tbuckley/cabot-search huggingface dataset:
Hematemesis from ruptured aberrant right hepatic artery aneurysm eroding through the duodenal wall
Authors: Y. Kim, S. Satapathy, L. Law, A. Volfson, B. Friedman, S. Yang, C. Sung, D. Siegel, B. DeVito
Journal: Endoscopy (2011)

A 56-year-old man presented with hematemesis and multiple episodes of melena. He had a history of chronic lymphocytic leukemia and traumatic rupture of the spleen leading to splenectomy and splenic artery embolization 6 years earlier.
P21 Success rate of sputum induction in the Leicester paediatric severe asthma clinic using
Authors: R. Herzallah, K. Staley, M. M. Feeters, C. Brightling, P. Bradding, D. Parker, H. Pandya, E. Humphreys, E. Gaillard
Journal: Thorax (2010)

<h3>Background</h3> Asthma is a common disease affecting about one in four children in the UK. It is characterised by variable airway obstruction, bronchial hyper responsiveness and influx of inflammatory cells into the bronchial mucosa. However, the mechanism of childhood asthma is still not well understood. Moreover, a subgroup of children with asthma has difficult to treat asthma, defined as persisting symptoms despite maximal conventional therapy. Management decisions in this subgroup are particularly difficult. These patients are often on high doses of steroids, with the attendant risk. A recent study in adults showed that titrating the dose of steroids to sputum eosinophils provided better asthma control without increasing the cumulative doses received by a patient. Neutrophilc airway inflammation was also shown to be a feature of some patients with difficult asthma, which may explain their poor response to corticosteroids. Therefore, knowing the inflammatory cell pattern in our cohort of children with difficult to treat asthma could potentially be a very useful tool in their management. To aid in our understanding and management of our children with difficult asthma we routinely evaluate induced sputum from children over the age of 6 years for the presence of airway inflammatory cells. A dedicated paediatric sputum lab with negative pressure facilities was made available to us by the hospital. <h3>Study Aims</h3> To review the protocol, success rate and pattern of airway inflammation in our cohort of children with severe asthma. <h3>Methods</h3> Review of all paediatric sputum inductions performed between March 2008 and February 2010. <h3>Results</h3> Between March 2009 and February 2010, 57 sputum inductions were performed on 40 children, 50% males, between 6 and 18 years of age (median=12.5 years). A differential inflammation cell count was obtained from 52 of the 57 samples, giving a success rate of more than 90%. There was no significant difference in the inflammatory cell pattern between those on BTS step 3 and those on BTS steps 4 and 5. 42% of our patients had eosinophila (defined as more than 3% eosinophils), 31% had neutrophila (defined as more than 54% neutrophils), 13% had both eosinophilia and neutrophilia and only 13% had a normal inflammatory cell pattern (Abstract P21 Table 1). <h3>Conclusions</h3> 1. Adequate sputum samples are obtained from most children with severe asthma when performed in a dedicated induced sputum laboratory. 2. A sputum eosinophilia was present in 55% of children studied with severe asthma. 3. The clinical value of monitoring airway inflammation in children with severe asthma using sputum induction remains to be established.
Abstract 4644: PDGFRα/β and VEGFR2 SNPs incolorectal cancer.
Authors: Purificacion Estevez-Garcia, A Castaño, Ana Martin, Fernando Lopez-Rios, J Iglesias, Sandra Muñoz-Galvan, Iker Lopez-Calderero, Sonia Molina-Pinelo, Maria D. Pastor, Amancio Carnero, Luis Pa-Ares, Rocio Garcia-Carbonero
Journal: Cancer Research (2013)

Abstract Angiogenesis plays an essential role in tumor growth and metastasis, and is a major target in cancer therapy. VEGFR and PDGFR are key players involved in this process. The purpose of this study was to assess the incidence of genetic variants in these receptors and its potential clinical implications in colorectal cancer (CRC). VEGFR2, PDGFRα and PDGFRβ mutations were evaluated by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples of patients with CRC. Correlations with clinicopathological features and survival were analyzed. Four SNPs were identified, three in PDGFRα [exon 12 (A12): c.1701A&amp;gt;G; exon13 (A13): c.1809G&amp;gt;A; and exon 17 (A17): c.2439+58C&amp;gt;A) and one in PDGFRβ (exon19 (B19): c.2601A&amp;gt;G) (figure 1). SNP B19 was present in 58% of tumor samples and in 4 cell lines (LS174T, LS180, SW48, COLO205), and this was associated with higher PDGFR and pPDGFR protein levels. 5-year survival was greater for patients with PDGFR B19 wild type tumors (AA) than for those harboring the G-allele genotype (GA or GG) (51%vs17%; P=0.073). Multivariate analysis confirmed SNP B19 (P=0.029) was a significant prognostic factor for survival, independent of age (P=0.060) or TNM stage (P&amp;lt;0.001). In conclusion, PDGFRβ exon 19 c.2601A&amp;gt;G SNP is commonly encountered in CRC patients and is associated with increased pathway activation and poorer survival. Implications regarding its potential influence in response to PDGFR targeted agents remain to be ellucidated. Citation Format: Purificacion Estevez-Garcia, A Castaño, Ana Martin, Fernando Lopez-Rios, J Iglesias, Sandra Muñoz-Galvan, Iker Lopez-Calderero, Sonia Molina-Pinelo, Maria D. Pastor, Amancio Carnero, Luis Pa-Ares, Rocio Garcia-Carbonero. PDGFRα/β and VEGFR2 SNPs incolorectal cancer. [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 4644. doi:10.1158/1538-7445.AM2013-4644
Abstract 5105: Cyclosporin A and Cannabinoids induce autophagy-associated cell death in malignant glioma cells through inhibition of mTOR/S6K1 pathway
Authors: Iwona Ciechomska, Aleksandra Ellert-Miklaszewska, Bozena Kaminska
Journal: Cancer Research (2010)

Abstract Malignant gliomas, the most common and aggressive primary brain tumors, account for more than 40% of all central nervous system (CNS) neoplasms. Gliomas are highly resistant to available therapies (radiation, chemiotherapy) that induce apoptosis (type I programmed cell death). Autophagy is a self-digestion process important for cell survival during starvation but functioning also as an alternative death mechanism under certain conditions (type II programmed cell death). Autophagy is negatively regulated by mammalian target of rapamycin (mTOR) and can be induced by its inhibitor, rapamycin. Using a panel of glioma cell lines bearing mutations in TP53 or PTEN we have demonstrated that cyclosporin A (CsA, an immunophilins/calcineurin inhibitor) and synthetic cannabinoids (counterparts of marijuana active ingredient THC) inhibit growth of glioma cells in vitro and induce cell death with apoptotic features. However, CsA- and cannabinoids-induced death was accompanied by the appearance of numerous cytoplasmic vacuoles, therefore, we investigated whether and to what extent autophagy contributes to drug-induced cell death of human malignant glioma cells. Upon CsA and cannabinoids treatment several features characteristic of autophagy were observed: formation of the acidic vesicular organelles, increase in punctuate GFP-LC3 (microtubule-associated protein light-chain 3) and LC3-II accumulation. All of the drugs affected mTOR signaling pathway in glioma cells decreasing phosphorylation of 4E-BP1 (eukariotic initiation factor 4E binding protein 1), p70-S6 kinase 1 and its downstream target molecule S6 ribosomal protein. Our results demonstrate that CsA and synthetic cannabinoids induce some features of apoptosis and autophagy-associated cell death in malignant glioma cells via inhibition of mTOR/S6K1 pathway. We are currently investigating the role of autophagy in dying cells using pharmacological and genetic inhibition of autophagy. Studies supported by grant N N301 092036 from The Polish Ministry of Science and Higher Education. 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 5105.
Three-Dimensional Lymphoscintigraphy Using SPECT/CT and 123I-BMIPP for the Preoperative Detection of Anatomical Anomalies of the Thoracic Duct
Authors: Kentaro Takanami, Hirofumi Ichikawa, Hiroshi Fukuda, Shoki Takahashi
Journal: Clinical Nuclear Medicine (2012)

Orally administered I-labeled 15-(4-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP), a fatty acid analog, is absorbed from the intestine and ascends to the venous angle through the thoracic duct (TD). The objective of this study was to evaluate the clinical feasibility of 3-dimensional (3D) TD scintigraphy using SPECT/CT and BMIPP for the detection of anatomical anomalies of TD.This study included 35 consecutive patients with esophageal cancer who underwent tumor resection after TD scintigraphy. For scintigraphy, 111 MBq of BMIPP was orally administered, and static images and SPECT/CT images were obtained. On the basis of the SPECT/CT fusion images, TD was divided into the following 4 segments: cervical, upper thoracic, middle thoracic, and lower thoracic. The TD visualization was categorized into 5 grades, from grade 1 (poor) to 5 (excellent). In addition, the diagnostic accuracy of 3D TD scintigraphy for the detection of anatomical anomalies of TD was calculated using the intraoperative finding as a criterion standard.The TD visualization grades for the cervical, upper, middle, and lower thoracic segments were 4.4 ± 0.6, 3.7 ± 1.0, 3.1 ± 0.8, and 2.1 ± 0.9, respectively. The TD scintigraphy demonstrated an uncommon accumulation including that in the right- or bilateral-sided mediastinum or venous angle in 6 (17%) of the 35 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 3D TD scintigraphy for the detection of anatomical anomalies of TD were 0.75, 0.90, 0.5, 0.97, and 0.89, respectively.Three-dimensional TD scintigraphy by BMIPP is a simple and minimally invasive method for imaging the anatomical configuration of the TD and for detecting any anatomical anomalies, except in the lower thoracic segment.
Madelung's Disease
Authors: Luca Ampollini, Paolo Carbognani
Journal: New England Journal of Medicine (2011)

A 45-year-old man presented with a 3-year history of a painless, soft, and slow-growing swelling of the neck, upper trunk, upper back, and shoulders (Panels A and B). The patient had a history of heavy alcohol consumption and was a nonsmoker. Laboratory blood analysis showed minor elevations in aspartate aminotransferase (71 U per liter), alanine aminotransferase (49 U per liter), and total cholesterol (235 mg per deciliter [6.08 mmol per liter]). Triglycerides were very elevated at 1020 mg per deciliter (11.52 mmol per liter). Magnetic resonance imaging revealed diffuse, nonencapsulated fatty deposits in the mediastinum and in the subcutaneous and . . .
THU0341 Assessment of art therapy program for women with fibromyalgia: Randomized, controlled, blinded study
Authors: A.S. Baptista, A. Jones, F.P. Cardoso, B. Schaffir, E.R.W. Coelho, A. Orlandi, J. Natour
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia (FM) is a chronic non-inflammatory syndrome characterized by diffuse pain throughout the body, sleep disorder, stiffness, fatigue, depression and other psychological problems. Patients with FM feel incapable of performing the majority of activities of daily living. Medication offers only short-term benefits. Thus, it is necessary to include other measures for treatment, such as physical activity and patient education. Art therapy combine the field of psychology with artistic activities, working with therapeutic and instructive aspects as well as the potential for personal growth contained in all forms of art. <h3>Objectives</h3> The aim of the present study was to assess the effectiveness of an art therapy program for the treatment of pain and improvements in both quality of life and body image of patients with fibromyalgia. <h3>Methods</h3> A randomized, controlled study with a blinded evaluator and 20-week follow-up period was carried out involving 80 patients with fibromyalgia. A visual analog scale (VAS) pain and sleep the six-minute walk test, Fibromyalgia Impact Questionnaire (FIQ), Medical Outcome Survey Short Form 36 (SF-36), Beck Depression Inventory and Body Dysmorphic Disorder Examination (BDDE) questionnaire were used for the assessments, which were performed at baseline and after 10, 20 (end of intervention) and 40 weeks. <h3>Results</h3> The art group achieved statistically significant improvements in VAS for pain (p=0.001), VAS for sleep (p=0.027), FIQ (p=0.001), Beck Depression Inventory (p=0.038) and the physical functioning (p=0.027), role-physical, (p&lt;0.001), bodily pain (p=0.002), vitality (p=0.001), role-emotional (p=0.002) and mental health (p=0.010) subscales of the SF-36. Regarding body image no differences between groups was found over time. <h3>Conclusions</h3> Art therapy can be used in the treatment of fibromyalgia, leading to a reduction in pain and improvements in degree of depression and quality of life. <h3>References</h3> Valim V, Oliveira LM, Assis M, Barros TN, Feldman d, Natour J, et al. Aerobic fitness effects in fibromyalgia. J Rheumatol 2003; 30:1060-1069; E.H, Kowalski J, Theorell T, Anderberg U.M. Dance/movement therapy in fibromyalgia patients: Changes in self-figure drawings and their relation to verbal self-rating scales. Arts in Psychotherapy 2006; 33:11-25; SE, deHueck A., Voss S, Abbey SE. Six-Month and one-year followup of 23 weekks of aerobic exercise for individuals with fibromyalgia. Arthritis Care Res 2004; 51:890-98; AM, Komnaes HB, Forre O. The effects of 20 weeks of physical fitness training in female patients with fibromyalgia. Clin Exp Rheumatol 1992; 10(4):345-349. <h3>Disclosure of Interest</h3> None Declared
Successful treatment with an over-the-scope clip of Dieulafoy's gastric lesion resistant to conventional endoscopic treatment
Authors: B. Mangiavillano, M. Arena, E. Morandi, P. Viaggi, E. Masci
Journal: Endoscopy (2012)

Dieulafoy's lesion is a rare vascular abnormality in which a minute mucosal defect in an ectatic submucosal artery can be the cause of massive gastrointestinal hemorrhage [1].
AB0358 Umbilical cord mesenchymal stem cells inhibit the generation of t follicular helper cell in rheumatoid arthritis
Authors: R. Liu, M. Zhou, X. Li, D. Wang, L. Sun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The immune suppressive properties of mesenchymal stem cells (MSCs) have garnered increasing attention over the past decades. MSCs that derived from human umbilical cord (UC) share similar immunosuppressive properties as MSCs obtained from bone marrow and cord blood in vitro. Rheumatoid arthritis (RA) is characterized by persistent synovitis and systemic inflammation, frequently leading to cartilage and bone destruction. Previous studies showed that MSCs transplantation had effect in an animal model of RA. However, the mechanism remains largely unknown. <h3>Objectives</h3> The purpose of this study was to confirm the hypothesis that UC-MSCs might suppress the generation of T follicular helper (Tfh) cells in RA patients. <h3>Methods</h3> The percentages of CXCR5+PD-1+CD4+ cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMC) from RA patients and healthy controls. PBMC from RA patients stimulated with or without phytoagglutinin (PHA) were cultured with UC-MSCs supernatant or UC-MSCs at a ratio of 1 to 1, 1 to 10 or 1 to 100 in a cell-to-cell contact or in a transwell system for 3 days. Naïve T cells were isolated from PBMC of RA patients and then co-cultured with UC-MSC in the presence of anti-CD3, anti-CD28, anti-IFNg, anti-IL-4, anti-TGFb, IL-6, IL-21 and IL-12 for 4 days. The percentages of CXCR5+PD-1+CD4+ cells were tested by means of flow cytometry. <h3>Results</h3> The results showed that the circulating percentages of CXCR5+PD-1+CD4+ cells were significantly higher than that of healthy controls. UC-MSCs did not inhibit non-activated Tfh cells but dose-dependently inhibited the generation of Tfh cells when stimulated with PHA whether in a cell-to-cell contact or in a transwell system. The differentiation of Tfh cells were also blocked by UC-MSCs significantly. However, UC-MSCs supernatant was not able to suppress the generation of Tfh cells in RA. <h3>Conclusions</h3> These results suggest an inhibitory effect of UC-MSCs on the generation of Tfh cells via soluble factors secreted from UC-MSCs, which may be one the mechanism of UC-MSCs treatment in RA. <h3>Disclosure of Interest</h3> None Declared
P17 The burden of ICS/LABA-treated asthma patients in the UK adult population
Authors: D Price, N Mathieson, A Mulgirigama, A Scowcroft, R Pedersini, G Isherwood, ID Pavord
Journal: Thorax (2013)

<h3>Objectives</h3> According to NHS QOF (Quality and Outcomes Framework) figures, 3.3 million UK citizens have asthma. Previous studies have shown an association of asthma with increased direct and indirect healthcare costs, but similar studies have not been conducted specifically for UK asthma patients. The aim of the current study is to assess the impact of poor asthma control on UK patients treated with ICS + LABA maintenance treatment. <h3>Methods</h3> Data were from the 2010 and 2011 UK National Health and Wellness Survey (NHWS), an Internet-based questionnaire from a representative sample of UK adults stratified by age and gender. 701 respondents self-reported a diagnosis of asthma without concomitant COPD, chronic bronchitis, or emphysema and were currently being treated with ICS + LABA. Patients Not Well Controlled (NWC) according to ACT (score &lt; 20) were compared to well-controlled (WC) patients (score ≥ 20) on demographics, medications, health status, BMI, comorbidities, adherence (MMAS-4), healthcare use (number of physician visits, emergency visits and hospitalizations), work productivity and activity impairment (WPAI) and health-related quality of life (HR-QoL) (SF-12). <h3>Results</h3> A greater proportion of the 452 NWC patients (64% of the overall sample) go to emergency (21% vs. 14%, p = 0.016) or are hospitalised (13% vs. 8%, p = 0.022), in comparison with the WC; Their mental and physical HR-QoL is lower (SF-12 MCS: 43 vs. 47/100; PCS: 40 vs. 48/100; Health utility: 0.65 vs. 0.74/1.00; all p’s &lt; 0.001);while their work and activity impairment are greater: presenteeism (23% vs. 11%, p &lt; 0.001), overall work impairment (29% vs. 17%, p &lt; 0.001) and activity impairment (46% vs. 24%, p &lt; 0.001). In the current sample, NWC did not show significantly different levels of adherence from WC (50% vs. 55%, p = 0.361). <h3>Conclusions</h3> Over 60% UK ICS + LABA-treated adult patients are poorly controlled. Poor control is associated with lower HR-QoL, greater healthcare use and productivity impairment, but not with significantly different levels of adherence to WC patients. The recognition of patients remaining symptomatic and utilising healthcare resource whilst treated with ICS + LABA maintenance therapy is an important step to improving their management.
Abstract P6-04-15: The involvement of LMTK3 in endocrine resistance is mediated via multiple signaling pathways
Authors: G Giamas, Y Xu, A Filipovic, A Grothey, CR Coombes, J Stebbing
Journal: Cancer Research (2012)

Abstract We have previously identified new kinases that are able to phosphorylate and/or modulate ERα activity via a high-throughput RNA interference screening. Amongst the most potent novel regulators was LMTK3, a previously uncharacterized molecule. We found that LMTK3 confers its anti-tumor effects predominantly via ERα-regulated signaling. Evolutionary analyses revealed LMTK3 was the only kinase that has adaptively evolved and subjected to Darwinian positive selection, an intriguing and suggestive result given the unique susceptibility of humans to ERα+ breast cancer compared to the great apes (especially for chimpanzees [Pan troglodytes], our closest living relatives). Furthermore, in a large cohort of human breast cancer patients (n = 613), LMTK3 protein levels and intronic polymorphisms were significantly associated with disease-free and overall survival and predicted response to endocrine therapy. Finally, using an established orthotopic mouse model we demonstrated that inhibition of LMTK3 significantly reduces tumor volume and bioluminescence. Now, by performing: i) mass spectrometry (MS), ii) SILAC-based quantitative proteomics and iii) genome microarray experiments of ERα+ breast cancer cell lines (Tam-sensitive and Tam-resistant) in the presence or absence of various treatments (Tam, E2, ICI), we reveal certain genes, including well-defined oncogenes and tumor-suppressors that are statistically up- or down-regulated. Interestingly, amongst the newly identified LMTK3-regulated genes/proteins were targets belonging to already established signalling pathways implicated in cell survival, cytoskeletal rearrangement, transformation, and autophagy. In addition, inhibition of LMTK3 re-sensitised a Tam treatment breast cancer mouse model, to Tam treatment, leading to decreased tumour growth. Moreover, in patients' plasma samples, acquired LMTK3 gene amplification (copy number variation) was associated with relapse whilst receiving tamoxifen. In aggregate, these data support a role for LMTK3 in both innate (intrinsic) and acquired (adaptive) endocrine resistance in breast cancer. Further results and mechanistic data concerning LMTK3 actions will be presented, placing for the first time this new kinase in the maps of signal transduction. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-15.