tbuckley/cabot-search huggingface dataset:
OP0111 Arthritis secondary to epstein-barr virus: An infrequent reality
Authors: M. Fernández Matilla, C.M. Feced-Olmos, J.J. Alegre Sancho, D. Ybáñez García, M.A. Martínez Ferrer, E. Valls Pascual, M. Robustillo Villarino, I. de la Morena-Barrio
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Viral infections can cause inflammatory joint manifestations. Wide series regarding B19 Parvovirus have been published, but the arthritis secondary to Epstein - Barr virus (A-EBV), however, is infrequent and usually presents with multiple joint involvement during a systemic infection. <h3>Objectives</h3> To describe the epidemiological characteristics, clinical presentation and evolution of a series of patients with A-EBV. <h3>Methods</h3> Descriptive study of A-EBV cases diagnosed in our hospital in a 6-month period. In all cases, serological demonstration of EBV-IgM allowed us to confirm a recent viral infection. Clinical notes were reviewed to collect data in the virus presentation. <h3>Results</h3> Case 1: 27-year old woman with a 3-week history of progressive and asymmetrical oligoarthritis involving small joints and high levels of acute phase reactants. Treated with NSAIDs and corticosteroids. Clinical resolution within 3 months, with EBV-IgM clearance. Case 2: 54-year old woman with a 3-week history of progressive and symmetrical small joint polyarthritis. Treated with NSAIDs and corticosteroids. Persistence of symptoms, without EBV-IgM clearance, in spite of DMARD introduction. Case3: 32-year old woman with a 2-month history of progressive and symmetrical small joint polyarthritis, in association with a flu-like syndrome. Needed DMARDs because of the persistence of symptoms. EBV-IgM clearance within 5 months. Case 4: 37-year old woman with a 5-day evolution inflammatory polyarthralgia, associated with erythema, hypertransaminasemia and elevated acute phase reactants. Clinical resolution within 2 weeks. Awaiting check on EBV-IgM clearance. <h3>Conclusions</h3> A-EBV seems to affect young women preferably, with a seasonal predominance. It is not infrequent to find chronicity, which is associated with delay in specialist attendance. Given the possible relationship between Epstein-Barr virus and Rheumatoid Arthritis, we should not delay a DMARD treatment in those patients who develop chronic disease. <h3>Disclosure of Interest</h3> None Declared
P97 Lymphocyte-hepatocyte interactions: hepatitis C virus changes the rules
Authors: Z. Stamataki, O. S. Qureshi, G. M. Reynolds, L. Hibbert, J. Waters, G. R. Foster, J. Z. Rappoport, S. G. Hubscher, D. H. Adams, J. A. McKeating
Journal: Gut (2011)

<h3>Introduction</h3> Hepatitis C Virus (HCV) is a major cause of liver disease worldwide. Innate and adaptive cellular immune responses play a critical role in resolving acute HCV infection. However, the majority of infections are not cleared, resulting in a progressive chronic liver disease consistent with inadequate immune control. Evidence from human and animal models suggest that T cells play a critical role in controlling acute HCV infection, yet the mechanism(s) behind their failure to control chronic HCV replication are unknown. HCV replicates predominantly in the liver and virus specific immune cells need to target infected hepatocytes to control virus replication. HCV specific effector cells have been reported to home to the liver, however, little is known on their subsequent trafficking and fate within the organ. <h3>Aim</h3> Our aim is to investigate the role of HCV infection on lymphocyte-hepatocyte interactions, migration and immune cell effector function. <h3>Method</h3> We used in vitro and ex vivo models to study the effect of HCV infection on lymphocyte–hepatocyte interactions. Primary lymphocytes and hepatocytes were used in combination with hepatoma cell lines and replication competent HCV clones. Ex vivo lymphocyte migration assays were performed using biopsy material and tissue from explanted liver. Results were confirmed by in vivo observations using tissue sections from patients with end stage liver disease of viral and non-viral origin. Experimental techniques included immunohistochemistry, flow cytometry, fixed and live cell time-lapse confocal microscopy. <h3>Results</h3> We demonstrate: (1) A role for hepatocyte ICAM-1 in mediating T-lymphocyte adhesion and migration; (2) T-lymphocytes migrate spontaneously through hepatocyte monolayers via cell-cell junctions; (3). HCV enhances T-cell transmigration and pro-inflammatory cytokine expression. Our data demonstrate the existence of novel interactions between T cells and hepatocytes that are modulated in HCV infection. The nature of the T cell-hepatocyte interactions may have an impact on T-cell effector function and the outcome of anti-viral immune responses. <h3>Conclusion</h3> Interaction with HCV-infected hepatocytes alters T-cell trafficking and cytokine expression, providing a novel mechanism for HCV to persist in the liver.
Abstract 3186: Characterizing the antitumor effects of inhibiting translation initiation in glioblastoma multiforme.
Authors: Arjuna K. Rajakumar, Josephine Nalbantoglu
Journal: Cancer Research (2013)

Abstract Oncogene addiction is the process by which a tumor cell becomes increasingly dependent on the expression of a particular gene for the maintenance of its tumorigenicity. Alleviating this dependence via genetic or pharmacological means may profoundly inhibit tumor growth. However many cancers are not dependent on a single gene for survival. Glioblastoma Multiforme (GBM) presents itself with many genetic aberrations contributing to its aggressive phenotype. These include loss of PTEN, amplification of CDK4 and EGFR among others, making targeting a single genetic node ineffective where other oncogenic networks may buffer any therapeutic benefit. Over the last 10 years it has been shown that targeting protein translation initiation results in the simultaneous targeting of many oncogenic pathways. Translation initiation is highly implicated in tumorigenesis with over 10 initiation factors acting as either proto-oncogenes or tumor suppressors, the most well described being the eIF4E. The overexpression of eIF4E in many cancers results in messenger RNA discrimination giving rise to an increased translation of a subset of oncogenic mRNAs with highly structured 5’UTRs. However the precise role translation initiation plays in maintaining tumorigenicity in GBM and the subsequent anti-neoplastic properties of its inhibition are not known. Here, we characterize the anti-tumor effects of targeting protein translation in three glioblastoma cell lines U87MG, U251N and the highly aggressive U87ΔEGFR, using a small molecule inhibitor of eIF4E, 4EGI-1. We show that 4EGI-1 severely impairs cell survival over a 72 hour time interval, in a dose-dependent manner. This is marked by an arrest of cell proliferation starting at 24 hours, induction of apoptosis at 48 hours with increased annexin V staining and a decrease in cell motility. We found these effects coincide with a decrease in protein expression of several oncogenes with highly structured 5’UTRs after treatment with 4EGI-1 including cell proliferation proteins c-Myc and Cyclin D1 which are completely lost by 48 hours and regulators of apoptosis such as Bcl-xL, Mcl-1 and Survivin which decrease and are lost by 72 hours, while not affecting overall transcription of these genes. Our results demonstrate the sensitivity of gliomas towards inhibition of translation initiation. This further highlights translation regulation control as a strong force in cancer therapy, particularly in glioblastoma where options are limiting. Citation Format: Arjuna K. Rajakumar, Josephine Nalbantoglu. Characterizing the antitumor effects of inhibiting translation initiation in glioblastoma multiforme. [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 3186. doi:10.1158/1538-7445.AM2013-3186
A10.04 7WISP1, a downstream mediator of canonical wnt signalling, induces pathology in experimental osteoarthritis and predicts disease progression in early osteoarthritis patients
Authors: MH van den Bosch, AB Blom, A Maeda, TM Kilts, WB van den Berg, FP Lafeber, PL van Lent, MF Young, PM van der Kraan
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> An important role for canonical Wnt signalling in osteoarthritis pathology has been established. However, the role of Wnt1-induced secreted protein-1 (WISP1), which we found increased in experimental and human OA, remains to be elucidated. Here, we determined the relation between WISP1 expression and OA-progression in early OA patients. Additionally, we determined how WISP1 might be involved in OA pathology using experimental OA models. <h3>Methods</h3> WISP1 expression levels, determined with microarray analysis on synovial biopsies obtained from patients enrolled in the CHECK study of early OA patients, were coupled to OA-progression. Progression was defined as ≥1mm decrease in joint space width and ≥4x increased osteophyte size after 5 years. Human OA synovium was stimulated with WISP1. Joint pathology was assessed after induction of experimental OA models (DMM, ACLT and CIOA) in WT or WISP1-deficient mice. Immunohistochemical staining was used to visualise NITEGE aggrecan neoepitopes resulting from protease activity. Gene expression was evaluated using qRT-PCR. <h3>Results</h3> WISP1 expression at baseline was significantly higher in CHECK patients that showed OA-progression between baseline and the five-year follow-up measurement compared to non-progressors. Stimulation of human OA synovium with WISP1 increased the expression of the proteases MMP-2/-3/-9/-13 and ADAMTS-4/-5. To further pinpoint the role of WISP1 during OA, we induced three experimental OA models with different characteristics in WT and WISP1-deficient mice. We observed significantly decreased cartilage damage in the tibio-femoral joints of WISP1-deficient mice, compared with the WT controls in all models. Accordingly, we found decreased expression of MMP-3/-9 and the aggrecanases ADAMTS-4 and -5 in synovial tissue from WISP1-deficient mice. Moreover, we observed decreased expression of IL-1 and IL-6, which have the potential to induce protease expression, but not of the anti-inflammatory cytokine IL-10 in the WISP1-deficient mice. Finally, the protease activity in the cartilage, as assessed by the staining of the neoepitope NITEGE, was decreased in the WISP1-deficient mice. <h3>Conclusions</h3> Increased WISP1 expression in OA joints may play an important role in OA pathology via increased expression of MMPs and ADAMTSs in the synovium. Specific downregulation of WISP1 may avoid undesired side-effects that are likely to occur after targeting upstream Wnt signalling.
SAT0331 Effect of Methotrexate on the Immnunogenicity of TNF Inhibitors in Spondyloartrhitis Patients
Authors: A. Villalba Yllan, C. Plasencia, D. Pascual-Salcedo, D. Peiteado, L. Nuño, G. Bonilla, R. del Moral, A. Balsa, E. Martin Mola
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The spondyloarthritis (SpA) patients treated under TNF inhibitors (TNFi) with detectable antidrug antibodies (ADA) often develop loss of efficacy. Concomitant therapy with methotrexate (MTX) appears to reduce the the immunogenicity of biological drugs. <h3>Objectives</h3> To analyze if the use of combined therapy with MTX and TNFi can reduce the incidence of ADA and whether its effect is MTX dose dependent in SpA patients. <h3>Methods</h3> In this retrospective observational study, 162 SpA patients (including ankylosing spondylitis, Psoriatic SpA, SpA associated with <i>inflammatory bowel disease</i> and undifferentiated SpA) were included. The patients are treated with infliximab (Ifx) or adalimumab (Ada). The presence of ADA were measured at baseline and before each administration by ELISA to complete a follow up of 3 years. The patients were divided in two groups [MTX-15 (dose &lt;15 mg/week) and MTX+15 (≥15 mg/week)] to study the influence of baseline MTX dose on immunogenicity. The statistical analysis was performed using SPSS 11.0. <h3>Results</h3> Eighty nine out of 162 (54,9%) patients were male. Eighty five out of 162 (52,5%) patients received Ifx and 77 out of 162 (47,5%) Ada. The mean duration of treatment was 13.38±9.19 years to Ifx and 12.71±10.46 years for Ada. Forty five patients received MTX weekly at baseline [25/85 (29.4%)in Ifx and 20/77 (26%)in Ada]. The mean dose of MTX was 15,9±4.76 mg/week. Twenty nine out of 162 (17,9%) patients developed ADA, and ADA presence was significantly higher in SpA patients on Ifx therapy [21/85 (24.7%) in Ifx vs 8/77 (10.4%) in Ada, p=0.018)]. The presence of ADA was less frequent in SpA patients taking MTX [3/162 (1.8%) with MTX vs 26/162 (16%) without MTX, p=0.021]. No statistically differences were observed in the influence of baseline MTX dose on the ADA appearance (in Ifx: 2/18 (11,1%) in MTX+15 vs 1/9 (11,1%)in MTX-15, p=1,0; in Ada: 1/17 (5,9%) in MTX+15 vs 0/4 (0,0%)in MTX-15, p=1,0). <h3>Conclusions</h3> In this cohort of SpA patients treated with Ifx and Ada, the use of MTX has a preventive effect on the ADA development. However, the baseline MTX dose is not a determinant factor to get this effect. Further prospective studies are needed to confirm these data. <h3>Disclosure of Interest</h3> A. Villalba Yllan: None declared, C. Plasencia Grant/research support: Pfizer, D. Pascual-Salcedo Grant/research support: Pfizer, Speakers bureau: Pfizer, D. Peiteado: None declared, L. Nuño: None declared, G. Bonilla: None declared, R. del Moral: None declared, A. Balsa Grant/research support: Pfizer, Speakers bureau: Pfizer, Roche, Abbvie, E. Martin Mola Speakers bureau: Pfizer, Roche, Abbvie, Amgen <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5819
PROGNOSTIC VALUE OF RIGHT-SIDED VOLUME OVERLOAD IN PATIENTS PRESENTING WITH ACUTE HEART FAILURE: INSIGHTS FROM ASCEND-HF
Authors: Kishan S. Parikh, Adam DeVore, Allison Dunning, Robert Mentz, Phillip Schulte, Paul Armstrong, Wai Hong Tang, Justin Ezekowitz, John McMurray, Adriaan Voors, Mark Drazner, Christopher O’Connor, Adrian Hernandez, Chetan Patel
Journal: Journal of the American College of Cardiology (2016)
LA NEUMONÍA RECIENTE INCREMENTA LA MORTALIDAD DE LOS PACIENTES QUE SE REALIZAN UNA GASTROSTOMÍA ENDOSCÓPICA PERCUTÁNEA
Authors: RA Bendezú García, GO Patrón Román, A Gálvez Miras, M Lázaro Sáez, MA Rodríguez Manrique, S Amat Alcaraz, F Padilla Ávila, FM Bravo Castillo, A Hernández Martínez, JL Vega Sáenz
Journal: Endoscopy (2012)

Introducción: La Gastrostomía endoscópica percutánea (PEG), es una técnica de alimentación enteral con bajo índice de complicaciones. Sin embargo, grupos de pacientes se han relacionado con un peor pronóstico reflejado en mayores índices de morbi-mortalidad. Planteamos determinar la importancia de la neumonía reciente como factor predictivo de mortalidad en los pacientes que se realizan una PEG. Material y método: Entre enero del 2009 y diciembre del 2011 se evaluaron las comorbilidades, albúmina sérica, leucocitos, proteína C reactiva y hemoglobina de los pacientes que se realizaron la PEG, además de la patología que motivó su colocación y si se realizó durante un ingreso programado o por una neumonía. Asimismo se evaluaron las complicaciones posteriores a la técnica y la albúmina tres meses posteriores a la técnica. Resultados: Se incluyeron 110 pacientes, la mayoría de sexo femenino (57%) y 75 años como edad media. La mortalidad al primer mes fue del 9%, al sexto del 12% y al año del 21%. La neumonía se asoció a un incremento de la mortalidad al primer mes (HR: 7,72, C: 1,22–48.92) mientras que la diabetes con la mortalidad al sexto mes (HR:3,78, IC: 1,01–14,2) y las enfermedades cardiovasculares con la mortalidad al año (HR:17.23,IC:1.52–195.11). El valor medio de la albúmina antes de la PEG fue de 2,86 y el posterior a la colocación de la PEG fue de 2,83 sin demostrarse una mejoría en sus niveles después de colocada la PEG. Conclusiones: La colocación de la PEG durante el ingreso por una neumonía se asoció a un incremento de siete veces la mortalidad al primer mes, por lo que sería recomendable realizarla durante un ingreso programado. No se observó una mejoría en los niveles de albúmina de los pacientes que se sometieron a la PEG.
High rates of raised blood lead concentrations in Haitian infants and children
Authors: Chris Carpenter, Brittany Potts, Julia von Oettingen, Ric Bonnell, Michele Sainvil, Viviane Lorgeat, Mie Christine Mascary, Xin She, Eddy Jean-Baptiste, Sean Palfrey, Alan Woolf, Judy Palfrey
Journal: The Lancet Global Health (2016)

Background Lead exposure is a public-health issue throughout the world. Although many developed countries have implemented screening processes, there has not been a surveillance study of young children in Haiti. This pilot study sought to document baseline lead concentrations in the blood of healthy children living in Haiti and to quantify the prevalence of raised blood lead concentrations.
Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome
Authors: John E. Nestler, Daniela J. Jakubowicz, William S. Evans, Renato Pasquali
Journal: New England Journal of Medicine (1998)

Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene.
POST PROCEDURAL STROKE IN CORONARY ARTERY BYPASS GRAFTING AND PERCUTANEOUS INTERVENTIONS: AN 11 YEAR STATEWIDE ANALYSIS
Authors: Abel E. Moreyra, Gregory A. Maniatis, Hui Gu, William J. Kostis, Nora M. Cosgrove, John Pantazopoulos, John B. Kostis
Journal: Journal of the American College of Cardiology (2015)
ASSOCIATION OF CALCIUM AND PHOSPHATE PRODUCT WITH AMPUTATION-FREE SURVIVAL IN CRITICAL LIMB ISCHEMIA WITH MODERATE TO SEVERE CHRONIC KIDNEY DISEASE
Authors: Hirofumi Hioki, Yusuke Miyashita, Takashi Miura, Yasushi Ueki, Naoto Hashizume, Naoyuki Abe, Soichiro Ebisawa, Hirohiko Motoki, Atsushi Izawa, Jun Koyama, Uichi Ikeda
Journal: Journal of the American College of Cardiology (2015)
Long-term follow-up after dilation in symptomatic esophageal intramural pseudodiverticulosis: an observational study in 22 cases
Authors: Matthias Bechtler, Heiko Vollmer, Stephan Vetter, Erik-Sebastian Fuchs, Uwe Weickert, Ralf Jakobs
Journal: Endoscopy (2014)

Endoscopic bougienage seems to be the most effective therapy for dysphagia in esophageal intramural pseudodiverticulosis (EIPD), but nothing is known about the long-term success of this treatment option. This report presents long-term results for 21 of 22 patients with EIPD who were treated with bougienage. A total of 103 sessions of bougienage up to a diameter of 18 mm were performed, without major complications and with 100 % clinical success. During follow-up, symptom recurrence with further bougienage occurred in 12 /21 patients (57 %), who had variable symptom-free intervals (range 1.5 – 96 months). Symptom recurrence was associated with concomitant reflux esophagitis. Although this series demonstrates that bougienage is an effective method for relieving dysphagia in EIPD, the long-term effectiveness is limited.
The Will Rogers Phenomenon
Authors: Alvan R. Feinstein, Daniel M. Sosin, Carolyn K. Wells
Journal: New England Journal of Medicine (1985)

We found that a cohort of patients with lung cancer first treated in 1977 had higher six-month survival rates for the total group and for subgroups in each of the three main TNM stages (tumor, nodes, and metastases) than a cohort treated between 1953 and 1964 at the same institutions. The more recent cohort, however, had undergone many new diagnostic imaging procedures. According to the "old" diagnostic data for both cohorts, the recent cohort had a prognostically favorable "zero-time shift." In addition, by demonstrating metastases that had formerly been silent and unidentified, the new technological data resulted in a stage migration. Many patients who previously would have been classified in a "good" stage were assigned to a "bad" stage. Because the prognosis of those who migrated, although worse than that for other members of the good-stage group, was better than that for other members of the bad-stage group, survival rates rose in each group without any change in individual outcomes. When classified according to symptom stages that would be unaltered by changes in diagnostic techniques, the two cohorts had similar survival rates.
Abstract 2642: Dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas
Authors: Anna E. Arthur, Justin A. Colacino, Sonia A. Duffy, Dana C. Dolinoy, Jeffrey E. Terrell, Maureen A. Sartor, Douglas B. Chepeha, Jonathan B. McHugh, Carol R. Bradford, Gregory T. Wolf, Thomas E. Carey, Karen E. Peterson, Laura S. Rozek
Journal: Cancer Research (2012)

Abstract Background: Diet is associated with prognosis in several cancers, including head and neck, and has been hypothesized to influence epigenetic state by determining the availability of moieties involved in the modification of DNA and histone proteins. Tumor DNA methylation patterns are also hypothesized to be a prognostic factor in cancer, however, the link between diet and HNSCC tumor DNA methylation has not been characterized. Methods: Pretreatment data on usual food and nutrient consumption was collected via food frequency questionnaire (FFQ) on 49 cases identified through the UM Head and Neck SPORE. Tumor DNA methylation was assessed with the Illumina Goldengate Methylation Cancer Panel, which measures methylation at 1505 CpG sites across 807 genes related to cancer. To identify if dietary intake was associated with stochastic methylation in tumor suppressor genes, we calculated a “methylation score,” the sum of the individual hypermethylated tumor suppressor associated CpG sites. Gene specific analyses using linear modeling coupled with an empirical Bayes method of variance estimation were conducted to identify if methylation at individual CpG sites is associated with dietary intake. Results: Intake of antioxidant and methyl donor nutrients tended to be inversely associated with tumor suppressor methylation score. Individuals reporting the highest quartile of dietary folate, vitamin B12 and cruciferous vegetable intake, compared to those with lowest intake, had significantly less tumor suppressor gene methylation (p=0.04 and p=0.01, respectively), as did patients reporting the highest intake of cruciferous vegetables (p=0.04). In gene specific analyses, HPV positive individuals with the highest quartile of vitamin B12 intake were found to have significantly decreased methylation of four genes, RARB, PTHLH, SNRPN, and DCC. Conclusions: These preliminary results suggest that dietary intake may influence the tumor DNA methylation profile in HNSCC and that intake of specific micronutrients may enhance tumor suppression and possibly contribute to survival. Further studies will be needed to explore the effect of diet on head and neck cancer prevention and treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2642. doi:1538-7445.AM2012-2642