tbuckley/cabot-search huggingface dataset:
Endoscopic ultrasound-guided biliodigestive drainage is a good alternative in patients with unresectable cancer
Authors: M. Ramírez-Luna, F. Téllez-Ávila, M. Giovannini, F. Valdovinos-Andraca, I. Guerrero-Hernández, J. Herrera-Esquivel
Journal: Endoscopy (2011)

A total of 11 prospective cases of endoscopic ultrasound (EUS)-guided cholangio-drainage (EUCD) in patients with end-stage biliopancreatic cancer and biliary tract obstruction are reported. Other available drainage methods (endoscopic retrograde cholangiopancreatography and/or percutaneous transhepatic biliary drainage) of the biliary tract were attempted without success prior to EUS. Technical and clinical success was achieved in 10/11 patients (91 %) and in 9/10 patients (90 %), respectively. Bilirubin decreased by more than 50 % in 7/11 patients (64 %). One patient had a complication that required re-intervention and another patient developed biloma. No mortality directly related to the procedure was documented. In conclusion, EUCD is a good alternative for patients with malignant obstruction of the biliary tract in whom other drainage methods have failed.
THU0312 Microcirculation Comparative Study in Fibromyalgia Patients with and without Raynaud's Phenomenon: Table 1.
Authors: F. Araújo, A. Sepriano, T. Pedrosa, P. Nero, J.C. Branco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Previous studies demonstrated functional and morphological microcirculatory abnormalities that may be relevant to the pathophysiology and clinical manifestations of fibromyalgia (FM). <h3>Objectives</h3> To ascertain and compare capillary morphology of FM patients with and without Raynaud9s phenomenon (RP) using nailfold videocapillaroscopy (NVC). <h3>Methods</h3> Patients fulfilling the 2010 American College of Rheumatology Diagnostic Criteria for FM were allocated in 2 groups according to the presence or absence of RP (RP+ or RP-, respectively). All patients with secondary causes of RP other than FM were excluded. One blinded operator performed all the NVC using a 200x amplification digital microscope and analytical software. Capillary parameters evaluated in fingers II-V of both hands included: tortuosity, apex enlargement, branch enlargement, microhemorrhages, giant capillaries, capillary density, capillary branching and architectural derangements. Each parameter was rated 0-3 (0= no changes; 1= &lt;33% abnormalities; 2=33-66% abnormalities; 3= &gt;66% abnormalities) and the mean scores were calculated. The association of RP with the capillary parameters was assessed using multivariate linear regression adjusted for age, FM duration and occupation. <h3>Results</h3> Twenty FM patients were enrolled, 10 in each group, however 2 patients RP+ were excluded due to thyroid disease. Included patients were all female, had a mean age of 50.4 years and a mean duration of disease of 12.8 years. In both RP+ and RP- groups, the most frequently found abnormalities were minor dysmorphies, namely tortuosities, apex enlargement and branch enlargement. However, scoring of these parameters showed no significant difference between the 2 groups. More than half of RP+ and RP- patients presented slight focal decreases in capillary density, once again with no difference between groups. The only giant capillaries were found in a RP+ patient with an "early scleroderma pattern" as proposed by <i>Cutolo et al</i>. Hemorrhages were scarce and had a traumatic appearance, except in the previously mentioned patient. Interestingly, RP associated negatively with the capillary branching score. Table 1 summarizes the results. <h3>Conclusions</h3> No association was established between RP and microcirculatory abnormalities in FM patients. However, capillary tortuosity and enlargement were present in almost all subjects, supporting previous findings that FM may associate with minor NVC dysmorphies. Some authors suggest that tissue hypoxia arising from repeated autonomic-mediated vasoconstriction might explain these changes, as well as the apparent reduction in capillary density. Studies with a larger sample of FM patients are needed to confirm these results. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2157
Are endoscopists definitely stepping into the arena of weight-loss therapy?
Authors: Elisabeth Mathus-Vliegen
Journal: Endoscopy (2014)

Obesity, defined by a body mass index (BMI) ≥ 30 kg/m2, is a chronic, lifelong, multifactorial (including genetically-related) disease of excessive fat storage, which, in combination with the pattern of fat distribution, places the individual at increased risk of obesity-associated diseases and premature death. Almost every organ system is affected, with the gastrointestinal tract involved as well.
Abstract 63: Potential Genetic and Pharmacological Protection from Virus-induced Ventricular Arrhythmias and Sudden Cardiac Death
Authors: Nathalie Strutz-eebohm, Katja Steinke, Ulrike Henrion, Matthias Rohbeck, Karin Klingel, Guiscard Seebohm
Journal: Circulation Research (2014)

In patients as well as in mouse models, enteroviral infections, especially Coxsackie group B viruses (CVB1-6), frequently induce ventricular arrhythmias and sudden cardiac death. The cardiac action potential requires proper function of cardiac ion channels. CVB3 alters Kv7.1 channel trafficking potentially leading to changes in action potentials and increasing likelihood of arrhythmias. Genetic variants of cardiac ion channels can cause changes in channel trafficking that may preserve from CVB3 modulations and present an evolutionary advantage. Here, we show that a common polymorphic Kv7.1 channel variant uses alternative trafficking pathways and may thus exert a benefit during CVB3 infections. Genetic and pharmacological disruption of a CVB3-stimulated Serum- and Glucocorticoid inducible Kinase 1 (SGK1) pathways blunts Kv7.1 channel dysfunctions. Our results suggest that escape from CVB3-induced SGK1-stimulation by genetic variation in Kv7.1 may be protective and inhibition of SGK1 may present a pharmacological approach to reduce the pro-arrhythmic risk associated with acute coxsackievirus infections.
Mutation Analysis for Heterozygote Detection and the Prenatal Diagnosis of Cystic Fibrosis
Authors: Wanda K. Lemna, Gerald L. Feldman, Bat-sheva Kerem, Susan D. Fernbach, Elaine P. Zevkovich, William E. O'Brien, John R. Riordan, Francis S. Collins, Lap-Chee Tsui, Arthur L. Beaudet
Journal: New England Journal of Medicine (1990)

The cystic fibrosis gene was recently cloned, and a three-base deletion removing phenylalanine 508 from the coding region was identified as the mutation on the majority of cystic fibrosis chromosomes. We used the polymerase chain reaction and hybridization with allele-specific oligonucleotides to analyze the presence or absence of this mutation on 439 cystic fibrosis chromosomes and 433 normal chromosomes from non-Ashkenazic white families.
Necrotizing Fasciitis Due to<i>Photobacterium damsela</i>in a Man Lashed by a Stingray
Authors: Gerard R. Barber, Jeffrey S. Swygert
Journal: New England Journal of Medicine (2000)

To the Editor: In comparing osteopathic spinal manipulation with standard care for patients with low back pain, Andersson et al. (Nov.4 issue) 1 fail to recognize that many patients may have improvement with minimal or no treatment.This might have been evident had the authors included a control group of patients who received minimal or no intervention for back pain.Cherkin et al. compared the outcomes for patients with low back pain who received physical therapy, chiropractic treatment, or an educational booklet. 2 There was only a marginally better outcome in the physical-therapy and chiropractic-treatment groups than in the booklet group.Improvement with minimal or no treatment would also explain the similar outcomes reported by Carey et al. in their comparison of treatments by primary care practitioners, chiropractors, and orthopedic surgeons. 3 The only substantial differences in the results of these studies seem to be in the area of patient satisfaction and cost.Therefore, it would be erroneous to conclude from the study by Andersson et al. that either standard care or osteopathy is superior to the placebo effect.It is evident that in most cases, back pain resolves over time, regardless of the treatment used.
Multisensor navigation for visualization of the configuration of flexible endoscopes
Authors: A Schneider, D Wilhelm, M Polski, A Fiolka, A Meining, H Feussner
Journal: Endoscopy (2012)

Objective: For pure NOTES procedures flexible endoscopes are one precondition. However controlled steering is only possible for the tip of the scope, whereas the rest part of the endoscope places itself uncontrollable in the abdomen. Due to this fact, navigation of instruments is challenging and, moreover, adjacent structures could be injured by unintentional pressure or unintended instrument movements. Even more, the endoscopes tip position can only be assumed out of the images which could be challenging especially in an inverted position.
State of the Art Epilepsy Imaging
Authors: Surjith Vattoth, Fathima Fijula Palot Manzil, Aparna Singhal, Kristen O. Riley, Asim K. Bag
Journal: Clinical Nuclear Medicine (2014)

Drug-resistant epilepsy is a chronic debilitating disorder, but many cases are potentially curable by surgery. The key to the successful epilepsy surgery with complete postoperative seizure-free status is precise localization of the epileptic zone that must be resected and the adjacent eloquent areas of gray and white matter that must be preserved to avoid neurological defects. This article reviews the current state of the art epilepsy imaging techniques facilitating successful epilepsy surgery. The overview of the imaging appearances of the most common epileptogenic etiologies that are amenable to surgical resection is also included in this review.
The Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery
Authors: Don Poldermans, Eric Boersma, Jeroen J. Bax, Ian R. Thomson, Louis L.M. van de Ven, Jan D. Blankensteijn, Hubert F. Baars, Tik-Ien Yo, Giuseppe Trocino, Carlo Vigna, Jos R.T.C. Roelandt, Paolo M. Fioretti, Bernard Paelinck, Hero van Urk
Journal: New England Journal of Medicine (1999)

Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery.We performed a randomized, multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infarction within 30 days after major vascular surgery in patients at high risk for these events. High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography. Eligible patients were randomly assigned to receive standard perioperative care or standard care plus perioperative beta-blockade with bisoprolol.A total of 1351 patients were screened, and 846 were found to have one or more cardiac risk factors. Of these 846 patients, 173 had positive results on dobutamine echocardiography. Fifty-nine patients were randomly assigned to receive bisoprolol, and 53 to receive standard care. Fifty-three patients were excluded from randomization because they were already taking a beta-blocker, and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing. Two patients in the bisoprolol group died of cardiac causes (3.4 percent), as compared with nine patients in the standard-care group (17 percent, P=0.02). Nonfatal myocardial infarction occurred in nine patients given standard care only (17 percent) and in none of those given standard care plus bisoprolol (P<0.001). Thus, the primary study end point of death from cardiac causes or nonfatal myocardial infarction occurred in 2 patients in the bisoprolol group (3.4 percent) and 18 patients in the standard-care group (34 percent, P<0.001).Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction in high-risk patients who are undergoing major vascular surgery.
Abstract 945: Sca-1 deficiency enhances the chemopreventive activity of a peroxisome proliferator-activated receptorγ (PPARγ) agonist
Authors: Hongyan Yuan, Geeta Upadhyay, Yuzhi Yin, Claire Pollock, Levy Kopelovich, Robert I. Glazer
Journal: Cancer Research (2010)

Abstract Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored membrane protein that was first identified as a murine marker of activated lymphocytes with stem cell-like properties. Although Sca-1 is widely used to enrich for stem cells in various tissues, little is known about its function and associated signaling pathways in development and tumorigenesis. Therefore, the role of Sca-1 in mammary gland development and tumorigenesis was undertaken using Sca-1 null mice. Sca-1-deficient animals exhibited slower ductal development in an age-dependent manner, and expressed increased p21Cip1 and reduced pRB, as well as a diminished response to progestin and estrogen stimulation. Mammary epithelium from Sca-1-null mice expressed increased PTEN, and reduced PDK1, AKT and c-Src activation. Significantly, the Sca-1 null mammary gland expressed increased PPARγ and reduced PPARδ, which resulted in a 10-fold increase in the ratio of PPARγ to PPARδ. In concordance with this phenotype, Sca-1 null mice exhibited a delay in progestin/DMBA-mediated mammary carcinogenesis, and were highly sensitive to the chemopreventive effects of PPARγ agonist GW7845, where tumorigenesis was inhibited by 90%. In contrast, tumor formation in Sca-1 null mice was unaffected by PPARδ agonist GW501516. Since GPI-anchored receptors are known to be associated with members of the c-Src tyrosine kinase family, we assessed if reduction of Sca-1 by RNAi affected c-Src activity, and if reduced c-Src activity may have contributed to increased GW7845 sensitivity. Lentivirus-mediated expression of Sca-1 shRNA in mammary tumor cells markedly reduced c-Src activation. In contrast, overexpression of c-Src, but not kinase-dead c-Src, inhibited PPARγ-dependent reporter gene activity and associated with PPARγ. These data suggest for the first time that loss of Sca-1 upregulates PTEN, attenuates c-Src and enhances PPARγ agonist sensitivity. Thus, targeting Sca-1 or its human homolog may be a useful approach to amplify the chemopreventive activity of PPARγ agonists. 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 945.
678 VSL#3 PROBIOTIC TREATMENT DECREASES BACTERIAL TRANSLOCATION AND PROINFLAMMATORY STATE IN RATS WITH EXPERIMENTAL CIRRHOSIS
Authors: E. Sánchez, A. Boullosa, J.C. Nieto, S. Vidal, B. Mirelis, C. Juárez, G. Soriano, C. Guarner
Journal: Journal of Hepatology (2012)
SP0197 Making Mentoring Effective – The View of the Mentor
Authors: L. Gossec
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Mentoring is a process which involves both a mentor and a mentee, and facilitators to the process, as well as potential barriers, can come from both of the members of the team. Why do some mentoring processes work, and not others? This talk will review how one "grows" into the mentoring process, and what are the most important aspects of mentoring, from a mentor's point of view. <h3>Disclosure of Interest</h3> None Declared
The Role of Black and Hispanic Physicians in Providing Health Care for Underserved Populations
Authors: Miriam Komaromy, Kevin Grumbach, Michael Drake, Karen Vranizan, Nicole Lurie, Dennis Keane, Andrew B. Bindman
Journal: New England Journal of Medicine (1996)

Patients who are members of minority groups may be more likely than others to consult physicians of the same race or ethnic group, but little is known about the relation between patients' race or ethnic group and the supply of physicians or the likelihood that minority-group physicians will care for poor or black and Hispanic patients.
DETAILED MOLECULAR CHARACTERISATION OF DIFFUSE INTRINSIC PONTINE GLIOMAS IDENTIFIES THREE MOLECULAR SUBGROUPS AND A NOVEL CANCER DRIVER, ACVR1
Authors: C. Hawkins, P. Buczkowicz, C. Hoeman, P. Rakopoulos, S. Pajovic, A. Morrison, C. Jones, E. Bouffet, U. Bartels, O. Becher
Journal: Neuro-Oncology (2014)

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor with no effective therapy and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and choosing therapies based on assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic make-up of this brain cancer with nearly 80% harboring a K27M-H3.3 or K27M-H3.1 mutation. However, DIPGs are still thought of as one disease with limited understanding of the genetic drivers of these tumors. This data is critical for the development of better therapies for these children. METHODS: Here we describe deep-sequencing analysis of 36 tumor–normal pairs (20 whole genome sequencing (WGS; Illumina Hiseq 2000) and 16 whole exome sequencing (WES; Applied Biosystems SOLiD 5500xl)), integrated with comprehensive methylation (28 DIPGs; Illumina Infinium450K methylation array), copy number (45 DIPGs, Affymetrix SNP6.0) and expression data (35 DIPGs; Illumina HT-12 v4). RESULTS: Unsupervised subgrouping of DIPGs based on CpG island methylation resulted in three distinct subgroups; MYCN, Silent, and H3-K27M. This subgrouping was supported by multiple analyses including principal components analysis, non-negative matrix factorization and consensus clustering. Subgroup-specific differences were supported by integration of mutation, structural, expression and clinical data. The MYCN subgroup DIPGs are not associated with histone mutations and are instead characterized by hypermethylation and catastrophic shattering of chromosome 2p with high-level copy number amplifications of MYCN and ID2. The Silent subgroup has genomes with minimal instability, fewer mutations and over-expression of WNT pathway genes. The H3-K27M subgroup is highly K27M-H3 mutated but is typically associated with additional genetic alterations including activating mutations in ACVR1, frequent RB1 deletions, TP53 deletions/mutations, PVT-1/MYC or PDGFRA gains/amplifications, genomic instability and alternative lengthening of telomeres. After H3F3A and TP53, the next most frequently mutated gene in DIPG is ACVR1 (activin A receptor, type I), a novel cancer gene. Mutations of ACVR1 in four DIPGs (c.617G > A) result in a R206H substitution. One DIPG had a mutation of a neighboring codon (Q207E). Two DIPGs had a c.983G > A (G328E) mutation and five DIPGs in our cohort had a c983G > T mutation which results in a G328V substitution. In total 20% of DIPGs have ACVR1 mutations. CONCLUSIONS: Our results highlight the many pathways to tumorigenesis in DIPG. This complexity needs to be considered when designing new therapeutic approaches in order to improve outcome for these children. SECONDARY CATEGORY: n/a.
Abstract 291: ERK1/2 pathway activation controls epithelial-mesenchymal transition in NSCLC cells.
Authors: Janine M. Buonato, Matthew J. Lazzara
Journal: Cancer Research (2013)

Abstract Understanding and overcoming the cellular mechanisms that underlie de novo and acquired therapy resistance remains a challenge in treating many cancers including non-small cell lung cancer (NSCLC). Despite the prevalence of epidermal growth factor receptor (EGFR) over-activation in NSCLC and other cancers, most patients are resistant to EGFR inhibitors. A number of studies have linked mesenchymal cellular phenotypes and epithelial-mesenchymal transition (EMT) with resistance to chemotherapeutics and EGFR inhibitors across cancer types. Here, we demonstrate in NSCLC cells that MAPK/ERK signaling plays a key role in determining mesenchymal cellular characteristics and response to the EGFR inhibitor gefitinib. In cultured NSCLC cell lines, pharmacological inhibition of MEK pushed cells toward a more epithelial phenotype and prevented EMT induction by exogenous transforming growth factor beta. In addition, chronic MEK inhibition synergistically enhanced cellular sensitivity to gefitinib in a reversible manner and slowed cell migration in wound healing assays in NSCLC cell lines with both de novo and acquired resistance to gefitinib. Importantly, our results demonstrate that the observed cell phenotypic changes occur on a time scale corresponding to that with which epithelial and mesenchymal marker expression change in response to ERK inhibition. This time scale is much larger than that for changes in ERK activity itself, reflecting the need for downstream ERK-dependent processes to affect phenotypic changes. Changes in the same cellular phenotypes and associated changes in epithelial and mesenchymal markers also occurred as a result of KRAS mutant expression in a MEK-dependent manner. Overall, this study draws a strong connection between ERK pathway activation and mesenchymal characteristics in NSCLC and suggests potential new opportunities for expanding the efficacy of currently available EGFR inhibitors. Citation Format: Janine M. Buonato, Matthew J. Lazzara. ERK1/2 pathway activation controls epithelial-mesenchymal transition in NSCLC 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 291. doi:10.1158/1538-7445.AM2013-291
Abstract 1630: The PKC inhibitor Sotrastaurin selectively inhibits the growth of CD79 mutant diffuse-large B-cell lymphoma
Authors: Tara Naylor, Andreas Enns, Markus Warmuth, Georg Lenz, Frank P. Stegmeier
Journal: Cancer Research (2011)

Abstract The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by constitutive activation of the oncogenic NF-κB pathway and is associated with poor prognosis. Recent studies demonstrated dependence on NF-κB pathway activation and identified genetic lesions in NF-κB pathway regulators, including CARD11/CARMA1, A20/TNFAIP3, and CD79A/B. In this study, we evaluated the therapeutic potential of the selective PKC inhibitor sotrastaurin (STN) in preclinical models of DLBCL. We found that a significant fraction of ABC DLBCL cell lines exhibited strong sensitivity to sotrastaurin and detected that responsiveness can be predicted based on the molecular nature of NF-κB pathway lesions. While mutations in CD79A/B correlate with sensitivity to PKC inhibitors, mutations in CARD11 render ABC DLBCL cell lines insensitive to PKC inhibitors. The growth inhibitory effect of PKC inhibitors correlates with NF-κB pathway inhibition and is mediated by the induction of a G1 cell cycle arrest and/or apoptosis. Collectively, our study provides a strong rationale for the clinical evaluation of sotrastaurin in ABC DLBCL patients that harbor CD79 mutations, and furthermore illustrates the necessity to stratify DLBCL patients according to their genetic abnormalities. 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 1630. doi:10.1158/1538-7445.AM2011-1630
Endoscopic removal of a fractured partially covered Evolution esophageal stent
Authors: S. Mou, T. Kaltenbach, M. Yao, C. Corrales, S. McGill, R. Soetikno
Journal: Endoscopy (2012)

Self-expanding metal esophageal stents have been increasingly utilized in the treatment of benign strictures that are refractory to dilation [1] [2] [3]. The radial force of the stent and resulting tissue hyperplasia often make subsequent stent retrieval difficult. Complications range from a need for multiple repeat procedures to perforation requiring surgical intervention [4] [5].