tbuckley/cabot-search huggingface dataset:
PWE-110 Post Endoscopy Missed Colorectal Cancer at A Local DGH - Implication for Practice
Authors: S Sultan, M Mirzaali, A El-Sayed, I Jaly, MI Yahya, J Rademaker
Journal: Gut (2016)

<h3>Introduction</h3> Colonoscopy is the “gold standard” approach to investigating symptoms in relation to the colon. However, recent literature has shown that colonoscopy as a diagnostic test for colorectal cancer is far from perfect with a cancer missed rate of 8.6% in the UK. We aim to identify the rate of colorectal cancers diagnosed following a negative flexible sigmoidoscopy and/or colonoscopy and to explore contributing factors. <h3>Methods</h3> This is a retrospective case analysis investigating all patients who received a diagnosis of colorectal cancer over a five-year period (2010–2015). We used our local clinical databases in identifying those patients who had negative flexible sigmoidoscopy and/ or colonoscopies but subsequently received a diagnosis of colorectal cancer. <h3>Results</h3> 368 (Females 156; males 167; average age 76.71) patients were included in the initial sample. Of those 45 were excluded as an initial endoscope examination was not carried out and the cancers were identified by other means. Of 368 patients who were diagnosed with colorectal cancer, 35 (10.83%) had a previously normal endoscopic examination (19 flexible sigmoidoscopy; 16 colonoscopy) <h3>Conclusion</h3> This research has shown that despite being the gold standard, colonoscopy as a diagnostic test for colorectal cancer is still far from perfect. In keeping with current research there appears to be a missed rate in detection of colorectal cancers, polyps and adenomas. Factors contributing to missed lesions are thought to be the presence of &gt;2 lesions, lesions present in the left side of the colon, withdrawal time where longer withdrawal time was associated with higher lesion detection rate. Furthermore the smaller the lesion the lower the detection rate on colonoscopy (missed rate: 6% in adenomas &gt;1 cm; 27% in adenomas &lt;5 mm). It is worth bearing in mind that endoscopic procedures are very dependant on operator experience. We recommend longer and more rigorous training in endoscopic procedures and strongly advise following the standardised reporting systems in place. <h3>References</h3> 1 Rex DK, Cutler CS, Lemmel GT, Rahmani EY, Clark DW, Helper DJ, Lehman GA, Mark DG. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. <i>Gastroenterology</i> 1997;<b>112</b>(1):24–8. 2 Barclay RL, Vicari JJ, Doughty AS, Johanson JF, Greenlaw RL. Colonoscopic withdrawal times and adenoma detection during screening colonoscopy. <i>New England Journal of Medicine</i> 2006;<b>355</b>:2533–2541. <h3>Disclosure of Interest</h3> None Declared
Selective Reversible Inhibition of Autophagy in Hypoxic Breast Cancer Cells Promotes Pulmonary Metastasis
Authors: Christopher M. Dower, Neema Bhat, Edward W. Wang, Hong-Gang Wang
Journal: Cancer Research (2016)

Abstract Autophagy influences how cancer cells respond to nutrient deprivation and hypoxic stress, two hallmarks of the tumor microenvironment (TME). In this study, we explored the impact of autophagy on the pathophysiology of breast cancer cells using a novel hypoxia-dependent, reversible dominant-negative strategy to regulate autophagy at the cellular level within the TME. Suppression of autophagy via hypoxia-induced expression of the kinase-dead unc-51-like autophagy-activating kinase (ULK1) mutant K46N increased lung metastases in MDA-MB-231 xenograft mouse models. Consistent with this effect, expressing a dominant-negative mutant of ULK1 or ATG4b or a ULK1-targeting shRNA facilitated cell migration in vitro. Functional proteomic and transcriptome analysis revealed that loss of hypoxia-regulated autophagy promotes metastasis via induction of the fibronectin integrin signaling axis. Indeed, loss of ULK1 function increased fibronectin deposition in the hypoxic TME. Together, our results indicated that hypoxia-regulated autophagy suppresses metastasis in breast cancer by preventing tumor fibrosis. These results also suggest cautions in the development of autophagy-based strategies for cancer treatment. Cancer Res; 77(3); 646–57. ©2016 AACR.
Preliminary Results of a Phase I Study of the Pan-PI3 Kinase Inhibitor SF1126 in Patients with Relapsed and Refractory Myeloma.
Authors: Sagar Lonial, R. Donald Harvey, Dixil Francis, Engin Gul, Sundar Jagannath, Sherif Farag, Daniel Hoth, Robert Frumento, Joseph R. Garlich, Suzanne Trudel
Journal: Blood (2009)
FRI0153 Relationship between Serum Oxytocin Levels and Disease Activity, Depressive State, ADL, and QOL in Patients with Rheumatoid Arthritis
Authors: Y. Miwa, R. Takahashi, S. Isojima, M. Saito, Y. Miura, S. Ishii, Y. Ikari, T. Tokunaga, T. Kasama, Y. Toyoshima, K. Inagaki
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Oxytocin, which is also called a happy hormone, has been reported to be related to various conditions including depressive state. However, the positioning of oxytocin in rheumatoid arthritis (RA) remains unclear. <h3>Objectives</h3> The objective of this study was to investigate the relationship between serum oxytocin levels and disease activity, depressive state, activity of daily life (ADL), and quality of life (QOL) in RA. <h3>Methods</h3> The study included 20 patients with RA who received treatment with a biological agent. We measured the following items before and at 6 months after the start of treatment. The baseline characteristics included the age, sex, prednisolone dose, methotrexate dose, duration of disease, anti-cyclic citrullinated peptide antibody (anti-CCP antibody), rheumatoid factor (RF), serum matrix metalloproteinase-3 (MMP-3), erythrocyte sedimentation rate, and C-reactive protein (CRP). The disease activity of rheumatoid arthritis was assessed using the Simplified Disease Activity Index (SDAI), depressive state using Hamilton Depression Rating Scale (HAM-D), ADL using the Health Assessment Questionnaire (HAQ), and QOL using the 36-Item Short Form Health Survey (SF-36). Serum oxytocin levels were determined by enzyme-linked immunosorbent assay (ELISA). The correlation between each item and the serum oxytocin levels were examined. <h3>Results</h3> The serum oxytocin levels before the start of treatment were correlated with RF (r=−0.529), HAQ (r=0.446), HAM-D (r=0.508), and among the 8 categories of the SF-36, physical function (r=−0.676), role function (physical) (r=−0.801), pain (r=−0.506), general health perception (r=−0.787), role function (emotional) (r=−0.844), and mental health (MH) (r=−0.516). On the other hand, the serum oxytocin levels did not correlate with the SDAI (r=−0.078). The serum oxytocin levels after the start of treatment were correlated with the age (r=−0.549), SDAI (r=−0.539), HAQ (r=0.813), HAM-D (r=0.584), and all of the SF-36 categories except for MH (r=0.038) (r&gt;0.4). Other items did not correlate to the serum oxytocin levels. <h3>Conclusions</h3> The serum oxytocin levels before the start of treatment were correlated with depressive state, ADL, and QOL but not with disease activity. Those after the start of treatment were correlated with the SDAI, depressive state, ADL, and QOL. <h3>Disclosure of Interest</h3> Y. Miwa Grant/research support from: Tanabemitsubishi, Chugai, phizer, Ono, R. Takahashi: None declared, S. Isojima: None declared, M. Saito: None declared, Y. Miura: None declared, S. Ishii: None declared, Y. Ikari: None declared, T. Tokunaga: None declared, T. Kasama: None declared, Y. Toyoshima: None declared, K. Inagaki: None declared
Results of Tyrosine Kinase Inhibitors (TKI) Therapy of Patients (Pts) with Chronic Myeloid Leukemia (CML) In Clinical Practice Analysed In the Frame of International Research Project EUTOS In Russian Federation
Authors: Anna G. Turkina, Sergey Kulikov, Kudrat Abdulkadirov, Sergey Kutsev, Anatoly Golenkov, Valentina Ivanova, Tatiana Pospelova, Tatiana Konstantinova, Olga Lazareva, Nina Khoroshko
Journal: Blood (2011)
Constipation and Incident CKD
Authors: Keiichi Sumida, Miklos Z. Molnar, Praveen K. Potukuchi, Fridtjof Thomas, Jun Ling Lu, Kunihiro Matsushita, Kunihiro Yamagata, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy
Journal: Journal of the American Society of Nephrology (2016)

Constipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m 2 , we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope &lt;−10, −10 to &lt;−5, and −5 to &lt;−1 versus −1 to &lt;0 ml/min per 1.73 m 2 per year, 1.17; 95% CI, 1.14 to 1.20; 1.07; 95% CI, 1.04 to 1.09; and 1.01; 95% CI, 1.00 to 1.03, respectively). More severe constipation associated with an incrementally higher risk for each renal outcome. In conclusion, constipation status and severity associate with higher risk of incident CKD and ESRD and with progressive eGFR decline, independent of known risk factors. Further studies should elucidate the underlying mechanisms.
Erratum to: Making sense of big data in health research: towards an EU action plan
Authors: Charles Auffray, Rudi Balling, Inês Barroso, László Bencze, Mikael Benson, Jay Bergeron, Enrique Bernal-Delgado, Niklas Blomberg, Christoph Bock, Ana Conesa, Susanna Del Signore, Christophe Delogne, Peter Devilee, Alberto Di Meglio, Marinus Eijkemans, Paul Flicek, Norbert Graf, Vera Grimm, Henk-Jan Guchelaar, Yi-Ke Guo, Ivo Glynne Gut, Allan Hanbury, Shahid Hanif, Ralf-Dieter Hilgers, Ángel Honrado, D. Rod Hose, Jeanine Houwing-Duistermaat, Tim Hubbard, Sophie Helen Janacek, Haralampos Karanikas, Tim Kievits, Manfred Kohler, Andreas Kremer, Jerry Lanfear, Thomas Lengauer, Edith Maes, Theo Meert, Werner Müller, Dörthe Nickel, Peter Oledzki, Bertrand Pedersen, Milan Petkovic, Konstantinos Pliakos, Magnus Rattray, Josep Redón i Màs, Reinhard Schneider, Thierry Sengstag, Xavier Serra-Picamal, Wouter Spek, Lea A. I. Vaas, Okker van Batenburg, Marc Vandelaer, Peter Varnai, Pablo Villoslada, Juan Antonio Vizcaíno, John Peter Mary Wubbe, Gianluigi Zanetti
Journal: Genome Medicine (2016)
AB1049 Musculoskeletal Manifestations in Renal Hemodialysis Patients
Authors: T.A. Gheita, S. Sayed, A. Al-ghitany, H. Ezzat
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Pain is a significant problem in more than 50% of hemodialysis patients and is not being effectively managed<sup>1</sup>. In patients on regular dialysis, musculoskeletal pain was identified as the most disturbing pain and the majority reported that pain limited their daily life activities<sup>2</sup> <h3>Objectives</h3> The aim of the study is to detect and describe the incidence of musculoskeletal manifestations, comorbidities and gender differences in renal failure patients on regular hemodialysis <h3>Methods</h3> Forty-nine patients with renal failure and on regular dialysis were included in the present study. The patients were subjected to full history taking and clinical examination. Blood samples were collected before the mid-week session for laboratory investigations. The bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) in all patients. Kt/V was used as a marker of dialysis adequacy <h3>Results</h3> The 49 patients mean age was 54.41±15.9 years. They were 28 males and 21 females. The dialysis duration was 3±2.31 years. Comorbidities were present as diabetes (45%), hypertension (96%), cardiovascular (33%), cerebrovascular stroke (6%), hyperuricemia (37%), hepatitis C (16%) and amyloidosis (8%). The following musculoskeletal findings were present in descending frequency: fibromyalgia syndrome (51%), myalgias (37%), arthralgia (37%), flexor tenosynovitis (29%), cramps (29%), ectopic calcifications (25%), flexion deformity of the elbow (16%), carpal tunnel syndrome (14%), and destructive spondyloarthritis (8%). Vasculitis was present in 2. Positive anti-CCP was present in 1 female and rheumatoid factor in 4 females and 1 male. Otherwise, there was a tendency to a higher frequency of musculoskeletal findings in males. Vitamin D insufficiency (25.1±14.6ng/ml) and reduced bone mineral density were present. The DXA t-score at lumbosacral spine was -1.51±1.77, hip (-1.65±1.59) and forearm (-1.89±1.9). <h3>Conclusions</h3> Musculoskeletal manifestations and comorbidities are frequent and overlooked in hemodialysis patients especially males and the associated chronic pain may affect their quality of life. <h3>References</h3> Davison SN. Pain in hemodialysis patients: prevalence, cause, severity, and management. Am J Kidney Dis. 2003;42(6):1239–47. Gamondi C, Galli N, Schönholzer C, Marone C, Zwahlen H, Gabutti L, et al. Frequency and severity of pain and symptom distress among patients with chronic kidney disease receiving dialysis. Swiss Med Wkly. 2013;143:w13750 <h3>Disclosure of Interest</h3> None declared
PTH-085 Deoxythioguanosine (DTG) in DNA as a Pharmacological Endpoint of Thiopurine Treatment in Inflammatory Bowel Disease Patients
Authors: S Coulthard, P Berry, S McGarrity, T Kobayashi, T Toyonaga, A Ansari, C Redfern
Journal: Gut (2016)

<h3>Introduction</h3> We have used a sensitive assay to measure incorporated dTG in the DNA isolated from peripheral blood cells of patients treated with thiopurines with the aim of identifying a more appropriate pharmacological marker of response for patients on therapy with the thiopurines azathioprine (AZA) or mercaptopurine (MP). <h3>Methods</h3> DNA was isolated from blood samples collected from 38 IBD patients; 23 on AZA and 15 on MP. DNA was denatured, digested using P1 nuclease followed by treatment with alkaline phosphatase and finally diluted in MilliQ water prior to analysis. A total of 0.2 µg of DNA in 50 µL was injected for chromatographical separation followed by analysis on an API4000 triple quadrupole LC-MS/MS. Standard curves and controls were validated and samples analysed to determine number of moles of dTGN/ 105<sup>5</sup> moles of dA. <h3>Results</h3> A cohort of patients with Crohn’s Disease (CD) on AZA (n = 11) or MP (n = 5) or Ulcerative Colitis (UC); AZA (n = 12), MP (n = 10) established on thiopurine therapy for more than 25 weeks and in clinical remission were analysed. For those on AZA only there was a statistically significant correlation between dTG levels and AZA dose (Kendall Rank correlation, P &lt; 0.05; median =0.89, mean = 2.03, SD = 2.92; range 0.0–11.3); however there was no such correlation for the MP treated patients (Kendall Rank correlation, P &gt; 0.05; median =1.05, mean = 1.0, SD = 1.0; range 0.0–3.3). When disease was taken into account there was no statistical difference in dTG levels between those taking AZA (Mann-Whitney, P &gt; 0.9; for CD patients, median =0.89, mean = 2.13, SD = 3.34; for UC patients, median =1.11, mean = 1.19, SD = 2.61). However, for those taking MP there was a statistically-significant difference (Mann-Whitney, P &lt; 0.05; for CD patients, median =1.7, mean = 1.98, SD = 0.99; for UC patients, median =1.45, mean = 0.59, SD = 0.63) <h3>Conclusion</h3> This pilot study shows that the levels of dTG in treated patients are similar whether the patients are on AZA (average dose 118 mg) or MP (average dose 39 mg equivalent to approximately 81 mg AZA). However, there were clear differences between the two drug-treatment groups with respect to the correlation of dTG and drug dose and in the relationship between dTG incorporation and disease type. These results justify a larger cohort study to investigate the role of drug-DNA interactions in clinical responses to thiopurines <h3>Disclosure of Interest</h3> None Declared
Home Monitoring of Fasting and Postprandial Triglycerides in Late Pregnancy: A Pilot Study
Authors: Helen L. Barrett, H. David McIntyre, Michael D’Emden, Marloes Dekker Nitert, Leonie K. Callaway
Journal: Diabetes Care (2016)

Elevated maternal triglycerides are associated with adverse pregnancy outcomes (1). In pregnancy, triglycerides are measured infrequently and mostly fasting, leading to a lack of data on the variability and flux of triglycerides (1). This study explored capillary triglyceride concentrations in late pregnancy using a validated Roche Accutrend triglyceride meter (2).

This was a prospective observational cohort study that was approved by the local human research ethics committee. For 6 days, women monitored fasting and 2-h postprandial capillary glucose and triglyceride levels. Results are mean millimoles per liter with SD unless otherwise indicated. Women reported on the usability of the meter.

Twelve women enrolled at mean 258 (9) [mean (SD)] days’ gestation. Eight women (66%) had gestational diabetes mellitus, of whom four were prescribed insulin and one metformin. Mean (SD) fasting glucose levels were lower than postprandial glucose levels [4.67 (0.44) vs. 6.06 (1.11) mmol/L, P < 0.001]. Mean …
SAT0013 Juvenile Idiopathic Arthritis Association of PTPN22 rs2476601 SNP Is Specific To Females in A Greek Population
Authors: G.N. Goulielmos, R. Chiaroni-Clarke, D.G. Dimopoulou, M.I. Zervou, M. Trachana, P. Pratsidou-Gertsi, E. Myrthianou, A. Garyfallos, J. Ellis
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by persistent chronic arthritis [1] and is believed to be influenced by both genetic and environmental factors. <i>PTPN22</i> single nucleotide polymorphism (SNP) rs2476601 has been recently reported in an Australian study to be restricted to females and to not be observed in males [2]. <h3>Objectives</h3> Considering that a significant source of inconsistency amongst the literature on autoimmune disease susceptibility genes stems from an inability to replicate genetic findings across different racial or ethnic groups, we attempted to confirm the female-specific association of rs2476601 in a homogeneous Greek population. <h3>Methods</h3> The sample set consisted of 128 (70.3% female) Caucasian JIA patients and 221 (28.1% female) healthy controls from Northern Greece. Genotyping for the <i>PTPN22</i> rs2476601 (<i>Xcm</i>I) was performed by restriction fragment length polymorphism (RFLP) analysis [3]. Logistic regression or the Gart (Woolf) method were used to estimate ORs and 95% CIs. Analyses were performed using Stata v13 (StataCorp, College Station, TX, USA). <h3>Results</h3> The rs2476601 was genotyped in 128 Caucasian JIA patientsand 221 healthy controls from Northern Greece. Overall, <i>PTPN22</i> was associated with increased risk of JIA in this Greek sample (OR =2.3, 95% CI 1.1 – 5.1, p=0.038). Sex-stratified analyses showed that, once again, the risk association was restricted to females (Female: OR =19.9, 95% CI 1.2 – 342, p=0.0016; Male: OR =1.1, 95% CI 0.3 – 3.1, p=0.94) confirming the prior findings. Given that the sex bias differs by JIA subtype, ideally we would have liked to test for these associations in individual subtypes; however, small sample size prevented us from performing these analyses with any statistical certainty. <h3>Conclusions</h3> This data demonstrated that the sex-specific pattern of association detected is broadly applicable to different populations, and provided further impetus to undertake studies to understand the crucial role of rs2476601 in the mechanisms leading to disease9s development preferentially in females. Our work is of interest given the importance of comparative studies in populations of differing ethnic and/or racial origin in any attempt to conclusively define the genetic architecture of JIA and the magnitude of the effects of specific risk alleles globally. <h3>References</h3> Ravelli and Martini (2007). Lancet 369:767–778. Chiaroni-Clarke et al (2015). Genes Immun. 16:495–498. Eliopoulos et al (2010). Lupus 105:501–506. <h3>Disclosure of Interest</h3> None declared
A Pediatric Treatment of Ph-Negative Acute Lymphoblastic Leukemia (ALL) Is Effective and Safe In Adolescents and Young Adults (AYAs) until 29 Years of Age
Authors: Thomas Cluzeau, Nathalie Dhedin, Françoise Huguet, Emmanuel Raffoux, Sebastien Maury, Thierry Lamy, Lionel Mannone, Gaelle Guillerm, Andre Delannoy, Pascal Turlure, Norbert Vey, André Baruchel, Herve Dombret, Nicolas Boissel
Journal: Blood (2010)
Optimized inter-stimulus interval (ISI) and content design for evoking better visual evoked potential (VEP) in brain-computer interface applications
Authors: Jungnyun Lee, Mincheol Whang, Jaehong Yoon, Minji Park, Jonghwa Kim
Journal: Brain-Computer Interfaces (2016)

Brain-computer interfaces have been adopting visual evoked potential (VEP) signals to evaluate real-time cognitive responses, which have been shown to differ depending on the system's panel design and inter-stimulus interval (ISI). The objective of this study was to determine the optimal ISI and display contents for improved VEP signals. The panel contents consisted of six Korean texts or symbols from a television remote controller, and three levels of ISI were used. Subjects concentrated on a target stimulus while the panel randomly flashed different texts or symbols. Six local areas were measured by electroencephalogram based on the Extended International 10–20 system. P3 and N1 amplitudes and latencies were analyzed to determine the optimal combination of panel contents and ISI. Text-based panels were found to produce superior P3 and N1 responses compared with symbol-based panels. The ISI of 300 ms induced the best ERP responses for both text and symbol panels.