tbuckley/cabot-search huggingface dataset:
AB0300 Comparative Usability Study for A Certolizumab Pegol Auto-Injection Device in Patients with Rheumatoid Arthritis
Authors: B. Domanska, L. Peterson, I. Mountian, M.H. Schiff
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Impaired manual dexterity is common in patients (pts) with rheumatoid arthritis (RA), often resulting in difficulties with drug self-administration when using pre-filled syringes.<sup>1,2</sup> Auto-injection devices (AIs) have been shown to provide a number of benefits, including reduced discomfort and greater ease of use compared with manual injections.<sup>2,3</sup> A new certolizumab pegol (CZP) device was created, based on pt insights and capitalizing on the benefits of existing AIs. <h3>Objectives</h3> To compare the usability of a new CZP AI with alternative anti-tumor necrosis factor (anti-TNF) devices (adalimumab, etanercept and golimumab) in patients with moderate to severe RA. <h3>Methods</h3> Eligible pts had moderate to severe RA (fingers, hands and/or wrists affected) and no prior experience of using an AI for RA. Each pt tested 4 AIs (CZP, golimumab, etanercept and adalimumab) in a randomized order by performing a simulated self-injection on a training skin pad strapped to the upper thigh or lower abdomen. All identifications were removed from the AI devices and respective instructions for use. Pts were provided with instructions for use for each of the AIs, but were not trained on device use prior to testing. Following utilization of all four AIs, pts were asked to rank them in order of preference from 1–4 (1=the most preferred) and to provide feedback on their usability (easy to use, easy to start the injection, easy to tell when injection was finished and willingness to use). <h3>Results</h3> Overall, 76 pts took part in this study. 67.1% pts ranked the CZP AI as their most preferred device; 23.7% ranked it as their second most preferred (Figure). The preference in the overall ranking of the CZP AI over each of the other devices was statistically significant (p&lt;0.001). The majority of pts agreed, strongly agreed or very strongly agreed that the CZP AI was easy to use, easy to start the injection and that it was easy to determine when the injection was finished. Pts were significantly more willing to use the CZP AI compared with each of the other devices tested (p&lt;0.001). <h3>Conclusions</h3> In pts with moderate to severe RA, the CZP AI was the preferred choice compared to the golimumab, etanercept and adalimumab AIs, and was associated with a high level of patient satisfaction. <h3>References</h3> Keininger D. Health Qual Life Outcomes 2011;9:2; Kivitz A. Clin Ther 2006;28:1619–29; Schwarzenbach F. Patient Prefer Adherence 2014;8:199–209 <h3>Acknowledgement</h3> The authors acknowledge Costello Medical Consulting, funded by UCB Pharma, for writing and editorial assistance. <h3>Disclosure of Interest</h3> B. Domanska Employee of: UCB Pharma, L. Peterson Employee of: UCB Pharma, I. Mountian Employee of: UCB Pharma, M. Schiff Grant/research support from: UCB Pharma, Consultant for: UCB Pharma
Ex Vivo Expanded NK Cells Mediate Highly Efficient and Rapid Killing of Ewing Sarcoma Cells Through Degranulation with Tumor Cytotoxicity Controlled by the NKG2D, DNAM-1, and NKp30 NK Receptors
Authors: Amrita D. Karambelkar, Robert N. Reger, Mattias Carlsten, Richard W. Childs
Journal: Blood (2015)
Different Characteristics Identified by Single Nucleotide Polymorphism Array Analsysis in Leukemia Suggest the Need for Different Application Strategics Depending On Disease Category.
Authors: Jungwon Huh, Chul Won Jung, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Joon Ho Moon, Sang Kyun Sohn, Hee-je Kim, Woo-Sung Min, Dennis Dong Hwan Kim
Journal: Blood (2012)
PWE-109 Cytoplasmic Expression of HMGB1 is Associated with Early Colorectal Carcinogenesis
Authors: A Hay, CA Christopoulou, GI Murray, EM El-Omar, GL Hold, MH McLean
Journal: Gut (2016)

<h3>Introduction</h3> High Mobility Group Box-1 (HMGB1) is a ubiquitous nuclear protein that regulates gene expression. When phosphorylated, it translocates to the cytoplasm and extracellular space to stimulate pro-inflammatory responses and influence epithelial cell behaviour. Our aim was to assess expression of HMGB1 in colorectal neoplastic progression. <h3>Methods</h3> Epithelial nuclear and cytoplasmic subcellular expression of HMGB1 was assessed immunohistochemically in a tissue microarray, representing 650 colorectal cancers and 50 paired normal colorectal mucosa samples, and 25 endoscopically resected paraffin embedded polyp cancer lesions (CaP), sourced from the Grampian Biorepository. Ethical approval was granted by the Grampian biorepository scientific committee. Intensity of HMGB1 expression (none, weak, moderate or strong) in all samples and proportion of positive cells/total CaP compartment (normal, adenoma, carcinoma) were double scored. Relative frequencies of staining across the tumour microarray were calculated and correlated to clinico-pathological data. In CaP, expression analysis used Fisher’s exact test of 2X2 contingency tables. <h3>Results</h3> Increased intensity of nuclear HMGB1 expression was correlated with increasing TNM tumour stage (p = 0.006) and Dukes stage (p = 0.016). Loss of nuclear HMGB1 intensity was identified at the early cancer stages compared to normal, followed by increased expression as the cancer progressed. No (p = 0.001) or low (p = 0.01) nuclear staining was associated with defective mismatch repair protein. Across the microarray, expression of cytoplasmic HMGB1 was significantly associated with malignancy (p &lt; 0.0001). In CaP, both increased intensity and proportion of cytoplasmic expression was significantly associated with the area of carcinoma compared to adjacent normal (p &lt; 0.0002) and adenoma (p &lt; 0.0002). There was a significant reduction in proportion of nuclear HMGB1 positive cells in the CaP carcinoma compartment (p = 0.0001), due to foci displaying loss of nuclear and emergence of cytoplasmic HMGB1. The leading edge of cancer invasion had strong expression in both nuclear and cytoplasmic compartments (77% of CaP). <h3>Conclusion</h3> Dynamic subcellular localisation of HMGB1 expression is associated with colorectal neoplastic progression with cytoplasmic HMGB1 a feature of early carcinogenesis. The functional impact of this warrants further investigation and may reveal new insight into the pathogenesis of colorectal cancer. <h3>Disclosure of Interest</h3> None Declared
Mapping the Targets of Dasatinib in Chronic Lymphocytic Leukemia Reveals Distinct Roles for Abl and Btk in Drug Resistance and Adhesion, and Explains Clinical Effects On Lymph Node Reduction
Authors: Eric Eldering, Christian R Geest, Martin FM de Rooij, Nora Liu, Bogdan I Florea, Marinus H.J. Van Oers, Hermen S Overkleeft, Marcel Spaargaren, Arnon P. Kater
Journal: Blood (2012)
Drug firms need to tackle affordability
Authors: Anne Gulland
Journal: BMJ (2016)

Drug companies need to do more to make their products affordable to patients in low and middle income countries, an investigation into drug firms’ access to medicines policies has found.

The Access to Medicines Index, which is published every two years and ranks companies according to how they make their products available to patients in poorer countries, found little progress in improving affordability.1

There are currently 850 products on the market for the 51 most burdensome diseases in low and middle income countries. Companies are developing another 420, which includes more than 100 products that have entered the pipeline since 2014 …
Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study
Authors: Kala Visvanathan, MaryJo S. Fackler, Zhe Zhang, Zoila A. Lopez-Bujanda, Stacie C. Jeter, Lori J. Sokoll, Elizabeth Garrett-Mayer, Leslie M. Cope, Christopher B. Umbricht, David M. Euhus, Andres Forero, Anna M. Storniolo, Rita Nanda, Nancy U. Lin, Lisa A. Carey, James N. Ingle, Saraswati Sukumar, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2017)

Purpose Epigenetic alterations measured in blood may help guide breast cancer treatment. The multisite prospective study TBCRC 005 was conducted to examine the ability of a novel panel of cell-free DNA methylation markers to predict survival outcomes in metastatic breast cancer (MBC) using a new quantitative multiplex assay (cMethDNA). Patients and Methods Ten genes were tested in duplicate serum samples from 141 women at baseline, at week 4, and at first restaging. A cumulative methylation index (CMI) was generated on the basis of six of the 10 genes tested. Methylation cut points were selected to maximize the log-rank statistic, and cross-validation was used to obtain unbiased point estimates. Logistic regression or Cox proportional hazard models were used to test associations between the CMI and progression-free survival (PFS), overall survival (OS), and disease status at first restaging. The added value of the CMI in predicting survival outcomes was evaluated and compared with circulating tumor cells (CellSearch). Results Median PFS and OS were significantly shorter in women with a high CMI (PFS, 2.1 months; OS, 12.3 months) versus a low CMI (PFS, 5.8 months; OS, 21.7 months). In multivariable models, among women with MBC, a high versus low CMI at week 4 was independently associated with worse PFS (hazard ratio, 1.79; 95% CI, 1.23 to 2.60; P = .002) and OS (hazard ratio, 1.75; 95% CI, 1.21 to 2.54; P = .003). An increase in the CMI from baseline to week 4 was associated with worse PFS ( P &lt; .001) and progressive disease at first restaging ( P &lt; .001). Week 4 CMI was a strong predictor of PFS, even in the presence of circulating tumor cells ( P = .004). Conclusion Methylation of this gene panel is a strong predictor of survival outcomes in MBC and may have clinical usefulness in risk stratification and disease monitoring.
Phase I Trial Results for SL-401, a Novel Cancer Stem Cell (CSC) Targeting Agent, Demonstrate Clinical Efficacy at Tolerable Doses In Patients with Heavily Pre-Treated AML, Poor Risk Elderly AML, and High Risk MDS
Authors: Marina Konopleva, Donna E. Hogge, David A. Rizzieri, Thomas P. Cirrito, Jen Sing Liu, Steven M. Kornblau, Margarite Grable, Il-Ran Hwang, Gautam Borthakur, Allison Mankin, Carol Bivins, Guillermo Garcia-Manero, Tapan Kadia, David Harris, Farhad Ravandi, Michael Andreeff, Jorge E. Cortes, Robert Niecestro, Ivan Bergstein, Hagop M. Kantarjian, Arthur E. Frankel
Journal: Blood (2010)
AB0347 The Retention Rates of The Second Biologic Agents in Rheumatoid Arthritis Patients with Inadequate Response To TNFα Inhibitors, Single-Center, Retrospective, Observational Study
Authors: E. Kikuchi, K. Uekubo, N. Aoki, T. Yoshioka, T. Okai
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> There are few data about the safety of biologics switching for rheumatoid arthritis in clinical practice conditions. <h3>Objectives</h3> To analyze the retention rates of biologics switch therapies for rheumatoid arthritis patients after inadequate response to TNFα inhibitors. <h3>Methods</h3> Data was collected retrospectively from medical records of RA patients in our center. We divided the RA patients with inadequate response to TNFα inhibitors into the two groups. The first group is consists of the patients who switched to other TNFα inhibitors. The other is consists of the patients who switched to non-TNFα inhibitors. We analyzed the retention rate of each group by Kaplan-Meier curves and log-rank test. <h3>Results</h3> In the "<i>another TNFα inhibitor</i>" group (31 cases, 59.4±14.8 years, women: 90.3%, ACPA-positive 74.2%, MTX use 93.3%, oral steroid use 30.0%), infliximab (IFX): 11, etanercept (ETN): 7, adalimumab (ADA): 9, golimumab (GLM): 2 and certolizumab pegol (CZP): 2 are administered as the first biologics, discontinued due to adverse events: 4, inadequate efficacy:26 and other: 1 respectively), IFX: 4, ETN: 17, ADA: 3, GLM: 2 and CZP: 5 were chosen as the second biologics. The cumulative retention rates of the second biologics in 12 and 24 months were 0.628 and 0.547 respectively. The reasons for discontinuation of secondary used TNFα inhibitors were adverse events: 4 and inadequate efficacy: 9. In the "<i>non-TNFα inhibitor</i>" group (27 cases, 64.0±14.2 years, women: 83.3%, ACPA-positive 92.6%, MTX use 57.7%, oral steroid use 30.8%, IFX: 8, ETN: 13, ADA: 4, GLM: 1 and CZP: 1 are administered as the first biologics, discontinued due to adverse events: 7, inadequate efficacy: 20 respectively), tocilizumab (TCZ): 8 and abatacept (ABT): 19 were chosen as the second biologics. The cumulative retention rates of the second biologics in 12 and 24 months were 0.920 and 0.871 respectively. Three TCZ used patients were discontinued biologics within 24 months due to adverse events: 2 and inadequate efficacy: 1. There was a significant difference in the retention rates in the two groups (log-rank test, p=0.0095) (figure). In the "non-TNFα inhibitor" group, the cumulative retention rates of TCZ and ABT in 24 months are 0.822 and 1.000 respectively. There is no significant difference (log-rank test, p=0.277). <h3>Conclusions</h3> Our data suggested that non-TNFα inhibitors can be used for a long period for the RA patients with inadequate response to TNFα inhibitors. <h3>References</h3> Hirabara S, et al. Clin Rheumatol. 2014, 33: 1247–54 Deighton C. Nat Rev Rheumatol. 2009, 5:596–7 <h3>Disclosure of Interest</h3> None declared
The HSP90 Inhibitor 17-DMAG Targets NF-κB to Induce Apoptosis in CLL and Prolongs Survival in a CLL Mouse Model.
Authors: Erin K Hertlein, Thomas S Lin, Wagner J Amy, Towns H William, Virginia M Goettl, Xiaoli Zhang, David Jarjoura, Chelsey A Raymond, Derek A West, John C. Byrd, Amy J. Johnson
Journal: Blood (2009)
Platelet Apoptosis in Adult Immune Thrombocytopenia. Relationship with Auto-Antibodies, Platelet Function and Treatment
Authors: Geraldine Contrufo, Ana C Glembotsky, Nora P Goette, Paola R Lev, Matías Grodzielski, Marta S Pierdominici, Dardo Alberto Riveros, Verónica S Montero, Alejandro García, Felisa C. Molinas, Paula G. Heller, Rosana F Marta
Journal: Blood (2014)
Treatment of Recurrent or Persistent AML/MDS After Allogeneic Hematopoietic Cell Transplantation with Azacitidine.
Authors: Jennifer Vaughn, Barry Storer, Marco Mielcarek, Edus H. Warren, Paul J. Martin, Brenda M. Sandmaier, Elihu H. Estey, Rainer Storb, H. Joachim Deeg, Bart Lee Scott
Journal: Blood (2010)
Artificial Hematopoietic Stem Cell Niche Sustains Growth and Differentiation of Human ES-Derived Early Hematopoietic Progenitors.
Authors: Babak Esmaeli-Azad, Anand S. Srivastava, Cybele Frederico, Geraldo Martinez, Satoshi Yasukawa, Ewa Carrier
Journal: Blood (2007)
Partial T-Cell Depletion By Low-Dose Anti-Thymocyte Globulin to Reduce Severe Acute and Chronic Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation
Authors: Osamu Imataki, Yumiko Ohbayashi, Yukiko Ohue, Harumi Matsuka, Makiko Uemura, Norimitsu Kadowaki
Journal: Blood (2015)
Total-Thrombus-Formation Analysis System Using a Microchip Flow Chamber Reflects Bleeding Severity of Patients with Type 1 Von Willebrand Disease.
Authors: Kenichi Ogiwara, Keiji Nogami, Tomoko Matsumoto, Shoko Furukawa, Hiroaki Minami, Kazuya Hosokawa, Midori Shima
Journal: Blood (2012)
Cardiac CTA for Evaluation of Prosthetic Valve Dysfunction
Authors: Gudrun Feuchtner, Fabian Plank, Silvana Mueller, Thomas Schachner, Nikolaos Bonaros, Philipp Burghard, Florian Wolf, Donya-el Alhassan, Philip Blanke, Jonathon Leipsic, Hatem Alkadhi, André Plass, Lloyd M. Felmly, Adam J. Spandorfer, Carlo N. De Cecco, U. Joseph Schoepf
Journal: JACC. Cardiovascular imaging (2016)
Psychosocial Research and Care in Diabetes: Altering Lives by Understanding Attitudes
Authors: Katie Weinger, Mary de Groot, William T. Cefalu
Journal: Diabetes Care (2016)

The philosophers of antiquity and others through the ages recognized the connection of human emotion and thought with physiological processes and behavior (1). The relatively recent increases in the human life span and the prevalence of significant chronic illnesses have generated a greater appreciation of the relationship between human emotional, social, cognitive, and behavioral processes and health and wellness. However, understanding human behavior remains challenging, and in the presence of a significant chronic illness such as diabetes, that challenge becomes even more daunting. Specifically, the interaction of individual differences in emotional responses, attitudes, thought processes, preferences, beliefs, and social situations appear amplified with the increased complexities of new diabetes treatments. With the realization that other factors such as quality of life are equally important as physiological outcomes, the necessity of understanding behavioral and psychosocial processes is evident (2,3). Thus, the era of simply outlining a broad plan and sending it home for the patient to implement, if that era ever existed, is over. The era of placing the person with diabetes and family in the center of health care decisions and understanding their individual challenges and barriers has begun. Given the emerging concepts in the psychosocial aspects of diabetes, the editorial committee of Diabetes Care wanted to highlight this area in this issue.

This special issue of Diabetes Care presents nine articles that represent a broad spectrum of behavioral and psychosocial issues that can influence treatment success and quality of life for those living with diabetes. Central to this topic and serving as the cornerstone of the special issue is the publication of the first Position Statement from the American Diabetes Association (ADA) for the psychosocial care of people with diabetes (4). This is followed by the presentation of a collection of articles that represent important aspects of …
THU0098 No Relationship between Low Serum 25-Hydroxyvitamin D Level and Decreased Bone Mass or Bone Quality in Patients with Rheumatoid Arthritis – Tomorrow Study: Table 1.
Authors: K. Inui, T. Koike, Y. Sugioka, T. Okano, K. Mamoto, M. Tada, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Vitamin D deficiency in patients with rheumatoid arthritis (RA) is commonly observed. Previous studies have investigated the relationship between vitamin D deficiency and RA and increased risk of cardiovascular events and the role of immunomodulation. While RA is recognized as a risk factor for osteoporosis, there are few reports examining the relationship between vitamin D level and bone mass or metabolism markers in RA patients compared with healthy controls. <h3>Objectives</h3> To examine the relationship between serum 25-hydroxyvitamin D (25(OH)D) level, bone mineral density, and bone metabolic markers of RA patients compared with age-and sex-matched healthy volunteers (Vo group) using a cross-sectional method. <h3>Methods</h3> In 2010, we began a prospective cohort study called the TOMORROW Study (UMIN000003876) which compares data from RA patients with age- and sex-matched controls (Vo) recruited through mass media. Laboratory data were collected for all participants, including 25(OH)D level, insulin resistance, bone metabolic markers (urinary pentosidine, homocysteine, collagen type 1 cross-linked N-telopeptide (NTX), and osteocalcin), and anthropometric parameters. Bone mineral density of the lower extremities and body composition were determined using whole-body dual-energy X-ray absorptiometry (DXA). The parameters were compared with healthy controls, and multiple regression analysis was carried out in the RA population only. In RA patients, disease activity score 28 was measured by clinical assessment. <h3>Results</h3> There were 413 participants (208 RA patients, 205 Vo group; 349 females; mean age of 58 years) enrolled in the study. In RA patients (mean disease duration of 13 years), bone density was significantly lower (p&lt;0.01; Student9s <i>t</i>-test), and urinary NTX (p&lt;0.01), pentosidine (p&lt;0.01), and homocysteine (p&lt;0.05) were higher compared with the Vo group. The serum 25(OH)D level was lower in RA patients compared with the Vo group (p&lt;0.01) (Table). Multiple linear regression analysis in the RA population revealed no significant relationship between DXA and vitamin D level (p=0.18) or pentosidine (p=0.61). <h3>Conclusions</h3> No relationship was found between low vitamin D level and decreased bone mass or bone quality in RA patients. <h3>Disclosure of Interest</h3> K. Inui: None declared, T. Koike Speakers bureau: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, Y. Sugioka: None declared, T. Okano: None declared, K. Mamoto: None declared, M. Tada: None declared, H. Nakamura: None declared
PTH-049 Successful Reversal of High Titre Antibodies to Infliximab and Adalimumab with The Addition of Immunomodulator Therapy
Authors: A Bond, K Clark, B Gregg, P Collins, M Dibb, C Probert, S Subramanian
Journal: Gut (2016)

<h3>Introduction</h3> Immunogenicity is a common problem associated with anti-tumour necrosis factor (TNF) therapy and is often associated with loss of clinical response. Concomitant immunomodulatory therapy reduces the rate of anti-drug antibody (ADA) formation with infliximab and is associated with better outcomes.<sup>1</sup> However, the impact of immunomodulator initiation specifically to reverse established ADA has not been adequately investigated. Current guidelines recommend switching of anti-TNF agent or class switch in the presence of ADA titre &gt;9 u/ml. However, outcomes with further biologics are poor and reversal of ADA may be preferable. We report the successful reversal of very high titre ADA with immunomodulator initiation. <h3>Methods</h3> This was a retrospective study of patients with established ADA on infliximab or adalimumab monotherapy, in whom an immunomodulator was commenced. Levels of ADA and trough levels of drug were monitored by ELISA (Theradiag). <h3>Results</h3> Four patients were included (3 Crohn’s disease and 1 ulcerative colitis), of which two patients were receiving infliximab and 2 adalimumab. There were 3 males and 1 female with a mean age of 50 years (SD ±17.6). All patients had initial titres of ADA &gt; 200 ng/ml for infliximab and &gt;160 ng/ml for adalimumab, with undetectable trough levels (&lt;0.1 µg/ml). Three patients were treated with thiopurines and one with methotrexate. Three patients (2 thiopurines, 1 methotrexate) had successful reversal of antibodies accompanied by an increase in trough levels and clinical improvement. One infliximab and one adalimumab patient also had dose escalation after reversal of ADA to achieve therapeutic drug concentration. One patient who achieved reversal stopped their thiopurine due to side effects and had recurrence of ADA and a subsequent loss of response. <h3>Conclusion</h3> In patients undergoing monotherapy with anti-TNF treatment who develop ADA, the addition of an immunomodulator agent has the potential to reverse even high antibody titres and regain clinical response. This strategy is particularly useful as the risk of ADA with a subsequent anti-TNF is higher in patients with ADA to one anti-TNF agent[2]. <h3>References</h3> 1 Ruffolo C, Scarpa M, Bassi N. Infliximab, azathioprine, or combination therapy for Crohn’s disease. <i>N Engl J Med</i> 2010;<b>363</b>:1086–8. doi:10.1056/NEJMoa0904492 2 Frederiksen MT, Ainsworth MA, Brynskov J, Thomsen OO, Bendtzen K SC. Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD. <i>Inflamm Bowel Dis</i> 2014;<b>20</b>:1714–21. <h3>Disclosure of Interest</h3> None Declared