tbuckley/cabot-search huggingface dataset:
Abstract 20603: Low Dose-High Frequency Psychomotor Cardiopulmonary Resuscitation Training in the Emergency Department Improves Simulated and Clinical Chest Compression Fraction
Authors: Michael C Kurz, Michael Lovelace, Randal Gray, Ashish Panchal, Emily Gibbons, Gregory Norton, David Slattery
Journal: Circulation (2016)

Background:  High-quality cardiopulmonary resuscitation (CPR) is essential for functional survival from cardiac arrest. However, the opportunity to perform CPR is too infrequent to maintain proficiency for most providers. Low dose-high frequency psychomotor simulation has demonstrated maintenance of CPR proficiency among inpatient providers. We evaluated this type of CPR training via mobile simulation stations (Resuscitation Quality Improvement™ [RQI], American Heart Association, Dallas, TX) in an emergency department (ED) setting.   Methods:  Two RQI simulation stations were placed in an 85,000 visit ED of a university teaching hospital and quarterly training simulations integrated into normal nursing duties. We measured simulated and clinically delivered CPR quality metrics before and 1 year following implementation using RQI and ED defibrillators equipped with thoracic impedance (Lifepak 20e, Physio-control Inc., Redmond, WA). Descriptive statistics are presented as means with 95% confidence intervals.   Results:  We enrolled 150 nurses in June 2015. When compared to baseline data, use of RQI for 1 year was associated with improved simulated chest compression fraction (CCF; 94.6 [86.0-100] vs. 99.1 [98.2-100]; p-value=0.039) and percentage of compressions with adequate recoil (98.2% [96.5-100] vs. 99.2% [99.0-99.4]; p=0.028) and depth (87.3% [74.4-100] vs. 96.7% [97.8-95.6]; p=0.004). In addition, analysis of 4513s of clinically delivered CPR before and 4781s after 1 year of RQI implementation demonstrated an association with improved CCF (71.9 [54.5-89.3] vs. 85.9 [81.1-90.7]; p=0.031).   Conclusions:  Low dose- high frequency psychomotor simulation is associated with achievement and retention of high-quality CPR skills in an ED setting. Furthermore, its use is associated with improved clinical CCF.
Abstract 378: Cholecystokinin Upregulates Cholesterol Absorption in Human Intestinal Epithelial Cells
Authors: Zhongmao Guo, Ningya Zhang, Lemuel Dent, Emmanuel U Okoro, Hong Yang
Journal: Circulation Research (2016)

Excessive absorption of intestinal cholesterol is a risk factor for atherosclerosis. We previously reported that cholecystokinin (CCK) increases intestinal cholesterol absorption and plasma cholesterol level in mouse models. The goal of this study was to investigate the effect of CCK on cholesterol absorption and Niemann-Pick C1 Like 1 (NPC1L1) expression in human primary intestinal epithelial cells (HPIECs). Normal HPIECs were isolated from small bowl resection specimens, and purchased from the Lonza Group (Walkersville, MD) . Cholesterol absorption was determined by measuring transcellular cholesterol transport in adherent cell culture and cholesterol association and release in suspension cell culture. Surface NPC1L1 was isolated using a biotinylation kit and detected by western blotting. Our data demonstrate that HPIECs express both CCK receptor-1 and -2 (CCK1R; CCK2R). Treatment of HPIECs with 3 nM [Thr28, Nle31]-CCK for 60 min increased transcellular cholesterol transport, cholesterol association and release by ~38, 32 and 44%. Selective inhibition of CCK1R and CCK2R with antagonists (1 μM lorglumide or L365260) or selective knockdown of CCK1R and CCK2R with siRNAs attenuated CCK-induced cholesterol absorption. In the cells cultured on transwell membranes, CCK increased the level of NPC1L1 in the apical membrane by ~35% but did not alter the total NPC1L1 protein expression. Inhibition or knockdown of NPC1L1 attenuated CCK-induced cholesterol absorption. These data imply that activation of CCK1R/2R enhances cholesterol absorption by induction of NPC1L membrane translocation. [This study was supported by NIH grants U54MD0007593, UL1TR000445, and SC1HL101431]
Bioterrorisme : crime et opportunité
Authors: D Byrne
Journal: Eurosurveillance (2001)

Les attaques terroristes sans precedent survenues aux Etats-Unis ont provoque des ondes de choc au sein des administrations nationales plus souvent habituees a debattre d'issues financieres dans le domaine de la sante qu'a coordonner la surveillance et la preparation aux situations d’urgence. Au vu des reactions immediates qui ont suivi l’horreur et les menaces de l’automne 2001, il apparait qu’en termes de securite sanitaire, les gouvernements ont jusqu'ici essentiellement mesure leur succes d’apres le calme et l'absence d'incident observes par les responsables de la sante. Le paradoxe de la securite sanitaire reside dans le fait d’etre gagnant lorsque rien ne se passe : toute publicite est vouee a etre une mauvaise publicite.
PDCT-08. TRAMETINIB AND DABRAFENIB FOR REFRACTORY/INOPERABLE PEDIATRIC LOW GRADE GLIOMAS
Authors: Maria Kondyli, Benjamin Ellezam, Christine Saint-Martin, Jean-Pierre Farmer, Louis Crevier, Sébastien Perreault, Nada Jabado
Journal: Neuro-Oncology (2017)

Low grade gliomas (LGG) are the most common pediatric brain tumors and frequently harbor BRAF mutations or fusions. In cases of refractory and progressing LGG, BRAF and MEK inhibitors now offer an interesting therapeutic approach. However, there are only few cases report on the use BRAF/MEK inhibitors in pediatric LGG. We here describe six children with LGG treated with a BRAF or MEK inhibitor. Charts from all patients that received dabrafenib or trametinib were retrieved and retrospectively reviewed. Demographic data, pathology, tumor location, toxicity and progression free survival were retrieved. The mean age at diagnosis was 3.2 years (range: 11mo-6 yo). There were 3 females and 3 males. Four children had a sporadic pilocytic astrocytoma of the optic pathway, one patient with NF1 had an optic pathway glioma and subsequently developed a glioblastoma and one had a ganglioglioma. KIAA1549-BRAF fusion was found in all four sporadic OPG tumors and BRAF v600e mutation was found in the ganglioglioma. Five patients received at least one previous line of chemotherapy (range 1-4) and for one patient it was a first line treatment. Five patients received trametinib (BRAF fusion patients and NF1 patient) and one patient received dabrafenib (BRAFv600e). The mean time on treatment was 13.1 months (range 4-21). Four patients had partial response, one had stable disease and one had progressive disease. Three patients are still on treatment. One patient stopped treatment due to progressive disease (after 10 months) and two patients stopped due to toxicity (1 severe skin toxicity, 1 for suspicion of retinitis pigmentosa, finally ruled out). The most frequent toxicities were minor skin and gastro-intestinal toxicities. In conclusion, BRAF/MEK inhibitors seem to be an interesting option for refractory pediatric LGG. More studies are warranted to better define their role in pediatric LGG and their toxicity profile.
CMET-26. DIAGNOSTIC VALUE OF FDG-PET/CT FOR PATIENTS WITH BRAIN METASTASIS FROM UNKNOWN PRIMARY SITE
Authors: Fabian Wolpert, Michael Weller, Anna Sophie Berghoff, Elisabeth Jane Rushing, Lisa Michaela Füreder, Gregory Petyt, Henning Leske, Nicolaus Andratschke, Luca Regli, Marian Christoph Neidert, Roger Stupp, Rolf Stahel, Reinhard Dummer, Thomas Frauenfelder, Patrick Roth, Nicolas Reyns, Philipp Antonio Kaufmann, Emilie Le Rhun
Journal: Neuro-Oncology (2017)

In 30% of patients with brain metastasis (BM), BM are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). The value of 18F-fluordesoxyglucose positron emission tomography (FDG-PET)/CT in the work-up of BM-CUPS patients remains to be defined. We screened 566 patients operated for BM at the University Hospital Zurich between 2004 and 2014 and identified 127 BM-CUPS patients. A validation cohort from two independent centers (n=100 and 120 patients) was available. FDG-PET/CT was not superior to CT in localizing the primary lesion (FDG-PET/CT: 73/78, 93.6%; CT: n=70/78, 89.7%; p=0.25, McNemar’s test). Thirty-six of 64 patients (56.3%) showed the same result in spotting the primary tumor. FDG-PET/CT identified additional lesions suspicious for extracranial metastases in 28 patients (43.7%). The graded prognostic assessment (GPA) score was determined post-hoc to objectify clinical relevance of additional findings. Information from CT only or FDG-PET/CT was used to assess extracranial metastases. Median GPA was 3 for CT vs. 2.5 for PET/CT (p= 3.8x10-5, McNemar’s test), resulting in a predicted survival of 5.3 vs. 3.8 months (p= 6.1x10-5; Wilcoxon’s test). Sensitivity of CT and FDG-PET/CT and staging capabilities were comparable in all cohorts. FDG-PET/CT shows similar sensitivity to detect the primary tumor in BM-CUPS patients as CT, but may improve the accuracy of staging by detecting of more metastases. GPA scores and predicted survival differ significantly when calculated based on CT versus FDG-PET/CT. FDG-PET/CT should be prioritized for planning the diagnostic algorithm of BM-CUPS patients and redundant CT imaging should be avoided. Further, randomized trials on BM patients should standardize the methods when stratifying for GPA.
P3.16-050 Stromal PDGFR-β Expression Influences Postoperative Survival of NSCLC Patients Receiving Preoperative Chemo- or Chemo-Radiotherapy
Authors: R. Kanzaki, H. Naito, D. Eino, T. Kawamura, N. Ose, S. Funaki, Y. Shintani, M. Minami, M. Okumura, N. Takakura
Journal: Journal of Thoracic Oncology (2017)
SCDT-37. MODULATION OF CONVECTION ENHANCED DELIVERY (CED) DISTRIBUTION USING FOCUSED ULTRASOUND (FUS)
Authors: Melanie Schweitzer, Mihaela Stavarache, Nicholas Petersen, Spyridon Bakas, Apostolos John Tsiouris, Christos Davatzikos, Michael G Kaplitt, Mark M Souweidane
Journal: Neuro-Oncology (2017)

INTRODUCTIONIneffective drug delivery across the blood brain barrier (BBB) is one purported factor that contributes to the lack of therapeutic benefit of systemic chemotherapy for brain tumors. Convection enhanced delivery (CED) is an appealing form of therapeutic drug delivery to the brain that bypasses the BBB while avoiding systemic toxicity. When considering highly diffuse and infiltrative tumors, adequate tumor coverage might not always be possible. Catheter design, infusion parameters, and multi-centric targeting have all been explored as means to alter distribution following CED. The ability to actively modulate infusion volume would be an appealing feature of a CED-based platform. We hypothesize that magnetic resonance-guided focused ultrasound (MRgFUS) may provide a means for modulating CED distribution.
Novos factos epidemiológicos da infecção meningocócica na Bélgica
Authors: F Carion, M van Looveren, H Goossens
Journal: Eurosurveillance (1997)

Na Belgica, depois da epidemia, do inicio dos anos 70, causada por Neisseria Meningitidis B:2b:P1.2 (picos de incidencia em 1971 e 1972 com 5 casos, por 100 000 habitantes, por ano), a incidencia da infeccao meningococica baixou as proporcoes interepidemicas normais de 1/100 000 por ano. No entanto, desde o inicio dos anos 90, a incidencia anual da doenca aumentou progressivamente para 2/100 000. O numero total de Isolados, recebidos pelo laboratorio nacional de referencia, subiu de 96, em 1991, para 210, em 1996. A maior parte dos casos ocorreu no Norte da Belgica: foi observado, em 1993, um aumento mantido na provincia de Antuerpia e, em 1995, na Flandres Ocidental.
Fentanyl pectin nasal spray for breakthrough cancer pain treatment: a single center experience
Authors: E. Lai, S. Tolu, R. Mascia, V. Impera, A. Pretta, N. Liscia, A.G. Pireddu, G. Pusole, S. Camera, A. Cubeddu, M. Dessì, M. Puzzoni, L. Demurtas, P. Ziranu, F. Atzori, V. Pusceddu, E. Massa, C. Madeddu, G. Astara, M. Scartozzi
Journal: Annals of Oncology (2017)
NIMG-38. QUALITY OF SURGICAL DECISION MAKING FOR PATIENTS WITH A GLIOBLASTOMA IS SIMILAR BETWEEN NEURO-ONCOLOGICAL CARE TEAMS FROM THE UNITED STATES OF AMERICA AND THE NETHERLANDS
Authors: Domenique M J Müller, Pierre Robe, Seunggu J Han, Frederik Barkhof, William Peter Vandertop, Mitchel S Berger, Philip C de Witt Hamer
Journal: Neuro-Oncology (2017)

The extent of resection is important to improve survival in patients with a glioblastoma. The neurosurgeon’s aim is to maximize the extent of resection, while preserving functional integrity. Standards to aid in patient counselling and guide surgical decision making are nevertheless lacking, hence quality of surgical care might differ between neuro-oncological care teams. In this study we present a novel volumetric method to quantify post-resection residual tumors throughout the brain for patient populations. This allows direct comparison of surgical results between care teams. All adults with first-time glioblastoma surgery in 2012-2013 in each of two Dutch and one United States tertiary referral centres for neuro-oncological care were included in this study. From each of these patient populations preoperative tumors and postoperative residual disease were segmented on MRI and registered to standard space. Brain maps of tumor and residual tumor locations were constructed for each country. Differences between these brain maps were analysed to explore patient selection and treatment variation. This study cohort consisted of 403 patients (the Netherlands: 268; the United States: 135). Of these, 111 tumors were biopsied and 292 resected. Tumor localization maps illustrate established preferential sites for glioblastoma distributions for each cohort, indicating similar patient referral patterns, selection or recruitment. Resection probability maps demonstrate no differential residual tumor localization throughout the brain, indicating similar surgical decision making. Brain maps were reviewed by the care teams and arguments for future decision making were discussed. Brain maps of tumor localization convey important information that can be used to compare neuro-oncological care teams in terms of patient selection. In addition, surgical decision making can be made explicit through resection probability maps. This novel volumetric approach can provide objective arguments for discussions between care teams on the quality of neurosurgical care for patients with a glioblastoma.
P1.01-041 Role of Re-Biopsy During Disease Progression Non-Small Cell Lung Cancer for Acquired Resistance Analysis and Directing Oncology Treatments
Authors: M. Kakihana, J. Maeda, J. Matsubayashi, S. Maehara, M. Hagiwara, T. Okano, N. Kajiwara, T. Ohira, T. Nagao, N. Ikeda
Journal: Journal of Thoracic Oncology (2017)
SCDT-12. IN VITRO STUDY OF ROLE OF ASTROCYTIC S1P3 IN REGULATING BLOOD-BRAIN/TUMOR BARRIER PERMEABILITY
Authors: Anurag N Paranjape, Brunilde Gril, Stephan Woditschka, Jeffrey Hanson, Xiaolin Wu, Gary T Pauly, Joel P Schneider, Patricia S Steeg
Journal: Neuro-Oncology (2017)

Incidence of breast cancer brain metastasis is increasing. Prognosis of patients with brain metastases is extremely poor. One of the major impediments in treating brain metastases is the presence of a blood-brain/tumor barrier that limits the permeability of chemotherapeutic drugs into the brain parenchyma. Blood-tumor barrier (BTB) has been shown to be heterogenous, and only at highly permeable lesions do drugs reach the tumor cells. To explore the molecular differences between highly and poorly permeable BTBs, gene profiling was done on laser microdissected brain tissues from mice bearing breast cancer brain metastases. Sphingosine-1-phosphate receptor 3 (S1P3) was overexpressed in astrocytes at highly permeable lesions. To explore the functional role of S1P3 in BTB permeability we established an in vitro blood brain/tumor model. Inhibition of S1P3 using a specific chemical inhibitor TY-52156 (2µM) significantly increased barrier integrity as shown by increase in transendothelial electrical resistance (TEER) in BBB (1.3 folds, p<0.05) and BTB (1.45 folds, p<0.001). Additionally, there was a significant decrease in permeability for doxorubicin in BBB (1.78 folds, p<0.01) and BTB (2.1 folds, p<0.01), with concomitant increase in membranous ZO-1 and VE-cadherin. Increase in TEER was dependent on astrocytes. Similar results were observed when S1P3 was stably knocked-down in astrocytes. As astrocytes were grown away from the endothelial monolayer, we hypothesized that astrocyte-secreted molecules regulated barrier integrity. Analysis of supernatant from astrocytes revealed that various cytokines including IL-6, IL-8, CCL2, CXCL1, and GM-CSF were downmodulated upon S1P3 knockdown. Inhibition of IL-6 and CCL2 individually using neutralizing antibodies recapitulated the effects of S1P3 inhibition. This study provides a proof of concept for role of S1P3 and downstream cytokine signaling in regulating BTB permeability in breast cancer brain metastases which might lead to discovery of novel strategies for augmenting drug efficacy.
SURG-32. COMBINED INTRACAVITARY THERMOTHERAPY WITH IRON-OXIDE NANOPARTICLES AND RADIOTHERAPY AS A PROMISING TREATMENT MODALITY IN RECURRENT GBM
Authors: Oliver Grauer, Mohammed Jaber, Katharina Hess, Matthias Weckesser, Stephan Maring, Wolfram Schwindt, Walter Stummer, Johannes Wölfer
Journal: Neuro-Oncology (2017)

Treatment options for glioblastoma patients (GBM) at the time of recurrence are still limited. We report a series of six recurrent GBM patients (median age: 62.5 years, median time to first recurrence: 5.7 months, range 2.9 to 15.0) who were treated with intratumoral thermotherapy using superparamagnetic iron-oxide nanoparticles (NanoTherm®, MagForce AG, Munich, Germany) combined with external beam radiotherapy. After resection, tumor cavities were covered with nanoparticles using hydroxycellulose mesh and fibrin glue to create high local particle concentrations for subsequent heating in an alternating magnetic field („NanoPaste” technology). Patients underwent six 1-hour hyperthermia sessions and received concomitant or sequential radiotherapy at a dose of 39.6 Gy (5 x 1.8 Gy/week). During the course of the disease, four patients developed a clinical deterioration (median EFS=3.1 months, range 2.0 to 4.5). In all cases, CT scans showed contrast-enhancing lesions with prominent edema surrounding the resection cavity. Patients underwent re-surgery and were treated with tapered doses of dexamethasone. Histopathology revealed sustained necrosis and large amounts of iron-oxide nanoparticles without evidence for tumor activity or bacterial infection. Immunohistochemistry showed upregulation of HSP70, a prominent infiltration of CD68+ myeloperoxidase-positive macrophages with ingested nanoparticles and an increase of CD3+ and CD8+ T-cells which were not detectable in the pre-therapeutic tumor tissue. In addition, flow cytometric analysis of intratumoral T-cells showed a shift towards a Th1 phenotype with increased intracellular ratio of INF-γ to IL-4. Follow-up CT and PET-CT scans revealed no signs of tumor recurrence in 5 out of 6 cases, whereas one patient developed a definite tumor progress (median PFS=5.8 months, range 2.0 to 17.9). Local NanoTherm® treatment combined with radiotherapy can induce a persistent inflammatory reaction at the resection cavity which might lead to long-term stabilization of recurrent GBM patients. These results warrant further investigations in a prospective clinical trial.
Abstract 12442: Exception to Consent in Pediatric Resuscitation Research: Exploring the Experiences of Substitute Decision Makers
Authors: Melissa J Parker, Sonya de Laat, Lisa Schwartz
Journal: Circulation (2016)

Introduction: International research ethics standards endorse an exception to prospective informed consent for research in medical emergencies. While an exception to consent may be ethically justifiable to facilitate rigorous evaluation of time-sensitive interventions in acute life-threatening conditions, little information is available regarding the experiences of participants and substitute decision-makers (SDM). We sought to better understand the experiences of parents/guardians with an exception to consent process as implemented in a pilot RCT involving children with septic shock. Hypothesis: Use of an exception to consent process is acceptable to most SDMs. Methods: Design: qualitative research study. Participants: SDMs for children enrolled into the SQUEEZE pilot trial [NCT01973907]. Sample size: Up to 25 participants. Qualitative Methods: SDMs are invited to participate in the qualitative ethics study. Interviews with consenting SDMs are conducted in person or by telephone, taped and professionally transcribed. Participants are encouraged to elaborate on their experience of being asked to consent after the fact and how this process occurred. Analysis: Data gathering and analysis are undertaken simultaneously with qualitative data coded using NVivo. Outcome: Themes emerging from the data. Results: Interviews with 15 SDMs, including bereaved and non-bereaved parents/guardians, have been conducted to date. Preliminary findings: 1) SDMs recognized the need for use of an exception to consent process for research in individual medical emergencies; 2) Most SDMs viewed their child’s research participation positively, with many making altruistic statements about helping other children in the future; 3) Perceptions regarding the appropriateness of the timing of the consent approach following enrolment were variable, with some SDMs stating that it was the “right amount of information at the right time", while others felt that they had been approached too soon. Conclusions: Substitute decision makers, including bereaved parents/guardians, support use of an exception to consent process in research in individual medical emergencies.
P1.03-049 Phase II Study of S-1 plus Bevacizumab Combination Therapy for Patients Previously Treated for Non-Squamous Non–Small Cell Lung Cancer
Authors: K. Masuhiro, Y. Nishijima-Futami, S. Minami, S. Futami, T. Koba, M. Higashiguchi, M. Tamiya, H. Suzuki, T. Hirashima, K. Komuta, T. Kijima
Journal: Journal of Thoracic Oncology (2017)