tbuckley/cabot-search huggingface dataset:
P14.74 Remarkable response to Combined BRAF and MEK Inhibitors in two Adults with leptomeningeal carcinomatosis secondary to Pleomorphic Xantoastrocytoma grade II with BRAFv600E mutation
Authors: M Eoli, B Pollo, A Silvani, R Paterra, A Erbetta, E Anghileri, P Gaviani, G Finocchiaro
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Several cancers with the BRAF V600E mutations have been successfully treated with targeted therapy. Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor, with an incidence of 0.07cases per 100,000. The BRAFV600 mutation is present in 38–60% of PXA. Typical treatment is gross total resection, followed by radiotherapy and cytotoxic chemotherapy at recurrence MATERIAL AND METHODS Two cases are described. RESULTS The first case is a 37 old man with a left temporal lobe lesion who underwent a craniotomy with total tumor resection. Histological diagnosis was PXA WHO grade 2with BRAF V600E mutation.Five months after, MR imaging of his brain and spine showed tumor progression with extensive leptomeningeal disease. The patient received adjuvant brain and spinal radiotherapy Two weeks after, due to rapid clinical worsening he had a new brain and spinal MRI showing hydrocephalus and progression of the pachymeningeal-based masses and received an emergency ventricular -peritoneal shunt. Given the genetic analysis, the extent of disease and rapidity of the progression, BRAF and MEK inhibitors, dabrafenib (150 mg, twice daily) and trametinib (2 mg, daily) were started. Remarkably, within 2 week of initiating dual-targeted therapy, the patient experienced a dramatic improvement in consciousness and overall strength; brainand spinal MRI revealed initial reduction of the leptomenigeal enhacement and no evidence of progression of the intraparenchymal disease. The therapy was well-tolerated. Currently, after sixteen months,the patient remains on treatment with a consistent functional status improvement and no radiological evidence of disease progression. The second case is a 51 old women who developed leptomeningeal carcinomatosis seven year after resection of a frontal left PXA WHO grade 2 with BRAFv600E mutation. The patient had received brain radiotherapy five years after diagnosis and Cyber Knife for tumor progression. Ten months later MR imaging of his brain and spine showed tumor progression with extensive leptomeningeal disease, she was treated with temozolomide for 8 after clinical and radiological worsening she had a second surgery with resection of recurrent frontale left lesion Histopathology PXA WHO grade 2 with BRAF V600E mutation. She developed hydrocephalus, received an emergency ventricular -peritoneal shunt. BRAF and MEK inhibitors, dabrafenib (150 mg, twice daily) and trametinib (2 mg, daily) were started three months ago with initial clinical benefit CONCLUSION All patients with PXA should be tested for the BRAFV600 mutation, since, in these cases, targeted therapy with BRAF and MEK inhibitors seems to be a useful option for salvage treatment.
ESD, not EMR, should be the first-line therapy for early gastric neoplasia
Authors: Neal Shahidi, Michael J Bourke
Journal: Gut (2019)

With interest, we read the insightful recommendations by Banks et al 1 and the British Society of Gastroenterology on the management of precancerous conditions and lesions in the stomach. They rightly identify that the management of these conditions lacks consistency not only in the UK but also in the majority of Western societies.2 With a growing appreciation for quality indicators in upper GI endoscopy,3 these guidelines are an essential resource for both general endoscopists and tissue resection specialists.

Nevertheless, despite the increasing expertise in endoscopic submucosal dissection (ESD) outside of Japan,4 we were surprised that endoscopic mucosal resection (EMR) was recommended for lesions ≤10 mm. This is in contrast to recommendations by the Japan Gastroenterological Endoscopy Society (JGES)5 and the European Society of Gastrointestinal Endoscopy (ESGE).6 

Three systematic reviews7–9 have compared ESD versus EMR for early gastric cancer (EGC). In …
Soluble RANKL is physiologically dispensable but accelerates tumour metastasis to bone
Authors: Tatsuo Asano, Kazuo Okamoto, Yuta Nakai, Masanori Tsutsumi, Ryunosuke Muro, Ayako Suematsu, Kyoko Hashimoto, Tadashi Okamura, Shogo Ehata, Takeshi Nitta, Hiroshi Takayanagi
Journal: Nature Metabolism (2019)
P04.11 Voxelwise correlation between vascular MRI parameters obtained with ASL and DSC is decreased in IDH-wt non-enhancing glioma
Authors: E A H Warnert, F Incekara, A J P E Vincent, J W Schouten, M J van den Bent, P J French, H J Dubbink, J M Kros, J A Hernandez-Tamames, M Smits
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Comparative studies of dynamic susceptibility contrast (DSC) based measurement of cerebral blood volume (CBV) or cerebral blood flow (CBF) and arterial spin labelling (ASL) based measurement of CBF have previously shown good correlation of these parameters in human glioma. However, these studies were mostly done before inclusion of the mutation status of the isocitrate dehydrogenase (IDH) encoding gene in brain tumour classification. In light of the call for gadolinium-free imaging, here we investigate the effect of IDH-mutation status on the correlation between ASL and DSC-based perfusion measurements in non-enhancing glioma. MATERIAL AND METHODS Twenty-two patients with non-enhancing glioma and confirmed IDH-mutation status (next generation sequencing, 6 IDH-wildtype and 16 IDH-mutated) underwent 3T MRI scanning (GE, Milwaukee, WI, USA). Image acquisition included a 3D spiral pseudocontinuous ASL with time-encoded labelling (7 effective label delays from 0.8 to 2 s, reconstruction matrix 128x128x42, resolution 1.9x1.9x3.5 mm3), and 2D DSC imaging (122 TRs, TR/TE 1500m/18.6ms, 15 slices, voxel size: 1.88x1.88x4 mm3) in which a bolus of 7.5ml of gadolinium-based contrast agent (Gadovist, Bayer, Leverkussen, GE) was injected. A pre-load bolus of equal size was given 5 minutes prior to DSC imaging. DSC and ASL images were motion corrected and linearly registered to high resolution FLAIR images (FSL, version 5.0.9, Oxford, UK). DSC-relative CBV (rCBV), DSC-relative CBF (rCBF), and ASL-CBF maps were calculated via previously described methods. The glioma region of interest (ROI) was determined via manual segmentation on the FLAIR images. Voxel-wise Pearson’s linear correlation coefficients (ρ) within this ROI were calculated between ASL-CBF and DSC-rCBV, and between ASL-CBF and DSC-rCBF. RESULTS Normalised histograms indicate that IDH-wt glioma has higher values for ASL-CBF, DSC-rCBV, and DSC-rCBF than IDH-mutated glioma. IDH-wildtype glioma has a significantly lower ρ ASL-CBF vs DSC-rCBV and ρ ASL-CBF vs DSC-rCBF than IDH-mutated glioma (two-sample t-tests p &lt; 0.05). CONCLUSION IDH-mutation status of non-enhancing glioma potentially affects the correlation between ASL-CBF and DSC-rCBF/rCBV and should be taken into account when moving towards ASL-only imaging. The decreased correlation between ASL and DSC-based vascular parameters in IDH-wt gliomas may be due to more aggressive vasculature in subtypes of IDH-wt tumours. Future work includes expansion of the current patient cohort (part of the ongoing iGENE study).
Automated detection and classification of thyroid nodules in ultrasound images using clinical-knowledge-guided convolutional neural networks
Authors: Tianjiao Liu, Qianqian Guo, Chunfeng Lian, Xuhua Ren, Shujun Liang, Jing Yu, Lijuan Niu, Weidong Sun, Dinggang Shen
Journal: Medical Image Analysis (2019)
A case-control study evaluating differences in resource utilization between diabetic and non-diabetic cancer patients undergoing chemotherapy
Authors: M. D. Robertson, T. J. George, M. Chang, L. C. Richardson
Journal: Journal of Clinical Oncology (2006)

6126 Background: Patients with diabetes mellitus (DM) and cancer have been noted to have worse overall and disease-free survival compared to those without DM. However, there is a paucity of data addressing why diabetic cancer patients have worse outcomes. We performed a retrospective case-control study to evaluate cancer patients undergoing chemotherapy comparing persons with and without DM to evaluate differences in resource utilization and mortality. Methods: Using chart review and tumor registry data from January 2001 through December 2003, we identified DM patients 18 years or older, treated with chemotherapy at the Gainesville Veterans Administration Medical Center (GVAMC) for lung, colon, or head and neck cancer. Non-diabetic (Non-DM) controls were matched for age, cancer type and stage. A comorbidity score was calculated based on a previously validated measurement scale, Adult Comorbidity Evaluation 27 (ACE-27). The primary outcome measure was the number of inpatient hospital days in the first year after diagnosis. Secondary outcome measures included the total number of outpatient visits, emergency room (ER) visits, infusion room visits for chemotherapy, blood transfusions, home health consults, telephone calls, and mortality. Results: A total of 42 DM cases and 42 non-DM controls were identified who had undergone similar treatments with radiation and surgery. The DM patients had higher comorbidity ACE 27 scores when corrected for the cancer being treated, median 3.0 versus 2.0, p &lt; 0.005. The table summarizes the results. Mortality was the same (15) for both the DM and non-DM patients at one year. Conclusions: Cancer patients with DM undergoing chemotherapy have significantly more comorbidities and utilize more outpatient visits compared to non-DM. However, all other measures of resource utilization and mortality appear similar. Further studies to identify causes of increased utilization should be done. [Table: see text] No significant financial relationships to disclose.
Suz12 inactivation cooperates with JAK3 mutant signaling in the development of T-cell acute lymphoblastic leukemia
Authors: Michael Broux, Cristina Prieto, Sofie Demeyer, Marlies Vanden Bempt, Llucia Alberti-Servera, Inge Lodewijckx, Roel Vandepoel, Nicole Mentens, Olga Gielen, Kris Jacobs, Ellen Geerdens, Carmen Vicente, Charles E. de Bock, Jan Cools
Journal: Blood (2019)
Targeting B-cell malignancies: Impact of an educational curriculum on BTK inhibitors.
Authors: Lauren Willis, Mindy Tanzola, Richard Caracio, Katie S. Lucero, Bijal D. Shah, Jennifer Ann Woyach, Richard R. Furman, Michael Wang, Jennifer R. Brown
Journal: Journal of Clinical Oncology (2019)

10531 Background: We sought to determine if a curriculum of online continuing medical education (CME) activities could improve hematologists/oncologists (hem/onc) knowledge and competence related to clinical decision making in the use of BTKi in patients with B-cell lymphomas. Methods: An expert panel identified knowledge/competence gaps related to the use of Bruton's tyrosine kinase inhibitors (BTKi) in B-cell lymphomas. A clinical practice assessment (CPA) survey was launched May 2018 to further assess baseline educational needs. Based on the needs identified, 7 activities were posted online between May-Dec 2018. Multiple-choice questions were asked before and after participation in each activity and were grouped into learning topics. Mean knowledge/competence was calculated for the CPA and across all 7 activities. The impact of education was examined using a pre/post design. Statistical significance was assessed using a chi-square statistic ( P &lt; .05 level). Results: For all topics except foundational/differentiating BTKi, the audiences participating in the baseline CPA and the other 7 activities, were similar or lower at pre-test, suggesting that learning needs continued until our education addressed them. All changes from pre-to-post-test were significant ( P &lt; .001). The largest relative percent change from pre- to post-test was seen with knowledge of resistance mechanisms for BTKi as well as knowledge/competence managing AE of BTKi. Post-test there was a high level of knowledge about the selectivity seen with 2nd generation BTKi. Conclusions: This analysis shows that online CME, utilizing many different formats (video, text, panel discussions) can significantly improve the knowledge and competence of hem/oncs in multiple areas surrounding the use of BTKi for the treatment of B-cell lymphomas. Results also suggest the following areas warrant further education: awareness of clinical trial safety and efficacy data for BTKi and mechanisms for resistance to BTKi. [Table: see text]
Use of Bypassing Agents Prior to and Post Bypassing Agent Dosing Guidance during Emicizumab Prophylaxis: Analyses from the HAVEN 1 Study
Authors: Michael U. Callaghan, Claude Negrier, Guy Young, Liane Khoo, Johnny Mahlangu, Jerzy Windyga, Johannes Oldenburg, Jin Xu, Olivier Catalani, Elina Asikanius, Joanne I. Adamkewicz, Midori Shima
Journal: Blood (2017)
P04.07 Correlation of 18F-fluorethyl-L-tyrosine (18F-FET) uptake in positron emission tomography (PET) and MRI growth rate in low-grade glioma
Authors: M Mueller, M Kamp, M Sabel, G Stoffels, N Galldiks, K Langen, M Rapp
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Low-grade gliomas (LGGs, WHO grade II) are a heterogeneous group of tumors of the central nervous system with diverse behavior in histopathology, genetics and growth patterns. Therefore, different therapeutic strategies are discussed ranging from watchful waiting to radical resection and adjuvant radio-/chemotherapy. For a better evaluation of tumor progression or malignant transformation, the O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) uptake in PET or the tumor growth rate assessed on MRI are used depending on the neurooncological center. Here, we correlated both methods. MATERIAL AND METHODS Inclusion criteria for this retrospective study were (1) newly diagnosed and neuropathologically confirmed low-grade glioma; (2) at least two MRIs at initial diagnosis and follow-up for calculation of the tumor growth rate (using IDS7 by Sectra AB, Sweden, 2018); (3) and an additional preoperative 18F-FET PET scan. RESULTS From 2008 to 2018, 34 patients were identified (mean age 39.7 years; 68% diffuse astrocytoma). The mean tumor growth rate on MRI was 0.091 cm3/d. The average mean 18F-FET uptake was 1.42; the average maximum 18F-FET uptake was 2.18. The Pearson correlation coefficient between the tumor growth rate and the mean and maximum 18F-FET uptake was r=0.19, and r=0.10. In the group of diffuse astrocytomas, the mean growth rate in tumors with a mean 18F-FET uptake of &gt;1.5 was significantly higher than the mean growth rate of those with a mean 18F-FET uptake of ≤1.5 (p&lt;0.1). CONCLUSION Data suggest that astrocytic LGGs with increased 18F-FET uptake may show a more aggressive behaviour, with a potentially higher risk for an earlier tumor progression or malignant transformation. For further elucidation of a correlation between the tumor growth rate and the 18F-FET uptake, larger prospective studies are needed. In the future, the combination of both methods in the management of low-grade gliomas could help to detect tumor progression as well as tumor malignization more precisely.
Abstract 10843: Mutated Desmoglein-2 Proteins in Arrhythmogenic Right Ventricular Cardiomyopathy are Incorporated into the Desmosome and Exhibit Dominant-negative Effects
Authors: Torsten B Rasmussen, Johan Palmfeldt, Peter H Nissen, Raffaela Magnoni, Søren Dalager, Uffe B Jensen, Won Y Kim, Lene Heickendorff, Henning Mølgaard, Henrik K Jensen, Ulrik T Baandrup, Peter Bross, Jens Mogensen
Journal: Circulation (2012)

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure, and sudden death. The majority of ARVC p...
Schwann cells expressing nociceptive channel TRPA1 orchestrate ethanol-evoked neuropathic pain in mice
Authors: Francesco De Logu, Simone Li Puma, Lorenzo Landini, Francesca Portelli, Alessandro Innocenti, Daniel Souza Monteiro de Araujo, Malvin N. Janal, Riccardo Patacchini, Nigel W. Bunnett, Pierangelo Geppetti, Romina Nassini
Journal: Journal of Clinical Investigation (2019)

Excessive alcohol consumption is associated with spontaneous burning pain, hyperalgesia, and allodynia. Although acetaldehyde has been implicated in the painful alcoholic neuropathy, the mechanism by which the ethanol metabolite causes pain symptoms is unknown. Acute ethanol ingestion caused delayed mechanical allodynia in mice. Inhibition of alcohol dehydrogenase (ADH) or deletion of transient receptor potential ankyrin 1 (TRPA1), a sensor for oxidative and carbonyl stress, prevented allodynia. Acetaldehyde generated by ADH in both liver and Schwann cells surrounding nociceptors was required for TRPA1-induced mechanical allodynia. Plp1-Cre Trpa1fl/fl mice with a tamoxifen-inducible specific deletion of TRPA1 in Schwann cells revealed that channel activation by acetaldehyde in these cells initiates a NADPH oxidase-1-dependent (NOX1-dependent) production of hydrogen peroxide (H2O2) and 4-hydroxynonenal (4-HNE), which sustains allodynia by paracrine targeting of nociceptor TRPA1. Chronic ethanol ingestion caused prolonged mechanical allodynia and loss of intraepidermal small nerve fibers in WT mice. While Trpa1-/- or Plp1-Cre Trpa1fl/fl mice did not develop mechanical allodynia, they did not show any protection from the small-fiber neuropathy. Human Schwann cells express ADH/TRPA1/NOX1 and recapitulate the proalgesic functions of mouse Schwann cells. TRPA1 antagonists might attenuate some symptoms of alcohol-related pain.
A Central Venous Catheter That Cannot Be Dislodged Easily by a Confused Patient
Authors: Anil K. Agarwal
Journal: Annals of Internal Medicine (2019)

Letters3 September 2019A Central Venous Catheter That Cannot Be Dislodged Easily by a Confused PatientAnil K. Agarwal, MDAnil K. Agarwal, MDThe Ohio State University Wexner Medical Center, Columbus, Ohio (A.K.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0352 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Brown and Kim's (1) technique of posterior tunneling of a catheter is interesting. However, it creates challenges, such as as positioning on placement of the catheter to verify tip position under fluoroscopy, confirming the stability of sterile dressing, possible compression and kinking in the back, and positioning for dialysis to ensure flow and watching for disconnection. If the catheter becomes dysfunctional, an exchange would cause similar challenges. This technique can be considered in selected patients, but more information about outcomes is needed.Reference1. Brown RS, Kim D. A central venous catheter that cannot be dislodged easily by a confused patient. Ann Intern Med. 2019;170:503-4. [PMID: 30583294]. doi:10.7326/L18-0439 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: The Ohio State University Wexner Medical Center, Columbus, Ohio (A.K.A.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0352. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Central Venous Catheter That Cannot Be Dislodged Easily by a Confused Patient Robert S. Brown and Ducksoo Kim A Central Venous Catheter That Cannot Be Dislodged Easily by a Confused Patient Robert S. Brown and Ducksoo Kim A Central Venous Catheter That Cannot Be Dislodged Easily by a Confused Patient Bharat Nathoo , Marianne Stroz , and Peter Stroz Metrics 3 September 2019Volume 171, Issue 5Page: 386KeywordsCathetersConflicts of interestDisclosureMedical dialysis ePublished: 3 September 2019 Issue Published: 3 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Misinterpretation of time-to-first event curves can lead to inappropriate treatment
Authors: Benjamin Hartley, Gerard J. Criner, Mark T. Dransfield, David M.G. Halpin, MeiLan K. Han, C. Elaine Jones, Sally Kilbride, Peter Lange, David A. Lipson, David A. Lomas, Neil Martin, Fernando J. Martinez, Dave Singh, Robert A. Wise, Sally Lettis
Journal: European Respiratory Journal (2019)

<b>Evaluation of treatment effect durability over time cannot be based on analyses that examine the first of many events. Here, it is explained how misinterpretation of survival curves led to wrong conclusions in a recent <i>ERJ</i> editorial.</b>http://bit.ly/2K3amgQ
P13.14 Use of Foundation one CDx for molecular screening in patients with primary brain tumors: Gustave Roussy Experience
Authors: C Baldini, W Boulfoul, L Lacroix, E Rouleau, J Scoazec, A Varga, A Hollebecque, V Ribrag, J Soria, C Massard
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with primary brain tumors usually have poor prognosis and few therapeutic options. However recent report showed that they may benefit from molecular screening to improve treatment benefit and enrollment in clinical trials. We aimed to evaluate if molecular screening using Foundation One Dx may help therapeutic strategies in primary brain tumor patients. MATERIAL AND METHODS Between October 2018 and December 2018, we enrolled prospectively patients in the MOSCATO (Molecular Screening for cancer Treatment Optimization) 02 trial using the Foundation One Dx test. Patients were eligible if they had good Performans status (PS) (0 or 1) and tumor tissue material available. Results were reviewed during a molecular multidisciplinary meeting weekly at the Drug Development Department at Gustave Roussy to decide on orientation and matched therapy according to molecular alterations. RESULTS Finally thirty-three patients were enrolled in the study. Twenty six tumor tissues were analysed and 7 patients were screen failures due to tumor tissue unavailability. Median age was 49 years old (19 - 72). Patients had a good PS with a median of 1 (0–2) and were mostly males (76%). The most common tumor type was glioblastoma (79%). Five patients had a high grade tumor including 2 medulloblastomas. Median time between consent and multidisciplinary meeting was 70 days (49 - 156). Median percentage of tumor cells was 78% (30–80%). The tumor mutational burden (TMB) was available in 26 patients. The median TMB was 4 mutations per megabase (0 - 277). The most frequent alterations were TERT promoter mutation 22/26 (85%), CDKN2A loss 14/26 (54%), MTAP loss 11/26 (42%), EGFR amplification (38%) including 4 EGFRvIII amplification, TP53 mutation and PTEN deletion 9/26 (35%) respectively, PIK3CA mutation 5/26 (19%), CDK4 or 6 amplification 4/26 (15%), NF1 mutation 3/26 (12%), 2 IDH1 mutations, 2 MET amplifications, 2 HGF amplifications, 1 FGFR2 mutation, 1 BRAF V600E mutation, 1 PDGFRA amplification, 1 EZH2 mutation and 1 SMARCA4 mutation. Finally 11 patients (42%) were oriented according to molecular alterations (EGFR amplifications, BRAF mutation), 1 patient was treated and is ongoing with a BRAF inhibitor and 1 patient is in screening in atrial with an EGFR inhibitor. CONCLUSION Molecular screening with Foundation One Dx test is feasible in patients with primary brain tumors and can help therapeutic strategies. However the time between consent and multidisciplinary meeting was the main limitation to our study and affected enrollment in clinical trials.
Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis
Authors: Giammauro Berardi, Zenichi Morise, Carlo Sposito, Kazuharu Igarashi, Valentina Panetta, Ilaria Simonelli, Sungho Kim, Brian K.P. Goh, Shoji Kubo, Shogo Tanaka, Yutaka Takeda, Giuseppe Maria Ettorre, Gregory C. Wilson, Matteo Cimino, Chung-Yip Chan, Guido Torzilli, Tan To Cheung, Hironori Kaneko, Vincenzo Mazzaferro, David A. Geller, Ho-Seong Han, Akishige Kanazawa, Go Wakabayashi, Roberto Ivan Troisi
Journal: Journal of Hepatology (2019)