tbuckley/cabot-search huggingface dataset:
Abstract 2099: Pretransplant Toxoplasma Gondii Seropositivity Amongst Heart Transplant Recipients Is Associated With An Increased Risk Of All-cause And Cardiac Mortality
Authors: Satish Arora, Pål Jenum, Pål Aukrust, Halvor Rollag, Arne Andreassen, Svein Simonsen, Einar Gude, Arnt Fiane, Odd Geiran, Lars Gullestad
Journal: Circulation (2007)

Chronic Toxoplasma gondii (T. gondii ) infection is known to trigger potentially adverse immuno-regulatory changes, but the long-term implication for heart transplant (HTx) recipients has not been assessed previously. Hence, we evaluated the risk of mortality, development of cardiac allograft vasculopathy (CAV) and acute cellular rejection amongst T. gondii seropositive HTx recipients and the four donor/recipient seropairing groups. Methods: Frozen pre-HTx serum samples of 288 recipients and 246 donors were evaluated for T. gondii serostatus using Platelia IgG immunoassay method. All patients had also undergone prospective serostatus evaluation using alternative assays and results determined by the two methods were compared. Follow-up data regarding mortality, CAV development and acute cellular rejection was available for all patients. Results: Overall, 211 (73%) recipients were seronegative and 77 (27%) were seropositive. In total, 82 recipients died, 76 developed CAV and 82 had significant cellular rejection. Recipient seropositivity was associated with a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.9; 95% CI, 1.1–3.4; p= 0.02) and CAV mortality (HR=4.4; 95% CI, 1.3–15.6, p=0.02), but was not associated with earlier CAV development or higher rejection score. Donor/recipient seropairing status was not a risk factor for any endpoint. Conclusions: T. gondii seropositivity amongst HTx recipients is associated with a significantly increased risk of long-term total, and in particular CAV-related, mortality. This may be mediated via immunoregulatory changes triggered by chronic T. gondii infection and needs to be explored further.
PATH-11. DESIGNING A DIAGNOSTIC FGFR3-TACC3 FUSION ASSAY USING RT-PCR FOR GLIOBLASTOMA MULTIFORME PATIENTS
Authors: Wendy de Leng, Anne Hoskam, Joyce van Kuik, Wim Spliet, Wim Van Hecke, Pierre Robe, Filip de Vos
Journal: Neuro-Oncology (2017)

The FGFR3-TACC3 fusion protein is a recurrent translocation in glioblastoma (GBM) patients and other types of solid malignancies, and is hypothesized to confer oncogenic transformation. Preliminary evidence of FGFR3 tyrosine kinase inhibitor (TKI) therapy has shown significant effectivity in vitro, in vivo and in phase I clinical trials, validating FGFR as a potential therapeutic target. A screening assay for the FGFR3-TACC3 translocation can thus be of great value for GBM patients, a patient population that currently lacks effective therapeutic interventions. An RT-PCR assay was designed to detect the FGFR3-TACC3 fusion gene transcripts in FFPE tissue from archival glioma samples. FGFR3 N-terminal immunostaining preselection was performed to identify potential FGFR3-TACC3 fusion positive gliomas. Out of 467 gliomas, 14 (of which13 GBM) samples showed FGFR3 overexpression. Out of these 14, 12 were available for further RT-PCR analysis, revealing 7 FGFR3-TACC3 positive cases. All 7 cases were validated on FFPE, whereas 5/7 were validated on fresh frozen material, together revealing three of the most frequently observed fusion variants; FGFR3ex17-TACC3ex11, FGFR3ex17-TACC3ex8, and FGFR3ex17-TACC3ex10. The remaining FGFR3 immunopositive but FGFR3-TACC3 negative cases were analyzed by FISH, which revealed no FGFR3 amplification. In conclusion, this study is the first to validate an FFPE tissue based RT-PCR screening method for the FGFR3-TACC3 translocation, thereby contributing to personalized cancer treatment of glioma patients.
Syndrôme respitaroire aigu sévère (SRAS)
Authors: M. S. Vilayleck
Journal: Eurosurveillance (2003)

Le syndrome respiratoire aigu severe (SRAS) est une pneumopathie apparue ces derniers mois en Asie, en Amerique du nord et en Europe. Les scientifiques ont identifie un virus inconnu appartenant a la famille des coronavirus chez les patients atteints de SRAS.
EGFR status evaluation by liquid biopsy during first-line therapy in advanced NSCLC patients
Authors: M. Pagano, F. Zanelli, C. Bonelli, B. Casali, A. Cavazza, E. Farnetti, R. Gnoni, M. Larocca, D. Nicoli, C. Pinto
Journal: Annals of Oncology (2017)
Conducta a seguir por Enter-net en la investigación de brotes internacionales de intoxicaciones alimentarias
Authors: J C Desenclos, I. S.T. Fisher, O N Gill
Journal: Eurosurveillance (1999)

A pesar de las medidas de prevencion destinadas a reducir la contaminacion microbiologica de los alimentos, la libre circulacion de personas, articulos y alimentos entre los estados de la Union Europea (UE) favorece la aparicion de brotes internacionales de infecciones transmitidos por alimentos. La implantacion de la red internacional de vigilancia Enter-net (antes Salm-Net) deberia contribuir a detectar e investigar rapidamente estos brotes internacionales (1).
Abstract 19503: An Improved Potent Direct Thrombin Inhibitor Shows Efficacy With Low Bleeding Risk
Authors: Anirban Datta, Chengpei Xu, Daniel Clemens, Subhadra Dash, Kenneth Lin, Stephenie Chang, Georg Neckermann, Elaine To, Lev Igoudin, Samuel Keutzer, Piotr Zalicki, Sivan Sizikov, Angels Estiarte, Kevin Short, Timothy Shiau, David Williams, Mohan Sivaraja, David Kita
Journal: Circulation (2017)

Introduction:  The advent of the novel oral anticoagulants (NOACs) has had a profound impact on the treatment of venous and arterial thrombotic diseases, which are major clinical concerns with high prevalence and often fatal outcome. While the NOACs offer advantages such as more convenient dosing regimens, more predictable anticoagulant responses, and less frequent monitoring than the traditional options warfarin and heparins, their bleeding liability remains high.   Methods and Results:  We have developed a novel class of highly selective oral direct thrombin inhibitors that show significantly lower bleeding compared to the NOACs in preclinical testing. Previously, we presented data for an advanced lead compound, VE-1902. Here we will present VE-2851, another lead compound with good liver microsome and plasma stability, improved pharmacokinetic profile in rats, and better combined  in vitro  and  in vivo  activity. In contrast to the NOACs, VE-2851, like VE-1902, is preferentially excreted through the feces. In rodent models of venous stasis and arteriovenous shunt thrombosis, VE-2851 demonstrated efficacy comparable to the NOACs, and it is 5x more potent than VE-1902. Despite its strong anticoagulant properties, VE-2851 showed >15x lower blood cell loss relative to apixaban in a rodent tail bleeding time test and less extension of the bleeding time compared to the NOACs. This distinctive bleeding profile is associated with an approx. 200-fold reduced potency in inhibiting thrombin-mediated platelet activation  in vitro  compared to other direct thrombin inhibitors, while VE-2851 inhibits fibrinogen cleavage, TAFI activation, and protein C activation with similar potency to the NOACs.  In vivo , VE-2851 also shows >5x higher maximum platelet activation in the arteriovenous shunt thrombosis model compared to apixaban.   Conclusions:  The ability of VE-2851 to prevent thrombosis while preserving hemostasis could lead to a new anticoagulant therapy with lower bleeding risk when administered either as a monotherapy or as dual or triple therapy with antiplatelet agents. In addition, a favorable excretion profile with low renal clearance could provide benefits for patients with impaired kidney function.
Evidence-based framework for a pathomechanical model of patellofemoral pain: 2017 patellofemoral pain consensus statement from the 4th International Patellofemoral Pain Research Retreat, Manchester, UK: part 3
Authors: Christopher M Powers, Erik Witvrouw, Irene S Davis, Kay M Crossley
Journal: British Journal of Sports Medicine (2017)

The aetiology of patellofemoral pain (PFP) is a complex interplay among various anatomical, biomechanical, psychological, social and behavioural influences. Numerous factors associated with PFP have been reported in the literature, but the interaction between these proposed risk factors and the clinical entity of PFP remains unclear (figure 1).



Figure 1 
Schematic overview of potential pathways to elevated patellofemoral joint (PFJ) stress, a proposed contributor to patellofemoral pain.



The goal of this consensus document is to place known associated factors within the context of a pathomechanical model of PFP. An underlying assumption of the proposed pathomechanical model is that PFP is associated with abnormal loading of the patellofemoral joint (elevated joint stress). In this model, abnormal loading could affect the various patellofemoral structures that can contribute to nociception (ie, subchondral bone, infrapatellar fat pad, retinaculum and ligamentous structures); however, the specific tissue sources related to PFP are not known.

The experience of PFP is not just nociception.1 Persons with persistent PFP exhibit abnormal nociceptive processing (ie, widespread mechanical hyperalgesia, impaired pain modulation),2–5 altered somatosensory processing (implying neuropathic pain),6 impaired sensorimotor function (ie, proprioception and balance)7–10 and certain psychological factors (ie, catastrophising and kinesiophobia).11 The amount and quality of research in the non-‘patho-mechanical’ pathways to PFP are evolving, and will be included in future consensus statements emanating from the International Patellofemoral Pain Research Retreats.

At the 4th International Patellofemoral Pain  Research Retreat,12 Dr Christopher Powers presented a draft framework of the pathomechanical model, which was based on prior consensus statements from the three previous Patellofemoral Pain Research Retreats.13–15 At the meeting, all attendees (clinician-researchers and research scientists) participated in a comprehensive discussion of the draft model, and agreed on the overall framework (Figure 1). Following the retreat, the authors conducted a thorough review of pertinent literature related to …
MA 18.14 Non-Small Cell Lung Cancer (NSCLC) Treatment and Survival in Scandinavia: The SCAN-LEAF Study
Authors: S. Ekman, M. Planck, O.T. Brustugun, J. Rockberg, A. Juarez-Garcia, M.Manley Daumont, H. Huang, M. Pereira, J. Svärd, M. Rosenlund, O. Chirita, L. Jørgensen, M. Sandelin, J.B. Sørensen
Journal: Journal of Thoracic Oncology (2017)
PTU-014 Development of the multi-assistant rating scale (mars) for endoscopic non-technical skills performance in independently practising endoscopists
Authors: F Kokwara, B Davies, J Cornish, N Hawkes
Journal: Gut (2017)

Introduction  Endoscopic Non-Technical Skills (ENTS) are essential to high quality endoscopy. ENTS skills are not routinely assessed in independent practitioners. Endoscopy assistants work as members of the team and observe the performance of endoscopists at close hand. A reliable, validated 360-degree assessment tool based on assistant ratings for ENTS may provide performance enhancing feedback to independent practitioners. We aimed to develop a multi-assessor rating scale (MARS) to provide a global assessment of ENTS skills for endoscopists based.  Method  The MARS tool was developed with the four main domains – Communication (COMM), Situational Awareness (SITA), Leadership (LEAD) and Judgement and Decision-making (J and DM). All domains were based on previously validated questionnaire formats tested for factor and item analysis and construct validity with a standardised 7-point scoring scale and 10 items per domain. Experienced endoscopy nurses working regularly with the endoscopists provided a score reflecting their overall performance for each domain question. The internal reliability of the MARS items was assessed using the standardised Cronbach’s alpha statistic. Inter-rater reliability was assessed by calculation of Kappa alpha. Consent was obtained from all endoscopists prior to administering the MARS tool.  Results  9 endoscopists agreed to undergo an assessment of ENTS using the MARS tool. Each was assessed by 10 nurse raters (90 assessments, based on 40 item scores). The mean scores for each item within the 4 domains were calculated for each endoscopist. Cronbach’s alpha co-efficient showed a high level of reliability in each of the 4 questionnaire domains – COMM=0.98, SITA=0.86, Lead=0.97, J&DM=0.98. A performance threshold of 90% each domain was set as a nominal standard. Kappa statistics measuring inter-rater reliability in distinguishing between scores meeting or below this performance threshold for all rater combinations showed moderate to excellent agreement (range 0.54 to 0.8). The MARS tool was practical to administer, all ratings were obtained during a single afternoon. Results were expressed graphically as percentage acceptable ratings in each ENTS domain. Where 20% or more of specific questionnaire item scores were scored as poor or average each was highlighted in the more detailed feedback report given to the endoscopist.  Conclusion  The MARS tool is a practical way to measure of ENTS performance designed as a 360 degree feedback tool using 10 raters for administration every 6 months. The internal consistency of the questionnaire is good with acceptable inter-rater reliability. The feedback graphic enables rapid recognition of areas for improvement in ENTS domains.  Disclosure of Interest  None Declared
P1.01-060 Nivolumab after Progression to Platinum- Based Chemotherapy in Advanced Non-Small-Cell Lung Cancer (NSCLC)
Authors: M. López Flores, P. Diz Taín, I. Delgado Sillero, L. Sánchez Cousido, A. López González, M. Pedraza Lorenzo, Á. Rodríguez Sánchez, C. Castañón López, B. Nieto Mangudo, F. García Casabal, L. De Sande González, A. García Palomo
Journal: Journal of Thoracic Oncology (2017)
P3.16-052 Use of Decellularised Porcine Intestinal Submucosa Extracellular Matrix in Airway Reconstruction to Enable Lung-Sparing Oncological Surgery
Authors: M. Kim, N. Perera, S. Knight, S. Barnett, J. Gooi, S. Seevanayagam
Journal: Journal of Thoracic Oncology (2017)
MA 16.13 PD-L1 Expression Is a Prognostic Factor in Patients with Esophageal Squamous Cell Carcinoma Treated with Postoperative Adjuvant Radiotherapy
Authors: Y. Xu, C. Jiang, S. Han, H. Wu, Q. Lin, J. Hu, G. Zhang
Journal: Journal of Thoracic Oncology (2017)
SCDT-41. IN VIVO TESTING OF INTRACRANIAL DELIVERY OF RECOMBINANT HUMAN IL-12 AND IL-12Fc AND FUNCTIONAL ASSESSMENT ON HUMAN, PORCINE AND CANINE PERIPHERAL BLOOD MONONUCLEAR CELLS
Authors: Michal Beffinger, Linda Schellhammer, Stanislav Pantelyushin, Samantha K Wall, Ali Bienemann, Nicolas Granger, Thorsten Buch, Johannes vom Berg
Journal: Neuro-Oncology (2017)

Brain cancers are known to form a highly immunosuppressive microenvironment, suggesting that patients could benefit from immunomodulatory drugs. Moreover, the brain is per se an immunologically unique site with reduced cellular infiltration and antigen presentation. Multiple therapies focusing on local (re-)activation of the immune system in brain tumors are currently under development, including application of a potent activator of immune responses, interleukin (IL)-12. This cytokine stimulates the cytotoxic function of lymphocytes and can trigger rejection of glioma in preclinical studies. Even though IL-12 has a relatively short half-life, systemic IL-12 can quickly lead to severe adverse reactions. Local application or targeting to the tumor is therefore mandatory. Local IL-12 therapy is currently tested in clinical trials of intratumoral gene therapy using viral vectors. An alternative approach is the use of convection-enhanced delivery (CED). This way the IL-12 exposure can be precisely dosed by duration, concentration and volume of the infusion. Unfortunately in both methods leakage of IL-12 into the systemic circulation remains a problem, which may narrow the therapeutic window. We compared tissue retention and leakage into the systemic circulation of recombinant IL-12 and IL-12Fc. After local, intracranial application of IL-12 via bolus injection we measured residual amounts in the brain as well as in serum after 24 hours. Indeed IL-12Fc has a much lower ratio of serum to brain concentration. In order to evaluate its suitability in large animal proof of concept studies, we tested its activity on human, but also canine and porcine PBMCs. Similar as in human PBMCs IL-12Fc is able to stimulate canine and porcine PBMCs to secrete IFN-γ in a dose-dependent manner. Furthermore, stimulation with human IL-12Fc leads to phosphorylation via STAT4. We propose preclinical testing of human IL-12 in spontaneous canine brain tumors.
Programa de estudios para la formación de profesionales sanitarios en el control de enfermedades muy infecciosas
Authors: A Baka, F M Fusco, V Puro, N Vetter, P Skinhoj, K Ott, H Siikamäki, H R Brodt, R Gottschalk, P Follin, B Bannister, G De Carli, C Nisii, J Heptonstall, G Ippolito
Journal: Eurosurveillance (2007)

La epidemia del sindrome respiratorio agudo grave (SARS), la amenaza del terrorismo biologico y los recientes ejemplos de enfermedades muy infecciosas (EMI) importadas en Europa han puesto de relieve la importancia de contar con un sistema clinico y de salud publica competente para el control de las urgencias provocadas por enfermedades infecciosas.
Combined clinical and genetic risk prediction of central nervous system subsequent neoplasms (CNS SNs) in childhood cancer survivors (CCS): A report from the COG ALTE03N1 study.
Authors: Xuexia Wang, Canlan Sun, Lindsey Hageman, Kandice Barnett, Sunil Desai, Douglas S. Hawkins, Melissa M. Hudson, Leo Mascarenhas, Joseph Philip Neglia, Kevin C. Oeffinger, Arthur Kim Ritchey, Leslie L. Robison, Doojduen Villaluna, Wendy Landier, Smita Bhatia
Journal: Journal of Clinical Oncology (2016)

10511 Background: CCS are at a 10-fold increased risk of CNS SNs. Cranial radiation (CRT) for primary cancer increases the risk; dose-risk relation with CRT is linear. The substantial burden of CNS SN-related morbidity presents an unmet need for identifying high-risk patients to guide targeted interventions. We present a risk prediction model to address this gap. Methods: CCS with CNS SNs (cases: n=82) matched to CCS without CNS SNs (controls: n=228; matched on primary cancer diagnosis (dx), year of dx, race/ethnicity and follow-up), contributed germline DNA for genotyping 43 previously published candidate genes (97 SNPs). Risk prediction models were derived sequentially: Base Model (age at primary cancer dx, gender), Clinical Model (Base Model + CRT [Y/No]), Final Model (Clinical Model + SNPs). Receiver operating characteristic analysis was used to evaluate predictive utility of Final Model in assessing CNS SN risk. Two risk groups were derived using predicted values (high risk: ≥0.1; low risk: <0.1). Results: Median age at primary cancer dx was 3.5y (cases) and 5.0y (controls); time to CNS SNs was 13.2y; 91.5% of cases and 39.5% of controls had received CRT (p<0.001). Clinical Model (area under curve [AUC] = 0.82, 95%CI: 0.8-0.9) performed better than Base Model (AUC = 0.58, 95%CI, 0.5-0.7, p=0.001). Final Model performed best when five SNPs involved in DNA repair (forward stepwise selection: rs1805389 [LIG4], rs15869 [BRCA2], rs8079544 [TP53], rs498872 [PHLDB1], rs1673041 [POLD1]) were included (AUC = 0.86, 95%CI, 0.8-0.9, p = 0.04; reference: Clinical Model). Using high vs. low risk group as risk classifier, the accuracy of the prediction model was 91.7%, with a sensitivity of 96.3% and specificity of 57%. Similar observations emerged in analyses stratified by CNS SN type (meningioma [n=46]/ glioma [n=28]) and analyses restricted to CCS with CRT. Conclusions: We have developed a combined clinical and genetic risk prediction model that accurately identifies CCS at high and low risk of CNS SNs. This model, when validated externally, could serve as a useful risk classifier to assess the risk of CNS SNs when CRT is being considered.
QLIF-27. THE ADDED VALUE OF HEALTH-RELATED QUALITY OF LIFE (HRQoL) AS A PROGNOSTIC INDICATOR OF OVERALL SURVIVAL AND PROGRESSION FREE SURVIVAL IN GLIOMA PATIENTS: A META-ANALYSIS BASED ON INDIVIDUAL PATIENT DATA FROM RANDOMIZED CONTROLLED TRIALS
Authors: Marijke Coomans, Linda Dirven, Neil Aaronson, Brigitta G Baumert, Martin van den Bent, Andrew Bottomley, Alba Brandes, Olivier Chinot, Corneel Coens, Thierry Gorlia, Ulrich Herrlinger, Florence Keime-Guibert, Annika Malmström, Francesca Martinelli, Roger Stupp, Andrea Talacchi, Wolfgang Wick, Jaap C Reijneveld, Martin J B Taphoorn
Journal: Neuro-Oncology (2017)

Health-related quality of life (HRQoL) is of major importance in patients with glioma, the most common malignant primary brain tumor in adults. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression free survival (PFS) in a large heterogeneous sample of both low and high-grade glioma patients, besides the known prognostic factors. We included individual baseline data from previously published randomized controlled trials (RCTs) in glioma patients in which HRQoL was a (secondary) endpoint, assessed with the EORTC QOL-C30 and QLQ-BN20. Multivariable cox models were used, first with sociodemographic/clinical variables only, and next with HRQoL variables added, separately for OS and PFS. C-indices were calculated to investigate the added prognostic value of HRQoL. Baseline HRQoL and sociodemographic/clinical data from eleven RCTs were included, totaling 4399 patients. After controlling for the sociodemographic/clinical variables age, sex, tumor type and stage, performance status, allocated treatment and previous resection, results showed that better cognitive functioning and less constipation and drowsiness were independently associated with a longer OS, and only better cognitive functioning with prolonged PFS. C-indexes indicated a small improvement of the model for OS and PFS when adding HRQoL to the sociodemographic/clinical prognostic variables (+1,2% for both OS and PFS). Our findings demonstrate that several baseline HRQoL variables were of individual prognostic importance for OS and PFS, yet the added value of HRQoL in comparison to the sociodemographic/clinical prognostic variables was small. Rather than baseline HRQoL data, a change in HRQoL from baseline during treatment, reflecting the impact of treatment, may be of more prognostic value and remains to be investigated.
P3.02-031 Detection of Activating EGFR Mutations and Resistant T790M Mutation from cfDNA in Malignant Pleural Effusion(MPE-DNA)
Authors: K. Lee, O.S.h. Chan, T. Mok, A. Chan, C. Lee, A. Fontela, T. Yung, V. Chan, A. Wong, K.H. Wong, S. Fung, W. Gai
Journal: Journal of Thoracic Oncology (2017)