tbuckley/cabot-search huggingface dataset:
O09 * CLINICAL OUTCOME OF 50 CHILDREN WITH INTRACRANIAL EPENDYMOMA TREATED WITH PENCIL BEAM SCANNING PROTON THERAPY
Authors: C. Ares, F. Albertini, M. Frei-Welte, A. Bolsi, M. Grotzer, R. Schneider, G. Goitein, D. C. Weber
Journal: Neuro-Oncology (2014)

INTRODUCTION: To assess the clinical outcome of pencil beam scanning proton therapy (PT) for the treatment of pediatric patients with intracranial ependymoma. METHOD: Between July 2004 and March 2013, 50 patients (median age, 2.6 years) with WHO Grade 2-4 intracranial ependymoma (infratentorial; 36/50) received adjuvant local irradiation only with PT at Paul Scherrer Institute. Seventeen (34%) patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with residual tumor ≤ 1.5 cc and 9 with residual tumor >1.5 cc). Median prescribed dose was 59.4 Gy(RBE) (range, 54 - 60). RESULTS: With a mean follow-up time of 43.4 months (range, 8.5 -113.7) seven (14%) patients experienced local failure, 6 of them with infratentorial tumors and one with supratentorial tumors; 4 of the local failures were in patients presenting with residual disease ≥ 1.5 cc at the time of PT and 3 without residual macroscopic disease. One patient with local, infratentorial, tumor control developed supratentorial metastasis. Two patients with local failure developed microscopic dissemination at the time of the local failure with positive malignant cells into the CSF. Five patients died from tumor progression. Actuarial 5-year local control rates were 78 ± 7.5% and 5-year overall survival rates were 84 ± 6.8%. Three patients developed grade ≥ 3 toxicity (unilateral deafness in patients with infratentorial tumors; n = 2; fatal brainstem necrosis; n = 1). CONCLUSION: Local control and survival rates after PT for young ependymoma patients are excellent considering the high grade histology in 92% of the patients and the number of patients with residual tumor ≥ 1.5 cc.
Methotrexate in the Treatment of Corticosteroid-Dependent Asthma
Authors: M F Mullarkey, B A Blumenstein, W P Andrade, G A Bailey, I Olason, C E Wetzel
Journal: New England Journal of Medicine (1988)

To test our previous observation that methotrexate reduces corticosteroid requirements of patients with severe asthma, we studied 14 patients with corticosteroid-dependent bronchial asthma in a 24-week randomized double-blind crossover trial comparing a low dosage of methotrexate (15 mg per week) with placebo. At base line the mean dosage of prednisone was 173.5 mg per week (range, 70 to 420). On the average, 36.5 percent less prednisone was required when patients received methotrexate than when they received placebo (P = 0.01). Measurement of forced vital capacity and forced expiratory volume in one second showed that there was no deterioration in the condition of patients in whom the dosage of prednisone was reduced. The patients' subjective assessment of breathing ability indicated significant improvement (P = 0.01). The adverse effects of methotrexate were limited to transient nausea in three patients and an evanescent rash in one patient. Nine patients are still receiving methotrexate 3 to 10 months after the study's conclusion. The dosages of steroids have been further reduced in each of these patients, and prednisone has been discontinued in four. We conclude from this preliminary study that the use of methotrexate allows a significant reduction in the use of corticosteroids in patients with severe asthma without deterioration of pulmonary function.
Abstract 518: Plasminogen activator inhibitor-1 (PAI-1) protects tumor cells from extrinsic apoptosis
Authors: Hua Fang, Yves A. DeClerck
Journal: Cancer Research (2010)

Abstract Plasminogen-activator inhibitor-1 (PAI-1) is a member of the serine protease (serpin) family of inhibitors that control the proteolytic activity of urokinase and tissue-type PA. The expression of PAI-1 in most cancer types has been shown to be a marker of poor rather than favorable outcome, suggesting that PAI-1 has a pro-tumorigenic activity. The observation that PAI-1 positively contributes to angiogenesis has in part provided a mechanism in support of the pro-tumorigenic effect of PAI-1. Consistent with such a role, we have previously reported that PAI-1 protects endothelial cells (EC) from FasL-mediated apoptosis by controlling FasL cleavage by plasmin (Bajou et al, Cancer Cell, 2008). Here we hypothesized that PAI-1 may play a similar protective role in cancer cells by preventing them from undergoing apoptosis. We observed that downregulation of PAI-1 by small interfering RNA (siRNA) induces apoptosis in breast cancer MDA-MB-231 cells (14.1 ±1.1% apoptotic cells in PAI-1 siRNA-treated cells vs. 1.5 ± 0.5% apoptotic cells in scramble control; p &amp;lt; 0.001) and increases caspase-3 activity by 5 fold. Consistent with an involvement of the extrinsic apoptotic pathway, we observed that downregulation of PAI-1 in MDA-MB-231 cells did not alter mitochondrial membrane potential but resulted in an increase in caspase-8 activity by 3 fold. PAI-1 silencing also enhanced the production of urokinase (uPA) and the cell-associated activity of plasmin, and inhibited migration and invasion in vitro. The data thus suggest that like in EC, PAI-1 protects tumor cells from extrinsic apoptosis and provides an additional mechanism explaining the pro-tumorigenic activity of PAI-1. 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 518.
SP0050 The Spectrum of NLR AND Related Molecules in Human Disease
Authors: M. F. McDermott
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The nucleotide-binding and oligomerisation domain, leucine rich repeat (NOD-like receptors or NLRs) family of intracellular pathogen recognition receptors (PRRs) is involved in the pathogenesis of a number of rare and more common monogenic diseases, and is increasingly being recognised to play a pivotal role in polygenic complex diseases. The recognition of bacterial wall constituents and other cellular stressor molecules by different NLRs leads to activation of the innate immune response and upregulation of key proinflammatory pathways, such as IL-1β and IL-18 cytokine production and translocation of NF-κB transcription factor to the nucleus. These signalling pathways are increasingly being targeted as potential sites for new therapies. This presentation will discuss the role of NLRs in monogenic autoinflammatory disease and also in complex diseases, where IL-1β and IL-18 cytokines underlie the pathogenesis. It will also describe the success to date of therapeutic agents in treating some of the disorders associated with aberrant NLR function. <h3>Disclosure of Interest</h3> None Declared
P4-10-01: Tumor Markers Predicting Recurrence Type after a Primary Ductal Carcinoma In Situ.
Authors: W Zhou, C Johansson, K Jirström, A Ringberg, C Blomqvist, R-M Amini, M-L Fjällskog, F Wärnberg
Journal: Cancer Research (2011)

Abstract Background: The risk for recurrence after a primary ductal carcinoma in situ (DCIS) is approximately 8% after ten years. If a recurrence occurs, the risk of the recurrence being invasive is approximately 50%. However, the knowledge of determinants for type of recurrence is limited. The purpose of this study was to investigate the predictable effect of specific biologic markers on the type recurrence after a primary DCIS. Material and Methods: All women diagnosed with a primary DCIS between 1986 and 2004 in Uppsala and Västerås, Sweden were included (n=458). We also included all women from the SweDCIS Trial with a known recurrence (n= 166). TMA blocks were constructed and immunohistochemistry (IHC) was used to evaluate the status of estrogen receptor (ER), HER2, epidermal growth factor receptor (EGFR/HER1), cytokeratin 5/6 (CK 5/6), forkhead box A1 (FOXA1), forkhead box C1 (FOXC1), Ki 67, CD 10 and transacting T-cell-specific transcription factor GATA-3 (GATA-3) in the primary DCIS tumors. Logistic regression was employed to calculate the difference of expression status of biological markers between groups. Odds ratios (ORs) and 95% confidence interval (CI) were calculated, with adjustment for age, free margins, surgical type and molecular subtype by IHC. Results: Of the 624 patients, 358 without recurrence were grouped as controls. Of the 266 with recurrence, 130 developed an in situ recurrence, while the remaining 136 developed invasive recurrence. Mastectomy compared to breast conserving surgery (BCS) and free margins were associated with less recurrences (OR 0.07, 95% CI 0.03 — 0.15) and (OR 0.39, 95% CI 0.26 — 0.58). As compared with the most common molecular subtype Luminal A, the subtype Luminal B had statistically significant higher risk of recurrence (OR 2.01, 95% CI 1.12 — 3.59). Higher risk of all recurrences was also observed for FOXA1 (OR 3.16, 95% CI 1.48 — 4.74) and FOXC1 (OR 2.39, 95% CI 1.39 — 4.09). In the analyses of type of recurrence, ER-negative, HER2−positive and EGFR-positive tumors recurred more often as in situ; (OR 2.34, 95% CI 1.17 — 4.71), (OR 2.08, 95% CI 1.11 — 3.88) and (OR 2.20, 95% CI 1.11 — 4.36). The molecular subtype HER2+ was also associated with a lower risk of invasive recurrence (OR 0.27, 95% CI 0.11 — 0.67). Conclusion: As expected, mastectomy and free margins were associated with a lower risk of recurrence. Molecular subtype Luminal B and tumor markers FOXA1 and FOXC1 had a higher risk of recurrence. Recurrences after molecular subtype HER2+, ER-negative and EGFR-positive DCIS were more often of the in situ type. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-01.
Imported toxigenic cutaneous diphtheria in a young male returning from Mozambique to Norway, March 2014
Authors: A Jakovljev, M Steinbakk, A T Mengshoel, E Sagvik, P Brügger-Synnes, T Sakshaug, K Rønning, H Blystad, K Bergh
Journal: Eurosurveillance (2014)

In March 2014 a 20-year-old man was diagnosed with cutaneous diphtheria at St. Olavs University Hospital in Trondheim, Norway on his return from Africa. The man had been in Mozambique since autumn 2013 and had experienced persistent skin ulcer infections. His was in good general health. Toxin-producing Corynebacterium diphtheriae was grown from a wound specimen. He had completed the national childhood vaccination programme and received a diphtheria vaccine booster dose in 2005. Screening of close contacts revealed an asymptomatic person colonised with non-toxigenic C. diphtheriae.
Evaluation prospective de l'entérografie par IRM pour le diagnostic des tumeurs de l'intestin grêle
Authors: E Amzallag-Bellenger, A Ruiz, H Brixi-Benmansour, S Deguelte, G Cadiot, C Hoeffel
Journal: Endoscopy (2012)

Evaluer de manière prospective les performances diagnostiques de l'entéro-IRM pour le diagnostic des tumeurs de l'intestin grêle, avec les résultats anatomopathologiques, endoscopiques et du suivi clinique comme gold standard.
Cushing's Syndrome
Authors: David N. Orth
Journal: New England Journal of Medicine (1995)

Harvey W. Cushing's 1932 description1 of the syndrome that results from long-term exposure to glucocorticoids has not been improved upon, but our understanding of its pathophysiologic features and our ability to diagnose and treat the disorder have increased dramatically.Normal Hypothalamic–Pituitary–Adrenal PhysiologyCorticotropin-releasing hormone (CRH)2 is synthesized in the hypothalamus and carried to the anterior pituitary in portal blood (Figure 1). CRH, whose secretion is regulated by a variety of neurotransmitters,3 is the most potent regulator of corticotropin secretion. Arginine vasopressin and other hypothalamic agents also stimulate corticotropin secretion.4,5 Corticotropin is synthesized as a large precursor, pro-opiomelanocortin (POMC), which . . .
Imaging of a Case of Metaplastic Thymoma on 18F-FDG PET/CT
Authors: Yoshinori Ishikawa, Katsuhiko Kato, Tetsuo Taniguchi, Koji Kawaguchi, Kohei Yokoi
Journal: Clinical Nuclear Medicine (2013)

Metaplastic thymoma is a rare primary thymic epithelial tumor. This report presents the 18F-FDG PET/CT appearance of a metaplastic thymoma developed in a 61-year-old female patient. The FDG uptake of the mediastinal mass showed a high maximum SUV, thus suggesting the possibility of thymic cancer. Surgical resection was performed for both a definitive diagnosis and treatment of the mediastinal tumor. A histological examination of the resected specimen revealed metaplastic thymoma. Although rare, thymoma should be carefully considered in the differential diagnosis in cases of mediastinal masses presenting with highly positive findings on 18F-FDG PET/CT to avoid any inappropriate patient management.
P185 PROTEIN KINASE C-INDUCED ENDOCYTOSIS OF SODIUM TAUROCHOLATE COTRANSPORTING POLYPEPTIDE MEDIATES CELLULAR ENTRY OF HEPATITIS B VIRUS IN AN IN VITRO HBV MODEL
Authors: J.W. Chung, I.Y. Moon, S.W. Yang, E.S. Jang, S.-H. Jeong, J.-W. Kim
Journal: Journal of Hepatology (2014)
Abstract 5217: Integrative sequencing reveals novel alterations in untreated and castration resistant prostate cancer.
Authors: Matti J. Annala, Kati K. Waltering, Antti Ylipää, Kimmo Kartasalo, Kirsi Tuppurainen, Serdar Karakurt, Leena Latonen, Outi Saramäki, Simo-Pekka Leppänen, Janne Seppälä, Hanna E. Rauhala, Teuvo LJ Tammela, Olli Yli-Harja, Wei Zhang, Tapio Visakorpi, Matti Nykter
Journal: Cancer Research (2013)

Abstract Prostate cancer is the third most common source of male cancer deaths in developed countries. The standard of care for aggressive prostate cancer is androgen ablation, which prolongs survival until the tumor acquires a castration resistant phenotype. The molecular pathology underlying prostate cancer progression is not yet fully understood. We used integrative high throughput sequencing to study cancer-associated alterations in 53 prostate cancer related neoplasia at the DNA, RNA and epigenetic levels. The cohort included both hormone-naive and castration resistant prostate cancers, along with two neuroendocrine prostate cancers. We identified two new fusion genes, one of which associated with neuronal differentiation and castration resistance. We also identified a number of novel prostate cancer associated transcripts, including transcripts specific to castration resistant tumors. Based on ChIP-seq data from prostate cancer cell lines, many of the novel transcripts were regulated by known oncogenes such as ERG and AR. Methylation sequencing revealed a near-identical pattern of promoter hypermethylation in both hormone-naive and castration resistant tumors. Enrichment of hypermethylation was observed at EZH2 binding sites, supporting the role of EZH2 in the recruitment of DNA methyltransferase in prostate cancer. Promoter hypermethylation suppressed the expression of hundreds of genes, but a subset of genes characterized by promoter H3K27 trimethylation responded to hypermethylation with increased expression. Citation Format: Matti J. Annala, Kati K. Waltering, Antti Ylipää, Kimmo Kartasalo, Kirsi Tuppurainen, Serdar Karakurt, Leena Latonen, Outi Saramäki, Simo-Pekka Leppänen, Janne Seppälä, Hanna E. Rauhala, Teuvo LJ Tammela, Olli Yli-Harja, Wei Zhang, Tapio Visakorpi, Matti Nykter. Integrative sequencing reveals novel alterations in untreated and castration resistant prostate 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 5217. doi:10.1158/1538-7445.AM2013-5217
TREATMENT OF REFRACTORY HYPOXIC RESPIRATORY FAILURE DUE TO RIGHT-TO-LEFT SHUNT AFTER INFERIOR ST-ELEVATION MYOCARDIAL INFARCTION: A NOVEL USE OF PROSTACYCLIN THERAPY
Authors: Mohammad Amin Kashef, Ankur Gupta, Jaime Hernandez Montfort, Amir Lotfi
Journal: Journal of the American College of Cardiology (2016)
Fenestration of a covered metal stent during cystoduodenostomy using argon plasma coagulation
Authors: Alan Tieu, Payal Saxena, Vikesh Singh, Anne Lennon, Vivek Kumbhari, Ahmed Messallam, Mohamad Zein, Anthony Kalloo, Mouen Khashab
Journal: Endoscopy (2014)

The current endoscopic methods for the treatment of walled-off pancreatic necrosis (WOPN) include endoscopic ultrasound (EUS)-guided cystenterostomy with placement of a fully covered self-expandable metal stent (FCSEMS). Studies have shown that FCSEMSs designed specifically for drainage of pancreatic fluid collections have high technical success rates; however, these stents are not commercially available in the USA [1]. Esophageal FCSEMSs can also be used for the same purpose [2]. Technical success rates can be limited by the availability of appropriate endoscopic accessories and stents.
OP0227 Oral C5a Receptor Antagonist CCX168 Phase 2 Clinical TRIAL in Anca-Associated Renal Vasculitis:
Authors: D.R. Jayne, A. Bruchfeld, M. Schaier, K. Ciechanowski, L. Harper, M. Jadoul, M. Segelmark, D. Selga, I. Szombati, M. Venning, C. Hugo, P.L. Van Daele, O. Viklicky, A. Potarca, T.J. Schall, P. Bekker
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In ANCA vasculitis, the anaphylatoxin C5a amplifies neutrophil influx and activation through C5aR. CCX168, an oral specific C5aR antagonist, is in clinical development for ANCA-associated renal vasculitis (AARV). <h3>Objectives</h3> A Phase 2 clinical trial was conducted to investigate the potential of CCX168 to contribute to disease remission and permit glucocorticoid reduction or avoidance in patients with active AARV receiving cyclophosphamide (CYC). <h3>Methods</h3> This randomized, double-blind, placebo-controlled Phase 2 trial was performed in a stepwise manner. In Step 1 (N=12), CCX168+CYC+low dose prednisone (20 mg/day starting dose) was compared to standard-of-care (SOC) (CYC+high dose prednisone, 60 mg/day starting dose). In Step 2 (N=14), CCX168+CYC and no prednisone was compared to SOC. Eligible patients had GPA, MPA, or renal limited vasculitis, were PR3 or MPO-ANCA positive, and had active renal vasculitis with a GFR &gt;30ml/min. The dose of CCX168 was 30 mg BID PO for 12 weeks and the dose of CYC was 15 mg/kg IV q2-3 wks. <h3>Results</h3> Baseline characteristics and efficacy results at Week 12 are shown in the table. The number of steroid rescue events was not higher in the CCX168 groups compared to SOC. The incidence of renal remission was higher in the CCX168 groups compared to the SOC control group. The percent decrease from baseline in BVAS, urinary ACR and urinary MCP-1/creatinine was higher in the CCX168 groups compared to SOC. Renal function, as measured by eGFR, increased in all 3 groups, with the largest increase (6.8 mL/min/1.73 m<sup>2</sup>) in the CCX168+low dose steroids group. CCX168 appeared to be well tolerated. No unexpected serious adverse reactions were observed with CCX168 use. There was one early withdrawal from study, in the control, SOC, group. <h3>Conclusions</h3> CCX168 plus CYC appear to be at least as effective, if not more effective, as full dose steroids plus CYC in treatment of patients with an ANCA associated renal vasculitis flare. <h3>Disclosure of Interest</h3> D. Jayne Consultant for: ChemoCentryx, Inc., A. Bruchfeld Consultant for: ChemoCentryx, Inc., M. Schaier: None declared, K. Ciechanowski: None declared, L. Harper Consultant for: ChemoCentryx, Inc., M. Jadoul: None declared, M. Segelmark Consultant for: ChemoCentryx, Inc., D. Selga: None declared, I. Szombati: None declared, M. Venning Consultant for: ChemoCentryx, Inc., C. Hugo: None declared, P. Van Daele: None declared, O. Viklicky: None declared, A. Potarca Consultant for: ChemoCentryx, Inc., T. Schall Shareholder of: ChemoCentryx, Inc., Employee of: ChemoCentryx, Inc., P. Bekker Shareholder of: ChemoCentryx, Inc., Employee of: ChemoCentryx, Inc. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3728
OP0165 Rheumatoid Arthritis is Associated with Reduced Adiposity but Not with Unfavorable Major Cardiovascular Risk Factor Profiles and Enhanced Carotid Atherosclerosis in Black Africans from a Developing Population: A Case-Control Study
Authors: A. Solomon, G. Norton, A. Woodiwiss, P. H. Dessein
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterized by inflamed joint derived cytokine mediated high-grade systemic inflammation that enhances cardiovascular metabolic risk and disease in developed populations. <h3>Objectives</h3> We investigated the potential impact of RA on cardiovascular risk factors including systemic inflammation, atherosclerosis and their relationships in black Africans from a developing population. <h3>Methods</h3> We evaluated demographic features, adiposity indices, major traditional cardiovascular risk factors, circulating C-reactive protein and interleukin-6 concentrations and ultrasound determined carotid intima-media thickness (cIMT) in 274 black Africans; 115 had established RA. Data were analyzed in confounder adjusted mixed regression models. <h3>Results</h3> The body mass index and waist-height ratio were lower in RA compared to non-RA subjects (29.2 (6.6) versus 33.7 (8.0), <i>P</i>&lt;0.0001 and 0.58 (0.09) versus 0.62 (0.1), P=0.0003, respectively). Dyslipidemia was less prevalent in patients with RA (odds ratio (OR) (95% confidence interval (CI)=0.54 (0.30 to1.00)); this disparity was no longer significant after further adjustment for reduced adiposity and chloroquine use. RA was also not associated with hypertension, current smoking and diabetes. The number of major traditional risk factors did not differ by RA status (1.1(0.8) versus 1.2(0.9), P=0.7). Circulating C-reactive protein concentrations were similar and serum interleukin-6 concentrations reduced in RA (7.2 (3.1) versus 6.7 (3.1) mg/l, P=0.7 and 3.9 (1.9) versus 6.3 (1.9) pg/ml, P&lt;0.0001, respectively). The cIMT was 0.700 (0.085) and 0.701 (0.111) mm in RA and non-RA subjects, respectively (P=0.7). RA disease activity and severity parameters were consistently unrelated to systemic inflammation, despite the presence of clinically active disease in 82.6% of patients. In all participants, adiposity indices, smoking and converting angiotensin inhibitor non-use were associated with increased systemic inflammation, which related to more atherogenic lipid profiles, and circulating low density lipoprotein concentrations were associated with cIMT (partial R=0.153, P=0.032); RA did not impact on these relationships (interaction P&gt;0.1). <h3>Conclusions</h3> Among black Africans, patients with established RA experience reduced overall and abdominal adiposity but no enhanced major traditional risk factor and atherosclerosis burden. This study further suggests that an absent interleukin-6 release by inflamed RA joints into the circulation may account for this unaltered cardiovascular disease risk. <h3>Acknowledgements</h3> This study was supported by a South African Medical Research Council grant and the National Research Foundation. <h3>Disclosure of Interest</h3> None Declared
Risk Factors for Preeclampsia, Abruptio Placentae, and Adverse Neonatal Outcomes among Women with Chronic Hypertension
Authors: Baha M. Sibai, Marshall Lindheimer, John Hauth, Steve Caritis, Peter VanDorsten, Mark Klebanoff, Cora MacPherson, Mark Landon, Menachem Miodovnik, Richard Paul, Paul Meis, Mitchell Dombrowski, Gary Thurnau, James Roberts, Donald McNellis
Journal: New England Journal of Medicine (1998)

Women with chronic hypertension who become pregnant have an increased risk of preeclampsia and adverse neonatal outcomes. However, within this group, the risk factors for these adverse events are not known.
THE ROLE OF REMOTE ISCHEMIC PRECONDITIONING IN THE PREVENTION OF CONTRAST INDUCED NEPHROPATHY
Authors: Patrick Tobbia, Cassandra Kimber, Ben Jang, Micah Levine, Alisher Abdoullayev, Robert Funk, David Jacobs, Mark Wiley, Ashwani Mehta, Matthew Earnest, Peter Tadros, Buddhadeb Dawn, Kamal Gupta
Journal: Journal of the American College of Cardiology (2016)