tbuckley/cabot-search huggingface dataset:
GLOBAL BALLAD: An International Rare Cancers Initiative trial to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma (IRCI 002).
Authors: T.R. Jeffry Evans, Thomas Aparicio, Karine Le Malicot, Kenichi Nakamura, Yoshitaka Honma, Robert R. McWilliams, Albert J. Ten Tije, David Alan Anthoney, Ruth Boyd, Judith Dixon-Hughes, Janet Shirley Graham, Timothy Iveson, Jonathan Nicoll, James Paul, Manuel Salto-Tellez, Naureen Starling, Makoto Ueno, Kein Yim, John A. Bridgewater, Richard H. Wilson
Journal: Journal of Clinical Oncology (2016)

TPS4154 Background: Small bowel adenocarcinoma (SBA) is a rare cancer (< 5% of gastrointestinal tumours) with poor prognosis at all stages. There are no RCTs of adjuvant treatment following definitive surgery in stage I–III SBA, but the proven benefits of fluoropyrimidine-based adjuvant therapy (FP), with/without oxaliplatin (Ox), in colorectal cancer suggest this may be worthwhile. GLOBAL BALLAD aims to answer 2 questions in resected stage I–III SBA. (A)Where the clinician is uncertain, what is the value of adjuvant post-operative chemotherapy over observation? (B)Where the clinician is convinced of the value of adjuvant treatment, what is the value of adding Ox to FP chemotherapy? Methods: This is an open-label, randomised, controlled multi-centre trial with disease free survival as the primary endpoint. A standard frequentist phase III trial design results in an infeasible sample size. A hybrid approach has thus been adopted with a standard randomised phase II screening design augmented, using Bayesian techniques, by subjective clinician estimates of treatment effect based on external evidence. The study is designed to have 80–90% power to detect HR = 0.775 for each question at the 20% 1-sided significance level. If results are statistically significant, the study data will be combined with clinician estimates of treatment benefit to give an overall estimate. The numbers required are 580–880 patients. For question A, patients are randomised 1:1 between FP+/-Ox and observation. For question B, randomisation is 1:1 FP v FP +Ox. To ease recruitment choice of FP is allowed. Patients allocated to chemotherapy in A may also be randomised to have Ox or not, boosting recruitment to randomisation B and trial efficiency. All patients will have pre-treatment tumour samples and venous blood collected for genomic studies for exploratory prognostic and predictive markers. All patients complete a questionnaire for risk factors for SBA. The study is currently open in UK and France with funding from Cancer Research UK (grant CRUK/12/041) and Programme Hospitalier De Recherche Clinique respectively. It is under internal review in Japan. EudraCT No: 2013-003047-29 Clinical trial information: 15070952.
Change of Unresolved Attachment in Borderline Personality Disorder: RCT Study of Transference-Focused Psychotherapy
Authors: Anna Buchheim, Susanne Hörz-Sagstetter, Stephan Doering, Michael Rentrop, Peter Schuster, Peter Buchheim, Dan Pokorny, Melitta Fischer-Kern
Journal: Psychotherapy and Psychosomatics (2017)
Abstract 20313: Long-Term Prognostic Value of Myocardial Fibrosis in Chagas’ Disease
Authors: Tiago Senra, Barbara Ianni, Charles Mady, Martino Martinelli, Roberto Kalil Filho, Carlos E Rochitte
Journal: Circulation (2016)

Introduction:  Chagas’ disease (CD) affects 5.7 million people in Latin America, with 12,500 deaths/year. Chagas’ cardiomyopathy (CC) is the main cause of death and portends poorer prognosis than other cardiomyopathies. Cardiovascular magnetic resonance (CMR) detects myocardial fibrosis (MF), a marker of disease severity in CC.   Hypothesis:  We hypothesise that MF by CMR is a predictor of a composite endpoint of death from any cause, cardiac transplant, aborted sudden death and appropriated ICD therapy in long-term follow-up.   Methods:  Serologically positive CD patients (pts) who had a CMR study with late gadolinium enhancement (LGE) from 2001 to 2011 were followed-up by medical records/phone calls. We excluded pts with myocardial infarction, significant CAD, valvular disease and other cardiomyopathies. Cine and LGE images were acquired in a 1.5 T scanner (GE CV/i or Philips Achieva) with standard parameters for ventricular function and MF assessment. LGE images acquired 10-20 min after 0.2mmol/kg of IV gadolinium-based contrast. MF was quantified by threshold technique (5 SD above normal myocardium) using CVi42 software (Circle CVi).   Results:  We included 131 pts, 62(47%) women, mean age of 53.7±11.4 and a mean follow-up of 2182±1668 days. Fifty-eight (44.6%) pts reached the endpoint, with 51(87.9%) showing MF. MF was present in 93 (70.9%) pts, 51 (54.8%) pts reached endpoint. (p   Conclusions:  Myocardial fibrosis detected by CMR in patients with Chagas’ disease was significantly and independently associated to poor long-term prognosis. This original finding may help risk-stratification of this important and neglected disease.
AB1037 Interobserver reliability of knee osteoarthritis lesions using musculoskeletal ultrasound: differences between static versus real time reading
Authors: MJ Audisio, AM Bertoli, GE Py
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Musculoskeletal ultrasound (MSU) is an imaging technique proved to be valid in several musculoskeletal conditions. In osteoarthritis (OA) it allows the identification of inflammation and structural damage. However, MSU is an operator dependent method and its widespread use has been hampered by questions related to the reliability of both, image acquisition and image interpretation. <h3>Objectives</h3> The objective of this study was 1) to evaluate the interobserver reliability of knee OA according to the definitions used by the OMERACT reliability exercise of inflammatory and structural abnormalities in patients with knee osteoarthritis using ultrasound and 2) to compare the interobserver reliability on previous collected images (static reading, thereafter) versus after the acquisition and interpretation of images in real time (real time reading, thereafter). <h3>Methods</h3> A reliability exercise based on the reading of US images was conducted by two experienced rheumatologists in MSU. A set of 59 images of both, normal and OA knee lesions were collected for the static reading. A set of 20 knees were scanned by each rheumatologist for the real time reading. Dichotomous and semi-quantitative scoring (0–3) was performed for the presence of damage on the condrosynovial margin, osteochondral margin and matrix of the throchlear cartilage, osteophytes at the lateral and medial femoral condyle and proximal tibia, medial and lateral meniscal extrusion and Baker9s cyst. Interobserver reliability was calculated by the Cohen9s kappa coefficient. <h3>Results</h3> Interobserver reliability scores for the static reading were good for cartilage damage, meniscal extrusion and Baker9s cyst, while they were excellent for the presence of osteophytes. The scores for the real time reading were poor to moderate for cartilage damage, osteophytes and Baker9s cyst and good for meniscal extrusion. These results are shown in Table 1. <h3>Conclusions</h3> This exercise shows that the interobserver reliability of MSU for the detection of knee OA lesions is widely different depending on the type of reading (static versus real time). Although MSU seems to be reliable for the detection of knee OA lesions, caution needs to be taken in the interpretation of published data regarding the type of reading exercise performed. <h3>References</h3> Ann Rheum Dis 2016;75:842–846. <h3>Disclosure of Interest</h3> None declared
AB0059 Synovial secretion of pro-inflammatory and pro-oxidant molecules triggered by monosodium urate crystals induces ngf and h2o2 pain mediators in the chondrocyte
Authors: AG Lopez-Reyes, D Medina-Luna, M Satamaria-Olmedo, K Martinez-Flores, Y Zamudio-Cuevas, J Fernandez-Torres, G Martinez-Nava, D Clavijo-Cornejo, A Olivos-Meza, M Gutierrez, M Fernandez-Moreno, F Blanco, C Pineda
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout is the most prevalent inflammatory arthropathy in young men, in which clinical manifestations are triggered by the deposits of monosodium urate (MSU) crystals in and around joints. From a clinical perspective, gouty attacks and tophaceous deposits have been associated to nodal osteoarthritis [1,2]. <h3>Objectives</h3> To determine the molecular mechanisms associating MSU crystal deposits with chondrocyte activation and changes in articular cartilage. <h3>Methods</h3> Primary cultures of synoviocytes were activated with MSU crystals for 24 h, the resulting supernatant was used as a supplementary conditioning basal medium (CBM) for 24 h chondrocyte growth. The expression level profile of cytokines (IL-6, IL-8) and nerve growth factor (NGF) in the supernatant was measured. Production of reactive oxygen and nitrogen species, such as O<sub>2</sub><sup>●</sup>, H<sub>2</sub>O<sub>2</sub>, and NO<sup>●</sup>, was also measured intracellularly. <h3>Results</h3> Upon activation by MSU crystals, synoviocytes increased secretion of IL-6 and IL-8, as well as intracellular production of O<sub>2</sub><sup>●</sup>, H<sub>2</sub>O<sub>2</sub>, and NO<sup>●</sup> in comparison to non-stimulated synoviocytes. Additionally, the chondrocytes incubated with CBM for 24 h increased significantly IL-6, IL-8, and NGF levels, as well as O<sub>2</sub><sup>●</sup>, H<sub>2</sub>O<sub>2</sub>, and NO<sup>●</sup> levels when compared to non-stimulated chondrocytes. Secretion of these soluble mediators was even higher than the one observed in the synoviocytes and chondrocytes directly stimulated with MSU crystals. <h3>Conclusions</h3> Pro-inflammatory cytokine secretion induced by MSU crystals in synoviocytes triggers chondrocyte activation, intensifying the articular inflammatory state in gouty attacks. Furthermore, the increase in reactive species (particularly NO<sup>●</sup>, which inhibits proteoglycan synthesis) compromises the homeostasis of the extracellular matrix of the cartilage. Finally, overproduction of NGF and H<sub>2</sub>O<sub>2</sub> by the chondrocyte functions a pain modulator during gout attacks. <h3>References</h3> Fam AG, et al. Gouty arthritis in nodal osteoarthritis. J Rheumatol 1996; 23:684–9. Roddy E, et al. Gout and nodal osteoarthritis: a case-control study. Rheumatology (Oxford) 2008; 47:732–3. <h3>Disclosure of Interest</h3> None declared
AB0045 Il-17 induced glucocorticoid insensitivity might be dependent on the reduced 11beta-hsd1 enzyme activity
Authors: M Vitiello, V Kunnathully, G Orsolini, O Viapiana, F Poli, A Mattè, L De Franceschi, L Idolazzi, D Gatti, M Rossini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> It has been demonstrated that IL-17A is able to induce GC insensitivity. Although several studies have reported the role of IL-17 in GC insensitivity the mechanism underlying remains still largely unclear. <h3>Objectives</h3> To understand the effects of interleukin-17 (IL-17) on the enzyme 11β-hydroxysteroid dehydrogenases (11β-HSDs) in the two main classes of monocytes, CD14 and CD16. <h3>Methods</h3> Peripheral Blood Mononuclear Cells (PBMCs) were isolated from 5 healthy donors and were sorted into CD14 and CD16 subpopulations using cell sorting. Effect of IL-17 on 11β-HSD1 enzyme activity was measured in terms of conversion of cortisone to cortisol in sorted and unsorted monocytes using Homogeneous Time-Resolved Fluorescence (HTRF). The direct involvement of 11β-HSD1 in the conversion of cortisone to cortisol was confirmed using carbenoxolone, an inhibitor of 11β-HSD1. <h3>Results</h3> Monocytes showed a concentration-dependent decrease in the 11β-HSD1 enzyme activity when incubated with increasing concentrations of IL-17. CD14 and CD16 cells stimulated similarly with IL-17 showed a significant difference in the enzyme activity between the untreated and stimulated cells in all treatment groups. However, a dose dependent decrease was observed only in case of CD14 cells. Both unsorted monocytes and monocyte sub-populations showed a significant decrease in the concentration of cortisol measured when co-incubated with carbenoxolone, indicative of the direct involvement of 11β-HSD1 enzyme in the conversion of cortisone to cortisol. <h3>Conclusions</h3> The results of this study showed that IL-17 induced GC insensitivity might be dependent on the reduced 11β-HSD1 enzyme activity in inflammatory conditions. We showed that the pro-inflammatory cytokine IL-17 causes a significant decrease in the 11β-HSD1 enzyme activity. <h3>Disclosure of Interest</h3> None declared
Transcription repressor Slug promotes cancer cell invasion and predicts outcome of patients with lung adenocarcinoma.
Authors: Jin-Yuan Shih, Meng-Feng Tsai, Yih-Leong Chang, Ang Yuan, Chong-Jen Yu, Jen-Liang Su, Pan-Chyr Yang
Journal: Cancer Research (2006)

5132   In a previous genome-wide gene expression profiling analysis using an invasion cancer cell lines model, we have identified  Slug  was selectively overexpressed in the highly invasive cancer cells. Here, we investigated the clinical significance of  Slug  in lung adenocarcinoma and the role of Slug in the process of cancer cell invasion and metastasis. Real-time quantitative reverse transcription PCR was used to investigate  Slug  mRNA in surgically resected lung adenocarcinoma of 54 patients. There were no differences in age, gender, disease stage, tumor status and lymph node metastasis between the high and low  Slug  expression group. High expression of  Slug  mRNA in lung cancer tissue was significantly associated with post-operative relapse ( P  = 0.03) and shorter patient survival ( P   Slug  mRNA expression ( P  = 0.02), stage of disease ( P  = 0.01) and age ( P  = 0.002) were the significant prognostic factors for survival, whereas  Slug  mRNA expression ( P  = 0.002) and stage of disease ( P   Slug  in a lung adenocarcinoma cell line with very low Slug levels and investigated the  in vitro  and  in vivo  effects of  Slug  expression. The overexpression of  Slug  enhanced xenograft tumor growth and increased microvessel counts in angiogenesis assay. Both inducible and constitutive overexpression of  Slug  suppressed the expression of E-cadherin and increased the  in vitro  invasive ability. Overexpression of  Slug  did not affect the cancer cell migration on wound assay. Zymography revealed increased MMP-2 activity in  Slug  overexpressed cells. ELISA, RT-PCR and immunohistochemistry confirmed the increase of MMP-2 proteins and mRNA in  Slug  overexpressed cells and xenograft tumors. In conclusion,  Slug  expression can predict the clinical outcome of lung adenocarcinoma patients. Increase of cancer cell invasion by  Slug  is mediated through the suppression of E-cadherin and up-regulation of MMP-2.  Slug  is a novel invasion-promoting gene in lung adenocarcinoma.
Survival impact of aggressive treatment on patients with oligometastatic non-small cell lung cancer (NSCLC).
Authors: Camille Gauvin, Normand Blais, Mustapha Tehfe, Marie Florescu
Journal: Journal of Clinical Oncology (2017)

e20669 Background: The new 2016lung cancer classification differentiates oligometastatic (M1b) better prognostic from plurimetastatic (M1c) disease. A prospective study presented at 2016 ASCO showed improved PFS in patients with oligometastatic brain disease treated aggressively compared to a more palliative treatment but OS data is pending. Methods: This study is a single-center retrospective study including 643 patients with metastatic lung cancer diagnosed in an University center (CHUM) from 2005-2015 and followed more than 6 months (median follow up 13.3mo) . Only 67 patients (10.4%) were found to have synchronous oligometastatic disease at diagnosis. Results: Amongst the 67 patients, the localization of metastatic disease was as follows: 74% brain (n = 50), 9% adrenal gland (n = 6), 7% contralateral pulmonary lobe (n = 5), 6% bone (n = 4) and 3% liver (n = 2). 29 patients received radical treatment to primary and metastatic site (group A) and 36 patients received non-aggressive treatments (group B). There was no statistically significant difference between the two groups in terms of demographic and histological characteristics. The radical treatment group A had a mOS of 26mo and a mPFS of 12.8m compared to mOS of 5mo (p = 0.0001) and mPFS of 4.8mo (p = 0.010) for group B. This difference was observed when stratifying according to stage of primary lung disease (stage I mOS 42mo vs 16mo, stage II mOS 34mo vs 6mo and stage III mOS 22mo vs 4mo) and according to to oligometastatic site. Interestingly, addressing aggressively the primary lung cancer improved median survival even when the oligometastasis was not resected (26mo v and 24mo respectively), but not when oligometastasis only was resected and primary was treated palliatively (5mo vs 3 mo). Adjuvant chemotherapy given after radical treatment did not improve mPFS or mOS (12.83 vs12.47 months, p = 0.860). Conclusions: Radical treatment of oligometastatic NSCLC in this unselected population improved mPFS and mOS compared to other treatment strategies. As overall survival data of the prospective trial presented at 2016 ASCO meeting is pending, the more radical approach should be emphasized when patients present with oligometastatic lung cancer disease.
SAT0713 Survey on prevalence of rheumatic disorders in bangladeshi adults
Authors: S Ahmed, SA Haq, AZ Al-qadir, MM Rahman, S Paul
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> From Community based COPCORD (community oriented program for control of rheumatic diseases) study in Bangladesh about a quarter of people is suffering from musculoskeletal disorders. But the study was conducted over a small number of samples and some specific localities of the country. So further study was required, covering the whole Bangladesh to justify this high prevalence. <h3>Objectives</h3> To determine the prevalence of musculoskeletal symptoms and specific rheumatic disorders in adult population of Bangladesh. <h3>Methods</h3> In this survey, a total of 2000 individuals aged 18 years or older were selected in twenty clusters (primary sample unit) from the seven divisions of the country. Modified COPCORD (Community Oriented Program for Control of Rheumatic Disorders) questionnaire was used to detect positive respondents. Standard criteria were used for diagnosing rheumatic disorders. Clinical judgment was used to solve diagnostic problems. <h3>Results</h3> In total 1843 individuals were interviewed with a response rate of 92.1%. The point prevalence of musculoskeletal pain was 33.7%. It was higher in women (38.7%) than men (28.4%) and higher in rural (34.5%) than that in urban (32.4%) areas. Higher prevalence rates were observed in homemakers (16.0%), laborers (3.0%), business professionals (2.9%) and cultivators (2.8%). Low back (23.3%), knee (12.7%) and shoulder (6.1%) were the most frequent site of complaint. Non specific low back pain (12.7%) and knee osteoarthritis (7.3%) were the two top ranking disorders. The prevalence of rheumatoid arthritis was 1.6% and spondyloarthritis 1.2%. 5.5% of the respondents had disability from rheumatic problems. <h3>Conclusions</h3> About one third of the Bangladeshi adults suffer from musculoskeletal pain at a given point of time. There are residence and gender variation in the prevalence rates. Low back and knee pain were the principal sites of complaints. <h3>Disclosure of Interest</h3> None declared
Abstract P323: Waon Therapy, a Form of Thermal Therapy, Reduces Oxidative Stress Systemically and Inhibits the Progression of Cardiac Dysfunction in TO-2 Cardiomyopathic Hamsters with Heart Failure
Authors: Yoshiyuki Ikeda, Masaaki Miyata, Yuichi Akasaki, Takahiro Miyauchi, Yuko Furusho, Kanako Ide, Shuich Hamasaki, Chuwa Tei
Journal: Circulation Research (2011)

Background: Oxidative stress is one of the most crucial factors that develop chronic heart failure (CHF), leading to cardiac apoptosis and fibrosis and vascular endothelial dysfunction. We have reported that Waon therapy, which is a form of thermal therapy using a far infrared-ray dry sauna at 60 degrees centigrade, improves cardiac and vascular endothelial functions and prognosis in patients with CHF. The aim of this study is to investigate whether Waon therapy reduces oxidative stress and prevents from developing cardiac dysfunction in CHF. Methods: Thirty-week old male TO-2 cardiomyopathic hamsters with CHF were divided into Waon therapy or control group. Waon therapy group underwent Waon therapy daily for 4 weeks. Control hamsters did not take any treatment. We examined the amounts of reactive oxygen species of serum, hearts and aortas using ELISA and immunohistochemistry. We measured left ventricular % fractional shortening (LV%FS), and performed TUNEL and Azan staining of hearts to assess cardiac function, apoptosis and fibrosis, respectively. Anti-oxidants and apoptotic and angiogenetic factors were assessed by Western blot. All examinations were performed after 4 weeks of treatment. Results: Four-week Waon therapy significantly decreased oxidative stress of serum, hearts and aortas compared to those of controls. Waon therapy significantly increased LV%FS and decreased cardiac apoptosis and fibrosis (LV%FS, Waon therapy: 23.3±4.3 vs. control: 16.5±4.2%, P&lt;0.01, TUNEL positive nuclei, 22.0±2.6 vs. 49.3±7.2%, P&lt;0.01, % fibrosis, 20.6±5.3 vs. 47.6±4.8%, P&lt;0.01). Waon therapy significantly increased the expressions of manganese superoxide dismutase, heat shock protein 27 (HSP27) and HSP32 of hearts and aortas, which negatively modulate oxidative stress, compared to those of controls. Waon therapy significantly increased endothelial nitric oxide synthase and decreased plasminogen activator inhibitor-1 of aortas. In addition, Waon therapy significantly decreased Bax, cleaved caspase 3 and cytochrome c and increased Bcl-2 and hypoxia-inducible factor-1α of the failing hearts. Conclusions: Waon therapy reduces oxidative stress systemically and inhibits the progression of cardiac dysfuntion in TO-2 cardiomyopathic hamsters.
Credibility and trust are required to judge the benefits and harms of medicines
Authors: David B Menkes, Dick Bijl
Journal: BMJ (2017)

Freer and Godlee consider the serious doubts held by both the public and the profession regarding drug efficacy and safety, and they lament the weak recommendations made by the Academy of Medical Sciences to tackle the fundamental problem of conflicts of interest in drug information.12

Medical journals have a key role in accessing clinical trial and other evidence on drugs, …