tbuckley/cabot-search huggingface dataset:
Infectious Complications in Patients with Relapsed Acute Myeloid Leukemia (AML) Receiving Clofarabine Versus Fludarabine-Containing Salvage Chemotherapy Regimens
Authors: Michael S Mathisen, Hagop M. Kantarjian, Elias J. Jabbour, Guillermo Garcia-Manero, Farhad Ravandi, Stefan Faderl, Gautam Borthakur, Jorge E. Cortes, Alfonso Quintas-Cardama
Journal: Blood (2012)
Duodenal arteriovenous malformation: endosonographic diagnosis and coil embolization
Authors: Shibi Mathew, Prakash Zacharias, Lijesh Kumar, John Mathews, Prashanth Menon, Mathew Philip
Journal: Endoscopy (2016)

A 67-year-old man with a history of melena and a hemoglobin level of 4.8 g/dL was referred to our center for endoscopic evaluation. He had no significant comorbidities and his liver and renal functions were normal. His anemia was corrected with multiple blood transfusions. As upper gastrointestinal endoscopy showed fresh blood in the second part of the duodenum, a side-viewing endoscopy was carried out, which revealed a submucosal bulge with ulceration proximal to the ampulla ([Fig. 1 a]). Active bleeding from this lesion was noted during endoscopy ([Fig. 1 b]). Endosonography with color Doppler imaging showed arterialization of the venous spectral pattern and low resistance arterial flow supplying the lesion, suggestive of arteriovenous malformation (AVM) ([Fig. 2], [Video 1]). Subsequent computed tomography (CT) angiography confirmed a 6.1 × 6.2-mm AVM in the medial wall of the second part of the duodenum ([Fig. 3]). A subsequent angiography showed that this AVM was supplied by branches of the gastroduodenal artery and pancreatoduodenal branches of the superior mesenteric artery with an early draining vein. Superselective coil embolization of branches supplying the AVM was achieved with no residual blush ([Video 2]).
PWE-114 GP Participation in Increasing Uptake in Bowel Cancer Screening: The Pearl Project: Abstract PWE-114 Table 1
Authors: P Butler, S Duffy, K Reed, M Chesters, S Stanley, S Rickard, R Roope, S Benton
Journal: Gut (2016)

<h3>Introduction</h3> Uptake of bowel cancer screening in England is about 56%. The NHS Bowel Cancer Screening Programme (BCSP) in England is organised centrally, without the direct involvement of general practitioners (GPs). There is evidence to suggest that people are more likely to be screened if they are encouraged to do so by their GP. The Practice Endorsed Additional Reminder Letter (PEARL) project is a collaboration between the BCSP Southern Hub and a group of Wessex GPs working for Macmillan Cancer Support in partnership with the Wessex Strategic Clinical Network. <h3>Methods</h3> Wessex practices with BCSP uptake below 55% (prevalent episodes 2008–2013) were invited to participate. Between September 2014 and October 2015 subjects registered with participating practices who had not returned a test kit within 30 days of a standard reminder letter were identified on the BCSP database and their GPs asked to identify those who should <i>not</i> be sent a further reminder (end-of-life-care <i>etc</i>). The Hub then confirmed that GP-included subjects remained non-respondent and a second reminder letter was sent out with the appropriate GP letterhead and signature. Uptake was compared between PEARL and non-PEARL practices using logistic regression, adjusted for prior prevalent participation and using conservative variance estimation to take account of correlation of outcomes within practices. To estimate the absolute effect of the intervention, we selected 25 non-PEARL practices matched with PEARL practices for prior prevalent participation and number of invitees. <h3>Results</h3> The intervention significantly increased the odds of uptake by 12% (OR = 1.12, 95% CI 1.04–1.19, p = 0.001). Restricting analysis to subjects who had not completed a kit by the index date (date PEARL reminder letter was sent, or would have been sent if in a participating practice), also showed a significant effect of the intervention (2.13 [1.78–2.56]). <h3>Conclusion</h3> The PEARL intervention increased uptake by about 4 percentage points, both as a proportion of all invitees or only those who had not completed a kit by the index date. The extra work PEARL required will be evaluated and recommendations made on the viability of rolling this process out nationally within the BCSP. <h3>Disclosure of Interest</h3> None Declared
Downregulation of Mir-181a Restores Chemosensitivity to Imatinib Mesylate in Chronic Myeloid Leukemia Cells Resistant to Tyrosine Kinase Inhibitors
Authors: Anna Chorzalska, Javier F Kim, Karim Roder, Adam J Olszewski, Dmitry Terentyev, Patrycja M Dubielecka
Journal: Blood (2015)
PTH-110 Ten Year Follow Up Case Control Study of The Effect of Portal Vein Embolisation (PVE) On The Survival of Patients with Colorectal Liver Metastases (CRLM) and The Influence of Hypoxia Factors on Tumour Growth
Authors: PN Siriwardana, T Luong, J Watkins, D Hochhauser, A Harris, BR Davidson, W Ong
Journal: Gut (2016)

<h3>Introduction</h3> PVE facilitates hepatectomy in patients with a small anticipated future liver remnant, but stimulates tumour growth. Hypoxia may mediate this increased tumour growth as Hypoxia-Inducible-Factor-1α (HIF-1α) increases angiogenesis and invasion. A tendency to reduced survival following liver resection after PVE was noted in a previous study when compared with a case matched non PVE-group. We have performed a longer term follow up of patients who had a PVE prior to resection of CRLM and compared the outcome with a matched controlled group with measurement of tumour hypoxia. <h3>Methods</h3> Twenty-six patients who had PVE were compared with 25 case matched controls. Immunostaining was performed on serial formalin-fixed-paraffin-embedded CRLM sections for hypoxia regulated factors, HIF-1α and CA-9, vascular endothelial growth factor (VEGF) and a blood vessel marker, CD31. Disease progression, liver specific recurrence and actuarial survival were recorded. <h3>Results</h3> The clinicopathological characteristics of the cancers were comparable between the groups. The median follow-up was 115 months (range 106–124). Overall, 5 year, local hepatic recurrence-free survival and progression-free periods were reduced in those patients undergoing PVE (p = 0.026, p = 0.060, p = 0.001 and p = 0.008 respectively). The expression of hypoxia markers between the groups was similar. <h3>Conclusion</h3> This is the first long-term (&gt;5 year) case matched series on outcome of patients with CRLM resected following PVE. Whilst, PVE facilitates potentially curative resection of CRLM, prognosis is less than those patients not requiring PVE. The mechanism behind this survival difference has not been established. <h3>Disclosure of Interest</h3> None Declared
Fasudil, a Rho-Associated Protein Kinase (ROCK) Inhibitor, Decreases Disease Burden in a Cbl/Cbl-b Deficiency-Driven Murine Model for Myeloproliferative Disorders
Authors: Basem M. William, Dan Feng, Wei An, Scott Nadeau, Bhopal Mohapatra, Matt Storck, Hamid Band
Journal: Blood (2014)
NK-Cell Reconstitution after HLA-Identical Blood and Marrow Transplantations for CML: The Recovery of NKG2D Is Inversely Correlated with NKG2A and It Promotes the GVL Effect.
Authors: Juan Tong, Huilan Liu, Liangquan Geng, Zimin Sun, Baolin Tang, Zhentian Wu, Chunlan Qiao, Xin Chen, Bing Qian, Kaidi Song
Journal: Blood (2007)
Prospective Randomized Comparison of Cyclophosphamide Versus Cyclophosphamide Plus Fludarabine In Addition to Anti-Thymocyte Globulin for the Conditioning Therapy In Allogeneic Hematopoietic Cell Transplantation for Bone Marrow Failure Syndrome
Authors: Hawk Kim, Jae-Hoo Park, Je-Hwan Lee, Young Don Joo, Won-Sik Lee, Sung-Hwa Bae, Hun-Mo Ryoo, Myung Soo Hyun, Min Kyung Kim, Dae Young Zang, Hyo Jung Kim, Kyoo Hyung Lee
Journal: Blood (2010)
High Number of Successful Mobilizations Associated with the Use of Plerixafor and Colony Stimulating Factors In Patients with Multiple Myeloma (MM) and Lymphoma Treated at Memorial Sloan-Kettering Cancer Center
Authors: Nelly G. Adel, Mathew Sherry, Stephen J. Harnicar, Emily Mccullagh, Heather Landau, Sergio Giralt, Jill Vanak, Danielle Chimento, Charles Lucarelli, Matthew J. Matasar, Hani Hassoun
Journal: Blood (2010)
Durability of the Rituximab Response in Acetylcholine Receptor Autoantibody–Positive Myasthenia Gravis
Authors: Kimberly R. Robeson, Aditya Kumar, Benison Keung, Daniel B. DiCapua, Emily Grodinsky, Huned S. Patwa, Panos A. Stathopoulos, Jonathan M. Goldstein, Kevin C. O’Connor, Richard J. Nowak
Journal: JAMA Neurology (2016)

Myasthenia gravis (MG), an autoimmune disorder of neuromuscular transmission, is treated by an array of immunotherapeutics, many of which are nonspecific. Even with current therapies, a subset of patients has medically refractory MG. The benefits of B-cell-targeted therapy with rituximab have been observed in MG; however, the duration of these benefits after treatment is unclear.To evaluate the durability of response to rituximab in the treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG.This retrospective case series study included 16 patients with AChR+ MG referred to an MG clinic from January 1, 2007, to December 31, 2015. The patients were treated with rituximab and followed up for 18 to 84 months after treatment.Assessment of long-term clinical response, durability of response and/or relapse rate, AChR autoantibody levels, adverse effects, and inflammatory markers.In the 16 patients (6 men and 10 women; median age, 42 [range, 18-69] years), clinical improvement was observed in parallel with complete withdrawal or reduction of other immunotherapies, with all patients achieving complete stable remission, pharmacologic remission, or minimal manifestations based on the Myasthenia Gravis Foundation of America postintervention status criteria. Nine patients (56%) had a relapse during a mean follow-up of 36 (range, 24-47) months. Seven patients (44%) remained relapse free with a mean follow-up of 47 (range, 18-81) months since the last rituximab treatment. All values were normalized to a pretreatment anti-AChR antibody level of 100% and the mean levels after each rituximab cycle were calculated. A 33% decrease was seen after cycle 1 of rituximab treatment (100% vs 67%; P = .004); 20% after cycle 2 (compared with cycle 1) (67% vs 47%; P = .008); and 17% after cycle 3 (compared with cycle 2) (47% vs 30%; P = .02). However, the serum cytokine levels measured were found to be unchanged.Rituximab therapy appears to be an effective option in patients with refractory AChR+ MG, who were observed to have a durable response after treatment. Identification of markers of disease relapse and sustained remission are critical next steps in the development of pathophysiology-relevant, evidence-based practice parameters for rituximab in the treatment of MG.
CBIO-45DNA METHYLATION DICTATES TRANSCRIPTION FACTOR BINDING AND GENE ACTIVATION IN BRAIN TUMOR
Authors: Shuli Xia
Journal: Neuro-Oncology (2015)

Dysregulation of DNA methylation is a hallmark of cancers including malignant brain tumors; yet the functional impact of DNA methylation on tumor malignancy remains largely elusive. Classical dogma states that promoter CpG island methylation (mCpG) influences tumor biology by silencing tumor suppressor genes through interfering with transcription factor (TF)-DNA binding. In this study, we challenge this view by showing that many TFs, including kruppel-like factor 4 (KLF4), preferentially bind to mCpG-containing motifs, and have the ability to activate gene expression. KLF4 is a cancer driver gene up-regulated in high-grade gliomas. We found that KLF4 can bind to mCpG-containing motifs in a sequence-specific manner and activate gene expression. We generated a KLF4 mutant (R458A) that no longer bound to methylated DNA motif but retained KLF4 binding to unmethylated motif. We engineered GBM cell lines to express either doxycycline (Dox)-inducible KLF4 wild type (KLF4-wt) or Dox-inducible KLF4R458A mutant (KLF4-mut) transgenes. Neither KLF4-wt nor KLF4-mut had appreciable effect on cell proliferation and cell viability. However, KLF4-wt but not KLF4-mut induced noticeable morphology changes characterized by elongated, spindle-like phenotypes. We further showed that KLF4-wt but not KLF4-mut promoted GBM cell migration and adhesion. This cell response was partially reversed by the DNA methytransferase inhibitor 5-aza-2′-deoxycytidine (5-Aza), confirming by alternate methods a DNA methylation-dependent mechanism. We employed cell-motility q-PCR arrays and found that ∼10 genes involved in the cell motility pathway, including the small GTPase RhoC, were up-regulated by KLF4-wt but not KLF4-mut. ChIP-PCR demonstrated that KLF4 bound to its promoter region of RhoC via a mCpG-dependent mechanism. These data reveal the novel mechanism by which DNA methylation at CpG sites regulates cancer cell phenotype through transcription factor-dependent gene transactivation. Our studies will be paradigm shifting and will substantially impact our understanding on how CpG methylation influences tumor cell behavior such as migration and invasion.
FRI0646-HPR Does Painful Hand Arthritis Influence Motor Cortex Excitability and Motor Skill Learning?
Authors: R. Parker, G. Lewis, D. Rice, P. McNair
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Painful hand arthritis frequently leads to reduced quality of life [1] and impaired hand function [2]. This may be partially mediated by impaired motor control [3] and changes in primary motor cortex excitability [4]. Previous studies have shown that other chronic pain conditions are associated with reduced motor cortex inhibition [5], which is also associated with motor learning [6]. Therefore, impaired motor control and learning in arthritic pain populations is potentially due to changes in motor cortex excitability. Supporting this, previous studies have shown that motor learning may be influenced by acute experimental pain. However, no previous study has sought to establish whether chronic arthritic pain may influence motor learning and if this relates to changes in motor cortex excitability. <h3>Objectives</h3> To provide a thorough analysis of corticomotor and intracortical excitability in people with painful hand arthritis, and to examine the relationship between these measures and performance on a motor skill learning task. <h3>Methods</h3> Twenty three people with arthritic hand pain and 20 pain-free controls participated in a cross-sectional study. Hand pain and function were assessed using the AUSCAN osteoarthritis hand index. Transcranial magnetic stimulation was used to measure corticomotor and intracortical excitability of a finger muscle. Motor skill learning was assessed using a 30 minute training task involving the index finger of the same hand. <h3>Results</h3> Compared with controls, participants with hand arthritis showed evidence of reduced intracortical inhibition and enhanced facilitation (p&lt;0.05). However, overall corticomotor excitability was normal. Participants with arthritis were initially poorer at the motor skill task, but over the total training time performance was equivalent between groups. There were no associations found between measures of intracortical or corticomotor excitability and motor skill learning or hand function. <h3>Conclusions</h3> This study provides novel evidence that hand arthritis is associated with reduced intracortical inhibition similar to other chronic pain populations. However, no relationship was observed between these cortical alterations and impaired function or skill learning. <h3>References</h3> Dziedzic et al. Rheumatology. 2007:46:963–7. Allen et al. Arthritis Rheum. 2006:54:551–6. de Oliveira et al. J Hand Ther. 2011:24:345–55. Maihofner et al. Brain. 2007:130:2671–87. Lefaucheur et al. Neurology. 2006:67:1568–74. Smyth et al. Hum Mov Sci. 2010:29:618–30. <h3>Disclosure of Interest</h3> None declared
Follicular Lymphoma B Cells Generate Functional Regulatory T Cells Via ICOS/ICOSL Pathway and Are Inhibited By Intratumoral Tregs
Authors: Daniel Olive, Suong Khieu LE, marie-Laure Thibult, Francoise gondois-Rey, Samuel Granjeaud, Thierry Fest, Azzaoui Imene, Reda Bouabdallah, Florence Broussais, Luc Xerri, Dominique Leroux, Christophe Caux, Christine Caux
Journal: Blood (2015)
Targeting the Gatekeeper: Osimertinib in <i>EGFR T790M</i> Mutation–Positive Non–Small Cell Lung Cancer
Authors: Ferdinandos Skoulidis, Vassiliki A. Papadimitrakopoulou
Journal: Clinical Cancer Research (2016)

In 2015, the FDA approved an unprecedented number of new therapies for non-small cell lung cancer (NSCLC), among them therapies addressing specific genomic tumor subsets in the setting of development of resistance to first-line targeted therapy. Osimertinib (Tagrisso, formerly AZD9291; AstraZeneca) is indicated for patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy. It received breakthrough therapy designation, priority review status, and accelerated approval from the FDA. Clin Cancer Res; 23(3); 618-22. ©2016 AACR.
Molecular Profiling and Relationship with Clinical Response in Patients with IDH1 Mutation-Positive Hematologic Malignancies Receiving AG-120, a First-in-Class Potent Inhibitor of Mutant IDH1, in Addition to Data from the Completed Dose Escalation Portion of the Phase 1 Study
Authors: Courtney DiNardo, Stéphane de Botton, Daniel A Pollyea, Eytan M Stein, Amir T. Fathi, Gail J Roboz, Robert Collins, Ronan T. Swords, Ian W. Flinn, Jessica K Altman, Martin S Tallman, Hagop M. Kantarjian, Adnan Derti, Meredith Goldwasser, Malia Prahl, Bin Wu, Katharine Yen, Sam Agresta, Richard M. Stone
Journal: Blood (2015)
Identification of Initiating Trunk Mutations and Distinct Molecular Subtypes: An Interim Analysis of the Mmrf Commpass Study
Authors: Jonathan J Keats, Gil Speyer, Legendre Christophe, Christofferson Austin, Kristi Stephenson, Ahmet Kurdoglu, Megan Russell, Aldrich Jessica, Cuyugan Lori, Jonathan Adkins, Jackie McDonald, Adrienne Helland, Alex Blanski, Meghan Hodges, Dan Rohrer, Sundar Jagannath, David Siegel, Ravi Vij, Gregory Orloff, Todd Zimmerman, Ruben Niesvizky, Darla Liles, Joseph W. Fay, Jeffrey L. Wolf, Robert M. Rifkin, Norma C Gutierrez, Jen Toups, Mary Derome, Winnie Liang, Seunchan Kim, Daniel Auclair, Pamela G. Kidd, Scott Jewell, John David Carpten, Sagar Lonial
Journal: Blood (2015)
Minimal Residual Disease (MRD) Assessed By Multi-Parameter Flow Cytometry (MFC) Is Highly Predictive of Outcome in Adult Patients with Acute Lymphoblastic Leukemia (ALL)
Authors: Farhad Ravandi, Jorgensen L Jeffrey, Deborah A. Thomas, Susan O'Brien, Elias Jabbour, Gautam Borthakur, Rebecca Garris, Xuelin Huang, Guillermo Garcia-Manero, Jan A. Burger, Alessandra Ferrajoli, Tapan Kadia, Nitin Jain, Sa A. Wang, Partow Kebriaei, Richard E. Champlin, Zeev Estrov, Jorge E Cortes, Hagop M. Kantarjian
Journal: Blood (2014)
PTU-040 How Should Miss Rates for Cancer and Large Polyps Be Monitored at A Local Level? Retrospective Analysis of Repeat Colonoscopies at a District General Hospital
Authors: S Meade, A Mcnair
Journal: Gut (2016)

<h3>Introduction</h3> Caecal intubation and adenoma detection rates are key performance indicators (KPI) used to assess the quality of colonoscopy. Post-colonoscopy colorectal cancer (PCCRC) rates have recently been suggested as an additional KPI. Most studies estimate PCCRC rates by identifying the proportion of patients with diagnosed colorectal cancer (CRC) who have had a colonoscopy within 3 years of their diagnosis. This is labour intensive requiring evaluation of ≥2 databases. We describe a simplified method for estimating PCCRC rates. <h3>Aim</h3> To estimate the PCCRC rate using data from the endoscopy database alone. To identify all patients who had ≥2 colonoscopies over a 3 year period and those with CRC at the latest colonoscopy. To estimate the miss rate for larger (&gt;20 mm) polyps. <h3>Methods</h3> We identified all patients on our endoscopy database (Adam, Fujifilm) who had a colonoscopy from 2010–12 and had a repeat colonoscopy within the next 3 years. We merged initial colonoscopy data with data of those patients found to have CRC and used conditional formatting to flag up duplicate procedures. Patients found to have CRCs or polyps &gt;20 mm in the repeat procedure, not noted at their initial endoscopy, were identified. This data was used to calculate a ‘miss rate’ for these lesions. <h3>Results</h3> Between 2010 and 2012, 4961 colonoscopies were performed. In total 192 cancers were identified during this period. 237, 150, 225 and 128 repeat colonoscopies were performed within the same year and at 1, 2 and 3 years respectively. Of the 150 repeat procedures performed the following calendar year, indications included polyp surveillance (78), post-operative cancer surveillance (20), HNPCC or FAP (15), family history of CRC (8), anaemia (7), altered bowel habit (6) and other (16). In this group, 42 had polyps &gt;20 mm and 6 had cancers. 3 of the cancers were in the ascending colon and the remaining three were missed at sites reported to have been examined in the previous study. This resulted in a missed polyp rate of 38.6%, a ‘missed cancer rate’ at one year of 6/150 patients (4%) and an overall ‘missed cancer rate’ of 0.12% or 1 in 827 colonoscopies. 2 cancers were found in patients who had a repeat colonoscopy after 2 years, both in the ascending colon. There were no missed cancers on repeat colonoscopy within the same calendar year or at three years. <h3>Conclusion</h3> Data readily obtainable from the endoscopy reporting system can be used to determine the rate of missed cancers. Our results are similar to that reported in other studies employing more complex and time-consuming methodology. This alternative approach can be used by units to confirm their local PCCRC rate, large polyp miss rates and potentially identify endoscopists whose miss rates are unacceptably high. <h3>Disclosure of Interest</h3> None Declared
HLA DR15 Antigen Status Does Not Impact Graft-Versus-Host Disease or Disease-Free Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies
Authors: Minoo Battiwalla, Kristin Ellis, Steven Z. Pavletic, Gorgun Akpek, Peiman Hematti, Thomas R Klumpp, Richard T. Maziarz, Bipin N. Savani, Mahmoud Aljurf, Mitchell S. Cairo, William R. Drobyski, Biju George, Theresa Hahn, Nandita Khera, Mark R. Litzow, Alison W. Loren, Wael Saber, Mukta Arora, Alvaro Urbano-Ispizua, Corey S. Cutler, Mary E.D. Flowers, Stephen Spellman
Journal: Blood (2011)
G1 Cell-Cycle Arrest and Apoptosis by Histone Deacetylase Inhibition in MLL-AF9 Acute Myeloid Leukemia Cells Is MLL-AF9 Independent.
Authors: Roberto Tonelli, Roberta Sartini, Raffaele Fronza, Francesca Freccero, Monica Franzoni, Danilo Dongiovanni, Marco Ballarini, Simona Ferrari, Maria D’Apolito, Gabriella Di Cola, Giovanni Capranico, Andriy Khobta, Renato Campanini, Paolo Paolucci, Saverio Minucci, Andrea Pession
Journal: Blood (2005)