tbuckley/cabot-search huggingface dataset:
SP0158 Pain phenotype: can we take advantage of the placebo effect
Authors: A Abhishek
Journal: Annals of the Rheumatic Diseases (2017)

The discordance between pain and structural changes in osteoarthritis has been recognised for over two decades. Recent research has also identified different pain phenotypes in people with osteoarthritis. This suggests that the changes in the peripheral and central nervous system may affect both the severity and character of pain and associated features in osteoarthritis. Placebo response, the improvement in symptoms in those in the placebo arm of a randomized controlled trial, and placebo effect, the difference in improvement in those treated with placebo (in placebo arm of a randomized controlled trial) and those who have had no treatment (e.g. in the observation only arm of a three arm randomized controlled trial) are mediated by complex neural mechanisms and are especially relevant to the management of osteoarthritis. Indeed, the placebo response associated with most osteoarthritis treatments is stronger than their treatment effects. While a large placebo response is a significant obstacle to the development of new drugs and non-drug interventions for the treatment of osteoarthritis, it can be utilised as a "friend" in the day to day and long-term management of a person with osteoarthritis. This lecture will outline the pain phenotypes associated with osteoarthritis and describe the potential for placebo effect in improving osteoarthritis pain. The pain phenotypes associated with osteoarthritis that are most likely to be improved by optimizing placebo response and the underlying mechanisms will be discussed. <h3>Disclosure of Interest</h3> None declared
A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study
Authors: V. Chajès, N. Assi, C. Biessy, P. Ferrari, S. Rinaldi, N. Slimani, G.M. Lenoir, L. Baglietto, M. His, M.C. Boutron-Ruault, A. Trichopoulou, P. Lagiou, M. Katsoulis, R. Kaaks, T. Kühn, S. Panico, V. Pala, G. Masala, H.B. Bueno-de-Mesquita, P.H. Peeters, C. van Gils, A. Hjartåker, K. Standahl Olsen, R. Borgund Barnung, A. Barricarte, D. Redondo-Sanchez, V. Menéndez, P. Amiano, M. Wennberg, T. Key, K.T. Khaw, M.A. Merritt, E. Riboli, M.J. Gunter, I. Romieu
Journal: Annals of Oncology (2017)
Multispectral Optoacoustic Tomography (MSOT) of Human Breast Cancer
Authors: Gael Diot, Stephan Metz, Aurelia Noske, Evangelos Liapis, Barbara Schroeder, Saak V. Ovsepian, Reinhard Meier, Ernst Rummeny, Vasilis Ntziachristos
Journal: Clinical Cancer Research (2017)

Purpose: In a pilot study, we introduce fast handheld multispectral optoacoustic tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and noncancerous breast tissue.Experimental Design: We imaged 10 female patients ages 48-81 years with malignant nonspecific breast cancer or invasive lobular carcinoma. Three healthy volunteers ages 31-36 years were also imaged. Fast-MSOT was based on unique single-frame-per-pulse (SFPP) image acquisition employed to improve the accuracy of spectral differentiation over using a small number of wavelengths. Breast tissue was illuminated at the 700-970 nm spectral range over 0.56 seconds total scan time. MSOT data were guided by ultrasonography and X-ray mammography or MRI.Results: The extended spectral range allowed the computation of oxygenated hemoglobin (HBO2), deoxygenated hemoglobin (HB), total blood volume (TBV), lipid, and water contributions, allowing first insights into in vivo high-resolution breast tissue MSOT cancer patterns. TBV and Hb/HBO2 images resolved marked differences between cancer and control tissue, manifested as a vessel-rich tumor periphery with highly heterogeneous spatial appearance compared with healthy tissue. We observe significant TBV variations between different tumors and between tumors over healthy tissues. Water and fat lipid layers appear disrupted in cancer versus healthy tissue; however, offer weaker contrast compared with TBV images.Conclusions: In contrast to optical methods, MSOT resolves physiologic cancer features with high resolution and revealed patterns not offered by other radiologic modalities. The new features relate to personalized and precision medicine potential. Clin Cancer Res; 23(22); 6912-22. ©2017 AACR.
A Phase 1/2 Study of G-CSF, Cladribine, Cytarabine, and Dose-Escalated Mitoxantrone (G-CLAM) in Adults with Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)
Authors: Anna B. Halpern, Megan Othus, Emily M Huebner, Kaysey F. Orlowski, Bart L. Scott, Heather A. Smith, Pamela S. Becker, Mary-Elizabeth M. Percival, Paul C. Hendrie, Andrea M. Perdue, Tara L. Chen, Sarah A. Buckley, Harry P. Erba, Elihu H. Estey, Roland B. Walter
Journal: Blood (2016)
Tumor growth over time in patients with non-small cell lung cancer (NSCLC) of adenocarcinoma histology (ACH) treated with nintedanib and docetaxel or placebo and docetaxel: Analysis of data from the LUME-Lung 1 (LL1) study.
Authors: Martin Reck, Hannes Buchner, Maya Gottfried, Silvia Novello, Anders Mellemgaard, Birgit Gaschler-Markefski, Rolf Kaiser, Jean-Yves Douillard
Journal: Journal of Clinical Oncology (2015)

e19021 Background: Nintedanib (N; Vargatef), a triple angiokinase inhibitor, is approved in the EU in combination with docetaxel (D) for the treatment of patients (pts) with advanced NSCLC of ACH after 1st-line chemotherapy. In the pivotal LL1 study, N+D significantly improved overall survival (OS; secondary endpoint) vs D in pts with ACH (median OS: 12.6 vs 10.3 months (m); HR: 0.83 [95% CI: 0.70–0.99]; p = 0.0359) and in pts who progressed either during or within 9 m of 1st-line therapy (time[T] < 9m) (median OS: 10.9 vs 7.9 m; HR: 0.75 [95% CI: 0.60–0.92]; p = 0.0073). We explored the impact of on tumor growth over time as a treatment effect of N+D, with a specific focus on pts with poor prognosis – T < 9m and pts who had progressive disease as best response to 1st-line therapy (PD-FLT). Methods: Tumor growth was evaluated using all available tumor measurements. Mixed-effects models were used to quantify the non-linear individual relationships between time from randomization and tumor burden, measured as the sum of longest diameter of target lesions (SLD) and assessed by independent central review (RECIST 1.0). Analyses were conducted for the entire population of pts with ACH, T < 9m and PD-FLT. Results: Estimated mean baseline SLD was 82.5 mm in all pts with ACH, 88.3 mm in T < 9m and 98.1 mm in PD-FLT. N+D showed a significant reduction of tumor growth over time (p < 0.0001) in pts with ACH compared to D. Treatment difference at 6 months (SLD D group – SLD N+D group) for pts with ACH was 9.7 mm. This treatment difference was even more pronounced in the T < 9m group (16.9 mm) and in pts with PD-FLT (19.7 mm). Tumor growth over time for N+D showed a non-linear J-shaped curve, indicating a decline in SLD at the beginning of treatment, which was maintained over time followed by a linear increase. This relationship was consistently observed between populations. For pts treated with D, a linear increase in SLD from baseline over time in all ACH pts, T < 9m and PD-FLT was observed. Conclusions: N+D significantly decreased tumor burden and decelerated tumor growth over time compared to D in all pts with ACH and in the groups of pts with the poorest prognosis. Clinical trial information: NCT00805194.
FRI0451 Sex differences in disease activity according to composite indices in spondyloarthritis: a systematic review and meta-analysis
Authors: M Blasco-Blasco, I Castrejόn, V Jovaní, E Eliseo, M Ruiz-Cantero
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), an index of only patient-self-report measures, and AS Disease Activity Score (ASDAS)<sup>1</sup>, which adds patient global estimate and laboratory tests to BASDAI elements are widely used in Spondyloarthritis (SpA). Both indices are specifically designed to evaluate disease activity AS patients. Some studies have shown worse BASDAI in women, but sex-related differences by ASDAS remain unclear <sup>2,3</sup>. <h3>Objectives</h3> To analyze reports of sex-stratified disease activity measures -BASDAI and ASDAS- in patients with SpA. <h3>Methods</h3> Data sources included PubMed (1950 to December 2016), Embase, Web Of Science, and manual searches of references lists. We included observational studies and randomized trials comparing disease activity scores, specifically BASDAI and ASDAS, between men and women with SpA. Studies quality was determined in line with the STROBE statement for observational studies and CONSORT statement for RCT, considering &lt;50% positive items as low quality. Randomized effects were performed to report the mean difference (95% confidence interval) by gender, and heterogeneity was measured via I<sup>2</sup> statistic in order to check the results robustness. <h3>Results</h3> From 672 identified studies 18 cross-sectional studies, 3 cohort, 2 case-control studies, and 1 RTC reported sex-stratified BASDAI and ASDAS. ASDAS was evaluated in 3,758 patients (36.5% women) in 9 studies, and BASDAI included 12,329 patients (34.3% women) in 24 studies. In a metanalysis of mean difference BASDAI including 19 studies the mean difference was 0.56 (95% CI: 0.47, 0.66) and I<sup>2</sup>=43%, indicating a significantly higher disease activity in women (Figure). In a metanalysis of 7 studies ASDAS the mean difference was 0.06 (95% CI: -0.04, 0.16) and I<sup>2</sup>=41%, not showing statistically significant differences. <h3>Conclusions</h3> We identified relevant sex differences in disease activity according to BASDAI with higher disease activity in women, but not according to ASDAS. In SpA, women present more peripheral arthritis and higher pain, which may influence the BASDAI score, mainly based on patient-self-report measures. It is important to recognize these differences that may influence management decisions based on disease activity measures. <h3>References</h3> van der Heijde D et al. Ann Rheum Dis 2009;68:1811–18. van der Horst-Bruinsma IE et al. Ann Rheum Dis 2013;72:1221–1224. Arends S et al. heumatology 2015;54:1333–1335. <h3>Acknowledgements</h3> Faculty of Health Sciences and University Institute for Gender Studies of the University of Alicante supported M. Blasco-Blasco. <h3>Disclosure of Interest</h3> None declared
AB0962 Clinical and laboratory characteristics of non-bacterial osteomyelitis: data analysis of 91 patients
Authors: MM Kostik, O Kopchak, A Mushkin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Non-bacterial Osteomyelitis (NBO) is a sterile inflammatory bone disorder of unknown etiology. It typically affects children and most commonly presents with bone pain and/or swelling. <h3>Objectives</h3> The aim of study is to evaluate clinical and laboratory features of non-bacterial osteomyelitis in children. <h3>Methods</h3> Our retrospective – prospective study was included 91 patients with NBO. A routine blood test (WBC, platelets, ESR, C-reactive protein (CRP) and hemoglobin levels), a radiological examination and a bone biopsy with evaluation bacteriological and morphological data were performed in all patients. <h3>Results</h3> The mean age of onset NBO was 7.3 years (2.5; 10.6). We did not reveal any gender peculiarities in our study. Family history of immune-mediated diseases is found in 5/75 (6.7%) in prospective group. Concomitant immune-mediated diseases were noted in 62/89 (68.1%). Diagnostic delay was 6.3 (2.0; 17.8) months. The radiological examination was performed in the following ratio: X-rays - 91 (100.0%), CT - 79 (86.8%), MRI - 66 (72.5), including MRI "whole body" with 15 pts, bone scintigraphy - 54 (59.3%). Monofocal form was registered in 1/3 cases. 2/3 cases was presented as a typical multifocal process with predominant involvement femur - 37 (40.7%), bone of foot - 36 (39.6%), tibia - 33 (36.3%), spine – 29 (31.9%). The number of foci is 3.0 (1.0; 6.0). We did not revealed any significant differences in quantity of WBC, platelets, hemoglobin level, ESR, CRP). Evidence confirming NBO was a negative bone biopsy in 100.0% cases. However, morphological data were as non-specific, as granulomatous inflammation. <h3>Conclusions</h3> NBO is determined as a primarily chronic multifocal process without specific clinical and laboratory peculiarities, associated with immune-mediated diseases. Diagnose must be established on morphological and bacteriological data bone biopsy. <h3>Disclosure of Interest</h3> None declared
FRI0653 Salivary gland ultrasound is related to autoimmunity in primary sjÖgren syndrome
Authors: JC Nieto-González, FJ Lόpez-Longo, E Estrada, E Naredo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Primary Sjögren syndrome (pSS) is a systemic autoimmune disease involving exocrine glands, mainly ocular and salivary glands. Salivary gland ultrasound (SGU), of submandibular and parotid glands, in pSS is characterized by hypo/anechoic rounded areas within gland parenchyma, losing the normal homogeneity of the glands (typical SGU)<sup>1</sup>. SGU is a reliable imaging technique for assessing gland echostructure in pSS<sup>2</sup>. <h3>Objectives</h3> The aim of our study is to evaluate the relation between typical SGU and clinical and laboratory data in pSS <h3>Methods</h3> We performed SGU to 100 patients with pSS from our rheumatology department selected randomly from a database. We used a semiquantitative score from 0 to 3. Grades 0 and 1 were considered as normal and grades 2 and 3 were considered as typical for pSS. We retrospectively collected demographics (age, gender, disease duration), clinical (extra-glandular manifestations, parotid swelling and lymphoma) and laboratory data (ESR, CRP, rheumatoid factor (RF), antinuclear antibodies (AAN), anti-SSA and anti-SSB antibodies). We divided the patients into 3 groups depending on their autoimmunity profile. Complete seropositive group were patients with RF, AAN and antiSSA or antiSSB positives simultaneously or sequentially. Simple seropositive group were patients with any positive autoantibody (RF/AAN/antiSSA or antiSSB) but not all of them together. Finally, patients without positive autoantibodies were included in the seronegative group <h3>Results</h3> We excluded 7 patients because they were diagnosed with secondary SS. From 93 pSS patients analyzed, 32 (frequency 34.5%) had a typical SGU. Demographics, extra-glandular manifestations and lymphomas were similar between patients with typical SGU and patients with normal SGU. Parotid swelling and longer disease duration were associated with a typical SGU (p&lt;0.05). Patients with positive autoantibodies (AAN, RF, antiSSA and antiSSB) had more frequently a typical SGU. Complete seropositive group had the highest frequency of typical SGU, followed by simple seropositive group. All seronegative patients had a normal SGU. SGU relation with autoimmunity is shown in table 1 <h3>Conclusions</h3> Longer disease duration and parotid swelling were associated with typical SGU. Typical SGU was associated with positive autoimmunity, moreover all seronegative patients had a normal SGU <h3>References</h3> Bialek EJ. US of the major salivary glands: anatomy and spatial relationships, pathologic conditions, and pitfalls. Radiographics 2006. Damjanov N, Milic V, Nieto-González JC, et al. Multiobserver Reliability of Ultrasound Assessment of Salivary Glands in Patients with Established Primary Sjögren Syndrome. J Rheumatol. 2016. <h3>Disclosure of Interest</h3> None declared
OP0011 Does a very early therapeutic intervention in very early arthritis / pre-rheumatoid arthritis patients prevent the onset of rheumatoid arthritis: a systematic review and metanalysis
Authors: B Hugues, S Hilliquin, S Mitrovic, L Gossec, B Fautrel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recent progress in the understanding of rheumatoid arthritis (RA) pathogenesis leads to growing interest in the concept of pre-RA, a clinical stage in which very early intervention could be more efficacious. <h3>Objectives</h3> To assess the efficacy of very early therapeutic interventions in pre-RA patients, i.e., with either undifferentiated arthritis, or ACPA-positive arthralgia/arthritis (ie, very early RA, VERA), through a systematic literature review (SLR) and meta-analysis (MA). <h3>Methods</h3> The SLR was performed following Cochrane guidelines. The search used "undifferentiated arthritis" or "very early rheumatoid arthritis" (VERA) associated with "therapy" or "treatment", and was limited to randomized controlled trials (RCTs) published in English over the last five years. It was conducted in Pubmed, Embase and Cochrane RCT databases, as well as EULAR and ACR congress abstracts of the last two years. Two independent readers (SH, BH) extracted the following data through a standardized form: study quality, patient status at baseline (either undifferentiated arthritis or VERA), the type of intervention, and disease characteristics over time as well as occurrence of RA. The main outcomes that were analysed for the meta-analysis were RA occurrence at 52 weeks and beyond and the absence of radiographic progression at week 52. The meta-analysis was performed using RevMan with Mantel-Haenszel method. <h3>Results</h3> The search identified 595 abstracts, of which 9 RCTs were finally selected (including 2 congress abstracts). Eight were related to undifferentiated arthritis; 1 to VERA. The studies included 1156 patients, weighted mean age 45.8+/-15.2 years, mean symptoms duration 16.2+/-12.6 weeks; 66.0+/-17.7% were female. The occurrence of RA at week 52 or more was available in 7 studies (assessing 800 patients). Early therapeutic intervention – either methylprednisolone (80 to 120mg IM), methotrexate, TNF-blocker, abatacept or rituximab -reduced the risk of occurrence of RA with a pooled odds ratio (OR) of 0.72 (95% CI [0.54; 0.96]), p 0.02 (Figure). There was no statistically significant difference between the treatments or placebo, for the absence of radiographic progression (pooled OR 1.36 [0.82;2.27]) The outcome was assessed at Week 52 for all studies, except for Van Dongen 2007 (PROMPT), where it was assessed at Week 120. MethylPDN, methylprednisolone; MTX, methotrexate. <h3>Conclusions</h3> This meta-analysis demonstrates that early therapeutic intervention significantly reduces the risk of RA onset in pre-RA patients. The benefit /risk balance and feasibility in clinical practice remain to be further assessed. <h3>Disclosure of Interest</h3> None declared
SAT0021 Human CD4 T cells and synovial fibroblasts cooperate to promote inflammation in the RA synovial joint
Authors: A Petrasca, G Jameson, T McGarry, DJ Veale, U Fearon, JM Fletcher
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by synovial tissue proliferation and degradation of articular cartilage. Activated synovial fibroblasts proliferate and express matrix-degrading proteases, adhesion molecules and proinflammatory cytokines, which contribute to cartilage and joint destruction. Moreover, synovial cell activation correlates with infiltration of inflammatory lymphocytes and monocytes which in turn contribute to synoviocyte activation, thus further exacerbating inflammation. <h3>Objectives</h3> The functional relationship linking fibroblasts and T lymphocytes in this complex microenvironment has yet to be characterised. Therefore, we established an <i>in vitro</i> model to examine the outcomes of co-culturing activated human CD4 T cells with RA synovial fibroblasts. <h3>Methods</h3> Co-culture assays were carried out using immortalised K4IM RA synovial fibroblasts or synovial fibroblast cells derived from arthroscopy biopsies of RA patients. Human CD4 T cells were stained with a proliferation-tracking dye and co-cultured with pre-seeded synovial fibroblasts for 5 days. The resulting cell cultures and supernatants were examined for proliferation, cytokine production, secretion of matrix metalloproteinases and expression of adhesion molecules. <h3>Results</h3> We found that CD4 T cells and K4IM cells reciprocally induced an increased expression of adhesion molecules ICAM and VCAM. Furthermore, co-culture of CD4 T cells and synovial fibroblasts resulted in proliferation of CD4 T cells expressing increased levels of the proinflammatory cytokines IFN-γ and IL-17a and RANKL after 5 days. Lastly, co-culture of T cells and synovial fibroblasts resulted in secretion of IL-6, IL-8, IFN-γ and IL-17a and matrix metalloproteinases MMP-1 and MMP-3. <h3>Conclusions</h3> These results indicate that CD4 T cells work mutually with synoviocytes to create an inflammatory microenvironment likely to promote joint destruction. Future studies will characterise the role of glucose metabolism in these cells and investigate if metabolism is intrinsically coupled to effector functions in these cells. <h3>Disclosure of Interest</h3> None declared
SP0183 Failure of treg control to understand autoimmunity
Authors: JY Humrich
Journal: Annals of the Rheumatic Diseases (2017)

Regulatory T cells (Treg) expressing the transcription factor FoxP3 are crucial for the maintenance of immunological tolerance to self and thus for the control of autoimmunity. There is strong evidence that numeric or functional defects in Treg cell biology are involved in the pathogenesis of particular autoimmune diseases. Here we will focus on the fundamental role of Treg cells in diverse autoimmune and rheumatic diseases and will explain how a failure of the Treg cell system can evolve and contribute to the development of such diseases. Furthermore, therapeutic approaches aiming to overcome these Treg cell defects and to restore Treg cell activity in the patients will be discussed. <h3>Disclosure of Interest</h3> None declared