tbuckley/cabot-search huggingface dataset:
RARE-19. MULTICENTER, PHASE 2 STUDY OF BEVACIZUMAB IN CHILDREN AND ADULTS WITH NEUROFIBROMATOSIS 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS: AN NF CLINICAL TRIALS CONSORTIUM STUDY
Authors: Scott Plotkin, James Tonsgard, Nicole Ullrich, Jeffrey Allen, Jashri Blakeley, Tena Rosser, Jian Campian, Wade Clapp, Michael Fisher, Gary Cutter, Bruce Korf, Roger Packer, Coretta Thomas, Matthias Karjannis
Journal: Neuro-Oncology (2017)

Vestibular schwannomas (VSs) in patients with neurofibromatosis 2 (NF2) are associated with hearing loss. Recently published data from a prospective clinical trial showed that bevacizumab treatment at a fixed dose of 7.5 mg/kg every 3 weeks was associated with hearing improvement and tumor shrinkage in 36% and 43% of patients, respectively. The optimal treatment dose and schedule, however, are unknown. The primary aim of this study was to determine the hearing response rate during induction therapy with bevacizumab at 10 mg/kg every 2 weeks; secondary aims included radiographic response rate. This multicenter, phase II, open label study evaluated children and adults (≥6 years of age) with NF2 and progressive VSs treated with bevacizumab. Subjects received bevacizumab 10 mg/kg every 2 weeks during induction therapy (6 months), and 5 mg/kg every 3 weeks during maintenance therapy (18 months). Hearing response was defined as a significant increase in word recognition score above baseline. Radiographic response was defined as ≥20% decrease in tumor volume from baseline. The primary endpoint was hearing response rate in the target ear at 6 months. We enrolled 22 subjects (9M;13F) with a median age of 23 years (range 12-62 years). Nineteen subjects have completed induction therapy. 8/19 (42%) subjects had hearing response and 4/19 subjects (21%) had a radiographic response in the target VS. Bevacizumab was well tolerated. Adverse events included hypertension, proteinuria, arthralgias, AST/bilirubin elevation, delayed wound healing, fatigue, and irregular menstruation. 11/13 female subjects had elevated FSH and underwent evaluation for premature ovarian insufficiency. All continued treatment with bevacizumab. Bevacizumab treatment at 10 mg/kg every 2 weeks is associated with hearing and radiographic response rates at 6 months that are similar to previous studies using lower doses. Future analyses will address the durability of hearing and radiographic responses during 18 months of maintenance therapy.
Ubiquitin levels: the next target against gynecological cancers?
Authors: Diane L. Haakonsen, Michael Rape
Journal: Journal of Clinical Investigation (2017)

Ubiquitylation is a tightly regulated process that is essential for appropriate cell survival and function, and the ubiquitin pathway has shown promise as a therapeutic target for several forms of cancer. In this issue of the JCI, Kedves and colleagues report the identification of a subset of gynecological cancers with repressed expression of the polyubiquitin gene UBB, which renders these cancer cells sensitive to further decreases in ubiquitin production by inhibition of the polyubiquitin gene UBC. Moreover, inducible depletion of UBC in mice harboring tumors with low UBB levels dramatically decreased tumor burden and prolonged survival. Together, the results of this study indicate that there is a synthetic lethal relationship between UBB and UBC that has potential to be exploited as a therapeutic strategy to fight these devastating cancers.
NIMG-10. ATYPICAL RADIOLOGICAL FINDINGS OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): A 12-YEAR SINGLE-CENTER REVIEW
Authors: Ying Hao Christopher Seet, Wai-Yung Yu, Iram Rais Alam Khan, Hwei Yee Lee, Xuling Lin
Journal: Neuro-Oncology (2017)

PCNSL classically presents with homogeneously contrast-enhancing lesions. Atypical brain imaging findings, including non-enhancing lesions or lesions with hemorrhage, calcification, cyst and necrosis, often lead to delayed diagnosis and treatment. We aim to characterize the atypical radiological features of PCNSL in our local population. We retrospectively reviewed all patients with histological diagnosis of CNS lymphoma at our tertiary center from 2005 to 2016. We screened all initial pre-treatment MRIs, and excluded cases with typical imaging findings of contrast-enhancing lesions without intra-lesional susceptibility (hemorrhage/calcification) and central non-enhancement (cyst/necrosis). Additional exclusion criteria included (i) relapsed PCNSL, (ii) secondary CNS lymphoma, and (iii) positive HIV status. Two independent raters scored MRIs and CTs at presentation. Where multiple enhancing lesions were present, scoring was performed for the largest. Sixteen patients (8 men; 8 women) were analyzed; median age was 61 (range 22-81) years. Histological diagnoses were DLBCL (n=14) and intravascular lymphoma (n=2). Fifteen (93%) patients had enhancing lesions (5 solitary; 10 multifocal); one had non-enhancing lesion at the right cerebellar peduncle. Median maximum diameter of the largest enhancing lesion in each case was 41 (range 18-80) mm. Most enhancing lesions had T1 hypointense (67%) and T2 mixed (53%) signals. Five (33%) of 15 enhancing lesions did not diffusion-restrict; 6 (40%) had central non-enhancing regions. Of all 16 patients, 9 (56%) had lesions with susceptibility. Median T2-T2 diameter was 82 (range 14-116) mm; mass effect was absent in 3 (19%), mild-moderate in 11 (69%) and severe in 2 (13%). Pre-surgical radiological diagnoses were glioblastoma (n=9), demyelinating disease (n=2), malignant meningioma (n=1), vasculitis (n=1), and lymphoma (n=3). PCNSL lesions may be non-enhancing, non-diffusion restricted, contain hemorrhage/calcification and cyst/necrosis, and mimic other CNS diseases. A high index of suspicion with low threshold for biopsy is critical for early diagnosis of PCNSL with atypical presentation.
P1.03-006 Clinicopathological Features and Poor Outcome for ALK Inhibitors of Squamous Cell Lung Cancer with ALK-Rearrangement
Authors: H. Motomura, J. Watanabe, S. Togo, I. Sumiyoshi, Y. Namba, K. Suina, T. Mizuno, K. Kadoya, M. Iwai, T. Nagaoka, S. Sasaki, T. Hayashi, T. Uekusa, K. Abe, Y. Urata, F. Sakurai, H. Mizuguchi, S. Kato, K. Takahashi
Journal: Journal of Thoracic Oncology (2017)
MA 02.05 Nivolumab in Advanced Non-Squamous NSCLC Patients with KRAS Mutations: Results from the Italian Expanded Access Program (EAP)
Authors: A. Ardizzoni, P. Bidoli, R. Chiari, L. Bonomi, D. Turci, L. Landi, L. Toschi, M. De Tursi, G. Francini, M. Giordano, O. Alabiso, A. De Censi, L. Livi, A. Berruti, M. Minelli, E. Ricevuto, A. Illiano, G. Puppo, A. Delmonte, D. Galetta
Journal: Journal of Thoracic Oncology (2017)
Abstract 20715: Possibility for Successful Resuscitation From Sudden Cardiac Arrest in School; Difference by the Causative Disease
Authors: Mamoru Ayusawa, Masataka Kato
Journal: Circulation (2016)

Background:  Introduction of basic life support and automated external defibrillator has been contributing to improve prognosis of sudden cardiac arrest in school. It is necessary to evaluate the latest results of resuscitation according to the cause of cardiac arrest.   Methods:  All reports including ECG, death or health certificates, and autopsy reports of all sudden cardiac arrest (SCA) registered to the mutual aid system for schools between 2008 and 2013 were reviewed and summarized their causes.   Results:  There were 328 cases consisted of 121 death and 207 successfully resuscitated cases during these 6 years. Incidence(/100,000studente•year) of and recovery were 0.12 and 0.20, respectively. The ratio of resuscitated SCA to death cases was increased from 55.3% to 71.2% during 6 years. The number of cases / ratio of recovery of spontaneous circulation (ROSC) / Odds ratio of ROSC / p value for each cause of SCA were 40 / 53% / 0.61 / 0.14 in cardiomyopathy, 17 / 59% / 0.39 / 0.054 in congenital heart disease, 15 / 60% / 0.87 / 0.8 in congenital coronary anomaly, 8 / 25% / 0.19 / 0.031 in acute myocarditis, 8 / 0% / 0 / 0.001 in aortic dissection, 87 / 66% / 1.2 / 0.58 in ventricular fibrillation, 10 / 90% / 5.5 / 0.07 in long QT syndrome, 8 / 88% / 4.2 / 0.15 in commotio cordis, 3 / 33% / 1.2 / 0.28 in WPW syndrome, 120 / 73% / 2.1 / 0.004 in unknown cause.   Conclusions:  Although incidence of SCA including both decease and recovery is still around a total of 0.3, approximately two thirds of them have been resuscitated successfully in school from 2008 to 2013. Favorable outcomes in arrhythmic diseases are achieved, however, difficulty of resuscitation in structural disease are enhanced for rescue of SCA in school students. Strategy for aortic dissection and coronary anomaly has to be discussed.
MA 20.11 Chronic Obstructive Pulmonary Disease Prevalence in a Lung Cancer Screening Population
Authors: J. Goffin, G. Pond, A. Tremblay, M. Johnston, G. Goss, G. Nicholas, S. Martel, R. Bhatia, G. Liu, H. Roberts, M. Tammemägi, S. Atkar-Khattra, M. Tsao, S. Lam, S. Puksa
Journal: Journal of Thoracic Oncology (2017)
A epidemiologia da sífilis infecciosa na República de Irlanda
Authors: M Cronin, L Domegan, L Thornton, M Fitzgerald, S Hopkins, P O’Lorcain, E Creamer, D O'Flanagan
Journal: Eurosurveillance (2004)

Em resposta ao numero crescente de casos de sifilis em homens que tem relacoes com outros homens (HRSH) em Dublin, foi constituido ao fim do ano 2000 um grupo de controle dos surtos (Outbreak Control Team, OCT). A epidemia atingiu o seu ponto maximo em 2001 e acabou no fim de 2003. Para colher os dados desde Janeiro de 2000 formou-se um sistema reforcado para a vigilancia da sifilis. 
Entre Janeiro 2000 e Dezembro 2003, foram declarados em Irlanda 547 casos de sifilis infecciosa (dos quais 415 eram HRSH). Durante os tres meses precedentes, 4% dos casos tinham sido infectados pelo VIH e 15,4% por ao menos uma infeccao sexualmente transmissivel (IST) (excluindo o VIH). O numero medio de relacoes declaradas pelos casos masculinos nos tres meses anteriores ao diagnostico eram quatro (entre 0 e 8) para as relacoes heterosexuais e seis para as relacoes homosexuais (entre 1 e 90). Trinta e um por cento dos HRSH declararao ter tido relacoes sexuais orais sem proteccao recentes e 15,9% relacoes anais sem proteccao. Dezeseis porcento tinham tido relacoes sexuais no extrangeiro nos treis meses antes do diagnostico. Os resultados sugerem que as praticas sexuais a risco contribuirem a transmissao da infeccao em Dublin. A epidemia de Dublin pode ser considerada como parte de uma epidemia de sifilis europeia. As taxas de co-infeccao pelo VIH e a sifilis na Irlanda sao comparaveis as declaradas por outros centros. E necessario amelhorar os sistemas de vigilância para poder evaluar as intervencoes em tempo real e monitorizar regularmente a tendencia da infeccao.
Dados de vigilância sobre infecções pelo VIH e Sida pediátricos na Grécia
Authors: G Nikolopoulos, V Konte, A Masgala, E Eleni, A Tsantes, D Paraskeva
Journal: Eurosurveillance (2004)

Na Grecia, a vigilância do VIH/Sida e conduzida pelo Centro Helenico de vigilância das doencas infecciosas. O sistema de notificacao de casos do Sida foi iniciado em 1984, seguido pela notificacao de infeccoes pelo VIH em 1998. Este artigo presenta a vigilância e a analise de tendencia das infeccoes pelo VIH e Sida nas criancas, incluindo os casos identificados antes de 1998. 
O numero de criancas contaminadas pelo VIH em Grecia e relativamente baixo, atingindo um total acumulado de 69 casos em Junho 2003. Quarenta e quatro casos, ou 63,76% foram provavelmente infectados por transmissao de mae a filho. Desde o comeco do surto, foram notificados 33 casos de Sida em criancas, sendo a pneumonia por Pneumocystis carinii a infeccao opportunista mais frequente. 
Um numero significativo de criancas em Grecia foram diagnosticadas depois da idade de um ano. Isso pode ser devido ao facto que muitas mulheres contaminadas pelo VIH nao sao identificadas durante a gravidez, embora se ofereca a possibilidade de realizar testes de anticorpos de forma voluntaria. Tambem poderia ser atribuido ao facto que os dados incluem infeccoes pelo VIH coletadas retrospectivamente depois de 1998, e que as criancas estrangeiras contaminadas pelo VIH podem ter chegado mais idosas na Grecia. Os novos casos pediatricos de infeccoes declaradas durante os primeiros seis meses de 2003 eram criancas que tinham nascido em Europa de leste e na Africa sub-Sahariana. Esforcos deveriam ser feitos para a identificacao das mulheres dessas populacoes a tempo para uma intervencao efficaz. A infeccao pelo VIH em criancas continua sendo um problema essencial a nivel mundial e a reduccao do risco de transmissao de mae a filho deve seguir a ser uma prioridade.
P1.17-010 The Diagnostic Value of Serum Cytokeratin Fragment 19 (CYFRA21-1) for Thymic Squamous Cell Carcinoma
Authors: H. Shiiya, Y. Hida, K. Kaga, T. Kato, M. Aragaki, R. Kubota, Y. Matsui
Journal: Journal of Thoracic Oncology (2017)
Dernières informations en date concernant les maladies associées à Clostridium difficile causées par le PCR ribotype 027 en Europe
Authors: E J Kuijper, B Coignard, J S Brazier, C Suetens, D Drudy, C Wiuff, H Pituch, P Reichert, F Schneider, A F Widmer, K Ep Olsen, F Allerberger, D W Notermans, F Barbut, M Delmée, M Wilcox, A Pearson, B Patel, D J Brown, R Frei, T Akerlund, I R Poxton, Peet Tüll
Journal: Eurosurveillance (2007)

De recentes epidemies de diarrhees associees a Clostridium difficile (DACD), d’une severite accrue et dont les taux de rechute et de mortalite sont importants, ont ete mises en relation avec l’apparition d’une nouvelle souche de C. difficile tres virulente en Amerique du Nord, au Japon et en Europe.
GP is suspended for three months after “improper relationship” with patient
Authors: Clare Dyer
Journal: BMJ (2017)

A GP who sought to end a professional relationship with a patient while pursuing an “improper emotional relationship” with him has been suspended for three months by a medical practitioners tribunal.

Julien Nash, 54, a civilian doctor working at an air force base, RAF Cosford, urged “Patient A,” a serviceman, to find a new doctor when she realised that “a line had been crossed” after sharing a kiss with him in November 2015.

But, the tribunal found, this approach breached the General Medical Council’s good practice guidance, …
RARE-28. MALIGNANT TRANSFORMATION OF A LOW-GRADE MIDLINE GLIOMA WITH CONCOMITANT BRAFv600E AND H3.3K27 MUTATIONS
Authors: Richard Graham, Mohamed S AbdelBaki, Jonathan L Finlay
Journal: Neuro-Oncology (2017)

We present the case of a 9 year old boy who was diagnosed at the age of four with a midbrain mass projecting into the 3rd. The tumor had an expanding cystic portion which required surgical management and the pathology was a WHO Grade II glioma (Ki-67 of 3-8%). Parents chose to pursue holistic alternative therapies, as opposed to chemotherapy. The tumor was stable for almost 2 years before imaging showed progression in the solid component of the tumor. Parents again chose to continue homeopathic treatment and scans remained stable for 2 more years before the patient again developed worsening symptoms and tumor progression on imaging. Partial resection was done and pathology showed GBM with BRAFv600E mutation as well as H3.3K27 mutation, CMYC amplification and P53 mutation (not in germline). BRAFv600E is a well-known, targetable gene mutation in gliomas, including GBMs.H3.3k27 is a mutation associated with midline gliomas, particularly GBM and DIPG and is now included in the WHO grading system. Co-expression of these two mutations is rare and still of unclear significance. One report in gangliogliomas showed 5 cases of co-expression, interestingly however, in this collection only one of the 5 cases underwent malignant transformation and the other patients have continued without progression to the present. Some data seem to indicate that GBM with H3.3K27 mutations have a worse prognosis. Our patient was treated with a course of temozolamide and XRT and has just begun dual treatment with dabrafenib and trametinib awaiting scans to evaluate for response. Midline gliomas harboring both H3.3K27 as well as BRAFv600E mutations are extremely rare. Low grade gliomas with both mutations can be the reason behind their malignant transformation.
Role of kinase-coupled TRP channels in mineral homeostasis
Authors: Vladimir Chubanov, Lorenz Mittermeier, Thomas Gudermann
Journal: Pharmacology & Therapeutics (2017)

Transient receptor potential (TRP) proteins TRPM6 and TRPM7 are α-kinase-coupled divalent cation-selective channels activated upon a reduction of cytosolic levels of Mg2+ and Mg·ATP. Emerging evidence indicate that one of the main physiological functions of TRPM6 and TRPM7 is maintaining of cellular metabolism of Mg2+ and likely other essential metals such as Ca2+ and Zn2+. Recent experiments with genetic animal models have shown that TRPM6 and TRPM7 are essential for epithelial Mg2+ transport in the placenta and intestine. In addition, mutations in TRPM6 or TRPM7 have been linked to Mg2+ deficiency in humans. However, many key functional aspects of these remarkable proteins as well as mechanisms of the associated channelopathies remain incompletely understood. The present review article highlights the recent significant progress in the field with the focus on the vital roles of TRPM7 and TRPM7 in mineral homeostasis.
PUB024 Clusters Spatial Arrangement of Tumor Infiltrating Lymphocyte and Cancer Nuclei Predicts Recurrence in Early Stage Non-Small Cell Lung Cancer
Authors: X. Wang, G. Corredor, E. Romero, K. Schalper, M. Yang, D. Rimm, V. Velcheti, A. Madabhushi
Journal: Journal of Thoracic Oncology (2017)
DDIS-11. TTI-2341: A NOVEL, ORALLY BIOAVAILABLE, BRAIN-PENETRANT, COVALENT EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) INHIBITOR FOR TREATMENT OF GLIOBLASTOMA MULTIFORME (GBM) AND BRAIN METASTASES OF NON-SMALL CELL LUNG CANCER (NSCLC)
Authors: Zezhou Wang, Peter Dove, David Rosa, Andrew Marshall, Tina Catalano, Bolette Bossen, Jaehyun Choi, Chunlei Wang, Mark Wong, Jeff Winston, Malik Slassi, Penka S Petrova, Robert A Uger
Journal: Neuro-Oncology (2017)

Aberrant EGFR activity is implicated in certain central nervous system (CNS) tumors, including GBM and brain metastases of NSCLC, which occur in almost half of NSCLC patients. Current approved EGFR inhibitors, however, have very limited efficacy against those CNS tumors due to insufficient penetration of the blood-brain barrier (BBB). Thus, there is a strong unmet medical need to develop novel EGFR inhibitors that are able to effectively access the CNS. Here we report that TTI-2341, a novel covalent orally active EGFR inhibitor, demonstrates superior brain penetration and is reasonably well tolerated in preclinical studies. TTI-2341 displays potent inhibition of wild type and mutant EGFR (including resistance-associated variants L858R and T790M) with nanomolar or lower IC50s in vitro, while exhibiting selectivity for the EGFR family of kinases. TTI-2341 strongly inhibits auto-phosphorylation of EGFR at 10nM in GBM DKMG cells. Furthermore, TTI-2341 has equal or superior anti-proliferative activity compared to the benchmark marketed covalent EGFR inhibitor afatinib among most NSCLC and CNS tumor cell lines tested. ADME studies show that TTI-2341 has 3-fold higher cell permeability and 5-fold less efflux ratio than afatinib in Caco-2 cells, and is not a substrate of PgP (Efflux < 2 in MDCK-MDR1 cells). Importantly, TTI-2341 has superior oral bioavailability (86%), 13-fold higher Kpuu (unbound drug brain-to-plasma ratio) and 6-fold higher brain exposure compared to afatinib. Results from the 7-day repeat dose toxicology study in rats demonstrate that TTI-2341 is well tolerated up to a dose level of 8 mg/kg with no prominent signs of CNS toxicity by clinical and histopathological assessments. Together, these results indicate that TTI-2341 achieves superior brain penetration compared to afatinib. Our data highlight the potential of TTI-2341 to achieve best-in-class status among covalent EGFR inhibitors for the treatment of CNS tumors.
Infections à norovirus dans un hôtel situé dans l’ouest de l’Irlande, 2006
Authors: A Michel, R FitzGerald, D Whyte, A Fitzgerald, E Beggan, N O’Connell, T Greally
Journal: Eurosurveillance (2007)

Une epidemie de troubles gastro-intestinaux (nausees, vomissements ou diarrhees) est survenue parmi les invites d’un mariage, ainsi que parmi les membres du personnel et chez d’autres clients, dans un hotel situe dans l’ouest de l’Irlande, en octobre 2006.
Gripenet : un système basé sur Internet pour une surveillance uniforme de l’activité grippale en Europe
Authors: S P van Noort, M Muehlen, H Rebelo de Andrade, C Koppeschaar, J M Lima Lourenço, M Gm Gomes
Journal: Eurosurveillance (2007)

Grâce a Internet et avec l’aide de benevoles, Gripenet etudie l’activite grippale aux Pays-Bas et en Belgique depuis 2003 et au Portugal depuis 2005.
OA 17.05 IFCT-1502 CLINIVO: Real-Life Experience with Nivolumab in 600 Patients (Pts) with Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: O. Molinier, C. Audigier-Valette, J. Cadranel, I. Monnet, J. Hureaux, W. Hilgers, E. Fauchon, E. Fabre, B. Besse, P. Brun, D. Coëtmeur, E. Quoix, P. Mourlanette, F. Barlesi, S. Bordenave-Caffre, T. Egenod, P. Missy, F. Morin, D. Moro-Sibilot, N. Girard
Journal: Journal of Thoracic Oncology (2017)
CBIO-09. ONCOGENIC ROLE OF NFIA-NFκB IN GLIOMA
Authors: Hae-Ri Song, Edlira Hoxha, Hannah Cho
Journal: Neuro-Oncology (2017)

The NFIA transcription factor is a glioma tumor promoter. The mechanism by which NFIA regulates glioma cell survival and drug resistance is unknown. Here we report that the NFIA pro-survival effect is mediated via an NFIA-NFκB p65 feedforward loop. We examined effects of gain- and loss-of-function manipulations of NFIA and NFκB p65 on cell growth, apoptosis and sensitivity to chemotherapy in patient-derived GBM cells. NFIA inhibited apoptosis by activation of NFkB p65 and its downstream anti-apoptotic factors. Induction of NFκB by NFIA was required for apoptosis evasion, and inhibition of NFκB effectively reversed the NFIA anti-apoptotic effect. Conversely, NFIA knockdown decreased expression of NFκB and its downstream anti-apoptotic genes and increased baseline apoptosis. Using transcriptome- and genome-wide approach, we demonstrated that NFIA directly regulated NFκB transcription. In addition, we found that NFκB activated the NFIA transcription and that knockdown of NFIA was sufficient to attenuate the NFκB pro-survival effect, suggesting a reciprocal regulation between NFIA and NFκB in governing GBM cell growth and survival. Supporting this, NFIA and NFκB expression levels were highly correlated in human GBMs and patient-derived GBM cells. Interestingly, we found that NFIA has splice isoforms in human GBM, which significantly promoted growth of GBM cells and malignant transformation of normal astrocytes. Furthermore, NFIA and the two active isoforms potently increased activity of NFκB p65 in GBM cells. These findings suggest that GBM-active NFIA isoforms differentially affect GBM initiation and progression in part by activating NFκB p65. Collectively, these data define a novel NFIA-NFκB feedforward regulation that promotes GBM tumorigenesis and malignant behavior.