tbuckley/cabot-search huggingface dataset:
SAT0628 A retrospective observational study of azathioprine maintenance therapy on behcet’s disease with vascular involvement
Authors: S. Girgin, S. Yurumez, A. Omma, C. Bes, S. Celik, N. Alpay Kanitez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vascular disease which has potential to involve both arteries and veins of all size is one of the major causes of mortality and morbidity in Behçet's disease (BD). There is no controlled studies for the immunosuppressive (IS) therapy in vascular involvement of BD. For the induction and/or maintenance therapy, azathioprine (AZA) is widely used as a corticosteroid tapering IS agent in vascular BD although there are many different clinical presentation. <h3>Objectives</h3> The purpose of this study to investigate relapse rate and the clinical factors affecting it during AZA maintenance therapy. <h3>Methods</h3> Consecutive BD patients with a documentation for arterial or venous involvement were evaluated from two rheumatology centre between January-September 2017. Patients who have been treated for at least 3 months after the complete or partial remission were included to study. The baseline clinical and laboratory findings, treatment protocol, first vascular relapse time and adverse events were obtained medical records. Long-term outcome and factor associated with vascular relapse were assessed. <h3>Results</h3> Totally 78 patients were included to the study and majority of them [59 (%75.6)] was male. The mean age ±SD of the patients was 37.5±9 years. Clinical characteristics of patients are seen in table 1. The median duration of maintenance therapy with AZA was 25 (min 3- max 144) months and the mean dose ±SD of AZA was found as 1.7±0.3 mg/kg/day. AZA was withdrawn in 4 (%5.1) patients because of adverse events. Twenty patients (%25.6) were receiving anti-coagulant therapy. Vascular relapse was observed in 14 (%17.9) patients. In relapsing group, arterial involvement and uveitis was higher statistically (p=0.014 and 0.045 respectively). In regression analysis, arterial involvement was independent risk factor for relapse (p=0.016). The percentage of relapses was calculated as%39 (7/18) in patient subgroup with arterial involvement. Relapse free survival rates according to involving vessel were seen in figure 1. <h3>Conclusions</h3> According to our study, AZA is seen as safe in maintenance therapy of BD with vascular involvement, however it can be said that the relapse rate is not favourable especially in patients with arterial involvement. Vascular involvement is considered as related to endotel inflammation resulting BD activity and the effect of anti-coagulant therapy is still controversial. TNF inhibitors or other immunosuppressant may be alternative to AZA for maintenance therapy with the support of randomized-controlled studies. <h3>Disclosure of Interest</h3> None declared
Platelet Apoptosis and PAI-1 Content Are Involved in the Procoagulant Profile of Immune Thrombocytopenia Patients Responders to Agonists of Thrombopoietin Receptor.
Authors: Raul Justo Sanz, Elena Monzón Manzano, Ihosvany Fernandez-Bello, Teresa Álvarez-Roman, Mónica Martín, María Isabel Rivas Pollmar, Miguel A. Canales, Victor Jimenez-Yuste, Nora Butta
Journal: Blood (2018)
Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial
Authors: Arnaud Scherpereel, Julien Mazieres, Laurent Greillier, Sylvie Lantuejoul, Pascal Dô, Olivier Bylicki, Isabelle Monnet, Romain Corre, Clarisse Audigier-Valette, Myriam Locatelli-Sanchez, Olivier Molinier, Florian Guisier, Thierry Urban, Catherine Ligeza-Poisson, David Planchard, Elodie Amour, Franck Morin, Denis Moro-Sibilot, Gérard Zalcman, Didier DEBIEUVRE, Sandrine HIRET, Jacques CADRANEL, Séverine FRABOULET-MOREAU, Delphine CARMIER
Journal: The Lancet Oncology (2019)
Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load
Authors: Anita Schuch, Elahe Salimi Alizei, Kathrin Heim, Dominik Wieland, Michael Muthamia Kiraithe, Janine Kemming, Sian Llewellyn-Lacey, Özlem Sogukpinar, Yi Ni, Stephan Urban, Peter Zimmermann, Michael Nassal, Florian Emmerich, David A Price, Bertram Bengsch, Hendrik Luxenburger, Christoph Neumann-Haefelin, Maike Hofmann, Robert Thimme
Journal: Gut (2019)

Objective A hallmark of chronic HBV (cHBV) infection is the presence of impaired HBV-specific CD8+ T cell responses. Functional T cell exhaustion induced by persistent antigen stimulation is considered a major mechanism underlying this impairment. However, due to their low frequencies in chronic infection, it is currently unknown whether HBV-specific CD8+ T cells targeting different epitopes are similarly impaired and share molecular profiles indicative of T cell exhaustion. Design By applying peptide-loaded MHC I tetramer-based enrichment, we could detect HBV-specific CD8+ T cells targeting epitopes in the HBV core and the polymerase proteins in the majority of 85 tested cHBV patients with low viral loads. Lower detection rates were obtained for envelope-specific CD8+ T cells. Subsequently, we performed phenotypic and functional in-depth analyses. Results HBV-specific CD8+ T cells are not terminally exhausted but rather exhibit a memory-like phenotype in patients with low viral load possibly reflecting weak ongoing cognate antigen recognition. Moreover, HBV-specific CD8+ T cells targeting core versus polymerase epitopes significantly differed in frequency, phenotype and function. In particular, in comparison with core-specific CD8+ T cells, a higher frequency of polymerase-specific CD8+ T cells expressed CD38, KLRG1 and Eomes accompanied by low T-bet expression and downregulated CD127 indicative of a more severe T cell exhaustion. In addition, polymerase-specific CD8+ T cells exhibited a reduced expansion capacity that was linked to a dysbalanced TCF1/BCL2 expression. Conclusions Overall, the molecular mechanisms underlying impaired T cell responses differ with respect to the targeted HBV antigens. These results have potential implications for immunotherapeutic approaches in HBV cure.
THU0301 A novel role for the psoriatic arthritis impact of disease questionnaire (PSAID)
Authors: K. Johnson, J. Ye, V. Chandran, D. Gladman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in about 30% of patients with Psoriasis (Ps). Recently, a new Patient Reported Outcome Measure (PROM), Psoriatic Arthritis Impact of Disease (PsAID) was specifically developed for PsA Patients. The two versions of the PsAID, PsAID-9 and PsAID-12, are scored on a Numeric Rating Scale (NRS) of 0–10. The Minimal Disease Activity (MDA) is a composite outcome measure for PsA patients, which uses the Health Assessment Questionnaire (HAQ) as one criterion. However, the HAQ does not correlate well with measures of disease activity as PsA disease duration increases, and its use in the assessment of disease activity has been questioned. <h3>Objectives</h3> Our objectives were to 1) validate the PsAID within our patient cohort, 2) determine if the PsAID can replace any of the other PROMs administered in the clinic, and 3) determine if the PsAID can replace the HAQ in the MDA. <h3>Methods</h3> Patients were recruited from a large psoriatic arthritis clinic. All patients completed the PsAID and 10 other PROMs. Various measures of disease activity were recorded by a physician at each visit. Descriptive statistics (mean, median, SD, min, max) were calculated for all PROMs. PsAID cut-offs for use in the MDA were generated based on Remission (REM) and Low Disease Activity (LDA) disease states in the Clinical Disease Activity for Psoriatic Arthritis Index (cDAPSA). <h3>Results</h3> 115 patients completed the PsAID. There were 70 males, 45 females, with a mean PsA duration of 18.7 (±11.6) years. Mean scores of PsAID-9 and PsAID-12 were 3.4 (±2.4) and 3.2 (±2.3) respectively. The PsAID correlated moderately well with 9 of the PROMs administered in the clinic (R2=0.51–0.78). Four PsAID cutoffs were generated for use in the MDA: REM PsAID-9, REM PsAID-12, LDA PsAID-9, and LDA PsAID-12. All four versions of the PsAID MDAs had a sensitivity greater than 85% with the HAQ MDA, and three versions of the PsAID MDA had a specificity greater than 85% with the HAQ MDA. <h3>Conclusions</h3> Our cohort had lower mean PsAID scores than previously reported series suggesting that our patients are monitored carefully. The only moderate correlations with other PROMs suggest that the PSAID cannot replace any of these PROMs. The high sensitivity and specificity of the PsAID MDA with the HAQ MDA suggest that the PsAID is an effective replacement for the HAQ in the MDA. <h3>Disclosure of Interest</h3> None declared
Combining Whole Exome Sequencing and Rnaseq to Provide a Comprehensive Landscape of the Mechanisms of Post-Transplantation Leukemia Relapse
Authors: Lucia Zanotti, Gabriele Bucci, Francesco Santaniello, Cristina Toffalori, Donatella Biancolini, Ettore Zapparoli, Laura Zito, Matteo Giovanni Carrabba, Friedrich Stoelzel, Martin Bornhäuser, Massimo Bernardi, Jacopo Peccatori, Chiara Bonini, Davide Cittaro, Dejan Lazarevic, Giovanni Tonon, Fabio Ciceri, Luca Vago
Journal: Blood (2018)
Quantitative Evaluation of High-Risk Coronary Plaque by Coronary CTA and Subsequent Acute Coronary Events
Authors: Alexander R van Rosendael, Subhi J Al'Aref, Aeshita Dwivedi, Timothy S Kim, Jessica M Peña, Patricia C Dunham, Yong-Jin Kim, Kavitha Chinnaiyan, Gudrun Feuchtner, Fabian Plank, Daniel S Berman, Leslee J Shaw, Hyuk-Jae Chang, Fay Y Lin, Jeroen J Bax, Jagat Narula, James K Min
Journal: JACC. Cardiovascular imaging (2019)
AB0285 Do spouses’ illness perceptions affect the women with rheumatoid arthritis?
Authors: Y. Ulus, B. Tander, Y. Akyol, Y. Terzi, Y. Zahiroglu, G. Sarisoy, A. Bilgici, O. Kuru
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Spouses are often significant source of support and the spouse's views about rheumatoid arthritis (RA) are related to better psychological and physical health in women with RA. <h3>Objectives</h3> The aim was to investigate the effect of spouses' illness perceptions on health status of women with RA. <h3>Methods</h3> One-hundred and one married women diagnosed with RA and their husbands were enrolled. Husbands' beliefs about RA were assessed by husband-version of the Illness Perception Questionnaire-Revised (IPQ-R). Visual analogue scale-pain (VAS-pain), DAS-28, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and Beck Depression Inventory (BDI) were evaluated in patients. Kolmogorov-Smirnov and Spearman's correlation tests, multiple regression analyses were used for statistical analysis. <h3>Results</h3> Median age of patients and husbands were 57(<sup>22–75</sup> years and 60(<sup>24–77</sup> years, respectively. There were positive correlations between consequences subscale and VAS-pain, HAQ-DI, and BDI (p&lt;0.001). Positive correlations were detected between emotional subscale and HAQ-DI, BDI (p&lt;0.001) and VAS-pain (p=0.021). Timeline cyclical subscale was positively correlated with HAQ-DI (p&lt;0.001) and BDI (p=0.001). The husband-version of the IPQ-R domains was not correlated with DAS-28. In regression analysis; consequences (p&lt;0.001), emotional representations (p&lt;0.001) and timeline cyclical (p&lt;0.05) subscales were found to be influential variable on HAQ-DI. Significant correlation with VAS-pain was consequences, and BDI was associated with emotional representations (p&lt;0.05). <h3>Conclusions</h3> We found that in general having more pessimistic illness perceptions in spouses was related to higher disability, pain and depression levels in women with RA. Having more optimistic perceptions of spouses about RA may result in improved health status in women with RA. <h3>References</h3> [1] Matheson L, Harcourt D, Hewlett S. 'Your whole life, your whole world, it changes': partners' experiences of living with rheumatoid arthritis. Musculoskeletal Care2010;8:46–54. [2] Sterba KR, DeVellis RF. Developing a spouse version of the Illness Perception Questionnaire-Revised (IPQ-R) for husbands of women with rheumatoid arthritis. Psychol Health2009;24(4):473–87. [3] Sterba KR, DeVellis RF, Lewis MA, DeVellis BM, Jordan JM, Baucom DH. Effect of couple illness perception congruence on psychological adjustment in women with rheumatoid arthritis. Health Psychol2008;27(2):221–9. <h3>Disclosure of Interest</h3> None declared
Revisiting Minimally Invasive Surgery in the Management of Early-Stage Cervical Cancer
Authors: Kathryn P. Pennington, Renata R. Urban, Heidi J. Gray
Journal: Journal of the National Comprehensive Cancer Network (2019)

Minimally invasive surgery (MIS) was previously considered an acceptable alternative to open radical hysterectomy in the management of early-stage cervical cancer (ESCC), but adequately powered, high-quality prospective trials evaluating survival outcomes were lacking. Recently, a large randomized phase III trial, the Laparoscopic Approach to Cervical Cancer (LACC) trial, showed that MIS for ESCC is associated with a higher risk of recurrence and death compared with open surgery. We review the LACC trial findings in depth, as well as a recent National Cancer Database analysis using propensity score weighting that supports the LACC trial findings. Additional studies are needed to better understand the mechanisms explaining the worse survival associated with MIS for ESCC. This review discusses considerations for integrating the findings of the LACC trial into clinical practice. Based on the high-quality evidence now available, open radical hysterectomy should be offered as standard of care for stage IA2-IB1 cervical cancer and patients should be guided appropriately to make informed shared decision-making if they still desire MIS.
FRI0516 Insight into inflammatory cell and cytokine profiles in adult iga vasculitis
Authors: T. Kuret, K. Lakota, P. Žigon, M. Ogrič, S. Sodin-Šemrl, S. Čučnik, M. Tomšič, A. Hočevar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immunoglobulin A vasculitis (IgAV) is a small vessel, immune complex vasculitis, involving skin, joints, gastrointestinal tract (GIT) and kidney. While different diagnostic/prognostic and inflammatory markers have already been studied in paediatric IgAV, data on adult cases are scarce<sup>1</sup>. <h3>Objectives</h3> To examine the inflammatory cell profile in peripheral blood and cytokine profile in sera of newly diagnosed, biopsy-proven and treatment-naïve adult IgAV compared to healthy blood donors (HBD), and determine associations with IgAV clinical signs. <h3>Methods</h3> Flow cytometry of stained, lysed and fixed whole blood was performed in IgAV (n=30), and HBD (n=17) (Miltenyi). Cytokines were quantitated by multiplex bead assay (Luminex), ELISA (IL-6) and immunonephelometry (acute phase serum amyloid A (SAA)) in 57 IgAV vs. 53 HBD. <h3>Results</h3> Percentage of CD16<sup>+</sup> neutrophils was significantly higher, while percentages of CD3<sup>+</sup> T-cells (including CD4<sup>+</sup> and CD8<sup>+</sup> cells), as well as CD19<sup>+</sup> B-cells were significantly lower in peripheral blood of IgAV patients vs. HBD. The expression of l-selectin (CD62L) on CD16<sup>+</sup> neutrophils was significantly increased in IgAV vs. HBD, as were the sera levels of TNF-α (2-fold), IL-6 (3-fold), IL-8 (2.2-fold) and SAA (11.7-fold changed levels) (table 1). Association was found between GIT involvement and lower neutrophil expression of integrin αM (CD11b) (median; IQR: 7.2; 4.2–16.0), compared to skin limited (17.8; 9.9–40.5) IgAV cases (p=0.047). There was no association found between different cytokines and IgAV clinical phenotype. <h3>Conclusions</h3> We found significant up-regulation of neutrophils and their CD62L expression, as well as sera levels of IL-6, IL-8, TNF-α and SAA in IgAV, implying a pathogenic role of neutrophils in IgAV. CD11b might represent a promising surface marker of GIT involvement in adult IgAV. <h3>Reference</h3> [1] Nagy GE, Kemény L, Bata-Csörgő Z, et al. Neutrophil-to-lymphocyte ratio: A biomarker for predicting systemic involvement in adult IgA vasculitis patients. J Eur Acad Dermatol Venereol2017;31(6):1033–1037. <h3>Acknowledgements</h3> The authors would like to thank the Rotary club Zgornji Brnik, Slovenia, as well as Prof. Mauro Peretti and Dr. Suchita Nadkarni from WHRI, Queen Mary, University of London for their support. We would also like to thank the Sovenian Research Agency for financial support. <h3>Disclosure of Interest</h3> None declared
Abstract P338: Medical Cost Hardship and Incident Cardiovascular Disease (CVD) Among High Risk Individuals in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lindsay R Pool, Jared P Reis, Reto Auer, David R Jacobs, Catarina I Kiefe, Mercedes R Carnethon
Journal: Circulation (2017)

Introduction: Having trouble paying for medical care (i.e., medical cost hardship) may impair disease management and thus increase risk of clinical CVD events among adults with CVD risk factor conditions. Hypothesis: We hypothesized medical cost hardship was associated with incidence of CVD among individuals with diagnosed hypertension, hypercholesterolemia, or diabetes. Methods: CARDIA recruited 5,115 individuals aged 18-30 years in 1985-6 (year 0); we included 2,273 participants who self-reported hypertension, hypercholesterolemia, or diabetes or were taking prescription medications for these conditions at years 10, 15, 20, or 25 (45.2% of all participants). At these visits, medical cost hardship was also queried. CVD events were adjudicated from records of hospital admissions, outpatient procedures, and deaths through 2013. Median follow-up time from initial risk factor diagnosis was 12.4 years. Adjusted Cox proportional hazards models determined hazard ratios (HRs) for the first incident CVD event, examining initial and time-varying medical cost hardship. Results: At first report of hypertension, hypercholesterolemia, or diabetes, 27% of subjects reported medical cost hardship, while 51% did so at subsequent examinations. There were 131 CVD events during follow-up. Adjusting for demographic and socioeconomic factors, initial medical cost hardship was a more robust predictor of incident CVD than time-varying cost hardship, HRs 1.54 (95% CI: 1.03, 2.30) and 1.36 (0.88, 2.12), respectively (Table). Risk factor control partially attenuated the association between medical cost hardship and CVD, as did access to healthcare. We found no significant interaction by race and sex. Conclusions: Medical cost hardship was associated with incident CVD in this sample of high-risk individuals, possibly via risk factor control or access to care. Identification of cost hardship at the time of high-risk diagnosis may facilitate connection to low-cost care, improving risk factor control and preventing clinical CVD.
Combining Vascular Normalization with an Oncolytic Virus Enhances Immunotherapy in a Preclinical Model of Advanced-Stage Ovarian Cancer
Authors: Kathy Matuszewska, Lisa A. Santry, Jacob P. van Vloten, Amanda W.K. AuYeung, Pierre P. Major, Jack Lawler, Sarah K. Wootton, Byram W. Bridle, Jim Petrik
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Intravenous delivery of oncolytic viruses often leads to tumor vascular shutdown, resulting in decreased tumor perfusion and elevated tumor hypoxia. We hypothesized that using 3TSR to normalize tumor vasculature prior to administration of an oncolytic Newcastle disease virus (NDV) would enhance virus delivery and trafficking of immunologic cell subsets to the tumor core, resulting in systemically enhanced immunotherapy and regression of advanced-stage epithelial ovarian cancer (EOC). Experimental Design: Using an orthotopic, syngeneic mouse model of advanced-stage EOC, we pretreated mice with 3TSR (4 mg/kg per day) alone or followed by combination with fusogenic NDV(F3aa) (1.0 × 108 plaque-forming units). Results: Treatment with 3TSR normalized tumor vasculature, enhanced blood perfusion of primary EOC tumors, and induced disease regression. Animals treated with combination therapy had the greatest reduction in primary tumor mass, ascites accumulation, and secondary lesions (50% of mice were completely devoid of peritoneal metastases). Combining 3TSR + NDV(F3aa) led to enhanced trafficking of immunologic cells into the primary tumor core. Conclusions: We have shown, for the first time, that NDV, like other oncolytic viruses, is a potent mediator of acute vascular shutdown and that preventing this through vascular normalization can promote regression in a preclinical model of advanced-stage ovarian cancer. This challenges the current focus on induction of intravascular thrombosis as a requisite for successful oncolytic virotherapy. See related commentary by Bykov and Zamarin, p. 1446
AB0570 Association between sledai-2k domains and organ damage accrual
Authors: K. Zhang, S. Boyd, F. Petitjean, A. Hoi, R. Koelmeyer, E. Morand, H. Nim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Prevention of permanent organ damage is a key goal of SLE management1. Overall disease activity measured by SLE Disease Activity Index (SLEDAI-2k) is a risk factor for damage2, but the contribution of organ-specific activity to damage risk has not been enumerated. <h3>Objectives</h3> We sought to determine the degree to which organ domains of SLEDAI-2k are associated with damage accrual. <h3>Methods</h3> A dataset of SLE patients (2007 – 2017) at the Australian Lupus Registry was studied. Variables collected at each visit included all domains of SLEDAI-2k, Physician Global Assessment, and medications. Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) was recorded annually and each visit was labelled "damage transition" or "non-damage transition" based on whether SDI increased at the subsequent annual measure. The association of risk of SDI increase with SLEDAI-2k domains was assessed using multivariable logistic regression analysis adjusted for confounding by medication use. <h3>Results</h3> 5538 visits from 266 patients (86.5% female, 47.4% Caucasian, 66% dsDNA positive) were analysed; at enrolment median (range) SLEDAI-2k was 4 (0–26) and SDI was 0 (0–4 ). Upon multivariable regression analysis, domains found to be significant were: low complement, proteinuria, haematuria, leukopenia, pyuria, pericarditis, alopecia, rash and arthritis. Upon further adjustment for prednisolone exposure, the effects of some domains were attenuated, but pericarditis (odd ratio (OR)=4.06, 95%CI=1.68–9.83), pyuria (OR=1.94, 1.47–2.56), arthritis (OR=1.71, 1.35–2.16), and rash (OR=1.43, 1.20–1.70), alopecia (OR=1.43, 1.10–1.86) and leukopenia (OR=1.36, 1.03–1.78) remained significant. No other SLEDAI-2k domains showed a significant association, in part due to infrequent occurrence. SLEDAI-2k domains weightings were not congruent with the respective risk of damage accrual. <h3>Conclusions</h3> In study, only some SLEDAI-2k domains were significantly associated with organ damage accrual. Re-appraisal of weightings in SLE disease activity scores based on their association with outcome is potentially warranted. <h3>References</h3> [1] Van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Annals of the rheumatic diseases2014:annrheumdis-2013. [2] Bruce IN, O'Keeffe AG, Farewell V, et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Annals of the rheumatic diseases2015;74(9):1706–13. <h3>Disclosure of Interest</h3> None declared