tbuckley/cabot-search huggingface dataset:
OC-001 Clinical Factors that Determine Primary Non-Response (PNR) to anti-TNF Drugs in Patients with Active Luminal Crohn’s Disease (CD)
Authors: GA Heap, T Ahmad
Journal: Gut (2016)

<h3>Introduction</h3> 10–40% of patients with CD fail to respond to anti-TNF induction therapy at 10–14 weeks. The mechanisms underlying PNR are uncertain but a better understanding of these factors might allow more cost-effective, individualised anti-TNF treatment. We present an interim analysis of PNR in the PANTS cohort. <h3>Methods</h3> The PANTS study is a UK wide, multi-centre 3 year prospective, observational cohort study investigating PNR to Infliximab (IFX) and Adalimumab (ADA). Serial collection of clinical data and sampling of DNA, RNA, serum and stool will allow down-stream multi-omic studies. Inclusion criteria include active luminal Crohn’s disease supported by raised CRP or Calprotectin and no prior exposure to anti-TNF therapy. PNR was defined as failure of HBI to fall by ≥3 points or to ≤4 AND failure of CRP to fall by ≥50% or to ≤3 mg/dL OR failed steroid withdrawal. Drug and anti-drug antibody levels were measured using Immunodiagnostic drug tolerant assays. <h3>Results</h3> 1176 (568 male) patients aged 4.0–77.2 years have been recruited from 106 sites and reached 14 weeks after quality control. Patients were treated with IFX (695, 59.1%) or ADA (481, 40.9%). At entry 39.7% of patients had an HBI of ≤4, 32.14% ≥ 8, and 29.4% of patients had a CRP ≤ 3, 42.4% had a CRP ≥ 10. Concomitant drugs at entry included steroids 18.5%, azathioprine 39.2%, mercaptopurine 7.40%, methotrexate 5.4%. PNR could be assessed at week 14 for 1090 (92.7%) patients. PNR was observed in 16.9% and 23.7% of the IFX and ADA treated patients respectively. This difference was not significant once adjusted for baseline disease activity (P = 0.2). To date only 2 patients who met the week 14 PNR criteria achieved remission on anti-TNF at 1 year (sensitivity 0.99, specificity 0.4). A multivariate regression identified albumin (P = 0.0036) as associated with PNR at Week 14 in the IFX group and drug level (P = 0.00035), calprotectin (P = 0.033), albumin (P = 0.037) and anti-drug antibody level (P = 0.024) in the ADA group. In combined analysis BMI (P = 0.017) and drug level (P = 0.024) were associated with PNR. 75 IFX and 36 ADA patients had anti-drug antibodies at week 14, of which 33 and 6 patients had no detectable drug. Development of anti-drug antibodies in the first 14 weeks was associated with monotherapy (P = 0.00021) and was seen more commonly in patients with early infusion reactions (P = 2x10<sup>−16</sup>). <h3>Conclusion</h3> The PANTS study has provided a real world estimate of PNR and associated risk factors in a large prospective cohort using a simple clinical and biochemical definition at week 14 that predicts non-remission at week 54. Low drug level and immunogenicity are associated with PNR, infusion reactions and monotherapy suggesting early measurement might help prevent and manage PNR. <h3>Disclosure of Interest</h3> G. Heap Conflict with: Abbvie, T. Ahmad Grant/research support from: Abbvie, MSD, Hospira, Inflectra, Conflict with: Abbvie, MSD
THU0341 Correlation between Essdai and Clinessdai in A Real-Life Cohort of Sjögren's Syndrome Patients: Table 1
Authors: L. Quartuccio, C. Baldini, E. Bartoloni, F. Carubbi, R. Priori, A. Alunno, R. Gerli, G. Valesini, R. Giacomelli, S. Bombardieri, S. De Vita
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> ClinESSDAI has been recently proposed as a valid tool for the assessment of disease activity in Sjögren9s syndrome (SS) and it seems very close to the original ESSDAI (1, 2). The rationale of developing ClinESSDAI was to provide an accurate evaluation of disease activity independently of B-cell biomarkers, and it has been proposed to be used in biological/clinical studies to avoid data colinearity, in clinical trials, as secondary endpoint, to detect change independently of biological effect of the drug, and in clinical practice to assess disease activity for visits where immunological tests have not been done. However, validation in real-life cohorts is lacking, since 702 fictive vignettes derived from 96 real cases of primary SS of the ESSDAI development study were used. <h3>Objectives</h3> Primary objective of the study was to correlate ClinESSDAI and ESSDAI scores in large real-life cohorts of primary SS patients. <h3>Methods</h3> SS patients from 5 independent cohorts were studied. All patients fulfilled the American-European Consensus Group Criteria for primary SS. ESSDAI and ClinESSDAI scores were calculated at SS diagnosis. The whole population comprised 966 patients with primary SS (mean age 52±14, 95.4% female). Patients positive for anti-SSA antibodies were 684 (70.8%), for anti-SSB antibodies were 353 (46.5%), and negative for both anti-SSA/SSB antibodies were 271 (28.1%). Correlation between ClinESSDAI and ESSDAI scores was evaluated by Spearman9s test. <h3>Results</h3> ClinESSDAI score significantly correlated with ESSDAI score in the first cohort (p&lt;0.0001, r=0.972). Both ClinESDDAI and ESSDAI scores significantly correlated with all the single domains of the ClinESSDAI and ESSDAI, respectively, showing very similar results, even if the level of correlation was moderate to low in all the domains for both tools (table 1). Importantly, ClinESSDAI also significantly correlated with the biological domain of the ESSDAI score (table 1). Interestingly, focus score, available in 363/966 (37.6%) patients, did not correlate with both ClinESSDAI and ESSDAI scores (p=0.63, and p=0.426, respectively), while age at diagnosis inversely correlated with ClinESSDAI and ESSDAI scores (p&lt;0.0001, r=-0.151, p&lt;0.0001, r=-0.17, respectively). <h3>Conclusions</h3> ClinESSDAI is a valid tool to assess systemic disease activity in primary SS. <h3>References</h3> Seror R, et al. Ann Rheum Dis 2010;69:1103–9. Seror R, et al. Ann Rheum Dis 2015;74(Suppl2): 579. <h3>Disclosure of Interest</h3> None declared
Usefulness of microparticles's Release to Improve Diagnosis of Hereditary Spherocytosis: Results of a Multicentre Study
Authors: François Mullier, Elodie Lainey, Odile Fenneteau, Lydie M. Da Costa, Françoise Schillinger, Nicolas Bailly, Yvan Cornet, Christian Chatelain, Jean-Michel Dogné, Bernard Chatelain
Journal: Blood (2010)
Infection Burden of Double Stranded DNA (dsDNA) Viruses after CD34+ Selected, T-Cell Depleted (TCD) Hematopoietic Cell Transplantation (HCT) for Myeloid Malignancies at Memorial Sloan Kettering Cancer Center (MSK)
Authors: Yao-Ting Hayden Huang, Seong Jin Kim, Yeon Joo Lee, Daniel Burack, Paige Nichols, Molly Maloy, Roni Tamari, Miguel-Angel Perales, Sergio A. Giralt, Hugo R. Castro-Malaspina, Esperanza B Papadopoulos, Ann A. Jakubowski, Genovefa A Papanicolaou
Journal: Blood (2015)
AB1070 Could Enhanced Patient Education Improve The Outcome of Clinical Trials in Rheumatoid Arthritis?
Authors: R.M. Cseuz, M. Megyaszai, B. Shenker, A. Mirzahosseini
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Patient education is considered to be a highly cost-effective way to limit disability in rheumatic diseases as well as to achieve an improvement in quality of life. Since 1997 our team has carried out a variety of educational programs for RA patients [1]. Since the year 2000 several clinical trials have been carried out on RA patients at Revita Clinic. <h3>Objectives</h3> Internationally, medical teams involved in clinical trials work according to the "gold standard" (ICH-GCP) based on regular training and international guidelines. It is suggested that apart from the known and obvious prerequisites for clinical trials, individual sites could add to the process of developing a new molecular entity by enhancing the education of recruited patients thereby improving compliance and reducing the failure rate of investigational products used in such trials. <h3>Methods</h3> Data and statistical analyses from 16 RA studies on biologics &amp; JAK inhibitors from the last 5 years involving 185 patients are presented of which 144 were involved in customized educational programs utilizing an educational DVD, and 6-week courses involving meetings with other patients, doctors, and physiotherapists. Compliance measured using standard and site-specific questionnaires were compared with meta-analyses of international studies. Efficacy measures a) withdrawal risk [2]; b) HAQ; c) DAS28; d) GAD VAS; e) Physician Assessment, were analyzed and compared with meta-analyses of international studies. <h3>Results</h3> The mean withdrawal risk of Revita Clinic patients was found to be significantly lower compared to global data [2] (p&lt;0.05). The mean DAS28 value change is -2.23±1.68, significantly higher than the global average of -1.17±0.67 [3] (p&lt;0.0001). The mean HAQ value change is -0.39±0.54, significantly higher than the global average: -0.28±0.12 [3] (p&lt;0.0001). The mean GAD VAS and Physician Assessment, changes are -26 and -30, respectively. <h3>Conclusions</h3> The overall goal is to increase participation, reduce costs, and accelerate the time factor in clinical trials. The high failure rate of investigational products in such trials, especially in the later stages of development, is a significant contributor to the costs and time associated with bringing new molecular entities to market. Enhanced patient education might well help to overcome the present shortcomings thereby increasing the cost-effectiveness of clinical trials. <h3>References</h3> Cseuz et al. EULAR Meeting 2003 [AB0634] Aaltonen et al. PloS ONE, 2012; 7: e30275. Bujkiewicz et al. Value Health, 2014; 17: 109–115. <h3>Acknowledgement</h3> The painstaking work of the study nurse, A. Besenyei, and that of the study coordinator, K. Ivanics, are highly appreciated. <h3>Disclosure of Interest</h3> None declared
Shifts in Intra-Clonal Dynamics Rather Than Novel Mutations Are the Main Engine Driving Tumor Evolution in Relapsed CLL
Authors: Dan-Avi Landau, Petar Stojanov, Michael S Lawrence, Carrie Sougnez, Aaron McKeena, Scott Carter, Stacey Gabriel, Donna Neuberg, Nir Hacohen, Eric S Lander, Jennifer R. Brown, Gad Getz, Cathy Wu
Journal: Blood (2011)
A Phase 1 Trial of Alisertib and Romidepsin for Relapsed/Refractory Aggressive B-Cell and T-Cell Lymphomas
Authors: Paolo Strati, Yasuhiro Oki, Luis E. Fayad, Loretta Nastoupil, Nathan H. Fowler, F. B. Hagemeister, Larry W Kwak, Hun Ju Lee, Michael Wang, Jason R. Westin, Charnelle Ruben, Emily Wesson, Michelle A. Fanale
Journal: Blood (2014)
Mutations in the TNFRSF1A, CEBPE and ELANE genes in a Congenital Cyclic Neutropenia Patient: A New Syndrome?
Authors: Julia Skokowa, Olga Klimenkova, Maksim Klimiankou, Siarhei Kandabarau, Marlene Reuter, Anna-Lena Hagemann, Karl Welte
Journal: Blood (2012)
OP0124 Imaging Remission by Musculoskeletal Ultrasound Leads To A Better Functional Outcome – Results of The US Impera Study - Us 7-Score Implementation Study in Early Rheumatoid Arthritis
Authors: A.-M. Glimm, S. Ohrndorf, I. Fischer, J. Strunk, W. Schmidt, W. Hartung, H. Sattler, H. Kellner, G. Schmittat, G.-R. Burmester, M. Backhaus
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Novel treatment options together with a treat-to-target strategy present new challenges to imaging procedures in terms of therapy monitoring. <h3>Objectives</h3> To evaluate the functional outcome measured by Health Assessment Questionnaire (HAQ) as the primary outcome in patients with early rheumatoid arthritis (RA) who were treated by standard clinical care (clinical cohort) in comparison to patients in whom treatment decisions were additionally based on musculoskeletal ultrasound (US) using the US7 score (US-cohort) in a nationwide investigator initiated study in Germany. <h3>Methods</h3> Functional (HAQ), clinical (DAS28, patient9s Visual Analogue Scale [VAS] for disease activity) and laboratory parameters (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) were analyzed at seven different time points for a total of 18 months and compared between the two study cohorts. Treatment decision was made according to local standard of care (SOC) with a treatment goal of DAS28 &lt;3.2. In the US-cohort, imaging remission criteria were defined as Gray-scale US (GSUS) &lt;2 and Power Doppler-US (PDUS) =0 per joint level. In a subgroup analysis, US patients were analyzed separately with regard to imaging remission status and the parameters outlined above. <h3>Results</h3> Data of 313 patients (US-cohort [n=166], clinical cohort [n=147]) demonstrated a reduction of HAQ, DAS28, VAS and laboratory activity (ESR, CRP) to a low disease activity status 18 months after the beginning/change of antirheumatic therapy according to SOC (table 1). The results of functional and clinical outcome in both cohorts did not show significant differences. However, subgroup analysis of the US-cohort with imaging remission resulted in a significantly lower HAQ, DAS28 and VAS compared to patients not fulfilling these US remission criteria (table 1). <h3>Conclusions</h3> Treatment strategies by a treat to target approach in early RA patients reduced disease activity and improved functional outcome of HAQ irrespective of imaging guidance. However, patients with imaging remission by US exhibited a significantly better functional outcome and lower disease activity status. Accordingly, an additional ultrasound examination aiming at imaging remission should be strongly considered in clinical practice. <h3>Disclosure of Interest</h3> None declared
Alternate Week Administration of the Farnesyltransferase Inhibitor Tipifarnib (ZARNESTRA®, R115777) in Patients with Myelodysplastic Syndrome: Results of a Phase 1 Study.
Authors: Razelle Kurzrock, Srdan Verstovsek, John J. Wright, Susan R. Pilat, Jorge E. Cortes, Elihu H. Estey, Francis J. Giles, Miloslav Beran, Hagop M. Kantarjian
Journal: Blood (2005)
Control of Fulminant Juvenile Myelomonocytic Leukemia (JMML) Relapse and Gut GvHD III° with Purinethol Early after Unrelated Donor BMT.
Authors: Daniel Stachel, Chara Gravou-Apostolatou, Michaela Kuhlen, Alfred Leipold, Peter Bader, Jorn Beck, Wolfgang Holter
Journal: Blood (2004)
Analysis of Predictive Power of Prednisone Dose at 3 Months of Treatment on CGVHD Prognosis.
Authors: Pablo M. Parker, Ryotaro Nakamura, Vinod Pullarket, Joseph Rosenthal, Eileen P. Smith, David S. Snyder, Jasmine M. Zain, George Somlo, Annette Brown, Hanjoo Kim, Joycelynne Palmer, Ji-Lian Cai, Maria L. Delioukina, Peter M. Falk, Chatchada Karanes, Neil M. Kogut, Amrita Krishnan, Auayporn P. Nademanee, Margaret R. O’Donnell, Leslie Popplewell, Firoozeh Sahebi, Ricardo Spielberger, Anthony S. Stein, Stephen J. Forman
Journal: Blood (2007)
Expanded Human NKT Type II Cells: Effective Against Colon Cancer Cells, Safe across Major MHC Barriers and Successfully Expandable after Non-Myeloablative HCT for Solid Tumors.
Authors: Dario Sangiolo, Emanuela Martinuzzi, Fabrizio Carnevale-Schianca, Antonio Capaldi, Massimo Geuna, Katiuscia Vitaggio, Massimo Aglietta, Alessandro Cignetti
Journal: Blood (2005)
Effects Of Long-Term Exposure To Phytochemicals and Nsaids On The Self-Renewal Of Leukemic Blast Progenitors In Vitro
Authors: Ikuo Murohashi, Kazuma Miyahara, Mai Shimada, Yan Zhao, Yi Zhang, Ken-ichi Tanaka, Hiroyuki Hayashi, Noriko Ihara
Journal: Blood (2013)
DNA Flow Cytometry and Metaphase Cytogenetics Can Predict Progression of Asymptomatic Monoclonal Gammopathies (AMG) to Symptomatic Multiple Myeloma (MM).
Authors: Xenofon Papanikolaou, Sarah Waheed, Madhav V. Dhodapkar, Saad Z Usmani, Christoph Heuck, Frits van Rhee, Joshua Epstein, Bart Barlogie
Journal: Blood (2012)
Impact of Low-Dose TBI on Outcome of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation from HLA Identical Sibling for Acute Myeloid Leukemia
Authors: Jun Aoki, Sachiko Seo, Masatsugu Tanaka, Heiwa Kanamori, Takahiro Fukuda, Naoki Kobayashi, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta, Akiyoshi Takami
Journal: Blood (2014)
Hydrogels: Strong and Rapidly Self‐Healing Hydrogels: Potential Hemostatic Materials (Adv. Healthcare Mater. 21/2016)
Authors: Weijuan Huang, Yixiang Wang, Yun Chen, Yanteng Zhao, Qiang Zhang, Xiang Zheng, Lingyun Chen, Lina Zhang
Journal: Advanced Healthcare Materials (2016)

Chitosan, derived from shrimp and crab, is used to develop a self-healing hydrogel with four-armed polyethylene glycol by Lingyun Chen and co-workers on page 2813. The four-armed crosslinker dynamically grabbed the chitosan chains, and the resultant hydrogel can directly be injected through a needle onto internal bleeding site, serving as physical barrier to efficiently stop bleeding.
Reapplication of High-Dose Chemotherapy with Melphalan Followed by Autologous Hematopoietic Stem Cell Transplantation as Salvage Therapy for Patients with Relapsed Multiple Myeloma
Authors: Leopold Sellner, Sonja Teodorov, Christiane Heiss, Axel Benner, Gerlinde Egerer, Peter Dreger, Anthony D. Ho, Hartmut Goldschmidt, Kai Neben
Journal: Blood (2010)
BK Viruria in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: Increased Incidence in Patients Receiving Alemtuzumab (ALEM) as Conditioning Therapy and Lack of Efficacy of Cidofovir.
Authors: Terrance Comeau, T. Shea, D. Gabriel, D. Morris, R. Irons, D. Harvey, A. Sharf, C. Krasnov, C. Dunphy, N. Benderenko, M. Brecher, J. Serody
Journal: Blood (2004)
Controlling drug release from non-aqueous environments: Moderating delivery from ocular silicone oil drug reservoirs to combat proliferative vitreoretinopathy
Authors: Helen Cauldbeck, Maude Le Hellaye, Mark Long, Stephnie M. Kennedy, Rachel L. Williams, Victoria R. Kearns, Steve P. Rannard
Journal: Journal of Controlled Release (2016)

In a number of cases of retinal detachment, treatment may require the removal of the vitreous humour within the eye and replacement with silicone oil to aid healing of the retina. The insertion of silicone oil offers the opportunity to also deliver drugs to the inside of the eye; however, drug solubility in silicone oil is poor and release from this hydrophobic drug reservoir is not readily controlled. Here, we have designed a range of statistical graft copolymers that incorporate dimethylsiloxane and ethylene glycol repeat units within the side chains, allowing short chains of oligo(ethylene glycol) to be solubilised within silicone oil and provide hydrogen bond acceptor sites to interact with acid functional drug molecules. Our hypothesis included the potential for such interactions to be able to delay/control drug release and for polymer architecture and composition to play a role in the silicone oil miscibility of the targeted polymers. This strategy has been successfully demonstrated using both ibuprofen and all-trans retinoic acid; drugs with anti-inflammatory and anti-proliferation activity. After the copolymers were shown to be non-toxic to retinal pigment epithelial cells, studies of drug release using radiochemical approaches showed that the presence of 10 v/v% of a linear graft copolymer could extend ibuprofen release over three-fold (from 3 days to > 9 days) whilst the release of all-trans retinoic from the silicone oil phase was extended to > 72 days. These timescales are highly clinically relevant showing the potential to tune drug delivery during the healing process and offer an efficient means to improve patient outcomes.
Phase I and Pharmacokinetic Study of Inotuzumab Ozogamicin (CMC- 544) as a Single Agent in Japanese Patients with Follicular Lymphoma Pretreated with Rituximab.
Authors: Kensei Tobinai, Michinori Ogura, Kiyohiko Hatake, Yukio Kobayashi, Takashi Watanabe, Toshiki Uchida, Masanobu Kasai, Masahiro Yokoyama, Yasuhito Terui, Chiho Ono, Masanao Akiyama, Junko Ohata
Journal: Blood (2008)
Comparison of Two Regimens for the Treatment of Elderly Patients with Acute Lymphoblastic Leukaemia (ALL).
Authors: Massimo Offidani, Laura Corvatta, Lara Malerba, Monica Marconi, Massimo Catarini, Riccardo Centurioni, Franco Leoni, Anna Rita Scortechini, Maria Cristiana Masia, Pietro Leoni
Journal: Blood (2004)
Correlation of Serological and MRI-Based Treatment Response to Systemic Chemotherapy In 100 Patients with Multiple Myeloma
Authors: Jens Hillengass, Sofia Ayyaz, Kerstin Kilk, Marc-André Weber, Thomas Hielscher, Gerlinde Egerer, Hans-Ulrich Kauczor, Stefan Delorme, Anthony D. Ho, Hartmut Goldschmidt, Kai Neben
Journal: Blood (2010)
AB1022 Association between Psoriasis and Incident Diabetes Mellitus: A Population-Based Study in Taiwan
Authors: L.-H. Huang, C.-F. Kuo, S.-F. Luo, K.-H. Yu, Y.-F. Fang
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Psoriasis is a known risk factor of cardiovascular disorders in addition to traditional risk factors such as diabetes mellitus (DM). However, the association between psoriasis and DM is unclear. <h3>Objectives</h3> To quantify the risk by comparing the incidence of DM between patients with psoriasis and the general population in Taiwan. <h3>Methods</h3> The study cohort consisted of two populations. The first population is the whole patients first diagnosed with psoriasis in 2000 in Taiwan, and the second population is a nationally representative cohort of 1,000,000 individuals from the Longitudinal Health Research Database in 2000. Those who younger than age of 10 or had DM before 2000 were excluded from analysis. They were followed from 2000 until the occurrence of DM, death or 31 December 2012. Incidence rates of DM were calculated. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for DM, adjusted for age, gender and pre-existing comorbidity. <h3>Results</h3> The study cohort comprised 756,333 subjects with a mean follow-up of 11.27 years; among them 15,099 patients with incident psoriasis were identified. Patients with psoriasis had a higher comorbidity of renal disease (1.48%), congestive heart failure (0.91%), cardiac dysrhythmia (1.82%), cerebrovascular disease (2.74%) and peripheral vascular disease (0.94%) than the general population. The incidence rate for DM was 2.04 (95% CI, 2.01–2.08) per 100 person-years for psoriasis patients comparing to 1.10 (95% CI 1.03–1.16) per 100 person-year in the general population. The adjusted IRR of incident DM was 1.34 (95% CI 1.29–1.38) for patients with psoriasis. <h3>Conclusions</h3> Patients with psoriasis has an increased risk for DM. A vigilant monitoring for DM in patients with incident psoriasis is warranted to reduce long-term cardiovascular risks. <h3>Disclosure of Interest</h3> None declared
Group B <i>Streptococcus</i> circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor
Authors: Erica Boldenow, Claire Gendrin, Lisa Ngo, Craig Bierle, Jay Vornhagen, Michelle Coleman, Sean Merillat, Blair Armistead, Christopher Whidbey, Varchita Alishetti, Veronica Santana-Ufret, Jason Ogle, Michael Gough, Sengkeo Srinouanprachanh, James W. MacDonald, Theo K. Bammler, Aasthaa Bansal, H. Denny Liggitt, Lakshmi Rajagopal, Kristina M. Adams Waldorf
Journal: Science Immunology (2016)

Group B streptococci overcome neutrophils in placental membranes, inducing fetal injury and preterm labor.