tbuckley/cabot-search huggingface dataset:
Abstract 12349: 5 - Year Mortality in Patients With Left Ventricular Diastolic Dysfunction and Preserved Ejection Fraction
Authors: Salim H Memon, Sharma Kattel, Yuji Saito
Journal: Circulation (2013)

Background: Left ventricular diastolic dysfunction (DD) is an independent predictor of mortality in patients with preserved left ventricular ejection fraction. However, there is limited data on whe...
Caractéristiques des oesophagites disséquantes chroniques primitives et secondaires: résultats d'une étude prospective portant sur 20 cas
Authors: H Lamouliatte, F Zerbib, V Thétiot, G Belleannée, L Message
Journal: Endoscopy (2006)

Depuis sa description en 1997 (1), l'oesophagite disséquante chronique (ODC) est de plus en plus souvent retrouvée. Cependant, à côté des formes primitives (ODCI) il existe des formes secondaires (ODC2) à diverses affections. Le but de cette étude était de comparer les caractéristiques des ODC primitives et secondaires sur le plan clinique et évolutif.
PALB2 Mutational Status in Haematopoeitic Malignancies - a Potential Therapeutic Target?
Authors: Ceri Oldreive, Tatjana Stankovic, Philip J Byrd, Grant S Stewart, Anna Smith, Alexander J Taylor, Peggy Fooks, Robert Horsley, James I Last, Dragana Janic, Lidija Dokmanovic, A. Malcolm R Taylor
Journal: Blood (2016)
Neurocognitive outcome in children with sensorineural hearing loss after treatment of malignant embryonal brain tumors.
Authors: Christine Dahl, Iska Moxon-Emre, Vijay Ramaswamy, Ute Katharina Bartels, Uri Tabori, Annie Huang, Sharon Cushing, Vicky Papaioannou, Normand Laperriere, Donald J Mabbott, Eric Bouffet
Journal: Journal of Clinical Oncology (2017)

2029 Background: Neurological side effects associated with childhood brain tumors and their treatments contribute to long term neurocognitive morbidity. The aims of this study were to identify the incidence of sensorineural hearing loss (SNHL) in a large sample of children treated for malignant brain tumors, and to evaluate the potential relationship between SNHL and intellectual functioning following the completion of treatment. Methods: We conducted a prospective follow-up study at a single center with review of 119 patients treated for embryonal brain tumors at the Hospital for Sick Children, between 1996-2015, to analyze the impact of significant SNHL (Chang &gt; 2b) on intellectual function. Hearing was assessed post-treatment (median age: 13.5y (+4.5)) and the median age for neurocognitive testing was 12.8y (+ 4.1). The median interval from time of diagnosis was 5.8y (+ 3.7). Results: Severe SNHL was identified in half the patients (50.4%, n = 60/119). We identified a subset of patients (n = 61) who had assessments of intellectual function. In this cohort, intellectual function was significantly poorer in the group with severe SNHL, even after controlling for the effect of craniospinal radiation (severe SNHL 22.4 Gy + 13.3, no or mild hearing loss 20.4 Gy +12.8) and boost dose and volume. Children experiencing severe SNHL had lower overall IQ (severe SNHL 72.4 + 16.6; no/mild hearing loss 92.0 + 20.5) p &lt; 0.001 and in significantly lower verbal comprehension (severe SNHL 78.7 + 15.9; no/mild hearing loss 94.7 + 13.8) p &lt; 0.001, and working memory (severe SNHL 78.2+ 17.6; no/mild hearing loss 94.8 + 16.4) p &lt; 0.001, scores. Conclusions: Hearing loss is a much more significant complication in children with embryonal brain tumors than previously estimated. We show the profound impact of hearing loss on intellectual deficit in children. Namely, patients with severe SNHL have difficulty using and understanding verbal language, and they have a reduced ability to concentrate and manipulate information in short-term memory. Our results have implications on future trial designs and follow-up of children treated for embryonal brain tumors.
Abstract 13280: Localized Hydrogen Peroxide Production and Differential Activation of Redox-sensitive Transcription Factors Involved in Atherogenesis
Authors: Benjamin Steinhorn, Vselovod Belousov, Thomas Michel
Journal: Circulation (2016)

Reactive oxygen species modulate key physiological responses, yet ROS are also implicated in vascular disease states. At low concentrations, the stable ROS hydrogen peroxide (H 2 O 2 ) activates eNOS and enhances vascular barrier function. Yet at higher concentrations, vascular ROS lead to oxidative stress, increase permeability and promote atherosclerosis. The molecular events underlying the transition from “physiological” to “pathological” ROS in the endothelium are incompletely understood. Laminar shear stress activates “atheroprotective” redox-modulated transcription factors whereas turbulent/oscillatory flow activates “atherogenic” transcription factors that are sensitive to cellular redox state. In these studies, we constructed differentially-targeted HyPer biosensors for H 2 O 2 to identify the intracellular organelles and pathways responsible for dynamic mechanochemical regulation of endothelial H 2 O 2 metabolism. We discovered that laminar (physiological) shear stress increases H 2 O 2 in the endothelial cell nucleus much more than in the cytosol. By contrast, oscillatory (pathological) shear increases H 2 O 2 in the cytosol significantly more than in the nucleus. We next generated H 2 O 2 in specific subcellular locales in endothelial cells using recombinant constructs expressing a D-amino acid oxidase (DAAO) that robustly generates H 2 O 2 upon addition of D-alanine to the cells. By transfecting a series of differentially targeted DAAO constructs into endothelial cells, we discovered that generation of H 2 O 2 in distinct subcellular compartments differentially modulates transcriptional activation. Generation of H 2 O 2 by DAAO expressed in the endothelial cell nucleus led to enhanced transcription of Nrf2-modulated genes, whereas generation of H 2 O 2 by DAAO targeted to the cytosol instead activated NF-κB-regulated genes. This differential transcriptional response regulated by H 2 O 2 generated in distinct subcellular locales provides new insights into the roles of ROS and eNOS in mechanochemical coupling. Taken together, these findings have important implications for our understanding of flow-responsive genes in the normal blood vessel as well as in disease states associated with disordered blood flow and oxidative stress.
Regarding “Abbreviated Course of Radiation Therapy in Older Patients with Glioblastoma Multiforme: A Prospective Randomized Clinical Trial”
Authors: Marc C. Chamberlain, Lawrence D. Recht, Michael Glantz
Journal: Journal of Clinical Oncology (2005)

unconvincing on their own, but also favor acetaminophen.Improvements in pain, overall well-being, and strength of preference for acetaminophen were highly correlated with one another (Spearman's rank correlations 0.49 to 0.8; all P Ͻ .007).Differences in nausea, vomiting, drowsiness, constipation, and breakthrough doses were not expected for a 48-hour intervention that held baseline doses of opioids constant.The dose we tested (10 tablets per day, 1 g every 4 hours while awake) was based on acetaminophen's half-life and the usual dosing intervals for short-acting morphine.A lower dose of 8 tablets per day (1 g every 6 hours) is commonly used with long-acting opioids in people with cancer pain, and as an alternative to nonsteroidal anti-inflammatory drugs in people with degenerative joint disease.Hepatic toxicity is rare with doses less than 8 g daily, even in patients with chronic liver disease.We stand by our conclusion that the addition of acetaminophen is worth considering in all people with persistent cancer pain, despite a strong opioid regimen.Little is lost by letting such people try acetaminophen for a few days so that they can decide for themselves if the benefits are worth the extra tablets.Heterogeneity of practice (and prejudice) is common and provides a strong rationale for clinical trials.Studies of interventions for cancer pain are sorely needed.Trials testing a lower dose of acetaminophen for a longer duration in patients using a wide range of strong opioids and coanalgesics would be particularly welcome.
Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke
Authors: Craig S. Anderson, Hisatomi Arima, Pablo Lavados, Laurent Billot, Maree L. Hackett, Verónica V. Olavarría, Paula Muñoz Venturelli, Alejandro Brunser, Bin Peng, Liying Cui, Lily Song, Kris Rogers, Sandy Middleton, Joyce Y. Lim, Denise Forshaw, C. Elizabeth Lightbody, Mark Woodward, Octavio Pontes-Neto, H. Asita De Silva, Ruey-Tay Lin, Tsong-Hai Lee, Jeyaraj D. Pandian, Gillian E. Mead, Thompson Robinson, Caroline Watkins
Journal: New England Journal of Medicine (2017)

The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion.In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death).The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P<0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P=0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P=0.83). There were no significant between-group differences in the rates of serious adverse events, including pneumonia.Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours. (Funded by the National Health and Medical Research Council of Australia; HeadPoST ClinicalTrials.gov number, NCT02162017 .).
Insertional mutagenesis identifies drivers of a novel oncogenic pathway in invasive lobular breast carcinoma
Authors: Sjors M Kas, Julian R de Ruiter, Koen Schipper, Stefano Annunziato, Eva Schut, Sjoerd Klarenbeek, Anne Paulien Drenth, Eline van der Burg, Christiaan Klijn, Jelle J ten Hoeve, David J Adams, Marco J Koudijs, Jelle Wesseling, Micha Nethe, Lodewyk F A Wessels, Jos Jonkers
Journal: Nature Genetics (2017)
CheckMate 451: A randomized, double-blind, phase III trial of nivolumab (nivo), nivo plus ipilimumab (ipi), or placebo as maintenance therapy in patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC) after first-line platinum-based doublet chemotherapy (PT-DC).
Authors: Neal Ready, Taofeek Kunle Owonikoko, Pieter E. Postmus, Martin Reck, Solange Peters, Anne Pieters, Giovanni Selvaggi, Justin P. Fairchild, Ramaswamy Govindan
Journal: Journal of Clinical Oncology (2016)

TPS8579 Background: Most SCLC pts present with ED-SCLC. Initial response rates are high, but disease often rapidly recurs or progresses. Outcomes with second-line treatment are poor. No maintenance therapy has been approved for pts who respond to first-line PT-DC. Nivo, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor, is approved for previously treated metastatic NSCLC in the US and for previously treated squamous NSCLC in the EU based on 2 phase III trials demonstrating superior survival over docetaxel. Nivo monotherapy and nivo + ipi, a fully human IgG1 cytotoxic T lymphocyte antigen-4 immune checkpoint inhibitor, are being evaluated in previously treated pts with advanced or metastatic SCLC in a phase I/II trial (CheckMate 032, SCLC cohort). Nivo (vs chemotherapy) is also being evaluated in relapsed SCLC in a phase III trial (CheckMate 331). From CheckMate 032, preliminary data of nivo and nivo + ipi has shown antitumor activity with durable tumor responses and manageable safety profiles in pts with SCLC in the second-line setting or later. Responses were observed regardless of programmed death ligand 1 expression or platinum sensitivity/resistance. Based on these promising data, a phase III trial (CheckMate 451) was designed to evaluate nivo monotherapy, nivo + ipi followed by nivo monotherapy, and placebo as maintenance therapy for ED-SCLC after first-line PT-DC. Methods: Adult pts with ED-SCLC who achieve stable disease or better after first-line PT-DC and have ECOG performance status 0–1 are eligible. Pts with active central nervous system metastases, autoimmune disease, or toxicities attributed to prior anticancer therapy not resolved to grade ≤ 1 are ineligible. Primary endpoints are overall survival and progression-free survival. Approximately 810 pts will be enrolled and randomized to nivo monotherapy, nivo + ipi followed by nivo monotherapy, or placebo. Clinical trial information: NCT02538666.
NR4A orphan nuclear receptor family members, NR4A2 and NR4A3, regulate neutrophil number and survival
Authors: Lynne R. Prince, Svenja D. Prosseda, Kathryn Higgins, Jennifer Carlring, Elizabeth C. Prestwich, Nikolay V. Ogryzko, Atiqur Rahman, Alexander Basran, Francesco Falciani, Philip Taylor, Stephen A. Renshaw, Moira K. B. Whyte, Ian Sabroe
Journal: Blood (2017)
Controls on cosmetic treatments are “completely inadequate,” report warns
Authors: Sophie Arie
Journal: BMJ (2017)

Surgeons who wish to offer cosmetic procedures should have to put their names on a compulsory register, a report on this growing industry has urged.1

The report by the Nuffield Council on Bioethics calls on the government to do more to protect the public from the cosmetic treatments industry, estimated to have grown in value from £750m in 2005 to £3.16bn (€3.6bn; $4bn) in 2015. It said …
Validation of Whole Genome SNP Array As the Primary Genetic Test in Myelodysplastic Syndrome, to Replace Chromosome and FISH Copy Number Analysis, in a UK Diagnostic Genetic Laboratory
Authors: Sally Jeffries, Nicola Trim, Emma Huxley, Judith Caddick, Jane Soden, Laura Ford, Paula Wojtowicz, Charles Craddock, Michael John Griffiths
Journal: Blood (2016)
Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced gastric or gastroesophageal junction cancer from JAVELIN solid tumor phase Ib trial: Analysis of safety and clinical activity.
Authors: Hyun Cheol Chung, Hendrik-Tobias Arkenau, Lucjan Wyrwicz, Do-Youn Oh, Keun-Wook Lee, Jeffrey R. Infante, Sung Sook Lee, Jeeyun Lee, Ulrich Keilholz, Alain C. Mita, Elizabeth R. Plummer, Margaret Kemeny, Bohuslav Melichar, Denis Michel Smith, Kevin M. Chin, Anja von Heydebreck, Jean-Marie Cuillerot, Yoon-Koo Kang, Howard Safran
Journal: Journal of Clinical Oncology (2016)

4009 Background: Avelumab (proposed INN) is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab as a first-line maintenance (Mn) or second-line (2L) therapy in patients (pts) with advanced gastric or gastroesophageal junction cancer (GC/GEJ; NCT01772004), including activity associated with PD-L1 expression. Methods: Pts with GC/GEJ received avelumab at 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Response was assessed every 6 wks (RECIST 1.1). Best overall response and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI CTCAE v4.0. PD-L1 expression was assessed by IHC. Results: As of Oct 23 2015, 151 pts were treated with avelumab (62 pts, 2L; 89 pts, Mn) and followed for median of 49 wks (range 9-84). Treatment-related adverse events (TRAEs) of any grade occurred in 89 pts (58.9%); most common ( > 10%) were infusion-related reaction (19 [12.6%]) and fatigue (16 [10.6%]). Grade ≥ 3 TRAEs were reported in 15 pts (9.9%); fatigue, asthenia, increased GGT, thrombocytopenia, and anemia occurred in > 1 pt (2 each; 1.3%). There was 1 treatment-related death (hepatic failure/autoimmune hepatitis). Fourteen pts had an unconfirmed response: 2L 6/62 (9.7%), all PRs; Mn 8/89 (9.0%), 2 CRs, 6 PRs. In 2L and Mn pts, disease control rate was 29.0% and 57.3%, and median PFS was 6.0 wks (95% CI: 5.7, 6.4) and 12.0 wks (95% CI: 9.9, 17.6), respectively. PD-L1 expression was evaluable in 74 pts (22/62 2L, 52/89 Mn). Activity based on a ≥ 1% cutoff for tumor cell staining is shown in the table. Conclusions: Single-agent avelumab had an acceptable safety profile and promising clinical activity in unselected pts with GC/GEJ treated in Mn and 2L settings. These data represent the largest study of anti-PD-(L)1 agents in GC/GEJ. Two randomized phase III trials of avelumab in GC are open. Clinical trial information: NCT01772004. 2L (n = 22) Mn (n = 52) PD-L1+ (n = 11) PD-L1− (n = 11) PD-L1+ (n = 20) PD-L1− (n = 32) ORR, % (95% CI) 18.2 (2.3, 51.8) 9.1 (0.2, 41.3) 10.0 (1.2, 31.7) 3.1 (0.1, 16.2) Median PFS, wks (95% CI) 6.3 (5.4, 18.0) 10.4 (4.1, 21.9) 17.6 (6.0, 24.1) 11.6 (5.7, 14.1)
Traitement par endoprothese extractible des stenoses au cours de la maladie de Crohn
Authors: P Bulois, Y Bouhnik
Journal: Endoscopy (2006)

Elles constituent la première indication à un traitement chirurgical. Les sténoses courtes et accessibles sont traitées en première intention par dilatation endoscopique. Ce traitement est efficace mais il est associe a un taux de perforation proche de 10% dans certaines études. D'autre part, le risque de récidive est supérieur a 60% à 3 ans, conduisant a des séances de dilatation itératives ou a des interventions chirurgicales. Au cours des dernières années, les endoprothèses temporaires extractibles ont été proposées dans le traitement des sténoses bénignes de l'oesophage et du colon.
Study of the impact of cytomegalovirus-encephalopathy on survival of brain cancer patients undergoing treatment with radio(chemo)therapy.
Authors: Nicole Lydia Goerig, Benjamin Frey, Klaus Korn, Bernhard Fleckenstein, Klaus M Ueberla, Manuel A. Schmidt, Arnd Doerfler, Tobias Engelhorn, Ilker Eyüpoglu, Andreas Merkel, Paul F Ruehle, Florian Putz, Sabine Semrau, Udo S Gaipl, Rainer Fietkau
Journal: Journal of Clinical Oncology (2017)

2036 Background: As recently demonstrated (Neurooncology, 2016), neurological decline of patients with brain cancer (high grade glioma, brain metastases) during radio(chemo)therapy (RCT) of the brain is oftentimes caused by CMV-encephalopathy but not disease progression or therapeutic complications. We examined the impact of clinical and serological CMV-status on the survival one year after the onset of radio(chemo)therapy of the brain. Methods: 118 patients requiring whole-brain radiotherapy for brain metastases (n = 55) or local RCT of the brain for high-grade gliomas (n = 63) were observed in the prospective GLIO-CMV-01 study. MRIs and blood samples were obtained before, halfway through, and at the end of radiotherapy. MRIs were screened for disease progression or increased intracranial pressure. Blood was tested for anti-CMV immunoglobulin (Ig)M, anti-CMV IgG, and CMV DNA. Results: 68 of 118 (58%) patients were positive for anti-CMV IgG before radio(chemo)therapy. 28 of those 68 (41%) developed CMV-viremia during or up to 28 days after the end of irradiation. 21 of those 28 (75%) required treatment for symptomatic CMV-associated encephalopathy. One year after the start of RCT, survival was 72% (34/47) (no encephalopathy, anti-CMV-IgG+) or 68% (34/50) (no encephalopathy, anti-CMV-IgG-) versus 38% (8/21) (encephalopathy) (p = 0.0034). Conclusions: Symptomatic CMV-encephalopathy all but doubles the mortality of brain cancer patients within one year of RCT, despite antiviral treatment with ganciclovir. These findings heavily underline the importance to identify patients with increased risk profile for developing CMV-encephalopathy before initiating RCT.
Echographie anorectale sur sonde linéaire: intérêt pratique dans la prise en charge des cancers du rectum
Authors: P Senesse, H Audin, E Assenat
Journal: Endoscopy (2006)

L'évaluation tumorale pré-thérapeutique est déterminante pour une prise en charge adaptée en particulier dans les tumeurs rectales. Actuellement, il est proposé, pour les adénocarcinomes du bas rectum, dans le cadre de protocoles définis, une conservation sphinctérienne après radiothérapie ou radio-chimiothérapie pré-opératoire (1). Dans tous les cas, la détermination du stade tumoral, l'infiltration de la tumeur, l'intégrité du sphincter externe sont des éléments déterminants pour décider de la prise en charge thérapeutique.
T-DM1 to induce response in central nervous system (CNS) metastases from Her2 +ve metastatic breast cancer (MBC).
Authors: Yamini McCABE, Andrew M. Wardley, Anne Caroline Armstrong, Sacha Jon Howell
Journal: Journal of Clinical Oncology (2016)

582 Background: Radiotherapy (RT) remains the mainstay of treatment for breast cancer CNS metastases although responses to systemic therapy are seen. TDM1 is a novel antibody-drug conjugate of trastuzumab and the cytotoxic emtansine. The response rate of breast cancer CNS metastases to TDM1 was assessed retrospectively. Methods: Case notes were reviewed for all patients treated with T-DM1 for a diagnosis of HER2+ MBC treated at a single institution between 1/2/2010 and 1/12/2015. The proportion with CNS metastases progressing at commencement of TDM1 was determined to assess the activity of TDM1 in active CNS disease. Results: A total of 76 patients were identified with a median age of 56 years (range 32-81). TDM1 was given as 1st line in 7, 2nd line in 36, 3rd line in 8 and 4th or greater in 24.Patients received a median of 7 cycles of TDM1 (range 1-70) and were followed up for median of 460 days (range 29-2017days). CNS metastases were present in 23 of 76 patients at commencement of TDM1 and were actively progressing in 10/23. Of these 10 patients 4 (40%) had an objective response to therapy in the CNS (2 with meningeal and 2 with parenchymal metastases; 2 with and 2 without prior RT) and all 4 also responded in extra-cranial sites. CNS response was durable with a median duration of 17 cycles (range 4 – 31). Overall survival (OS) did not differ significantly between those with and without CNS metastases (median 85 weeks, 95% CI 81-107). In one other patient craniotomy was performed to excise an enlarging solitary CNS metastasis after 4 cycles of TDM1. Histopathology confirmed a diagnosis of radionecrosis. This may have been exacerbated by TDM1 as the lesion had been stable prior to commencement. Detailed treatment summaries will be presented. Conclusions: TDM1 is active in CNS metastases from HER2+ MBC. These data suggest that delaying CNS RT may be appropriate in a subset of patients. Randomised trials should be performed to assess this prospectively.
Gene Immunotherapy in Murine Acute Myeloid Leukemia: Granulocyte-Macrophage Colony-Stimulating Factor Tumor Cell Vaccines Elicit More Potent Antitumor Immunity Compared With B7 Family and Other Cytokine Vaccines
Authors: Kyriaki Dunussi-Joannopoulos, Glenn Dranoff, Howard J. Weinstein, James L.M. Ferrara, Barbara E. Bierer, James M. Croop
Journal: Blood (1998)