tbuckley/cabot-search huggingface dataset:
CMET-40. THE DEVELOPMENT OF BRAIN METASTASIS IN THE PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AND MELANOMA TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A RETROSPECTIVE ANALYSIS
Authors: Caroline Chaul-Barbosa, Kellyann Niotis, Matthew Hellmann, Margaret Callahan, Mariza Daras
Journal: Neuro-Oncology (2017)

AbstractBACKGROUNDSurvival benefit with immune checkpoints inhibitors in patients with metastatic NSCLC and Melanoma has been demonstrated. However, the published results do not describe the incidence of brain metastasis as a site of recurrence in these patients. We sought to determine the incidence of central nervous system (CNS) relapse/progression relative to systemic response in patients with NSCLC or Melanoma treated with a PD-1 inhibitor.METHODSWe retrospectively identified 217 patients (145 with metastatic NSCLC, 72 with metastatic Melanoma) treated with Pembrolizumab or Nivolumab, between 2009 and 2016. Demographic and clinical variable were assessed to determine CNS and systemic response using descriptive statistics.RESULTSThe median age of the cohort was 65 years (22–93), with a median of 1 (0–6) treatment prior to PD-1 inhibitor therapy and median follow-up of 344 days. Of the 217 patients, 213 received monotherapy with either Nivolumab (99) or Pembrolizumab (114). Four patients received Nivolumab combined with Bevacizumab. The median time on therapy was 113 days for Nivolumab (14–1598) and 149 for Pembrolizumab (21–1099). Forty patients had brain metastases at the time of initiation of treatment, and 28 of these patients received treatment for at least one brain metastasis prior to immunotherapy. Thirty-two patients (15%) had CNS disease progression during immunotherapy treatment: 15 patients (7%) developed new CNS disease and 17 (8%) had progression of pre-existing CNS metastasis (7/17 received prior CNS directed treatment). In these 32 patients, concomitant systemic disease progression was observed in 27, and 5 patients progressed only in the CNS.CONCLUSIONThis retrospective analysis showed that development/progression of CNS metastasis in patients on treatment with a PD-1 inhibitor has good concordance with systemic disease status. The incidence of CNS disease in patients on this therapy is comparable to historic cohorts treated with conventional chemotherapy.
SURG-24. OVERALL SURVIVAL IN A SYNGENEIC RODENT ORTHOTOPIC HIGH-GRADE GLIOMA MODEL IS SIGNIFICANTLY PROLONGED BY NEUROSURGICAL DELIVERY OF PLGA/PEG INTERSTITIAL CHEMOTHERAPY
Authors: Stuart Smith, Toby Gould, Betty Tyler, Alison Ritchie, Gareth Veal, Kevin Shakesheff, Henry Brem, Richard Grundy, Ruman Rahman
Journal: Neuro-Oncology (2017)

The blood brain barrier is a critical limiting step to achieving therapeutic CNS drug concentrations. We have developed a poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG)-based platform technology to interstitially deliver multiple chemotherapy agents from a single thermo-setting biodegradable paste, achieving high local but low systemic concentrations and sustained delivery of cytotoxic drugs directly to the CNS. Here we evaluate moldable PLGA/PEG paste for combined temozolomide (TMZ) and etoposide (ETOP) delivery in an orthotopic syngeneic high-grade glioma animal model. Drug release and preserved stability of the active TMZ molecule (AIC) was evaluated by fluoroscopic and LC-mass spectrometer based methods. In vitro cytotoxicity of released TMZ/ETOP was evaluated against high-grade glioma cell lines and patient-derived primary cultures using metabolic assays. In vivo efficacy and overall survival were evaluated in the syngeneic orthotopic 9L glioma rat model of intra cavity chemotherapy. TMZ and ETOP were released from PLGA/PEG alone or in dual combinations over 2 weeks in vitro. Cytotoxicity of released drugs in vitro is comparable to directly applied agents, demonstrating the retained molecular integrity of TMZ/ETOP upon loading and releasing from PLGA/PEG. Both high (20% w/w TMZ / 50% w/w ETOP) and low (10% w/w TMZ / 25% w/w ETOP) doses were well tolerated in vivo, with no observable weight loss nor neurological deficits. Significant positive survival benefits from PLGA/PEG/TMZ/ETOP therapy were observed in vivo compared to surgery alone, surgery with blank paste (49 vs. 14 days; p < 0.001) or surgery plus oral TMZ (49 vs. 33 days; p < 0.004). This study demonstrates that localized dual release of TMZ/ETOP achieves a significant extension to overall survival in vivo. As such, PLGA/PEG paste applied to the post-surgical resection cavity offers a realistic opportunity for localized control of residual malignant glioma cells.
QLIF-04. BRAIN TUMORS ASSOCIATED WITH PSYCHOGENIC NON EPILEPTIC SPELLS: CASE SERIES
Authors: Catherine Garcia, Priyanka Yadav, Amy Morrow, Tracy Howard, Donita Lightner, Gulam Khan, John Villano
Journal: Neuro-Oncology (2017)

Epileptic seizures (ES) are considered a main focus in assessing brain tumor treatment, yet, the role of psychogenic non epileptic spells (PNES) is known to be highly prevalent and is under-reported. In the neuro-oncology literature no cases have been well described having PNES. We present a series of five patients and identify risk factors, discuss the association of PNES with brain tumors and describe their role in brain tumor treatment. Patients were identified retrospectively from our practice with diagnosis of PNES and medical history of primary or secondary brain tumors. The diagnosis of psychogenic spells was based on history, seizure observation, routine EEG, and video-EEG. The mean age of presentation was 38 years, with a female gender predominance. The initial diagnosis of brain tumor was associated with a new onset seizure prior to diagnosis in the majority of the patients. Only one patient presented PNES alone, the rest of the patients presented both ES and PNES during the course of their disease. Most of the patients in this case series presented with mixed PNES and were treated with multiple anti-epileptic drugs (AED) prior and after PNES diagnosis. The most commonly used AED was gabapentin. All of the patients received a form of combination therapy. The preferred treatment modality was chemotherapy, followed by surgical resection. The patients manifested several distressing spells that affected their overall quality of life and required multiple medical consultations. None of these patients presented clinical evidence of tumor progression at the time of PNES presentation on imaging studies. Our findings offer a new perspective in PNES diagnosis and their involvement in brain tumor treatment along with possible prognosis implications. Further studies to analyze tumor localization or tumor behavioral patterns in association with PNES are warranted.
Vigilancia de la listeriosis en Finlandia, 1995-2004
Authors: O Lyytikäinen, U M Nakari, S Lukinmaa, E Kela, N Nguyen Tran Minh, A Siitonen
Journal: Eurosurveillance (2006)

El siguiente articulo presenta el analisis de los datos de vigilancia de los casos de listeriosis declarados al Registro nacional finlandes de enfermedades infecciosas entre 1995 y 2004, y la descripcion de las experiencias recientes de investigaciones de clusters de casos de listeriosis en este pais. El numero anual de casos oscilo entre 18 y 53, pero no se identificaron tendencias en la incidencia (incidencia anual media : 7 casos por millon de habitantes). Solamente un escaso numero de casos se producian en mujeres embarazadas o recien-nacidos. La mayoria de los pacientes eran personas ancianas con enfermedades benignas subyacentes ; el 25% de ellos fallecieron a causa de esas infecciones. Se detectaron varios clusters por medio del serotipado y del genotipado de los aislamientos de listeria hechos de forma rutinaria. El vehiculo de la infeccion se identifico en dos brotes solamente. Al menos, un cuarto de los casos de listeriosis (78/315) eran debidos a un sero-genotipo especifico o a genotipos ligados estrechamente, que se encontraron tambien en productos de la pesca ahumados o salados en frio y empaquetados al vacio. Durante el periodo 2000-2003, los consumidores finlandeses fueron informados varias veces de las recomendaciones de alimentacion en los grupos de riesgo. Esta informacion tambien se proporciono a los medicos y las clinicas prenatales.
JCES 01.11 A Multicenter, Non-Interventional Study on Real World EGFR Testing and in Patients with IIIB/IV NSCLC in Northern China
Authors: Y. Cheng, Y. Wang, J. Zhao, Y. Liu, H. Gao, K. Ma, S. Zhang, H. Xin, J. Liu, H. Chengbo, Z. Zhu, Y. Wang, J. Chen, F. Wen, J. Li, Z. Jie, Z. Zheng, Z. Dai, H. Piao, X. Li, Y. Li, M. Zhong, R. Ma, Y. Zhuang, Y. Xu, Z. Qu, H. Yang, C. Pan, F. Yang, D. Zhang, B. Li
Journal: Journal of Thoracic Oncology (2017)
Controlo da rubéola em França
Authors: D Lévy-Bruhl, C Six, I Parent du Châtelet
Journal: Eurosurveillance (2004)

A introducao, em 1983, da vacinacao contra a rubeola no programa nacional de vacinacao frances conduziu a uma reducao dramatica da incidencia de infeccoes da rubeola durante a gravidez e do sindrome de rubeola congenita, conforme demonstrado pela rede de vigilância que inclui todos os laboratorios de diagnostico que realizam analises de IgM contra a rubeola. Contudo, a cobertura subideal da vacinacao na crianca e mulher em idade reprodutora permite, respectivamente, a persistencia da transmissao da rubeola e a ocorrencia anual de duzias de infeccoes pela rubeola durante a gravidez. Devem ser envidados esforcos para aumentar a cobertura caso se pretendam evitar epidemias futuras decorrentes do nivel significativo de susceptibilidade nas mulheres jovens.
NIMG-96. DEEP LEARNING FOR SURVIVAL PREDICTING IN IDH WILD-TYPE GLIOMAS
Authors: Peter Chang, Daniel Chow, Daniela Bota, Laila Poisson, Christopher Filippi, Rajan Jain
Journal: Neuro-Oncology (2017)

Deep learning through convolutional neural networks (CNN) has recently emerged as a top-performing machine-learning algorithm across various image classification tasks. We propose a CNN approach that integrates multimodal MRI data, tumor volumetrics, and Karnofsky performance score (KPS) to predict overall survival (OS) in glioma patients with IDH wild-type mutation (IDHwt). High-grade and low-grade IDHwt glioma patients were identified from The Cancer Genome Atlas. Corresponding multimodal MRI (T2, FLAIR, T1-pre and post contrast) were obtained from The Cancer Imaging Archives. A fully-automated algorithm was used to segment tumor margins and determine whole tumor volumes as well as lobe locations. Patients with were stratified into three groups based on OS: poor (1-to-6 months), average (6-to-24 months), high (>24 months). A CNN was used to integrate multimodal MR, tumor volume and location, and KPS to predict patient OS. The 3D CNN is based on a generative-adversarial network for semi-supervised learning utilizing feature-matching. Non-imaging data were integrated into the classifier by concatenation with imaging features in the penultimate layer. A total of 110 patients were analyzed (26 poor-survival, 61 average-survival, 23 high-survival). Single-factor ANOVA did not detect a significant difference in OS based on tumor volume, lobe location, or KPS parameters individually. However, integrated multimodal CNN accurately predicted survival cohort in 82% of patients by five-fold validation. Features most highly correlated with survival were identified. A deep learning algorithm integrating imaging and clinical data can predict OS in IDHwt glioma with 82% accuracy. Future work will validate this methodology prospectively.
Flu vaccination by pharmacists leads to suboptimal medical records
Authors: Simon de Lusignan, Matthew Hoghton, Imran Rafi
Journal: BMJ (2017)

We don’t condone unfair pressure on patients to have their flu vaccine at their general practitioner’s surgery,1 but pharmacist vaccination leads to problems with data integrity.

The communication from pharmacist to general practitioner is suboptimal. It is often on paper and states only that the vaccination has occurred, without the vaccine manufacturer or batch number. In contrast to many other communications, it does not include a …
¡Gripe precoz en Europa, y el SRAS escapa de los laboratorios de alta seguridad!
Authors: J C Desenclos
Journal: Eurosurveillance (2003)

En este numero, Radun et al informan acerca de una investigacion retrospectiva de SRAS realizada en veintiun huespedes alemanes que se alojaron en el Hotel 'M' de Hong Kong del 21 de febrero al 3 de marzo de 2003 (1). Pudieron identificar de forma retrospectiva un caso no reconocido de SRAS en un paciente que se habia alojado en la novena planta la noche del 21-22 de febrero (la misma planta que el medico sintomatico que contrajo SRAS en la provincia de Guangdong, China). El caso aleman con serologia positiva de SRAS-CoV desarrollo sintomas compatibles con SRAS a los pocos dias de su regreso de Hong Kong. No habia tenido contacto directo con el caso indice. Sin embargo, la persona que compartio habitacion con el en el Hotel 'M' no desarrollo sintomas y dio negativo en el analisis de anticuerpos de SRAS-CoV. Aunque el modo de transmision principal de SRAS es el contacto estrecho con un caso sintomatico, esta investigacion sugiere que en ocasiones tambien se puede producir una transmision de origen ambiental, e indica que el riesgo de transmision es muy heterogeneo. Tambien documenta que este caso de SRAS no fue detectado por la vigilancia aunque, afortunadamente, no dio lugar a ninguna transmision. 
En el momento de notificar los resultados del Programa Europeo para la Vigilancia de la Gripe (European Influenza Surveillance Scheme; EISS) de la temporada 2002/2003 en esta edicion de Eurosurveillance (2), muchos paises europeos ya se han visto afectados por la epidemia gripal 2003/2004 (3). La llegada de la temporada gripal 2003/2004 suscito una preocupacion mayor que la habitual debido al temor de una reaparicion del SRAS y, en particular, debido a la dificultad potencial de reconocer casos de SRAS reemergentes en medio de una epidemia de gripe. Por otra parte, las leves temporadas de gripe registradas en los ultimos anos han contribuido a que una gran proporcion de la poblacion infantil tenga baja inmunidad y por consiguiente sean mas susceptibles, lo que daria lugar a una tasa de ataque infantil superior a la habitual.
HIV prevalence and behavioral and psychosocial factors among transgender women and cisgender men who have sex with men in 8 African countries: A cross-sectional analysis
Authors: Tonia Poteat, Benjamin Ackerman, Daouda Diouf, Nuha Ceesay, Tampose Mothopeng, Ky-Zerbo Odette, Seni Kouanda, Henri Gautier Ouedraogo, Anato Simplice, Abo Kouame, Zandile Mnisi, Gift Trapence, L. Leigh Ann van der Merwe, Vicente Jumbe, Stefan Baral
Journal: PLoS Medicine (2017)

Introduction Sub-Saharan Africa bears more than two-thirds of the worldwide burden of HIV; however, data among transgender women from the region are sparse. Transgender women across the world face significant vulnerability to HIV. This analysis aimed to assess HIV prevalence as well as psychosocial and behavioral drivers of HIV infection among transgender women compared with cisgender (non-transgender) men who have sex with men (cis-MSM) in 8 sub-Saharan African countries. Methods and findings Respondent-driven sampling targeted cis-MSM for enrollment. Data collection took place at 14 sites across 8 countries: Burkina Faso (January–August 2013), Côte d'Ivoire (March 2015–February 2016), The Gambia (July–December 2011), Lesotho (February–September 2014), Malawi (July 2011–March 2012), Senegal (February–November 2015), Swaziland (August–December 2011), and Togo (January–June 2013). Surveys gathered information on sexual orientation, gender identity, stigma, mental health, sexual behavior, and HIV testing. Rapid tests for HIV were conducted. Data were merged, and mixed effects logistic regression models were used to estimate relationships between gender identity and HIV infection. Among 4,586 participants assigned male sex at birth, 937 (20%) identified as transgender or female, and 3,649 were cis-MSM. The mean age of study participants was approximately 24 years, with no difference between transgender participants and cis-MSM. Compared to cis-MSM participants, transgender women were more likely to experience family exclusion (odds ratio [OR] 1.75, 95% CI 1.42–2.16, p < 0.001), rape (OR 1.95, 95% CI 1.63–2.36, p < 0.001), and depressive symptoms (OR 1.30, 95% CI 1.12–1.52, p < 0.001). Transgender women were more likely to report condomless receptive anal sex in the prior 12 months (OR 2.44, 95% CI 2.05–2.90, p < 0.001) and to be currently living with HIV (OR 1.81, 95% CI 1.49–2.19, p < 0.001). Overall HIV prevalence was 25% (235/926) in transgender women and 14% (505/3,594) in cis-MSM. When adjusted for age, condomless receptive anal sex, depression, interpersonal stigma, law enforcement stigma, and violence, and the interaction of gender with condomless receptive anal sex, the odds of HIV infection for transgender women were 2.2 times greater than the odds for cis-MSM (95% CI 1.65–2.87, p < 0.001). Limitations of the study included sampling strategies tailored for cis-MSM and merging of datasets with non-identical survey instruments. Conclusions In this study in sub-Saharan Africa, we found that HIV burden and stigma differed between transgender women and cis-MSM, indicating a need to address gender diversity within HIV research and programs.
EXTH-08. DISCOVERY OF CT-179: A SMALL MOLECULE INHIBITOR OF THE OLIG2 TRANSCRIPTION FACTOR WITH POTENT ANTI-TUMOUR ACTIVITY IN HIGH-GRADE GLIOMA
Authors: Terrance Johns
Journal: Neuro-Oncology (2017)

OLIG2 is a protein transcription factor (TF) expressed exclusively in progenitor cells in the brain and spinal cord during development and is re-expressed in most high-grade glioma (HGG) patients. Expression of OLIG2 drives the growth, invasiveness, and resistance to radiation of HGG cells and tumors in animal models. CT-179 is a novel small molecule (M.W. 397) that is a disruptor of OLIG2 homodimerization. We now show that CT-179 profoundly inhibited the growth, and induced apoptosis, in a range of patient-derived HGG cell lines at low nM concentrations. Treated cells showed substantial degradation of OLIG2 protein that was associated with G2/M arrest and mitotic catastrophe. CT-179 also caused significant down-regulation of receptor tyrosine kinases associated with HGG tumorigenicity, including EGFR and PDGFR. Orally administered CT-179 (20 mg/kg) crossed the blood-brain-barrier of intact mice reaching levels sufficient to inhibit HGG cells. Indeed, the growth of established orthotopic HGG xenografts in mice was significantly inhibited by CT-179. Our studies have provided the impetuses for moving CT-179 into the clinic as a novel therapy for patients with HGG.
DDIS-04. NITROXOLINE EXHIBIT ANTICANCER ACTIVITY INDUCING APOPTOSIS IN A TEMOZOLOMIDE-RESISTANT GLIOBLASTOMA
Authors: Nisha Kumari, Hye Rim Cho, Hyejin Jeon, Nishant Thakur, Jooyeon Chung, Seung Hong Choi
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival. Current standard treatment includes chemotherapy with DNA-alkylating agent temozolomide (TMZ), but the acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. In our study, we assessed whether nitroxoline has antiproliferative properties against TMZ-resistant cancer cell lines in vitro and in vivo using TMZ-resistant glioblastoma mouse model. Here, we prepared TMZ-resistant cancer cell lines and showed antiproliferative effect of nitroxoline by cytotoxic, migration and clonogenic assay. Anti-proliferative effect of nitroxoline was associated with G0-G1 arrest determined by fluorescence-activated cell sorting (FACS) which ultimately leads to decreased in protein levels of cyclin D1, phosphorylated Rb and cyclin A. In addition, nitroxoline treated cells showed apoptosis confirmed by increased expression of cleaved caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Furthermore, nitroxoline slow down the tumor progression in TMZ-resistant GBM mouse model confirmed by T2WI-MRI, in contrast tumor was significantly increased in non-treated mice. In terms of DWI, we also observed the increased apparent diffusion coefficient (ADC) value, suggestive of decreased cellularity, in nitroxoline treated GBM in mice model, while significantly decreased in non-treated. These results suggest the potential role of nitroxoline for therapeutic development against TMZ-resistant GBM.
Evaluation of stromal tumour-infiltrating lymphocytes (TILs) in breast cancer by Dynamic contrast–enhanced magnetic resonance (DCE-MR) imaging
Authors: M. De Lisa, M. Pistelli, R. Giampieri, M. Macchini, M. Ponzani, G.M. Giuseppetti, A. Santinelli, L. Bastianelli, Z. Ballatore, N. Battelli, R. Berardi
Journal: Annals of Oncology (2017)
P1.09-006 JMJ and BRD Domain Family Members in Malignant Pleural Mesothelioma: Potential Therapeutic Targets or Not?
Authors: S. Gray, M. Breslin, S. Cregan, L. Quinn, S. Wennstedt, A. Singh, L. Macdonagh, G. Roche, Y. Gao, C. Albadri, K. Griggs, M. Kirschner, K. O’Byrne, S. Klebe, G. Reid, S. Finn, S. Cuffe
Journal: Journal of Thoracic Oncology (2017)
Abstract 384: Evaluating Late Sodium Current in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Derek Schocken, Jayna Stohlman, Xiaoyu Zhang, Yama Abassi, Lars Johannesen, Jose Vicente, David Strauss, Ksenia Blinova
Journal: Circulation Research (2016)

Background: Inhibiting late sodium current (I NaL ) reduced drug-induced QTc prolongation in a recent clinical trial. Induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) have emerged as a valuable tool in preclinical assessment of multichannel blocking drugs’ potential to prolong QT and induce arrhythmias. However, sodium channels in commercially available iPSC-CMs are known to be under expressed, necessitating investigation into the presence and effects of I NaL in this electrophysiological model. Methods and Results: A platform combining simultaneous measurements of field potential and contraction (xCELLigence RTCA CardioECR, ACEA Biosciences) was used to assess the acute effects of three I NaL enhancing drugs, ATX-II, ibutilide, and alfuzosin, given alone or in combination with an I NaL blocker, lidocaine in iPSC-CMs (iCell Cardiomyocytes 2 , Cellular Dynamics). Additionally, dofetilide, diltiazem, and lidocaine alone were included as positive controls for hERG, L-type calcium, and sodium channel block. ATX-II, a potent and specific I NaL enhancer, caused significant dose dependent rate-corrected field potential duration (FPDc) prolongation, which was then subsequently reduced in a dose dependent manner by the addition of lidocaine. At 100 nM ATX-II prolonged the FPDc by 1153.8 ± 135.8 ms from 360.5 ± 16.4 ms at the baseline, which was then reduced to 537 ± 37.4 ms with the addition of 30 μM lidocaine. Ibutilide (0.1-1 μM), a class III antiarrhythmic, caused beating rate decreases and early after depolarizations (EADs) that were not affected by lidocaine addition. Alfuzosin, which increases both peak and late sodium currents, caused dose-dependent reduction of beating rate, FPDc prolongation, and EADs at 5 μM and 10 μM. Alfuzosin-induced EADs were mitigated by addition of lidocaine (5-15 μM). Conclusions: Late sodium current enhancers prolonged repolarization and induced arrhythmias in human iPSC-CMs. These effects were reversed by addition of lidocaine, a specific late sodium current blocker. These results are consistent with the late sodium current being present in iPSC-CMs in the presence of a late sodium current enhancer, which may have implications for drug safety testing.
MA 01.01 Metastatic Behavior of Pulmonary Neuroendocrine Carcinomas Is Associated with Epithelial to Mesenchymal Transition Gene Profile
Authors: T. Prieto, V. De Sá, E. Olivieri, E. Da Silva, R. Reis, D. Carraro, V. Capelozzi
Journal: Journal of Thoracic Oncology (2017)