tbuckley/cabot-search huggingface dataset:
NIMG-41. ACCURATE AND GENERALIZABLE PRE-OPERATIVE PROGNOSTIC STRATIFICATION OF GLIOBLASTOMA PATIENTS USING INTEGRATIVE QUANTITATIVE RADIOMIC ANALYSIS OF CONVENTIONAL MRI
Authors: Spyridon Bakas, Gaurav Shukla, Hamed Akbari, Aristeidis Sotiras, Guray Erus, Martin Rozycki, Gregory S Alexander, Joseph Lombardo, Russell T Shinohara, Christos Davatzikos
Journal: Neuro-Oncology (2017)

Glioblastoma, the most common and aggressive adult brain tumor, is considered non-curative at diagnosis, with 14.6 months median survival following treatment, and 4 months otherwise. There is increasing evidence that non-invasive radiomic markers can predict survival, using advanced multiparametric magnetic resonance imaging (A-mpMRI). If successfully applicable, such non-invasive markers can considerably influence patient management. However, most patients typically undergo only conventional mpMRI (C-mpMRI) pre-operatively (i.e., T1,T1-Gd,T2,T2-FLAIR), rather than A-mpMRI that provides additional vascularization (DSC-MRI) and cell-density (DTI) related information. Therefore, existing prognostic A-mpMRI radiomic markers are not applicable/generalizable across institutions for most patients. This study demonstrates that accurate prognostic models may be constructed pre-operatively using integrative radiomic analysis of widely-available C-mpMRI. We hypothesized that appropriate extraction and selection of advanced radiomic feature panels can potentially compensate for the lack of A-mpMRI, thereby rendering such radiomic predictors more amenable to broad clinical use. A retrospective cohort of 101 de novo glioblastoma patients with preoperative C-mpMRI and A-mpMRI was segmented into various sub-regions (e.g., enhancing/non-enhancing/necrotic). Both visually (e.g., volume, location, intensity), and non-visually (e.g., tumor growth model parameters) interpretable radiomic features (n=1612) were extracted for these sub-regions. We assessed two feature configurations: our advanced feature panel (A-FP), and a subset feature panel (S-FP) based on an existing published prognostic A-mpMRI model. The classification accuracy (ACC) of the prognostic model configurations to classify short-(<12months), long-(>14months), and intermediate-survivors was quantitatively evaluated using a 5-fold cross-validation scheme. The performance of the previously published model (S-FP/A-mpMRI) was replicated (ACC:78.71%), and degraded to 75.74% when using C-mpMRI. The A-FP/C-mpMRI model demonstrated superior performance (ACC:89.11%), also supported by Cox regression (HR:2.84, 95%CI:2.42-3.34). These results suggest that accurate pre-operative prognostic stratification, which is important for personalized treatment decisions in glioblastoma patients, is feasible based solely on integrative quantitative radiomic analysis of C-mpMRI, showing promise for generalization across multiple clinics.
HOUT-06. TTFIELDS FOR NEWLY DIAGNOSED GLIOBLASTOMA: IMPACT OF CONSULTATION STRATEGY
Authors: Martin Proescholdt, Julia Onken, Peter Hau, Christian Doenitz, Martin Misch
Journal: Neuro-Oncology (2017)

After a positive randomized clinical trial showing significant survival benefits, Tumor Treating Fields (TTFields) have been implemented in the management of newly diagnosed glioblastoma (GBM). However, this treatment critically depends on patient’s motivation for this therapy plus a high compliance rate. Hair shaving, skin care, application of the arrays and carrying the power source in daily life requires an adequate level of commitment from the patients and their relatives. Based on our clinical experience, it became evident that structure and didactics of the initial and follow up consultations profoundly influence these parameters. In the primary time segment of 4 months after publication of the EF-14 trial results, we have informed our patients during inpatient stay shortly after resection and histological diagnosis about this treatment option. After initially unsatisfactory experiences regarding patient motivation for TTFields treatment, we have initiated a designated outpatient clinic for TTFields therapy consultation in analogy to consultation for radiation and chemotherapy. In this setting, we allow about one hour for each patient appointment to meet the need for information about mode of action, clinical efficacy, compliance aspects as well as practical issues with the device application. We developed a standardized patient education concept for intense and open communication about the disease, prognosis and treatment options with advantages and drawbacks. Using the initial consultation strategy, we were unable to motivate any patients with newly diagnosed GBM to get TTFields treatment. In contrast, after changing the setting into a more patient – centered approach, and standardization of the consultation didactics, 68% of all newly diagnosed patients agree to apply TTFields therapy. In addition, the average compliance rate was well above 90%, which ensures clinical efficacy of this treatment modality. Motivation for and compliance to TTFields therapy may critically depend on the consultation setting and strategy.
Early psychosis for the non-specialist doctor
Authors: Musa Basseer Sami, David Shiers, Saqib Latif, Sagnik Bhattacharyya
Journal: BMJ (2017)

#### What you need to know

A general practitioner may support four to eight patients with psychotic disorder and see one new presentation each year.12 Other non-specialist doctors will encounter patients presenting to an emergency department or complicating comorbid illness.

Psychosis often emerges for the first time in adolescence and young adulthood.3 In around four out of five patients symptoms remit, but most experience relapses and further difficulties.4 The first two to five years of psychosis are considered a critical period for intervening to improve long term outcome.567 The non-specialist plays a key role in early identification. The challenge is to identify a relatively rare but serious disorder and distinguish this from more common but less severe disorders, occurring in a typically young population experiencing developmental and often stressful transitions.

#### Methods

We searched the Medline database over 10 years (1 January 2007 to 31 January 2017) for review articles on “early psychotic illness” or “early psychosis.” This yielded 779 including Narrative and Systematic Reviews and Meta-analyses. 125 articles were reviewed for relevance and methodology and analysis of data.



Fig 1  Where the soft winds blow by Bryan Charnley (1949-1991), who had schizophrenia (www.bryancharnley.info). ©The estate of Bryan Charnley, reproduced with permission



The term psychosis embraces a constellation of symptoms characterised by hallucinations, delusions, or disorganised behaviour or thought (“positive …
Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC)
Authors: S. Spazzapan, P. Conte, E. Simoncini, M. Campone, M. Miller, G. Sonke
Journal: Annals of Oncology (2017)
GENE-16. Brd4-BOUND STRETCH/SUPER ENHANCER USAGE UNDERLIES SEXUAL DIMORPHISM IN GLIOBLASTOMA
Authors: Najla Kfoury, Zongtai Qi, Sumithra Sankararaman, Michael Wilkinson, Lauren Broestl, Kristopher Berrett, Jason Gertz, Robi Mitra, Joshua Rubin
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is among the most aggressive and frequent forms of adult brain cancer with a very poor survival rate despite decades of research and a myriad of clinical trials. Similar to other tumors, such as bladder and lung cancer, GBM is reported to have a higher incidence in males than females. This consistent sex difference in incidence demands understanding at a molecular level. RNA sequencing of a murine model of male and female mesenchymal glioblastoma revealed significant sex differences in gene expression. We hypothesized that sex-dependent differences in gene expression and tumorigenic phenotype are achieved through differential stretch/super enhancer (SE) usage. Genome-wide mapping of SEs with ChIP-seq for H3K27Ac and transposon “Calling Cards” for Brd4 revealed robust sex differences in SE usage that correlated with differential gene expression. The functional significance of differential SE usage was demonstrated by pharmacological (JQ1) and genetic inhibition of Brd4, which reproducibly abrogated the sex differences in SE usage, gene expression, and critical elements of the cancer phenotype, including stem-like cell frequency and in vivo tumorigenesis. These data establish for the first time that cellular sex-identity is driven by differential SE usage and accounts for critical sex differences in GBM phenotype. Increasing our knowledge of these sex-specific genetic and epigenetic mechanisms will lead to a greater understanding of cancer biology and its relationship to normal development, as well as identify novel therapeutic targets to improve outcome for all patients with GBM and potentially other cancers that exhibit substantial sex differences in incidence or outcome.
Oitava Reunião internacional do Grupo de trabalho europeio de difteria e da Rede europeia de vigilancia da difteria – Junho de 2004: è preciso melhorar o controle da difteria na Região Europeia
Authors: A De Zoysa, A Efstratiou
Journal: Eurosurveillance (2004)

O oitavo encontro internacional do Grupo de trabalho europeu sobre a difteria (ELWGD) e da Rede europeia de vigilância da difteria (DIPNET) foi co-organisado com a Sede regional para a Europa da OMS em Copenhague, Dinamarca, em junho de 2004. O artigo seguinte apresenta uma atualisacao internacional dos progressos clinicos, epidemiologicos e microbiologicos da difteria na Europa, tal como foram apresentados durante a reuniao. O conjunto destes dados mostra a necessidade de melhorar a cobertura vacinal, reforcar a vigilância e os estudos epidemiologicos para manter um controle da difteria na Regiao Europeia.
SCDT-23. VISUALIZATION OF BRAIN TUMOR BY NEAR-INFRARED FLUORESCENCE IMAGING VIA TUMOR-TARGETING NOVEL PEPTIDE IDENTIFIED BY PHAGE DISPLAY
Authors: Jongmyung Kim, Ping Huang, Jeremy Rich, James Liu
Journal: Neuro-Oncology (2017)

One of the most promising strategies to treat cancer is the specific delivery of theranostic reagents to tumor-initiating and chemoradiation-resistant cell populations for early diagnosis and eradication of tumor cells with minimizing toxicity to normal tissues. Glioblastoma stem cells (GSCs) have earned a great deal of focus due to their pivotal role in tumorigenesis and therapeutic resistance. To further develop strategies to more specifically detect and target this subpopulation of tumor cells, we employed a phage display (PhD) biopanning against GSCs to isolate tumor-homing peptides. In vitro and in vivo screening on GSCs isolated from patient GBM tumors with PhD library of 7-amino acid-length peptides recovered a consensus peptide, GBMIC2, which demonstrated strong GSC-specific affinity. To achieve efficient signal penetration through skull bone and reduce autofluorescence in biological tissues during in vivo imaging, we utilized near-infrared fluorescence with a cyanine 5.5-conjugated synthetic peptide (GBMIC2-Cy5.5) and confirmed the specificity to GSCs by flow cytometry analysis and immunocytochemistry. This peptide was also co-localized with SOX2 in GBM patient tissues. GBMIC2-Cy5.5 was delivered to subcutaneous or intracranial GBM patient-derived xenograft models via intravenous injections. Tumor specificity and dynamics of fluorescence signals were monitored and analyzed using IVIS SpectrumCT In Vivo Imaging System for 72 hours. Signals were highly specific and constant to xenografted tumors with a low intensity from normal brain and surrounding tissues. Immunohistochemistry analysis of xenografted tumors confirmed that GBMIC2-Cy5.5 was specific for tumor cells and was localized to the perivascular niche. These data corresponded to previous results matching GBMIC2 with EYA1, a protein involved in tumor cell proliferation and migration, that also localized to perivascular niche. These studies confirm the applicability of phage display biopanning to isolate tumor tropic peptides, and that GBMIC2 has the potential to selectively target GSCs for imaging and anticancer drug delivery for GBM treatment.
TMOD-17. BRAIN TUMOR PATIENT DERIVED XENOGRAFT FROM LUNG TUMOR METASTASIS: ESTABLISHMENT AND CHARACTERIZATION
Authors: C David James, Roger Stupp, Rimas V Lukas, John A Kalapurakal, Batula Akhtar-Zaidi, Craig M Horbinski
Journal: Neuro-Oncology (2017)

Metastatic cancers to the brain far outnumber those that arise in the brain, yet preclinical models to study such tumors are relatively uncommon. In order to address this deficiency, we are creating a series of novel patient-derived xenografts (PDX) from common metastatic brain cancers. Here, we describe the development, luciferase modification, orthotopic growth, and radio-responsiveness of a metastatic lung adenocarcinoma PDX. The tumor was taken from the brain of a 75-year old woman who had had received carboplatin, taxol, and radiotherapy for her primary lesion, which had been classified as a mucinous micropapillary adenocarcinoma. The tumor was subcutaneously engrafted in nu/nu athymic mice, with the first generation PDX used to establish intracranial PDX in the same mouse strain. Intracranial xenografts showed a remarkable preservation of the original tumor micropapillary architecture, including mucin secretion. Cells from initial subcutaneous growths were also grown in vitro, modified with lentivirus to express luciferase, and re-established as subcutaneous PDX in mice. These luciferase-modified tumors were then established as intracranial PDX, in order to characterize intracranial growth and response to radiation. Serial bioluminescence imaging revealed progressive growth of intracranial tumors in all mice. Four weeks following intracranial implantation, mice were randomized to no treatment vs. 2 Gy whole brain radiation per day, for 5 consecutive days (10 Gy total). Radiotherapy significantly reduced tumor growth rate and extended the survival of engrafted mice (p < 0.05: median survival control/untreated mice = 69 days; median survival for mice receiving RT not yet reached). Whole exome sequencing and RNA-Seq of this PDX are underway, including comparison with the original metastatic tumor exome and mRNA profile. We will use the molecular results to test targeted therapeutics, and to compare PDX response to treatment when established intracranially vs. response when established in primary organ site.
Evoluzione della resistenza agli antibiotici delle salmonelle non tifoidee in Grecia negli anni 1990-97
Authors: E N Velonakis, A Markogiannakis, L Kondili, E Varjioti, Z Mahera, N Vakalis, E Dedouli, A Karaitianou, K Bethimouti
Journal: Eurosurveillance (2001)

E' stata testata la suscettibilita a 15 antibiotici di 1548 ceppi non tifoidei di salmonella isolati in Grecia tra il 1990 e il 1997. La prevalenza totale di resistenza sia della Salmonella enterica sierotipo Enteritidis sia della Salmonella enterica sierotipo Typhimurium e aumentata durante i primi anni dello studio. E' stata osservata una diminuzione dal 1996, specialmente della S. Enteritidis, che ha mostrato la resistenza agli antibiotici piu alta. S. Typhimurium e risultato il sierotipo con la maggiore multiresistenza agli antibiotici. Gli altri sierotipi mostravano una prevalenza di resistenza molto bassa rispetto ai sierotipi Enteritidis e Typhimurium.
Infecciones nosocomiales en hospitales universitarios de Letonia, Lituania y Suecia : un protocolo sencillo para un control de calidad
Authors: J Struwe, U Dumpis, J Gulbinovic, Å Lagergren, U Bergman
Journal: Eurosurveillance (2006)

La vigilancia de las infecciones nosocomiales es un parametro de buenas practicas clinicas demasiado descuidado en las instituciones sanitarias, debido al trabajo que implica cuando no existe un sistema informatico adecuado. El objetivo de este estudio fue evaluar si se podia utilizar un protocolo sencillo para estimar la carga de las infecciones nosocomiales y si dicho protocolo pudiera ser la base de un sistema de vigilancia a largo plazo. Esa evaluacion se llevo a cabo en tres centros hospitalarios universitarios, en Huddinge en Suecia, Riga en Letonia y Vilnius en Lituania. 
Se analizaron los registros medicos de todos los pacientes tratados con antibioticos de acuerdo a un protocolo estandardizado, segun las indicaciones para el tratamiento y la frecuencia de las infecciones nosocomiales obtenidas de una encuesta de prevalencia. Solamente se incluyeron las especialidades comparables.
La proporcion de pacientes tratados por antibioticos (excepto las profilaxis) fue de 63/280 (22 %) en Huddinge, 73/649 (11 %) en Riga y de 99/682 (15 %) en Vilnius. La proporcion de pacientes hospitalizados tratados por una infeccion nosocomial fue del 15%, 3% y 4%, respectivamente (en los dos casos, Huddinge comparado con los otros centros, pl0,001). Las infecciones en la herida quirurgica fueron las mas frecuentes, seguidas por las infecciones sucedidas mas de dos dias despues de la hospitalizacion, en ausencia de otro factor de riesgo. 
Nuestro metodo sencillo y barato mostro que las infecciones nosocomiales son un problema importante en los pacientes hospitalizados en Huddinge. Los resultados obtenidos pueden servir para una discusion posterior y para un seguimiento a nivel local. La comparacion de los resultados entre los centros es mucho menos relevante que todo el proceso que acompano a este estudio.
P1.05-008 A Comparison of the Imaging Features of Early Stage Primary Lung Cancer in Patients Treated with Surgery, SABR and Microwave Ablation
Authors: A. Talwar, N. Jenko, J. Willaime, S. Ather, W. Hickes, L. Pickup, N. Rahman, T. Kadir, F. Gleeson
Journal: Journal of Thoracic Oncology (2017)
P1.02-045 PIK3CA Mutations in Chinese Patients with Non-Small-Cell Lung Cancer
Authors: B. Wu, C. Xu, W. Wang, X. Zheng, W. Zhuang, Z. Song, G. Lin, X. Chen, R. Chen, Y. Guan, X. Yi, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
Survival of metastatic colorectal cancer patients at Candiolo Cancer Institute
Authors: E. Fenocchio, F. Colombi, M.G. Calella, R. Filippi, I. Depetris, G. Chilà, P. Lombardi, D. Marino, C. Cagnazzo, R. Ferraris, M. Aglietta, F. Leone
Journal: Annals of Oncology (2017)
PALL-10. INCREASED FATIGUE ASSOCIATED WITH TUMOR PROGRESSION IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) PATIENTS
Authors: Katherine B Peters, Mary Lou Affronti, Stevie Threatt, Patrick Healy, James E Herndon, Eric S Lipp, Sujata Panta, Dina Randazzo, Henry S Friedman, Annick Desjardins
Journal: Neuro-Oncology (2017)

Fatigue is one of the most common symptoms experienced by patients with GBM. Whether it is associated with disease or treatment, we have shown in previous studies that fatigue is an independent prognostic factor for survival, and more fatigue is associated with a poorer overall survival. The association between tumor progression and fatigue in newly diagnosed GBM patients was explored within a clinical study investigating the use of bevacizumab (BV) with concurrent chemoradiation, followed by BV and temozolomide with the continuation of BV following progression. In this prospective single-center study, fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at time of study enrollment (before chemoradiation), after chemoradiation, and then every 6 mos until study discontinuation or subject demise. Higher scores on the FACIT-F indicate less reported fatigue. 68 newly diagnosed GBM patients were enrolled with a mean age of 55.4 yrs (sd=10.7 yrs). KPS ranged 70-100 with the following distribution: 70 (n=4), 80 (n=28), 90 (n=34), and 100 (n=2). Subjects who continued study participation 6 mos after the completion of chemoradiation were divided into two groups: subjects with (n=15) and without (n=35) tumor progression 6 mos after chemoradiation completion. Both groups had similar FACIT-F scores at baseline (group with progression mean=38.33 (sd=10.91) and group without progression mean=38.48 (sd=9.30)). Fatigue increased in subjects that had tumor progression to mean=33.60 (sd=11.94) and remained relatively stable in subjects that did not progress with mean=39.05 (sd=9.77). These findings suggest that newly diagnosed GBM patients with similar levels of baseline fatigue will experience increased fatigue when tumor progression occurs. With the association of fatigue levels and survival, more research is needed to combat fatigue and deleterious effects of this symptom on morbidity and mortality in GBM patients.
Voluntarily Stopping Eating and Drinking Among Patients With Serious Advanced Illness—Clinical, Ethical, and Legal Aspects
Authors: Timothy E. Quill, Linda Ganzini, Robert D. Truog, Thaddeus Mason Pope
Journal: JAMA Internal Medicine (2017)

Patients with advanced illnesses sometimes request that physicians help hasten their death. Increasingly in North America and Europe, legal options allow physicians to perform this role. Among death-hastening options, the spotlight has been on physician-assisted death. However, voluntarily stopping eating and drinking (VSED) is also a course that patients may choose. Although VSED theoretically does not require physician involvement, clinician participation is critical in terms of initial assessment and ongoing management. In this review, we examine both clinical issues in assessing patients who are considering VSED and the clinical challenges that may emerge during VSED. We also explore some of the underlying ethical and legal considerations for physicians who either care for or decline to care for these patients. Physicians who care for seriously ill patients should be prepared to respond to patients' requests to participate in VSED.
P2.02-027 Are Inflammatory Markers Predictive of Nivolumab Efficacy in Advanced Non-Small-Cell Lung Cancer (NSCLC)?
Authors: J. Rogado, M.D. Fenor De La Maza, V. Pacheco-Barcia, J.M. Serra, P. Toquero, B. Vera, A. Ballesteros, R. Mondéjar, O. Donnay, B. Obispo, R. Colomer, J.M. Sánchez-Torres
Journal: Journal of Thoracic Oncology (2017)