tbuckley/cabot-search huggingface dataset:
Recomendações para a profilaxia pós-exposição ao VIH após uma exposição sexual, parenteral ou outra na Europa
Authors: J Almeda, J Casabona Barbarà, B Simon, M Gérard, D Rey, V Puro, T Thomas
Journal: Eurosurveillance (2004)

A profilaxia pos-exposicao (PEP) constitui o padrao de cuidados para um trabalhador de cuidados de saude (HCW) acidentalmente exposto a uma pessoa fonte de VIH infectada (exposicao profissional), mas este nao e o caso para as exposicoes nao profissionais. As normas nacionais existentes para o tratamento de exposicoes nao profissionais a VIH na Europa sao muito poucas, ao contrario do que sucede para as exposicoes profissionais. 
A administracao da profilaxia pos-exposicao nao profissional (NONOPEP) ao VIH pode ser justificada por: uma plausibilidade biologica, a eficacia da PEP em estudos efectuados no animal e exposicoes profissionais no homem, eficacia na prevencao da transmissao mae-filho do VIH e estudos de custo-eficacia. Estas evidencias, o risco semelhante de transmissao do VIH de algumas exposicoes nao profissionais e profissionais e as informacoes contraditorias sobre atitudes e praticas entre medicos no âmbito da NONOPEP conduziram a proposta destas recomendacoes europeias.
Os membros participantes no projeto europeu sobre VIH NONOPEP, financiado pela Comissao Europeia e reconhecidos como peritos na transmissao e prevencao de agentes patogenicos transmitidos pelo sangue, reuniram-se de Dezembro de 2000 a Dezembro de 2002 em tres encontros formais e num seminario de dois dias de duracao, para uma revisao da literatura sobre avaliacao da exposicao ao risco e desenvolvimento de recomendacoes europeias para a administracao de VIH NONOPEP.
NONOPEP esta recomendada em casos de sexo anal receptivo nao protegido e troca de agulhas ou seringas quando o individuo fonte for conhecido como positivo para o VIH ou pertencer a um grupo da populacao com prevalencia elevada de infeccao por VIH. Pode ser utilizada como PEP qualquer combinacao de farmacos disponiveis para o tratamento de doentes infectados pelo VIH, sendo preferiveis os regimes mais simples e menos toxicos. PEP deve ser administrado no prazo de 72 horas depois do momento da exposicao, iniciado logo que possivel e com uma duracao de quatro semanas. Todos os doentes devem ser periodicamente sujeitos a avaliacao medica, incluindo a realizacao de exames de anticorpos contra o VIH, monitorizacao da toxicidade dos farmacos e aconselhamento, durante pelo menos 6 meses depois da exposicao.
NONOPEP parece constituir uma pratica clinica exequivel e frequente na Europa. As recomendacoes para a sua administracao foram obtidas mediante consenso, mas algumas permanecem controversas e devem ser actualizadas periodicamente. NONOPEP nunca deve ser considerada como uma estrategia de prevencao primaria e a decisao final de prescricao deve ser feita com base na relacao medico-doente. Finalmente, sera util a implementacao de um sistema de vigilância para estes casos, que vise monitorizar as praticas de NONOPEP na Europa.
EXTH-17. MEK KINASE INHIBITOR, TRAMETINIB, SUPPRESSES MACROPHAGE-SECRETED TNF-α ON ONCOLYTIC HSV-1 THERAPY, ENHANCING VIROTHERAPY
Authors: Ji Young Yoo, Tae Jin Lee, Joseph Liu, Alena Cristina Jaime-Ramirez, Alexander Weiss, Luke Russell, Tejaswini Nallanagulagari, Jianying Zhang, Balveen Kaur
Journal: Neuro-Oncology (2017)

Oncolytic herpes simplex viruse-1 (oHSV) therapy is currently FDA-approved for advanced melanoma and is currently being evaluated in several clinical trials. However, its clinical success has been limited and various combinatorial treatment modalities are being investigated to enhance the efficacy of each treatment. Microglia/macrophage-secreted TNFα reduces oHSV replication through the induction of apoptosis in oHSV-infected tumor cells. In this study, we tested the potential role of trametinib, a highly potent MAPK/ERK kinase (MEK) inhibitor, against oHSV-induced TNFα response in macrophage/microglia, and analyzed the underlying mechanisms. In vitro co-culture assays of infected glioma cells with microglia/macrophage cells treated with/without trametinib (100nM) were used to test the effect of trametinib effect on oHSV replication. Q-PCR and ELISA for TNFα were used to test trametinib-mediated TNFα gene expression and protein secretion. Bone marrow derived primary macrophages from wild-type and TNFα-knockout mice were used to evaluate the biologic effects of TNFα on virus replication. Western Blot analysis was used to evaluate the induction of apoptosis. Bioluminescence mice imaging were used to measure changes in virus replication in vivo. Intracranial tumor xenografts were utilized to evaluate anti-tumor efficacy. Trametinib resulted in a significant dose dependent reduction of TNFα gene expression and protein secretion in microglia (BV2) or macrophage (Raw264.7) cells. A significant reduction of microglia/macrophage derived TNFα (gene expression and protein secretion) was also observed in response to oHSV-infected glioma cells in vitro and in vivo, resulting in increased oHSV replication. Furthermore, trametinib treated BV2 or Raw264.7 cells significantly inhibited BV2-/Raw264.7-mediated apoptotic cell death in the oHSV-infected glioma cells. Finally, combination treatment with trametinib and oHSV significantly enhanced murine survival. This study provides strong evidence to combine MEK inhibitor and oHSV, which significantly enhance survival in mice bearing intracranial glioma, leading to future clinical testing of oHSV with trametinib in patients.
Woman in minimally conscious state should be allowed to die, says judge after hearing evidence from family
Authors: Clare Dyer
Journal: BMJ (2017)

A 72 year old woman in a minimally conscious state who was kept alive by artificial feeding would have found her situation “not only intolerable but humiliating” and it would be in her best interests to withdraw feeding, a High Court judge has said.1

“Mrs P” was being fed through a nasogastric tube, which she had pulled out around 50 times, after suffering a subarachnoid haemorrhage following a fall a year ago. Salford Royal NHS Foundation Trust applied to the Court of Protection for a ruling that continuing the feeding was in her best interests, although her daughter, “Q,” opposed it.

The official solicitor, representing Mrs P, originally took a neutral stance. But by the end of the hearing, after several family members had given evidence, he accepted …
DDIS-18. TARGETING DIPGs THROUGH SUPER-ACTIVATION OF STEROID RECEPTOR CO-ACTIVATOR: AN IN VIVO STUDY IN PATIENT-DERIVED INTRA-BRAIN STEM XENOGRAFT MOUSE MODELS
Authors: Yuchen Du, Lin Qi, Mari Kogiso, Frank Braun, Huiyuan Zhang, Holly Lindsay, Sibo Zhao, Sarah Injac, Bert O’Malley, David M Lonard, Xiao-Nan Li
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine glioma (DIPG) is the most lethal childhood cancer. The oncogenic steroid receptor co-activator proteins (SRCs) are over-expressed in cancer cells, favoring of tumor growth and progression. By over-stimulating SRCs, MCB-613 leads to tumor cells death while remains minimal disturbance of normal cell homeostasis. Ionizing radiation is the current standard treatment to DIPG. We aimed to determine if combining ionizing radiation with MCB-613 would lead to significantly improved therapeutic efficacy. We developed a novel panel of orthotopixenograft mouse models of DIPG in the brain stems from biopsy or autopsied tumor tissues. Cell killing assay under MCB-613 (from 0.125uM to 8uM) treatment followed by systematic examination of animal survival time in intra-brain stem PDOX tumors treated by MCB-613 alone (15mg/kg) or in combination with fractionated radiation (10Gy) were conducted. In vitro studies demonstrated that this drug had strong anti-tumor effects against DIPGs on CHLA07, A0417, 0406, 0708DIPG and 2373DIPG cells, the last exhibited the most responsivenenss to MCB-613 at 2uM. When administered i.p. in PDOX model of 2373DIPG, however, there was no statistically significant difference in animal survival between either MCB-613 or irradition-treated and untreated xenografts. However, when combined with irradiation the longer survival was note significantly (median time: 82 days vs 66 days). 4 survivors (167 days) from combination group (10 mice/group) are still active to the present. Combining ionizing radiation with the MCB-613 leads to enhanced tumor cell killing in vitro and significantly improved therapeutic efficacy in patient tumor-derived orthotopic xenograft (PDOX) mouse models of diffuse intrinsic pontine glioma (DIPG). This study will provide critical insight about the use of SRCs as predicative marker of MCB-613 responsiveness. In future, we plan to investigate drug resistance mechanisms of MCB-613 in vivo in DIPG xenograft tumors.
Trump’s promises on opioids not backed by funds
Authors: Owen Dyer
Journal: BMJ (2017)

Two weeks after President Donald Trump declared the US opioid epidemic a national public health emergency,1 and nearly a week after his special commission on combating drug addiction released 56 recommendations on ways to tackle the crisis, there are few signs that money will be forthcoming to turn words into action.

Most experts and advocates have praised the commission’s recommendations, which included better pain management training for doctors, use of less punitive drug courts that swap treatment for incarceration, an advertising campaign that draws on research to find a more effective message than “just say no,” and a focus on stopping imports of deadly fentanyl.2

But neither Trump nor the commission’s head, New Jersey governor Chris Christie, put a figure on the funding that would be needed to enact these measures and to reduce the toll of deaths from overdose, which is …
A retrospective analysis of patients (pts) with non-small-cell lung cancer (NSCLC) with uncommon or complex epidermal growth factor receptor (EGFR) mutations treated with tyrosine kinase inhibitors (EGFR-TKIs): clinical features and outcome
Authors: I. Stasi, A. Farnesi, E. Vasile, I. Petrini, M. Luccchesi, C. Lupi, E. Sensi, R. Giannini, L. Fornaro, C. Caparello, G. Pasquini, G. Puppo, C. Finale, M. Barletta, A. Chella, G. Allegrini, A. Falcone, G. Fontanini
Journal: Annals of Oncology (2017)
El impacto de las olas de calor del verano de 2003 sobre la mortalidad en cuatro ciudades italianas
Authors: P Michelozzi, F de Donato, L Bisanti, A Russo, E Cadum, M DeMaria, M D'Ovidio, G Costa, C. A. Perucci
Journal: Eurosurveillance (2005)

Este informe evalua el impacto de la ola de calor de 2003 sobre la tasa de mortalidad especifica por causa y el papel de las caracteristicas demograficas y de las condiciones socioeconomicas capaces de haber aumentado el riesgo de mortalidad en cuatro ciudades italianas: Bolonia, Milan, Roma y Turin. 
Se realizo un recuento diario de la mortalidad para la poblacion permanente por edad, sexo y causa de muerte. La diferencia entre el numero observado y el numero medio ajustado de defunciones sirvio para calcular el exceso diario de mortalidad. El impacto del calor sobre la salud se midio en terminos de temperatura maxima aparente. 
El exceso de mortalidad mas importante fue observado en el noroeste de Italia, siendo superior al 23% en Turin y Milan. Las personas mayores (75-84 anos) y los ancianos de mas de 85 anos fueron los grupos de edad mas afectados, y la estratificacion por sexo mostro un aumento de la mortalidad superior en las mujeres. En Roma, el exceso de mortalidad mas alto, superior al 17,8%, afecto a los mas pobres, y en Turin a las personas con niveles de educacion mas bajos (mas del 43%). 
El analisis de la tasa de mortalidad por causa confirma los resultados de estudios previos sobre el aumento de la mortalidad asociada al calor en enfermedades respiratorias y cardiovasculares, y tambien muestra un exceso de mortalidad significativo en casos de enfermedades del sistema nervioso central y de trastornos metabolico/endocrinos. 
Los resultados de 2003 subrayan la necesidad de dirigirse en los futuros programas de prevencion a estos grupos susceptibles identificados. La implementacion de sistemas de alerta junto a programas de prevencion eficaces y la monitorizacion de la mortalidad durante las olas de calor pueden representar un instrumento util para la disminucion del numero de defunciones asociadas al calor.
P1.05-002 Characteristics and Prognosis of Ground Glass Opacity Predominant Primary Lung Cancer Larger Than 3.0 Cm on Thin-Section Computed Tomography
Authors: S. Suzuki, H. Sakurai, K. Masai, K. Asakura, K. Nakagawa, N. Motoi, S. Watanabe
Journal: Journal of Thoracic Oncology (2017)
OA 03.01 Prevalence of Autoimmune Diseases in Thymic Epithelial Tumors (TET) Insights from RYTHMIC
Authors: M. Boucher, E. Dansin, M. Kerjouan, J. Mazieres, E. Pichon, F. Thillays, G. Massard, X. Quantin, O. Youssef, V. Westeel, L. Thiberville, C. Clement-Duchene, F. Morin, P. Thomas, N. Girard, B. Besse
Journal: Journal of Thoracic Oncology (2017)
P1.04-007 Rovalpituzumab Tesirine Maintenance Therapy Following 1st Line Platinum-Based Chemotherapy Small Cell Lung Cancer
Authors: P. Komarnitsky, H. Lee, M. Shah, S. Wong, S. Gauthier, J. Dziubinski, S. Osbaugh, F. Zhang
Journal: Journal of Thoracic Oncology (2017)
Les maladies rares méritent l’attention
Authors: S Salmaso
Journal: Eurosurveillance (1999)

En aout dernier, Eurosurveillance publiait deux rapports sur des epidemies de trichinellose survenues en 1998 en France et en Italie, et associees a la viande de cheval importee de Yougoslavie. Ce numero publie les resultats de l’investigation d’une troisieme epidemie analogue aux precedentes, et est par ailleurs consacre au botulisme. Les articles sur ces deux maladies montrent la capacite des aliments, en tant que source de dissemination de maladies rares, mais graves.
Abstract 20629: Long-Term Outcomes Disparities in Survivors of Cardiac Arrest
Authors: Patrick J Coppler, Jonathan Elmer, Jon C Rittenberger, Clifton W Callaway, David J Wallace
Journal: Circulation (2017)

Introduction:  Sex, race and socioeconomic status may affect long-term mortality after cardiac arrest (CA). It is unknown if this is mediated by differential access to cardiac catheterization (cath), implanted cardioverter-defibrillator (ICD) placement, and/or geographic proximity to care.   Hypothesis:  1) Female sex, black race and residence in a low income neighborhood independently predict reduced odds of undergoing cath and ICD placement after CA. 2) These demographics predict worse long-term survival. 3) The protective effects of cath and ICD differs across demographics.   Methods:  We included CA patients surviving to hospital discharge at five hospitals in Pennsylvania from 2005 to 2013, with follow-up through 2014. We obtained sex, race, arrest location, initial rhythm, median ZIP code income, post-arrest illness severity, cath, ICD placement, urban residence and drive time from residence to the nearest acute care hospital. We used logistic regression to test if demographic features predict ICD and cath, and Cox proportional hazard models identify predictors of survival.   Results:  We included 891 patients followed for 2,081 patient-yrs. There were 340 deaths with median survival 6 yrs. Female sex, black race and low income were independently associated with reduced odds of cath after controlling for rhythm, arrest location and illness severity. Black race and residence >30 minutes from a hospital predicted worse survival (black race hazards ratio (HR) 1.16; 95%CI 1.02 - 1.31), residence HR 1.50; 95%CI 1.15 - 2.59). In adjusted models, female sex predicted better survival (adjusted HR (aHR) 0.83; 95%CI 0.75 - 0.91) whereas residing >30 minutes from a hospital predicted worse survival (aHR 1.86; 95%CI 1.15 - 3.00). The protective effects of cath and ICD were lower in poor and female subjects, respectively.   Conclusions:  Race, proximity to hospital and sex predict long-term outcome after CA. Female and low-income subjects benefited less from ICD and cath.
Country Immunization Information System Assessments — Kenya, 2015 and Ghana, 2016
Authors: Colleen Scott, Kristie E. N. Clarke, Jan Grevendonk, Samantha B. Dolan, Hussein Osman Ahmed, Peter Kamau, Peter Aswani Ademba, Lynda Osadebe, George Bonsu, Joseph Opare, Stanley Diamenu, Gregory Amenuvegbe, Pamela Quaye, Fred Osei-Sarpong, Francis Abotsi, Joseph Dwomor Ankrah, Adam MacNeil
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The collection, analysis, and use of data to measure and improve immunization program performance are priorities for the World Health Organization (WHO), global partners, and national immunization programs (NIPs). High quality data are essential for evidence-based decision-making to support successful NIPs. Consistent recording and reporting practices, optimal access to and use of health information systems, and rigorous interpretation and use of data for decision-making are characteristics of high-quality immunization information systems. In 2015 and 2016, immunization information system assessments (IISAs) were conducted in Kenya and Ghana using a new WHO and CDC assessment methodology designed to identify root causes of immunization data quality problems and facilitate development of plans for improvement. Data quality challenges common to both countries included low confidence in facility-level target population data (Kenya = 50%, Ghana = 53%) and poor data concordance between child registers and facility tally sheets (Kenya = 0%, Ghana = 3%). In Kenya, systemic challenges included limited supportive supervision and lack of resources to access electronic reporting systems; in Ghana, challenges included a poorly defined subdistrict administrative level. Data quality improvement plans (DQIPs) based on assessment findings are being implemented in both countries. IISAs can help countries identify and address root causes of poor immunization data to provide a stronger evidence base for future investments in immunization programs.
MA 15.11 CCNE1, PTGS2, TGFA and WISP2 Predict Benefit from Bevacizumab and Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer (SAKK19/09)
Authors: S. Rothschild, M. Amrein, C. Riether, O. Gautschi, N. Schuster, Q. Li, S. Savic, M. Schneider, C. Biaggi, L. Bubendorf, M. Brutsche, A. Zippelius, T. Zander, D. Betticher, M. Früh, R. Stahel, R. Cathomas, D. Rauch, M. Pless, A. Ochsenbein, R. Jaggi
Journal: Journal of Thoracic Oncology (2017)
Il controllo della rosolia in Francia
Authors: D Lévy-Bruhl, C Six, I Parent du Châtelet
Journal: Eurosurveillance (2004)

L'introduzione nel 1983 della vaccinazione contro la rosolia nel calendario vaccinale francese ha portato a una drastica riduzione dell'incidenza delle infezioni da rosolia durante la gravidanza e della sindrome da rosolia congenita. Questa riduzione e attestata dai dati della sorveglianza realizzata dall'insieme dei laboratori diagnostici che eseguono la ricerca dell'IgM anti-rosolia. Tuttavia, l'insufficiente copertura vaccinale nei bambini e nelle donne in eta fertile porta rispettivamente a mantenere la circolazione del virus e alla comparsa, ogni anno, di diverse dozzine di infezioni durante la gravidanza. Bisogna proseguire nell'impegno recentemente intrapreso di migliorare la copertura vaccinale se si vogliono prevenire le epidemie dovute ai significativi livelli di suscettibilita nelle giovani donne.
Thrombin generation for prediction of early cancer recurrence in breast cancer patients undergoing post-surgical adjuvant therapy: data from the prospective HYPERCAN study
Authors: C. Giaccherini, C. Verzeroli, M. Marchetti, G. Masci, L. Celio, B. Merelli, R. Sarmiento, S. Brevi, S. Gamba, V. Milesi, D. Raffaeli, L. Russo, C.J. Tartari, P. Malighetti, D. Spinelli, F. De Braud, R. Labianca, G. Gasparini, A. Santoro, A. Falanga
Journal: Annals of Oncology (2017)
DRES-09. THERAPEUTIC TARGETING OF CLK2 AND PI3K/mTOR IN GLIOBLASTOMA STEM CELLS
Authors: Soon Young Park, Jianwen Dong, Emmanuel Martinez-Ledesma, Yuji Piao, Roel Verhaak, Veerakumar Balasubramaniyan, John de Groot
Journal: Neuro-Oncology (2017)

Key signaling genes of the PI3K pathway are mutated in a large proportion of human glioblastoma (GBM), leading to persistent activation of the pathway. To determine the efficacy of inhibiting multiple components or the RTK/PI3K pathway, we examined GSK2126458 (PI3K/mTOR inhibitor) in a panel of glioma stem cell (GSC) lines. GSK2126458, a dual phophoinositide 3-kinase/mammalian target of rapamycin, had the lowest IC50 values in all of the GSCs with an IC50 below 0.5 μM. We confirmed the efficacy of these inhibitors in two orthotopic xenograft models of glioma. GSK2126458 prolonged survival in GSC272 implanted mice but not in the resistant line GSC7-2. Dual targeting of CLK2 and PI3K was pursued to overcome heterogeneity-related resistance from multiple signaling pathways. The survival of mice orthotopically implanted with CLK2 knockdown cells was significantly prolonged compared to mice implanted with GSC272 and GSC7-2-shRNA control cells. No significant prolongation in survival was observed with CLK2 knockdown combined with GSK212468 but tumor volumes were significantly decreased in the CLK2 knockdown plus drug combination groups with GSK212468 compared to drug treatment alone. Our findings suggest that the combination of CLK2 knockdown with PI3K/mTOR inhibitor may provide an effective therapeutic approach for glioblastoma.
PATH-27. A RAPID COLORIMETRIC PEPTIDE NUCLEIC ACID LOOP-MEDIATED ISOTHERMAL AMPLIFICATION METHOD FOR THE DETECTION OF THE IDH1 MUTATION IN GLIOBLASTOMA
Authors: Edward Raack, Matthew Jennings, Robert Belton, Johnathan Lawrence, Christopher McMahon, Robert Winn, Paul Mann
Journal: Neuro-Oncology (2017)

The IDH1 mutation is an important diagnostic and prognostic biomarker used to characterize glioblastoma (GBM). Patients harboring the IDH1 mutation have improved overall survival following maximal resection. Knowledge of the IDH1 mutation status allows the surgeon to modify the surgical plan; however, no existing molecular test can provide this information intraoperatively. We designed a novel colorimetric peptide nucleic acid loop-mediated isothermal amplification (PNA-LAMP) method that rapidly detects the IDH1 R132H mutation in GBM. PNA-LAMP amplifies target DNA under isothermal conditions with high specificity and speed. The PNA prevents amplification of wild-type IDH1 DNA, while amplifying the R132H variant if present. We used a pH-sensitive colorimetric detection method to allow visual determination of amplification, eliminating the need for specialized instrumentation. Initial characterization of the assay was performed with plasmid DNA containing the wild-type and R132H variant sequences. Initially, we were able to amplify exon four of the IDH1 gene in both genomic DNA and whole cell lysates using the conventional LAMP method. However, when LAMP was applied to plasmid DNA containing the R132H variant, it could not differentiate between wild-type and mutant. The inclusion of the PNA prevented amplification of wild-type while allowing amplification of the R132H variant. This assay allowed for the visual detection of the mutant sequence in under one hour. Amplification was confirmed using agarose electrophoresis, and this analysis suggests that sensitivity of the visual detection method can be improved up to six-fold. This novel molecular assay is a simple, specific, and rapid way to identify the presence of the IDH1 R132H variant associated with GBM. Our current efforts are focused to develop this assay for intraoperative diagnostics.
Populations vulnérables : les leçons de la canicule de l’été 2003 en Europe
Authors: G Brücker
Journal: Eurosurveillance (2005)

Quelle lecon devons-nous tirer de la vague de chaleur, exceptionnelle par sa severite et sa duree, que l’Europe a connu en 2003 ? Tout d’abord que ces vagues de chaleur peuvent etre responsables d’un exces considerable de mortalite : certainement plus de 50 000 morts pour l’Europe en aout 2003. Les consequences ont ete probablement sous evaluees dans beaucoup de pays, tout au moins dans les premieres evaluations. Cet exces de mortalite touche des groupes vulnerables, personnes âgees et personnes malades surtout. L’identification des facteurs de risques est une tâche prioritaire pour mettre en œuvre les actions indispensables de prevention.