tbuckley/cabot-search huggingface dataset:
FRI0038 Anti-Hinge Antibodies Recognize IGG Subclass- and Protease-Restricted Hinge neo-Epitopes
Authors: W. Falkenburg, D. van Schaardenburg, P. Ooijevaar-de Heer, M. Tsang-A-Sjoe, I. Bultink, A. Voskuyl, A. Bentlage, G. Vidarsson, G. Wolbink, T. Rispens
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Anti-hinge antibodies (AHAs), autoantibodies that target neo-epitopes exposed in the hinge of IgG molecules after cleavage by proteases, can be found in healthy individuals but more frequently and at higher levels in rheumatoid arthritis (RA) patients. Recently, our group reported that AHAs in RA patients specifically target pepsin-cleaved hinge of IgG4. <h3>Objectives</h3> Determine the presence of AHAs and their specificity for protease- and IgG subclass-restricted neo-epitopes in healthy donors (HDs) and patients with RA or systemic lupus erythematosus (SLE). <h3>Methods</h3> Presence of AHA-reactivity and specificity of AHAs for protease- and IgG subclass-restricted neo-epitopes was determined with newly developed enzyme-linked immunosorbent assays (ELISAs) that measure AHA-reactivity against the hinge of F(ab9)2-fragments generated by cleaving the four IgG subclasses with pepsin or IdeS, an IgG-degrading enzyme of Streptococcus pyogenes (Figure 1). Inhibition experiments were performed to investigate cross-reactivity and results were confirmed using a novel Surface Plasmon Resonance imaging (SPRi) array. <h3>Results</h3> Reactivity against at least one of eight F(ab9)2-targets was found in 68% (51/75) of HDs, 65% (47/72) of SLE patients, and 83% (59/73) of RA patients. Individual AHA responses targeted protease-restricted neo-epitopes. Reactivity against IdeS-generated F(ab9)2-targets was found more frequently in all three groups, but reactivity against pepsin-generated F(ab9)2-targets better discriminated between RA patients and HDs or SLE patients, with significantly higher levels of AHAs against pepsin-cleaved IgG1 and IgG3 in RA compared to SLE and HDs respectively. The most discriminatory AHA-reactivity in RA was against pepsin-cleaved IgG4, with at least 5x more positive sera compared to HDs and SLE and significantly higher levels (P&lt;0.0001). Cross-reactivity for different IgG subclasses was only observed for subclasses having homologous F(ab9)2 C-termini (IgG1, IgG3, IgG4). <h3>Conclusions</h3> Anti-hinge antibodies specifically recognize IgG subclass- and protease-restricted hinge neo-epitopes, possibly generated under (chronic) inflammatory conditions. The protease-restricted specificity of AHAs suggests that different AHA responses have developed under distinct inflammatory or infectious conditions and may be markers of -and participants in such conditions. In the proteolytic environment of the inflamed joint AHAs may contribute to immune complex formation, promoting further tissue destruction and inflammation. <h3>Disclosure of Interest</h3> None declared
Serum Alkaline Phosphatase Level On Day 4 Of G-CSF Administration Could Be a Simple Yet Practical Surrogate Marker For CD34 Mobilization and Collection
Authors: Yousef Zakharia, Vamsi Kota, Joshua Mansour, Radhika Prabhakar, Ling Lan, Farrukh T Awan, Anand Jillella
Journal: Blood (2013)
Mutated EZH2 Collaborates with Myc in Inducing Lymphoma in a Mouse Model
Authors: Tobias Berg, Damian Yap, Silvia Thoene, Tracee Wee, Nathalie Schoeler, Patricia Umlandt, Harry Chang, Lisa Yue, David Lai, Grace Cheng, Ryan D Morin, Martin Hirst, Marco A. Marra, Gregg B. Morin, Randy D. Gascoyne, Samuel A. Aparicio, R. Keith Humphries
Journal: Blood (2011)
AB0897 Evaluation of Clinical Factors Affecting The Diagnosis Time in Familial Mediterranean Fever
Authors: C. Bes, N. Alpay Kanıtez, S. Yılmaz Öner, B. Yılmazer, S. Çelik, M. Soy
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Familial Mediterranean fever (FMF) is the most frequent periodic febrile syndrome among the autoinflammatory disease, characterized by recurrent, self-limiting episodes of fever and serositis. FMF is a common disease in mediterranean countries although the diagnosis may be delayed due to especially patients-related reasons. <h3>Objectives</h3> In this study, we aimed to investigate the relationship between the diagnosis time and clinical features in patients with FMF. <h3>Methods</h3> Consecutively 44 patients diagnosed with FMF were recruited for this cohort study. The diagnosis time, clinical features, genetic mutations of MEFV genes and disease severity calculated with the Tel-Hashomer Severity Score were recorded retrospectively. The period from disease onset to diagnosis was named as undiagnosed time (UT). Correlation coefficients and significance were calculated by Pearson9s test to assess the differences between groups. For all the tests, a two-tailed p value of &lt;0.05 was considered statistically significant. Statistical analysis were performed using the software package SPSS 17 running on Windows NT. <h3>Results</h3> The mean age was 27.25±5.83 years, (59% female). The mean disease severity score was 6.25±2.06. Patient9s clinical features included fever (79.5%), peritonitis (95.4%), arthralgia and/or arthritis (36.6%), pleuritis (13.6%), and erysipelas-like erythema (13.6%). Genetic analysis of 44 patients revealed that M694V was the most frequent mutation (63.6%). The mean UT was found 12.72±7.08 years. Amyloidosis was diagnosed in 3 (6.8%) patients with UT of up to 27 years. There was a negative correlation between UT and disease severity (p&lt;0.05). <h3>Conclusions</h3> Our study, although a small patient group, suggested that the time from disease onset to diagnosis may still be longer in FMF. Disease severity is seen as an important factor for diagnosis time. Mild attacks or the lack of any symptom in the attack intervals may be reasons for late admission to physician. We have considered that emphasizing of patient education is substantial especially in countries which have high FMF prevalence. <h3>Disclosure of Interest</h3> None declared
SAT0419 Gender Differences in Disease Activity, Physical Function and Quality of Life in Patients with Ankylosing Spondylitis Treated with TNF-α Inhibitors
Authors: B.P. van der Slik, S. Arends, E. Brouwer, F.R. Wink, M. Efde, H. Bootsma, F. Maas, A. Spoorenberg
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The clinical presentation of ankylosing spondylitis (AS) can be different between genders. <h3>Objectives</h3> To investigate differences in clinical assessments of disease activity, physical function and quality of life between male and female AS patients before the start of TNF-α inhibitors and after 2 years of follow-up. <h3>Methods</h3> Patients from the Groningen Leeuwarden AS (GLAS) cohort who started TNF-α inhibitors because of active disease with baseline and 2-year follow-up visits were included. Disease activity was assessed using the BASDAI, ASDAS, CRP, and patient GDA. Physical function and quality of life were assessed using the BASFI and ASQoL, respectively. <h3>Results</h3> Of the 220 included AS patients with active disease, 69% were male, 78% HLA-B27 positive, mean age was 43±12 years, and median duration of symptoms 16 years (IQR 8–25). Patient characteristics were comparable between men and women. At baseline, female patients with AS experienced significantly higher disease activity according to BASDAI, ASDAS, and patient GDA compared to male patients. Baseline CRP levels were comparable between genders. Furthermore, physical function (BASFI) and quality of life (ASQoL) were significantly worse in female patients (Table 1). After staring TNF-α inhibitors, all clinical assessments improved significantly during 2 years of follow-up. The change over 2 years was comparable between male and female patients for all measures of disease activity, physical function, and quality of life (Table 1). After 2 years, significantly less women were still using their first TNF-α inhibitor (53% vs. 81%) and significantly more women had switched to a second TNF-α inhibitor (31% vs. 15%). <h3>Conclusions</h3> In this large cohort of AS patients with active disease, cross-sectional analysis showed that women experience higher disease activity and worse physical function and quality of life on self-reported assessments than men. Longitudinal analysis after starting TNF-α inhibitors showed that the changes in clinical assessments over 2 years were comparable between genders. <h3>Acknowledgement</h3> The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. <h3>Disclosure of Interest</h3> B. van der Slik: None declared, S. Arends Grant/research support from: Pfizer, E. Brouwer Grant/research support from: Pfizer, F. Wink Consultant for: Abbvie, M. Efde: None declared, H. Bootsma: None declared, F. Maas: None declared, A. Spoorenberg Grant/research support from: Abbvie, Pfizer, UCB, Consultant for: Abbvie, Pfizer, MSD, UCB, Novartis
A Phase I Study of the Kinesin Spindle Protein Inhibitor Ispinesib (SB-715992) in Relapsed/Refractory Acute Leukemia
Authors: Lisa M. Arfons, Mark H. Kirschbaum, Timothy W. Synold, Hillard M. Lazarus, Tamila L. Kindwall-Keller, Mary J. Laughlin, Maureen G. Conlan, Joe Seroogy, Larry Doyle, Brenda W. Cooper
Journal: Blood (2008)
ACTR-03. SAFETY AND FEASIBILITY OF RAPID RITUXIMAB INFUSIONS IN PATIENTS WITH PRIMARY CNS LYMPHOMA
Authors: Lisa Modelevsky, Richard Tizon, Rachel Garonce, Samantha Reiss, Thomas Kaley
Journal: Neuro-Oncology (2016)

To establish the safety and feasibility of rapidly infusing rituximab over 90 minutes in patients with primary CNS lymphoma. Administering rituximab at standard rate is meant to minimize infusion reactions though results in long infusion times with first doses averaging six hours and subsequent doses four hours. In a subset of patients with systemic B-cell mediated diseases, rapidly infusing subsequent rituximab doses over 90 minutes is safe, feasible, decreases healthcare costs, and improves patient satisfaction. We initiated a pilot study to determine if rapid infusion of rituximab is safe in patients with CNS lymphoma. We reviewed all patients with CNS lymphoma who received rapid rituximab infusions from January 2016 to June 2016. Pilot inclusion criteria include age ≥18 years, tolerated ≥1 previous rituximab infusions at standard rate without reaction, and did not receive concurrent chemotherapy on day of infusion. Concomitant corticosteroids to control disease related neurologic symptoms were allowed. The primary endpoint was incidence of infusion reactions. Five out of nine patients screened for rapid rituximab infusion met criteria and a total of 21 infusions were administered. Patients had a median age of 61 years (range 45–63 years) and 4 were female. All patients received rituximab dosed at 500 mg/m2 for diagnosis of primary CNS lymphoma. Pre-medication consisted of acetaminophen and diphenhydramine. Prior to first rapid infusion, four patients received one standard infusion and one patient had received three. None of the five patients experienced a reaction during any rapid infusion. Two patients were on dexamethasone 2mg daily during their first rapid infusion. Steroids were not administered with any other infusion. Rapid administration of rituximab was safe and feasible for patients with primary CNS lymphoma.
THU0400 Relationship between Health Quality of Life and Other Indicators in Patients with Axial Spondyloarthritis: Table 1
Authors: J.L. Garrido-Castro, C. Gonzalez-Navas, J. Castro-Jimenez, P. Font-Ugalde, E. Collantes-Estevez
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Axial spondyloarthritis (AxSpA) is an inflammatory disease that mainly affects the spine. As the disease progresses, there is a reduction of quality of life (QOL) in patients due to loss of mobility and function, and also by episodes of inflammation and stiffness (disease activity). <h3>Objectives</h3> To Analyze relationship between QOL of patients with AxSpA and other commonly used indicators in assessing these patients. <h3>Methods</h3> 100 patients with AxSpA (67% male, age 48.38±11.05, disease duration 14.37±10.74, HLAB27 + 85%) were included. QOL of patients was assessed by the Ankylosing Spondylitis Quality of Life index (ASQoL). Mobility was evaluated by conventional metrology and by a new motion capture system (UCOTrack) and UCOASMI as its metrological index [1]. PRO questionnaries were completed to evaluate activity, function and overall status. Structural damage was scored by mSASSS index. To analyze relationship, Spearman tests, ANOVA and multiple linear regression were performed. <h3>Results</h3> ASQoL showed statistically significant correlations with BASFI, BAS-G, ASDAS and UCOASMI. No significant correlations between QOL and structural damage, neither B27+, or having nr-AxSpA were found. Table shows results groupped by sex, B27, duration, nr-AxSpA (mSASSS &lt;5 Duration&gt;5 years) high activity level and poor mobility with statistical significance. Variables that were independently associated with ASQOL, in a multivariable linear regresion, were gender (p=0.027), BASDAI (p=0.008) and BASFI (p&lt;0.001) R<sup>2</sup> =0.676. Repeating this analysis, but including mobility measures obtained by motion capture, variables that were independently associated with ASQoL were BASDAI (p=0.000) lateral flexion defined by the position of shoulders and hips (p=0.004) and tilt of C7-L4 (p=0.023) R<sup>2</sup> =0.609. <h3>Conclusions</h3> QOL in AxSpA is influenced by the activity of the disease, and by decreased mobility. Women perceive a lower QOL. The best measure related to QOL is lateral bending. Improving patient mobility through exercise and finding appropriate treatment to decrease disease activity, you can improve QOL of patients with AxSpA. <h3>References</h3> Garrido-Castro JL, et al. Validation of a new objective index to measure spinal mobility: the University of Cordoba Ankylosing Spondylitis Metrology Index (UCOASMI). Rheumatol Int. 2014 Mar;34(3):401–6 <h3>Disclosure of Interest</h3> None declared
Phase II Study of Bortezomib Added to Standard Daunorubicin and Cytarabine Induction and Dose Escalation of Bortezomib with Intermediate-Dose Cytarabine Consolidation Therapy for Patients with Previously Untreated Acute Myeloid Leukemia Age 60–75 Years: Cancer and Leukemia Group B (CALGB) Study 10502
Authors: Eyal C Attar, Kathleen A. Donohue, Philip C. Amrein, Martha Wadleigh, Daniel J DeAngelo, Jonathan E Kolitz, Bayard L. Powell, Peter M Voorhees, Eunice S. Wang, William Blum, Allison Booth, Richard M Stone, Barry K Moser, Richard Larson
Journal: Blood (2010)
Comparison of Single Versus Multiple Unit Umbilical Cord Blood Transplantation for Adult Hematologic Malignancy Patients
Authors: Ronald Sobecks, Edward A. Copelan, Matt Kalaycio, Medhat Askar, Lisa Rybicki, Sheila Serafino, Mary Serafin, Robert Dean, Brad Pohlman, Steven Andresen, Brian J. Bolwell
Journal: Blood (2010)
Conventional Anti-CD45 Radioimmunotherapy Comparing 90Y or 177Lu for Treatment of AML in a Syngeneic Disseminated Murine Leukemia Model,
Authors: Johnnie J. Orozco, Aimee Kenoyer, Amanda Axtman, Shani L. Frayo, Paul J. Morris, Donald K. Hamlin, D. Scott Wilbur, Darrell R. Fisher, Mark D. Hylarides, Damian J. Green, Ajay K. Gopal, Ted Gooley, Oliver W. Press, John M. Pagel
Journal: Blood (2011)
PTH-120 How Can We Improve Recruitment and Support Gastroenterology Trainees in The UK? Results from The Supporting Women in Gastroenterology (SWIG) Survey
Authors: E Arthurs, A Brooks, E Taylor, J Solomon, P Neild, S Thomas-Gibson, M Lockett, C Edwards, J Eaden
Journal: Gut (2016)

<h3>Introduction</h3> In gastroenterology, whilst numbers are increasing, women remain under-represented at both trainee and consultant grade compared with other medical specialties at 52% and 34% respectively.<sup>1</sup> The aim of this survey was to identify the key issues around recruitment and support of trainees and consultants. <h3>Methods</h3> A comprehensive survey was designed and circulated to consultants and trainees in gastroenterology, all of whom were members of the BSG. Data regarding demographics, working patterns, professional experiences and opinions was collected and analysed. <h3>Results</h3> The survey was sent to 1900 people, 600 people opened the email and 186 responded, a response rate of 9.79%. 107 of respondents were female (62.9%), 16 respondents did not declare gender. Data was available for 183 responses. Important reasons for choosing a career in gastroenterology were practical procedures (23.3% of responses; n = 117, 59.8% female versus 39.3% male (gender not declared n = 1), a positive prior gastroenterology job (19.9%; n = 100, 66% female versus 34% male) and an inspirational local gastroenterologist (14.7%; n = 74; 63.5% female versus 35.1% male (gender not declared n = 1)).155 (94.5%) respondents would recommend a career in gastroenterology to a junior doctor (60% female versus 38.7% male (gender not declared n = 1)). Important factors in encouraging junior doctors to become gastroenterologists were reducing GIM activity (17.7% of responses; n = 91, 60.4% female versus 38.4% male (gender not declared n = 1)), role models (14.2%; n = 73, 68.5% female versus 31.5% male) and mentorship schemes (11.9%; n = 61, 60.7% female versus 37.7% male (gender not declared n = 1)). Factors thought to be helpful in supporting existing trainees were mentorship schemes (17.1% of responses; n = 78, 60.3% female versus 39.7% male), additional training and networking (14.5%; n = 66, 51.5% female versus 48.5% male) and reducing out of hours activity (13.1%; n = 60, 68.3% female versus 31.7% male). <h3>Conclusion</h3> Recruitment to gastroenterology could be improved by reducing GIM activity and developing mentorship schemes. Mentorship schemes, access to additional training and networking and reducing out of hours commitments were thought to be the most useful factors that would support existing trainees. It would be beneficial to focus on developing solutions for these key issues. <h3>Reference</h3> 1 Census of consultant physicians and higher speciality trainees in the UK, 2014-2015. Royal College of Physicians, 2016. <h3>Disclosure of Interest</h3> None Declared
Longitudinal Pharmacokinetic/Pharmacodynamic Profile of AG-120, a Potent Inhibitor of the IDH1 Mutant Protein, in a Phase 1 Study of IDH1-Mutant Advanced Hematologic Malignancies
Authors: Bin Fan, Kha Le, Erika Manyak, Hua Liu, Malia Prahl, Chris J Bowden, Scott Biller, Sam Agresta, Hua Yang
Journal: Blood (2015)
Global perspectives
Authors: Sing Lee
Journal: BMJ (2007)

The debate on whether depression is overdiagnosed should take global and epidemiological perspectives into account.1 2

Recent transnational epidemiological surveys have not confirmed that medicalisation of sadness is a general phenomenon in the community.3 Rather, a substantial proportion of individuals with depression, even of severe degree, do not receive drug or other professional treatments. This is especially so in developing countries (including Beijing and Shanghai in China), where typically less than 10% of people with mood disorders will ever receive any form of professional treatment.4

The epidemiological meaning of a “case” of depression (such as mild major depressive episode) may have little to do with whether the affected person needs psychiatric evaluation or drug treatment, or both. This is not unlike increasingly lenient public health definitions of physical conditions such as obesity or serum cholesterol concentrations in the general population. In the spirit of early intervention, psychosocial intervention or a change in lifestyle may work better than drugs in alleviating such mild metabolic disturbances.

The real problem for the increasing diagnosis of depression is the poor access to quality psychosocial interventions such as cognitive therapy not only in developing countries but also in much of the developed West. This is despite a strong base of evidence showing that such interventions are at least as effective as drugs in treating and preventing depression. In many parts of the world clinical psychology does not exist.
Changes in factors influencing doctors’ career choices between one and five years after graduation: questionnaire surveys of UK doctors
Authors: Trevor W Lambert, Fay Smith, Michael J Goldacre
Journal: Journal of the Royal Society of Medicine (2016)

Objectives To study changes in factors influencing doctors’ career specialty choices between one and five years after graduation. Design Questionnaire survey. Setting UK. Participants A total of 10,473 doctors who replied to our surveys both one and five years after graduating from all UK medical schools between 1993 and 2008. Main outcome measures The importance of each of 12 specified factors in influencing the doctors’ choice of future specialty ‘a great deal’. Method Questionnaires by post and email. Results Enthusiasm for and commitment to the specialty was the greatest influence on career choice at year 1 (66%) and year 5 (74%). Domestic circumstances increased in importance more than any other factor (from 22.5% to 41.3%); 26% of doctors rated this as important in year 5 but not in year 1. Other factors which increased in importance from year 1 to year 5 included hours/working conditions, experience of the job so far and self-appraisal of own skills. There was an increase in the importance of promotion/career prospects, self-appraisal of own skills, student experience of subject and enthusiasm/commitment for more recent cohorts compared with older cohorts. Between years 1 and 5, there was a greater increase in the importance of domestic circumstances, hours/working conditions and eventual financial prospects for intending General Practitioners than for other doctors. Conclusions Doctors remain committed to their specialty between years 1 and 5, but the influence of domestic circumstances and hours and working conditions grew stronger.
Cooperative Targeting of Bcl-2 Family Proteins By ABT-199 (GDC-0199) and Tyrosine Kinase Inhibitors to Eradicate Blast Crisis CML and CML Stem/Progenitor Cells
Authors: Bing Z Carter, Po Yee Mak, Hong Mu, Hongsheng Zhou, Duncan H Mak, Wendy D. Schober, Joel Leverson, Bin Zhang, Ravi Bhatia, Marina Konopleva, Jorge E. Cortes, Michael Andreeff
Journal: Blood (2014)
Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose
Authors: Sachiko Fukui, Hideki Yano, Shuichi Yada, Tsuyoshi Mikkaichi, Hidemi Minami
Journal: Asian Journal of Pharmaceutical Sciences (2016)

The purpose of this study was to develop an extended-release (ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS) and hydroxypropylcellulose (HPC) were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.