tbuckley/cabot-search huggingface dataset:
Chez les patients à haut risque, l'endoscopie haute avec coloration par lugol dépiste des lésions oesophagiennes précoces curables. Etude prospective nationale de la SFED
Authors: JL Legoux, G Sauvé, JY Scoazec, T Barrioz, P Renkes, JP Avignon, R Mas, P Jacob, S Olivier, O Favre, T Ponchon
Journal: Endoscopy (2006)

L'étude prospective nationale de la SFED a montré (1) que la fibroscopie oesogastro- duodénale (FOGD) avec coloration par lugol à 2% permet d'augmenter de 20% la sensibilité du dépistage de lésions oesophagiennes dysplasiques ou malignes, notamment chez les malades ayant un antécédent de cancer des voies aéro-digestives supérieures. Cette étude a permis de dépister, dans les populations sélectionnées comme les plus à risque (antécédents de cancers ORL ou trachéo-bronchiques, cirrhose alcoolique) des dysplasies de haut grade et des cancers. Le but de ce travail complémentaire était d'évaluer la pertinence d'un dépistage chez ces patients présentant des pathologies associées liées au tabagisme et à l'alcoolisme chronique, et des contrindications thérapeutiques liées au traitement de leur premier cancer.
Occurence of clostridium difficile infection in a county general hospital
Authors: FU Khan, M Moloney
Journal: Endoscopy (2006)

Introduction and Aims: In our study we have observed the number of cases of C. difficile in our Hospital over one year period, from January to December 2004. We have also observed the relation of C. difficile infection to different antibiotics and proton pump inhibitors which have also been implicated in this infection.
Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase
Authors: Jonatan Ersching, Alejo Efeyan, Luka Mesin, Johanne T. Jacobsen, Giulia Pasqual, Brian C. Grabiner, David Dominguez-Sola, David M. Sabatini, Gabriel D. Victora
Journal: Immunity (2017)
Characterization of cell-free circulating tumor DNA in patients with brain metastases.
Authors: Nadia Faiq, Sandip Pravin Patel, Lyudmila Bazhenova, Barbara A. Parker, Steven C. Plaxe, Razelle Kurzrock, Santosh Kesari, David Eric Piccioni
Journal: Journal of Clinical Oncology (2016)

2023 Background: Brain metastases are the most common malignant brain tumor and a significant cause of morbidity and mortality. As patients live longer from more effective systemic therapies, they are at increased risk of developing brain metastases. Genetic profiling of tumor tissue allows for targeted therapy, though biopsy of brain metastases is not always feasible. Cell-free circulating tumor DNA (ctDNA) testing carries diagnostic potential for targeted therapy without the need for repeat biopsies, and the ability to rapidly respond to changes in the molecular profile. Methods: 37 patients with brain metastases (15 lung, 12 breast, 5 ovarian, 3 renal, 2 melanoma) were tested prospectively with the Guardant360 ctDNA panel at a CLIA-certified, CAP-accredited clinical laboratory. Samples were analyzed for amplifications in 18 genes, single nucleotide variants in 68 genes, and select fusions, rearrangements and indels. Results: 29/37 (78.4%) patients tested harbored at least one detectable genomic alteration. The median number of alterations was 3 (range, 1-12). The most frequently detected alterations were in EGFR (19), TP53 (18), APC (6), NF1 (6), PIK3CA(6). The median ctDNA concentration was 0.50% (range, 0.10-43.80%). 11/37 patients had a subsequent test. 4/11 patients were tested within 50 days of initial testing; the median number of new alterations detected was 0.5 (range, 0-1). 7/11 patients were tested greater than 50 days of initial testing; the median number of new alterations detected was 2 (range, 0-4). Conclusions: CtDNA testing was able to detect alterations in a majority of patients with brain metastases. An increasing number of alterations were observed with time, suggesting the utility of ctDNA analysis in monitoring changes in tumor biology, response to therapy, and the ability to refine treatment plans with changes in the molecular profile.
Place de l'endoscopie en pratique libérale en France dans la prise en charge des MICI: A partir d'une enquête portant sur 1065 patients
Authors: J Lapuelle, G Tucat, PH Guyot, P Lévy, PH Houcke, B Richard-Molard
Journal: Endoscopy (2005)

Le but de ce travail était d'évaluer la place de l'endoscopie dans la prise en charge des MICI en milieu libéral en France.
Chlamydial and gonococcal infections are rare causes of vaginal discharge
Authors: A Edwards
Journal: BMJ (1995)

problem of stratification and selection for admission to those units.Finally, it is worth emphasising that not all investigations are of unproved value and that effective strategies for managing high risk patients do exist.We can avoid surgery altogether, and, indeed, quantification of risk may be particularly important in those operations, such as carotid endarterectomy, in which the benefit of surgery disappears at a given (and low) rate of perioperative complications.'As we stated in our last paragraph, further studies are urgently needed; these should not only assess methods of stratifying risk but also evaluate their effectiveness in reducing morbidity.Until such evidence is forthcoming, our article sum- marises the best methods available.
Phase 1 single-center, dose escalation study of D2C7-IT administered intratumorally via convection-enhanced delivery for adult patients with recurrent malignant glioma.
Authors: Dina Randazzo, Annick Desjardins, Vidyalakshmi Chandramohan, John H. Sampson, Katherine B. Peters, Gordana Vlahovic, Stevie Threatt, James Emmett Herndon, Susan Boulton, Denise Lally-Goss, Patrick Healy, Eric S Lipp, Allan H. Friedman, Darell D. Bigner
Journal: Journal of Clinical Oncology (2017)

e13532 Background: D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin consisting of EGFR-wt and EGFRvIII monoclonal antibodies with a genetically engineered Pseudomonas exotoxin, PE-38KDEL. The primary objective is to determine the maximum tolerated dose of D2C7-IT when delivered intratumorally by convection enhanced delivery (CED). Methods: Inclusion criteria includes subjects with a single, recurrent supratentorial WHO grade III or IV glioma, KPS ≥ 70 and a washout of chemotherapy, bevacizumab or study drug of ≥ 4 weeks. Prior to administration of D2C7-IT, recurrent tumor must be confirmed by histopathology. A minimum of 2 subjects are accrued by dose level. Results: Currently, 23 subjects have been treated (16 male, 7 female) with a median age of 54 years. Out of 9 dose levels, 2 subjects have been treated at every dose except for 4 at dose level 3 (120 ng/ml) and 5 at dose 6 (405ng/ml). Adverse events possibly, probably or definitely related to D2C7-IT are mostly grade 1 or 2 events consisting of, but not limited to: intracranial hemorrhage (n = 1), stroke (n = 2), headache (n = 15), seizure (n = 5), confusion (n = 4), paresthesia (n = 4), dysarthria (n = 1), dysphasia (n = 4), visual disturbances (n = 7), fatigue (n = 4), gait disturbance (n = 2), elevated transaminases (n = 5), decreased platelets (n = 3), decreased neutrophil count (n = 1), nausea (n = 3), vomiting (n = 1), and thromboembolic event (n = 1). There was 1 dose limiting toxicity (grade 4 seizure at dose level 3), 2 grade 3 headaches and 1 grade 3 elevated ALT. 14 subjects are still alive with 6 remaining on study. So far, the longest survival time from infusion is 18.2+ months. Conclusions: D2C7-IT infusion via CED is safe with encouraging results. This dose escalation Phase I study is ongoing and will set the stage for the Phase II trial. Clinical trial information: NCT02303678.
Safety, efficacy and survival of patients (pts) with primary CNS tumors in phase 1 (Ph1) trials: A 12-year single institution experience.
Authors: Niamh Coleman, Vasiliki Michalarea, Scheryll Paula Alken, Karim Rihawi, Kathy Greenwood, Raquel Perez Lopez, Nina Tunariu, Timothy Anthony Yap, Udai Banerji, Johann S. De Bono, Liam Welsh, L. Rhoda Molife, Frank Saran, Juanita Lopez
Journal: Journal of Clinical Oncology (2016)

2043 Background: Malignant primary CNS tumors constitute less than 2% of all malignancies and carry a dismal prognosis. Treatment (tx) options at relapse are limited. First-in-human solid tumor studies have historically excluded pts with CNS tumors due to the poor prognosis, concomitant drug interactions, concerns about excessive toxicities and limited efficacy. Methods: Retrospective data were collected on clinical tx and tumor characteristics of pts referred for consideration of Ph1 trials in the Royal Marsden Hospital between 06/2004 and 01/2016. Survival analyses were performed using the Kaplan-Meier method, Cox proportional hazards model, and associations with relevant clinical prognostic parameters were tested with Fischer’s Exact test. Statistical analysis was performed using Graphpad Prism 6.0 and SPSS 23. Results: 117pts with advanced, refractory primary CNS tumors were referred. At initial consultation, pts had a median ECOG PS of 1, median age of 49 years (range 18-70); 81pts (69%) were men, 90 (77%) had glioblastoma; 71pts (61%) were on anti-epileptic drugs, 76pts (65%) required steroid therapy. The median number of prior systemic therapies was 2. 75 pts (64%) were allocated to a Ph1 trial; 55 (73%) were treated with a study drug. 25pts (21%) were not allocated due to lack of slots on relevant trials and 14 (12%) were not allocated due to poor PS. The median PFS for pts treated on a Ph1 trial was 6.5 months (m) with a median OS of 11m (vs 4m in pts that did not proceed with a Ph1 trial) HR 0.49, 95% CI:0.27-.0.67, p = 0.0005. 5 pts (9%) had grade 3 drug-related toxicities. There were no study-related deaths. No correlation between RMH score, age, ECOG PS, previous lines of tx or neutrophil -lymphocyte ratio and outcome was found. Conclusions: We report a significant survival benefit for pts with primary CNS tumors treated on Ph1 trials. Toxicity and efficacy outcomes are comparable to the general Ph1 pt population. In the absence of an internationally recognized standard second line tx for pts with recurrent primary malignant CNS tumors, more Ph1 trials should allow enrolment of these pts and Ph1 trial participation should be considered at an earlier stage.
Coffee consumption is not associated with prevalent subclinical cardiovascular disease (CVD) or the risk of CVD events, in nonalcoholic fatty liver disease: results from the multi-ethnic study of atherosclerosis
Authors: Tracey G. Simon, Maria Esther Perez Trejo, Irfan Zeb, Alexis C. Frazier-Wood, Robyn L. McClelland, Raymond T. Chung, Matthew J. Budoff
Journal: Metabolism (2017)
Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population: a cross-sectional study
Authors: Andy C Rawstron, Aloysius Ssemaganda, Ruth de Tute, Chi Doughty, Darren Newton, Anna Vardi, Paul A S Evans, Kostas Stamatopoulos, Roger G Owen, Tracy Lightfoot, Katie Wakeham, Alex Karabarinde, Gershim Asiki, Robert Newton
Journal: The Lancet Haematology (2017)
Integrative network analysis identifies novel drivers of pathogenesis and progression in newly diagnosed multiple myeloma
Authors: A Laganà, D Perumal, D Melnekoff, B Readhead, B A Kidd, V Leshchenko, P-Y Kuo, J Keats, M DeRome, J Yesil, D Auclair, S Lonial, A Chari, H J Cho, B Barlogie, S Jagannath, J T Dudley, S Parekh
Journal: Leukemia (2017)
Osimertinib for patients (pts) with leptomeningeal metastases (LM) from EGFR-mutant non-small cell lung cancer (NSCLC): Updated results from the BLOOM study.
Authors: James Chih-Hsin Yang, Byoung Chul Cho, Dong-Wan Kim, Sang-We Kim, Jong-Seok Lee, Wu-Chou Su, Tom John, Stephen Chuan-Hao Kao, Ronald Natale, Jonathan Wade Goldman, Philip Overend, Karthick Vishwanathan, Xin Ye, Zhenfan Yang, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2017)

2020 Background: LM due to NSCLC progression are associated with poor prognosis. Osimertinib is an oral, CNS-active, irreversible EGFR-TKI selective for sensitizing (EGFRm) and T790M resistance mutations. Methods: In the BLOOM study (NCT02228369), pts with EGFRm advanced NSCLC who had progressed on prior EGFR-TKI therapy and had LM confirmed by positive cerebrospinal fluid (CSF) cytology received osimertinib 160 mg once daily (qd). Response was assessed (by investigator) in 2 cohorts: T790M unselected and T790M positive (by central test); results are presented as a combined analysis set. Analyses were based on CSF cytology, brain MRI imaging, and neurological examination every 6 weeks (wk; relative to first dose) until progression. Adverse events (AEs) were graded according to CTCAE. EGFR-mutant DNA in CSF was determined by ddPCR. Plasma and CSF samples were collected for PK analyses. Results: As of 24 Sep 2016,32 pts had received treatment: 21 T790M unselected; 11 T790M positive. Max treatment duration was 17.5 months (m; median 6.0 m); 21 pts ongoing. 23/32 pts had a 12-wk brain image assessment: 10 had radiological improvement, 13 had stable disease (SD). The same 23 pts had a 12-wk neurological assessment: of 8 symptomatic pts, 7 improved, 1 had SD; of 15 asymptomatic pts, 2 worsened, 13 remained asymptomatic. The geometric mean decrease in EGFR-mutant DNA copy was 57% (95% CI 30, 74) in 22 pts with pre-dose and Cycle 2 Day 1 CSF samples. Most common AEs were skin effects (n = 20), diarrhea (n = 13), nausea (n = 11) and paronychia (n = 9). All were grade (G) 1/2 except 1 case each of diarrhea and nausea (both G3). 9 pts had dose interruptions and 4 had dose reductions to 80 mg qd. Osimertinib mean concentration in CSF was 7.51 nM (range 2.19–21.1 nM) at steady state (N = 16); CSF:free plasma ratio: 16%. Accrual is now complete (n = 41; 21 T790M unselected, 20 T790M positive) and updated data (including overall survival) will be presented. Conclusions: Osimertinib penetrates the blood-brain barrier. Encouraging activity and manageable tolerability in pts with LM from EGFRm NSCLC was observed at 160 mg qd, with a median treatment duration of 6.0 m; continued evaluation is ongoing. Clinical trial information: NCT02228369.
Increased antimicrobial resistance in clonal clostridium difficile isolates in Dublin Ireland
Authors: D Drudy, N Harnedy, S Fanning, R O'Mahony, L Kyne
Journal: Endoscopy (2006)

Clostridium difficile is a major cause of infectious diarrhoea in hospitalised patients. While antibiotics are a major risk factor predisposing to C. difficile diarrhoea, few studies have examined antimicrobial resistance in C. difficile isolates. We described previously an outbreak of C. difficile diarrhoea in Dublin, Ireland. The aim of this study was to determine antimicrobial susceptibilities of the C. difficile isolates collected during the outbreak period. C. difficile isolates were cultured on CCFA agar. PCR ribotyping was used to determine genomic relatedness between C. difficile isolates. Antimicrobial susceptibilities to macrolide and fluoroquinolone antibiotics were determined using E-tests. 90 isolates were collected during the outbreak period. PCR ribotyping profiles divided the isolates into two clusters, a major outbreak cluster of 85 isolates and a second cluster of 5 strains. The clonal outbreak isolates (n=85) were resistant to all fluoroquinolones (Ofloxacin, Ciprofloxacin, Levofloxacin, Moxifloxacin and Gatifloxacin) and MLS (Erythromycin, Clarithromycin, Clindamycin) antibiotics tested. In contrast non-clonal isolates were sensitive to MLS antibiotics and Levofloxacin, Moxifloxacin and Gatifloxacin. Acquired antimicrobial resistance may be an additional virulence factor in C. difficile isolates by allowing persistence of clonal strain types in the hospital environment.
Phase I trial of a novel stapled peptide ALRN-6924 disrupting MDMX- and MDM2-mediated inhibition of <i>WT p53</i> in patients with solid tumors and lymphomas.
Authors: Funda Meric-Bernstam, Mansoor N. Saleh, Jeffrey R. Infante, Sanjay Goel, Gerald Steven Falchook, Geoffrey Shapiro, Ki Y Chung, Robert Martin Conry, David S. Hong, Judy Sing-Zan Wang, Ulrich Steidl, Loren D. Walensky, Vincent Guerlavais, Marie Payton, D. Allen Annis, Manuel Aivado, Manish R. Patel
Journal: Journal of Clinical Oncology (2017)

2505 Background: ALRN-6924 is a cell-penetrating stapled alpha-helical peptide designed to equipotently disrupt the interaction between the p53 tumor suppressor protein and its endogenous inhibitors, murine double minute X (MDMX) and 2 (MDM2). For TP53 wild-type (WT) tumors, pharmacological disruption of this interaction offers a means to restore p53-dependent cell cycle arrest and apoptosis, resulting in antitumor efficacy via a novel mechanism. Methods: The study evaluated safety, PK, PD and anti-tumor effects of ALRN-6924 in patients (pts) with advanced solid tumors or lymphomas in a standard 3+3 design. Pts received ALRN-6924 IV once weekly for 3 consecutive wks on a 28-day cycle (arm A), or 2/wk for 2 consecutive wks on a 21-day cycle (arm B). Results: As of Dec 2016, 69 pts were enrolled with median age 61 yrs (25-78). Pts received a median of 2 (1-19) cycles in arm A [0.16-4.4 mg/kg] and 3 (1-19) cycles in arm B [0.32-2.7 mg/kg]. ALRN-6924 showed a t 1/2 of 5.5 hours, dose-dependent PK, and an increase in serum macrophage inhibitory cytokine-1. Treatment-related AEs seen in 96% of pts were primarily grade 1 and 2; most frequent were GI side effects, fatigue, anemia, and headache. DLTs were G3 fatigue at 3.1 mg/kg, and G3 hypotension, G3 alkaline phosphatase elevation, G3 anemia and G4 neutropenia at 4.4 mg/kg all in 5 pts in arm A. No G3/4 thrombocytopenia was observed. All DLTs resolved with dose hold. Infusion-related reactions were seen in 7 pts, with 3 treatment discontinuations. The RP2D was determined to be at MTD: 3.1 mg/kg QW for 3 wks every 28 days. In 55 pts evaluable for efficacy, disease control rate (DCR) was 45%, including 2 CR (Peripheral T-cell Lymphoma [PTCL], Merkel Cell Carcinoma), 2 PRs (Colorectal Cancer, Liposarcoma) and 21 pts with SD. In WT TP53 pts who initiated ALRN-6924 at ≥0.8 mg/kg, DCR was 57%. 9 pts remain on treatment post data cutoff including 3 pts exceeding 1 year of treatment. Conclusions: ALRN-6924 was well tolerated and demonstrated intriguing anti-tumor activity in this first-in-human phase I trial. An expansion phase IIa cohort in PTCL opened in August 2016 using 3.1 mg/kg (arm A) and is currently enrolling. Clinical trial information: NCT02264613.
Hypofractionated whole breast IMRT and brachytherapy boost after conservative surgery for breast cancer: Early results of a prospective non-randomised trial.
Authors: Benjamin Guix, Ivan Garcia, Ines Guix, Juan Antonio Lejarcegui, Jose Ignacio Tello, Miquel Prats, Luis Quinzaños, Joel Mases, Teresa Guix
Journal: Journal of Clinical Oncology (2016)

1062 Background: To report early results obtained in a prospective group of patients (pts) treated with whole breast IMRT radiotherapy plus a brachytherapy boost to the tumor bed after conservative surgery, given either with hypofractionated or normofractionated radiotherapy Methods: Between 12/2008 and 06/2014, 829 pts with < 4cm, N0-2 breast cancers treated conservatively were assigned to enter the study. Patients were offered to be treated either with IMRT hypofrationated whole breast and lymphnode areas (if needed) radiotherapy 42.6 Gy (266cGyx16 fractions) plus a 7 Gy boost to the tumor bed, (hypofractionated group) or IMRT normofractionated 50 Gy (200cGyx25) to the whole breast and lymphatic areas (when needed) plus 16 Gy brachytherapy boost (200cGyx8 fractions) (normofractionated group). Treatment assignation was done according to the patients preference or, if none, were randomly assigned to have both groups uniformly balanced. During treatment and follow-up special attention was taken to side-effects, breast fibrosis, arm lymphedema, skin reaction, patient satisfaction and local, regional and distant disease control. Results: 309 pts were included in the hypofractionated group and 520 in the normofractionated group. All patients completed treatment. Patients were evaluated every 3 months for the first 5 years of follow-up. Photographs were taken at each visit. SOMA-LENT scales were used in every visit. For quality of life EORTC QLQ-C30 plus the BR-15 module were used. No patient had adverse side-effect that required treatment ending in any group. In the hypofractionated group, there were 1 LR, 1 distant metastases and 1 death due to the disease. In the normofractionated group there were 12 local recurrences, 7 distant metastases and 4 patients died due to the disease. Conclusions: Hypofractionated IMRT to the whole breast followed by a 1 fraction HDR breast implant was a safe and effective method of treatment for early breast cancer treated with conservative surgery, even in those patients N+ in which the supraclavicular fossa was included in the treatment fields. Patient satisfaction was greater in the hypofractionated group.
In situ expression of hypoxia inducible factor 2-alpha in gliomas.
Authors: Jaclyn Renfrow, Ryan Mott, Yue Huang, Tai Wong, Glenn Jay Lesser, Waldemar Debinski, Roy E. Strowd
Journal: Journal of Clinical Oncology (2017)

e13534 Background: Hypoxia, a driver of malignancy, is fundamental to glioblastoma (GBM). Of the hypoxia inducible transcription factors (HIFs), HIF-2a is expressed in GBM tumor cells, responds to prolonged hypoxia, and is a prime candidate for HIF therapeutic targeting. PT2385 is a novel, orally available, first-in-class, HIF-2a inhibitor with a brain:plasma ratio of 0.9 in rats. To establish HIF-2a as a therapeutic target in GBM, in situ expression needs to be described. Methods: Twenty-two paraffin-embedded gliomas (grade II-IV) underwent immunohistochemistry for HIF-2a. After rehydration, a hot Tris EDTA pH 9.0 solution retrieved epitopes, non-specific sites were blocked, and HIF-2a antibody (Santa Cruz, sc-13596) was added. A horseradish peroxidase detection system identified staining. Representative samples were digitally scanned. Localization and quantification of HIF-2a was independently verified by a neuropathologist. Patient survival and molecular genetics were retrospectively collected with Institutional Review Board approval. Results: HIF-2a expression was not detected in the 4 Grade II and 2 Grade III gliomas.Of the 16 GBMs, HIF-2a was expressed in 13 specimens (81%) - highly in 7 ( &gt; 10% cells positive), intermediate in 6 ( &lt; 10% cells positive), and minimally in 3. Recurrent disease stained highly for HIF-2a. Staining was specific to tumor cells and occasionally monocytic cells, clustering in perivascular and perinecrotic regions. Amongst the 16 GBMs, median patient age and survival was 58 and 13.9 months. The two longest survivors harbored positive prognostic genetics (six-year survival with a 1p/19q co-deletion and ten-year survival with MGMT gene methylation). Twelve of 16 patients received chemoradiation. Survival was not correlated with HIF-2a. Conclusions: This first in situ description of HIF-2a demonstrates expression is absent in low-grade gliomas, present in the majority of GBMs, and high in recurrent GBMs. HIF-2a abundance varies with clustering in perivascular and perinecrotic niches. Survival did not appear to be correlated with HIF-2a in this small cohort though well-known prognostic genetic mutations and treatment heterogeneity limit firm conclusions. Preclinical studies with PT2385 are in progress.
Syk inhibitors interfere with erythrocyte membrane modification during P falciparum growth and suppress parasite egress
Authors: Antonella Pantaleo, Kristina R. Kesely, Maria Carmina Pau, Ioannis Tsamesidis, Evelin Schwarzer, Oleksii A. Skorokhod, Huynh D. Chien, Marta Ponzi, Lucia Bertuccini, Philip S. Low, Francesco M. Turrini
Journal: Blood (2017)

Key Points Inhibitors of human Syk kinase suppress parasite egress. Syk inhibitors prevent the tyrosine phosphorylation of band 3 in P falciparum parasitized red blood cells, reducing the release of microparticles.