tbuckley/cabot-search huggingface dataset:
Implementation of a family history questionnaire to identify patients appropriate for hereditary cancer testing.
Authors: Sameer P. Desai, Jennifer Saam
Journal: Journal of Clinical Oncology (2014)

e12504 Background: The NCCN has developed guidelines for identifying and testing patients for Hereditary Breast and Ovarian Cancer (HBOC) syndrome, due to mutations in BRCA1 or BRCA2, and Lynch syndrome (LS), due to mutations in MLH1, MSH2, MSH6, PMS2 or EPCAM. In order to follow these guidelines, standard methods for collecting patient and family cancer history and acting on this information should be established. In response to ASCO’s QOPI family history initiative, we examined hereditary cancer testing at a 5-physician oncology practice that was already testing for hereditary cancer to determine what percentage of patients were missed based on family history. Methods: Historically, family histories were taken orally by the treating physician without a specific or consistent set of questions. Patients who met NCCN criteria were then referred to a practice physician (S.D.) for counseling and testing. For the week of November 18th 2013, a cancer family history questionnaire (FHQ) was given to every patient who presented to one office of the practice. The completed questionnaires were reviewed by the practice physician to determine how many patients were appropriate for hereditary cancer testing and how many of these patients or family members had been tested previously. Results: For the five years previous to this pilot, this practice tested an average of 92 patients/year for LS or HBOC (1.8 patients/week). During the 1-week pilot period, 148 FHQs were completed by patients. Ninety-two patients had no family history to suggest genetic testing. Another 10 patients needed clarification of their family history. The remaining 46 were considered appropriate for genetic testing; 16 indicated they or a family member had been tested previously but 30 patients had not been tested previously. Conclusions: Historically this practice tests 1.8 patients/week, but during a 1-week period, at least 30 patients were identified as appropriate for testing based on a family history questionnaire. Even in this practice, where hereditary cancer testing is already a routine part of patient care, this analysis shows that a systematic approach to family history collection identifies patients who were missed by previous efforts.
SCDT-10. OVERALL SURVIVAL IN AN ORTHOTOPIC MALIGNANT GLIOMA MODEL IS SIGNIFICANTLY PROLONGED BY NEUROSURGICAL DELIVERY OF PLGA/PEG INTERSTITIAL CHEMOTHERAPY PASTE
Authors: Stuart Smith, Betty Tyler, Toby Gould, Gareth Veal, Alison Ritchie, Phillip Berry, Annette Otto, Jonathan Rowlinson, John Choi, Nicolas Skuli, 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 mouldable PLGA/PEG paste for combined temozolomide (TMZ) and etoposide (ETOP) delivery in an orthotopic 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, previously utilised pre-clinically to develop Gliadel®. 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 localised 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 localised control of residual malignant glioma cells.
STEM-15. IDENTIFYING NICHE-INDEPENDENT PRO-TUMORIGENIC FACTORS IN GLIOBLASTOMA
Authors: Leo Kim, Xun Jin, Tanwarat Sanvoranart, Lisa C Wallace, Jeremy Rich
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor with conventional therapy offering only palliation. Despite extensive genomic and epigenetic studies, clinical breakthroughs in GBM remain elusive, in part, due to intratumoral heterogeneity. To overcome differential expression of diverse oncogenic drivers in tumor microenvironments, we interrogated the Ivy Glioblastoma Atlas Project dataset — an RNA-seq database of GBM specimens microdissected based on pathognomonic histological features — to identify niche-independent pro-tumorigenic factors that may be targeted to improve clinical outcomes. Based on this analysis and cross-referencing TCGA GBM RNA-seq and clinical data, 46 genes were identified as differentially expressed in GBM compared with non-tumor tissue and predicted significantly worse clinical outcomes. Through multivariate analysis adjusted for age, treatment regimen, and gene expression level, the gene Tapasin-binding protein-like (TAPBPL) was identified as an independent negative predictor of GBM patient survival. Interrogation of patient tissues and glioma stem cells (GSCs) revealed elevated TAPBPL expression in primary GBM tissues relative to non-tumor brain tissues and in GSCs compared with neural progenitor cells (NPCs). We further investigated the functional role of TAPBPL the GBM hierarchy through CRISPRi- and shRNA-mediated knockdown in our panel of patient-derived GSCs. Depleting TAPBPL attenuated self-renewal and viability of both proneural and mesenchymal GSCs. To infer TAPBPL-associated biological programs in GBM, we examined gene signatures positively and negatively correlated with TAPBPL expression or TAPBPL-correlated genes. In addition to antigen presentation, TAPBPL expression was most positively correlated with interferon responses and apoptosis signatures. As predicted by promoter and enhancer analysis, TAPBPL expression is modulated by IRF1, concordantly increased by exogenous treatment with IFN-γ in a dose-dependent manner. Collectively, our results suggest that TAPBPL promotes GBM progression and GSC maintenance across all tumor microenvironments.
Evolución reciente de la epidemiología del vih/sida en Polonia, 1999-2004
Authors: M Rosinska
Journal: Eurosurveillance (2006)

Los primeros casos de vih/sida fueron diagnosticados en Polonia a mediados de los anos 80, y en 1989 se observo el primer brote en usuarios de drogas inyectadas. Durante muchos anos, la epidemia de vih en Polonia afecto principalmente los usuarios de drogas inyectadas. En este articulo, se presentan las tendencias de la epidemia de vih/sida segun los datos de vigilancia de 1999 a 2004. Durante ese periodo, fueron declarados 3.561 nuevos casos de infecciones por el vih (tasa anual 15,4 por 1.000.000) y diagnosticados 803 casos de sida (incidencia 3,5 por 1.000.000). El numero anual de nuevos casos de infecciones por el vih y la incidencia anual de casos de sida muestran un ligero aumento. Aumentaron particularmente los casos de sida por transmision vertical, pasando de 0,46 casos por millon en ninos menores de 15 anos en 1999-2000 a 0,91 en 2003-2004. El 36% de los pacientes afectados por el sida de 15 anos o menos no habian sido diagnosticados de vih. El numero anual de pacientes con retraso diagnostico aumento sensiblemente entre 1999 y 2004 y era mayor en personas infectadas por via sexual (51,0%) que en las infectadas por inyeccion de drogas (20,1%). Los usuarios de drogas inyectadas representaban el 78,6% de los nuevos casos de infeccion por el vih cuando se conocia la ruta de transmision, pero esta no era conocida en el 47,9% de los casos. 
Para disponer de datos mas fiables, la vigilancia de la infeccion por el vih debe mejorarse. Los datos muestran de forma evidente la necesidad de llevar a cabo un programa completo de prevencion de la transmision vertical y un programa de concienciacion para la deteccion del vih, especialmente para los grupos de riesgo de transmision sexual. Es importante que se hagan esfuerzos para mejorar la vigilancia de la infeccion por el vih y la prevencion en los programas para las infecciones de transmision sexual.
DRES-14. OVERCOMING TEMOZOLOMIDE RESISTANCE IN EXPERIMENTAL GLIOMAS: MRI-GUIDED FOCUSED ULTRASOUND-MEDIATED BLOOD-BRAIN BARRIER OPENING FACILITATES THE LOCAL DELIVERY OF LIPOSOME ENCAPSULATED MGMT INHIBITORS
Authors: Patrick Roth, Alex Papachristodoulou, Rea Deborah Signorell, Beat Werner, Davide Brambilla, Joanes Grandjean, Markus Rudin, Ernst Martin, Jean-Christophe Leroux, Michael Weller
Journal: Neuro-Oncology (2017)

The standard of care for patients with newly diagnosed glioblastoma comprises surgical resection followed by radiation therapy and chemotherapy with the alkylating agent, temozolomide (TMZ). Still, the median overall survival of glioblastoma patients is only approximately 16 months in clinical trial populations. Importantly, the survival benefit derived from the addition of TMZ is almost exclusively restricted to the rather small subgroup of patients with tumors harboring a methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. The clinical development of drugs that inhibit MGMT in order to sensitize tumors to TMZ was largely unsuccessful because of systemic toxicity. We applied magnetic resonance image-guided focused ultrasound (MRIgFUS) to transiently open the blood brain barrier (BBB) in mice bearing MGMT-expressing experimental gliomas. We generated a novel MGMT inhibitor that was encapsulated in liposomes and resulted in a potent down-regulation of MGMT levels in glioma cells in vitro. The systemic administration of this liposomal MGMT inhibitor in combination with MRIgFUS strongly reduced MGMT levels in orthotopically growing gliomas. Transient opening of the BBB by MRIgFUS and subsequent treatment with the MGMT inhibitor and TMZ reduced the growth of experimental gliomas as assessed by MRI and conferred a significant survival benefit without signs of systemic toxicity. Our dataset demonstrates that MRIgFUS allows for transient and circumscribed BBB opening in the tumor region which can be used for targeted MGMT downregulation. Overcoming MGMT-mediated alkylator resistance sensitizes gliomas in vivo to TMZ, ultimately resulting in a survival benefit. Based on these data, a clinical assessment of this approach in human patients is warranted.
P1.01-063 Are the Real World Patients with Advanced Non-Small Cell Lung Cancer Represented in Phase III Immunotherapy Trials?
Authors: J. Cé Coelho, T. Rebelato, A. Gelatti, R. D'Avila, G. Geib, P. Rubini Liedke, R. Peres Pereira, G. Werutsky, S. Jobim De Azevedo
Journal: Journal of Thoracic Oncology (2017)
P1.04-006 Rovalpituzumab Tesirine vs Topotecan in Patients with Advanced Small Cell Lung Cancer Following 1st Line Chemotherapy
Authors: P. Komarnitsky, H. Lee, M. Shah, S. Wong, S. Gulbranson, J. Dziubinski, L. Caffrey, P. Tanwani, M. Motwani, F. Zhang
Journal: Journal of Thoracic Oncology (2017)
IMMU-31. IN VIVO CELLULAR TRACKING WITH 13C LABELING OF ADOPTIVELY TRANSFERRED T CELLS FOR THE TREATMENT OF BRAIN TUMORS
Authors: Farhad Dastmalchi, Aida Karachi, Jonathan R Allison, Kari B Basso, Duane Mitchell, Maryam Rahman
Journal: Neuro-Oncology (2017)

Immunotherapy with adoptive transfer T cells is an effective treatment for cancer. We have recently demonstrated the ability to overcome chemotherapy resistance in a mouse model of malignant glioma with an adoptive T cell. This platform is dependent on effective migration of cells to the tumor site. Therefore, tracking of transferred cells is critical to the evaluation of the immunotherapy efficacy. The objective of this project was to establish a novel method to track immune cells in vivo using 13C-labeling of nucleic acids. Human T cells were isolated from peripheral blood mononuclear cells (PBMCs). The T cells were stimulated and were grown in glucose-free media supplemented with 13C-labeled glucose in different concentrations (5.5mM, 10mM, 15mM) for 5-7 days. DNA was extracted at various time points and cellular dilutions. Samples were digested and Tandem mass spectrometry (MS/MS) scan events were performed for the 4 nucleosides as well as their most abundant 13C labeled isotope or a plus 5 mass shift resulting from 13C5 incorporations into the ribose backbone. An extracted Ion Chromatogram (EIC) was done for the MS/MS the mass fragments and the peak areas were analyzed. 13C-labeling was identified in all samples including the most diluted and the latest time point. The 13C detection was confirmed to be from labeled T cells as naturally abundant 13C does not incorporate into all of the carbons of the DNA ribose backbone and would not result in a 5 mass shift. Adenosine 13C labeling was the most sensitive. dA/idA ratio in different dilutions (1, 0.25, 0.1, 0.01, 1x10-2, 1x10-3, 1x10-4) were 0.26, 2.47, 2.51, 13.33, 85.74, 118, 190.01. Even cells removed from 13C labeled glucose for 7 days demonstrated detectable levels of 13C-labeled DNA. 13C-labeled glucose can be used to label immune cell DNA for sensitive in vivo tracking.
Physical Activity to Prevent Cardiovascular Disease
Authors: Scott A. Lear, Salim Yusuf
Journal: JAMA Cardiology (2017)

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OA 05.03 Clinical Activity of ASP8273 in Asian Non-Small Cell Lung Cancer Patients with EGFR Activating and T790M Mutations
Authors: K. Park, K. Azuma, C. Tsai, T. Seto, H. Nokihara, J.C. Yang, S. Kim, H. Murakami, M. Nishio, K. Kiura, A. Inoue, K. Takeda, J. Kang, H. Hayashi, T. Nakagawa, Y. Kaneko, R. Akazawa, M. Shimazaki, S. Morita, M. Fukuoka, K. Nakagawa
Journal: Journal of Thoracic Oncology (2017)
OC-053 Uk clinical experience at 52 weeks with linaclotide for irritable bowel syndrome with constipation
Authors: A Emmanuel, J McLaughlin, Y Yiannakou, S McLain-Smith
Journal: Gut (2017)

Introduction  Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to relieve constipation and improve abdominal pain and discomfort in patients with irritable bowel syndrome with constipation (IBS-C), but there are limited UK-specific real-world data to support this.  Method  A multi-centre, observational, prospective 52 week study was conducted in 8 specialist hospitals in England and Scotland, with the primary objective to describe the change in IBS-Symptom Severity Scale (IBS-SSS) score from baseline at 12 weeks after linaclotide initiation. Consenting patients aged ≥18 years initiated on linaclotide (290 mcg) for IBS-C were recruited. Data on patient demographic and clinical characteristics, concomitant medications, patient-reported outcomes (including IBS-SSS) and adverse events (AEs) were collected. Results at 12 weeks (primary endpoint) have been presented previously; here we report analysis of real-world clinical experience 52 weeks post-linaclotide initiation.  Results  202 patients were recruited; 185 (92%) female. At baseline, median age was 44.9 (range 18–77) years; 84 (42%) reported concomitant laxative use. Mean baseline IBS-SSS score was 339 (SD ±92; n=193); 129 (67%) patients had IBS-C classified as severe (score ≥300), 54 (28%) moderate (175  Conclusion  Linaclotide was associated with a significant improvement in IBS-SSS score at 52 weeks and was reasonably well tolerated. These results provide valuable insights into the longer-term outcomes of linaclotide treatment in patients with IBS-C in real-world clinical practice.  Disclosure of Interest  A. Emmanuel Conflict with: Has acted on advisory boards for Allergan, J. McLaughlin: None Declared, Y. Yiannakou Conflict with: Has received an educational grant from Allergan, Conflict with: Has received advisory board fees from Allergan, Conflict with: Has received speaker fees from Allergan, S. McLain-Smith Conflict with: Employee of pH Associates, which was commissioned by Allergan to provide support with research design, conduct, analysis and scientific editorial services
OA 05.08 Final Result of Phase I/II Study (AF-001JP) of Alectinib, a Selective CNS-Active ALK Inhibitor, in ALK+ NSCLC Patients (Pts)
Authors: M. Nishio, K. Kiura, T. Seto, K. Nakagawa, M. Maemondo, A. Inoue, T. Hida, H. Yoshioka, M. Harada, Y. Ohe, N. Nogami, H. Murakami, K. Takeuchi, S. Inamura, H. Kuriki, T. Shimada, T. Tamura
Journal: Journal of Thoracic Oncology (2017)
Brote de gastroenteritis aguda en un internado austriaco, septiembre de 2006
Authors: D Schmid, E Gschiel, M Mann, S Huhulescu, W Ruppitsch, G Bohm, J Pichler, I Lederer, G Höger, S Heuberger, F Allerberger
Journal: Eurosurveillance (2007)

En septiembre de 2006 se declaro un brote de gastroenteritis aguda en un internado de la region oriental de Austria. De los 113 afectados, 101 tuvieron que ser hospitalizados. Para identificar el origen del brote se llevo a cabo un estudio retrospectivo de cohortes en el grupo de riesgo, formado por 222 alumnos y 30 trabajadores. Se identifico que la exposicion alimentaria en el comedor del colegio era el nexo mas relevante y frecuente entre los afectados que se investigaron en la serie de casos.
P3.01-019 Canadian Multicenter Validation Study of Plasma Circulating Tumor DNA for Epidermal Growth Factor (EGFR) T790M Testing
Authors: M. Tsao, T. Zhang, P. Cheema, J. Laskin, A. Karsan, T. Barnes, G. Liu, S. Owen, J. Rothenstein, R. Burkes, M. Iqbal, A. Spatz, I. Izevbaye, L. Kempen, S. Kamel-Reid, N. Leighl
Journal: Journal of Thoracic Oncology (2017)
Harmoniser la prise en charge des expositions au VIH en Europe
Authors: R Tubiana
Journal: Eurosurveillance (2004)

Le besoin d'une harmonisation des recommandations, a l'echelle europeenne, pour la prise en charge des expositions au VIH etait ressenti depuis longtemps. Ainsi, deux groupes d'experts venant de 14 pays differents ont realise un important travail sur le sujet. Les articles de Jesus Almeda et al et de Vincenzo Puro et al [1,2] reprennent leurs conclusions et leurs recommandations.
Deux series de recommandations specifiques aux circonstances de l'exposition ont ainsi ete emises ; une distinction pouvant paraitre contestable si l'objectif est d'eviter ou de prevenir une infection confirmee apres une exposition au VIH (ou bien au VHC ou au VHB). Comme le soulignent les auteurs, la prophylaxie post-exposition (PEP) est appliquee systematiquement chez les professionnels de la sante dans la quasi totalite des pays dont les Etats-Unis. Ceci n'est en revanche pas le cas lors d'expositions sexuelles, a des drogues injectables ou autres expositions non-professionnelles au VIH. Dans le cas d'expositions professionnelles, le role des auteurs etait d'harmoniser les recommandations et strategies nationales existantes. Pour les expositions non professionnelles, il s'agissait de rediger des recommandations europeennes, car tres peu de pays ont des recommandations nationales. 
Ces deux articles montrent que l'expose des motifs, l'environnement, la gestion et le choix du traitement pour une PEP sont tres similaires dans les deux situations.
NTOX-13. NEUROLOGIC COMPLICATIONS OF IMMUNE CHECKPOINT INHIBITORS
Authors: Avi Fellner, Chen Makrans, Felix Bokstein, Deborah T Blumenthal, Alisia Taliansky, Shai Rosenberg, Israel Steiner, Tali Siegal, Shlomit Yust-Katz
Journal: Neuro-Oncology (2017)

Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause autoimmune side effects which can involve any organ, including the nervous system. In this study, we present 9 patients with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, polyradiculitis, multicranial neuropathy, myasthenic syndrome and myositis. Five patients received dual ICPI therapy comprised of programed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. The time between initiation of ICPI and neurologic manifestation ranged between 5 days to 19 weeks. In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with polymyositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse effect. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that early withholding ICPIs treatment, accompanied with high dose steroid therapy carries the potential of complete resolution of the neurological immune-mediated condition. Thus, high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which can potentially be fatal.