tbuckley/cabot-search huggingface dataset:
EPID-17. A SINGLE CENTER RESTROSPECTIVE REVIEW OF RECURRENT OR TREATMENT REFRACTORY PEDIATRIC MEDULLOBLASTOMA
Authors: Michelle Kameda-Smith, Branavan Manoranjan, Olufemi Ajani, Blake Yarascavitch, Tina Petrelli, Sheila Singh, Adam Fleming
Journal: Neuro-Oncology (2017)

The outcome of pediatric refractory or relapsed brain tumours remains a concern for treating neurooncology teams with the most effective salvage therapy yet to be established. Upfront therapy for primary medulloblastoma (MB) is dependent on age, post-operative residual and evidence of metastasis at diagnosis. Children diagnosed with aggressive subtypes of MB that are refractory to upfront therapy or recur either in the resection cavity or as distant metastases have a very poor prognosis. Reports of phase I and II studies for these children exist, but these therapies bear significant treatment related morbidity and mortality. A retrospective review of children diagnosed with a pediatric MB from 2002–2017 from the McMaster Pediatric Brain Tumour Study Group (PBTSG) captured a number of pediatric recurrent MB. Subsequently the treatments received and outcomes were identified. Over the 15-year period, 30 children with a histological diagnosis of MB were treated. Ten children were recurrent or treatment refractory MB. The 5-year outcome survival (OS) for this group of patients as compared to no recurrence was 20% and 90% respectively. The mean follow-up for survivors of recurrent MB however was 3.2 years. In 4 of 10 recurrent MB, the disease had significantly progressed and palliated. For the remaining children, therapy offered included cyberknife, imatinib, etoposide, vinblastine, temsirolimus, imatinib, tipifarnib, temozolamide, and irinotecan either in isolation or in varying combinations. Congruent to the literature, recurrent MB in our single center cohort carried a poor prognosis despite administration of salvage therapy.
EPID-14. HISPANIC ETHNICITY AND SOCIOECONOMIC STATUS ARE INDEPENDENTLY ASSOCIATED WITH IMPROVED PROGNOSIS IN GLIOBLASTOMA PATIENTS
Authors: Michael E Ivan, Angela M Richardson, Kevin Moore, Antonio Omuro, Macarena De La Fuente, Tulay Koru-Sengul
Journal: Neuro-Oncology (2017)

Significant racial and social disparities have previously been identified in outcomes from glioblastoma. Although some epidemiologic studies have shown Hispanic ethnicity to be protective, other studies have not replicated this finding. As many studies do not consider race separately from ethnicity, the role of Hispanic ethnicity in glioblastoma survival is not well understood. Florida has one of the largest Hispanic populations in the United States. Using a population-based cancer database, this study examines sociodemographic and survival disparities in glioblastoma patients. Data from the Florida Cancer Data System(FCDS) and the US Census were linked for adult (>18yrs) glioblastoma patients to determine disease burden and survival. A multivariable Cox regression model was used to model patient survival adjusting for sociodemographic, tumor, age, surgical resection, adjuvant therapy and clinical characteristics. Adjusted hazard ratios(aHR) and 95% confidence intervals (95% CI) were calculated for overall sample. All statistical analyses were completed with SAS v.9.4. In total, 16,180 Florida adults were diagnosed with glioblastoma between 1981 and 2013. The majority were male (56.0%) and white (93.0%), and 11.2% of glioblastoma patients identified as Hispanic with 2.4% self-identifying as Cuban. Hispanics had significantly better survival compared to non-Hispanics (aHR 0.84; 95% CI 0.78–0.90). Current smokers fared significantly worse (aHR 1.11; 95% CI 1.04–1.18). Higher socioeconomic status was also associated with increased survival (aHR 0.91, 95% CI 0.84–0.99). Younger age at diagnosis, surgical resection, chemotherapy, radiation therapy, and female sex were also associated with significantly improved outcomes. This study demonstrates clear sociodemographic and survival disparities for glioblastoma patients. This analysis considers race and ethnicity as two distinct variables and shows improved survival outcomes for Hispanic patients. Additionally, patients from neighborhoods with higher socioeconomic status have increased survival. Further analysis is needed to assess the role of histologic and molecular subtypes in these ethnic groups.
P2.03-008 Phase I/II Study of Intermitted Erlotinib in Combination with Docetaxel in Patients with Recurrent NSCLC with Wild-Type EGFR: WJOG 4708L
Authors: T. Kimura, T. Kawaguchi, S. Kudoh, Y. Chiba, H. Yoshioka, K. Watanabe, T. Kijima, Y. Kogure, T. Oguri, N. Yoshimura, T. Niwa, T. Kasai, H. Hayashi, A. Ono, H. Tanaka, S. Yano, S. Nakamura, N. Yamamoto, Y. Nakanishi, K. Nakagawa
Journal: Journal of Thoracic Oncology (2017)
P3.03-004 The Frequency and Clinical Implication of ALK, ROS1, RET and NTRK1 Gene Rearrangements in Adenosquamous Lung Carcinoma Patients
Authors: X. Shi, S. Wu, H. Duan, Y. Liu, X. Zeng, Z. Liang
Journal: Journal of Thoracic Oncology (2017)
Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department
Authors: Andrew K. Chang, Polly E. Bijur, David Esses, Douglas P. Barnaby, Jesse Baer
Journal: JAMA (2017)

<h3>Importance</h3> The choice of analgesic to treat acute pain in the emergency department (ED) lacks a clear evidence base. The combination of ibuprofen and acetaminophen (paracetamol) may represent a viable nonopioid alternative. <h3>Objectives</h3> To compare the efficacy of 4 oral analgesics. <h3>Design, Settings, and Participants</h3> Randomized clinical trial conducted at 2 urban EDs in the Bronx, New York, that included 416 patients aged 21 to 64 years with moderate to severe acute extremity pain enrolled from July 2015 to August 2016. <h3>Interventions</h3> Participants (104 per each combination analgesic group) received 400 mg of ibuprofen and 1000 mg of acetaminophen; 5 mg of oxycodone and 325 mg of acetaminophen; 5 mg of hydrocodone and 300 mg of acetaminophen; or 30 mg of codeine and 300 mg of acetaminophen. <h3>Main Outcomes and Measures</h3> The primary outcome was the between-group difference in decline in pain 2 hours after ingestion. Pain intensity was assessed using an 11-point numerical rating scale (NRS), in which 0 indicates no pain and 10 indicates the worst possible pain. The predefined minimum clinically important difference was 1.3 on the NRS. Analysis of variance was used to test the overall between-group difference at<i>P</i> = .05 and 99.2% CIs adjusted for multiple pairwise comparisons. <h3>Results</h3> Of 416 patients randomized, 411 were analyzed (mean [SD] age, 37 [12] years; 199 [48%] women; 247 [60%] Latino). The baseline mean NRS pain score was 8.7 (SD, 1.3). At 2 hours, the mean NRS pain score decreased by 4.3 (95% CI, 3.6 to 4.9) in the ibuprofen and acetaminophen group; by 4.4 (95% CI, 3.7 to 5.0) in the oxycodone and acetaminophen group; by 3.5 (95% CI, 2.9 to 4.2) in the hydrocodone and acetaminophen group; and by 3.9 (95% CI, 3.2 to 4.5) in the codeine and acetaminophen group (<i>P</i> = .053). The largest difference in decline in the NRS pain score from baseline to 2 hours was between the oxycodone and acetaminophen group and the hydrocodone and acetaminophen group (0.9; 99.2% CI, −0.1 to 1.8), which was less than the minimum clinically important difference in NRS pain score of 1.3. Adverse events were not assessed. <h3>Conclusions and Relevance</h3> For patients presenting to the ED with acute extremity pain, there were no statistically significant or clinically important differences in pain reduction at 2 hours among single-dose treatment with ibuprofen and acetaminophen or with 3 different opioid and acetaminophen combination analgesics. Further research to assess adverse events and other dosing may be warranted. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02455518
GENE-15. CHARACTERIZATION OF DIFFERENTIAL 5-HYDROXYMETHYLCYTOSINE IN IDH1 MUTANT VERSUS IDH1 WILD-TYPE HIGH-GRADE GLIOMAS
Authors: Wioletta Glowacka, Harshika Jain, Makiko Okura, Abulizi Maimaitiming, Mamatjan Yasin, Hamza Farooq, Kenneth Aldape, Paul Kongkham
Journal: Neuro-Oncology (2017)

Glioblastoma demonstrates significant epigenetic dysregulation, with subgroup differences highlighted by the Glioma CpG-island methylator phenotype (G-CIMP) seen in IDH1 mutant tumors. 5-hydroxymethylcytosine (5hmC) has been implicated in IDH1 wild-type tumors (Johnson et al, Nat Commun Nov 2016), however its role in IDH1 mutant gliomas remains undescribed. We examined the 5hmC and methylcytosine (5mC) profiles in high grade (WHO III/IV) IDH1 mutant (n = 12) and IDH1 wild-type (n = 9) tumors using the Illumina EPIC platform. Gene expression was profiled using the Affymetrix Human Gene 2.0 ST array. Cumulative density plots for mean 5hmC across IDH1 mutant samples demonstrated 5hmC accumulation within the last 10th percentile. To focus on probes with greatest 5hmC abundance, we assessed probes in the top 1% mean 5hmC. In addition, differentially methylated (DMR) and hydroxymethylated (DHMR) regions were identified using the R package “ChAMP” comparing IDH1 mutant to wild-type tumors. No significant difference in 5hmC between groups was evident, with a mean 5hmC of 18.9% and 15.7% for IDH1 mutant and wild-type, respectively. Top 1% 5hmC probes preferentially marked Open Sea and CpG island shores and predominantly associated with intronic genomic regions. Enhancer probes were enriched in both subgroups. Of genes defining the G-CIMP phenotype, 28/50 were differentially methylated, while 22/50 G-CIMP genes were differentially hydroxymethylated suggesting that 5hmC may contribute to aberrant methylation defining G-CIMP tumors. Among 1367 differentially expressed genes, 48 demonstrated positive Spearman correlation between 5hmC and gene expression (r=0.5 or greater, p < 0.05) including genes implicated in gliomagenesis and novel candidates. FAM171B demonstrated the highest correlation (r = 0.80, p = 0.00002). DHMR genes were enriched for members of several biologic processes (including nervous system development, cell adhesion, cell-cell signalling, cell differentiation, response to hypoxia) and pathways (including ERK signalling, Wnt/Hedgehog/Notch signalling, targets of C-MYC transcriptional regression).
GENE-38. DISRUPTED ENDOTHELIAL CELL GENE EXPRESSION PROFILE PREDICTS GBM CLINICAL RESPONSE TO ANTI-ANGIOGENIC THERAPY
Authors: Tansy Zhao, Julie Metcalf, Mamatjan Yasin, Ken Aldape, Gelareh Zadeh
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is one of the most aggressive adult brain tumors, with the histopathologic hallmark of increased abnormal vasculature. While anti-angiogenesis therapy had shown value in pre-clinical and early clinical studies, in particular targeting vascular endothelial growth factor (VEGF), the durability of response to anti-angiogenic therapy varies and hence efficacy remains a limitation. There is data to suggest that certain subtypes of GBM however have a more effective response to anti-angiogenic therapy. Therefore, there is a need to identify prognostic markers that can determine the subpopulation of GBM patients that response to AA therapy. We established five genetic expression profiles (group A~E) by stimulating endothelial cells (ECs) with different combinations of ionizing radiation (IR) and mesenchymal stem cells (MSCs) before performing angiogenesis array analysis. Bioinformatics analysis of Group A~E identified the combination of HGF and CXCL10 alterations as the differentiators that separated the AVAglio patients into 3 groups (group 1~3). We found that GBM patients with high HGF and low CXCL10 levels had the worst clinical response to AA therapy. Further qPCR analysis of gene expression levels among different cell types revealed that GBM cells have the highest expression of HGF and the lowest expression of CXCL10 relative to ECs. Similar trend were detected in MSCs relative to ECs but to a lesser degree. Thus we propose that such genetic parameter in GBM could potentially be a prognostic marker for AA therapy.
Vigilância da resistência antimicrobiana na Bulgaria – uma sinopsis de BulSTAR 2003
Authors: M Petrov, N Hadjieva, T Kantardjiev, Tz Velinov, A Bachvarova
Journal: Eurosurveillance (2005)

O artigo seguinte apresenta o sistema de vigilância bulgaro da resistencia antimicrobiana (Bulgarian Surveillance Tracking Antimicrobial Resistance, BulSTAR) e os dados de vigilância de 2003. Este programa de vigilância longitudinal esta encarregado do isolamento e da sensibilidade aos antibioticos de todos os micro-organismos que tem uma importância clinica isolados pelos laboratorios de microbiologia participantes nas culturas de sangue, o liquido cefalo- raquideo, as vias respiratorias altas e baixas, a urina e as amostras de feridas. Participaram no BulSTAR 2003 vinte e oito laboratorios publicos, 45 hospitalares e seis privados na totalidade dos 28 distritos da Republica de Bulgaria. O numero total de isolamentos provindo de fontes controladas durante o periodo do estudo era de 98 929. Sete micro-organismos representavam 72% de todas as bacterias no BulSTAR 2003: Escherichia coli, Staphylococcus aureus, o grupo Proteus-Providencia- Morganella, Klebsiella spp., Pseudomonas spp, Streptococcus pneumoniae e Streptococcus pyogenes. 
A resistencia antimicrobiana de bacterias clinicas Gram positivas e Gram negativas na Bulgaria foi estimada de nivel medio comparada com outras fontes de vigilância no mundo. Uma experiencia unica na populacao sobre um periodo de 32 anos que consistia em tratar todas as infeccoes severas com uma combinacao de ampicilina e gentamicina conduziu a taxas de resistencia aos aminoglycosides duas vezes mais altas quando comparadas com outros paises no mundo. Este e o resultado de esquemas terapeuticos extremamente conservativos utilisados nos ex-paises socialistas, basados em diretivas nacionais e numa produccao interna de gentamicina e ampicilina a baixo custo. A implementacao proxima de uma rede computerizada e as melhoras para a deteccao de erros deveriam aumentar a sensibilidada e o impacto do sistema de vigilância BulSTAR – um instrumento indispensavel na luta contra o fenomeno mundial da resistencia antimicrobiana.
NIMG-52. RADIATION-INDUCED VASCULAR MALFORMATIONS MIMICKING TUMOR IN MRI-BASED TREATMENT RESPONSE ASSESSMENT MAPS (TRAMs)
Authors: Leor Zach, David Guez, David Last, Dianne Daniels, Shirley Sharabi, Dvora Nass, Ouzi Nissim, Roberto Spiegelmann, Galia Tsarfaty, Chen Hoffmann, Alisa Talianski, Yigal Shoshan, Yakov Fellig, Sagi Harnof, Zvi Cohen, Yael Mardor
Journal: Neuro-Oncology (2017)
SCDT-28. THE SHORT PEPTIDE INTERFERING WITH GM-CSF BLOCKS GLIOMA-MICROGLIA INTERACTIONS AND ANTI-TUMOR EFFECTS ON ORTHOTOPIC U87 GLIOMAS IN NUDE MICE
Authors: Maria Pasierbinska, Katarzyna Poleszak, Bozena Kaminska, Pawel Wisniewski
Journal: Neuro-Oncology (2017)

Glioblastoma (WHO grade IV, GBM) is a malignant, very aggressive, primary brain tumor which due to tumor cell heterogeneity, genetic alterations and therapy resistance remains incurable. GBM is heavily infiltrated with microglia and macrophages which play an important role in proliferation, diffusive growth and responses to treatment. Microglia and peripheral macrophages accumulate in malignant gliomas and constitute 30-50% of the tumor mass. Glioma cells overexpress and secrete proteins that reprogram microglia and peripheral macrophages into cells which potentiate tumor invasion and growth, at the same suppressing antitumor immunity. We have previously demonstrated that glioma-derived granulocyte macrophage colony-stimulating factor - GM-CSF (encoded by a CSF-2 gene) induces accumulation and protumorigenic activation of microglia/macrophages. We hypothesized that a humanized peptide that selectively binds to GM-CSF, would block its binding to respective receptors on myeloid cells, and inhibit activation of the receptors and downstream signaling pathways, which should result in inhibition of glioma invasiveness. First, we designed a peptide library containing 27 peptides, each 14-residues long. Next, we identified the peptide binding to GM-CSF using peptide microarrays, enzyme-linked immunosorbent assay (ELISA) and a technique based on surface plasmon resonance (SPR). Subsequently, using the Matrigel Matrix cell invasion assay we selected the peptide (G7) with most potent capacity for inhibition of human U87 MG and LN18 glioma cell invasiveness in the presence of glioma-microglia co-cultures. We further confirmed that this peptide blocks binding of GM-CSF to its receptor using SPR and its relatively good stability using mass spectrometry. Anti-tumor activity of G7 peptide in vivo was confirmed in orthotopic U87 xenograft mouse model. Intracranial delivery of this peptide inhibitor omits blood-brain barrier and minimizes nonspecific toxicity.
Evaluación del impacto sobre la mortalidad de la ola de calor de 2003 en Francia
Authors: P Pirard, S Vandentorren, M Pascal, K Laaidi, A Le Tertre, S Cassadou, M Ledrans
Journal: Eurosurveillance (2005)

Entre el 2 y el 15 de Agosto de 2003 tuvo lugar en Francia un periodo de calor de intensidad excepcional. Todas las regiones francesas fueron afectadas por esa ola de calor, que provoco un exceso de 14.800 defunciones entre el 1 y el 20 Agosto. El aumento en el numero de defunciones seguia la misma curva que el aumento de las temperaturas. La mortalidad observada volvio a su nivel normal en la ultima decada del mes de Agosto y durante los tres meses posteriores. El impacto sanitario de esa ola de calor fue muy variable segun las ciudades. No todo el exceso de mortalidad observado se puede explicar solo por la duracion y la intensidad excepcional de las temperaturas minimas. Las mujeres mayores de mas de 75 anos fueron las mas afectadas. Las tasas de mortalidad mas importantes se observaron en defunciones asociadas con el calor. Frente al impacto sanitario de esa ola de calor, las autoridades sanitarias francesas implementaron en 2004 un sistema de alerta nacional asi como un plan de accion preventivo en cada region.
P1.02-066 Cancer Stem Cells in Pulmonary High Grade Neuroendocrine Carcinoma: a Series of 23 Cases from Eastern India
Authors: S. Patra, P. Mishra, S. Purkait, M. Sable, S. Padhi, M. Sethy, P. Mohapatra, N. Sahoo, M. Nayak, R. Gharei, S. Bhuniya, M. Panigrahi
Journal: Journal of Thoracic Oncology (2017)
Pacientes hospitalizados en unidades de aislamiento por sospecha de Síndrome Respiratorio Agudo grave o severo (SRAS) durante la epidemia: la experiencia francesa
Authors: B Issartel, O Lesens, C Chidiac, Y Mouton, D Christmann, D Peyramond
Journal: Eurosurveillance (2005)

Durante el brote de SRAS, segun las recomendaciones de la Organizacion Mundial de la Salud (OMS), se realizaron pruebas en numerosos pacientes en Francia y ninguno llego a desarrollar la enfermedad. En Mayo de 2003, al inicio del brote, se llevo a cabo un estudio retrospectivo para describir a los pacientes sospechosos de SRAS hospitalizados en Francia, y compararlos con los casos confirmados de SRAS, con el objeto de evaluar la estrategia de cribado. Se incluyeron 117 pacientes en el estudio. Solo un 3,4% de ellos habian tenido contacto estrecho con un paciente infectado, pero el 73,5% procedian de una region afectada por el brote. En el momento de su hospitalizacion, el 67,5% presentaban fiebre y sintomas respiratorios y el 49,6% tenian fiebre y sintomas no especificos. Los sintomas clinicos significativamente mas frecuentes en pacientes con SRAS son la fiebre, mialgias, disneas, y mareos o vomitos. Los diagnosticos mas corrientes fueron fiebre de origen virico e infeccion del tracto respiratorio. Los signos clinicos no permiten establecer la diferencia con un SRAS precoz, confirmando asi la utilidad de las definiciones de casos de la OMS en cuanto a la decision de aislamiento, para evitar la transmision de la enfermedad.
P1.17-015 Long Acting Octreotide plus Prednisone in Advanced Thymic Epithelial Tumors: A Real Life Clinical Experience
Authors: M. Ottaviano, V. Damiano, M. Tortora, M. Capuano, P. Perrone, C. Forino, E. Matano, G. Palmieri
Journal: Journal of Thoracic Oncology (2017)
EXTH-47. DEVELOPMENT OF NANOFIBER-BASED CONTROLLED LOCAL DRUG DELIVERY AS A NOVEL ADJUVANT MODALITY FOR TREATMENT OF GLIOBLASTOMA
Authors: Nazanin Majd, Dawewoo Han, Mika Sasaki, Hirofumi Yoshino, Kofuji Satoshi, Rekha Chaudhary, Ronald Warnick, Andrew Steckl, Atsuo Sasaki
Journal: Neuro-Oncology (2017)

There are only two chemotherapeutic agents that are approved by US Food and Drug Administration (FDA) for treatment of newly diagnosed glioblastoma. Gliadel wafer implantation was approved in 2003 as it improved survival in newly diagnosed glioblastoma patients. However, Gliadel wafer use is currently topic of controversy given its toxicity profile and difficult drug loading and drug release maintenance properties. Temozolamide was approved in 2005 but it only marginally improves patients’ survival. Despite rigorous research efforts, the life span of patients with glioblastoma has not significantly changed over the past two decades and further research efforts are crucial. We have discovered that Mycophenolic Acid (MPA), an FDA approved immunosuppressant, inhibits glioblastoma cell growth by depleting cells from their major energy source, GTP, which is reversed by addition of guanosine. Local drug delivery of MPA to glioblastoma is preferable over systemic delivery because i) recurrence predominantly appears adjacent to the original lesion, ii) MPA is metabolized in the liver and high systemic concentrations will be needed for effective tumor penetration, iii) the effect of MPA’s systemic immunosuppressive properties is not well characterized in glioblastoma patients. We therefore aimed to develop MPA-integrated nanofibers for post-surgical local MPA therapy in glioblastoma patients. We have formed MPA-containing electrospun fiber membranes and shown that coaxial MPA nanofibers release and maintain an MPA concentration of 10uM. In addition, these MPA-containing fiber membranes effectively inhibit glioblastoma cell lines and patient-derived neurospheres growth. This is rescued by addition of guanosine indicating that release of MPA is the active element in glioblastoma growth inhibition by MPA nanofibers. Our results indicate that MPA-containing electrospun membranes have a promising prospect for local treatment of glioblastoma. In addition, nanofiber membranes have the potential to be used as a novel platform in delivery of other molecularly targeted therapies in treatment of glioblastoma patients.
Tendance du SIDA en Europe : diminution à l'ouest, augmentation à l'est
Authors: F F Hamers, A M Downs, J Alix, J B Brunet
Journal: Eurosurveillance (1997)

En 1996, 24 920 cas de SIDA ont ete declares dans la Region Europe de l'OMS, ce qui amene le total cumule a 185 808 cas, dont 6969 (4%) cas pediatriques (<13 ans) (1). Pour la premiere fois depuis le debut de l'epidemie, le nombre de cas declares dans l'annee a diminue par rapport a l'annee precedente (-5% entre 1995 et 1996, apres avoir augmente de 1% en 1995).