tbuckley/cabot-search huggingface dataset:
Prognostic Effects of Pretreatment Statuses at Diagnosis in Patients with Chronic Myeloid Leukemia: Results of the New Target Observational Study 1
Authors: Takaaki ONO, Naoto Takahashi, Masahiro Kizaki, Tatsuya Kawaguchi, Ritsuro Suzuki, Kazuhito Yamamoto, Kazunori Ohnishi, Tomoki Naoe, Itaru Matsumura
Journal: Blood (2019)
Long-Term Safety and Efficacy of Mitapivat (AG-348), a Pyruvate Kinase Activator, in Patients with Pyruvate Kinase Deficiency: The DRIVE PK Study
Authors: Rachael F. Grace, D. Mark Layton, Frédéric Galactéros, Wilma Barcellini, Eduard J. van Beers, Hassan M. Yaish, Yaddanapudi Ravindranath, Kevin H. M. Kuo, Sujit Sheth, Janet L. Kwiatkowski, Lei Hua, Peter F. Hawkins, Chris Mix, Bertil Glader
Journal: Blood (2019)
Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma Treated with Isatuximab Plus Pomalidomide and Dexamethasone: Icaria-MM Study
Authors: Katherine Houghton, Meletios A. Dimopoulos, Peggy Lin, Sophie Guillonneau, Denise Bury, Michel Attal, Paul G. Richardson, Michel Delforge
Journal: Blood (2019)
Phase I Study of Pracinostat in Combination with Gemtuzumab Ozogamicin (PraGO) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)
Authors: Talha Badar, Guru Subramanian Guru Murthy, Lyndsey Runaas, Karen-Sue B. Carlson, Laura C. Michaelis, Alexandra M. Harrington, Ehab L. Atallah, Sameem Abedin
Journal: Blood (2019)
A novel technique in the management of refractory variceal bleeding
Authors: Gustavo Oliveira Luz, Sérgio Eiji Matuguma, Antonio Coutinho Madruga Neto, Igor Braga Ribeiro, Fernanda Dal Bello, Diogo Turiani Hourneaux de Moura, Eduardo Guimarães Hourneaux de Moura
Journal: Endoscopy (2019)

Acute esophageal variceal bleeding is a complication with high morbidity and mortality, causing 70 % of upper gastrointestinal bleeding in patients with liver disease [1]. The first-line treatment of bleeding combines the use of vasoactive drug therapy, endoscopic band ligation, and prophylactic antibiotic administration, following initial hemodynamic resuscitation efforts [2]. Around 10 % – 20 % of cases are refractory to conventional therapy, necessitating alternative therapies for hemorrhagic control [1]. Among the rescue therapies for variceal hemorrhage are the traditional use of balloon tamponade and transjugular intrahepatic portosystemic shunt (TIPS). The current use of a self-expanding metal stent (SEMS) has also been utilized as a new option for refractory bleeding [3].
Implantable and degradable antioxidant poly(ε-caprolactone)-lignin nanofiber membrane for effective osteoarthritis treatment
Authors: Ruiming Liang, Jinmin Zhao, Bo Li, Peian Cai, Xian Jun Loh, Chuanhui Xu, Peng Chen, Dan Kai, Li Zheng
Journal: Biomaterials (2019)
RARE-31. TREATMENT OUTCOME OF CHILDREN WITH PLEOMORPHIC XANTHOASTROCYTOMA: RETROSPECTIVE ANALYSIS – A SINGLE INSTITUTION EXPERIENCE
Authors: Ossama Maher, Toba Niazi, Ziad Khatib, John Ragheb
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Pleomorphic xanthoastrocytoma (PXA) and anaplastic pleomorphic xanthoastrocytoma (APXA) are two types of rare astrocytomas in pediatrics. There is limited literature reporting their outcomes. METHODS A retrospective analysis of pediatric patients with diagnosis of PXA and APXA treated at Nicklaus Children’s Hospital was conducted using descriptive measures. RESULTS A chart review of patients with brain tumors from 2001 to 2019 revealed that 13 patients (median age 6 years, range 2–17 years) were diagnosed with non-metastatic PXA (n=12) and APXA (n=1). Six patients (46%) were male. Clinical presentation included seizures (n=8), headaches (n=2) cranial nerve palsies (n=2). Diagnostic imaging showed tumor in the temporal lobe (n=5), parietal lobe (n=2), temporoparietal lobe (n=2), frontal lobe (n=1), occipital lobe (n=1), others (n=2). BRAF V600E mutation were identified in three of five analyzed tumors including PXA (n=4) and APXA (n=1). Surgical intervention consisted of gross total resection (n=8) and near/subtotal resection (n=5). Ten patients (76%) required a second surgery (median 2; range 1–4) due to local recurrence. The median time to recurrence was 3 years (range 6 months - 7 years). Three patients (23%) had malignant transformation of PXA, which occurred three to eight years from the initial surgery; one of them also had extensive spinal metastasis. Focal radiation was given to six patients (46%) due to multiple recurrence (n=2), malignant transformation (n=3), APXA (n=1). At a median follow up of 8 years (range 3 to 20 years), eight patients remain alive, three patients had lost to follow up, two patients died from progressive disease. Long-term sequelae varied as follows; seizures (n=5), motor weakness (n=4), cranial nerve palsies (n=2), and learning disability (n=1). CONCLUSION PXA is associated with high local recurrence rate and uncommonly malignant transformation to APXA in pediatrics, which requires close follow-up due to unpredictable biological behavior of these tumors.
INNV-08. VALIDATION OF READIBAND™ ACTIGRAPH AND ASSOCIATED SLEEP/WAKE CLASSIFICATION ALGORITHMS IN PREDICTING CANCER-RELATED FATIGUE IN HIGH GRADE GLIOBLASTOMA
Authors: Megan Tipps, Meghan Hultman, Nilanjana Banerji, Kelsey Jackson, Minda Liu, Amy Ellenberger, Emily Sanville, John Trusheim
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Standard care for glioblastoma consists of maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide. Fatigue and sleep disturbances are among the most common side-effect reported by these patients. Monitoring long-term sleep patterns and fatigue levels in this population would allow for comparison between iatrogenic sleep disturbances, disease progression, treatment tolerance, and self-reported levels of fatigue. Wearable actigraph devices provide a potential alternative approach to polysomnography for long-term sleep monitoring. Here, we describe initial results from the implementation of the Readiband™ Sleep Tracker (Fatigue Science) for monitoring sleep patterns and fatigue in newly diagnosed glioblastoma patients. PATIENTS AND METHODS Patients with primary glioblastoma were prospectively enrolled and asked to wear the Readiband™ Sleep Tracker for a maximum of twelve months or until disease progression. Data regarding alertness levels and sleep patterns were collected from Fatigue Science. Patients were also asked to report fatigue levels and sleep quality via the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Pittsburg Sleep Quality Index (PSQI) questionnaires, respectively. Demographic, pathologic, and clinical information was abstracted from electronic medical records. RESULTS The Readiband™ data includes sleep/wake assessments, as well as sleep quality, sleep efficiency, and alertness scores. The overall sleep patterns reported by Readiband™ align with self-reported sleep times and sleep quantity. In addition, the SAFTE™ alertness scores show a positive correlation with FACIT-F (r=0.80) scores, and the sleep quality scores generated by Readiband™ show a negative correlation with PSQI (r=-0.83) scores. CONCLUSION The Readiband™ Sleep Tracker is a convenient and viable approach for monitoring sleep and fatigue in glioblastoma patients. Our preliminary findings suggest that actigraph measures can be used to monitor sleep quality and predict fatigue in this population. The study is ongoing to understand implications of sleep patterns on disease progression and treatment tolerance in primary glioblastoma.
Lung ultrasound‐guided treatment in ambulatory patients with heart failure: a randomized controlled clinical trial (LUS‐HF study)
Authors: Mercedes Rivas‐Lasarte, Jesús Álvarez‐García, Juan Fernández‐Martínez, Alba Maestro, Laura López‐López, Eduard Solé‐González, Maria J. Pirla, Nuria Mesado, Sonia Mirabet, Paula Fluvià, Vicens Brossa, Alessandro Sionis, Eulàlia Roig, Juan Cinca
Journal: European Journal of Heart Failure (2019)
Germline Mutations in ETV6 are Associated with In Vivo cytoplasmic Localization of ETV6 and Cause Transcriptional Dysregulation of Interferon Response Genes
Authors: Marlie H Fisher, Greg Kirkpatrick, Courtney L Jones, Brett M. Stevens, Michael Callaghan, Eric Pietras, Kenneth L. Jones, Christopher C. Porter, Jorge Di Paola
Journal: Blood (2019)
TMIC-43. ROLE OF EXTRACELLULAR FERRITIN HEAVY CHAIN PROTEIN IN GLIOBLASTOMA MULTIFORME
Authors: Bhavyata Pandya, Vagisha Ravi, James Connor
Journal: Neuro-Oncology (2019)

Abstract Increased expression of Ferritin heavy chain (FHC) protein has been associated with poor prognosis in Glioblastoma Multiforme (GBM) which is one of the most aggressive and common types of brain cancer. GBM patients have also been found to have increased extracellular ferritin levels, in their serum and cerebrospinal fluid (CSF), which are lowered once the source/tumor has been resected. Extracellular FHC can function as an iron delivery protein, and increasing amount of iron has been known to contribute to tumor initiation and proliferation. To study the effect of extracellular FHC in GBM cells we used patient derived GBM, CD133+ cancer stem cells (GSCs) from the pro-neural (T3691) and mesenchymal (T387) subtypes. Using recombinant FHC, conjugated with quantum dots (QD), we observed significant increase in cellular viability and intracellular uptake of FHC by the GSCs in a dose dependent manner. Our lab has previously shown that extracellular FHC interacts with T-Cell Immunoglobulin Mucin Receptor 1 (Tim-1) in the human oligodendrocytes. In order to determine if GSCs express the Tim-1 receptor we first confirmed its expression on GSCs using immunoblotting and immunocytochemistry. To test if FHC interacts with Tim-1, we performed knockdown of Tim-1 using siRNAs. However, the siRNA was not able to downregulate the Tim-1 receptors. Next, we exposed the GSCs to Sema4A, which has been shown in our previous studies to interact with Tim-1 receptor on human oligodendrocytes and is toxic to oligodendrocytes. The GSCs however were not affected by the saturable concentration of Sema4A. Thus, through this study we have shown the expression of potential FHC receptors on GSCs and a robust effect of H-ferritin on GSCs proliferation. Further experiments are warranted in this direction to understand this extracellular FHC uptake pathway and its role in GBM cell proliferation.
The Genomic and Transcriptomic Landscape of Double-Refractory Multiple Myeloma
Authors: Bachisio Ziccheddu, Giulia Biancon, Chiara De Philippis, Filippo Bagnoli, Francesco Maura, Matteo Dugo, Andrea Devecchi, Loris De Cecco, Marialuisa Sensi, Carolina Terragna, Marina Martello, Tina Bagratuni, Eftathios Kastritis, Meletios A. Dimopoulos, Michele Cavo, Cristiana Carniti, Vittorio Montefusco, Paolo Corradini, Niccolo Bolli
Journal: Blood (2019)
GENE-15. TARGETING OF EPENDYMOMA AS INFORMED BY ONCOGENIC 3D GENOME ORGANIZATION
Authors: Konstantin Okonechnikov, Jens-Martin Hübner, Owen Chapman, Abhijit Chakraborty, Rosalind Bump, Sahaana Chandran, Katerina Kraft, Rocio Acuna Hidalgo, Stefan Mundlos, Nicole Coufal, Michael Levy, John Crawford, Ferhat Ay, Jill Mesirov, Kristian Pajtler, Jesse Dixon, Stefan Pfister, Marcel Kool, Lukas Chavez
Journal: Neuro-Oncology (2019)

Abstract By profiling enhancers in primary ependymoma tumors, we have recently identified putative oncogenes, molecular targets, and functional pathways. Inhibition of selected targets diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymoma. While enhancers frequently regulate the nearest gene, unambiguous identification of enhancer target genes remains to be a challenge in the absence of chromosome conformation information. Consequently, we have now used HiC to map the 3-dimensional organization of tumor chromatin in the two most common and aggressive ependymoma subgroups: posterior fossa group A (PF-EPN-A) and supratentorial ependymomas with gene fusions involving the NF-κB subunit gene RELA (ST-EPN-RELA). By an integrative analysis of enhancer and gene expression in the context of the newly derived HiC data, we find that a large amount of the previously predicted enhancer target genes can be confirmed by physical interactions. Importantly, we also identify many new putative tumor-dependency genes activated by long-range promoter-enhancer interactions. Complementary to the analysis of gene-enhancer interactions, we have also leveraged the HiC data for resolving structural rearrangements underlying copy number alterations frequently observed in PF-EPN-A tumors. Especially copy number gains of the 1q arm of chromosome 1 are associated with poor survival. Our preliminary results reveal complex structural variants that underlie 1q gains, which lead to inter-chromosomal rearrangements and affect several genes that potentially contribute to poor survival. We now aim to test the relevance of the novel candidate tumor-dependency genes for tumor cell growth and proliferation in patient derived ependymoma models.
From the Authors
Authors: C.M.J.M. Gerrits, R.M.C. Herings, H.G.M. Leufkens, J.W.J. Lammers
Journal: European Respiratory Journal (2003)

N-acetylcysteine is unlikely to reduce hospitalisation for chronic obstructive pulmonary diseaseTo the Editor:We read with interest the recent paper by GERRITS et al.[1] reporting on the effectiveness of N-acetylcysteine in reducing re-hospitalisations for chronic obstructive pulmonary disease (COPD).We are concerned, however, that the apparent benefit is actually the result of bias in study design and analysis.The paper mentions that patients were considered users if they received N-acetylcysteine "immediately" after discharge.However, we are not given the definition of "immediately" nor are we provided with the average and range of the length of time from hospital discharge to dispensing of the first prescription for N-acetylcysteine.Since follow-up time starts at discharge from hospital for all subjects, irrespective of whether they will or will not be dispensed N-acetylcysteine, there is a strong possibility of immortal time bias [2].Indeed, the time period from discharge to the first dispensing is "immortal" by definition since re-admissions could not occur during this period; if they did occur before the first prescription, the subject would have been classified as "unexposed".Moreover, this immortal time period is in fact unexposed, since the subject has not yet received the drug, but is misclassified as exposed by this approach to data analysis.Consequently, such misclassified immortal time will cause the rate of re-admission in the "unexposed" to be artificially inflated resulting in an impression of a protective rate ratio for exposure.This bias will also accentuate the apparent dose/ response effect, since the daily dose calculation uses the immortal unexposed time and also considers it as exposed.It would be useful to redo these analyses, after properly classifying exposures.
RTHP-20. MULTI-INSTITUTIONAL ANALYSIS OF HIGH-RISK WHO GRADE II OLIGODENDROGLIOMA TREATED WITH ADJUVANT RADIOTHERAPY PLUS TEMOZOLOMIDE (TMZ) VERSUS PROCARBAZINE, LOMUSTINE, AND VINCRISTINE (PCV)
Authors: Martin Tom, David Routman, Nadia Laack, Kelsey Frechette, Deborah Park, Wei (Auston) Wei, Marc Leyrer, David Peereboom, Manmeet Ahluwalia, Samuel Chao, John Suh, Erin Murphy
Journal: Neuro-Oncology (2019)

Abstract PURPOSE To compare outcomes of adults with high-risk grade II oligodendroglioma treated with adjuvant radiotherapy plus adjunctive TMZ versus PCV. METHODS We queried a multi-institutional database from the Cleveland Clinic and Mayo Clinic of 158 adults with WHO grade II glioma who were high-risk (age &gt; 40 and/or subtotal-resection [STR]) and underwent adjuvant chemoradiation (TMZ or PCV) between 1997–2017. We included patients with oligodendroglioma by 1p/19q-codeletion or traditional histopathology. Fisher’s exact test was used to associate factors with chemotherapy group. The log-rank test was used to compare OS and PFS by chemotherapy group and clinical characteristics. RESULTS 52 patients were included with a median follow-up of 44 months (range, 3–259). Median age was 44 (range, 22–73), 49 (94%) underwent STR, and 28 (54%) were male. Presenting symptoms were seizure in 35 (67%) patients, sensory in 14 (27%), and motor in 8 (15%). Oligodendroglioma classification was by 1p/19q-codeletion in 27 (52%) and traditional histopathology in 25 (48%) patients. Median radiation dose was 54 Gy (range, 45–60). Chemotherapy was TMZ in 34 (65%) patients and PCV in 18 (35%). Patients who were older (P=0.003), lacked seizures (P=0.03), or had motor symptoms (P=0.04) were more likely to receive TMZ. Median OS was 223 months (95% CI, 181-not estimable) and median PFS was 118 months (95% CI, 69–223). Treatment with TMZ versus PCV was not associated with OS (median 186 vs. 223 months, respectively; P=0.71) or PFS (median 110 vs. 131 months, respectively; P=0.19). Age &gt;40 (P=0.009) and motor symptoms (P=0.027) were associated with adverse OS. Presence of motor symptoms was associated with worse PFS (P=0.008). CONCLUSION There was no statistically significant difference in OS or PFS between adjunctive TMZ versus PCV for adult high-risk grade II oligodendroglioma. A larger cohort with longer follow-up will provide additional insight.
TMIC-27. GLUTAMATERGIC NEURON-GLIOMA SYNAPSES DRIVE BRAIN TUMOUR PROGRESSION
Authors: Varun Venkataramani, Dimitar Tanev, Christopher Strahle, Alexander Studier-Fischer, Laura Fankhauser, Tobias Kessler, Maria Losada Perez, Christoph Körber, Markus Kardorff, Miriam Ratliff, Ruifan Xie, Heinz Horstmann, Mirko Messer, Sang Paik, Johannes Knabbe, Felix Sahm, Felix Kurz, Azer Acikgoez, Frank Herrrmannsdörfer, Amit Agarwal, Dwight Bergles, Anthony Chalmers, Hrvoje Miletic, Sevin Turcan, Christian Mawrin, Daniel Hänggi, Hai-Kun Liu, Sergio Casas Tinto, Wolfgang Wick, Frank Winkler, Thomas Kuner
Journal: Neuro-Oncology (2019)

Abstract A network of communicating tumour cells established by tumour microtubes (TMs) is supposed to mediate relevant aspects of progression and resistance of incurable gliomas. Moreover, neuronal activity has been shown to foster malignant behavior of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here, we report an unexpected direct communication channel between neurons and glioma cells in multiple disease models as well as in astrocytomas and glioblastomas (GBs) of adult patients: functional bona fide chemical synapses formed between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses (NGS) show a typical synaptic ultrastructure, are located on TM networks, and produce depolarizing postsynaptic currents mediated by glutamate receptors of the AMPA subtype. AMPA-type glutamate receptors (AMPAR) are expressed by a molecularly and morphologically distinct subpopulation of network-integrated glioma cells. Increased neuronal activity under epileptic conditions ex vivo or neuronal optogenetic stimulation in vivo enhanced, while general anesthesia diminished synchronized calcium transients in TM-connected glioma networks. Accordingly, anesthesia reduced invasiveness of TM-positive tumour cells in mice. Genetic perturbation of AMPAR or chronic AMPAR inhibition by perampanel decreased glioma invasion and proliferation in mice and deletion of GluRII in Drosophila glioma increased survival. These findings reveal a hitherto unappreciated direct synaptic communication between neurons and glioma cells that appears relevant for brain tumour biology, implying new avenues for glioma treatment.
Benzydamine inhibits osteoclast differentiation and bone resorption via down-regulation of interleukin-1 expression
Authors: Han Saem Son, Jiae Lee, Hye In Lee, Narae Kim, You-Jin Jo, Gong-Rak Lee, Seong-Eun Hong, Minjeong Kwon, Nam Young Kim, Hyun Jin Kim, Jin Ha Park, Soo Young Lee, Woojin Jeong
Journal: Acta Pharmaceutica Sinica B (2019)

Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Here, we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism. BA inhibited osteoclast differentiation and strongly suppressed interleukin-1β (IL-1β) production. BA inhibited osteoclast formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1β treatment. The reporter assay and the inhibitor study of IL-1β transcription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase, extracellular signal regulated kinase and P38, resulting in the down-regulation of IL-1β expression. BA also promoted osteoblast differentiation. Furthermore, BA protected lipopolysaccharide- and ovariectomy-induced bone loss in mice, suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.
Patient-Level Meta-Analysis of End-of-Therapy PET-CR as a Surrogate Endpoint for PFS and OS in Patients with Previously Untreated DLBCL: Implications for Clinical Trial Design
Authors: Donald Berry, Kristine Broglio, Carol Ward, Federico Mattiello, Deniz Sahin, Tina G Nielsen, Anna McGlothlin, Corrine Elliott, Thomas E. Witzig, Laurie H Sehn, Marek Trněný, Umberto Vitolo, Maurizio Martelli, Lale Kostakoglu, Grzegorz Nowakowski
Journal: Blood (2019)
Third-Party Rounds
Authors: Patrick B. Storey
Journal: JAMA (1974)

<h3>To the Editor.—</h3> I have just read the editorial (227:317, 1974) on the new term, "Third Party Rounds." What attracted my attention was the fact that I have just heard the term used for the first time by our American Medical Association inspector as we went through the survey process of our house staff program. I agree with you, and I hope the term can be headed off. But a new term seems to have all the potential of a prairie fire to spread crazily until it burns itself out. A rather good example of recent vintage is "health maintenance organization" (HMO) which means nothing more than prepaid group practice, with an almost limitless number of organizational variations possible. It will be interesting to see what happens to "Third-Party Rounds"— but I'm afraid!
A Phase II, Multicenter Study of High Dose Chemotherapy with Autologous Stem Cell Transplant Followed By Maintenance Therapy with Romidepsin for T-Cell Lymphoma
Authors: Niloufer Khan, Andrei R Shustov, Farhad Khimani, Mazyar Shadman, Ryan D. Cassaday, Jia Ruan, Alison J. Moskowitz, Andrew D. Zelenetz, Ariela Noy, David J. Straus, Pamela Drullinsky, Audrey Hamilton, Anita Kumar, Craig S. Sauter, Gunjan L. Shah, Matthew J Matasar, Esther Drill, Theresa Davey, Helen Hancock, Alexandra Bahgat, William Blouin, Karen Marie Schiavo, Heather Smith, Koen Van Besien, Sergio A. Giralt, Steven M. Horwitz, Parastoo B. Dahi
Journal: Blood (2019)
Battle Neurosis Treated with Leucotomy
Authors: B. Saaler
Journal: BMJ (1947)

Sudden Death after Intravenous Injection of Mercurial Diuretic SIR,-A.G. Oettle's case of sudden death after intravenous "neptal " (Oct.4, p. 530) prompts me to a few remarks.Such disasters cannot always be avoided-e.g., if they happen after the first injection to a patient, where there is no reason to expect untoward reactions.Such cases, fortunately, are extremely rare.More often, faulty.choice of the case and an overdose are the cause of toxic reactions.The following rules should help to restrict fatal or toxic reactions.Mercury administration must never be given in excess of the excretory power of the kidneys.Low con- centrating power and poor response to a previous injection are warning signals.The minimal injection-free interval should be three days, except in acute emergencies.Digitalis, strophanthin, urea, and ammonium chloride help to make this possible.The