tbuckley/cabot-search huggingface dataset:
Guanfacine Augmentation of a Combined Intervention of Computerized Cognitive Remediation Therapy and Social Skills Training for Schizotypal Personality Disorder
Authors: Margaret M. McClure, Fiona Graff, Joseph Triebwasser, Mercedes Perez-Rodriguez, Daniel R. Rosell, Harold Koenigsberg, Erin A. Hazlett, Larry J. Siever, Philip D. Harvey, Antonia S. New
Journal: American Journal of Psychiatry (2019)

Impaired cognition is a hallmark of schizophrenia spectrum disorders, including schizotypal personality disorder, and it is the best predictor of functional outcome. Cognitive remediation therapy has demonstrated efficacy for improving cognition, augmenting other rehabilitation efforts in schizophrenia, and effecting gains in real-world functioning. Pharmacological augmentation of cognitive remediation has been attempted, but the effects of augmentation on combined therapies, such as cognitive remediation and social skills training, have not been studied.Twenty-eight participants with schizotypal personality disorder enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of guanfacine plus cognitive remediation and social skills training (15 guanfacine, 13 placebo). Cognition was assessed with the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB), social cognition with the Movie for the Assessment of Social Cognition (MASC), and functional capacity with the University of California San Diego Performance-Based Skills Assessment (UPSA).A statistically significant pre- versus posttreatment effect was observed for MCCB speed of processing, verbal learning, and visual learning and UPSA total score. A significant time-by-medication (guanfacine, placebo) interaction was observed for MCCB reasoning and problem solving and UPSA total score; the time-by-treatment interaction approached significance for MASC hypomentalizing errors.Both guanfacine and cognitive remediation plus social skills training were well tolerated, with no side effects or dropouts. Participants treated with cognitive remediation, social skills training, and guanfacine demonstrated statistically significant improvements in reasoning and problem solving, as well as in functional capacity and possibly social cognition, compared with those treated with cognitive remediation, social skills training, and placebo. Cognitive remediation plus social skills training may be an appropriate intervention for individuals with schizotypal personality disorder, and guanfacine appears to be a promising pharmaceutical augmentation to this psychosocial intervention.
Self-Awareness: Nucleic Acid–Driven Inflammation and the Type I Interferonopathies
Authors: Carolina Uggenti, Alice Lepelley, Yanick J. Crow
Journal: Annual Review of Immunology (2019)

Recognition of foreign nucleic acids is the primary mechanism by which a type I interferon-mediated antiviral response is triggered. Given that human cells are replete with DNA and RNA, this evolutionary strategy poses an inherent biological challenge, i.e., the fundamental requirement to reliably differentiate self-nucleic acids from nonself nucleic acids. We suggest that the group of Mendelian inborn errors of immunity referred to as the type I interferonopathies relate to a breakdown of self/nonself discrimination, with the associated mutant genotypes involving molecules playing direct or indirect roles in nucleic acid signaling. This perspective begs the question as to the sources of self-derived nucleic acids that drive an inappropriate immune response. Resolving this question will provide fundamental insights into immune tolerance, antiviral signaling, and complex autoinflammatory disease states. Here we develop these ideas, discussing type I interferonopathies within the broader framework of nucleic acid-driven inflammation.
Outcome of Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) Treated with Ibrutinib within a Named Patient Program (NPP) in Italy. a Real-Life Retrospective Study
Authors: Francesca Romana Mauro, Stefano Soddu, Annamaria Maria Frustaci, Lorella Orsucci, Marina Motta, Lydia Scarfo, Pier Luigi Zinzani, Franca Falzetti, Lucia Farina, Roberto Marasca, Agostino Cortelezzi, Carmelo Carlo-Stella, Stefano Molica, Marta Coscia, Francesco Zaja, Luca Laurenti, Paolo de Fabritiis, Gianluca Gaidano, Marco Gobbi, Monica Tani, Nicola Di Renzo, Paola Fazi, Marco Vignetti, Antonio Cuneo, Robin Foà
Journal: Blood (2018)
Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer
Authors: Amy S. Clark, Nicholas P. McAndrew, Andrea Troxel, Michael Feldman, Priti Lal, Mark Rosen, Jessica Burrell, Colleen Redlinger, Maryann Gallagher, Angela R. Bradbury, Susan M. Domchek, Kevin R. Fox, Peter J. O'Dwyer, Angela M. DeMichele
Journal: Clinical Cancer Research (2019)

The CDK 4/6 inhibitor palbociclib rapidly and reversibly inhibits the cell cycle. The goal of this study was to exploit the cell cycle through intermittent, alternating dosing with palbociclib/paclitaxel to enhance efficacy. We determined the combination dose-limiting toxicity (DLT) in patients with Rb protein-expressing, advanced breast cancer.This open-label, phase I trial (NCT01320592) enrolled patients to sequential cohorts of palbociclib orally dosed intermittently between days 1 and 19 of a 28-day cycle alternating with weekly paclitaxel. Dose escalation proceeded in a standard 3 + 3 design. Ten additional patients received the combination at the recommended phase II dose (RP2D). Those who reached response plateau ≥6 cycles could continue on palbociclib alone on a 3 week on/1 week off schedule at one dose level above their combination dose.Twenty-seven patients enrolled. Although there was only 1 DLT (grade 3 alanine aminotransferase/aspartate aminotransferase at 125 mg), neutropenia (NTP) requiring dose modification in cycle 1 (C1) resulted in an RP2D of 75 mg palbociclib/80 mg/m2 paclitaxel. During C1, the most common adverse event was NTP, occurring in 15 patients (55.6%); grade 1 or 2 nausea and peripheral neuropathy were also observed in 8 patients each (29.6%). The clinical benefit rate was 55% at the RP2D; benefit was observed across all receptor subtypes.Alternating sequential palbociclib/paclitaxel in patients with Rb+ advanced breast cancer is feasible and safe, without evidence of additive toxicity. This represents a new application for CDK 4/6 inhibitors in Rb+ breast cancer regardless of subtype; efficacy trials are warranted.
Coronary Artery Plaque Characteristics Associated With Adverse Outcomes in the SCOT-HEART Study
Authors: Michelle C. Williams, Alastair J. Moss, Marc Dweck, Philip D. Adamson, Shirjel Alam, Amanda Hunter, Anoop S.V. Shah, Tania Pawade, Jonathan R. Weir-McCall, Giles Roditi, Edwin J.R. van Beek, David E. Newby, Edward D. Nicol
Journal: Journal of the American College of Cardiology (2019)

Unlike most noninvasive imaging modalities, coronary computed tomography angiography can characterize subtypes of atherosclerotic plaque. The purpose of this study was to investigate the prognostic implications of adverse coronary plaque characteristics in patients with suspected coronary artery disease. In this SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) post hoc analysis, the presence of adverse plaque (positive remodeling or low attenuation plaque), obstructive disease, and coronary artery calcification within 15 coronary segments was assessed on coronary computed tomography angiography of 1,769 patients who were followed-up for 5 years. Among study participants (mean age 58 ± 10 years; 56% male), 608 (34%) patients had 1 or more adverse plaque features. Coronary heart disease death or nonfatal myocardial infarction was 3 times more frequent in patients with adverse plaque (n = 25 of 608 [4.1%] vs. n = 16 of 1,161 [1.4%]; p < 0.001; hazard ratio [HR]: 3.01; 95% confidence interval (CI): 1.61 to 5.63; p = 0.001) and was twice as frequent in those with obstructive disease (n = 22 of 452 [4.9%] vs. n = 16 of 671 [2.4%]; p = 0.024; HR: 1.99; 95% CI: 1.05 to 3.79; p = 0.036). Patients with both obstructive disease and adverse plaque had the highest event rate, with a 10-fold increase in coronary heart disease death or nonfatal myocardial infarction compared with patients with normal coronary arteries (HR: 11.50; 95% CI: 3.39 to 39.04; p < 0.001). However, these associations were not independent of coronary artery calcium score, a surrogate measure of coronary plaque burden. Adverse coronary plaque characteristics and overall calcified plaque burden confer an increased risk of coronary heart disease death or nonfatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)
SAT0277 Immunogenicity and loss of response to tnf inhibitors in axial spondyloarthritis: results from an observational cohort study
Authors: C.I. Ancuta, C. Pomirleanu, R. Paiu, G. Strugariu, L. Petrariu, E. Ancuta, C. Iordache, R. Chirieac
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> We aimed to evaluate the immunogenicity of TNF-α inhibitors and to assess potential influence on serum drug levels and clinical efficacy in patients with axial spondyloarthritis (axSpA). <h3>Methods</h3> We performed a cross sectional observational cohort study in 87 consecutive axSpA receiving anti-TNFs (either for the first time or switched), followed-up in a single outpatient rheumatology department. Treatment with anti-TNF agents was recommended in accordance with the local regulations on the initiation and continuation of biologics, as well as ASAS/EULAR guidelines. Disease activity scores were assessed at baseline (V1) and study visit (V2), while drug trough levels and anti-drug antibodies were measured in serum samples (ELISA, Progenika) and collected before the next administration as a single-point data. Serum drug levels were considered positive if &gt;0.035 µg/mL IFX,&gt;0.024 µg/mL ADL and &gt;0.035 µg/mL ETN, while the cut-offs for anti-IFX was 5AU/mL, anti-ADL 10AU/mL, anti-ETN 142 AU/mL. Statistical analysis was performed using SSPS version 19.0, p&lt;0.05. <h3>Results</h3> Among 150 axSpA treated with TNF inhibitors in our centre, 28 (32.18%) receiving adalimumab (ADL), 19 (21.83%) infliximab (IFX) and 40 (45.97%) etanercept (ETN) were included in the immunogenicity analysis. Only 11 patients (12.64%) developed anti-drug antibodies, 8 under ADL (28.57%) and 3 under IFX (15.78%), with significant decrease in drug levels (3.97 µg/mL vs. 0.07 µg/mL ADL, p&lt;0.05; 1.82 µg/mL vs. 0.05 µg/mL IFX, p&lt;0.05) and impact on disease outcomes (p&lt;0.05). Higher disease activity scores (BASDAI, ASDAS-CRP) were reported in anti-drug positive axSpA irrespective of the background therapy (p&lt;0.05), with more patients classified as being in a high or very high disease activity status at V2. Furthermore, a relation between clinical improvement (change in ASDAS) and immunogenicity was reported: positive anti-drug antibodies axSpA achieved worse clinical response than negative anti-drug antibodies cases, with a significant association between ADL respectively IFX levels and ASDAS (p&lt;0.05). No anti-drug antibodies were found in patients treated with ETN; significant higher persistence on ETA than under monoclonal antibodies was registered in our axSpA (p&lt;0.05). <h3>Conclusions</h3> Immunogenicity may impact disease outcomes and drug survival, particularly in the adalimumab and infliximab treated axSpA. Measuring anti-drug antibodies and serum drug levels may help to optimise therapeutic strategies in selected patients. <h3>Disclosure of Interest</h3> None declared
THU0125 Prevention of the progressive biochemical cartilage destruction under methotrexate therapy in early rheumatoid arthritis
Authors: P. Sewerin, A. Müller-Lutz, S. Odendahl, M. Eichner, M. Schneider, B. Ostendorf, C. Schleich
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Can methotrexate (MTX) stop cartilage loss measured by Delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) in patients with early rheumatoid arthritis (eRA)? <h3>Objectives</h3> Objective of the study was to investigate biochemical cartilage composition under MTX therapy and to intra-individually assess the impact of inflammation severity on cartilage composition by using dGEMRIC MRI in patients with eRA. <h3>Methods</h3> dGEMRIC of MCP joints of the index and middle finger of 28 patients from the AthroMark cohort were examined prior to MTX-therapy as well as after 3 and 6 month. OMERACT RA MRI score and clinical parameters (CRP and DAS28) were registered at any time point. Each patient's second and third MCP joints were dichotomized into the joint with more severe synovitis versus the joint with less severe synovitis according to the RAMRIS synovitis subscore. <h3>Results</h3> MCP joints with more severe synovitis ('bad joints') demonstrated significantly lower dGEMRIC values compared to MCP joints with less severe synovitis ('good joints') at time-points 0 and 3 months (p=0.002; p=0.019, respectively). After 6 months of MTX therapy no significant difference of dGEMRIC index was found between good and bad joint (p=0.086). <h3>Conclusions</h3> Under MTX therapy, biochemical cartilage integrity remains stable; no further cartilage destruction occurred if patients are treated early in the course of the disease. In addition, six months of MTX therapy triggered an alignment of dGEMRIC index of MCP joints with initially severe synovitis and less severe synovitis in an intra-individual assessment. This underlines the importance of an early treatment in eRA to reduce further cartilage damage of the inflamed joints. <h3>Acknowledgements: Funding</h3> The ArthroMark project was founded by the <i>Bundesministerium für Bildung und Forschung(BMBF)</i> grant number FKZ 01EC1009A <h3>Disclosure of Interest</h3> None declared
Abstract 16214: Percutaneous Intra-myocardial Injection of Exosomes From Cardiosphere-derived Cells (CDCs) Halts Adverse Remodeling and Decreases Scar Size in Porcine Ischemic Cardiomyopathy
Authors: Romain Gallet, James Dawkins, Eli Simsolo, Jackelyn Valle, Michel Kreke, Rachel Smith, Linda Marbán, Eduardo Marbán
Journal: Circulation (2015)

Background: Multiple lines of evidence indicate that the beneficial effects of CDCs in heart disease are mediated by exosomes. So far, no study has assessed the benefit of CDC-derived exosomes in a translationally-realistic large-animal model. Objective: Exosomes are nanoscale particles, few of which may linger in the heart after routine intracoronary delivery. Previous work in rodents shows efficacy in myocardial infarction (MI) with intramyocardial injection. We therefore sought to evaluate the efficacy of trans-endocardial delivery of CDC-secreted exosomes using the NOGA MYOSTAR injection catheter in a porcine model of post-MI cardiomyopathy. Methods: MI was induced in 7 mini-pigs by balloon occlusion of the mid-LAD for 2.5h, then the MI was allowed to heal for 4 weeks. At that point, and at the end of the study one month later, MRI was performed to measure LV volumes and ejection fraction (EF), scar mass and viable mass. Just after the first MRI, the left ventricle (LV) was mapped using a NOGA catheter to delineate infarcted, border and remote areas. After mapping, human CDC-secreted exosomes (7.5mg of exosome protein divided into 10-15 injections, n=4) or vehicle (n=3) were injected in the border zone (4-7 mV tip potentials). Results: EF was identical in the two groups at baseline (38±4%). All pigs were successfully injected with exosomes or vehicle after comprehensive LV mapping. One month post-injection, EF was preserved in exosome-treated pigs but dramatically decreased in placebo-treated animals (ΔEF=-1.2±2.2% vs. -7.6±2.8%, p&lt;0.02). LV adverse remodeling was attenuated in CDC-injected pigs (less increase in end-systolic and end-diastolic volumes, P=0.08 and P=0.03 respectively). Additionally, exosomes reduced scar mass (-1.6±0.6g vs. +1.2±0.5g, P=0.001) and scar size (P&lt;0.05). Conclusions: CDC-secreted exosomes halt adverse remodeling and decrease scar size when injected in the border zone using an injection catheter. This demonstration of safety and efficacy motivates testing of exosomes as cell-free therapeutic agents in humans.
SAT0414 Development of malignancy in korean sjogren’s syndrome patients; whole national health insurance data based analysis
Authors: C.H. Lee, J.S. Park, H.S. Lim, H.Y. Pak
Journal: Annals of the Rheumatic Diseases (2018)

Background: With the increasing use and wide variety of biological therapies, there is a concomitant increase in concern for associated opportunistic infections, especially for Mycobacterium tuberculosis.¹ Objectives: The aim of this study was to identify patients who have developed tuberculosis (TB) reactivation during treatment with a biological agent.Methods: We included patients treated with biological agents in a tertiary Department of Rheumatology who had developed TB and were registered in the national registry for biological therapy.Demographic (urban or rural environment), clinical, therapeutic (biologic agent used) and comorbidities data were retrieved from the database.Results: The database included 505 patients: 314 patients with rheumatoid arthritis (RA), 129 patients with ankylosing spondylitis (SA) and 62 patients with psoriatic arthritis (PsA).Prior to the start of biological therapy, tuberculosis screening for latent infection was conducted in all patients.Eight patients (1,58%) were identified as being diagnosed with TB reactivation during biological therapy: 5 RA and 3 SA patients Two had positive tuberculin test (TST) at baseline and required chemoprevention therapy prior to the initiation of the biological agent (respecting the preexisting guidelines).Demographic data shows 62.5% patients from urban areas, 50% female and 50% male.Regarding comorbidities, one patient had biapical pachypleuritis (probably TB sequelae), antiphospholipid syndrome and pulmonary hypertension; one had chronic kidney failure and inflammatory bowel disease.The other six patients had minor comorbidities.62,5% of patients were treated with oral corticosteroids combined with DMARDs.Four patients have been treated with infliximab, three with adalimumab and one with etanercept.The average time to TB reactivation was 19.6 months (range 2 months to 52 months).Patients who had TB reactivation after two months of biologic therapy were treated with infliximab.Four patients had developed pulmonary TB; one case was described as a miliary complicated with bacillary peritonitis (peritoneal biopsy).One patient had developed lymph node TB (lymph node biopsy) and one TB of the wrist (switch therapy was not chosen yet).One particular case was of a patient that had developed TB meningitis with lymphadenitis and a compressible tuberculoma with spastic paraparesis.Switching of biological agent was chosen in 5 patients without another reactivation of tuberculosis.The biological agents chosen in 40% was rituximab, 20% was etanercept, 20% was adalimumab and 20% was infliximab.Conclusions: Pulmonary and extrapulmonary TB reactivation equally occurred during anti TNF therapy.In some cases, reactivation of tuberculosis occurred even with chemoprevention.
SAT0191 The patient perspective on bdmard dose reduction: a mixed methods study
Authors: L. M. Verhoef, E. M. Selten, J. E. Vriezekolk, A. J. de Jong, F. H. van den Hoogen, A. A. den Broeder, M. E. Hulscher
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Dose reduction of bDMARDs, after low disease activity is reached, is safe and effective.(1) To date, few studies have focused on bDMARD dose reduction from the patient perspective. <h3>Objectives:</h3> The aim of this study was to identify the factors that play a role for patients with RA when considering bDMARD dose reduction, and to determine their relative importance. <h3>Methods:</h3> A mixed methods design was used in which we 1) identified influencing factors with interviews and 2) ranked these factors using a Maximum Difference Scaling (MaxDiff) survey. Sub study 1: We performed semi-structured interviews with 22 RA patients. Interviews were transcribed verbatim and two researchers analyzed the transcriptions by inductive thematic analysis. Sub study 2: The influencing factors were derived from the interviews and used in a MaxDiff survey with RA patients from 3 different centers in the Netherlands (N=192; an academic hospital, a specialized hospital and a large general hospital). Besides questions about patient characteristics, the survey included 18 MaxDiff questions in which patients were asked to choose the most and least important factor from a subset of 5 factors. A relative importance score for each factor was calculated using hierarchical Bayes modeling. <h3>Results:</h3> Thirty factors were identified from the interviews and used in the survey. Most respondents had a positive attitude towards bDMARD dose reduction (table 1). The top-10 of factors (table 2) shows that patients are concerned that dose reduction will lead to a disease flare that affects their daily life (pain, function). It is important for them to know that it is possible to increase the dose if (further) reduction is not possible and that the bDMARD will be effective again. Patients value the opinion of their rheumatologist, and being involved in the decision to start tapering is highly ranked as well. <h3>Conclusions:</h3> The results from this study could facilitate implementation of bDMARD dose reduction by informing care providers on what is important for patients and providing a basis for shared decision making. <h3>Reference</h3> [1]Nam JL, et al. Ann Rheum Dis2017Jun;76(6):1113–1136. <h3>Disclosure of Interest:</h3> None declared
Circulating Lymphoma Cells in Mycosis Fungoides/Sezary Syndrome Show Heterogeneity of the Cell-of-Origin and Variable PD-1 Expression By Flow Cytometric Analysis
Authors: Mariko Yabe, Natasha Lewis, Qi Gao, Allison Sigler, Jeeyeon Baik, Melissa Pulitzer, Patricia Myskowski, Alison J. Moskowitz, Steven M. Horwitz, Ahmet Dogan, Mikhail Roshal
Journal: Blood (2018)
Risk of Diabetes Associated With Cancer Development
Authors: Dan Hu, Feng Peng, Wenquan Niu
Journal: JAMA Oncology (2019)

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