tbuckley/cabot-search huggingface dataset:
FRI0447 Severity of sacroiliitis and erythrocyte sedimentation rate are associated with a low trabecular bone score in young male patients with ankylosing spondylitis
Authors: KY Kang
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The trabecular bone score (TBS) is a novel method used to evaluate bone microarchitecture. To date, the risk factors associated with a low TBS in AS are unknown and no study has examined the association between TBS and vertebral fracture in ankylosing spondylitis (AS) patients. <h3>Objectives</h3> To examine factors related to a low trabecular bone score (TBS) and the association between TBS and vertebral fracture in patients with (AS). <h3>Methods</h3> One hundred patients (all male, aged &lt;50 years) who fulfilled the modified New York criteria for the classification of AS were enrolled. The TBS and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry (DXA). Clinical variables, inflammatory markers, and the presence of vertebral fracture were also assessed. Spinal radiographic progression was measured using the Stokes AS spine score (SASSS). Multivariate linear regression analysis was performed to identify factors associated with TBS. <h3>Results</h3> The mean TBS at the lumbar spine was 1.38±0.13. The TBS showed a negative correlation with disease duration and inflammatory markers, and a positive correlation with BMD at the lumbar spine, femoral neck, and total hip. It also showed a negative correlation with sacroiliitis grade. BMD at the lumbar spine positively correlated with SASSS, whereas TBS showed a negative correlation. A significant decrease in TBS values was observed in patients with spinal radiographic progression (p=0.001). Multivariate analysis showed that ESR and sacroiliitis were independently associated with TBS (p=0.006 and &lt;0.001, respectively). Ten patients had morphometric vertebral fractures. The mean TBS was lower in patients with vertebral fracture than in age-matched patients without fracture (p=0.028). <h3>Conclusions</h3> The TBS in young male patients with AS is associated with the ESR and severity of sacroiliitis. The TBS may be useful as a tool for assessing osteoporosis in AS. <h3>Disclosure of Interest</h3> None declared
AB0872 Diagnostic efficiency of determining the purine metabolism enzymes activity in the differentiation of gout
Authors: E Mozgovaya, A Trofimenko, S Bedina, I Zborovskaya
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Serum uric acid (UA) level is the most important risk factor for gout. At the same time many people with hyperuricemia do not suffer from gout, and UA level can return to normal during gout exacerbation. <h3>Objectives</h3> to improve the diagnostics of the gout. <h3>Methods</h3> 53 gout patients were the target group. The mixed control group was consisted of 150 rheumatoid arthritis patients, 95 osteoarthritis patients, 55 ankylosing spondylitis patients. The diseases were diagnosed in accordance with the international standards. Adenine deaminase, Adenosine deaminase (ADA), AMP-deaminase (AMPDA), Guanine deaminase, Guanosine deaminase, Guanosine phosphorylase, 59-nucleotidase, Xanthin dehydrogenase (XDG), Xanthin Oxidase, Purine nucleoside phosphorylase activities were determined in blood serum with subsequent evaluation of sensitivity (Se), specificity (Sp), likelihood ratio of positive (LRP) and, likelihood ratio of negative (LRN) result, predictive value of positive and negative results. <h3>Results</h3> The AMFDA and ADA activities were defined as a screening marker to diagnose of the gout from a joint syndrome another genesis. Threshold AMPDA activity 1,67 IU was characterized with the predictive value of negative results (without taking into account the prevalence) near 100%, Se 98%, Sp 62,45%. Cutoff value (CV) of ADA activity (9,57 IU) was characterized with LRN 0,104, Se 92,45%, Sp 72,65%, the sum (Se+Sp 165,10%), which was maximum not only for this test but for all the studied enzymes. The predictive value of negative results (without taking into account the prevalence) was 98,20%. The clinically significant CV of positive result for the ADA activity definition was identified also: LRP was 6,93 (Se 22,64%, Sp 96,73%) for the range of 12.58 IU and above. This fact allows the use of this test not only for the screening, but also, in some cases, for the verification of gout with significant pretest probability of this disease. Two CV were selected for the XDG activity: 7,49 μM/l×min (Se 47,17%, Sp 97,14%) and 8,39 μM /l×min (Se 39,62%, Sp 99,59%). The result of XDG activity determining in the range of 7.49 - 8.39 μM /l×min is an important argument in favor of the gout presence, but this may be useful for differential diagnosis only at high pretest probability of the gout. <h3>Conclusions</h3> Determination of the ADA activity was gave way to AMPDA activity determination at the gout screening and to XDG activity determination at gout verification. However, the ADA multifunctionality, evidenced clinically significant presence of the second CV (positive results) and a small proportion of the cases, which covered a "grey area" between CV (27.48%), provided the ability to use this marker as a backup in the absence of diagnostically relevant AMPDA and XDG activities. <h3>Disclosure of Interest</h3> None declared
AB0360 Clinical and high resolution ct study of the lungs in 96 egyptian patients with rheumatoid arthritis
Authors: S Tharwat, D Shahin, A Abdesalam, AF Barakat
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lung involvement is a common extra-articular manifestation of rheumatoid arthritis (RA) that confers significant morbidity and mortality. However, this issue has not been sufficiently studied in Egyptian patients. <h3>Objectives</h3> To assess the prevalence of pulmonary abnormalities by high resolution computed tomography (HRCT) chest in RA patients and their association with clinical variables. <h3>Methods</h3> Ninty-six patients with RA were assessed regarding their age, gender, duration of RA disease, sicca symptoms, presence of subcutaneous rheumatoid nodules, rheumatoid factor, respiratory symptoms, use of medications, disease activity of RA using Disease Activity Score 28 (DAS28), basic laboratory investigations and pulmonary abnormalities in plain x-ray and HRCT. <h3>Results</h3> HRCT abnormalities were identified in 25% of the patients; 58.3% had respiratory symptoms while 41.7% were subclinical. Dyspnea and cough were the most frequent symptoms. HRCT abnormalities were interstitial lung disease (ILD) in 11 patients (11.5%), pleural involvement in 8 patients (8.3%), consolidation in 4 patients (4.2%), diffuse alveolar hemorrhage in 3 patients (3.1%), bronchiectasis in 2 patients (2.1%), and apical fibrosis with cavitation in only 1 patient (1%). Patients with dyspnea, cough, chest rales, cutaneous rheumatoid nodules, and who received disease modifying antirheumatic drugs (DMARDs) combination were more likely to have HRCT abnormalities. <h3>Conclusions</h3> Pulmonary involvement is not uncommon in RA patients, and HRCT is a sensitive tool in pulmonary evaluation. <h3>Disclosure of Interest</h3> None declared
A randomized controlled trial evaluating efficacy of adjuvant oral uracil-tegafur (UFT) with leucovorin (LV) after resection of colorectal cancer liver metastases: The UFT/LV study.
Authors: Akira Kobayashi, Kiyoshi Hasegawa, Akio Saiura, Tadatoshi Takayama, Shinichi Miyagawa, Junji Yamamoto, Yasutsugu Bandai, Masanori Teruya, Fuyo Yoshimi, Seiji Kawasaki, Hiroto Koyama, Masaru Oba, Michiro Takahashi, Nobuyuki Mizunuma, Yutaka Matsuyama, Toshiaki Watanabe, Masatoshi Makuuchi, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2014)

3584 Background: Surgical resection has been accepted as the standard therapy for colorectal cancer liver metastases (CRLM), however, high recurrence incidence even after curative resection remains an unsolved problem. There is no established adjuvant chemotherapy for CRLM, although efficacy of several adjuvant treatments for stage III colorectal cancer has been confirmed. Oral UFT/LV is one of the standard therapies in stage III colorectal cancer. We conducted this randomized, open-label, phase III trial to evaluate efficacy of adjuvant UFT/LV therapy for CRLM (stage IV). Methods: A patient undergoing curative resection of CRLM was randomly assigned to either UFT/LV or surgery alone (control) group. In the UFT/LV group, 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75 mg/day for 28 days followed by 7 days rest in one cycle) were administered. The primary endpoint was relapse-free survival (RFS), while secondary endpoints were overall survival (OS) and safety. Results: Between February 2004 and December 2010, total 180 patients were enrolled to this trial, among whom 3 patients were ineligible for analysis. The baseline characteristics were well-balanced in the UFT/LV (n=88) and control (n=89) groups. Median follow-up was 4.76 years. The 3y-RFS rate in the UFT/LV group was 38.6%, which was significantly higher than the control group (32.3%). The hazard ratio for relapse in the UFT/LV relative to the control was 0.56 (95% confidence interval: 0.38-0.83, P=0.003). The 3y-OS rates were similar between the UFT/LV and control groups (82.8% vs. 81.6%, P=0.41). In the UFT/LV group without treatment-related death, the scheduled cycles was completed in 45 patients among 82 (54.9%), and the mean dose intensity ratio was 70.8%. As adverse events at any grade, hyperbilirubinemia (28.0%), liver dysfunction (23.2%), diarrhea (26.9%) and anorexia (28.0%) occurred. Conclusions: Adjuvant UFT/LV therapy is effective to prevent recurrence after surgical resection of CRLM. Clinical trial information: C000000013.
SAT0666 Sample size for RA clinical trials using ultrasound outcome measures may be reduced by novel joint selection methods: a pilot study
Authors: JC Allen, J Thumboo, WK Lye, PG Conaghan, LC Chew, YK Tan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Novel outcome measures selecting a reduced joint count for ultrasonography can be highly responsive in demonstrating the improvement in joint inflammation seen in rheumatoid arthritis (RA) patients on treatment [1]. <h3>Objectives</h3> To determine whether the use of the novel methods can translate into smaller sample sizes for subject recruitment into RA clinical trials. Results from the existing methods are used for comparison. <h3>Methods</h3> 24 RA patients with treatment starts or escalation had clinical and ultrasound joint assessment at baseline and 3 months. The novel methods select joints based on (A) ultrasound joint findings (i.e. Individualized Ultrasound (IUS) method) or (B) a composite of ultrasound and clinical joint findings (i.e. Individualized Composite Ultrasound (ICUS) method). In contrast, the existing methods utilize pre-determined joint sites for ultrasonography. Scores at the relevant joints per patient are summed up to obtain the total inflammatory score (TIS). The effect size (ES) was measured as the mean change of the TIS divided by the standard deviation of the change in the TIS. Sample sizes were calculated from confidence intervals (CIs) on ES that reflect uncertainty in estimating ES. For a given CI on ES, sample sizes are computed as the minimum number of patients required to provide ≥80% power at α =0.05 for rejecting the null hypothesis (defined as no difference in the 3-month mean change in TIS comparing novel versus existing methods). <h3>Results</h3> Based on the 95% CI analysis, sample sizes using existing joint assessment methods in conjunction with the 12-joint approach ranged from 10 to 234. The corresponding sample sizes using the ICUS method with the 12-joint approach ranged from 7 to 39, and using the IUS method with the 12-joint approach ranged from 6 to 37. The corresponding sample sizes using the ICUS method with the 7-joint approach ranged from 6 to 24, and using the IUS method with the 7-joint approach ranged from 6 to 35. <h3>Conclusions</h3> Our findings strongly suggest that novel ultrasound joint selection methods result in smaller sample size requirements compared to existing methods, and provide justification for larger studies to confirm these observations. <h3>References</h3> Tan YK et al. Novel Ultrasound Joint Selection Methods Using a Reduced Joint Number Demonstrate Inflammatory Improvement when Compared to Existing Methods and Disease Activity Score at 28 Joints. J Rheumatol. 2016;43:34–7. <h3>Disclosure of Interest</h3> None declared
Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial
Authors: Pedro Cahn, Richard Kaplan, Paul E Sax, Kathleen Squires, Jean-Michel Molina, Anchalee Avihingsanon, Winai Ratanasuwan, Evelyn Rojas, Mohammed Rassool, Mark Bloch, Linos Vandekerckhove, Peter Ruane, Yazdan Yazdanpanah, Christine Katlama, Xia Xu, Anthony Rodgers, Lilly East, Larissa Wenning, Sandy Rawlins, Brenda Homony, Peter Sklar, Bach-Yen Nguyen, Randi Leavitt, Hedy Teppler, PE Cahn, I Cassetti, M Losso, MT Bloch, N Roth, J McMahon, RJ Moore, D Smith, N Clumeck, L Vanderkerckhove, B Vandercam, M Moutschen, J Baril, B Conway, F Smaill, GHR Smith, A Rachlis, SL Walmsley, C Perez, M Wolff, MF Lasso, CE Chahin, JD Velez, O Sussmann, J Reynes, C Katlama, Y Yazdanpanah, S Ferret, J Durant, C Duvivier, I Poizot-Martin, F Ajana, JK Rockstroh, G Faetkanheuer, S Esser, H Jaeger, O Degen, M Bickel, J Bogner, K Arasteh, H Hartl, A Stoehr, EM Rojas, E Arathoon, LD Gonzalez, CR Mejia, E Shahar, D Turner, I Levy, Z Sthoeger, H Elinav, A Gori, A D'Arminio Monforte, G Di Perri, A Lazzarin, G Rizzardini, A Antinori, BM Celesia, F Maggiolo, TS Chow, CKC Lee, R Iskandar Shah Raja Azwa, M Mustafa, M Oyanguren, RA Castillo, L Hercilla, C Echiverri, F Maltez, JG Saraiva da Cunha, I Neves, E Teofilo, R Serrao, F Nagimova, I Khaertynova, E Orlova-Morozova, E Voronin, V Sotnikov, AA Yakovlev, NG Zakharova, OA Tsybakova, ME Botes, L Mohapi, R Kaplan, MS Rassool, JR Arribas, JM Gatell, E Negredo, E Ortega, J Troya, J Berenguer, K Aguirrebengoa, A Antela, A Calmy, M Cavassini, A Rauch, M Stoeckle, WH Sheng, HH Lin, HC Tsai, D Changpradub, A Avihingsanon, S Kiertiburanakul, W Ratanasuwan, MR Nelson, A Clarke, A Ustianowski, A Winston, MA Johnson, DM Asmuth, J Cade, JE Gallant, PJ Ruane, PN Kumar, AE Luque, L Panther, KT Tashima, D Ward, DS Berger, CA Dietz, C Fichtenbaum, S Gupta, KM Mullane, RM Novak, DE Sweet, GE Crofoot, DP Hagins, ST Lewis, CK McDonald, E DeJesus, L Sloan, DJ Prelutsky, JC Rondon, S Henn, AJ Scarsella, JO Morales, None Ramirez, L Santiago, CD Zorrilla, MS Saag, CB Hsiao
Journal: The Lancet HIV (2017)
Immunotherapy of Lymphoma and Myeloma: Facts and Hopes
Authors: Matthew J. Pianko, Alison J. Moskowitz, Alexander M. Lesokhin
Journal: Clinical Cancer Research (2017)

Abstract Immune checkpoint blockade has driven a revolution in modern oncology, and robust drug development of immune checkpoint inhibitors is underway in both solid tumors and hematologic malignancies. High response rates to programmed cell death 1 (PD-1) blockade using nivolumab or pembrolizumab in classical Hodgkin lymphoma (cHL) and several variants of non-Hodgkin lymphoma (NHL) revealed an intrinsic biological sensitivity to this approach, and work is ongoing exploring combinations with immune checkpoint inhibitors in both cHL and NHL. There are also preliminary data suggesting antitumor efficacy of PD-1 inhibitors used in combination with immunomodulatory drugs in multiple myeloma, and effects of novel monoclonal antibody therapies on the tumor microenvironment may lead to synergy with checkpoint blockade. Although immune checkpoint inhibitors are generally well tolerated, clinicians must use caution and remain vigilant when treating patients with these agents in order to identify immune-related toxicities and prevent treatment-related morbidity and mortality. Autologous stem cell transplant is a useful tool for treatment of hematologic malignancies and has potential as a platform for use of immune checkpoint inhibitors. An important safety signal has emerged surrounding the risk of graft-versus-host disease associated with use of PD-1 inhibitors before and after allogeneic stem cell transplant. We aim to discuss the facts known to date in the use of immune checkpoint inhibitors for patients with lymphoid malignancies and our hopes for expanding the benefits of immunotherapy to patients in the future. Clin Cancer Res; 24(5); 1002–10. ©2017 AACR.
RNAi-mediated beta-catenin inhibition to promote T-cell infiltration and antitumor activity in combination with immune checkpoint blockade.
Authors: Shanthi Ganesh, Serena Shui, Cheng Lai, Hank Dudek, Weimin Wang, Bob D Brown, Marc Abrams
Journal: Journal of Clinical Oncology (2017)

e14608 Background: Recent research suggests an important role for Wnt/β-catenin signaling in mediating cancer immune evasion and resistance to immune checkpoint therapy. The mechnism is believed to involve blocking of specific cytokines which trigger immune cell recruitment to the tumor, resulting in the phenomenon of T-cell exclusion and rendering the tumor to a non-inflamed state. Inhibition of β-catenin may be an effective strategy for increasing the low response rate to these effective medicines in numerous cancer populations. DCR-BCAT is an advanced preclinical development candidate that has a potent and specific chemically-optimized RNA interference (RNAi) trigger targeting CTNNB1, the gene that encodes β-catenin, formulated in a tumor-selective lipid nanoparticle. Methods: Syngeneic murine models and transgenic MMTV-Wnt1 mouse models were used in this study. In both cases, a sequential dose regimen was employed where, in each dosing cycle, animals received DCR-BCAT, followed by a combination of anti-PD-1 and anti-CTLA-4 on subsequent days. Pharmacodynamic endpoints included CTNNB1 (β-catenin), CCL4, PD-1, PD-L1 mRNA measurement by quantitative PCR, as well as β-catenin, perforin, and granzyme B immunohistochemistry. Results: In syngeneic models, β-catenin inhibition with DCR-BCAT significantly improved the T-cell infiltration. The combination of DCR-BCAT and immune checkpoint blockade yielded significant tumor growth inhibition compared to monotherapy in B16F10, 4T1, Neuro2A and Renca tumors. The combination therapy was associated with high levels of granzyme B and perforin, strongly suggesting that the mechanism of sensitization to checkpoint therapy was a sharp increase in T-cell mediated cytotoxicity. Finally, when DCR-BCAT was combined with anti-PD-1/CTLA-4 antibodies in mice which develop spontaneous Wnt-driven mammary tumors, checkpoint therapy potentiation yielded complete tumor regressions. Conclusions: These data offer proof-of-concept for conversion of non-inflamed tumors to inflamed tumors by β-catenin inhibition, and support clinical evaluation of this combination approach using a first-in-class RNAi-based agent.
AB0944 Use,safety and efficacy of etanercept in jia–a single centre retrospective study from north india
Authors: A Shivpuri, S Mittal, M Agarwal, S Sawhney
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The treatment paradigm for Juvenile Idiopathic Arthritis (JIA) has changed in last decade:Early diagnosis,objective assessment &amp; appropriate use of biologic response modifiers (BRMs) are common place.Etanercept (Et) is available in India for 15yrs. BRM use in developing world is fraught with challenges: cost, high burden of Tuberculosis (TB) &amp; retention. In view of the cost &amp; safety concerns regarding TB, at our centre, full dose Et is used for 3–6 mths, followed by dose tapering as tolerated. <h3>Objectives</h3> 1. To determine the use, safety &amp; efficacy of Et in JIA. 2. To determine the factors that determine responders vs non responders. 3. To determine the factors that determine disease free survival on stopping Et <h3>Methods</h3> This study was done from 15thJune915 to15thDec916 (18mths) at Sir GangaRam Hospital. <i>Inclusion criteria:</i> All JIA pts who took Et for min 12 wks &amp; attended the outpatients during the study period. <i>Outcome:</i> All pts who achieved the Wallace criteria of inactive ds, clinical remission on (CRoM) or off medication within 4 months were termed as responders. <h3>Results</h3> <i>Use:</i> 46pts recd Et (29M,17F). Median (Md) age at JIA onset: 9.08yrs (1.16–16.5).Md delay to diagnosis: 4mths (0.5–63). Md age at initiation of Et: 11.6yrs (4.25–20.3). <i>Indications:</i> Partial response to Intraarticular steroids/bridging steroids &amp; DMARD-32; Started upfront for high ds.burden: 14. <i>Diagnoses:</i> ERA30 (65%), Poly JIA8 (17%), OJIA 3 (7%), SOJIA 3 (7%) &amp; UJIA 2 (4%). <i>Safety:</i> Screening: Mantoux +ve: 6, Quantiferon+ve: 2,antitubercular therapy for latent TB: 8. Side effects: 41 (88%) had no adverse event. 5 pts - 1 each had enteric fever, varicella, uveitis, hemolysis, malaria. <i>Follow up:</i> Md duration of follow up-47.5 mths (2–147). <i>Medications at last follow up:</i> Et ongoing in 20 (43.5%), 12 on 2nd BRM, 12 off BRM &amp; 2 lost to follow up. <i>Status at last follow up:</i> Of 37 responders - 8 currently active. <i>Responders vs non responders:</i> 37 responded (2 excluded duration &lt;12 wks). In all responders drug was tapered/stopped. No demographic, clinical, lab criteria could predict responder from non responder (Table 1). Of 37 responders, 15 (40.5%) did not show any flare (Table 2). <i>Disease free survival on Et:</i> Of 37 responders, 22 flared. No factors could predict flare in pts who recd tapering Et dose or after stopping Et. Some needed repeat cycles of Et/2nd BRM. Kaplan Meier curve of responders confirmed that no pt would be flare free at 63mths of follow up. <h3>Conclusions</h3> Et is safe to use &amp; had no adverse events in 89%. Needed most for ERA. Effective in 84%. On using shortterm Et, 59% flared either on tapering/stopping. These pts responded to reinitiation of Et/BRM. On long term follow up (63mth) there were no flare free pts. <h3>Disclosure of Interest</h3> None declared