tbuckley/cabot-search huggingface dataset:
SAT0228 Step-down methotrexate therapy in rheumatoid arthritis (STEMETRA): a pilot study to assess the safety and the tolerability of high-dose methotrexate.
Authors: G. Bianchi, D. Camellino, A. Locaputo, P. Diana, A. Giusti, G. Girasole, J. Kremer, M. Weinblatt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Methotrexate (MTX) remains the cornerstone of the treatment of rheumatoid arthritis (RA). However, MTX is frequently underutilized in terms of suboptimal dosage, insufficient duration of treatment, and route of administration. <h3>Objectives:</h3> To evaluate the tolerability and the safety of higher-dose, subcutaneous methotrexate (MTX) in patients with rheumatoid arthritis (RA). <h3>Methods:</h3> The STEp-down MEthotrexate Therapy in Rheumatoid Arthritis (STEMETRA) was an open-label, monocentric, pilot study of 12-week duration. The protocol treatment schedule consisted of subcutaneous (SC) MTX 50 mg/week for 4 consecutive weeks, followed by 25 mg/week for 4 weeks and then 15 mg/week for 4 weeks. All patients received oral supplementation of folinic acid (leucovorin) 12 mg, administered twelve hours after the injection of SC-MTX. <h3>Results:</h3> Ten patients (7 females and 3 males), with a mean age of 58.1 (±12.1), were enrolled in this study; one of them withdrew consent before taking study drug. Therefore, nine patients were treated. MTX was well tolerated: a total of 5 adverse events (AEs) occurred in 4 patients, none of which was severe. AEs consisted in: transient elevation of alanine aminotransferase (&lt;2 ULN), which resolved spontaneously, and vertigo, in the same patient; moderate fatigue in one patient; one case of urinary tract infection; low back pain in one patient. At week 12, four patients (44,4%) achieved DAS28(ESR) remission, two (22,2%) reached low disease activity, one (11,1%) patient showed moderate disease activity, and two (22.2%) had still had high disease activity. Overall, 8 out of 9 patients (88,8%) showed a reduction in DAS28&gt;1.2 from baseline. <h3>Conclusions:</h3> In this study, short-term higher dose MTX was well tolerated. Based on the tolerability observed in this preliminary study, a randomized controlled study of higher dose induction therapy versus traditional dosing will be conducted. <h3>Disclosure of Interest:</h3> None declared
A Clinical Trial of the STAT3 Inhibitor Pyrimethamine in Chronic Lymphocytic Leukemia
Authors: Jennifer R. Brown, Sarah R. Walker, Lisa N. Heppler, Svitlana Tyekucheva, Erik Nelson, Josephine L. Klitgaard, Maria Nicolais, Yasmin Kroll, Michael Xiang, Jennifer E. Yeh, Mousumi Chaudhury, Zachary T. Giaccone, Stacey Fernandes, Jeffrey G. Supko, Catherine J. Wu, David A. Frank
Journal: Blood (2018)
AB1199 Dynamic ultrasound for multilevel evaluation of motion and posture in lower extremity and spine
Authors: R.V. Bubnov, L. Kalika, L. Babenko
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Evaluation of motion and posture is a crucial task in management patient with rheumatic diseases and pain. Integrative protocol including multilevel assessment of intrinsic/extrinsic muscles postural imbalance for disease staging and treatment efficacy control has not been finally developed. <h3>Objectives</h3> The aim was to study feasibility of multilevel motion and posture analysis using dynamic M-mode ultrasound in foot, ankle, gluteus region, pelvis and spine. <h3>Methods</h3> We included 21 patients (13 females, aged 18–52 y.o.) with clinically diagnosed reduced motility in spine, pelvis and lower extremity levels due to detected back leg, pain, muscle spasticity, joints effusion, tissue swelling, etc. Another healthy 20 patients (aged 18–50 y.o.) without movement rstriction and pain were controls. We conducted precise physical tests, extensive neuromuscular ultrasound (US) using M-mode to evaluate muscle thickness, CSA and motion in intervetrebral spaces, pelvis, intrinsic/extrinsic muscles in foot and ankle gluteus region and pelvis, central and peripheral trigger points identification.<sup>1</sup> <h3>Results</h3> We obtained sufficient quality panoramic scans on leg using convex 5–8 MHz probe in 2 approaches to evaluate structure and motion of extrinsic/intrinsic portion of muscles during one session. Thickness measurements of peroneal portion, plantar intrinsic foot muscles on the plantar surface in two transverse positions and one longitudinal using linear probe; contractility using M-mode tested in walking were most representative data. We evaluated different patterns of decreasing motility, contractility (muscle contracted/rested thickness) on M-mode during functional tests and walking in all levels in group 1 (p&lt;0.05). We observed the preliminary correlation between the changes (muscle hypertrophy) in contralateral extrinsics and intrinsics muscles at the same levels, due to biomechanical instability; local areas of spasticity (trigger points) were successfully detected on distal/proximal leg, pelvis and spine. Documented pictures were collected and accessible for telemedical consulting. <h3>Conclusions</h3> Extensive evaluation of motion posture in foot, ankle, and gluteus region, pelvis and spine is feasible and informative protocol for patient with pain and rheumatic diseases. Further studies needed to evaluate reliability studies, comparative RCT using US, CAREN, static and dynamic balance tests, pressure analysis, and extensive molecular profiling, to study crosslinks with immune phenotype of the patients; and to develop educational programs. <h3>Reference</h3> [1] Bubnov R Trigger Points Dry Needling Under Ultrasound Guidance for Low Back Pain Therapy. Comparative Study. Annals of the Rheumatic Diseases2015;74:624. http://dx.doi.org/10.1136/annrheumdis-2015-eular.2323 <h3>Disclosure of Interest</h3> None declared
SAT0631 Lack of association between clinical and ultrasound measures of disease activity in rheumatoid arthritisclinical remission: a cross-sectional analysis
Authors: K.F. Baker, B. Thompson, D. Lendrem, A.G. Pratt, J.D. Isaacs
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ultrasound (US) measures of synovitis and tenosynovitis have been shown to persist in patients with rheumatoid arthritis (RA) who achieve clinical remission. <h3>Objectives</h3> To assess the prevalence of such US findings in RA clinical remission, and analyse whether the US abnormalities found in this group of patients could be predicted by their clinical parameters. <h3>Methods</h3> Patients with established RA (1987 or 2010 diagnostic criteria) in clinical remission (DAS28-CRP&lt;2.4) on conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) were recruited as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study. Patients who had received systemic glucocorticoids in the past 3 months were excluded. All patients underwent baseline clinical assessment followed by a 7-joint US scan (Backhaus et al). US assessment was performed by the same operator (KB) blinded to disease activity score. Synovial Power Doppler (SPD) and greyscale (SGS) change were measured using a 4-point semi-quantitative scale (0–3); tendon GS (TGS) and erosions were classified as either present<sup>1</sup> or absent (0). Intra- and inter-rater scoring agreement was good (Cohen's kappa 0.72 and 0.61 respectively). The association between individual dependent variables (SPD, SGS, TGS, and erosions) and clinical parameters was assessed by multivariate ordinal logistic regression, with Benjamini-Hochberg adjustment for multiple testing. <h3>Results</h3> 66 patients with RA in remission (median disease duration 6 years, median age 66 years) were included in the analysis. US abnormalities were common in both DAS28-CRP and ACR/<sup>EULAR 2011</sup> Boolean remission (table 1). Seven associations were significant at the unadjusted p&lt;0.05 level (figure 1). Only two associations remained statistically significant after multiple test correction, namely those of disease duration and TJC with higher and lower erosion scores respectively (table 2). <h3>Conclusions</h3> We demonstrate considerable subclinical US findings in RA patients in clinical remission, even when remission is defined using the more stringent ACR/EULAR Boolean criteria. Patients with longer disease duration and fewer tender joints had more joint erosions, though no other significant associations were seen after multiple test correction. Most strikingly SPD, which portends a poor prognosis, failed to show significant association with any of the clinical parameters. Our results suggest that clinical and ultrasound examinations may serve complementary, rather than duplicative, roles in the assessment of RA remission. <h3>Reference</h3> [1] Backhaus, et al. Arthritis Rheum;61:1194–201. <h3>Disclosure of Interest</h3> None declared
<i>Notes from the Field:</i> Fentanyl Drug Submissions — United States, 2010–2017
Authors: Yuri P. Springer, R. Matthew Gladden, Julie O’Donnell, Puja Seth
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Trend does not control for changes in the National Forensic Laboratory Information System participation rate (percentage of the national drug caseload represented by laboratories that have joined the system), which varied from 88% in 2010 to 98% in 2017 (midyear estimate).
The Genes for Tissue Factor F3 and Nuclear Receptor 4A Are Down-Regulated in Early Death Acute Promyelocytic Leukemia Patients
Authors: Miriam Frech, Kathleen Stabla, Andrea Nist, Marco Mernberger, Heidi Altmann, Uwe Platzbecker, Christian Thiede, Prema Erramsetti, Sabine Teichler, Cornelia Brendel, Richard F. Schlenk, Thorsten Stiewe, Andreas Neubauer
Journal: Blood (2018)
Adversarial training with cycle consistency for unsupervised super-resolution in endomicroscopy
Authors: Daniele Ravì, Agnieszka Barbara Szczotka, Stephen P Pereira, Tom Vercauteren
Journal: Medical Image Analysis (2019)

In recent years, endomicroscopy has become increasingly used for diagnostic purposes and interventional guidance. It can provide intraoperative aids for real-time tissue characterization and can help to perform visual investigations aimed for example to discover epithelial cancers. Due to physical constraints on the acquisition process, endomicroscopy images, still today have a low number of informative pixels which hampers their quality. Post-processing techniques, such as Super-Resolution (SR), are a potential solution to increase the quality of these images. SR techniques are often supervised, requiring aligned pairs of low-resolution (LR) and high-resolution (HR) images patches to train a model. However, in our domain, the lack of HR images hinders the collection of such pairs and makes supervised training unsuitable. For this reason, we propose an unsupervised SR framework based on an adversarial deep neural network with a physically-inspired cycle consistency, designed to impose some acquisition properties on the super-resolved images. Our framework can exploit HR images, regardless of the domain where they are coming from, to transfer the quality of the HR images to the initial LR images. This property can be particularly useful in all situations where pairs of LR/HR are not available during the training. Our quantitative analysis, validated using a database of 238 endomicroscopy video sequences from 143 patients, shows the ability of the pipeline to produce convincing super-resolved images. A Mean Opinion Score (MOS) study also confirms this quantitative image quality assessment.
SAT0721-HPR Improvement in clinical results by enhancing adherence to a healthcare model in rheumatoid arthritis
Authors: D. Buitrago-Garcia, L. Villarreal, F. Rodriguez, I. Mendez, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> A Centre of Excellence (CoE) healthcare model aims to obtain a high quality results from the appropriate and minimal use of resources in rheumatoid arthritis (RA); Enhancing adherence of patients to healthcare model and treatment using a Treat to Target approach and patient education has demonstrated the improvement of patient conditions and clinical results.<sup>1</sup> <h3>Objectives</h3> To describe the adherence patterns to a centre of excellence model and clinical outcomes in patients with RA in a specialised centre. For this study researchers defined adherence as the attendance to an appointment with our healthcare team for more than three times during 12 months. <h3>Methods</h3> We reviewed the clinical records of patients with RA in a specialised centre during a 12 month period. We included socio demographic variables and the attendance to consultations to rheumatology, physiatry, physical therapy, occupational therapy, nutrition, and psychology consultations. Descriptive epidemiology was done, percentages and averages were calculated We analysed bivariate association with Pearson's X<sup>2</sup>. <h3>Results</h3> We included 5413 patients, where 83% were female and 17% were male; mean age was 59 years±12. Mean DAS28 of patients was 2.82±0.84, where 46% of patients were on remission, 27% in low disease activity, 24% in moderate disease activity and 3% in severe disease activity. The specialty were the adherence was higher was in rheumatology 98%, followed by physiatry 33%, psychology 29%, physical therapy 28%, occupational therapy 20% and nutrition 13%. In our study 47% of patients were considered as adherents; from all patients who were adherent 75% were in remission or low disease activity. When we compared disease activity with the attendance to all specialties there was statistical association between disease activity and the patients who attended to more than four visits. <h3>Conclusions</h3> Patients who attend satisfactory to a multidisciplinary healthcare approach team can achieve better results compared to those who doesn't attend to all medical specialties; thus it is relevant to implement patient education processes in order to create awareness about the importance and value of each medical specialty, mainly in patients with moderate or severe disease activity. <h3>Reference</h3> [1] Santos-Moreno P, Castaneda O, Garro B, Flores D, Sanchez G, Castro C. From the model of integral attention to the creation of centers of excellence in rheumatoid arthritis. Clinical rheumatology2015;(34Suppl 1):S71–7. <h3>Disclosure of Interest</h3> None declared
Combined Effect of By-Pass Agents and a Sequence Identical Analogue of Emicizumab on Fibrin Clot Turbidity and Structure in Factor VIII Deficient Plasma
Authors: Iva Pruner, Yanan Zong, Nida Mahmoud Hourani Soutari, Roza Chaireti, Aleksandra Antovic, Jovan Antovic
Journal: Blood (2018)
Abstract MP023: Changes in Systolic Blood Pressure Differs by Immigration History in a Cohort of Older Mexican Americans
Authors: Tu My To, John M Neuhaus, May Sudhinaraset, Michelle A Albert, Mary N Haan
Journal: Circulation (2017)

Background: Studies on immigrant health suggest that foreign-born individuals have better health outcomes than their native-born counterparts due to health selection. However, effects of immigration history on changes in cardiovascular conditions and risk factors are less well understood. Objective and Hypothesis: We examined the association between immigration history and change in systolic blood pressure (SBP). We hypothesized that Mexican Americans born outside the US and immigrated after age 30 (FB30+), would have lower SBP at baseline and have slower increase in SBP compared to people who were born in the US (US-B) or immigrated from Mexico before age 30 (FB&lt;30). Methods: Participants come from the Sacramento Area Latino Study on Aging (n=1789), a longitudinal cohort of community-dwelling older Mexican Americans (mean age=70.6 years); 51% were born in Mexico. Immigration history was categorized as US-B, FB&lt;30, and FB30+. SBP measures were available at baseline and at five follow-ups over ten years. A mixed effects linear model was used to examine the association between immigration history and SBP. Other covariates included gender, education, current hypertension medication use, and baseline measures of age, BMI, and diabetes. Follow up time was defined as time since enrollment. Quadratic time was included to account for non-linear change in SBP. Two interaction terms (immigration history x linear time and immigration history x quadratic time) were included to assess differences in SBP change by nativity. Results: The study included 1598 participants after exclusions. The figure shows the predicted average SBP by immigration history over the study period, derived from the mixed linear model. Compared to US-B, the FB&lt;30 and FB30+ experienced an average of 7.3 (95% CI 2.0-12.7) and 7.9 (95% CI 2.2-13.5) mmHg increase in SBP over the study period, respectively. Conclusions: In contrast to current literature, immigrants appeared to be at greater risk for adverse cardiovascular risk factors.
c-FLIP inhibits Fas-mediated apoptosis in response to chemotherapy.
Authors: Daniel B. Longley, Wendy L. Allen, Timothy R. Wilson, Ultan McDermott, Patrick G. Johnston
Journal: Cancer Research (2004)

3396  The Fas (CD95/Apo-1) death receptor is a member of the tumour necrosis factor cell surface receptor family. Receptor binding results in formation of the death inducing signalling complex (DISC), at which caspase 8 molecules are activated leading to activation of pro-apoptotic downstream molecules. We found that expression of Fas was up-regulated by >10-fold in MCF-7 breast and HCT116 colon cancer cell lines following treatment with IC60 doses of the fluoropyrimidine 5-Fluorouracil (5-FU), the antifolate tomudex (TDX) and the DNA-damaging agent oxaliplatin (OXA). However, drug treatment failed to activate caspase 8, indicating that Fas up-regulation alone was insufficient to activate apoptosis in these cell lines. However, combined treatment with the Fas-targeted agonistic antibody CH-11 and 5-FU, TDX or OXA resulted in potent activation of caspase 8 and apoptosis. Activation of caspase 8 in 5-FU and CH-11 co-treated cells coincided with complete processing of its inhibitor c-FLIPL. Importantly, overexpression of c-FLIP abrogated the synergistic activation of caspase 8 and apoptosis in cells co-treated with each drug and CH-11, while siRNA-mediated down-regulation of c-FLIP increased the sensitivity of both MCF-7 and HCT116 cells to drug-induced activation of caspase 8 and apoptosis. Collectively, these results indicate that c-FLIP inhibits drug-induced Fas-mediated apoptosis in these cell lines.
Radius: A Phase 2 Randomized Trial Investigating Standard of Care ± Midostaurin after Allogeneic Stem Cell Transplant in FLT3-ITD-Mutated AML
Authors: Richard Thomas T. Maziarz, Mrinal M. Patnaik, Bart L Scott, Sanjay R. Mohan, Abhinav Deol, Scott D. Rowley, Dennis Kim, Kelly Haines, Gaetano J Bonifacio, Patrice Rine, Das Purkayastha, Hugo F. Fernandez
Journal: Blood (2018)
Eliciting Anti-Tumor T Cell Immunity in Chronic Lymphocytic Leukemia (CLL) with PD-L1/PD-1 Blockade Is Enhanced By Avadomide Immunotherapy through the Triggering of Immunogenic Interferon Signaling
Authors: Nikolaos Ioannou, Patrick R. Hagner, Fadi Towfic, Anita K. Gandhi, Kostas Stamatopoulos, Piers E.M. Patten, Anna Vardi, Alan G. Ramsay
Journal: Blood (2018)
OP0241 Efficacy of tocilizumab in takayasu arteritis: multicenter french retrospective study of 46 patients
Authors: A Mekinian, M. Resche-Rigon, C. Comarmond, A. Soriano, J. constans, P. alric, P. Jego, F. Bussato, R. Dhote, E. lazaro, I. Kone pault, C. Landron, C. Lavigne, B. Lioger, M. Michaud, M. Ruivard, K. Sacre, J.E. Gottenberg, T. Goulenok, C. Salvarini, P. Cacoub, O. Fain, D. Saadoun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> <h3>Objectives</h3> We report the long term outcome of 46 TA patients treated with tocilizumab, describe the factors of response and compare the vascular event free survival to DMARDs. <h3>Methods</h3> retrospective nationwide french study <h3>Results</h3> We observed a decrease in the NIH scale; in C-reactive protein levels and in daily prednisone dose at 3 and 6 months, respectively; p&lt;0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% [95% CI: 0.7 to 0.95], 72% [95% CI: 0.55 to 0.95] and 48% [95% CI: 0.2 to 0.1] at 12, 24 and at 48 months, respectively. The presence of constitutional symptoms at the time of tocilizumab initiation (hazard ratio 5.6 [95% CI: 1.08 to 29], p=0.041), C-reactive protein level (hazard ratio 1.16 [95% CI: 1.01 to 1.31] for every 10 mg/L, p=0.003) were significantly associated with tocilizumab-failure-free survival. The incidence of vascular complications of TA decreased significantly under tocilizumab compared to DMARDS therapy. <h3>Conclusions</h3> This nationwide study shows that tocilizumab may reduce the incidence of vascular complications in TA. <h3>Disclosure of Interest</h3> None declared
3-Iodothyronamine—A Thyroid Hormone Metabolite With Distinct Target Profiles and Mode of Action
Authors: Josef Köhrle, Heike Biebermann
Journal: Endocrine Reviews (2019)

The rediscovery of the group of thyronamines (TAMs), especially the first detailed description of their most prominent congener 3-iodothyronamine (3T1AM) 14 years ago, boosted research on this thyroid hormone metabolite tremendously. TAMs exert actions partly opposite to and distinct from known functions of thyroid hormones. These fascinating metabolic, anapyrexic, cytoprotective, and brain effects quickly evoked the hope to use hormone-derived TAMs as a therapeutic option. The G protein-coupled receptor (GPCR) TAAR1, a member of the trace amine-associated receptor (TAAR) family, was identified as the first target and effector of TAM action. The initial enthusiasm on pharmacological actions of exogenous TAMs elicited many questions, such as sites of biosynthesis, analytics, modes of action, inactivation, and role of TAMs in (patho)physiology. Meanwhile, it became clear that TAMs not only interact with TAAR1 or other TAAR family members but also with several aminergic receptors and non-GPCR targets such as transient receptor potential channels, mitochondrial proteins, and the serum TAM-binding protein apolipoprotein B100, thus classifying 3T1AM as a multitarget ligand. The physiological mode of action of TAMs is still controversial because regulation of endogenous TAM production and the sites of its biosynthesis are not fully elucidated. Methods for 3T1AM analytics need further validation, as they revealed different blood and tissue concentrations depending on detection principles used such as monoclonal antibody-based immunoassay vs liquid chromatography- matrix-assisted laser desorption/ionization mass spectrometry or time-of-flight mass spectrometry. In this review, we comprehensively summarize and critically evaluate current basic, translational, and clinical knowledge on 3T1AM and its main metabolite 3-iodothyroacetic acid, focusing on endocrine-relevant aspects and open but highly challenging issues.