tbuckley/cabot-search huggingface dataset:
The overview of H. pylori prevalence in patients with dyspepsia and its association with gastric adenocarcinoma at different locations.
Authors: S. Aghayeva
Journal: Annals of Oncology (2018)

Introduction: H. pylori is proved to be strongly associated with development of gastric cancer. The aim of our study is to check H. pylori in newly diagnosed patients with gastric malignancy at different parts of the stomach and to define a correlation of it with H. pylori infection. Methods: The study included 2500 patients (1133 males, 1367 females, age range 18-97) with dyspepsia who underwent upper GI endoscopy with rapid CLO-test biopsy, screened from January 2015 until June 2017. All patients were aged ≥18 years with no PPI and antibiotic use for the past month. Control group of 100 random people were evaluated for H. pylori with urea breath test. Out of 2500 patients, 126 with newly diagnosed and histologically submitted adenocarcinoma of different locations were also screened for Helicobacter pylori with rapid CLO-test obtained from antrum. Associated factors were analyzed by the chi-square and multiple logistic regression with SPSS 20.0 and dispersion analysis (ANOVA). Results: The overall prevalence of H. pylori infection in patients with dyspepsia was 87.6% (2189 patients) and 81% (81 patients) in control patient group with no symptoms. In a group of 126 patients (median age 64,5±9.8; 78 (61.9%) males and 49 (38.9%) females with newly diagnosed adenocarcinoma, in 58 (46%) the tumor was located in antrum, in 33 (26.2%) at the lesser curvature, in 13 (10.3%) at the greater curvature, in 17 (13.5%) at the cardial part and in 5 (4%) patients in the fundus. H. pylori test was positive in 52 (89.6%) of 58 patients with antral malignancy, in 29 (87.9%) of 33 patients with lesser curvature cancer, in 7 (53.8%) of 13 patients with greater curvature cancer, in 5 (29.4) of 17 patients with cardial malignancy and in 2 (40%) of 5 patients with fundus and body malignancy. Conclusion: The prevalence of H.Pylori in patients with dyspeptic symptoms is 87.6% comparing to 81% of general population. Besides age and gender predisposion, H.Pylori infection is strongly associated with the development of antral and lesser curvature adenocarcinoma comparing to cardia, fundus and greater curvature malignancy locations. (P value <0.001 in females; P value <0.007 in males).
PCLN-01. GENERATION, CHARACTERIZATION AND TREATMENT OF NOVEL MURINE MODELS FOR HUMAN PEDIATRIC GLIOMA
Authors: Britta Ismer, Itai Moshe, Dinorah Friedmann-Morvinski, David T W Jones
Journal: Neuro-Oncology (2018)

In the last few years, the extent of heterogeneity between tumors of a given class has become increasingly evident. Thus, tumors should optimally be treated differently according to their individual genetic alterations. Within the ICGC PedBrain Tumor Project, we have analyzed >150 low-grade and high-grade pediatric gliomas with whole-genome DNA and RNA sequencing, and have identified a wide variety of genetic alterations responsible for tumor growth. This includes novel point mutations, fusions and duplications in oncogenes such as NTRK2, FGFR1 and ALK. In some cases these alterations also define distinct molecular subgroups of glioma as judged by DNA methylation profiling. In order to identify new targeted therapy options for pediatric gliomas, mouse models recapitulating the human disease are required for testing of more specific inhibitors. We have therefore generated a series of novel models which are now being characterized and pre-clinically treated. Initial results with ALK or NTRK fusions show that our somatic gene transfer methods (RCAS- or in utero electroporation-based) can be used to rapidly generate new orthotopic brain tumor models, and that specific inhibitors against chosen oncogenes have a greater effect on tumor growth compared to standard therapy. The murine tumor cells can also be cultivated as neurospheres for functional testing and e.g. high-throughput screens. In addition to the basic biological understanding of tumorigenic mechanisms that can now be elucidated in more detail, we aim to rapidly translate our pre-clinical results in a manner that we hope will directly benefit patients in the clinic.
Abstract 195: Cardioprotective and Anti-inflammatory Effects of Treatment With Adenocaine/mg2+ in a Porcine Model of Endotoxemia
Authors: Asger Granfeldt, Hayley L Letson, Geoffrey P Dobson, WeiWei Shi, Jakob Vinten-Johansen, Else Tønnesen
Journal: Circulation (2013)

Introduction: The combination of adenosine + lidocaine (adenocaine) and Mg2+ (ALM) has demonstrated cardioprotective properties in models of cardiac arrest and hemorrhagic shock, and anti-neutrophil effects in vitro. This study evaluates whether ALM also demonstrates cardioprotective and anti-inflammatory properties in an endotoxemic porcine model. Methods: Pigs (37-42kg) received lipopolysaccharide (LPS) at 1 μg/kg/h for 5 hours, and were randomized to: LPS (control) (n=8) or LPS + ALM (n=8). Pigs received a bolus of ALM at start of LPS infusion followed by 4 hours of infusion. Cardiac function was evaluated using pressure-volume loops, and inflammation was assessed by plasma TNF-α and leukocyte superoxide generation. Results: Infusion of ALM maintained mean arterial pressure (MAP) at a lower level during the 4 hour infusion period (ALM: 47 ± 1.6 mmHg vs. control: 80 ± 2.9 mmHg, p&lt;0.0001). After discontinuation of ALM, MAP immediately returned to and was maintained at baseline group values (ALM: 89 ± 5 mmHg vs. control: 86 ± 3 mmHg). The slope of the end-systolic pressure-volume relationship (ESPVR) was unchanged during the experiment in both groups. However, a rightward shift of the volume axis intercept (V0) in the control group indicated decreased contractility; this shift was not observed in the ALM group (control: -0.1 ± 12 ml vs. ALM: -32.5 ± 7.6 ml, p= 0.04). Preload recruitable stroke work (PRSW), an index of overall cardiac performance, decreased in the control group (baseline: 71 ± 4: end: 37 ± 4 mmHg · ml / ml), but was preserved in the ALM group (baseline: 72 ± 5; end: 62 ± 4 mmHg · ml / ml, p&lt;0.001 between groups). Diastolic function evaluated by dP/dtmin (ALM 2221 ± 170 vs. 1793 ± 89 mmHg/sec; p=0.04) and Tau (ALM 36 ± 1.2 vs. 44 ± 2.2 msec; p=0.007) was also significantly improved in the ALM group. Peak TNF-α levels were lower in the ALM group (ALM 7653 ± 1092 vs. 11989 ±1057 pg/ml; p=0.01). While neutrophil superoxide anion release increased by 19 ± 27 % in the control group, it decreased by 74 ± 8% in the ALM group (p=0.0006). Conclusions: In this porcine model of endotoxemia, ALM improved cardiac function and reduced the inflammatory response to LPS, thereby extending the beneficial effects of ALM as reported for cardiac surgery, hemorrhagic shock and cardiac arrest.
Resuscitation Education Science: Educational Strategies to Improve Outcomes From Cardiac Arrest: A Scientific Statement From the American Heart Association
Authors: Adam Cheng, Vinay M. Nadkarni, Mary Beth Mancini, Elizabeth A. Hunt, Elizabeth H. Sinz, Raina M. Merchant, Aaron Donoghue, Jonathan P. Duff, Walter Eppich, Marc Auerbach, Blair L. Bigham, Audrey L. Blewer, Paul S. Chan, Farhan Bhanji
Journal: Circulation (2018)

The formula for survival in resuscitation describes educational efficiency and local implementation as key determinants in survival after cardiac arrest. Current educational offerings in the form of standardized online and face-to-face courses are falling short, with providers demonstrating a decay of skills over time. This translates to suboptimal clinical care and poor survival outcomes from cardiac arrest. In many institutions, guidelines taught in courses are not thoughtfully implemented in the clinical environment. A current synthesis of the evidence supporting best educational and knowledge translation strategies in resuscitation is lacking. In this American Heart Association scientific statement, we provide a review of the literature describing key elements of educational efficiency and local implementation, including mastery learning and deliberate practice, spaced practice, contextual learning, feedback and debriefing, assessment, innovative educational strategies, faculty development, and knowledge translation and implementation. For each topic, we provide suggestions for improving provider performance that may ultimately optimize patient outcomes from cardiac arrest.
First‐line mFOLFOX6 for peritoneally disseminated gastric cancer with massive ascites or inadequate oral intake
Authors: H. Osumi, D. Takahari, K. Chin, M. Ogura, T. Ichimura, T. Wakatsuki, I. Nakayama, Y. Ota, M. Suenaga, E. Shinozaki, K. Yamaguchi
Journal: Annals of Oncology (2018)

Introduction: Oral fluoropyrimidine plus platinum is a standard 1st line treatment of the advanced gastric cancer (AGC). However, it is difficult to use it for AGC patients with massive ascites or inadequate oral intake. There were a few evidences about the efficacy and safety of FOLFOX for them. This study aimed to evaluate the efficacy and safety of modified FOLFOX-6 (mFOLFOX6) regimen for patients with massive ascites or inadequate oral intake. Methods: This retrospective study was conducted at a single Japanese institute from November 2015 to December 2017. The mFOLFOX6 regimen consisted of oxaliplatin 85 mg/m2, bolus of 5-FU 400 mg/m2 and leucovorin (LV) 400 mg/m2 on the first day, followed by 2400 mg/m2 of 5- FU as a continuous infusion in 46 hours for first-line treatment. The definition of inadequate oral intake was the need for total parenteral nutrition (TPN). The massive ascites was defined as continuous ascites from the pelvic cavity to the upper abdomen. Improvement in oral intake was defined as no TPN for more than 7 days and improvement in ascites was defined as a decrease in ascites of more than one grade defined by the JCOG0106 trial. Results: Among the 364 patients with gastric cancer who received first-line therapy, a total 17 patients (4.7%, 11 males, 6 females) with a median age of 67 (29-74) were included. The median follow up time of the study was 8.8 months. Among all the patients, four patients (23.5%) had ECOG PS of 2, Two patients (11.7%) had human epidermal growth receptor 2 (HER2)-positive tumors. 16 patients had metastasis at the beginning of the treatment and only one patient had locally advanced tumors. Median number of metastatic organs was 2 (1-5). 13 (76.4%) were inadequate oral intake and 4 (23.5%) had massive ascites. The median PFS and OS were 4.8 months [95% confidence interval (CI), 1.5–7.5] and 8.8 months (95% CI, 2.3–NA), respectively. 10 of 17 patients (58.8%) had target regions and objective response rate was 50%. Objective improvement in oral intake was seen in 11 of 13 patients (84.6%). Improvement of ascites was observed in 6 of 12 patients (50%). Major grade 3 or 4 adverse events were neutropenia (35.2%), febrile neutropenia (5.8%), fatigue (5.8%), anorexia (5.8%) and infection (5.8%); no treatment-related deaths were observed. Conclusion: Our study suggests that mFOLFOX6 is feasible and has a clinical activity and regarded as a newly treatment option in AGC patients with massive ascites or inadequate oral intake.
A Novel Mutation In Bruton Tyrosine Kinase Confers Acquired Resistance To Ibrutinib (PCI-32765) In CLL
Authors: Richard R. Furman, Shuhua Cheng, Pin Lu, Menu Setty, Alexandar Perez, Ailin Guo, Joelle Racchumi, Jiao Ma, Morton Coleman, Kabaleeswaran Venkataraman, Guozhou Xu, Wei Chen, Hao Wu, Betty Y. Chang, Christina Leslie, Y. Lynn Wang
Journal: Blood (2013)
Measures of Clinical Efficacy
Authors: Barbara J. McNeil, Paul D. Varady, Belton A. Burrows, S. James Adelstein
Journal: New England Journal of Medicine (1975)

The sensitivity and specificity of the hypertensive intravenous pyelogram and the iodohippuran renogram have been determined for the diagnosis of renovascular disease, and cost-effectiveness calculations have been made for the diagnosis and surgical treatment of patients with renovascular hypertension. When the intravenous pyelogram alone is used to screen a representative hypertensive population, 78 per cent of patients with renovascular disease are located, but at the same time an equal number of patients without renovascular disease have abnormal pyelograms. The renogram, on the other hand, is associated with varying true-positive and false-positive ratios. These data can be plotted in the form of a receiver-operating-characteristic curve. The cost of finding a patient with renovascular disease is about $2,000, and that of a surgical cure is about $20,000. The number of deaths for 100 surgical cures is approximately 15. The dollar cost of screening and treating the total American renovascular hypertensive population is of the order of 10 to 13 billion dollars. (N Engl J Med 293:216–221,1975)
LGG-36. IMPACT OF BRAFv600e MUTATION 7q34 DUPLICATION AND CDKN2A DELETION IN A MONOCENTRIC COHORT OF 86 PEDIATRIC LOW GRADE GLIOMAS (PLGG)
Authors: Benoit Lhermitte, Eric Guerin, Michelle Legrain, Marc Arca, Marie Coutant, Consuelo Sebastia, Valérie Douzal, Flaviu Gabor, Natacha Entz-Werlé
Journal: Neuro-Oncology (2018)

The main diagnosis in pediatric brain tumor setting is PLGG, where BRAF is the more recurrent gene deregulated in those tumors (e.g. mutation v600e or 7q34 duplication). The molecular research of such abnormalities is performed now routinely for a diagnostic purpose. Recently, few publications were highlighting differently the impact of BRAF rearrangements and CDKN2A deletion, as independent prognostic factors linked to a worst outcome. Therefore, we were looking to our monocentric cohort of PLGG. Among 185 PLGGs diagnosed during the 10 last years, 86 were surgically resected or biopsied and diagnosed as a pilocytic astrocytoma or ganglioglioma. The molecular diagnosis was performed in all those PLGGs. The BRAF v600e mutation was detected by immunohistochemistry and confirmed by NGS (Next Generation Sequencing) analysis and the 7q34 duplication was assessed by reverse transcription polymerase chain reaction-based sequencing. We also detected the CDKN2A deletion by our NGS technique. 12 out of 86 tumors were bearing the BRAF mutation and 66 had a BRAF-KIAA1549 fusion transcript. Six patients with a BRAF mutation were relapsing after first line treatment and only one had a concomitant CDKN2A deletion and died rapidly. Among the tumors with a 7q34 duplication, one third (22) were relapsing and 2 were bearing also a CDKN2A deletion. All patients with this deletion died after first relapse or rapidly after diagnosis. No correlation was observed between those molecular abnormalities and the age of patients, whereas quantitative MRI parameters were significantly linked to the molecular diagnosis.
Regorafenib or trifluridine/tipiracil in refractory metastatic colorectal cancer: The optimization of pharmacological costs
Authors: J. Giuliani, A. Bonetti
Journal: Annals of Oncology (2018)

Introduction: The introduction of active new agents for refractory metastatic colorectal cancer (mCRC), such as regorafenib and trifluridine/tipiracil, is associated with a relevant increase of costs and it might be interesting to make a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as OS (overall survival). Methods: Pivotal phase III randomized controlled trials (RCTs) of regorafenib and trifluridine/tipiracil in refractory mCRC were considered. Differences in OS (expressed in months) between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital) needed to get one month of OS. The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). We assumed the following costs: 2299 € for 1 month of therapy with regorafenib at dose of 160 mg daily, 1160 € for 1 month of therapy with trifluridine/tipiracil at dose of 35 mg per square meter twice daily. Calculations were based on an "ideal patient" (BSA 1.8 sqm; weight 70 Kg). The dosage of drugs were considered according to those reported in each RCT. We have subsequently applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to the above phase III RCTs. Results: Three phase III RCTs (RECOURSE, CORRECT and CONCUR trials), including 1764 patients, were considered. ESMO-MCBS reached grade 3 for the CONCUR trial, grade 2 for the RECOURSE trial and grade 1 for the CORRECT trial. Combining the costs of therapy with the measure of efficacy represented by the OS, we get the costs for obtaining the advantage in OS, for each arm of the analyzed trials. Trifluridine/tipiracil (RECOURSE trial) resulted the less expensive, with 967 € per month OS-gained towards the CONCUR trial and CORRECT trial, with 2207 € and 2956 € per month OS-gained, respectively, mainly due to the increase in OS difference compared to placebo. Conclusion: Combining pharmacological costs of drugs with the measure of efficacy represented by the OS, trifluridine/tipiracil is a cost-effective treatment for patients with refractory mCRC.
NSRG-12. EXPERIENCE WITH THE INTRAOPERATIVE MAGNETIC RESONANCE IN PEDIATRIC BRAIN TUMOR SURGERY
Authors: Sonia Tejada, Shivaram Avula, Benedetta Pettorini, Conor Mallucci
Journal: Neuro-Oncology (2018)

The intraoperative magnetic resonance scanner (ioMR) is a diagnostic tool that can be used to improve brain tumor resection in pediatric patients. was introduced in our unit in 2009, and has been used routinely since then. To describe indications, radiological features and clinical outcomes of the patients operated on with ioMRI and analyze our experience. A retrospective analysis of a prospective surgical database has been performed, including surgical procedure, intent, radiological reports, need for second look surgery and complications, supplemented by further review of the clinical notes and the scans. From 2009 to 2015, 216 surgical procedures with ioMR for patients with brain tumors were performed: 204 were craniotomies and 12 were biopsies or cyst drainages. The mean age was 9.3y. One ioMR was performed in 56% patients; the mean duration of the MR was 32 min. In 129 cases (60%) no actions followed the ioMR. When the aim of the surgery was debulking of the tumor, the percentage of patients in which the ioMR was followed by resection was higher than when complete resection was the aim (55 vs 29%). The complication rate was not increased when compared with our previous results (infection 1%, neurological deficits 12%). We have demonstrated that the ioMR can be used safely and routinely in pediatric neurosurgical procedures for brain tumors at any age, assisting the surgeon in achieving the best extent of resection and aiding in intra-operative decision-making for tumor related intracranial pathology.
DIPG-17. ONCOLYTIC VIRUS FOR pHGG AND DIPGs: FROM THE BENCH TO THE BEDSIDE
Authors: Sonia Tejada, Naiara Martinez-Velez, Maider Varela, Pablo Dominguez, Juan Fueyo, Candelaria Gomez-Manzano, Javier Aristu, Ricardo Diez, Marta Alonso
Journal: Neuro-Oncology (2018)

Oncolytic adenoviruses are emerging as serious candidates for cancer treatment. Delta-24-RGD (DNX-2401) is an oncolytic adenovirus designed to infect and replicate in tumor cells. DNX-2401 has been evaluated in adult patients with gliomas showing a safe profile and antitumor effect. These results encouraged us to translate this strategy to pediatric gliomas. The aim of this work was to evaluate the safety and the antitumor effect of DNX-2401 alone or combined with radiotherapy in High Grade Gliomas (pHGGs) and Diffuse Intrinsic Pontine Gliomas (DIPGs). DNX-2401 showed a potent antitumor effect in pHGG (N=5) and DIPGs (N=6) cell lines (IC50 ranging from 1 to 50 MOIs) that was mediated by an effective viral replication. Addition of radiotherapy improved the antitumor effect of DNX-2401, due to synergistic effect (CI<1). Intratumoral delivery of DNX-2401 in nude mice bearing orthotopic pHGG and DIPG tumors did not showed any toxicity and increased significantly the survival of mice, due to an effective antiglioma effect These preclinical results allowed us to propose a phase 1 clinical trial for naïve DIPGs to evaluate the safety and feasibility of injecting this virus into the pons. The patients are subjected to a tumor biopsy and intratumoral infusion of DNX-2401. Up to date two patients have been treated with the 1x1010vp and the procedure were well tolerated. We believe that the information acquired through this study could serve to develop or improve new therapies in the battle against DIPG and constitute a paradigm change in the treatment of this devastating tumor.
HGG-14. IRRADIATION OF PEDIATRIC GLIOBLASTOMA CELLS INDUCES DOWNREGULATION OF TUMOR SUPPRESSOR MICRORNA GENES AND UPREGULATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)
Authors: Hisham Alhajala, Ninh Doan, Mona Al-Gizawiy, Jeffrey Knipstein, Kathleen Schmainda, Cristopher Chitambar
Journal: Neuro-Oncology (2018)

Recurrent glioblastoma (GBM) is known to be more aggressive and resistant to therapy when compared to the de-novo GBM tumor. Our previous in vivo studies showed that irradiated SJ-GBM2 cells exhibit greater radiological differences in angiogenesis and biological aggressiveness when compared with untreated (control) SJ-GBM2 cells. This may be explained by biological changes that occur after treatment with radiation and chemotherapy. Herein, we present evidence of changes in 21 gene expression and invasion protein markers between irradiated and non-irradiated cells. Pediatric GBM cells (SJ-GBM2) were irradiated with a total dose of 10Gy (SJGBM2-10gy). Irradiated and untreated control cells were tested for viability and changes in microRNA (miRNA) expression using miRNA microarrays that analyze more than 2000 genes. Samples were analyzed in duplicate. Western blots of the irradiated and control cell lysates and dot blots of the cell conditioned serum-free media were immunostained for pro-cathepsin B and VEGF. Only a relatively small set of miRNAs exhibited differential expression; 21 miRNAs genes were downregulated and none were upregulated in SJGBM2-10gy compared with SJ-GBM2 cells. Many of these down-regulated miRNAs were found to be tumor suppressor genes. This study also identified multiple novel downregulated miRNAs that have not yet been characterized. VEGF secretion was increased in the irradiated cells. Our study demonstrates increased biological aggressiveness in irradiated SJGBM2-10gy cells and suggests that this is due to multiple mechanisms that are activated following irradiation. These mechanisms include down-regulation of tumor suppressors’ miRNA genes and changes in the secretion of VEGF.