tbuckley/cabot-search huggingface dataset:
CMET-38. HEMORRHAGIC BRAIN METASTASES UNDERGOING SURGICAL RESECTION ARE ASSOCIATED WITH INCREASED RISK OF LEPTOMENINGEAL DISSEMINATION
Authors: Robert Press, Chao Zhang, Mudit Chowdhary, Karen Xu, Roshan Prabhu, Matthew Ferris, Jeffrey J Olson, Bree R Eaton, Hui-Kuo Shu, Walter Curran, Ian Crocker, Kirtesh Patel
Journal: Neuro-Oncology (2017)

Brain metastases treated with surgical resection and focal post-operative radiotherapy have been associated with increased risk of leptomeningeal disease (LMD). Resection of hemorrhagic brain metastases can be more technically challenging and may be associated with higher risk of operative spill. In this study, we investigate the association of hemorrhagic resected brain metastases (rBM) and the risk of LMD. A total of 102 consecutive patients with a single rBM treated with post-operative stereotactic radiosurgery (SRS) from 2008–2016 were identified. Intracranial outcomes, including LMD, were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis (UVA) and multivariable analysis (MVA) were assessed using the Fine & Gray model. Overall survival (OS) was analyzed using the Kaplan-Meier method. 24 patients (23.5%) had hemorrhagic lesions at time of surgical resection based on preoperative imaging. Baseline patient and treatment characteristics were well balanced between cohorts except for higher incidence of melanoma primary histology (50% vs. 12.8%, p=0.003) within the hemorrhagic cohort. Median follow up for hemorrhagic vs. non-hemorrhagic rBM was similar at 20.3 vs. 23.1 months, respectively. Hemorrhagic rBM were associated with a higher risk of LMD at 1 year: 26.7% vs. 10.9%, p=0.043. MVA confirmed hemorrhagic lesions were a predictor for increased risk of LMD (Hazard Ratio: 2.16, 95% Confidence interval [CI]: 1.06 – 4.39, p=0.033). Melanoma primary histology (95% CI 0.76–5.13, p=0.16) was not a significant factor on UVA for LMD. Hemorrhagic rBM were not a significant factor on UVA for OS, local control, or symptomatic radiation necrosis. Patients with hemorrhagic brain metastases appear to be at increased risk of LMD compared to those with non-hemorrhagic brain metastases after surgical resection and post-operative SRS. Prospective studies investigating optimal delivery of SRS for resectable brain metastases should consider stratifying for hemorrhagic lesions.
ACTR-54. OPEN-LABEL PHASE 1 CLINICAL TRIAL TESTING PERSONALIZED AND TARGETED INTERVENTION WITH SKULL REMODELLING SURGERY TO MAXIMIZE LEVELS OF TTFIELDS INTENSITY FOR HIGHER TREATMENT BENEFIT - THE OPTIMAL TTF STUDY
Authors: Anders Rosendal Korshoej, Frederik Lundgaard Hansen, Lukacova Slavka, Søren Ole Stigaard Cortnum, Yasmin Lassen-Ramshad, Trine Lignell Guldberg, Christian Rahbek, Nikola Mikic, Axel Thielscher, Jens Christian Hedemann Sørensen, Gorm Burckhardt von Oettingen
Journal: Neuro-Oncology (2017)

We present an ongoing open label phase 1 investigator-sponsored trial (NCT02893137) testing safety/efficacy of a novel therapeutic concept for recurrent glioblastoma (GBM). The intervention combines best choice chemotherapy with tumor treating fields (TTFields) and personalized targeted skull remodeling surgery. The objective of skull remodeling surgery is to create paths, which facilitate electric current flow through into the region of pathology. This may involve formation of strategically placed minor craniectomies or burr holes and thinning of the skull. Finite element (FE) calculations indicate that skull remodeling surgery provides a marked and focal enhancement (~100%) of TTFields intensity without significantly compromising patient safety. Patient accrual began Dec 2016. As of June 2017 seven patients have been screened and six out of fifteen patients enrolled. Major eligibility criteria include age > 18 years, first recurrence supratentorial GBM, Karnofsky performance score (KPS) > 60, focal tumor < 2 cm to cortical surface, lack of uncontrollable epilepsy, and lack of significant co-morbidity. Upon inclusion, personalized FE-calculations are performed to validate TTFields enhancement > 25% due by skull remodeling surgery. The primary endpoint is toxicity assessed by CTCAEv4.0. Secondary endpoints include overall survival, progression free survival (PFS), PFS at six months (PFS6), objective response rate (RANO), quality of life (EORTC QLQ-C30 and BN20), KPS, and steroid dose. Follow-up is 18 months and includes regular toxicity assessment (6 week intervals) as well as quality of life and response assessments (3 month intervals). Patients are censored at the end of scheduled follow-up, occurrence of serious or unacceptable adverse events, withdrawal of consent, or loss to follow-up. Interim analysis will be performed upon censoring of the first five patients. The tested concept holds promising potential for improving TTFields outcome by enhancing field intensity in the tumor. The trial will hopefully lay the foundation for future efficacy investigation.
Surto de Hepatite A em Puglia, Itália, 1996
Authors: P Malfait, P L Lopalco, S Salmaso, C A Germinario, G Salamina, M Quarto, S Barbuti, R Cipriani, A Mundo, G Pesole
Journal: Eurosurveillance (1996)

Na regiao de Puglia no sudeste da Italia (populacao: 4 milhoes de habitantes), o numero de notificacoes de hepatite a virus A (HAV) aumenta em ciclos de 2 anos. Em 1992 registou-se um grande surto, mas nao foi feita qualquer investigacao epidemiologica. A maior parte dos casos sao notificados no inicio do ano (figura 1). Em finais de 1995, Puglia aderiu ao projecto nacional para a informatizacao do sistema de vigilância das doencas infecciosas (Sistema de Informacao das Doencas Infecciosas, SIDI).
TMIC-04. A POTENT MICROGLIAL RESPONSE TO BLOCKING THE CD47-SIRPα ANTI-PHAGOCYTIC AXIS OVERCOMES DEFICIENT MACROPHAGE RECRUITMENT DURING ANTI-CD47 IMMUNOTHERAPY AGAINST GLIOBLASTOMA
Authors: Gregor Hutter, Johanna Theruvath, Claus Moritz Graef, Irving Weissman, Siddhartha S Mitra, Samuel H Cheshier
Journal: Neuro-Oncology (2017)

Modulation of tumor-associated macrophages and microglia (TAMs) in glioblastoma (GBM) is a promising anti-tumor strategy. However, little is known about the phenotypic organization of the TAM-pool and the role of GBM subtypes in shaping their specific immunologic environment. Therefore, we sought to model the composition of microglia and peripheral macrophages within the GBM-TAM-pool. Further, we aimed at assessing the response of the TAM pool to CD47-Sirpα blockade. Using novel orthotopically xenografted, immunodeficient mice with genetically color-coded macrophages and microglia, termed NSG-Ccr2RFP/+Cx3cr1GFP/+ mice, we found that the TAM composition was dependent on the rate of tumor growth. While microglia dominated TAMs in slow growing tumors, high passaged cell lines induced a more mixed pool of both microglia and macrophages. Blockade of the “don’t eat me” signal CD47 by anti-CD47 antibodies prompted both macrophage and microglial-induced phagocytosis in vivo and led to marked microglial morphological changes assessed by intracranial in vivo imaging. The therapeutic efficacy of anti-CD47 treatment was preserved in mice lacking Ccr2, which limits macrophage recruitment to the brain. Anti-CD47-induced microglial phagocytosis alone was sufficient to reduce tumor burden. Under anti-CD47 treatment, macrophages changed their transcriptional profile towards a more pro-inflammatory, “M1”-polarized signature, whereas the microglial transcriptome remained unchanged as assessed by RNAseq analysis. These results emphasize the importance of both resident microglia and infiltrating macrophages in GBM progression and potential of GBM control. Moreover, CD47-Sirpα disruption promotes important phenotypic and functional status changes of resident microglia, which has critical implications for central nervous system (CNS) immunotherapies in the future.
Harmonização entre o Sistema de notificação das infecções respiratorias agudas na República Checa e as Redes europeias
Authors: J Kyncl, W J Paget, M Havlickova, B Kriz
Journal: Eurosurveillance (2005)

Na Europa, a actividade dos virus respiratorios e detectada cada inverno, embora o inicio e a amplitude desta actividade sejam praticamente imprevisiveis. O impacto da infeccao gripal e/ou das infeccoes respiratorias agudas nos paises europeos e monitorizado continuamente por varios sistemas de vigilância. Todas estas fontes de informacao sao utilizadas para avaliar a natureza e amplitude da actividade gripal e dos outros virus respiratorios e propor recommendacoes sobre a prevencao e controle da morbidade e mortalidade devidas a gripe, tanto ao nivel local como nacional e internacional. 
O sistema de alerta precoce para um surto de gripe esta baseado principalmente na utilizacao de uma serie de limiares. Na Republica Checa, o sistema de notificacao das infeccoes respiratorias agudas (IRA), com um tratamento automatizado de dados, utiliza um modelo estatistico para a deteccao precoce de taxas anormalmente altas dos indicadores vigilados. Estao recolhidos os dados sobre o numero de IRA, o numero de complicacoes devidas a estas infeccoes e a populacao registrada a traves das notificacoes dos medicos generais e dos pediatras, distribuindo os dados em cinco grupos etarios. Para melhorar o sistema de notificacao na Republica Checa, desde janeiro de 2004 estao recolhidos na mesma populacao e por grupos de idade, os dados clinicos sobre a incidencia semanal do sindrome gripal (SG). Estes dados correspondem a definicao de caso de SG recentemente adoptada pela Commissao Europeia, permitindo a comparacao com outros paises europeos, especialmente com os que participam a rede EISS (European Influenza Surveillance Scheme).
Staphylococcus aureus Virulent PSMα Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation
Authors: Seitaro Nakagawa, Masanori Matsumoto, Yuki Katayama, Rena Oguma, Seiichiro Wakabayashi, Tyler Nygaard, Shinobu Saijo, Naohiro Inohara, Michael Otto, Hiroyuki Matsue, Gabriel Núñez, Yuumi Nakamura
Journal: Cell Host & Microbe (2017)
El sistema de vigilancia epidemiológica implementada en el área de los Altos Alpes durante los Juegos Olímpicos de invierno, Turín 2006
Authors: F Franke, L Coulon, C Renaudat, B Euillot, N Kessalis, P Malfait
Journal: Eurosurveillance (2006)

Algunas competiciones deportivas de los Juegos Olimpicos de invierno de Turin en Italia, organizadas de febrero a marzo de 2006, tuvieron lugar cerca de la ciudad de Briancon, en el departamento frances de los Altos Alpes. 
Se llevo a cabo un sistema de vigilancia sanitaria por las autoridades sanitarias locales, para detectar rapidamente cualquier fenomeno que justificara una accion de prevencion o de control sanitario y guiara las intervenciones en caso de brote o polucion ambiental. 
Se desarrollo la vigilancia en el area de Briancon entre el 30 de enero y 15 de marzo de 2006. Fueron analizados el numero y causas de defunciones. 
Una red de medicos generalistas controlaba las gastroenteritis, la gripe y el sarampion. Los laboratorios de Briancon proporcionaron los resultados de los analisis realizados. Se estudiaron las actividades de las urgencias del Centro hospitalario de Briancon y del Samu de los Altos Alpes. Se reforzaron los sistemas de vigilancia de enfermedades de notificacion obligatoria y de intoxicaciones de monoxido de carbono (CO). 
Los datos analizados se transmitian diariamente a las autoridades sanitarias. Cada semana se enviaba a los participantes un informe en frances e ingles. La tasa de participacion fue cercana al 100% y los tiempos de transmision de las informaciones fueron respetados. No se identifico ningun evento de salud en la zona vigilada. 
Este sistema de vigilancia fue bien aceptado, estructurado alrededor del sistema de vigilancia no especifico implementado en los hospitales, Samu y estados civiles, completado con sistemas puntuales, y permitio constituir la base de una colaboracion necesaria en caso de brote o de polucion ambiental.
P1.07-009 PD-L1 Expression in Circulating Tumor Cells and Response to PD-1 Inhibitor Treatment in Non-Small Cell Lung Cancer Patients
Authors: N. Guibert, M. Delaunay, N. Boubekeur, I. Rouquette, A. Lusque, E. Clermont, A. Fortoul, M. Farella, G. Favre, A. Pradines, J. Mazieres
Journal: Journal of Thoracic Oncology (2017)
Gemcitabine/nabpaclitaxel in elderly patients with metastatic or locally advanced pancreatic adenocarcinoma: a retrospective analysis on the efficacy and safety profile
Authors: J. Ventriglia, M.M. Laterza, B. Savastano, A. Petrillo, G. Tirino, L. Pompella, A. Pappalardo, M. Orditura, F. Ciardiello, F. De Vita
Journal: Annals of Oncology (2017)
P1.16-004 Intubated Versus Non-intubated Anesthesia for Lung Cancer VATS in Octogenarians
Authors: N. Ilic, D. Ilic, J. Juricic, D. Krnic, D. Orsulic, I. Simundza, N. Frleta Ilic
Journal: Journal of Thoracic Oncology (2017)
CMET-35. PRELIMINARY SCREENING OF A NOVEL EpCAM BISPECIFIC T-CELL ENGAGER (BiTE) ANTIBODY TO TARGET A BMIC POPULATION IN HUMAN BRAIN METASTASES
Authors: Mohini Singh, Chitra Venugopal, Parvez Vora, Jarrett Adams, James Pan, Chirayu Chokshi, Naresh Murty, Sachdev Sidhu, Jason Moffat, Sheila Singh
Journal: Neuro-Oncology (2017)

Brain Metastases (BM) are the most common type of cerebral tumor in adult, occurring at a rate 10 times greater than that of primary brain cancers. The inherent abilities of a primary tumor cell capable of initiating a BM resembles that of a cancer stem cell (CSC). Utilizing primary patient samples of BMs, we have characterized a subpopulation of CSC-like cells, termed brain metastasis-initiating cells (BMICs), which are responsible for initiating BMs. Due to the fluctuating nature of BMICs as they undergo the metastatic cycle, there currently exists a scarce few biomarkers that can faithfully identify this BMIC population. One such marker is epithelial cell adhesion molecule (EpCAM), that is utilized to identify cells of epithelial origin and has recently shown to a possible therapeutic option for the immunological treatment of BMs. Using CellectSeq, a novel methodology that combines use of phage-displayed synthetic antibody libraries and high-throughput DNA sequencing technology, a novel EpCAM-specific monoclonal antibody was generated. EpCAM-specific BiTEs were constructed to consist of two arms; one arm recognizes the tumor antigen (EpCAM) while the second is specific to CD3 antigen. The BiTEs were constructed in various conformations and dual binding specificity was confirmed using flow cytometry. Preliminary screening was performed to test the ability of BiTEs to functionally elicit EpCAM-specific cytotoxic responses in vitro. Future work will go to validate the efficacy of EpCAM-specific BiTES in targeting EpCAM positive BMICs in vivo while maintaining minimal off target cytotoxicity. Ultimately, we aim to apply the novel field of immunotherapies to block the metastatic process, transforming a uniformly fatal systemic disease into a locally controlled and eminently more treatable one.
PATH-25. CHANGES IN THE EGFR AMPLIFICATION BETWEEN PAIRED PRIMARY AND RECURRENT GLIOBLASTOMAS
Authors: Manmeet Ahluwalia, Peter J Ansell, Maria Guseva
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most common malignant primary brain tumor in United States. The current standard of care for GBM includes surgical resection followed by chemo-radiation. However, tumors invariably relapse, and treatment options are limited at relapse. Efforts to improve treatment involve personalized medicine approach that use novel agents, which target tumors that harbor specific biomarkers. The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently (~50%) amplified and mutated in GBMs and is potential target for the treatment. A substantial difference in EGFR amplification level between newly diagnosed and recurrent tumors will indicate that patients may require repeat surgery for inclusion into a personalized medicine trial. We compared paired tumor samples of glioblastoma patients at diagnosis and at relapse. The mutational spectrum (using whole exome sequencing) of the tumor sample resected at relapse was compared to the tumor sample from diagnosis or initial surgery prior to therapy to identify progression-specific mutations. EGFR amplification was determined by FISH analysis both at diagnosis and relapse. Retrospective chart review of patients was conducted to collect disease specific and treatment specific information. We report the FISH analysis on nine samples. Our data demonstrate that EGFR amplification status, as determined by FISH, remained stable in 5 of the 6 samples that were positive at diagnosis. Three samples negative at diagnosis remained negative at relapse. Prevalence and sustainability of EGFR amplification on additional cases (undergoing analysis), as determined by FISH and WES will be presented. In current dataset, EGFR amplification was noted to be stable in 89% cases (5/6 EGFR positive and 3/3 EGFR negative) based on FISH analysis.
P1.01-055 Spectrum of Early Progression in Advanced NSCLC Patients Treated with PD-1 Inhibitors: Identifying Markers for Poor Outcome
Authors: M. Nishino, A. Adeni, C. Lydon, H. Hatabu, P. Jänne, F.S. Hodi, M. Awad
Journal: Journal of Thoracic Oncology (2017)
QLIF-14. CLINICAL OUTCOME AND SOCIAL-EMOTIONAL FUNCTIONING OF CHILDREN AND ADOLESCENTS TREATED ACCORDING TO THE SIOP CNS GCT PROTOCOLS
Authors: Irene Slavc, Ulrike Leiss, Andreas Peyrl, Monika Chocholous, Amedeo A Azizi, Karin Dieckmann, Thomas Czech
Journal: Neuro-Oncology (2017)

We assessed the clinical outcome, educational and/or job situation of patients with intracranial germ cell tumors treated at a single institution according to the SIOP CNS GCT protocols. From 1998 to 2016, 32 consecutive patients (27 male, 5 female) with a median age of 13 years (6 to 23) were treated. Tumor location was pineal in 14, suprasellar/3rd ventricular in 10, bifocal in 5, and multifocal in 3. Two patients had mature teratomas, 19 germinomas and 11 secreting non-germinomatous germ cell tumors (NGGCT). 23/30 patients were treated according to the SIOP CNS GCT 96 protocol with craniospinal irradiation for pure germinomas or chemotherapy followed by involved field irradiation for NGGCTs. Seven patients with germinomas were treated according to the SIOP CNS GCT II protocol with chemotherapy followed by whole ventricular irradiation plus/minus boost in non-metastatic tumors. Eight patients had metastases. Surviving patients were assessed repeatedly with a comprehensive neuropsychological test-battery. 28/32 patients are alive, 2/11 patients with NGGCT died of metastases, one patient died of another cause 7 years after diagnosis. Five- and 10-year OS for NGGCTs was 90.9 ± 8.7% and 70.7 ± 14.3%, respectively. For germinomas 5-year OS was 100% and 10-year OS 83.3 ± 15.2%. 1/19 patients with a germinoma died of a secondary anaplastic astrocytoma 8 years after diagnosis of her germinoma. While the majority of the detected deficits in the neuropsychological test results were subtle, their negative impact on well-being, educational or job situation was significant for two thirds of the patient group. Survival rates for NGGCTs may be further improved by intensifying chemotherapy for patients with high markers but do not seem to justify craniospinal irradiation for all patients. Reduced field irradiation also in germinomas and future novel therapies may help to decrease the risk of radiation induced secondary tumors and improve social-emotional functioning in long-term survivors.
Diabetes Care Disparities in Long-standing Type 1 Diabetes in Canada and the U.S.: A Cross-sectional Comparison
Authors: Alanna Weisman, Leif E. Lovblom, Hillary A. Keenan, Liane J. Tinsley, Stephanie D’Eon, Genevieve Boulet, Mohammed A. Farooqi, Julie A. Lovshin, Andrej Orszag, Yuliya Lytvyn, Michael H. Brent, Narinder Paul, Vera Bril, David Z. Cherney, Bruce A. Perkins
Journal: Diabetes Care (2017)

OBJECTIVE To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. RESEARCH DESIGN AND METHODS Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. RESULTS Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], P &amp;lt; 0.0001), lower QOL (36.9% vs. 48.7% with “excellent” QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003) and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively. CONCLUSIONS Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.
NCOG-04. ANALYSIS OF EXAMINER ERRORS ON COGNITIVE TESTING IN MULTI-SITE STUDIES
Authors: Jane H Cerhan, S Keith Anderson, Alissa M Butts, Paul D Brown
Journal: Neuro-Oncology (2017)

There is increasing interest in cognitive function as an outcome measure in brain tumor clinical trials. A 3-test battery has been recommended, including the Trail Making Test, Parts A and B (TMT A and TMT B), the Hopkins Verbal Learning Test-Revised (HVLT-R), and the Controlled Oral Word Association Test (COWAT). Use of this battery allows direct comparison and pooling of data across studies. We have used this battery with robust outcomes (e.g., Brown et al 2016). By necessity, psychometric examiners must be trained at many sites for multi-site studies, and some examiner error in testing and recording results is inevitable. To manage this, we re-score all cognitive test protocols for our studies prior to data entry. However, there is a growing interest in on-site data entry as an efficiency measure. We looked at error rates in cognitive testing using the aforementioned 3-test battery and standard training of examiners to inform quality-improvement measures and assess whether on-site entry would be prudent. In 500 consecutive exams, we found that 189 (37.8%) had at least one error. Of 274 total errors, 29 were not correctible upon review, leading to invalidation (1.3% of 2,277 tests administered). 48.5% of the errors would not have been detected with basic electronic on-site entry. Error rates (one or more errors/times given) for each test were TMT A 6%, TMT B 9%, COWAT 21.2%, HVLT-R Learning 7.5%, HVLT-R Delayed Recall 7.1% and HVLT-R Recognition 11.6%. The majority of the invalidating errors 26/29 (89.7%) were on the Trail Making Test. Examiner errors are common in multi-site studies, but most are correctable upon review. We will discuss these results as well as the types of errors that might occur that cannot be detected, how these results should inform test selection and examiner training, and implications for on-site data entry.