammatory, stricturing and penetrating disease in 63%, 14% and 23% respectively. In the corticosteroid group, 53% were females (median age 48; mean disease duration 13.2yrs). Disease location was ileal (44%), colonic (27%), ileocolonic (29%) and perianal (14%) with inflammatory, stricturing and penetrating disease in 75%, 20% and 5% respectively. The anti-TNF cohort had a significant reduction in the cumulative radiation dose (4.2 <i>vs.</i> 1.8 mSv, p &lt; 0.0001) compared to the previous year. There was no change in the cumulative radiation dose in the corticosteroid group (7.5 vs.7.3 mSv, p = 0.8). The number of CT scans reduced from 3.3 to 1.2 (p &lt; 0.0001) in the anti-TNF cohort. There was no reduction the number of CT scans in the corticosteroid group after one year (2.7 <i>vs</i>. 2.5, p = 0.006). In 31 patients with 3-year exposure to corticosteroids, there was a significant increase in the cumulative radiation dose (7.0 <i>vs.</i> 13.8 mSv, p &lt; 0.0003) compared to the anti-TNF group (3.5 vs. 4.8 mSv, p = 0.7). There was a significant increase in the number of CT scans in the corticosteroid group (2.6 vs. 4.9, p &lt; 0.001) compared to the anti-TNF group (2.5 <i>vs</i>. 2.8, p = 0.9). Linear regression analysis showed a decrease in cumulative radiation dose by 2.7 mSv (p = 0.07) and number of CT scans by 2 (p &lt; 0.001) in the anti-TNF group compared to the corticosteroid group within a year of therapy after adjusting for age, gender, disease duration, disease location and disease behaviour. <h3>Conclusion</h3> Anti-TNF but not corticosteroid therapy is associated with a significant reduction in diagnostic radiation exposure a year after treatment and persisted after 3 years although not statistically significant <h3>Disclosure of Interest</h3> None Declared.
Abstract 685: Epigenetic modulators and calcium-sensing receptor expression in colorectal cancer cells.
Authors: Irfete Sh. Fetahu, Julia Höbaus, Abhishek Aggarwal, Samawansha Tennakoon, Ildiko Mesteri, Sabina Baumgartner-Parzer, Enikoe Kallay
Journal: Cancer Research (2013)

Abstract Introduction: Epidemiological studies suggest a role for calcium in prevention of colorectal cancer. The antiproliferative action of calcium in colon might be mediated by the calcium-sensing receptor (CaSR). The CaSR expression is lost in human colorectal cancer. We hypothesized that DNA methylation and histone modifications may be the cause of CaSR silencing in tumors. Material and methods: We analyzed CaSR mRNA and protein expression in colorectal tumors and cell lines by real time qRT-PCR and immunofluorescence. We determined the methylation pattern in the second promoter of the CaSR that contains a large CpG island by bisulfite sequencing. To induce the expression of the CaSR we treated colon tumor cell lines with 5-aza-2-deoxycytidine (5-aza-dC) and RG108, two DNA methyltransferase inhibitors, three different histone deacetylase inhibitors (HDACIs) Trichostatin A, suberoylanilide hydroxamic acid, sodium butyrate in the presence or absence of a lysine specific demethylase 1 (LSD1) inhibitor to prevent demethylation of mono- and dimethylated histone H3 lysine 4. Results: In our patient cohort we observed significantly less CaSR mRNA expression (n=57, P&amp;lt;0.001) in colorectal tumors compared with adjacent mucosa from the same patient. Immunofluorescence staining confirmed downregulation of CaSR protein in tumors. The CaSR promoter was stronger methylated in tumors compared with adjacent mucosa and we found an inverse correlation between extent of methylation and mRNA expression (n=20, Spearman's rho = - 0.3, P&amp;lt;0.05). Treatments with 5-aza-dC and the HDACIs restored the expression of CaSR in a compound and cell line dependent manner. However, treatments with the LSD1 inhibitor caused only modest increase of CaSR expression. Conclusion: In summary, DNA methylation and histone deacetylation seem to be important factors in silencing the expression of CaSR in colorectal cancer, although additional mechanism or factors might be also involved. Citation Format: Irfete Sh. Fetahu, Julia Höbaus, Abhishek Aggarwal, Samawansha Tennakoon, Ildiko Mesteri, Sabina Baumgartner-Parzer, Enikoe Kallay. Epigenetic modulators and calcium-sensing receptor expression in colorectal cancer cells. [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 685. doi:10.1158/1538-7445.AM2013-685
Abstract 1450: Targeting the ATM kinase as a novel strategy for radiosensitizing glioblastoma multiforme in mice
Authors: Laura Biddlestone-Thorpe, Sajjad Muhammad, Elizabeth Rosenberg, Sarah E. Golding, Bret R. Adams, Mary Tokarz, Ashraf Khalil, Donna Gilfor, Mark O'Connor, Kristoffer Valerie
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) is the most lethal type of brain cancer. At best, mean survival is only 12-15 months so an improvement of current therapy is long overdue. Current treatment includes surgery and chemoradiation. The short survival of GBM patients is due, in part, to the innate radioresistance and vicious invasiveness of GBM. ATM, ataxia telangiectasia (A-T) mutated, would be an excellent target for radiosensitizing GBM because of its critical role in regulating the DNA damage response (DDR) and other cellular processes. As a first step towards this goal, we tested the ability of the novel ATM kinase inhibitor KU-60019 to radiosensitize GBM in mice. Using an orthotopic xenograft model of GBM, nude mice were implanted with human glioma cells expressing reporter genes for monitoring tumor growth and spread. KU-60019 was administered intra-cranially by convection-enhanced delivery or by osmotic pump. Imaging, survival, and signs of inhibiting the DDR using immunohistochemistry were used to characterize the effects of KU-60019 on tumor and normal brain. Our results show that compared with untreated, KU-60019 alone, or radiation alone treated mice, the combined effect of KU-60019 and radiation significantly increased survival at least 2-fold and sometimes even cured the animals. Multiple glioma cell lines with varied genetic backgrounds are currently being tested. Altogether, our results show that KU-60019 is able to overcome GBM radioresistance, a major obstacle in the treatment of GBM, and significantly prolong the survival of animals. Thus, an ATM kinase inhibitor may have great potential as adjuvant therapy in the clinic. 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 1450. doi:1538-7445.AM2012-1450
Positron Emission Tomography in Intussusception of Colon Cancer, Where Computed Tomography Failed
Authors: CHICHUAN Y. KAMINSKI, JOSEPH M. KAMINSKI, ADAM R. GUTTENTAG, HUYEN TRAN
Journal: Clinical Nuclear Medicine (2003)

KAMINSKI, CHICHUAN Y. M.D., M.S.*; KAMINSKI, JOSEPH M. M.D.†; GUTTENTAG, ADAM R. M.D.*; TRAN, HUYEN M.D.* Author Information