tbuckley/cabot-search huggingface dataset:
EXTH-84. TARGETING THE SALVAGE PATHWAY OF NAD+ GENERATION IN GLIOMAS BY KPT-9274, A NOVEL DUAL INHIBITOR OF PAK4 AND NAMPT
Authors: Pratibha Sharma, Divya Kesanakurti, Pei-Jung Wu, Jihong Xu, Deepa Sampath, William Senapedis, Erkan Baloglu, Vinay K Puduvalli
Journal: Neuro-Oncology (2017)

Current treatment of glioblastoma (GBM) with surgery and chemoRT yields an average survival of ~1.5 years, highlighting the need for more effective therapies. We have previously reported that PAK4 is a key modulator of radioresistance in GBM. Additionally, pathways that regulate differential energy metabolism in gliomas and circumvent tumor heterogeneity have recently emerged as promising therapeutic targets. We hypothesized that inhibition of NAMPT, the rate-limiting enzyme of the NAD+ salvage pathway, a key pathway preferentially used in glioma energy metabolism, would be effective against GBM. We tested the efficacy of KPT9274, a potent first-in-class dual inhibitor of PAK4 and NAMPT, currently in human trials against solid tumors and lymphomas (NCT02702492), on NAD levels and cell viability in glioma cell lines and patient-derived glioma stem-like cells (GSC). We also examined enzyme-kinetics of various components of the NAD salvage pathway and effects of NADH rescue by nicotinamide, NMN and NAD. Lastly, we examined the biological relevance of NAMPT inhibition in glioma cells and GSC using a combination of cell adhesion, wound-healing, transwell-migration and microtubule formation assays. Treatment with KPT9274 resulted in potent depletion of NAD in glioma cells which was rescued by nicotinamide, NMN and NAD demonstrating its specificity against NAMPT. KPT-9274 treatment resulted in potent inhibition of cell adhesion, migration, cell invasion, endothelial tube formation and proliferation in glioma cells and GSC. In vivo studies in mouse bioluminescent intracranial glioma PDX model as well as PK studies are ongoing to confirm the pre-clinical significance of targeting NAMPT in gliomas and will be presented. Our study demonstrates a key role for NAMPT in NAD generation in gliomas as seen by the potent biological effects of KPT-9274 against these tumors and supports the potential for targeting the NAD salvage pathway as a novel therapeutic strategy for treatment of GBM.
Osteonecrosis of jaw (ONJ) after antiresorptive treatment (bisphosphonates, denosumab) of cancer-treatment induced bone loss (CTIBL): a negligible risk?
Authors: A. Gambino, M. Cabras, V. Fusco, O. Bertetto, I. De Martino, M. Alessio, G. Numico
Journal: Annals of Oncology (2017)
Abstract 20478: A Novel AED Electrode Design Significantly Improves Laypersons Abillities to Correctly Place AED Electrodes
Authors: Henrik Bødtker, Mathilde Stærk, Kasper G Lauridsen, Bo Løfgren
Journal: Circulation (2017)

Introduction:  Defibrillation with an automated external defibrillator (AED) improves survival after cardiac arrest. Laypersons rarely place the left apical AED electrodes according to international guidelines. Incorrect electrode placement may reduce the chance of successful defibrillation.   Hypothesis:  Novel AED electrodes with pictures of correct electrode placement on a human improves left apical AED electrode placement compared with conventional AED electrodes with standard pictograms.   Methods:  Untrained laypersons were randomized to apply A) Novel AED electrodes with pictures of correct electrode placement on a human (Figure), or B) conventional AED electrodes with pictograms on a resuscitation manikin. Positioning of AED electrodes was compared to the recommended electrode position. Time to AED electrode placement was measured. Participants were asked to rate the user-friendliness of the two electrode designs on a 10 point-scale. The primary endpoint was ratio of correct left apical AED electrode placement defined as ≤5 cm from the recommended position.   Results:  In total, 84 participants were randomized to novel (n=39, female: 62% median age: 41.5 years (±10.3)) and standard (n=45, female: 64% median age: 43.5 (±8.2)) electrodes. The left apical AED electrode placement was improved when using novel electrodes with pictures compared with standard electrodes (51% vs 18%, (P   Conclusion:  A novel AED electrode design with pictures results in faster and better electrode placement compared with conventional AED electrodes using standard pictograms. Novel electrodes with pictures were preferred by laypersons.
OA 06.07 Survival Trends Among Non-Small Cell Lung Cancer (NSCLC) Patients Over A Decade: Impact of Initial Therapy at Academic Centers
Authors: B. Dholaria, S. Ailawadhi, A. Soyano, D. Hodge, R. Manochakian, M. Menefee, E. Johnson, M. Thomas, S. Ko, R. Miller, M. Johnson, N. Patel, K. Mody, R. Joseph, Y. Lou
Journal: Journal of Thoracic Oncology (2017)
OA 12.01 The Preclinical and Clinical Activity of Poziotinib, a Potent, Selective Inhibitor of EGFR Exon 20 Mutant NSCLC
Authors: Y. Elamin, J. Robichaux, V. Lam, A. Tsao, C. Lu, G. Blumenschein, J. Kurie, J. Brahmer, S. Li, T. Chen, A. Estrada-Bernal, A. Truini, M. Nilsson, A. Le, Z. Tan, S. Zhang, R. Doebele, K. Politi, Z. Yang, S. Liu, K. Wong, J. Heymach
Journal: Journal of Thoracic Oncology (2017)
Epidemiologia da rubéola e síndrome de rubéola congénita na Grécia, 1994-2003
Authors: T Panagiotopoulos, T Georgakopoulou
Journal: Eurosurveillance (2004)

Em 1993, foi registada uma grande epidemia de rubeola e sindrome de rubeola congenita (CRS) na Grecia. Neste artigo, descreve-se a epidemiologia da rubeola e CRS depois de 1993, utilizando-se informacoes provenientes de dados de vigilância e estudos e relatorios publicados. A incidencia da rubeola desceu nitidamente depois de 1993, mas em 1999 foi registada uma epidemia mais pequena, principalmente em adultos jovens, tendo-se tambem registado quatro casos de CRS (4,0 por 100 000 nados vivos). Actualmente, uma proporcao muito elevada da populacao infantil na Grecia esta vacinada contra a rubeola, enquanto que os adolescentes apresentam uma cobertura inadequada (60 a 80% em diferentes estudos). Uma proporcao significativa das mulheres em idade reprodutora e susceptivel a rubeola (10 a 20% nas areas urbanas). Tal podera conduzir a epidemias locais ou mais disseminadas. Esta situacao mostra que deve ser implementada uma politica preventiva compreensiva.
HOUT-16. NON-ROUTINE DISCHARGE DISPOSITION IS ASSOCIATED WITH POST-DISCHARGE COMPLICATIONS AND 30-DAY READMISSIONS FOLLOWING CRANIOTOMY FOR BRAIN TUMOR RESECTION
Authors: Nikita Lakomkin, Constantinos Hadjipanayis
Journal: Neuro-Oncology (2017)

Several studies have reported an association between high-volume brain tumor centers and greater rates of routine discharge disposition in the context of better outcomes. However, the relationship between in-hospital complications, discharge destination, and postoperative adverse events (AEs) remains unexplored. The purpose of this study was thus to use a large, prospectively collected database to examine the association between discharge destination, post-discharge complications, and readmissions among patients undergoing craniotomy for brain tumor. The 2011-2014 National Surgical Quality Improvement (NSQIP) database was employed to identify all adult patients who underwent a craniotomy for tumor resection and had a histologic brain tumor diagnosis via ICD-9 coding. Demographics, comorbidities, and perioperative variables were collected for each patient. Univariate statistics with subsequent binary logistic regression analyses were used to explore the relationship between these perioperative factors and postoperative events, including major post-discharge complications, minor post-discharge AEs, and 30-day readmissions. Significant variables such as demographics, comorbidities, operative time, body mass index, ASA classification and pre-discharge complications were controlled for in each model. Of the 14,854 patients identified, 11,409 (77.9%) were discharged home. After controlling for comorbidities and in-hospital AEs, non-home discharge was an independent predictor of major post-discharge complications (OR: 1.74, 95%CI: 1.36-2.22, p<0.001), minor post-discharge events (OR: 1.45, 95%CI: 1.01-2.07, p=0.045), and readmissions (OR: 2.06, 95%CI: 1.48-5.12, p<0.001). Non-routine discharge disposition is predictive of an array of complications as well as readmission following discharge. These factors may be considered in discharge planning and perioperative counseling for patients undergoing brain tumor resection.
PDCT-11. COMPUTER BASED NEUROCOGNITIVE ASSESSMENT IN CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMORS TREATED WITH PROTON BEAM RADIOTHERAPY
Authors: Jessika Contreras, Hayley Stowe, Todd Dewees, Allison King, Hannah Heimos, Laura Mccommis, Stephanie Perkins
Journal: Neuro-Oncology (2017)

Advances in the treatment of pediatric central nervous system (CNS) malignancies have improved survival in this patient population. However, long term survivors can experience adverse late effects including neurocognitive dysfunction. In this study we prospectively performed neurocognitive testing on pediatric patients receiving proton therapy (PT) for CNS malignancies using the National Institutes of Health (NIH) Toolbox Cognitive Battery (TCB). This was a prospective cohort. Between 2014 and 2017, children ages 4-21 years with a CNS malignancy treated with PT, were consented and completed NIH TCB testing prior to or within the first week of PT and at 6-18 months of follow-up. Age corrected scores were reported and compared to normative data using a mean of 100 and a standard deviation of 15. Impairment in a specific domain was defined as one standard deviation below the mean. A paired sample t-test was used to compare age adjusted scores to normative data. Twenty children participated with a median age of 11 years (range 4-19). Median follow up time was 12 months (range 6-18) months. At baseline, 33.3% of patients had an impairment in the cognitive fluid composite (p=0.022), 52% in processing speed (p<0.01), and 44% in attention (P<0.01). Median time to retest after PT was 8 (range 6-17) months. At follow-up, impairments persisted in the fluid composite (59%, p<0.01), processing speed (63%, p<0.01), and attention (55%, p<0.01) with the addition of episodic memory (33%, p=0.02), executive function (37%, P<0.01) and the early childhood composite score (41%, p<0.01). For these pediatric CNS tumor patients, attention and processing speed were significantly impaired at the beginning of radiation therapy. Early follow-up testing showed new impairments in episodic memory and executive function. Continued follow up and correlation of PT dosimetry may provide further information regarding potential predictors of neurocognitive impairment.
Chronic inflammation is a feature of Achilles tendinopathy and rupture
Authors: Stephanie Georgina Dakin, Julia Newton, Fernando O Martinez, Robert Hedley, Stephen Gwilym, Natasha Jones, Hamish A B Reid, Simon Wood, Graham Wells, Louise Appleton, Kim Wheway, Bridget Watkins, Andrew Jonathan Carr
Journal: British Journal of Sports Medicine (2017)

Background Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture. Methods We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers. Results Tendinopathic and ruptured Achilles highly expressed CD14+ and CD68+ cells and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased PTGS2 and interleukin-8 expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells. Conclusions Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease.
STEM-32. PRE-CLINICAL SAFETY AND EFFICACY STUDIES OF NEURAL STEM CELL MEDIATED CARBOXYLESTERASE/IRINOTECAN ENZYME/PRODRUG GENE THERAPY FOR RECURRENT GLIOMA LEADING TO FIRST-IN-HUMAN PHASE I CLINICAL TRIAL
Authors: Lucy Ghoda, Marianne Metz, Revathiswari Tirughana, Soraya Aramburo, Megan Gilchrist, Margarita Gutova, Timothy Synold, Michael Barish, Christine Brown, Massimo D’Apuzzo, Rex Moats, Phil Potter, Suzette Blanchard, Jana Portnow, Karen Aboody
Journal: Neuro-Oncology (2017)

Human neural stem cells (NSCs) are inherently tumor-tropic, localizing to invasive brain tumor foci following intracerebral administration in preclinical models of primary and secondary brain tumors, thus overcoming obstacles limiting current therapeutic modalities. These NSCs can be engineered to express numerous anti-cancer agents, making them attractive drug delivery vehicles. By concentrating therapy selectively at the tumor sites, toxicity to normal tissues and associated side effects are minimized, improving quality of life. A first-in-human pilot safety/feasibility clinical trial for recurrent glioma patients using a clonal, allogeneic NSC line (HB1.F3.CD21) for cytosine deaminase/5-fluorocytosine (5-FC) enzyme/prodrug gene therapy demonstrated safety, proof of concept for brain tumor localized NSC-mediated conversion of prodrug to active chemotherapeutic agent, non-tumorigenicity, and non-immunogenicity with a single round of treatment (Portnow et al, 2016). HB1.F3.CD21 NSCs were further engineered to secrete a modified human carboxylesterase (hCE1m6) that converts irinotecan (IRN) to the potent topoisomerase-1 inhibitor SN-38. Presented are the preclinical in vitro and in vivo pharmacokinetic studies optimizing dose and scheduling of hCE1m6-NSCs and a clinically equivalent bolus dose of IRN. Efficacy studies in orthotopic glioma models with multiple treatment cycles demonstrated a highly significant increase in the long-term survival distribution in mice treated with hCE1m6-NSCs + IRN as compared to IRN alone (Holm-Bonferroni adjusted p-value <0.0001). Results of IND-enabling safety/toxicity studies showed no significant increase in toxicity, as determined by daily clinical observations, blood chemistries, CBCs, and histopathology, in mice treated with hCE1m6-NSCs + IRN as compared to IRN alone. These results led to FDA approval for a recently initiated first-in-human phase I dose escalation, multiple treatment cycle study of intracranially administered carboxylesterase expressing NSCs in combination with intravenous irinotecan for the treatment of recurrent high grade gliomas (IND 16265; clincialtrial.gov ID NCT02192359).
RTHP-34. STEREOTACTIC RADIOSURGERY FOR GLIOBLASTOMA
Authors: Tomoo Matsutani, Yasuo Iwadate
Journal: Neuro-Oncology (2017)

Recently, additional radiation boost including stereotactic radiosurgery (SRS) has been argued as a treatment for glioblastoma. In our institute, SRS was occasionally used for glioblastoma as an initial post-operative treatment for elderly or irradiated patient, or as a salvage therapy at recurrence. To clarify the benefit of SRS in the treatment for glioblastoma, survival benefit was retrospectively considered. Of 118 pathologically-proven glioblastoma patients from 2005 to 2016, 9 patients were irradiated by SRS. None of six investigated tumor presented IDH1 R132H mutation, and two of six showed methylated MGMT promotor by methylation-specific PCR. Of nine, 2 were treated as an initial therapy and 7 were as a salvage treatment for recurrence. 7 were single and 2 were multicentric, and median single enhancing tumor volume is 1.67cm3 (099-9.52). Median therapeutic dose was 23.0Gy (20-26) and staged treatment was performed in two patients. Four of 7 recurrence were followed by Bevacizumab for a few months. 6-months and 1-year local progression-free survival rate is 72.9% and 43.8%, respectively. Of seven recurrence, 6-months and 1-year post-recurrent survival rate is 71.4% and 28.6%, and median post-recurrent over-all survival is 9.9 months. Of note, overall survival of two elderly patients, initially treated by SRS without conventional radiation therapy, are 23.0 and 24.2 months. SRS is beneficial treatment for recurrent glioblastoma or elderly glioblastoma patients.
Vigilancia de la listeriosis humana en Francia, 2001-2003
Authors: V Goulet, C Jacquet, P Martin, V Vaillant, E Laurent, H de Valk
Journal: Eurosurveillance (2006)

La declaracion obligatoria de la listeriosis se inicio en Francia en 1999. La vigilancia reforzada de la salud publica, incluyendo la caracterizacion molecular rutinaria de las cepas de L. monocytogenes, el seguimiento epidemiologico de los casos y la recogida de muestras de alimentos, mejoraron la sensibilidad de la deteccion de los brotes y la respuesta. La incidencia de la listeriosis disminuyo de 4,5 casos/millon en 1999-2000 a 3,5 casos/ millon aproximadamente durante el periodo 2001-2003. Las caracteristicas clinicas, demograficas y microbiologicas de la listeriosis en Francia permanecieron estables en ese periodo. Las infecciones materno-neonatales representaron el 24% de todos los casos. El serotipo 4b estaba presente en el 49% de los casos y en el 60% de las agrupaciones. La incidencia de la listeriosis en Francia ha bajado y ahora es inferior que la de algunos paises europeos.
P1.05-009 Analysis of Postoperative Prognosis in Terms of the Difference Between the Invasive Growth Area and the Total Tumor Diameter
Authors: M. Yotsukura, Y. Suzuki, K. Kaseda, K. Masai, Y. Hayashi, T. Hishida, T. Ohtsuka, H. Asamura
Journal: Journal of Thoracic Oncology (2017)
Addressing the best treatment for non-clear cell renal cell carcinoma (nccRCC): a meta-analysis of randomized clinical trials comparing VEGFR-TKis versus mTORi targeted therapies
Authors: C. Ciccarese, R. Iacovelli, F. Massari, M. Brunelli, D. Bimbatti, E. Fantinel, V. De Marco, A.B. Porcaro, G. Martignoni, W. Artibani, G. Tortora
Journal: Annals of Oncology (2017)
Colon-rectal follow-up program: a monocentric experience
Authors: E. Stratta, R. Murialdo, M. Sparavigna, S. Scabini, E. Romairone, G. Zoppoli, L. Tixi, A. Ghiglione, E. Harusha, A. Ballestrero
Journal: Annals of Oncology (2017)
ESEN : una comparación de programas de vacunación – Tercera parte: sarampión, parotiditis y rubéola
Authors: D Lévy-Bruhl, R G Pebody, I Veldhuijzen, M Valenciano, K Osborne
Journal: Eurosurveillance (1998)

Este articulo es el ultimo de una serie de tres articulos, aqui publicados, que compara en ocho paises europeos (Dinamarca, Inglaterra y Gales, Finlandia, Francia, Alemania, Italia, Suecia y Paises Bajos), los programas de inmunizacion, calendarios vacunales y el impacto epidemiologico de la vacunacion contra la difteria, la tos ferina, el sarampion, la parotiditis y la rubeola. Este analisis se ha llevado a cabo en el marco de la Red Europea de Vigilancia Serologica (ESEN), proyecto financiado por la Union Europea (1). La metodologia del analisis, las caracteristicas de los programas de inmunizacion y los resultados correspondientes a la difteria y tos ferina fueron ya presentados en los dos primeros articulos de la serie (2,3). El presente articulo ofrece los resultados correspondientes a sarampion, parotiditis y rubeola (SPR).
ACTR-60. TOO YOUNG TO DIE! – OUTCOME OF GLIOBLASTOMA IN YOUNG ADULTS
Authors: Thomas Hundsberger, Andreas Hottinger, Ulrich Roelcke
Journal: Neuro-Oncology (2017)

Glioblastoma is common in elderly patients, but is quite rare in young adults with an annual incidence of 0.41 and 1.23/100000 in 20–34 and 35-44-year-old patients, respectively, compared to 13.09/100000 (65–74 years) in the typical elderly population. Accordingly, there is a striking paucity of outcome analysis for younger glioblastoma patients as opposed to the elderly population. Outcome analysis of young adults with glioblastoma (18–46 years) by retrospective chart review in 3 neuro-oncology centers in Switzerland. Between 2004 and 2017 29 patients (median age, 39.8 years; range, 20–45) were identified. Initial treatment consisted of surgery (28, resection; 1, biopsy), combined radiochemotherapy (all) and adjuvant temozolomide (n=26). Median PFS and OS was 11.7 months (range, 1.6–101.6) and 20.0 (range, 6.3.-147.3) months, respectively. OS after one and two years were 79% and 41%, respectively. All 21 patients with a recurrence received a 2nd- line therapy (6, re-surgery; 1, reRT; 9, RT/Tem; 8, Bev; 3, Bev/Lom). PFS after 2nd-line treatment was poor with a median of 5.9 months (range, 1.9–62.1). At second recurrence 12 patients received a 3rd-line therapy. Occasionally, 4th and 5th-line treatment were applied (n=5). Twelve patients are still alive. Four patients experienced a lower than expected median survival of 14.2 months of the pivotal RT/Tem+Tem trial (2, gross total resection; 2, partial resection). Although younger glioblastoma patients in this cohort had a better prognosis than the mixed population of the pivotal RT/Tem+Tem trial, occasional patients (4/29) experienced a very bad outcome. Molecular data and treatment related issues may provide more insights into the course of glioblastoma in younger adults.