tbuckley/cabot-search huggingface dataset:
PTU-105 Expression Of Micrornas Mir-31, Mir-146a And Mir-155 Is Significantly Elevated In Anti-tnf-alpha Treatment Failure In Colonic Cd
Authors: M Gwiggner, RT Martinez-Nunez, T Sanchez-Elsner, J Cummings
Journal: Gut (2014)

<h3>Introduction</h3> Crohn’s disease (CD) is a Th1/Th17 driven disease in which TNF-α and INF-γ play important roles. Anti-TNF-α drugs are used in moderate-severe CD to induce and maintain remission. Mucosal healing is an aim of therapy. MicroRNAs are non‐coding RNAs which control translation of mRNA. MiR-31, miR-146a and miR-155 are involved in the regulation of immune responses and are deregulated in CD. Aim of this study is to evaluate the impact of medical treatment on microRNA expression in CD and to investigate microRNAs as biomarkers in CD. <h3>Methods</h3> 37 patients with colonic CD undergoing colonoscopy were recruited. A partial Simple Endoscopic Score for CD (SES-CD) was assessed. Sigmoid biopsies were taken from 19 patients in remission (SES-CD=0) and 18 patients with active sigmoid CD (SES-CD<b>≥</b>1). Remission (R) was defined as mucosal healing (SES-CD=0) and treatment failure (F) as an SES-CD<b>≥</b>1 in the left colon. MicroRNA (miR-31, miR-146a and miR-155) and mRNA expression (TNF- α, INF-γ) were evaluated by qPCR. Sub-analysis compared treatment naïve patients (6 inactive/8 active) to patients on thiopurines (TP) (R= 5/F= 5) and anti-TNF-α therapy (R=6/F=7). <h3>Results</h3> miR-31, miR-146a and miR-155 were significantly up-regulated as were TNF-α and INF-γ in active sigmoid CD compared to patients in remission. Patients on TP compared to treatment naïve patients showed significant down-regulation of TNF-α and INF-γ in remission, compared to treatment naïve patients with active CD. MicroRNA levels in TP failure were interstingly lower compared to patients in remission. In contrast, microRNA levels in the anti-TNF-α group in therapy failure were significantly elevated compared to active treatment naïve patients, behaving opposite to patients on TP. MicroRNA expression in remission showed levels similar to treatment naïve patients in remission. While TNF-α and INF-γ returned to base levels in remission on anti-TNF-α drugs, significantly lower compared to active treatment naïve CD, in therapy failure TNF-α remained elevated and INF-γ was significantly raised. <h3>Conclusion</h3> Our data reveals a clear up-regulation of miR-31, miR-146 and miR-155 as well as of TNF- α and INF-γ in active colonic CD. TP and anti-TNF-α drugs significantly alter the expression of microRNAs miR-31, miR-146a and miR-155 compared to treatment naïve patients behaving in an opposing manner. MicroRNAs remain significantly elevated in patients with sigmoid CD failing to respond to anti-TNF-α treatment. MicroRNAs expression profiles may have a role as biomarkers in predicting treatment failure in CD. <h3>Disclosure of Interest</h3> None Declared.
P81 Pre-transplant histological assessment in patients with alcoholic liver disease does not predict risk of recidivism post liver transplantation
Authors: J. Prentis, S. McPherson, A. Burt, D. Manas, C. Snowden, M. Hudson, S. Masson
Journal: Gut (2011)

<h3>Introduction</h3> Liver transplantation for alcoholic liver disease (ALD) is well established, but it remains a controversial indication. Assessment of patients in whom alcohol has been a contributing factor to chronic liver disease aims to identify those at risk of relapse. As well as psychological assessment, histological evidence of steatohepatitis may indicate ongoing alcohol consumption. <h3>Aim</h3> To determine the prevalence of histological evidence of ongoing alcohol use among patients undergoing liver transplant assessment for ALD and its affect on listing and risk of recidivism. <h3>Method</h3> Consecutive patients with ALD assessed for liver transplantation between 2006 and 2010 were included. Transjugular liver biopsy was performed routinely in all patients and specimens were reviewed by an expert hepatopathologist. Outcomes including decision to list for transplant, survival and recidivism (patient admission or blood alcohol detection) were recorded <h3>Results</h3> 122 patients were included (70% male, median age 55) with diagnoses of lone ALD (92), ALD/HCV (10) and HCC (10). Histology was insufficient for analysis in four. Most patients (108, 89%) had histological evidence of micronodular cirrhosis without evidence of steatosis or steatohepatitis, suggesting abstinence. Of these, 52 were listed for transplantation though two were subsequently removed for recidivism. To date, 39 have been transplanted; 1-year follow-up was available in 28. The overall 1-year survival was 90% and 28% had returned to drinking alcohol (n=7), although none were ‘problem’ drinkers. In the remaining 10 patients, histology revealed cirrhosis with active steatohepatitis (n=2), chronic viral hepatitis (n=1) and mild steatosis (n=7). One patient with steatohepatitis was known to be drinking at the time of assessment; the remainder were listed for transplant. Subsequently, one patient with steatosis was found to be drinking and removed. To date, six have been transplanted and survived to 1 year, with two returning to alcohol post-transplant. <h3>Conclusion</h3> Histological analysis during liver transplant assessment does not determine the decision to list for liver transplantation nor predict the risk of recidivism. As a result, we no longer routinely perform liver biopsy during liver transplant assessment. A significant proportion of patients return to alcohol consumption post liver transplantation.
1223 HEPATITIS C VLPS DELIVERED TO DENDRITIC CELLS BY A TLR2 TARGETING LIPOPEPTIDE RESULTS IN ENHANCED NEUTRALIZING ANTIBODY AND CELL-MEDIATED RESPONSES
Authors: J. Torresi, R. Chin, B. Chua, D. Johnson, L. Earnest-Sliveira, W. Zeng, E. Gowans, T.C. Bock, D.C. Jackson
Journal: Journal of Hepatology (2013)
AB0251 The Impact of Missing Anti-Citrullinated Protein Antibody (ACPA) Serology on Outcomes in Early Rheumatoid Arthritis: Results from Catch (Canadian Early Arthritis Cohort): Table 1.
Authors: J. Shu, V. Bykerk, G. Boire, B. Haraoui, C. Hitchon, C. Thorne, D. Tin, E. Keystone, J. Pope
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Anti-citrullinated protein antibody (ACPA) is a serum biomarker that is as sensitive as, but more specific than the rheumatoid factor (RF) and detected earlier in RA [1,2]. Although ACPAs are part of the ACR RA classification criteria, ACPA testing is not routinely paid for/accessible in all jurisdictions. <h3>Objectives</h3> The impact of missing ACPA in early inflammatory arthritis patients was studied to determine if failure to perform ACPA testing could cause a gap in care. <h3>Methods</h3> 2191 patients recruited to CATCH were allocated to 3 groups: 1. seropositive (rheumatoid factor positive (RF+) and/or ACPA+), 2. seronegative (RF−/ACPA−) and 3. missing ACPA (RF negative [RF−]). Adjustments were made using regression analyses for age, sex, symptom duration, and smoking status if p&lt;0.1 from Pearson9s Chi-squared or Analysis of variance (ANOVA) tests. <h3>Results</h3> Refer to Table 1 for characteristics of three groups. More seropositive patients fulfilled 2010 ACR/EULAR RA criteria (Table 1). At 3 months, group 3 was treated with less DMARDs and methotrexate, but there were no significant differences in DAS28, HAQ-DI, corticosteroids, or physician/patient global assessments (Table 1). <h3>Conclusions</h3> Patients with missing ACPAs were less likely to fulfill RA criteria and were treated differently with fewer medications. There may be a care gap in the unknown ACPA group who were RF negative, but there were no significant differences in outcomes such as DAS28, 3 month change in DAS28, or HAQ-DI despite less treatment. Further study is needed regarding the cost-effectiveness of ensuring ACPA testing is available for patients with new onset inflammatory arthritis. <h3>References</h3> Whiting PF, Smidt N, Sterne JA, Harbord R, Burton A, Burke M, et al. Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis. Annals of internal medicine. 2010;152(7):456-64; W155-66. Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis and rheumatism. 2003;48(10):2741-9. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2635
Abstract 1750: Identification of genes involved in chemoradiation response of head and neck cancer by functional genetic screens
Authors: Sanne R. Martens-de Kemp, Arjen Brink, Ida H. van der Meulen, Dirk J. Kuik, Renee Menezes, Boudewijn JM Braakhuis, Victor W. van Beusechem, Ruud H. Brakenhoff
Journal: Cancer Research (2011)

Abstract Introduction: Patients with advanced head and neck squamous cell carcinoma (HNSCC) are treated with cisplatin-containing chemoradiation protocols, but tumor responses can be short-lasting. For these patients surgery combined with postoperative radiotherapy is preferred over chemoradiation. Currently, there are no strong predictors of chemoradiation response that would allow to personalize treatment. We performed a functional genetic siRNA screen to identify genes that can be used to predict upfront which tumors are likely to respond to chemoradiation. Methods: A large panel of HNSCC cell lines was characterized for cisplatin sensitivity. A suitable HNSCC cell line was selected and forward transfected with a genome-wide library of short interfering RNAs (siRNAs), followed by cisplatin (IC20 and IC80) or mock treatment. Genes influencing cellular response to cisplatin were identified by comparing cell viability between the different conditions. The screen was carried out in duplicate and data were analyzed by Z-score calculation using two independent statistical methods. Results: Scrambled siRNAs and siRNAs targeting genes known to influence cell viability or cisplatin sensitivity were included as controls and gave the expected results: less than 10% toxicity and &amp;gt;80% knock-down. Hit lists obtained with both methods of data analysis revealed 86 siRNAs that appeared to influence cisplatin response significantly. Some of these 86 siRNAs target genes that are known to cause sensitivity to cisplatin, thereby confirming the reliability of the approach. We also obtained a list of 80 genes that influenced basic cell viability of HNSCC cells independent of cisplatin. Conclusion: By specifically knocking down all human genes in HNSCC cells, we obtained an unbiased list of at least 86 candidate genes that seem to influence the cellular response to cisplatin. Refined statistical analysis combined with bioinformatics, the exclusion of off-target effects, as well as confirmation of the hits in multiple cell lines is needed to validate these results. Validated hits will be evaluated as predictive markers in clinical samples. This research was supported by the Center for Translational Molecular Medicine (AIRFORCE project). 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 1750. doi:10.1158/1538-7445.AM2011-1750
Abstract 2047: Betulinic acid exerts anti-angiogenic activity via regulation of HIF-1 alpha and STAT3 in PC-3 prostate cancer cells under hypoxia
Authors: Bong I. Kim, Jimin Shin, Deok B. Jung, Moon Y. Park, Hyun Suk Ko, Hyo Sook Song, Wonil Koh, Ji Hoon Jung, Tae-Rin Kwon, Ihn Han, Ji-Hyun Kim, Sun-Mi Yun, Yun-Hee Rhee, Sung Yun Cho, Hyo-Jung Lee, Hyo-Jeong Lee, Soo-Jin Jeong, Eun-Ok Lee, Sung Hoon Kim
Journal: Cancer Research (2011)

Abstract Signal transducer and activator of transcription 3 (STAT3) is a transcription factor constitutively overexpressed in several human cancer cells and related to various cellular processes such as cell survival, angiogenesis and proliferation. In the present study, we examined whether betulinic acid (BA), a triterpene from the bark of white birch, could inhibit hypoxia-mediated activation of STAT3 and HIF-1 alpha in androgen independent human prostate cancer PC-3 cells. Our results show that BA inhibited the transcriptional activities and nuclear accumulation of both HIF-1 alpha and STAT3 under hypoxia. In addition, BA significantly reduced cellular and secreted levels of hypoxia-induced vascular endothelial growth factor (VEGF), a critical angiogenic factor, in PC-3 cells. BA prevented in vitro capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxia-induced PC-3 cells. Moreover, silencing HIF 1 alpha and STAT3 by siRNA transfection augmented the suppression of VEGF expression by BA under hypoxia. Mechanistically, BA inhibited the recruitment of HIF-1 alpha and STAT3 on the VEGF promoter. Taken together, these findings suggest that BA may exert angio-prevention via inactivation of hypoxia-induced STAT3 and HIF-1 alpha in PC-3 cells. The in vivo anti-angiogenic and anti-PCa efficacy are being evaluated. 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 2047. doi:10.1158/1538-7445.AM2011-2047
Location of Aldosterone-Producing Adenomas with<sup>131</sup>I-19-Iodocholesterol
Authors: Michael J. Hogan, James McRae, Morris Schambelan, Edward G. Biglieri
Journal: New England Journal of Medicine (1976)

We used 131I-19-iodocholesterol as an adrenal-imaging agent in 27 hypertensive patients who had biochemical evidence of abnormalities in the renin-angiotensin-aldosterone system. In 10 of 12 patients in whom the biochemical findings suggested the presence of an aldosterone-producing adenoma the adrenal uptake was asymmetric. The adenoma was subsequently confirmed in all eight patients in this group who underwent operation. In contrast, the adrenal uptake was asymmetric in only one of 13 patients with biochemical evidence of iodopathic hyperaldosteronism or low-renin essential hypertension. Two patients with adrenal carcinoma causing primary aldosteronism did not concentrate the isotope in their tumors. When metabolic studies suggest an aldosterone-producing adenoma, adrenal imaging with 131I-19-iodocholesterol may locate the tumor before operation.
Improvement by Acetylcysteine of Hemodynamics and Oxygen Transport in Fulminant Hepatic Failure
Authors: Phillip M. Harrison, Julia A. Wendon, Alexander E.S. Gimson, Graeme J.M. Alexander, Roger Williams
Journal: New England Journal of Medicine (1991)

When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption.
Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study
Authors: Liesbet De Bus, Wouter Denys, Julie Catteeuw, Bram Gadeyne, Karel Vermeulen, Jerina Boelens, Geert Claeys, Jan J. De Waele, Johan Decruyenaere, Pieter O. Depuydt
Journal: Intensive Care Medicine (2016)
A MEMORABLE PATIENT
Authors: R G Crawford
Journal: BMJ (1996)

A few years before the second world war I was acting as a house surgeon. A patient was admitted with a hand injury. He was a manual worker, right handed. He had tried to catch a falling carving knife with his right hand. All the fingers were deeply cut at the base of the fingers. The resident surgical officer told me to cut the fingers off, keeping a good flap of skin so that I could sew and leave the scar away from the metacarpal heads. …
S53 Outcomes of the RePneu Endobronchial Coils For the Treatment of Severe Emphysema with HyperinflaTion (RESET) Trial: Abstract S53 Table 1
Authors: Z Zoumot, S Kemp, R Chaudhuri, C Caneja, S Bicknell, N Hopkinson, S Singh, E Ross, P Shah
Journal: Thorax (2012)

<h3>Background</h3> The predominant pathophysiology in severe emphysema with gas trapping and hyperinflation is that of dynamic airway collapse on minimal expiratory effort. This limits the benefit from drug therapy. Safer and cheaper alternatives to lung volume reduction surgery (LVRS), which has success in selected patients with low exercise capacity and upper lobe-predominant emphysema, are being developed. Endobronchial valve treatment has been shown to be beneficial to patients with heterogenous disease in the absence of collateral ventilation. RePneu Lung Volume Reduction Coils (LVRCs) are self-actuating implantable devices composed of nitinol. They are implanted bronchoscopically using conscious sedation. The LVRC is delivered into targeted airways using fluoroscopic guidance, and when its sheath is removed recoils to it original pre-determined shape. <h3>Methods</h3> In a prospective randomised study of LVRCs on patients with severe emphysema and hyperinflation, 63 patients were screened at 3 centres in the United Kingdom with 23 randomised to treatment with LVRCs and 24 to best medical care (control). LVRC patients were initially treated in one lung, with the contralateral lung treated after one month if appropriate. The primary end point was the difference between treatment and control groups in the St. George’s Respiratory Questionnaire (SGRQ) 90 days post-final treatment. The trial is registered with ClinicalTrials.gov (NCT01334307). <h3>Results</h3> Significant improvements in the treatment group compared to control group were observed for the primary end point mean SGRQ (Δ-10.54 points, p=0.004), as well as secondary end points mean six-minute walk distance (Δ+70.39 metres, p&lt;0.001) and forced expiratory volume in one second (Δ+12.81%, p=0.009). Between group difference in change in mean residual volume did not reach significance (Δ-0.35 litres, p=0.051), despite a 0.64 litre reduction in the treatment group. There was a good safety profile with treatment. <h3>Conclusions</h3> Treatment with endobronchial coils in patients with severe emphysema and hyperinflation significantly improves quality of life, exercise capacity and pulmonary function with a good safety profile. LVRCs present a novel, safe, and minimally invasive treatment option for patients with both homogenous and heterogenous emphysema, with benefits unaffected by collateral ventilation. A larger randomised controlled pivotal trial with longer follow-up is now needed. Funding shared by PneumRx and study sites.
Abstract 3720: Obesity and mortality among black women and white women with invasive breast cancer
Authors: Yani Lu, Huiyan Ma, Kathleen E. Malone, Sandra A. Norman, Jane Sullivan-Halley, Brian L. Strom, Polly A. Marchbanks, Robert Spirtas, Ronald T. Burkman, Dennis Deapen, Suzanne G. Folger, Michael S. Simon, Michael F. Press, Jill A. McDonald, Leslie Bernstein
Journal: Cancer Research (2011)

Abstract PURPOSE To evaluate the effect of obesity on survival among black and white women with invasive breast cancer; and determine whether different distribution of obesity accounts for the poorer survival of black women. METHODS 4538 (1604 black, 2934 white) women ages 35 to 64 years when diagnosed with first incident invasive breast cancer between 1994 and 1998, who participated in the Women's Contraceptive and Reproductive Experiences Study, were followed up for a median of 8.6 years. Multivariate Cox regression models were used to examine height, body mass index (BMI, kg/m2) at different ages on the risk of all-cause mortality and breast cancer-specific mortality. RESULTS During follow-up, 1053 (519 black, 534 white) women died, 828 (412 black, 416 white) from breast cancer. Compared to women with a recent (5 years before diagnosis) BMI of 20-24.9 kg/m2, those who were obese (BMI≥30 kg/m2) had a greater risk of all-cause mortality (relative risk [RR], 1.23; 95% confidence interval [CI], 1.04-1.47) and breast cancer-specific mortality (RR, 1.20; 95% CI, 0.99-1.46). However, these risk patterns were only observed among white women (all-cause RR, 1.54; 95% CI, 1.21- 1.96; breast cancer RR, 1.46; 95% CI, 1.11-1.92), but not among black women (all-cause RR, 1.03; 95% CI, 0.81-1.29; breast cancer RR, 1.02; 95% CI, 0.79-1.33).Similar risk patterns were observed in different strata of estrogen receptor(ER) status, tumor stage, menopausal status, and education level. CONCLUSION Obesity may play an important role in mortality among white but not black breast cancer patients. It is unlikely that differences in obesity distributions between black and white women account for the poorer survival of black women. 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 3720. doi:10.1158/1538-7445.AM2011-3720
A clinico-pathological analysis of breast cancer patients with a family history.
Authors: T Hojo, T Kinoshita, M Kikuyama, E Nakano, S Akashi, T Khono, M Ando, N Katsumata, Y Fujiwara
Journal: Cancer Research (2009)

Abstract Abstract #6090 Background: It has been said that the high incidence of breast cancer within family lines could be investigated efficiently from genetic and environmental aspects. There could be a strong enough relationship between various carcinogenic factors and these family members. In this study, we examined the clinical and pathological characteristics of breast cancer among patients with a family history.&amp;#x2028; Patients and Methods: We put the definition of 'Positive for a family history (FH+)' for patients who had one or more members within three generations apart from the proband. Patients with family history of breast cancer were selected out of 10506 patients who were treated in our hospital between 1962 and 2007.&amp;#x2028; Results: There were 1272 cases in FH+ and 9234 cases in 'Negative for a family history (FH-)' group. Distribution within the family line showed the highest percentage for sisters at 37%, aunts at 25% and a mother at 25%. The family history positive breast cancer patients were around 5% in 1960-1970 although the number increased up to 18% in 2007. There was similar increasing pattern in Europe and America. The survival rate had no significant difference between FH+ and FH- statistically, but the trend was toward a better prognosis in FH+ cases. There was no relationship between family history and body mass index (BMI). The outbreak of contralateral breast cancer of FH+ was significantly higher than FH-. FH+ patients had significantly higher prevalence of a mastopathy compare to FH- patients. As for the history of other cancer species, the FH+ breast cancer patients within first generation apart from the proband had significantly higher chances compared to FH- patients.Conclusion: The breast cancer patients with family history require more detail examinations especially for the development of contralateral breast cancer. Also carcinomatous examinations are important other than breast cancer to those patients who are in the first generation apart from the proband. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6090.