tbuckley/cabot-search huggingface dataset:
Outcomes of Gene Therapy for Severe Sickle Disease and Beta-Thalassemia Major Via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector
Authors: Marina Cavazzana, Jean-Antoine Ribeil, Emmanuel Payen, Felipe Suarez, Yves Beuzard, Fabien Touzot, Resy Cavallesco, Francois Lefrere, Stany Chretien, Philippe Bourget, Fabrice Monpoux, Corinne Pondarre, Benedicte Neven, Manfred Schmidt, Christof von Kalle, Frans A. Kuypers, Laura Sandler, Sandeep Soni, Olivier Hermine, Stephane Blanche, Mariane De Montalembert, Salima Hacien-Bey-Abina, Philippe Leboulch
Journal: Blood (2015)
Clinical Relevance of Concomitant Gene Mutations in CEBPA Double-Mutated Acute Myeloid Leukemia.
Authors: Vera Grossmann, Susanne Schnittger, Niroshan Nadarajah, Sandra Weissmann, Annette Fasan, Christiane Eder, Elisa Stopp, Wolfgang Kern, Torsten Haferlach, Alexander Kohlmann, Claudia Haferlach
Journal: Blood (2012)
Genetic Polymorphisms in NEDD4L Are Associated with Pulmonary Hypertension of Sickle Cell Anemia.
Authors: Elizabeth S Klings, Daniel A Dworkis, Amanda Sedgewick, Stephen W Hartley, Ashley-Koch Allison, Marilyn J. Telen, Gregory J. Kato, Mark Gladwin, Paola Sebastiani, Clinton T. Baldwin, Martin H Steinberg
Journal: Blood (2009)
Defining High Risk Myeloma Using Co-Segregating FISH Variables; Results of MRC Myeloma IX
Authors: Kevin D Boyd, Fiona M. Ross, William J Tapper, Laura Chiecchio, GianPaolo Dagrada, Rebecca Protheroe, David Stockley, Zoe Konn, Walter M Gregory, Brian A Walker, Christopher P Wardell, Faith E Davies, Gareth J Morgan
Journal: Blood (2010)
P07.18 Characterization and identification of glioblastoma progression on preoperative multimodal MRI
Authors: J. Yan, A. van der Hoorn, N. R. Boonzaier, T. Matys, S. J. Price
Journal: Neuro-Oncology (2016)

The treatment failure of Glioblastoma (GBM) is mostly due to the inadequate identification of its invasive margin. We aimed to characterize the peri-tumoral area, the predominant site of tumor progression by using multi-modal MRI. Thereafter, a robust method to preoperatively identify regions progression was developed. We retrospectively included 38 newly diagnosed cerebral glioblastoma patients. All patients were treated with 5-aminolevulinic acid (5-ALA) fluorescence guidance surgery and standard postoperative concomitant chemoradiotherapy. Preoperative MRI data acquisition was performed using a 3T MRI. Imaging included volumetric post contrast T1-weighted, perfusion MR, and DTI. DTI was decomposed into isotropic (p) component and anisotropic (q) components. Follow up MRI at time point of progression were co-registered to the preoperative MRI. Imaging characteristics of the peritumoral tumor progression regions were selected and compared to 5mm peri-tumoral non-progression regions. These imaging characteristics were then used to undergo convoluted neural network training which was further applied to develop an automated drawing of the tumor progression map on the preoperative MRI. Multimodal MRI characterization FLAIR. In areas of later progression, there was significant increase in the FLAIR signal compared to non-progression area ( p = 0.003) and control ( p < 0.001). Diffusion MR. Characterizing isotropic p component showed a significant decrease in progression area than contrast enhanced area and non-progression area ( p < 0.001). In areas of progression, anisotropic q was lower than non-progression peri-tumoral area ( p =0.001) and control ( p =0.009). The ADC values in the progression area were lower than peri-tumoral non-progression area ( p =0.008) and control ( p < 0.001). Fractional anisotropy (FA) showed no difference between progression area and non-progression area ( p =0.537). DSC-MRI. Relative cerebral blood volume, compared to control, was increased in the contrast enhanced lesion and progression areas ( p <0.0001), but there was no difference in progression and non-progression area. Identification of the tumour progression By using the above significant imaging features to train the model, an average accuracy of 85.1% with sensitivity of 86.5% and specificity of 83.8% was achieved using the convoluted neural network. Further application of the trained model can be used to generate predicted areas of progression on the preoperative MRI. Multimodal MR imaging, particularly diffusion tensor imaging, can demonstrate distinct characteristics in areas of potential progression on preoperative MRI. Moreover, by using these imaging features, the site of tumor progression can be identified and drawn automatically via a trained machine learning model which provides a direction for future study and treatment target.
PTH-013 Endorings™ In Screening Colonoscopy: Results of A Single Centre Pilot Study
Authors: B Hayee, G Chung-Faye
Journal: Gut (2016)

<h3>Introduction</h3> Colonoscopy remains the gold standard procedure for screening and polyp detection, with adenoma detection rate (ADR) being a widely-accepted key performance indicator (KPI). It has long been recognised that even experienced endoscopists incur an appreciable ‘miss-rate’ and a number of novel devices have been marketed to assist this aspect of practice. The Endorings™ device is a simple soft silicone, single-use device consisting of a series of rings arranged around a central tubular core. As the colonoscope is inserted the rings fold backward to allow intubation and flare on withdrawal to flatten colonic folds and aid inspection. <h3>Methods</h3> Prospective data was collected during screening colonoscopy (performed by two accredited colonoscopists) when the Endorings™ device was used and compared the KPI results to outcomes from the previous few months, for the same two colonoscopists) when the device was not in use (ie. historical controls). <h3>Results</h3> The ADR without Endorings™ (n = 85) was 49.4% with a per-procedure detection rate (ppr) of 0.97. With Endorings (n = 66) 66.7% (p = 0.0006) with ppr of 1.625. This represents a 35% increase in ADR and a 68% increase in the number of polyps detected at any given procedure. There were no significant differences in completion rates, withdrawal time, use of sedation or comfort scores. The device was removed in 5/66 procedures due to interference with intubation (in the presence of either an angulated sigmoid or diverticulosis). No complications were recorded. <h3>Conclusion</h3> Use of the Endorings™ device was associated with a significant increase in ADR. Qualitatively, the three-ring design was felt to interfere with normal intubation such that insertion technique had to be modified. An updated design iteration with two rings in slightly different positions along the central tube, has been produced and appears to offer a significant advantage in this regard. Furthermore, the central tube can be pushed further along the distal end of the colonoscope to allow the terminal ileum to be intubated with the device in place. The Endorings™ may offer an advantage in screening colonoscopy and, in this cohort, further prospective investigation is warranted. <h3>Disclosure of Interest</h3> None Declared
Donor's Genetic Variability in NFAT5 and ATBF1, Transcriptional Factors Involved in Cellular Growth and Proliferation, Are Prognostic Factors for Disease Free Survival After Allogeneic Stem Cell Transplantation (Allo-SCT).
Authors: Beatriz MArtin Antonio, Isabel álvarez, Francisco Máarquez-Malaver, Pablo Trujillo, Magdalena Carmona, Jose F Falantes, Ildefonso Espigado, A. Urbano-Ispizua
Journal: Blood (2009)
Mistargeting of Normal Cells in Anti-CD30 Immunotherapy of Lymphoma Cells Is Blocked by Selective Metalloproteinase Inhibitor.
Authors: Vijaya L. Simhadri, Elke Pogge von Strandmann, Dennis A. Eichenhauer, Andreas Ludwig, Katrin S. Reiners, Andreas Engert, Hinrich P. Hansen
Journal: Blood (2006)
PTU-138 Feasibility Study of Volatile Organic Compounds in Constipation in Parkinson’s Disease
Authors: S Qureshi, A Bond, L Iwanejko, C Probert
Journal: Gut (2016)

<h3>Introduction</h3> Patients with Parkinson’s disease (PD) have constipation. Constipation often precedes the classical motor signs. Enteric neuropathy may play a role of the aetiology of PD. Exposure to fungi is a risk factor for PD: in vitro models have shown specific fungi-produced volatile organic compounds (VOC), 1 octen-3-ol and 2 octanone, may cause loss of dopaminergic neurones in fruit flies. We propose the hypothesis that intestinal fungal metabolites may a risk factor for PD. This study assessed the feasibility of performing faecal VOCs analysis in people with PD and controls. <h3>Methods</h3> 8 patients with diagnosed PD were invited from an exercise class (Dancing for Parkinson’s). Their partners/carers were also invited as aged-matched controls. Samples from lab volunteers (14) were also analysed. Patients or controls that had taken any antibiotics or antifungals in the 4 weeks prior to sampling were excluded. VOCs from 2 aliquots per donor were extracted using Solid Phase Micro Extraction (SPME), separated by gas chromatography–mass and analysed by gas spectrometry (GC-MS). VOCs were identified using AMDIS and comparison with the current NIST library of mass spectra. Reported were prepared using Metab, and statistical analysis undertaken using Metaboanalyst software. <h3>Results</h3> All 8 PD patients provided samples, despite their constipation. 5 of 6 aged-matched controls provided samples. The average result from the paired technical replicates was used for statistical analysis. There were significantly fewer VOC in samples from PD patients (63), than from controls (74, p &lt; 0.007). Young and older controls had a similar number of VOCs (80 and 71 respectively, p = ns). The abundance of VOCs in PD and all controls was compared: 33 differed, 7 of which persisted after correction for multiple comparison, including 2 octanone. <h3>Conclusion</h3> The study of VOCs in people with constipation is feasible. Those with constipation have fewer VOCs that controls as a whole. There were clear differences in the VOCs from patients with Parkinson’s disease in the control group. One of the VOCs that was increased, 2 octanone, in Parkinson’s disease is a fungal metabolite that causes damage to dopaminergic neurones in an insect model. More work is necessary to explore the association between PD: a full study will need to include more patients and controls with constipation. <h3>Disclosure of Interest</h3> None Declared
Pentostatin Therapy for Steroid-Refractory Acute Graft Versus Host Disease: Identifying Those Who May Benefit
Authors: Brittany Knick Ragon, Alison M Gulbis, Rima M Saliba, Julianne Chen, Gabriela Rondon, Uday R. Popat, Yago Nieto, Betul Oran, Amanda L. Olson, Krina Patel, Chitra M. Hosing, Muzaffar H. Qazilbash, Nina Shah, Partow Kebriaei, Elizabeth J. Shpall, Richard E. Champlin, Amin M. Alousi
Journal: Blood (2015)
OP0225 Three Months' Clinical Outcomes from A Nationwide Non-Medical Switch from Originator To Biosimilar Infliximab in Patients with Inflammatory Arthritis. Results from The Danbio Registry: Table 1
Authors: B. Glintborg, I. Juul Sørensen, D. Vendelbo Jensen, N.S. Krogh, A.G. Loft, A. Colic, J. Espesen, J. Olsen, O. Hendricks, J. Grydehøj, I.M.J. Hansen, M.V. Sørensen, S. Chrysidis, N. Manilo, M. Klarlund, L.S. Andersen, H. Nordin, S. Kristensen, M.L. Hetland
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> According to national guidelines issued in 2015, a non-medical switch from originator infliximab (IFX) (Remicade) to biosimilar Remsima was conducted in all Danish patients with inflammatory rheumatic diseases treated in routine care. <h3>Objectives</h3> To investigate 3 months9 clinical outcomes in Remicade-treated patients (pts) with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthrits (SpA) who switched to Remsima and were monitored prospectively in the DANBIO registry. <h3>Methods</h3> Disease activity at 3 mths before switch (pre-switch), at the switch and after 3 mths (70–120 days) (post-switch) and changes over time (Δpre-switch and Δpost-switch) were calculated. Disease flare was defined as ΔDAS28≥1.2 (RA/PsA) or ΔASDAS≥1.3 (SpA). Reasons for withdrawal (adverse events (AE), lack of effect (LOE) or other) were registered. <h3>Results</h3> 647 of 693 switching pts (300 RA, 96 PsA, 219 SpA, 32 other) had available data (52% women, age (median (IQR) 56 (45–66) yrs)). Prior Remicade treatment duration was 6.7 (4.1–9.4) yrs and in 77% it was the first biological treatment. Remsima dose was in RA+PSA 3.3 (3.0–4.8) mg/kg every 7 (6–8) wks and in SpA 4.8 (3.6–5.1) mg/kg every 6 (6–9) wks. Concomitant MTX was given in 69% (RA+PsA)/25% (SpA). Median follow-up time was 139 (98–160) days. Disease activity remained largely unchanged 3 months prior to vs. after the switch (Table). The proportion of patients with disease flare pre-/post switch was 10%/10% (RA+PsA) (p=1.0) and 10%/0% (SpA) (p=1.0) (related samples McNemar test). Overall, 45 ptts (7%) stopped Remsima treatment during follow-up (AE 16 (allergic 3, infection 2, rash 2, unspecific 9), LOE 20, remission 3, cancer 2, other 4). Prior Remicade treatment duration in these patients was 5.9 (3.5–9.1) yrs. <h3>Conclusions</h3> In 647 patients with inflammatory rheumatic diseases treated with Remicade for &gt;4 years, disease activity was largely unaffected in the majority of patients 3 months after non-medical switch to biosimilar Remsima and comparable to the fluctuations observed in the 3 months prior to the switch. However, several patients (∼6%) stopped treatment due to LOE or AE. This warrants further investigation before such a non-medical switch can be recommended. <h3>Disclosure of Interest</h3> None declared
AB1004 Sources of Information Used by Patients with Rheumatic Diseases Treated with Subcutaneous Biological Therapy. Rheu-Life Survey:
Authors: F.J. de Toro, E. Batlle, C.M. González, L. Cea-Calvo, M.A. Pérez-Calvo, L. Carmona
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Adequate information to patients on disease and therapies is important to improve lifestyle, adherence to treatments and outcomes. <h3>Objectives</h3> To describe which are the main sources of information for patients with rheumatic diseases treated with subcutaneous (SC) biological drugs, which ones they consider relevant, and their satisfaction with the information received from the clinical team. <h3>Methods</h3> RHEU-LIFE was a survey to patients &gt;18 years with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis treated with SC biological drugs, from 50 rheumatology outpatient clinics from Spain. The patients completed the survey anonymously at home. They selected from a list: 1) their sources of general information on disease (multiple choice), 2) the most important (one option), 3) who had informed them about the treatment alternatives (multiple choice) and 4) about the SC biological drug (multiple choice). <h3>Results</h3> The survey was given to 1000 patients, 592 responded (59.2%, mean age 51.7 years [SD 13.2], 42.4% men, 57.6% women). The main source of general information on disease was the rheumatologist (92.3%). Other sources mentioned were the primary care physician (21.7%), nurses (19.3%), medical websites (19.8%) or health related blogs (5.6%), brochures for patients (11.5%), friends or relatives (6.3%), patient associations (4.4%) or other patients (3.1%) and pharmacists (3.4%). Information about treatment options and the SC biological drug came mainly from the rheumatologist (&gt;90%) and infrequently from nurses or hospital pharmacists (Table). 46.1% mentioned having received only oral information, 6.0% only written and 45.2% both ways. Some 44.5% and 42.6% reported to be “very satisfied” and “satisfied” with the information received respectively, 10.6% “neither satisfied nor dissatisfied” and 2.1% and 0.2% “dissatisfied” or “very dissatisfied”. 45.2% alleged to search for information about the biological treatment in sources other than the hospital clinical staff. <h3>Conclusions</h3> The rheumatologist is the main source of information for patients on SC biological drugs. Nurses and hospital pharmacists are seldom mentioned, even though being very often visited for drug dispensing. Satisfaction with the information received is high, however nearly half said to have searched for information on the biological drug in alternative sources. <h3>Acknowledgement</h3> This survey was financed by Merck Sharp &amp; Dohme of Spain and endorsed by the patient9s association ConArtritis (Arthritis National Coordinator). <h3>Disclosure of Interest</h3> None declared
Next generation of small molecules in inflammatory bowel disease
Authors: Pablo Olivera, Silvio Danese, Laurent Peyrin-Biroulet
Journal: Gut (2016)

Inflammatory bowel disease (IBD) encompasses two major entities: ulcerative colitis (UC) and Crohn's disease (CD).1 Both are chronic, progressive, disabling conditions that require lifelong medical treatment in most cases. IBD has a major impact on the patient's health-related quality of life,2 and the treatment-related costs place a significant burden on healthcare systems.3

Historically, the medical management of IBD has been based on the use of several small-molecule drugs (SMDs), including corticosteroids, immunomodulators (such as azathioprine, 6-mercaptopurine and methotrexate) and aminosalicylates.4 The introduction of biologic anti-tumour necrosis factor-α (TNF-α) agents in the first few years of this century has revolutionised the clinical management of IBD. In parallel, treatment goals have shifted from symptomatic control towards more objective endpoints (such as mucosal healing and deep remission) associated with better long-term outcomes.5 ,6 Over the past 20 years, drug research in the field of IBD has focused on the development of new, large-molecule biologics; hence, several anti-TNF-α monoclonal antibodies (including infliximab,7 ,8 adalimumab,9 ,10 certolizumab pegol,11 ,12 and golimumab)13 and, most recently, antibodies with other targets (such as vedolizumab14 ,15 and ustekinumab)16 have become available in clinical practice.

However, monoclonal antibodies have limitations in terms of efficacy, safety and cost. First, the available biologics are only moderately efficacious17 since up to 30% of patients show a lack of improvement after induction therapy with anti-TNF drugs (ie, primary non-response).18 Furthermore, a significant proportion of patients (between 13% and 25% per year)19–21 may develop a loss of response to anti-TNF agents over time (ie, secondary non-response).20 ,21 This loss of response may be due to pharmacodynamic, pharmacokinetic and/or immunogenic factors.22 Combination therapy is the best way to prevent the formation of antibodies,23 which …
Assessment of Use vs Discontinuation of Oral Anticoagulation After Pulmonary Vein Isolation in Patients With Atrial Fibrillation
Authors: Sara Själander, Fredrik Holmqvist, J. Gustav Smith, Pyotr G. Platonov, Milos Kesek, Peter J. Svensson, Carina Blomström-Lundqvist, Fariborz Tabrizi, Jari Tapanainen, Dritan Poci, Anders Jönsson, Anders Själander
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> Pulmonary vein isolation (PVI) is a recommended treatment for patients with atrial fibrillation, but it is unclear whether it results in a lower risk of stroke. <h3>Objectives</h3> To investigate the proportion of patients discontinuing anticoagulation treatment after PVI in association with the CHA<sub>2</sub>DS<sub>2</sub>-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65-74 years, sex category [female]) score, identify factors predicting stroke after PVI, and explore the risk of cardiovascular events after PVI in patients with and without guideline-recommended anticoagulation treatment. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted using Swedish national health registries from January 1, 2006, to December 31, 2012, with a mean-follow up of 2.6 years. A total of 1585 patients with atrial fibrillation undergoing PVI from the Swedish Catheter Ablation Register were included, with information about exposure to warfarin in the national quality register Auricula. Data analysis was performed from January 1, 2015, to April 30, 2016. <h3>Exposures</h3> Warfarin treatment. <h3>Main Outcomes and Measures</h3> Ischemic stroke, intracranial hemorrhage, and death. <h3>Results</h3> In this cohort of 1585 patients, 73.0% were male, the mean (SD) age was 59.0 (9.4) years, and the mean (SD) CHA<sub>2</sub>DS<sub>2</sub>-VASc score was 1.5 (1.4). Of the 1585 patients, 1175 were followed up for more than 1 year after PVI. Of these, 360 (30.6%) discontinued warfarin treatment during the first year. In patients with a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of 2 or more, patients discontinuing warfarin treatment had a higher rate of ischemic stroke (5 events in 312 years at risk [1.6% per year]) compared with those continuing warfarin treatment (4 events in 1192 years at risk [0.3% per year]) (<i>P</i> = .046). Patients with a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of 2 or more or those who had previously experienced an ischemic stroke displayed a higher risk of stroke if warfarin treatment was discontinued (hazard ratio, 4.6; 95% CI, 1.2-17.2;<i>P</i> = .02 and hazard ratio, 13.7; 95% CI, 2.0-91.9;<i>P</i> = .007, respectively). <h3>Conclusions and Relevance</h3> These findings indicate that discontinuation of warfarin treatment after PVI is not safe in high-risk patients, especially those who have previously experienced an ischemic stroke.
Combination of Bortezomib with Tipifarnib (R115777) Induces Synergistic Myeloma Cell Apoptosis Via Down-Regulation of HDAC6 and Inhibition of Aggresome Formation.
Authors: Ebenezer David, Katherine Schafer-Hales, Adam I. Marcus, Jonathan L. Kaufman, Sagar Lonial
Journal: Blood (2007)
Comparison of Toxicity and Outcomes of BCNU-Containing Conditioning Regimens Vs LACE in Lymphoma Transplants: A Retrospective Multicenter Analysis
Authors: Navin Khattry, Reetu Jain, Ravi Thippeswamy, Adwaita Gore, Bharat Bhosale, Nandish Jeevangi, Sadhana Kannan, Amit Joshi, Reena Nair, Tapan Saikia
Journal: Blood (2011)
Expression Differences of Prognostic Biomarkers in Mononuclear Cells (MNCs) and Malignant Blasts of Acute Myeloid Leukemia (AML) Patients
Authors: Era L. Pogosova-Agadjanyan, Soheil Meshinchi, Hana Lee, Brent L. Wood, Derek L. Stirewalt
Journal: Blood (2011)